olanzapine and Psychotic-Disorders

Neuropsychiatric symptoms affect most patients with dementia over the course of the disease. They include a wide variety of symptoms from apathy and depression to psychosis, irritability, impulsivity and agitation. These symptoms are associated with significant distress to the patient and caregivers, as well as more rapid progression of dementia, institutionalisation and higher mortality. The first-line management of the neuropsychiatric symptoms of dementia should be non-pharmacological. If medications are required, antipsychotics are commonly chosen. Second-generation antipsychotics such as risperidone, olanzapine, quetiapine and aripiprazole are prescribed more often than first-generation antipsychotics, such as haloperidol. The aim of this review is to provide an update on findings on adverse outcomes and clinical implications of antipsychotic use in dementia. These medications may increase mortality and can be associated with adverse events including pneumonia, cerebrovascular events, parkinsonian symptoms or higher rates of venous thromboembolism. Risks related to antipsychotic use in dementia are moderated by a number of modifiable and non-modifiable factors such as co-prescribing of other medications, medical and psychiatric co-morbidities, and demographics such as age and sex, making individualised treatment decisions challenging. Antipsychotics have further been associated with an increased risk of reliance on long-term care and institutionalisation, and they might not be cost-effective for healthcare systems. Many of these risks can potentially be mitigated by close physical health monitoring of antipsychotic treatment, as well as early withdrawal of pharmacotherapy when clinically possible.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Patients with first-episode psychosis or early-phase schizophrenia are susceptible to olanzapine-associated weight gain and cardiometabolic dysregulation. This meta-analysis characterized weight and metabolic effects observed during olanzapine treatment in randomized clinical trials in this vulnerable patient population.. PubMed, EMBASE, and Dialog were searched for randomized controlled trials (RCTs) reporting weight or cardiometabolic outcomes associated with olanzapine treatment in first-episode psychosis or early-phase schizophrenia. Random-effects meta-analysis and meta-regression were conducted using R v4.0.5.. Of 1203 records identified, 26 RCTs informed the analyses. The meta-analytic mean (95% CI) weight gain was 7.53 (6.42-8.63) kg in studies (n = 19) that reported weight gain with olanzapine treatment. Stratified by duration, the mean (95% CI) weight gain was significantly higher in studies >13 weeks in duration than in those lasting ≤13 weeks: 11.35 (10.05-12.65) vs 5.51 (4.73-6.28) kg, respectively. Despite between-study variability, increases from baseline in most glycemic and lipid parameters were generally small in studies of both ≤13 and >13 weeks. There were no correlations, however, between weight gain and metabolic parameter changes when stratified by study duration.. In RCTs enrolling patients with first-episode psychosis or early-phase schizophrenia, olanzapine was consistently associated with weight gain that was greater in studies lasting >13 weeks compared with those of ≤13 weeks. Metabolic changes observed across studies suggest that RCTs may underestimate metabolic sequelae vs real-world treatment observations. Patients with first-episode psychosis or early-phase schizophrenia are vulnerable to olanzapine-associated weight gain; strategies minimizing olanzapine-associated weight gain should be carefully considered.

Topics: Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Humans; Olanzapine; Psychotic Disorders; Schizophrenia; Weight Gain

Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP.. We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs).. Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94).. Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dementia; Humans; Network Meta-Analysis; Off-Label Use; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

To provide updated guidance for the medication treatment of acute agitation in the setting of psychosis or mania on inpatient psychiatric units.. This topic presented challenges: studies are sparse, tend to be under-powered, and are difficult to compare. Though there have been few recent studies, there have been several recent meta-analyses, Cochrane reviews, and published guidelines that sift through the primarily older evidence as well as more recent trials. The reviewers often do not agree on what seems to have the best evidence for efficacy and safety.. We conclude that the best approach is to summarize in some detail the evidence for each possible treatment and the interpretations published recently on each of those treatments, and then present recommendations for medication management in tiered rankings, based on the authors' qualitative review of the data and opinions. For oral treatment, the first-tier options are (alphabetically) haloperidol with lorazepam, lorazepam alone, and olanzapine. The second tier includes haloperidol with promethazine, loxapine inhaler, and risperidone alone. Tier 3 includes asenapine and quetiapine. For intramuscular treatment, the first-tier includes haloperidol plus promethazine, and olanzapine alone, and the second-tier includes haloperidol with lorazepam, and lorazepam alone.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Mania; Olanzapine; Promethazine; Psychomotor Agitation; Psychopharmacology; Psychotic Disorders

Psychiatric illness is associated with both chronic pain syndromes and opioid use disorder, further complicating how we care for patients with psychiatric issues. We report a unique case of a de novo and persistent psychotic disorder after complicated opioid withdrawal in a patient without any psychiatric history. The patient developed persistent auditory hallucinations after discontinuation of chronic opioid therapy that responded only to atypical antipsychotic (olanzapine) treatment. This case illustrates the neuropsychiatric effects of chronic opioid exposure, as well as layered clinical management dimensions related to opioid detoxification and psychosis treatment. Long-term opioid therapy may have lasting neuropsychiatric effects, including playing a role in the development and/or expression of psychotic disorders. Here we review the limited literature on the effects of opioids on psychosis. This complex case also demonstrates a clinical approach for effectively co-managing psychiatric symptoms in the context of chronic pain and chronic opioid therapy.

Topics: Analgesics, Opioid; Antipsychotic Agents; Chronic Pain; Humans; Olanzapine; Psychotic Disorders

To evaluate the comparative efficacy, safety, tolerability, and effectiveness of atypical antipsychotics (AAPs) for the treatment of dementia related psychosis (DRP) in older adults.. In this systematic literature review (SLR), we qualitatively synthesized evidence on the comparative efficacy (based on neuropsychiatric inventory), tolerability (weight gain), and safety (cerebrovascular adverse events [CVAE], cardiovascular events, mortality, somnolence, extrapyramidal symptoms [EPS]) of AAPs used to treat DRP. We also assessed effectiveness based on all-cause discontinuations and discontinuations due to lack of efficacy or adverse events (AE). Published articles from through March 2021 from PubMed, EMBASE, PsycINFO, and Cochrane databases evaluated. We included double-blind, active-comparator/placebo-controlled randomized trials, open-label trials, and observational studies.. This qualitative synthesis included 51 eligible studies with sample size of 13,334 and mean age of 79.36 years. Risperidone, olanzapine, quetiapine, and aripiprazole demonstrated numerically small improvement in psychotic symptoms among patients with DRP. Somnolence was the most reported AE for all the AAPs, with weight gain and tardive dyskinesia more common with olanzapine and risperidone, respectively. These AAPs are associated with falls, EPS, cognitive declines, CVAE, and mortality. Aripiprazole and olanzapine had lower odds of discontinuation due to lack of efficacy, with olanzapine having greater discontinuation odds due to AEs.. This SLR demonstrated that AAPs used off-label to treat DRP are associated with small numerical symptom improvement but with a high risk of AEs, including cognitive decline and potentially higher mortality. These results underscore the need for new treatments with a favorable benefit-risk profile for treating DRP.

Topics: Antipsychotic Agents; Aripiprazole; Dementia; Humans; Olanzapine; Psychotic Disorders; Risperidone

Over the last ten years, the treatment of psychosis has seen a near explosion of creative development in both novel agents and new delivery modalities. The current review summarizes these developments over the past decade (2011-2020). We performed a systematic review utilizing PubMed and PsychInfo with the aim of identifying all the RCT and related analyses in adults with psychosis (schizophrenia and mania).. We identified 11 significant developments: the introduction of new antipsychotics cariprazine, brexpiprazole, lumateperone, and pimavanserin; introduction of new delivery methods: subcutaneous long-acting risperidone, aripiprazole lauroxil, transdermal asenapine, and inhaled loxapine; and the introduction of new approaches such as olanzapine/samidorphan for olanzapine-associated weight gain, examination of the TAAR1 agonist SEP 363,856 as a test of concept, and the combination of Xanomeline/Trospium, an M

Topics: Adult; Antipsychotic Agents; Humans; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia

This study aimed to compare the treatment effects of different antipsychotics for methamphetamine psychosis (MAP).. Clinical Trials, Cochrane Library, Pubmed, Scopus, and Web of Science were searched for short-term, randomized controlled trials (RCTs) from the inception to June 15, 2020. Standardized mean differences (SMDs) and odds ratios (ORs) were aggregated using random-effects pairwise comparisons and frequentist network meta-analyses (NMAs). Primary outcomes of interest were the main psychotic symptoms and dropout rates. We also rated the quality of NMA estimates.. This NMA included six RCTs of 395 patients with MAP. Six studied antipsychotics were aripiprazole, haloperidol, olanzapine, paliperidone extended-release, quetiapine, and risperidone. Risperidone is the most frequently studied antipsychotic, being investigated in four trials. Low quality of evidence was available to determine the efficacy of those antipsychotics for main psychotic symptoms. Aripiprazole was significantly inferior to olanzapine (SMD = 1.36, 95 % CI = 0.46-2.26), quetiapine (SMD = 1.13, 95 % CI = 0.28-1.98), haloperidol (SMD = 0.87, 95 % CI = 0.14-1.60), and paliperidone extended-release (SMD = 0.60, 95 % CI = 0.06-1.14). Olanzapine and quetiapine were superior to risperidone (SMD = -1.09, 95 % CI = -1.89 to -0.28 and SMD = -0.86, 95 % CI = -1.61 to -0.11, respectively). The dropout rates were not significantly different among the studied antipsychotics.. This analysis suggests that olanzapine or quetiapine may be a preferred antipsychotic for MAP, although the evidence for this was rated low-quality due to the high risk of bias or indirectness/intransitivity.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Haloperidol; Humans; Methamphetamine; Network Meta-Analysis; Olanzapine; Patient Dropouts; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

This study compared relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses.. The authors searched MEDLINE, Embase, PsycINFO, CINAHL, CENTRAL, and online registers for randomized controlled trials published until June 2020. Relative risks and standardized mean differences were pooled using random-effects pairwise and network meta-analysis. The primary outcomes were relapse rate and all-cause discontinuation ("acceptability"). The quality of included studies was rated with the Cochrane Risk of Bias tool, and the certainty of pooled estimates was measured with GRADE (Grading of Recommendations Assessment, Development, and Evaluation).. Of 86 eligible trials, 78 (N=11,505) were included in the meta-analysis. Regarding relapse prevention, most of the 12 LAIs included outperformed placebo. The largest point estimates and best rankings of LAIs compared with placebo were found for paliperidone (3-month formulation) and aripiprazole. Moderate to high GRADE certainty for superior relapse prevention compared with placebo was also found for (in descending ranking order) risperidone, pipothiazine, olanzapine, and paliperidone (1-month formulation). In head-to-head comparisons of LAIs, only haloperidol was inferior to aripiprazole, fluphenazine, and paliperidone. For acceptability, most LAIs outperformed placebo, with moderate to high GRADE certainty for (in descending ranking order) zuclopenthixol, aripiprazole, paliperidone (3-month formulation), olanzapine, flupenthixol, fluphenazine, and paliperidone (1-month formulation). In head-to-head comparisons, only LAI aripiprazole had superior acceptability to other LAIs (bromperidol, fluphenazine, paliperidone [1-month formulation], pipothiazine, and risperidone).. LAI formulations of paliperidone (3-month formulation), aripiprazole, olanzapine, and paliperidone (1-month formulation) showed the highest effect sizes and certainty of evidence for both relapse prevention and acceptability. Results from this network meta-analysis should inform frontline clinicians and guidelines.

Topics: Antipsychotic Agents; Aripiprazole; Clopenthixol; Delayed-Action Preparations; Flupenthixol; Fluphenazine; Haloperidol; Humans; Injections, Intramuscular; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Patient Acceptance of Health Care; Phenothiazines; Psychotic Disorders; Risperidone; Schizophrenia; Secondary Prevention

Psychotic episodes in the postpartum period are life-threatening psychiatric emergencies, requiring urgent medical attention and admission to a psychiatric hospital.. Although the postpartum psychosis (PPP) is the most severe psychiatric disorder associated with parturition, there is little information about what interventions are most effective. Because there are no specific guidelines for the treatment of PPP, the aim of the present review was to examine the available evidence regarding the treatment of PPP.. The PubMed database was searched based on the title and the abstract, using the key words "postpartum psychosis," "postpartum psychosis antipsychotics," "postpartum psychosis treatment," and "postpartum psychosis pharmacotherapy," for both interventional and observational, irrespective of language.. A number of 14 publications met the study criteria, including case reports and case series. The antipsychotics (APs) use included both first generation APs, such as haloperidol and chlorpromazine, and second generation APs, mainly, olanzapine, quetiapine, and risperidone. The most frequently used AP was olanzapine. Olanzapine and quetiapine seem to be the most acceptable during breastfeeding. Proposed treatment algorithms for the successful management of PPP are discussed.. The existing studies to date do not allow to draw a definitive conclusion regarding which treatment is the most effective or the most adequate. Existing evidence suggests that APs alone or in combination are responsible for sustained remission and that treated PPP has a higher pace of improvement of the mental status, with a rapid discharge from the hospital. Clinical studies to compare the efficacy and safety of different APs in the PPP are needed to provide guidance on treatment interventions.

Topics: Antipsychotic Agents; Benzodiazepines; Female; Humans; Olanzapine; Postpartum Period; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Disturbed eating behaviours have been widely reported in psychotic disorders since the early 19th century. There is also evidence that antipsychotic (AP) treatment may induce binge eating or other related compulsive eating behaviours. It is therefore possible that abnormal eating patterns may contribute to the significant weight gain and other metabolic disturbances observed in patients with psychosis. In this scoping review, we aimed to explore the underlying psychopathological and neurobiological mechanisms of disrupted eating behaviours in psychosis spectrum disorders and the role of APs in this relationship. A systematic search identified 35 studies that met our eligibility criteria and were included in our qualitative synthesis. Synthesizing evidence from self-report questionnaires and food surveys, we found that patients with psychosis exhibit increased appetite and craving for fatty food, as well as increased caloric intake and snacking, which may be associated with increased disinhibition. Limited evidence from neuroimaging studies suggested that AP-naïve first episode patients exhibit similar neural processing of food to healthy controls, while chronic AP exposure may lead to decreased activity in satiety areas and increased activity in areas associated with reward anticipation. Overall, this review supports the notion that AP use can lead to disturbed eating patterns in patients, which may contribute to AP-induced weight gain. However, intrinsic illness-related effects on eating behaviors remain less well elucidated, and many confounding factors as well as variability in study designs limits interpretation of existing literature in this field and precludes firm conclusions from being made.

Topics: Antipsychotic Agents; Appetite; Brain; Bulimia; Case-Control Studies; Clozapine; Craving; Diet Surveys; Energy Intake; Feeding Behavior; Food Preferences; Humans; Hunger; Neuroimaging; Olanzapine; Psychotic Disorders; Reward; Satiation; Self Report; Snacks; Weight Gain

Because women are often perceived as having better outcomes than men in psychotic illnesses such as schizophrenia - women are less often in hospital, have a lower suicide rate, are less often involved with the law, enjoy better relationships with family and friends - the question arises as to whether or not this apparent advantage is attributable to a gender difference in antipsychotic response.. The aim of this paper is to critically review the quantitative and qualitative literature on gender difference in antipsychotic response sourced mainly from medical databases of the last ten years.. There are theoretical reasons why women's effective doses of antipsychotics might need to be lower than guidelines recommend for men, especially as regards olanzapine and clozapine, but, because there are so many variables that impinge on antipsychotic response, it is difficult to provide definitive guidance. What is evident is that some antipsychotic side effects, weight gain for instance, are more worrisome for women than for men. It is also evident that, after menopause, women need an increase in their antipsychotic dose; other reproductive stages in women's lives require special prescribing considerations as well.. There is a science, and an art, to prescribing antipsychotics, which needs to take gender into account. This article is part of the issue entitled 'Special Issue on Antipsychotics'.

Topics: Antipsychotic Agents; Clozapine; Female; Humans; Male; Olanzapine; Psychoses, Substance-Induced; Psychotic Disorders; Risperidone; Schizophrenia; Sex Factors

Children and adolescents are a special group in the context of psychopharmacotherapy. Given the limited choice of registered antipsychotics permitted in childhood, caution should be exercised in the choice of medication. This literature review reviews the current evidence base for pharmacotherapy of acute psychotic episode and schizophrenia in children and adolescents. The results of major systematic reviews and meta-analyses are compared. Meta-analyses of pharmacotherapy studies of the first psychotic episode are considered separately. Antipsychotics of the first and second generation are comparable in effectiveness for children and adolescents with acute psychotic episode. Olanzapine demonstrates higher efficacy in reducing negative symptoms. Ziprasidone and asenapine are less effective in treating schizophrenia in children and adolescents than other antipsychotics. Compared to adults, children and adolescents are at higher risk of metabolic impairments when taking antipsychotics.. Дети и подростки - особый контингент в контексте применения психофармакотерапии. Учитывая ограниченный выбор зарегистрированных антипсихотиков, разрешенных к применению в детском возрасте, следует осторожно подходить к выбору препарата. В настоящем обзоре литературы рассмотрена современная доказательная база по фармакотерапии острого психотического эпизода и шизофрении у детей и подростков. Сопоставлены результаты крупных систематических обзоров и метаанализов. Отдельно были рассмотрены метаанализы исследований фармакотерапии первого психотического эпизода. Антипсихотики первой и второй генерации сопоставимы по эффективности у детей и подростков с острым психотическим эпизодом. Оланзапин демонстрирует более высокую эффективность по редукции негативной симптоматики. Зипрасидон и азенапин по сравнению с другими антипсихотиками менее эффективны при лечении шизофрении у детей и подростков. У детей и подростков отмечается бо`льшая склонность к метаболическим нарушениям при приеме антипсихотиков по сравнению со взрослыми.

Topics: Adolescent; Antipsychotic Agents; Child; Evidence-Based Medicine; Humans; Olanzapine; Psychotic Disorders; Schizophrenia

Non-pharmacological interventions preferably precede pharmacological interventions in acute agitation. Reviews of pharmacological interventions remain descriptive or compare only one compound with several other compounds. The goal of this study is to compute a systematic review and meta-analysis of the effect on restoring calmness after a pharmacological intervention, so a more precise recommendation is possible.. A search in Pubmed and Embase was done to isolate RCT's considering pharmacological interventions in acute agitation. The outcome is reaching calmness within maximum of 2 h, assessed by the psychometric scales of PANSS-EC, CGI or ACES. Also the percentages of adverse effects was assessed.. Fifty-three papers were included for a systematic review and meta-analysis. Most frequent studied drug is olanzapine. Changes on PANNS-EC and ACES at 2 h showed the strongest changes for haloperidol plus promethazine, risperidon, olanzapine, droperidol and aripiprazole. However, incomplete data showed that the effect of risperidon is overestimated. Adverse effects are most prominent for haloperidol and haloperidol plus lorazepam.. Olanzapine, haloperidol plus promethazine or droperidol are most effective and safe for use as rapid tranquilisation. Midazolam sedates most quickly. But due to increased saturation problems, midazolam is restricted to use within an emergency department of a general hospital.

Topics: Aggression; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Hypnotics and Sedatives; Lorazepam; Midazolam; Olanzapine; Promethazine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome

To compare the efficacy and safety of olanzapine and risperidone in children and adolescents (aged ≤18 years) with psychosis by conducting a meta-analysis of randomized controlled trials (RCTs).. Several English and Chinese databases were searched for studies published before February 8th, 2017. Two independent investigators screened the studies according to prespecified criteria and extracted the data. Review Manager 5.3 was used to conduct the data synthesis.. Eight RCTs involving 457 participants (225 participants in the olanzapine group and 232 participants in the risperidone group) were included. No significant differences were observed in the mean scores on the Positive and Negative Syndrome Scale/Brief Psychiatric Rating Scale (standard mean difference [SMD] = -0.06, 95% confidence intervals [CI] = [-0.31, 0.19], p = 0.63), the positive symptom scores (SMD = -0.09, 95% CI = [-0.32, 0.15], p = 0.48), or the negative symptom scores (SMD = -0.11 95% CI = [-0.34, 0.13], p = 0.38) between the two groups. Regarding adverse effects, the mean increases in weight (MD = 2.90, 95% CI = [1.41, 4.39], p = 0.0001), body mass index (MD = 0.90, 95% CI = [0.42, 1.38], p = 0.0003), and incidence of hypersomnia (risk ratios [RR] = 1.98, 95% CI = [1.15, 3.43], p = 0.01) were higher in the olanzapine group, while the incidence of insomnia (RR = 0.31, 95% CI = [0.11, 0.85], p = 0.02), prolactin elevation (RR = 0.11, 95% CI = [0.01, 0.85], p = 0.03), myotonia (RR = 0.12, 95% CI = [0.03, 0.49], p = 0.003), tremor (RR = 0.22, 95% CI = [0.08, 0.63], p = 0.005), and akathisia (RR = 0.27, 95% CI = [0.12, 0.57], p = 0.0007) was higher in the risperidone group.. There is no significant difference in efficacy between olanzapine and risperidone for the treatment of children and adolescents with psychosis, but the side effect profiles of these two medications differ. High-quality RCTs are needed before recommending clinical treatment in children and adolescents.

Topics: Adolescent; Antipsychotic Agents; Child; Humans; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

A plethora of data deriving from single studies as well as meta-analyses demonstrates that weight gain is associated with the exposure to the majority of antipsychotics (AP). However, potential sex differences have widely evaded the attention of AP treatment trials. It is hypothesised that female patients gain more weight compared with male patients due to their enhanced susceptibility to adverse drug reactions.. A meta-analysis was conducted using clinical trials of AP that reported weight change separately for female and male patients. Duration of AP use was stratified in four categories: <6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots were generated for men and women separately, stratified by AP as well as by duration of use. Sex differences were tested by performing meta-regression.. Data of 26 studies were used in the present analysis because sufficient data were available only for olanzapine, risperidone and the no-medication group. Both female and male patients showed considerable weight gain after switch or initiate of olanzapine or risperidone, but meta-regression analyses did not show significant sex differences.. The present meta-analysis revealed that sex differences in AP-related weight gain have been under investigated hampering the detection of sex-specific patterns. In chronic patients switching to olanzapine or risperidone receiving short-or middle-term treatment, AP were associated with weight gain in both sex subgroups and no significant differences were reported.

Topics: Adult; Aged; Antipsychotic Agents; Body Mass Index; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Risperidone; Weight Gain

Switching between different antipsychotic therapies is a frequent occurrence in the management of patients with schizophrenia and other psychotic disorders. This paper provides a review of the principles of antipsychotic switching and discusses pharmacological principles underlying adverse events that occur while switching olanzapine to another antipsychotic medication. It offers suggestions for management of switch-associated adverse events in clinical settings.. Few publications explore olanzapine switch-related adverse events, the underlying pharmacological principles and appropriate switching strategies to minimise the risk of adverse events. There is still a need for further studies to verify existing knowledge and assist in the development of 'gold standard' guidelines that outline appropriate switching strategies and duration of the switching process to reduce and avoid adverse events.

Topics: Antipsychotic Agents; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Humans; Olanzapine; Psychotic Disorders; Schizophrenia

To summarize and evaluate the existing literature regarding medications to treat Parkinson's disease (PD) psychosis.. MEDLINE (1946 to March 2017), EMBASE (1980 to March 2017), CINAHL (1982 to March 2017), and PsychInfo (1887 to March 2017) were searched using the following terms: Parkinson disease, Parkinson's disease, psychotic disorders, psychosis, delusions, and hallucinations.. The search was limited to randomized controlled trials (RCTs) reporting human outcomes. Data extracted included the following: study design, population, setting, intervention, control, outcomes related to psychosis and safety, and potential biases assessed using Cochrane Collaboration's Risk of Bias Assessment Tool.. After assessment, 16 of 235 studies were included; 11 articles reported comparisons between active drug and placebo, whereas 5 compared clozapine and an active comparator. Placebo-controlled trials demonstrated benefit for clozapine (n = 2) and pimavanserin (n = 2), with no firm benefits observed for quetiapine (n = 4) or olanzapine (n = 3). Comparative studies demonstrated improved efficacy in symptom scores when clozapine or comparator agent (n = 2, quetiapine; n = 1, olanzapine; n = 1, risperidone; and n = 1, ziprasidone) was assessed alone. However, no comparator data suggest that one agent is better than another, and none are yet available for pimavanserin. Overall risk of bias across all studies was moderate to high.. Despite lack of rigor in study designs, published data to date suggest that clozapine and pimavanserin should be considered drugs of choice to treat PD psychosis.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Piperazines; Piperidines; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; Urea

Second generation antipsychotics (SGAs) are associated with metabolic disturbances. Diabetic ketoacidosis (DKA) is a rare, but potentially fatal sign of acute glucose metabolism dysregulation linked to the use of SGAs. The aims of this article are to present patients with a history of psychotic disorders and of severe metabolic diabetic ketoacidosis, possibly associated with the use of antipsychotics, and to review the current literature on the topic of antipsychotic-induced DKA.. PubMed/Medline and EBSCO databases were searched using the keywords: diabetic ketoacidosis, antipsychotics, atypical antipsychotics, second generation antipsychotics, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, paliperidone, amisulpride and haloperidol. Case reports, case series and reviews of case series were included in the review.. The majority of patients who developed DKA following treatment with antipsychotics were treated with olanzapine and clozapine in monotherapy or in combination with other antipsychotics. DKA mostly occurred in the first six months of antipsychotic treatment. Other risk factors included insulin resistance prior to antipsychotic treatment, male gender and middle age.. Clinicians should consider the risk of DKA when starting treatment with SGAs. Preventive measures for patients with psychotic disorders using antipsychotics should include regular assessment of risk factors and screening for diabetes before and after administering antipsychotics, especially in the first months of treatment. Whenever possible, polypharmacy should be avoided.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Clozapine; Diabetic Ketoacidosis; Drug Therapy, Combination; Female; Haloperidol; Humans; Insulin; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Young Adult

Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Behavior Therapy; Benzodiazepines; Cognitive Behavioral Therapy; Dementia; Emotions; Humans; Hypotension, Orthostatic; Metabolic Syndrome; Neuroleptic Malignant Syndrome; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Psychotic disorders can lead some people to become agitated. Characterised by restlessness, excitability and irritability, this can result in verbal and physically aggressive behaviour - and both can be prolonged. Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users; it is a frequent cause for admission to inpatient facilities. If people continue to be aggressive it can lengthen hospitalisation. Haloperidol is used to treat people with long-term aggression.. To examine whether haloperidol alone, administered orally, intramuscularly or intravenously, is an effective treatment for long-term/persistent aggression in psychosis.. We searched the Cochrane Schizophrenia Group Trials Register (July 2011 and April 2015).. We included randomised controlled trials (RCT) or double blind trials (implying randomisation) with useable data comparing haloperidol with another drug or placebo for people with psychosis and long-term/persistent aggression.. One review author (AK) extracted data. For dichotomous data, one review author (AK) calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a fixed-effect model. One review author (AK) assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.. We have no good-quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression. One study randomising 110 chronically aggressive people to three different antipsychotic drugs met the inclusion criteria. When haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for 'total aggression'. Data were available for only one other outcome, leaving the study early. When compared with other antipsychotic drugs, people allocated to haloperidol were no more likely to leave the study (1 RCT, n=110, RR 1.37, CI 0.84 to 2.24, low-quality evidence). Although there were some data for the outcomes listed above, there were no data on most of the binary outcomes and none on service outcomes (use of hospital/police), satisfaction with treatment, acceptance of treatment, quality of life or economics.. Only one study could be included and most data were heavily skewed, almost impossible to interpret and oflow quality. There were also some limitations in the study design with unclear description of allocation concealment and high risk of bias for selective reporting, so no firm conclusions can be made. This review shows how trials in this group of people are possible - albeit difficult. Further relevant trials are needed to evaluate use of haloperidol in treatment of long-term/persistent aggression in people living with psychosis.

Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Haloperidol; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia

People experiencing acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone antipsychotic, has been used for this purpose in several countries.. To estimate the effects of droperidol, including its cost-effectiveness, when compared to placebo, other 'standard' or 'non-standard' treatments, or other forms of management of psychotic illness, in controlling acutely disturbed behaviour and reducing psychotic symptoms in people with schizophrenia-like illnesses.. We updated previous searches by searching the Cochrane Schizophrenia Group Register (18 December 2015). We searched references of all identified studies for further trial citations and contacted authors of trials. We supplemented these electronic searches by handsearching reference lists and contacting both the pharmaceutical industry and relevant authors.. We included all randomised controlled trials (RCTs) with useable data that compared droperidol to any other treatment for people acutely ill with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode.. For included studies, we assessed quality, risk of bias and extracted data. We excluded data when more than 50% of participants were lost to follow-up. For binary outcomes, we calculated standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI). We created a 'Summary of findings' table using GRADE.. We identified four relevant trials from the update search (previous version of this review included only two trials). When droperidol was compared with placebo, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 227, RR 1.18, 95% CI 1.05 to 1.31, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for the droperidol group (1 RCT, N = 227, RR 0.55, 95% CI 0.36 to 0.85, high-quality evidence). There was no evidence that droperidol caused more cardiovascular arrhythmia (1 RCT, N = 227, RR 0.34, 95% CI 0.01 to 8.31, moderate-quality evidence) and respiratory airway obstruction (1 RCT, N = 227, RR 0.62, 95% CI 0.15 to 2.52, low-quality evidence) than placebo. For 'being ready for discharge', there was no clear difference between groups (1 RCT, N = 227, RR 1.16, 95% CI 0.90 to 1.48, high-quality evidence). There were no data for mental state and costs.Similarly, when droperidol was compared to haloperidol, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 228, RR 1.01, 95% CI 0.93 to 1.09, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for participants in the droperidol group (2 RCTs, N = 255, RR 0.37, 95% CI 0.16 to 0.90, high-quality evidence). There was no evidence that droperidol caused more cardiovascular hypotension (1 RCT, N = 228, RR 2.80, 95% CI 0.30 to 26.49,moderate-quality evidence) and cardiovascular hypotension/desaturation (1 RCT, N = 228, RR 2.80, 95% CI 0.12 to 67.98, low-quality evidence) than haloperidol. There was no suggestion that use of droperidol was unsafe. For mental state, there was no evidence of clear difference between the efficacy of droperidol compared to haloperidol (Scale for Quantification of Psychotic Symptom Severity, 1 RCT, N = 40, mean difference (MD) 0.11, 95% CI -0.07 to 0.29, low-quality evidence). There were no data for service use and costs.Whereas, when droperidol was compared with midazolam, for the outcome of tranquillisation or asleep by 30 minutes we found droperidol to be less acutely tranquillising than midazolam (1 RCT, N = 153, RR 0.96, 95% CI 0.72 to 1.28, high-quality evidence). As regards the 'need for additional medication by 60 minutes after initial adequate sedation, we found an effect (1 RCT, N = 153, RR 0.54, 95% CI 0.24 to 1.20, moderate. Previously, the use of droperidol was justified based on experience rather than evidence from well-conducted and reported randomised trials. However, this update found high-quality evidence with minimal risk of bias to support the use of droperidol for acute psychosis. Also, we found no evidence to suggest that droperidol should not be a treatment option for people acutely ill and disturbed because of serious mental illnesses.

Topics: Acute Disease; Aggression; Antipsychotic Agents; Benzodiazepines; Droperidol; Haloperidol; Humans; Midazolam; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic

Most of the 13 542 trials contained in the Cochrane Schizophrenia Group's register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered. For example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia.. We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial.. We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode patients are treated with amisulpride for 4 weeks, followed by a 6-week double-blind RCT comparing continuation of amisulpride with switching to olanzapine and ultimately a 12-week clozapine treatment in nonremitters. A subsequent 1-year RCT validates psychosocial interventions to enhance adherence.. Current literature fails to provide basic guidance for the pharmacological treatment of schizophrenia. The OPTiMiSE trial is expected to provide a basis for clinical guidelines to treat patients with a first episode of schizophrenia.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clinical Trials, Phase III as Topic; Disease Management; Europe; Humans; Multicenter Studies as Topic; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Sulpiride

This is an updated version of the original Cochrane review published in Issue 4, 2008.People suffering from epilepsy have an increased risk of experiencing psychotic symptoms. The psychotic syndromes associated with epilepsy have generally been classified as ictal, postictal, and interictal psychosis. Anticonvulsant drugs have been reported to precipitate psychosis. Moreover, all antipsychotic drugs have the propensity to cause paroxysmal electroencephalogram abnormalities and induce seizures.. To evaluate the benefits of interventions used to treat clinically significant psychotic symptoms occurring in people with epilepsy with regard to global improvement, changes in mental state, hospitalization, behavior, quality of life, effect on the frequency of seizures, and interaction with antiepileptic drugs.. We searched the Cochrane Epilepsy Group's Specialized Register (23 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies Online (CRSO), 23 March 2015), MEDLINE (Ovid, 1946 to 23 March 2015), PsycINFO (1887 to 23 March 2015), CINAHL (1937 to 23 March 2015), and BIOSIS Previews (1969 to 23 March 2015).Two review authors (SF and AS) independently inspected the citations identified from the search. We identified potentially relevant abstracts and assessed full papers for inclusion and methodological quality.. All randomized controlled trials comparing drugs, behavior therapy, cognitive behavior therapy, or other non-pharmacological interventions used to relieve psychotic symptoms in people with epilepsy.. We planned to extract and analyze the data from all relevant studies using standardized methods. As only one study met the inclusion criteria, we attempted no meta-analysis.. After independently assessing the abstracts and titles of 618 articles, we selected five relevant abstracts. Ultimately we found only one study meeting the inclusion criteria, which was available only as an abstract. This study compared the use of olanzapine (10 mg/day) with haloperidol (12 mg/day) in 16 people suffering from schizophrenia-like psychosis of epilepsy. Thirteen participants completed the study. Significant improvement was associated with use of olanzapine. We did not identify any study on psychosocial interventions in people suffering from epilepsy and psychosis.. We found only one randomized controlled trial, which lacked the power to test the efficacy of antipsychotics in those suffering from psychosis concomitant with epilepsy.Limited evidence from this small randomized controlled trial suggests an improvement in psychotic symptoms, but not other outcome measures, with the use of an antipsychotic. The effects on seizure control are not well studied. Further trials are required to inform practice.

Topics: Antipsychotic Agents; Benzodiazepines; Epilepsy; Humans; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic

Insufficient treatment of psychosis often manifests as violent and aggressive behaviors that are dangerous to the patient and others, and that warrant treatment strategies which are not considered first-line, evidence-based practices. Such treatment strategies include both antipsychotic polypharmacy (simultaneous use of 2 antipsychotics) and high-dose antipsychotic monotherapy. Here we discuss the hypothesized neurobiological substrates of various types of violence and aggression, as well as providing arguments for the use of antipsychotic polypharmacy and high-dose monotherapy to target dysfunctional neurocircuitry in the subpopulation of patients that is treatment-resistant, violent, and aggressive. In this review, we focus primarily on the data supporting the use of second-generation, atypical antipsychotics both at high doses and in combination with other antipsychotics.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain; Clozapine; Dibenzocycloheptenes; Drug Therapy, Combination; Heterocyclic Compounds, 4 or More Rings; Humans; Impulsive Behavior; Isoxazoles; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Piperidines; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Risperidone; Thiazoles; Violence

Acute psychotic illness, especially when associated with agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome.. To estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared with placebo or antipsychotics, alone or in combination with antihistamines, to control disturbed behaviour and reduce psychotic symptoms.. We searched the Cochrane Schizophrenia Group's register (January 2012), inspected reference lists of included and excluded studies and contacted authors of relevant studies.. We included all randomised clinical trials (RCTs) comparing benzodiazepines alone or in combination with any antipsychotics, versus antipsychotics alone or in combination with any other antipsychotics, benzodiazepines or antihistamines, for people with acute psychotic illnesses.. We reliably selected studies, quality assessed them and extracted data. For binary outcomes, we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI) using a fixed-effect model. For continuous outcomes, we calculated the mean difference (MD) between groups. If heterogeneity was identified, this was explored using a random-effects model.. We included 21 trials with a total of n = 1968 participants. There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo, although there was a higher risk of no improvement in people receiving placebo in the medium term (one to 48 hours) (n = 102, 1 RCT, RR 0.62, 95% CI 0.40 to 0.97, very low quality evidence). There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics (n = 308, 5 RCTs, RR 1.10, 95% CI 0.85 to 1.42, low quality evidence); however, people receiving benzodiazepines were less likely to experience extrapyramidal effects (EPS) in the medium term (n = 536, 8 RCTs, RR 0.15, 95% CI 0.06 to 0.39, moderate quality of evidence). Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results. When comparing combined benzodiazepines/antipsychotics (all studies compared haloperidol) with the same antipsychotics alone (haloperidol), there was no difference between groups in improvement in the medium term (n = 155, 3 RCTs, RR 1.27, 95% CI 0.94 to 1.70, very low quality evidence) but sedation was more likely in people who received the combination therapy (n = 172, 3 RCTs, RR 1.75, 95% CI 1.14 to 2.67, very low quality evidence). However, more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine (n = 60,1 RCT, RR 25.00, 95% CI 1.55 to 403.99, very low quality evidence) or ziprasidone (n = 60, 1 RCT, RR 4.00, 95% CI 1.25 to 12.75 very low quality evidence). When haloperidol and midazolam were compared with olanzapine, there was some evidence the combination was superior in terms of improvement, sedation and behaviour.. The evidence from trials for the use of benzodiazepines alone is not good. There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects. Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects. Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify. Much more high quality research is needed in this area.

Topics: Acute Disease; Aggression; Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Emergency Treatment; Haloperidol; Humans; Lorazepam; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic

When treating schizophrenia and other psychotic disorders, clinicians often encounter the problems of non-adherence, which is almost the most common drawback of achieving remission and a better quality of life. The uncertain oral drug taking habits may lead to relapses and rehospitalizations. Using second generation long acting injectables we have more possibilities to avoid these problems. This review attempts to present and describe the pharmacological background of the modern long acting injectables including patient cases where olanzapine pamoate long acting injectable provided remission and better quality of life for the patients.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Female; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Medication Adherence; Middle Aged; Olanzapine; Psychotic Disorders; Recurrence; Schizophrenia; Schizophrenic Psychology

Schizophrenia often presents in adolescence, but current treatment guidelines are based largely on studies of adults with psychosis. Over the past decade, the number of studies on treatment of adolescent-onset psychosis has increased. The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis.. To investigate the effects of atypical antipsychotic medications in adolescents with psychosis. We reviewed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose.. We searched the Cochrane Schizophrenia Group Register (October 2011), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies and contacted study authors and relevant pharmaceutical companies to ask for more information.. We included all relevant randomised controlled trials (RCTs) that compared atypical antipsychotic medication with placebo or another pharmacological intervention or with psychosocial interventions, standard psychiatric treatment or no intervention in children and young people aged 13 to 18 years with a diagnosis of schizophrenia, schizoaffective disorder, acute and transient psychoses or unspecified psychosis. We included studies published in English and in other languages that were available in standardised databases.. Review authors AK and SSD selected the studies, rated the quality of the studies and performed data extraction. For dichotomous data, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model. When possible, for binary data presented in the 'Summary of findings' table, we calculated illustrative comparative risks. We summated continuous data using the mean difference (MD). Risk of bias was assessed for included studies.. We included 13 RCTs, with a total of 1112 participants. We found no data on service utilisation, economic outcomes, behaviour or cognitive response. Trials were classified into the following groups. 1. Atypical antipsychotics versus placebo: Only two studies compared one atypical antipsychotic medication with placebo. In one study, the number of non-responders treated with olanzapine was not different from the number treated with placebo (1 RCT, n = 107, RR 0.84, 95% CI 0.65 to 1.10); however, significantly more (57% vs 32%) people left the study early (1 RCT, n = 107, RR 0.56, 95% CI 0.36 to 0.87) from the placebo group compared with the olanzapine group. With regard to adverse effects, young people treated with aripiprazole had significantly lower serum cholesterol compared with those given placebo (1 RCT, n = 302, RR 3.77, 95% CI 1.88 to 7.58). 2. Atypical antipsychotics versus typical antipsychotics: When the findings of all five trials comparing atypical antipsychotic medications with a typical antipsychotic medication were collated, no difference in the mean end point Brief Psychiatric Rating Scale (BPRS) score was noted between the two arms (5 RCTs, n = 236, MD -1.08, 95% CI -3.08 to 0.93). With regard to adverse effects, the mean end point serum prolactin concentration was much higher than the reference range for treatment with risperidone, olanzapine and molindone in one of the studies. However, fewer adolescents who were receiving atypical antipsychotic medications left the study because of adverse effects (3 RCTs, n = 187, RR 0.65, 95% CI 0.36 to 1.15) or for any reason (3 RCTs, n = 187, RR 0.62, 95% CI 0.39 to 0.97).3. One atypical antipsychotic versus another atypical antipsychotic: The mean end point BPRS score was not significantly different for people who received risperidone compared with those who received olanzapine; however, the above data were highly skewed. Overall no difference was noted in the number of people leaving the studies early because of any adverse effects between each study arm in the three studies comparing olanzapine and risperidone (3 RCTs, n = 130, RR 1.15, 95% CI 0.44 to 3.04). Specific adverse events were not reported uniformly across the six different studies included in this section of the review; therefore it was difficult to do a head-to-head comparison of adverse events for different atypical antipsychotic medications.4. Lower-dose atypical antipsychotic versus standard/higher-dose atypical antipsychotic: Thre. No convincing evidence suggests that atypical antipsychotic medications are superior to typical medications for the treatment of adolescents with psychosis. However, atypical antipsychotic medications may be more acceptable to young people because fewer symptomatic adverse effects are seen in the short term. Little evidence is available to support the superiority of one atypical antipsychotic medication over another, but side effect profiles are different for different medications. Treatment with olanzapine, risperidone and clozapine is often associated with weight gain. Aripiprazole is not associated with increased prolactin or with dyslipidaemia. Adolescents may respond better to standard-dose as opposed to lower-dose risperidone, but for aripiprazole and ziprasidone, lower doses may be equally effective. Future trials should ensure uniform ways of reporting.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Molindone; Olanzapine; Piperazines; Psychotic Disorders; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Weight gain as a result of atypical anti-psychotic treatment is a common issue with different atypical anti-psychotic treatments causing differing magnitudes of weight gain. Although differing amounts of weight gain result from different atypical agents little is known about the temporal course of weight gain in anti-psychotic treatment. Specifically is the time course of weight gain comparable across different agents. Therefore this article reviews the temporal course of weight gain for three common atypical anti-psychotics namely; clozapine, olanzapine and risperidone. It is evident that all three of these agents exhibit similar although at distinct magnitudes temporal courses of weight gain. That is an initial rapid increase from baseline to 3 months (stage 1), a steady increase from 3 months to 18 months (stage 2) and a plateau after this point (stage 3) with continued anti-psychotic treatment. It is postulated that each of these stages of weight gain result from distinct neural mechanisms. The hypothesized neural correlates for each stage of weight gain are reviewed and discussed. The article concludes with recommendations for future research.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Nervous System Physiological Phenomena; Olanzapine; Psychotic Disorders; Risperidone; Time Factors; Weight Gain

In The Netherlands, no guidelines exist for rapid tranquillisation in the context of acute agitation, excitement or aggression secondary to a psychiatric disorder.. To generate an overview of medication regimes suitable for rapid tranquillisation.. A literature search was conducted focussing on the effect of medical interventions in acute excitement, agitation or aggression. Primary outcome measurements were tranquillity, being calm, sedation, or asleep within two hours. Secondary outcome measures were frequency of re-administration and adverse side effects.. Haloperidol appears as effective as lorazepam; haloperidol in combination with lorazepam does not have added value to lorazepam or haloperidol alone. Dehydrobenzperidol, risperidone, olanzapine and aripiprazole are comparable in effectiveness to lorazepam or haloperidol. Haloperidol in combination with promethazine is associated with a more rapid onset of effect than lorazepam, haloperidol or olanzapine. Midazolam is faster than the combination of haloperidol and promethazine, but requires more frequent re-administration of medication and increases the risk for respiratory depression. The literature on quetiapine was insufficient. The level of evidence, however, is modest.. Haloperidol in combination with promethazine, and olanzapine, are effective in psychotic agitation, although haloperidol plus promethazine has a more rapid onset of effect faster; lorazepam is effective in non-psychotic agitation, aggression or excitement as well as in acute agitation of unknown origin.

Topics: Aggression; Benzodiazepines; Conscious Sedation; Drug Therapy, Combination; Haloperidol; Humans; Hypnotics and Sedatives; Lorazepam; Midazolam; Olanzapine; Practice Guidelines as Topic; Promethazine; Psychotic Disorders; Time Factors; Treatment Outcome

Parkinson's disease (PD) patients often develop psychotic symptoms that severely affect quality of life and limit the use of medications to ameliorate motor symptoms. Psychotic symptoms are a major cause for nursing home placement. While these symptoms do not always require treatment, they often do but antipsychotic drugs all share the common pharmacological mechanism of blocking dopamine D2 receptors which may worsen motor problems in this very vulnerable population. Double blind, placebo controlled trials (DBPCT) have shown that clozapine is effective at controlling the psychotic symptoms at doses far below those used in schizophrenia, without worsening motor function, even improving tremor. DBPCT have demonstrated that olanzapine worsens motor function without improving psychosis. Quetiapine has been shown in DBPCT to be free of motor side effects in PD patients but not effective, whereas many open label studies have indicated that quetiapine is effective. The other atypical have been the subjects of conflicting open label reports. The effects of the atypicals in PD psychosis is reviewed.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Evidence-Based Medicine; Humans; Olanzapine; Parkinson Disease; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Our aim in this article is 2-fold: first, to examine the mid-term to long-term data on efficacy, from controlled and naturalistic and other studies, in order to determine if they are consistent with the quantitative meta-analyses of mostly short-term, randomized controlled trials Our second (and most important) aim is to use these and other data to provide guidance about the potential relationship of these differences among antipsychotics to the individual patient's own experience with antipsychotic drugs in the process of shared decision-making with the patients and their significant others.. A search of PubMed, Embase, and PsychINFO was conducted for articles published in English between January 1, 1999, and April 2011, using the search terms double-blind AND randomized AND olanzapine AND (ziprasidone OR risperidone OR quetiapine OR haloperidol OR fluphenazine OR perphenazine OR aripiprazole).. Studies with a duration 3 months or longer, including patients with schizophrenia or schizoaffective disorder, reporting survival analysis for all-cause discontinuation and relapse or dropout due to poor efficacy were selected.. We extracted the number of patients relapsed due to poor efficacy and hazard rates for relapses.. Overall, the efficacy patterns of both controlled effectiveness and observational long-term studies closely parallel the efficacy observed in the short-term, controlled studies. The results of Phase 1 Clinical Antipsychotic Trials of Intervention Effectiveness are very similar to, but not identical with, the controlled short-term efficacy studies, the European First-Episode Schizophrenia Trial, and naturalistic studies. The mid-term and long-term data suggest that olanzapine is more effective than risperidone and that both of these are better than the other first- and second-generation antipsychotics except for clozapine, which is the most efficacious of all. Further large differences emerged regarding the specific mid-term and long-term safety profiles of individual antipsychotics.. Despite intraclass differences and the complexities of antipsychotic choice, the second-generation antipsychotics are important contributions not only to the acute phase but, more importantly, to the maintenance treatment of schizophrenia.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Combined Modality Therapy; Humans; Olanzapine; Patient Participation; Psychotherapy; Psychotic Disorders; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Time Factors; Treatment Outcome

The objective of this article is to assess the clinical characteristics of akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder receiving aripiprazole, haloperidol, olanzapine, or placebo. We conducted post hoc analyses of pooled safety data from trials in patients with schizophrenia, schizoaffective disorder, and bipolar I disorder. Outcome measures included the incidence of akathisia, time to onset, duration, severity, and discontinuation due to akathisia, concomitant use of benzodiazepines and/or anticholinergics, Barnes Akathisia Rating Scale (BARS) scores, and the correlation between antipsychotic efficacy and akathisia. The results for schizophrenia and schizoaffective disorder were as follows: akathisia in 9% of aripiprazole- and 6% of placebo-treated patients; 12.5% of aripiprazole- versus 24% of haloperidol-treated patients; 11% of aripiprazole- versus 6% of olanzapine-treated patients. Bipolar I disorder: akathisia in 18% of aripiprazole- and 5% of placebo-treated patients. The clinical characteristics of akathisia were similar between each data set, regardless of disease. Akathisia was generally mild-to-moderate in severity. Discontinuation due to akathisia was low in both the schizophrenia trials (aripiprazole 0.3%; placebo 0%; aripiprazole 0.9%; haloperidol 2.3%; aripiprazole 1.2%; olanzapine 0.2%) and the bipolar trials (aripiprazole 2.3%; placebo 0%). Treatment-emergent akathisia was not associated with a poorer clinical response. In conclusion, akathisia with aripiprazole occurred early in treatment, was mild-to-moderate in severity, led to few study discontinuations, and did not compromise therapeutic efficacy.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Haloperidol; Humans; Hypnotics and Sedatives; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Quinolones; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To examine the pharmacokinetic implications and potential clinical effects of tobacco smoking cessation in patients on stable clozapine or olanzapine treatment.. A literature search of MEDLINE (1950-November 2009) and EMBASE (1980-November 2009) was conducted using the search terms smoking, tobacco, cigarette, cannabis, smoking cessation, cytochrome P450, antipsychotic, clozapine, and olanzapine. In addition, reference lists from publications identified were searched manually.. English-language articles and human studies were identified, yielding 111 returns. Articles that reported clinical outcomes following smoking cessation were selected. Pharmacokinetic data for these drugs were reviewed and articles that provided relevant background information were also included.. Pharmacokinetic studies have demonstrated more rapid clearance of olanzapine and lower clozapine and norclozapine (desmethylclozapine) concentrations in smokers compared to nonsmokers. These studies also found that smokers require higher doses of these agents than nonsmokers. There are case reports of adverse clinical outcomes following smoking cessation in patients being treated with olanzapine and clozapine. Reports that included serum concentrations consistently found elevations following smoking cessation, and dosage reductions of 30-40% were required to achieve pre-cessation concentrations. Worsening psychiatric symptoms, somnolence, hypersalivation, extreme fatigue, extrapyramidal effects, and seizures have all been reported following smoking cessation in this patient group.. Pharmacists need to be aware of potential risks associated with smoking cessation in patients stabilized on clozapine or olanzapine. Toxicity as a result of recent smoking reduction or cessation may be a reason for hospital admission. For hospitalized patients, pharmacists should obtain information concerning smoking status, including cessation attempts. Nonspecific signs and symptoms of elevated clozapine or olanzapine concentrations should be considered in relation to clinical status while the patient is hospitalized. Measurement of baseline serum clozapine concentrations and/or empiric dosage adjustment in patients expected to have a prolonged hospital stay with forced smoking cessation may be appropriate.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia, Paranoid; Smoking Cessation

Women who are pregnant and who have a history of psychosis are commonly managed with antipsychotic medications. The evidence regarding the use of antipsychotics in pregnancy has been insufficient to provide adequate support for this practice and is a concern for clinicians and women alike. This review presents literature surrounding the use of antipsychotic medications in pregnancy, providing an overview of the historical and contemporary perspectives which influence clinicians prescribing practices. Data were sourced from Medline, CINAHL, PsycINFo, using the terms antipsychotics with pregnancy and psychosis or schizophrenia. This was expanded to include the most common atypical antipsychotics: olanzapine, risperidone, clozapine, quetiapine, ziprasidone and aripiprazole. Literature was found reporting the use of antipsychotic medications in pregnancy since the introduction of antipsychotics in the 1950s, comprising mainly of authors' reviews of the literature, case studies, retrospective reports, drug company registries and more recently a prospective comparative study. This review identifies that the literature provides no clear answer for clinicians as to the risk associated with the use of antipsychotics in pregnancy. To this effect, recently in Australia, the National Register of Antipsychotic Medications in Pregnancy was established to prospectively collect information regarding outcomes for mother and baby, when antipsychotic medications have been used during pregnancy.

Topics: Abnormalities, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Diabetes, Gestational; Dibenzothiazepines; Female; Humans; Infant, Newborn; Olanzapine; Piperazines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

Metabolic syndrome and cardiovascular diseases are important causes of morbidity and mortality among patients with severe mental illnesses. Atypical or second-generation antipsychotics (SGAs) are associated with obesity and other components of metabolic syndrome, particularly abnormal glucose and lipid metabolism. This review aims to provide a summary of recent evidence on metabolic risks associated with SGAs, current recommendations for metabolic monitoring, and efficacy of treatment options currently available.. Studies have identified younger, antipsychotic-naive patients with first-episode psychosis as a population vulnerable to adverse metabolic effects from SGAs. These patients gained more weight and developed evident lipid and glucose abnormalities as soon as 8-12 weeks after treatment initiation. Findings are more striking among children and adolescents. The differential effects of various SGAs are well described, with clozapine and olanzapine associated with the highest metabolic risk. In addition to behavioral therapy, emerging data suggest that pharmacological therapy, most notably metformin, is efficacious in the treatment and possibly prevention of SGA-associated metabolic derangements.. More data have become available on the burden from metabolic complications associated with SGAs. New and effective treatment options are required in the near future to improve cardiovascular health in this susceptible population.

Topics: Antipsychotic Agents; Benzodiazepines; Cardiovascular Diseases; Clozapine; Humans; Metabolic Syndrome; Metformin; Obesity; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Severity of Illness Index; Weight Gain

As an extension of the early intervention in psychosis paradigm, different focused treatments are now offered to individuals at ultra high risk of psychosis (UHR) to prevent transition to schizophrenia, however the effectiveness of these treatments is unclear. A systematic literature search in PubMed/Medline and PsycINFO was performed to derive information on randomized control trials (RCTs) in UHR samples. Seven reports were identified detailing results from five independent RCT studies. Two studies used antipsychotic drugs (one in combination with cognitive behavior therapy); one study employed cognitive therapy; one study used a two-year program of intensive community care with family psychoeducation; one study assessed the effectiveness of 3-months omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) supplementation. Intensive community care and the Omega-3 PUFAs supplementation were effective in reducing the transition to psychosis at 12 months. Overall, rates of transition to psychosis at 1 year were 11% for focused treatment groups (n=180) and 31.6% for control UHR groups (n=157). Receiving any of the focused treatment was associated with a lower risk of developing psychosis if compared with no treatment or treatment as usual (Relative Risk=0.36; 95%CI: 0.22-0.59). The available evidence at 2/3 years follow-up indicates that the effects of focused treatments are not stable after intervention cessation and when treatment is delivered over a restricted time (e.g. 6 months or less), it may achieve only a delay in psychosis onset. Due to the heterogeneity in the interventions considered, the current results do not allow recommendation for any specific treatment.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

To examine potential differences in efficacy and safety of treatment with olanzapine in patients with schizophrenia of white and black descent.. A post-hoc, pooled analysis of 6 randomized, double-blind trials in the treatment of schizophrenia, schizophreniform disorder, or schizoaffective disorder compared white (N = 605) and black (N = 375) patients treated with olanzapine (5 to 20 mg/day) for 24 to 28 weeks. Efficacy measurements included the Positive and Negative Syndrome Scale (PANSS) total score; and positive, negative, and general psychopathology scores; and the Clinical Global Impression of Severity (CGI-S) scores at 6 months. Safety measures included differences in the frequencies of adverse events along with measures of extrapyramidal symptoms, weight, glucose, and lipid changes over time.. 51% of black patients and 45% of white patients experienced early study discontinuation (P = .133). Of those who discontinued, significantly more white patients experienced psychiatric worsening (P = .002) while significantly more black patients discontinued for reasons other than efficacy or tolerability (P = .014). Discontinuation for intolerability was not different between groups (P = .320). For the estimated change in PANSS total score over 6 months, there was no significant difference in efficacy between white and black patients (P = .928), nor on the estimated PANSS positive (P = .435), negative (P = .756) or general psychopathology (P = .165) scores. Overall, there was no significant difference in the change in CGI-S score between groups from baseline to endpoint (P = .979). Weight change was not significantly different in white and black patients over 6 months (P = .127). However, mean weight change was significantly greater in black versus white patients at Weeks 12 and 20 only (P = .028 and P = .026, respectively). Additionally, a significantly greater percentage of black patients experienced clinically significant weight gain (≥ 7%) at anytime compared to white patients (36.1% vs. 30.4%, P = .021). Changes across metabolic parameters (combined fasting and random lipids and glucose) were also not significantly different between groups, with the exception of a greater categorical change in total cholesterol from borderline to high among white subjects and a categorical change from normal to low in high density lipoprotein (HDL) cholesterol among white males.. The findings did not demonstrate overall substantive differences in efficacy or safety between white and black patients diagnosed with schizophrenia or related disorders treated with olanzapine. However, a significantly greater percentage of black patients (36.1%) experienced clinically significant weight gain compared to white patients (30.4%).

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Black or African American; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Obesity; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome; Weight Gain; White People

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Decision Making; Female; Humans; Olanzapine; Piperazines; Polypharmacy; Psychotic Disorders; Quinolones; Schizophrenia; Schizophrenic Psychology; Weight Gain

Turner syndrome encompasses several chromosomal abnormalities and includes a typical clinical manifestation. While common somatic symptoms are often described, neuropsychiatric alterations are rare and not frequently mentioned in the literature.. In this paper, we report on a subject with Turner syndrome who also showed psychotic symptoms.. The theoretical background and the relevance of this observation are discussed. Furthermore, this article briefly reviews existing reports on Turner syndrome and psychosis and presents neuropsychiatric changes in patients with Turner syndrome.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Chromosome Aberrations; Citalopram; Combined Modality Therapy; Drug Therapy, Combination; Female; Hallucinations; Humans; Middle Aged; Olanzapine; Patient Education as Topic; Psychotherapy; Psychotic Disorders; Risperidone; Turner Syndrome

Traumatic brain injury (TBI) can result in serious and disabling neuropsychiatric disorders.. The authors report a case of a 51-year old male, admitted to the psychiatric ward for acute psychosis and suicidal ideation, probably associated with TBI. After a temporal head trauma he initiated auditory/verbal hallucinations and subsequently developed paranoid delusions. The electroencephalography showed slow bilateral temporal activity and the neuropsychological testing showed several impairments. The patient improved with olanzapine at a dosage of 20 mg daily.. This case shows the difficulty of differential diagnosis between schizophrenia and psychotic disorder due to traumatic brain injury.. The authors conducted a revision of literature about the diagnosis, epidemiology, clinical aspects, laboratory and structural investigations and the treatment of this condition. Based on this revision work, the authors sketch some recommendations about the work-up that should be done when faced with this diagnostic hypothesis.

Topics: Antipsychotic Agents; Benzodiazepines; Brain Injuries; Diagnosis, Differential; Electroencephalography; Hallucinations; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Paranoid Disorders; Portugal; Psychotic Disorders; Schizophrenia

Akathisa is one of the most common and distressing neuroleptic-induced extrapyramidal side effects. Although it is well recognized in the context of conventional antipsychotic medications, there have been recent concerns raised by clinicians and researchers that this syndrome is overlooked in relation to second-generation or atypical antipsychotics. This review examines the recent literature relevant to second-generation antipsychotic (SGA)-induced akathisia.. Recent studies using large databases clearly indicate that extrapyramidal side effects, in particular akathisia, do occur with the SGAs, although the frequency is not as high as with the conventional antipsychotics. Risk factors include use of high doses, high potency SGAs, or combinations of SGAs with other psychotropic drugs, bipolar depression, palliative care settings, and comorbid substance abuse in psychosis. The dopamine hypothesis remains plausible for understanding the pathophysiology of akathisia. There is emerging evidence that mirtazapine may be useful in the treatment of acute akathisia.. Even though akathisia is less prevalent with SGAs than with the first-generation drugs, it remains clinically important and all clinicians should be conversant with its recognition and management.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Isoxazoles; Olanzapine; Piperazines; Piperidines; Prevalence; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Sulpiride; Thiazoles

Health services often manage agitated or violent people, and for emergency psychiatric services such behaviour is particularly prevalent (10%). The drugs used in this situation should ensure that the person swiftly and safely regains composure.. To examine whether haloperidol plus promethazine is an effective treatment for psychosis induced agitation/aggression.. We searched the Cochrane Schizophrenia Group's Register (January 2008).. We included all randomised clinical trials involving aggressive people with psychosis for which haloperidol plus promethazine was being used.. We reliably selected, quality assessed and extracted data from all relevant studies. For binary outcomes we calculated standard estimations of risk ratio (RR) and their 95% confidence intervals (CI). Where possible we estimated weighted number needed to treat or harm (NNT/H).. We identified four relevant high quality studies. One compared the haloperidol plus promethazine mix with midazolam (n=301), one with lorazepam (n=200), one with haloperidol alone (n=316) and one with olanzapine IM (n=300). In Brazil, haloperidol plus promethazine was an effective means of tranquillisation with over two thirds of people being tranquil or sedated by 30 minutes, but midazolam was more swift (n=301, RR 2.9 CI 1.75 to 4.80, NNH 5 CI 3 to 12). In India, compared with lorazepam, more people were tranquil or sedated by 30 minutes if allocated to the combination treatment (n=200, RR 0.26 CI 0.10 to 0.68, NNT 8 CI 6 to 17). Over the next few hours of treatment reported differences are negligible. One person given midazolam had respiratory depression (0.7%, reversed by flumazenil); one given lorazepam (1%) had respiratory difficulty. About 1% of people given any haloperidol treatment experienced a seizure. By 20 minutes intramuscular haloperidol plus promethazine was more tranquillising than intramuscular haloperidol (1 RCT, n=316, RR 0.65 CI 0.49 to 0.87, NNT 7 CI 5 to 17). Haloperidol given without promethazine in this situation causes frequent serious adverse effects (NNH 15 CI 14 to 40). Olanzapine is as rapidly tranquillising as the haloperidol/promethazine combination (1 RCT, n=300, RR tranquil or asleep at 15 mins 0.74 CI 0.38 to 1.41), but did not have an enduring effect and more people needed additional drugs within four hours (1 RCT, n=300, RR 0.48 CI 0.33 to 0.69, NNT 5 CI 4 to 8) and to be re-assessed by the doctor (1 RCT, n=300, RR 0.47 CI 0.30 to 0.73, NNT 6 CI 5 to 12).. All treatments evaluated within the included studies are effective. Benzodiazepines, however, have the potential to cause respiratory depression, probably midazolam more so than lorazepam, and use of this group of drugs outside of services fully confident of observing for and managing the consequences of respiratory distress is difficult to justify. Haloperidol used on its own is at such risk of generating preventable adverse effects that unless it is the only choice, this evidence directs that this sole treatment should be avoided. Olanzapine IM is valuable when compared with haloperidol plus promethazine but its duration of action is short and re-injection is frequently needed. Haloperidol plus promethazine used in two diverse situations in Brazil and India has much evidence to support its swift and safe clinically valuable effects.

Topics: Aggression; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Midazolam; Olanzapine; Promethazine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic

Early-onset psychotic illnesses in children and adolescents are not as rare as is commonly believed. These disorders, which include schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, and major depression with psychotic features, often have a chronic and severe course and poor long-term outcome. Many patients with early-onset schizophrenia have greater functional impairments than most patients with adult-onset schizophrenia. Magnetic resonance imaging studies show that patients with early-onset schizophrenia experience substantial gray matter loss during adolescence, which is not observed in studies of patients with adult-onset schizophrenia. The chronic course, severe functional impairments, and poor prognosis of early-onset psychosis create a great need to identify effective and safe treatments for youth with psychosis. Although atypical anti-psychotics have been considered superior to traditional antipsychotics, there has been little controlled information to inform clinical decisions until recently. Over the past 5 years, several studies have been initiated to address these questions. The results of the studies completed to date are reviewed.

Topics: Adolescent; Adult; Age of Onset; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Brain Diseases; Child; Chronic Disease; Clozapine; Comorbidity; Disease Progression; Humans; Magnetic Resonance Imaging; Olanzapine; Piperazines; Prognosis; Psychotic Disorders; Quinolones; Schizophrenia; Thiazoles; Treatment Failure

The management of patients with first-episode psychosis (FEP) is a difficult, but challenging task. Early and efficient treatment may influence long-term clinical outcome. Atypical antipsychotics (A-AP) are commonly prescribed in this population, but few data exist to establish their appropriate usage in the management of FEP. Our purpose is to review the literature and to summarize current data on the prescription of A-AP in FEP.. Studies assessing efficacy or safety of A-AP in FEP were identified by searches in Medline (up to April 2006). The following nine drugs were considered for this review: clozapine, olanzapine, risperidone, amisulpride, aripiprazole, quetiapine, ziprasidone, zotepine, and sertindole.. Only four A-AP (clozapine, quetiapine, olanzapine, and risperidone) were evaluated as treatment of FEP. All of them show the same efficacy as conventional antipsychotics (C-AP). Clozapine has no benefit over C-AP in the treatment of naive patients. It entails a high rate of treatment discontinuation because of the need for regular white blood cell monitoring explained by the risk of agranulocytosis. Hence, clozapine may not be a first-line treatment of FEP. Tolerance to quetiapine and olanzapine is better than C-AP regarding extrapyramidal side effects, but weight gain induced by these two A-AP may be very disabling in a young population. Considering results from head-to-head comparative studies, olanzapine may be more effective than risperidone when an affective component is associated with the FEP symptomatology, but more data are needed to demonstrate this point. Risperidone is a relatively well-tolerated compound when it is prescribed at doses lower than 4 mg/d. It is the only A-AP that showed greater efficacy than C-AP to prevent relapse in patients with FEP. Unfortunately, information regarding the preventive efficacy of the other A-AP are lacking.. Further studies, particularly longer-term studies, are needed to explore the impact of A-AP prescription in FEP on the course of psychotic disorders. The common use of A-AP as treatment of FEP is justified by a relatively better tolerance compared to C-AP, and by the hypothesis-not demonstrated-of a better effect on long-term outcome.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index

People suffering from epilepsy have an increased risk of suffering from psychotic symptoms. The psychotic syndromes associated with epilepsy have generally been classified as ictal, postictal and interictal psychosis. Anticonvulsant drugs have been reported to precipitate psychosis. Moreover, all antipsychotic drugs have the propensity to cause paroxysmal EEG abnormalities and induce seizures.. To evaluate the benefits of interventions used to treat clinically significant psychotic symptoms occurring in people with epilepsy with regard to global improvement, changes in mental state, hospitalization, behavior, quality of life, effect on the frequency of seizures and interaction with antiepileptic drugs.. We searched the Trials Registers of the Cochrane Schizophrenia Group and the Cochrane Epilepsy Group (May 2008), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2008), MEDLINE (Ovid, 1950 to 14 May 2008), EMBASE (1980 to 2006), PsycINFO (1872 to 12 May 2008), CINAHL (1981 to 9 May 2008) and Biological Abstracts using the Cochrane Schizophrenia Group's phrase for randomized controlled trials and schizophrenia or psychotic disorders combined with the phrase [and {epilepsy* or seizure disorders* }].Two review authors (SF and AS) independently inspected the citations identified from the search. We identified potentially relevant abstracts and assessed full papers for inclusion and methodological quality.. All randomized controlled trials comparing drugs, behavior therapy, cognitive behavior therapy or other non-pharmacological interventions used to relieve psychotic symptoms in people with epilepsy.. We planned to extract and analyze the data from all relevant studies using standardized methods. As only one study met the inclusion criteria, no meta-analysis was attempted.. After independently assessing the abstracts and titles of 492 articles, we selected five relevant abstracts. Ultimately we found only one study meeting the inclusion criteria, which was available only as an abstract. This study compared the use of olanzapine (10 mg/day) with haloperidol (12 mg/day) in 16 patients suffering from schizophrenia-like psychosis of epilepsy (SLPE). Thirteen patients completed the study. Significant improvement was associated with use of olanzapine. We did not identify any study on psychosocial interventions in patients suffering from epilepsy and psychosis.. Only one randomized controlled trial was found which lacked the power to test the efficacy of antipsychotics in those suffering from psychosis concomitant with epilepsy.Limited evidence from this small RCT suggests an improvement in psychotic symptoms, but not other outcome measures, with the use of an antipsychotic. The effects on seizure control are not well studied. Further trials are required to inform practice.

Topics: Antipsychotic Agents; Benzodiazepines; Epilepsy; Haloperidol; Humans; Olanzapine; Psychotic Disorders

This study was conducted to determine the effect of olanzapine treatment on cognition in elderly patients with behavioral and psychiatric symptoms (BPSD) associated with dementia.. This was a post-hoc analysis of three randomized double-blind, clinical trials of olanzapine (n = 682) vs placebo (n = 257) in dementia patients with BPSD in long-term or continuing-care settings. One study was 6 weeks long; the other two were 10 weeks duration, and their data were combined. Patients were subgrouped according to baseline Mini Mental State Examination (MMSE) scores: Group I = 23-26; Group II = 19-22; Group III = 14-18; Group IV = 7-13; Group V = 1-6. BPSD was assessed by the Neuropsychiatric Inventory (NPI).. Within-treatment group cognitive decline in patients was significant in the combined studies, but not in the 6-week study. Between-treatment cognitive changes were non-significant in the 6-week study, but showed a statistical trend in the combined studies (olanzapine, -0.78 +/- 0.19 vs placebo, -0.32 +/- 0.25; p = 0.06). In the subgroup analysis, there was a significant between-treatment difference in cognitive changes in MMSE subgroup IV in the combined studies (olanzapine, -0.63 +/- 0.26 vs placebo, 0.27 +/- 0.41, p = 0.04). Improvement in BPSD was correlated with better cognitive outcome (r = -0.2; p < 0.01).. Although the overall differences in cognitive changes in patients treated with olanzapine vs placebo were small and non-significant, negative effects on cognition in some patients cannot be excluded, especially in patients with more pronounced cognitive decline or whose behavioral and psychiatric symptoms are not responding to treatment.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dementia; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Randomized Controlled Trials as Topic; Social Behavior Disorders

Psychosis due to dopamimetic treatment is a difficult problem in patients with Parkinson's disease (PD). The aim of this structured review with meta-analysis was to evaluate which neuroleptic drugs can efficiently be used to treat drug-induced psychosis (DIP) in Parkinson's disease. Electronic databases were screened for the key words Parkinson's disease and psychosis. Only 7 trials with a satisfactory allocation concealment and data reporting were included into the study. Two trials compared low-dose clozapine versus placebo with a significantly better outcome for clozapine regarding efficacy and motor functioning. In one trial clozapine was compared against quetiapine showing equivalent efficacy and tolerability. However, in two placebo controlled trials quetiapine failed to show efficacy. In two further placebo controlled trials olanzapine did not improve psychotic symptoms and significantly caused more extrapyramidal side effects. Based on randomized trial-derived evidence which is currently available, only clozapine can be fully recommended for the treatment of DIP in PD. Olanzapine should not be used in this indication.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Data Interpretation, Statistical; Dibenzothiazepines; Dopamine; Dopamine Agents; Humans; Olanzapine; Parkinson Disease; Psychotic Disorders; Quality Assurance, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Compared with the first-generation, or "typical" antipsychotic drugs, second-generation or atypical antipsychotics cause fewer extrapyramidal (motor) problems, but they pose new challenges, as they often contribute to metabolic disturbances such as weight gain, hyperlipidemia, insulin resistance, and type 2 diabetes mellitus. Patients taking atypical antipsychotics should be monitored for glycemic and cardiovascular risk factors and should receive treatment for such problems as they arise.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus; Humans; Olanzapine; Psychotic Disorders; Risk Factors; Risperidone; Weight Gain

Aggression, agitation or psychosis occur in the majority of people with dementia at some point in the illness. There have been a number of trials of atypical antipsychotics to treat these symptoms over the last five years, and a systematic review is needed to evaluate the evidence in a balanced way.. To determine whether evidence supports the use of atypical antipsychotics for the treatment of aggression, agitation and psychosis in people with Alzheimer's disease.. The trials were identified from a last updated search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 7 December 2004 using the terms olanzapine, quetiapine, risperidone, clozapine, amisulpride, sertindole, zotepine, aripiprazole, ziprasidone. This Register contains articles from all major healthcare databases and many ongoing trials databases and is updated regularly.. Randomised, placebo-controlled trials, with concealed allocation, where dementia and psychosis and/or aggression were assessed.. 1. Two reviewers extracted data from included trials2. Data were pooled where possible, and analysed using appropriate statistical methods3. Analysis included patients treated with an atypical antipsychotic, compared with placebo. Sixteen placebo controlled trials have been completed with atypical antipsychotics although only nine had sufficient data to contribute to a meta-analysis and only five have been published in full in peer reviewed journals. No trials of amisulpiride, sertindole or zotepine were identified which met the criteria for inclusion. The included trials led to the following results:1. There was a significant improvement in aggression with risperidone and olanzapine treatment compared to placebo.2. There was a significant improvement in psychosis amongst risperidone treated patients.3. Risperidone and olanzpaine treated patients had a significantly higher incidence of serious adverse cerebrovascular events (including stroke), extra-pyramidal side effects and other important adverse outcomes.4. There was a significant increase in drop-outs in risperidone (2 mg) and olanzapine (5-10 mg) treated patients.5. The data were insufficient to examine impact upon cognitive function.. Evidence suggests that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extra-pyramidal symptoms. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is marked risk or severe distress. Although insufficient data were available from the considered trials, a meta-analysis of seventeen placebo controlled trials of atypical neuroleptics for the treatment of behavioural symptoms in people with dementia conducted by the Food and Drug Administration (using data not in the public domain) suggested a significant increase in mortality (OR 1.7).

Topics: Aggression; Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone

To assess the efficacy and adverse reactions of typical and atypical antipsychotics in the treatment of neuropsychiatric symptoms in dementia, and to examine the evidence for the cerebrovascular events warning for atypical antipsychotics.. Systematic review.. Using Medline, Cinahl, PsyclNFO, Embase and the Cochrane central register of controlled trials (1980-2005), double-blind randomized controlled trials with intention-to-treat analysis were selected, which evaluated efficacy and adverse reactions of antipsychotics in the treatment of neuropsychiatric symptoms in dementia. The studies underwent a standardised validity assessment.. After screening 950 studies, 14 studies on the effect of haloperidol, risperidone, olanzapine, quetiapine, tiapride, loxapine and perphenazine were selected. In 7 out of 10 studies, haloperidol, risperidone and olanzapine appeared to be more effective than placebo in the treatment of aggression and psychosis. Direct comparison between typical and atypical antipsychotics revealed no statistically significant difference. The most common adverse reactions were extrapyramidal symptoms and somnolence. These adverse reactions were less frequent with low-dose risperidone than with haloperidol or olanzapine, but risperidone and olanzapine were found to be associated with a higher risk of cerebrovascular events in two studies.. The efficacy of typical and atypical antipsychotics is comparable, but only low-dose risperidone seems to be associated with fewer (extrapyramidal) side effects. The adverse reactions are inadequately described in the published data and consequently the warning of an increased risk of mortality could not be confirmed.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Dementia; Haloperidol; Humans; Olanzapine; Psychotic Disorders; Risperidone; Treatment Outcome

Thirty years ago, psychiatrists had only a few choices of old neuroleptics available to them, currently defined as conventional or typical antipsychotics, as a result schizophrenics had to suffer the severe extra pyramidal side effects. Nowadays, new treatments are more ambitious, aiming not only to improve psychotic symptoms, but also quality of life and social reinsertion. Our objective is to briefly but critically review the advances in the treatment of schizophrenia with antipsychotics in the past 30 years. We conclude that conventional antipsychotics still have a place when just the cost of treatment, a key factor in poor regions, is considered. The atypical antipsychotic drugs are a class of agents that have become the most widely used to treat a variety of psychoses because of their superiority with regard to extra pyramidal symptoms. We can envisage different therapeutic strategies in the future, each uniquely targeting a different dimension of schizophrenia, be it positive, negative, cognitive or affective symptoms.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptors, Dopamine; Receptors, Serotonin; Risperidone; Schizophrenia; Thiazoles

Agitation is common in patients with acute schizophrenia or bipolar mania, and when severe can result in aggressive or violent behaviour. Pharmacotherapy for acute psychotic agitation includes the use of antipsychotic and benzodiazepine drugs, either alone or in combination. Although oral treatment is preferred, options in the pharmacotherapy of acute agitation include the parenteral administration of antipsychotics in order to facilitate onset of drug action and quickly alleviate symptoms. Until recently only conventional antipsychotic and benzodiazepine drugs were available as intramuscular injections. Olanzapine has been one of the first atypical antipsychotics available for intramuscular administration. Four randomized placebo and comparator controlled , double-blind clinical trials have demonstrated the efficacy of olanzapine in reducing acute agitation in patients with schizophrenia, bipolar mania and Alzheimer and vascular dementia. Evidence from these clinical trials has shown that IM olanzapine associated with faster onset of action and more favorable profile of adverse events, than monotherapy with IM haloperidol. Current clinical experience and one naturalistic study with intramuscular olanzapine suggest that it is efficacious and can be safely used in "real world" patients with severe agitation. Intramuscular olanzapine have shown ease of transition to same agent oral therapy once the acute agitation has diminished. The orally disintegrating tablet formulation of olanzapine was effective rapidly reducing psychopathology, while improving medication compliance, attitudes and behaviours. This new formulation of olanzapine may offer an alternative strategy in the treatment of acutely ill, noncompliant schizophrenic patients. Evidence suggests that the new formulations of olanzapine should be among the first-line choices in the treatment of agitation in acute psychosis.. olanzapine, intramuscular, orally disintegrating tablet, agitation, psychosis.

Topics: Acute Disease; Administration, Oral; Antipsychotic Agents; Attitude; Benzodiazepines; Bipolar Disorder; Dementia; Humans; Injections, Intramuscular; Olanzapine; Patient Compliance; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs.. To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses.. We updated the first search [Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000)] in October 2004 using the Cochrane Schizophrenia's Group's register of trials. We also searched references of all included studies for further trials, and contacted relevant pharmaceutical companies and authors.. We included all randomised clinical trials comparing olanzapine with placebo or any antipsychotic treatment for people with schizophrenia or schizophreniform psychoses.. We independently extracted data and, for homogeneous dichotomous data, calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences.. Fifty five trials are included (total n>10000 people with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by six weeks, leaving interpretation of results problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27). Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight. When compared with typical antipsychotic drugs, data from several small trials are incomplete. With high attrition in both groups (14 RCTs, n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions included in all data are considerable. For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated olanzapine experienced fewer extrapyramidal adverse effects than those given typical antipsychotics. Weight change data for the short term are not statistically significant but results between three to 12 months suggest a clinically important average gain of four kilograms for people given olanzapine (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64). Twenty three percent of people in trials of olanzapine and other atypical drugs left by eight weeks; 48% by three to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose between the atypicals, although olanzapine may cause fewer extrapyramidal adverse effects than other drugs in this category. Olanzapine produces more weight gain than other atypicals with some differences reaching conventional levels of statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7). There are very few data for people with first episode illness (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457).. The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia

People presenting with agitated or violent behaviour thought to be due to severe mental illness may require urgent pharmacological tranquillisation. Several preparations of olanzapine, an antipsychotic drug, are now being used for management of such agitation.. To estimate the effects of intramuscular, oral-velotab, or standard oral olanzapine compared with other treatments for controlling aggressive behaviour or agitation thought to be due to severe mental illness.. We searched the Cochrane Controlled Trials Register (Issue 1, 2002), The Cochrane Schizophrenia Group's Register (November 2004) and reference lists. We contacted authors of trials and the manufacturers of olanzapine.. Randomised clinical trials comparing oral-velotab or intramuscular, or standard oral olanzapine to any treatment, for agitated or aggressive people with severe mental illnesses.. We reliably selected, quality assessed and data extracted studies. For binary outcomes we calculated a fixed effects Risk Ratio (RR) and its 95% Confidence Interval (CI) with a weighted Number Needed to Treat/Harm statistic (NNT/H). For continuous outcomes, we preferred endpoint data to change data and synthesised non-skewed data from valid scales using a weighted mean difference (WMD).. Four trials compared olanzapine IM with IM placebo (total n=769, 217 allocated to placebo). Fewer people given olanzapine IM had 'no important response' by 2 hours compared with placebo (4 RCTs, n=769, RR 0.49 CI 0.42 to 0.59, NNT 4 CI 3 to 5) and olanzapine IM was as acceptable as placebo (2 RCTs, n=354, RR leaving the study early 0.31 CI 0.06 to 1.55). When compared with placebo, people given olanzapine IM required substantially fewer additional injections following the initial dose (4 RCTs, n=774, RR 0.48 CI 0.40 to 0.58, NNT 4 CI 4 to 5). Olanzapine IM did not seem associated with extrapyramidal effects (4 RCT, n=570, RR experiencing any adverse event requiring anticholinergic medication in first 24 hours 1.27 CI 0.49 to 3.26). Two trials compared olanzapine IM with haloperidol IM (total n=482, 166 allocated to haloperidol). Studies found no differences between olanzapine IM and haloperidol by 2 hours for the outcome of 'no important clinical response' (2 RCTs, n= 482, RR 1.00 CI 0.73 to 1.38) neither was there a difference for needing repeat IM injections (2 RCTs, n=482, RR 0.99 CI 0.71 to 1.38). More people on haloperidol experienced akathisia over the five day oral period compared with olanzapine IM (1 RCT, n=257, RR 0.51 CI 0.32 to 0.80, NNT 6 CI 5 to 15) and fewer people allocated to olanzapine IM required anticholinergic medication by 24 hours compared with those given haloperidol IM (2 RCTs, n= 432, RR 0.20 CI 0.09 to 0.44, NNT 8 CI 7 to 11). Two trials compared olanzapine IM with lorazepam IM (total n=355, 119 allocated to lorazepam). For the outcome of 'no important clinical response' , there was no difference between people given olanzapine IM and those allocated to lorazepam at 2 hours (2 RCTs, n=355, RR 92 CI 0.66 to 1.30) but fewer people allocated to olanzapine IM required additional injections by 24 hours compared with those on lorazepam IM (2 RCTs, n=355, RR 0.68 CI 0.49 to 0.95, NNT 10 CI 6 to 59). People receiving IM olanzapine were less likely to experience any treatment emergent adverse events, than those on lorazepam (1 RCT, n=150, RR at 24 hours 0.62 CI 0.43 to 0.89, NNT 5 CI 4 to 17) and over the same time period there were no clear differences in the use of anticholinergic medication between groups (1 RCT, n=150, RR 1.16 CI 0.38 to 3.58).No studies reported outcomes related to hospital and service use. Nor did any report on issues of satisfaction with care or suicide, self-harm or harm to others. No studies evaluated the oro-di. Data relevant to the effects of olanzapine IM are taken from some studies that may not be considered ethical in many places, all are funded by a company with a pecuniary interest in the result. These studies often poorly report outcomes that are difficult to interpret for routine care. Other important outcomes are not recorded at all. Nevertheless, olanzapine IM probably has some value in helping manage acute aggression or agitation, especially where it is necessary to avoid some of the older, better, known treatments. Olanzapine causes fewer movement disorders than haloperidol and more than lorazepam. The value of the oro-dipersable velotab preparation is untested in trials. There is a need for well designed, conducted and reported randomised studies in this area. Such studies are possible and, we argue, should be designed with the patient groups and clinicians in mind. They should report outcomes of relevance to the management of people at this difficult point in their illness.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Injections, Intramuscular; Lorazepam; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic

The first compounds showing efficacy in the treatment of schizophrenia and other psychotic disorders was chlorpromazine, an anti-histaminic compound casually observed to possess antipsychotic effects. The discovery of the real mechanism of action of antipsychotic substances dates back to the 1960s, when researchers found that these compounds act as dopamine receptor antagonists. Unfortunately, this type of drugs cannot block the D2 receptors only in the mesolimbic dopaminergic pathway (which mediates their therapeutic effects), because of their non-selective D2 receptor blockage in both the mesolimbic and striatal regions, and the consequent appearance of side effects related to striatal interaction in the same dosage range as is needed for the therapeutical effects. Clozapine, discovered in the early 1970s, seemed to represent the solution to contrast these side effects, as it possesses antipsychotic activity without inducing extrapyramidal disorders in humans or catalepsy in rats; for this reason, it was defined as an "atypical" antipsychotic drug. Later, other beneficial properties, such as improvement of negative symptoms and of cognitive dysfunction and efficacy in neuroleptic-resistant schizophrenia, were included in the definition of "atypical". In recent years, the appearance of new atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone) has opened new ways to therapy. The aim of this paper is to review literature about newer antipsychotics, focusing on their advantages in terms of efficacy and side effect profiles when compared to classical and older atypical antipsychotics, and to evaluate the efficacy of the different new antipsychotics when compared to one another.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Cognition; Dibenzothiazepines; Drug Interactions; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Novel antipsychotics are increasingly used in the treatment of bipolar and schizoaffective mania. This paper presents an overview of the controlled studies in this field.. Using cross-references, a computerized search was performed on MEDLINE and EMBASE psychiatry covering the period 1990-2002.. Olanzapine and risperidone, added to mood stabilizers, and olanzapine as monotherapy enjoy the most evidential support in terms of efficacy and side-effect profile for their use in acute bipolar mania. The use of modern antipsychotics in bipolar prophylaxis and in both the short- and long-term treatment of schizomania has not been widely studied yet.. More controlled trials are still needed comparing modern antipsychotics as monotherapy and adjunctive to mood stabilizers with conventional antipsychotics, lithium, anticonvulsants and with each other in short-term and, especially, maintenance treatment of (schizo)mania. Partly based on controlled studies, olanzapine, risperidone and other modern antipsychotics could become preferable for these indications.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Psychotic Disorders; Risperidone

Tardive dyskinesia is a chronic drug-induced movement disorder that tends to be persistent in older adults who are treated with antipsychotics. Tardive dyskinesia can affect older patients both physically and psychologically, leading to frequent falls, difficulty eating, and depression. While atypical antipsychotics may cause tardive dyskinesia, the percentage is usually significantly lower than with conventional antipsychotics. Using atypical antipsychotics, particularly at lower doses, may aid in preventing symptoms of tardive dyskinesia in older adults.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Humans; Incidence; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Lewy body dementia, also referred to as dementia with Lewy bodies (DLB), is a neurodegenerative disorder now considered to be the second most common cause of dementia after Alzheimer's disease. Postmortem findings suggest that DLB accounts for 20% to 34% of all dementia cases and is often underdiagnosed. Salient features of DLB include fluctuations in cognition, perceptual abnormalities (e.g., visual hallucinations), and mild parkinsonism. Other symptoms include frequent falls, nighttime agitation, and depression. DLB symptomatology can be partly explained by the extensive destruction of dopaminergic and acetylcholinergic pathways caused by neurodegeneration. For this reason, DLB patients are especially vulnerable to the antidopaminergic and anticholinergic actions of most conventional antipsychotics, which makes treatment of the psychotic symptoms of DLB extremely difficult. Patients are particularly sensitive to developing extrapyramidal symptoms (EPS) and also to the potentially fatal complication of neuroleptic sensitivity, which affects approximately 50% of DLB patients. Therefore, a need exists for antipsychotic drugs with less propensity to induce EPS and reduced affinity for dopamine and acetylcholine receptors. Here we review studies evaluating the efficacy and tolerability of atypical antipsychotics for the treatment of psychoses associated with DLB. Olanzapine appears to be poorly tolerated, and risperidone has been associated with high risk of neuroleptic malignant syndrome. Clozapine use remains controversial because of its potent anticholinergic action and risk of agranulocytosis. Quetiapine has been shown to reduce psychiatric manifestations of DLB without causing neuroleptic sensitivity or increasing EPS. Hence, quetiapine is an attractive candidate for the treatment of psychoses in DLB and other dementias.

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

The literature continues to highlight the debate on the ethics and merits of trials sponsored by the pharmaceutical industry. This study attempts to determine the prevalence and outcomes of industry-sponsored trials involving clozapine, risperidone, or olanzapine.. We searched the literature from January 1, 1990, to December 31, 2001, to capture all eligible clinical trials involving clozapine, risperidone, or olanzapine. The primary outcome measured was the clinical outcome of industry-sponsored studies. Secondary outcome measures included the following parameters: disclosure of any sponsorship and financial support, author(s) employed by the industry, use of comparator drug(s) within the trial, sample size, blinding, and use of placebo.. The database comprised 372 articles. Of these trials, 124 (33.3%) were sponsored by the pharmaceutical industry. In general, trials sponsored by Eli Lilly or Janssen had better research design than trials not funded by the pharmaceutical industry. With regard to authorship, more trials funded by Eli Lilly (74.6%) were coauthored by an employee of the company, compared with trials funded by either Janssen (23.3%) or Novartis/Sandoz (5.6%). Further, more trials sponsored by Eli Lilly reported positive outcomes (92.1%), compared with Janssen-sponsored trials (88.4%) and Sandoz/Novartis-sponsored trials (72.2%). No negative results were reported in any of the industry-funded trials.. One-third of the published clinical trials involving clozapine, risperidone, or olanzapine were funded by their respective manufacturer. The reported outcomes of the sponsored trials highly favour the manufacturer's product.

Topics: Benzodiazepines; Clinical Trials as Topic; Clozapine; Drug Industry; Humans; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Risperidone

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Serotonin Antagonists; Thiazoles; Treatment Outcome; United States

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

Atypical antipsychotics are widely used in clinical practice for several psychiatric disorders. Between 1994 and 1999, 26 cases of manic and hypomanic syndromes were reported with olanzapine and risperidone and were described in a previous review article.. An updated MEDLINE search (1999-2003) using the terms atypical antipsychotics, amisulpride, aripiprazole, clozapine, flupenthixol, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine, hypomania, and mania showed that 34 new cases of induced hypomanic or manic syndromes have been published, not only with olanzapine (N = 5) and risperidone (N = 6), but also with quetiapine (N = 5) and ziprasidone (N = 11) treatment. Six cases have been reported with flupenthixol and 1 with amisulpride, two antipsychotics considered as "partial" atypicals.. A critical analysis of these case reports revealed that the effects on mood were insufficiently documented in some of the reports but that for 20 of them, evidence is highly suggestive of a causative role of atypical antipsychotics in the induction of manic/hypomanic symptomatology.. This updated review continues and extends the results of the initial review and suggests that atypical antipsychotics have some intriguing effects on mood. Such effects have never been reported with conventional antipsychotics. The mechanisms involved in this phenomenon of mood switch remain to be elucidated.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Olanzapine; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Risperidone; Schizophrenia

Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs.. To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses.. The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials.. All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses.. Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences.. Twenty one trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0.7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27) and global mental state scores. Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. Tthe olanzapine group gained more weight. When compared to typical antipsychotic drugs, data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0.86-1.02), the assumptions included in all continuous data are considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness.. The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia

The frequency of neuroleptic malignant syndrome (NMS) after clozapine or olanzapine is low and often of non-serious nature. A 49 year-old female patient developed NMS 12 days after olanzapine re-exposure. Olanzapine was stopped, the patient was transferred to an ICU and received a course of nine uni- and bilateral ECT treatments. This led to remission. 14 months earlier the patient had presented with a first severe NMS episode after haloperidol depot injection and 4 days after starting oral clozapine. Following the first NMS episode olanzapine (20 mg per day) was administered for 11 months without adverse effects.

Topics: Antipsychotic Agents; Benzodiazepines; Critical Care; Electroconvulsive Therapy; Female; Haloperidol; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Recurrence

To evaluate the efficacy and safety of olanzapine for the treatment of psychotic and behavioral disturbances in Alzheimer disease.. MEDLINE (1966-January 2003) and Science Citation Index searches were performed. Key search terms included olanzapine, Alzheimer(s), and dementia.. Four trials of olanzapine and subsequent post hoc analyses were reviewed. Three trials found a benefit associated with olanzapine use, but a fourth trial did not.. Olanzapine appears to be effective in treating psychotic and behavioral disturbances associated with Alzheimer disease. However, the most appropriate dose remains to be determined. The benefit of olanzapine therapy must be weighed against the adverse effect profiles of olanzapine and alternative treatment options.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Humans; Mental Disorders; Olanzapine; Pirenzepine; Psychotic Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

Psychotic symptoms are seen in numerous psychiatric illnesses afflicting the elderly. This article reviews the efficacy of the pharmacologic management of psychotic symptoms in primary psychotic disorders, affective disorders, and neurodegenerative disorders.. A comprehensive literature review.. Evidence to support the use of pharmacologic interventions to manage psychotic symptoms in elderly patients afflicted with primary psychotic disorders and affective disorders is limited by the absence of randomized, placebo-controlled trials (RCTs). The use of low-dose clozapine is supported by RCTs in Parkinson's disease. The efficacy of risperidone and olanzapine for the treatment of psychotic symptoms has been demonstrated by large RCTs in Alzheimer's disease.. There is evidence of the efficacy of antipsychotic medications to manage psychotic symptoms in elderly patients. However, the absence of published evidence from RCTs in primary psychotic and affective disorders, and the limited evidence in the neurodegenerative illnesses, is notable.

Topics: Aged; Alzheimer Disease; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder; Drug Administration Schedule; Humans; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Risperidone

Drug-induced iatrogenic hallucinations and psychosis occur in about 30% of Parkinson's disease (PD) patients and are the single most important precipitant for nursing home placement, which carries a grave prognosis. In addition, parkinsonism is a frequent accompaniment to the more common dementing syndromes, Alzheimer's disease (AD), vascular dementia, and dementia with Lewy bodies (DLB). The five most recent antipsychotic drugs approved by the Food and Drug Administration in the United States have been marketed as "atypical" antipsychotics (AA) due to their relative freedom from extrapyramidal symptoms when used in schizophrenia patients. The use of these newer antipsychotic drugs in PD and other parkinson-sensitive populations represents the most stringent test to their freedom from motor side effects. To date, clozapine, risperidone, olanzapine, and quetiapine have been studied in parkinson-vulnerable populations. This article reviews the data and highlights the differences that these four drugs have on motor function. It also emphasizes the challenges in evaluating the available data on the motor effects of AA, especially on the non-PD elderly and cognitively impaired population. Suggestions are made for future research to improve the interpretability of these studies.

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia, Vascular; Dibenzothiazepines; Hallucinations; Humans; Iatrogenic Disease; Lewy Body Disease; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Delusions; Hallucinations; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone

Topics: Anti-Dyskinesia Agents; Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Piperazines; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Thiazoles

During 20th century serious mental disorders were divided into two groups according symptomatology and course of disorder. Individuals with dominating disturbance of perception, thinking and cognition were basically diagnosed having schizophrenic. Individuals with mood disturbance were basically diagnosed having affective disorders. However, there were patients who did not fit neatly into either category. In 1933 Jocob Kasanin introduced the term "schizoaffective psychosis". Scientific discussions involved the possibility that schizoaffective disorder was conceptualized most accurately as following: a type of schizophrenia, a type of affective disorder, a unique disorder that was separate from both schizophrenia and bipolar disorder, an arbitrary categorization of clinical symptoms that marked a continuum between schizophrenia and affective illness, a heterogeneous collection of "interforms" between schizophrenia and affective disorders. However, diagnosis of schizoaffective disorder is included both in DSM-IV-TR and ICD-10. Schizoaffective disorder is listed in the category "schizophrenia and other psychotic disorders". The differential diagnosis includes basically either schizophrenia or affective disorder. The epidemiological status of schizoaffective disorder is somewhat uncertain compared with schizophrenia because of dilemmas related to diagnosis and classification of the disorder. Treatment of schizoaffective disorder comprises psychotropic medication, supportive psychotherapy, social care, rehabilitation. The most important groups of psychotropic medications are: antipsychotics, antidepressants and mood stabilizers. Atypical antipsychotics are the first-line medication for schizoaffective disorder due to their pharmacological properties. In the case of schizoaffective disorders combination of atypical antipsychotics with antidepressants seems to be useful. Novel antidepressants have priority for the combination mentioned above. Peculiarities of mechanism of action of antidepressant are important for combinations. Mood stabilizers seem to be useful for treatment of certain type of schizoaffective disorder as well.

Topics: Adolescent; Amisulpride; Animals; Antidepressive Agents; Antidepressive Agents, Tricyclic; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Carbamazepine; Child; Diagnosis, Differential; Dibenzothiazepines; Dogs; Female; Humans; Imidazoles; Indoles; Lithium Carbonate; Male; Mianserin; Middle Aged; Mirtazapine; Olanzapine; Piperazines; Pirenzepine; Placebos; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Sulpiride; Thiazoles; Time Factors

Currently, tardive dyskinesia (TD) remains an important clinical problem. The average prevalence is estimated at 30%. The appearance of antipsychotics has opened new paths. The extrapyramidal profile of these molecules is more favorable than that of conventional neuroleptics. In order to assess their prophylactic as well as curative potential, we reviewed the literature concerning four of these atypical antipsychotics: clozapine, risperidone olanzapine and amisulpride. Clozapine seems to induce fewer cases of TD than the conventional neuroleptics, and has a specific therapeutic effect. However, the risk of agranulocytosis reduces the possibility of utilisation. Risperidone appears to be an effective therapy, but several authors report cases of TD during treatment. Furthermore, larger studies and longer follow-ups are necessary to confirm the efficiency of olanzapine and amisulpride. Further studies and observations are still necessary before drawing any conclusion for these new atypical antipsychotic actions. They are doubtlessly promising, but we cannot ignore the notion of risk-benefit; regular monitoring and listening to the subjective experience of the patients must remain uppermost in the choice of therapy.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Prevalence; Psychotic Disorders; Risperidone; Sulpiride

The use of control placebos in clinical trials of new antipsychotic medications is increasingly under examination. The active controlled equivalence study could offer a potential alternative design. First, however, it must be clear that any proposed standard control agent has been consistently superior to placebo in previous studies.. Through a Freedom of Information Act request, we identified nine placebo-controlled trials of risperidone, olanzapine, or quetiapine.. Meta-analysis indicated that the pooled estimate of the true population effect size +/- SE was 0.46 +/- 0.06 for categorical response rates and >0.53 +/- 0.07 for the continuous Brief Psychiatric Rating Scale change score outcome measure. If the desired detectable effect size is set very conservatively at a 95% confidence lower bound for the estimate of true effect size, statistical power for random samples of 80 per group drawn from a population of subjects similar to that of the nine meta-analyzed studies is.67 for categorical response rates and >.82 for the continuous measure, based on one-sided alpha =.05.. These data suggest substantial confidence that a therapeutic dose of an atypical antipsychotic will be statistically superior to placebo in an adequately sized randomized trial, when reporting a continuous measure as the principal outcome.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Although atypical antipsychotics are becoming the treatment of choice for schizophrenia, what makes an antipsychotic "atypical" is not clear. This article provides a new hypothesis about the mechanism of action of atypical antipsychotics.. Published data regarding the molecular, animal model, neuroimaging, and clinical aspects of typical and atypical antipsychotics were reviewed to develop this hypothesis. Particular attention was paid to data regarding the role of the serotonin 5-HT(2) and dopamine D(4) receptors in atypicality.. Neuroimaging data show that optimal dopamine D(2) occupancy is sufficient to produce the atypical antipsychotic effect. Freedom from motor side effects results from low D(2) occupancy, not from high 5-HT(2) occupancy. If D(2) occupancy is excessive, atypicality is lost even in the presence of high 5-HT(2) occupancy. Animal data show that a rapid dissociation from the D(2) receptor at a molecular level produces the atypical antipsychotic effect. In vitro data show that the single most powerful predictor of atypicality for the current generation of atypical antipsychotics is fast dissociation from the D(2) receptor, not its high affinity at 5-HT(2), D(4), or another receptor.. The authors propose that fast dissociation from the D(2) receptor makes an antipsychotic more accommodating of physiological dopamine transmission, permitting an antipsychotic effect without motor side effects, prolactin elevation, or secondary negative symptoms. In contrast to the multireceptor hypotheses, the authors predict that the atypical antipsychotic effect can be produced by appropriate modulation of the D(2) receptor alone; the blockade of other receptors is neither necessary nor sufficient.

Topics: Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Dopamine D2 Receptor Antagonists; Haloperidol; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Receptors, Dopamine D2; Receptors, Dopamine D4; Receptors, Serotonin; Risperidone; Schizophrenia; Terminology as Topic; Tomography, Emission-Computed

Alterations of electrocardiogram results and cases of sudden cardiac death have been reported since the beginning of neuroleptic treatment. In particular, a temporal association exists between some antipsychotics and prolongation of the heart rate-corrected QT interval (QTc), an event that may increase the risk for developing a potentially fatal ventricular tachycardia arrhythmia known as torsades de pointes if it significantly exceeds normal intraindividual and interindividual variation. Although the incidence of serious adverse cardiac events in response to antipsychotic medications is relatively low, any possibility for the occurrence of cardiotoxicity warrants continued study. The present article reviews important differences among antipsychotic drugs in the potential for, and occurrence of, serious adverse cardiac outcomes and suggests that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute significantly to a QTc prolongation that could result in potentially fatal ventricular arrhythmias.

Topics: Acute Disease; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Death, Sudden; Female; Humans; Long QT Syndrome; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Torsades de Pointes

The history of antipsychotic medications begins in the 1950s with chlorpromazine, developed originally as an antihistamine but found to be an aid in the reduction of symptoms of delusions and hallucinations. This phenothiazine derivative was followed by numerous others in the same class (e.g., thioridazine) and then by antipsychotics in other classes (e.g., the popular haloperidol of the butyrophenone class). This group of medications is associated with a number of unpleasant side effects and complications. These included extrapyramidal symptoms (EPS), orthostatic hypotension, hyperprolactinemia and last, but certainly not least, tardive dyskinesia (TD). As a consequence, other alternative antipsychotics were developed in which D(2) blockade effect generally associated with EPS and TD was offset by 5-HT(2) antagonism. The first of this class was clozapine; however, it is associated with agranulocytopenia of sudden onset as well as seizure induction. However, olanzapine, a close structural relative, was soon synthesised for treatment of psychosis and particularly schizophrenia (Zyprexatrade mark, Eli Lilly). It was released in the US in November 1996 with FDA approval for that indication. However, antipsychotics have always been used for other psychiatric disorders, aside from schizophrenia. This includes, in particular, mania, where chlorpromazine use predated lithium as an effective treatment. Other uses for antipsychotics have included other mood disorders, dementia, childhood disorders and personality problems. Here, information on the application of olanzapine to non-schizophrenic disorders is reviewed. Despite the fact that the research post-dates FDA approval in 1996, there was already sufficient evidence for olanzapine's effectiveness in acute mania to obtain approval from the US FDA in March 2000. Other research supports its use as adjunctive therapy in depressive disorders. Phase IV studies and case reports have found limited support for olanzapine's use in a variety of other psychiatric disorders, behavioural disorders of dementia (including Alzheimer's disease), pervasive developmental disorder of childhood, obsessive-compulsive disorder and borderline personality disorder. In each of these latter diagnoses, double-blind studies are either underway or are planned to establish efficacy.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

In general, antipsychotic agents have diverse actions on a wide range of neurotransmitter systems. Data strongly suggest that a number of these systems may play a role in the regulation of body weight. In addition to having very distinct pharmacologic profiles, individual agents possess discrete weight gain liabilities. This article briefly reviews the evidence for the involvement of specific neurotransmitter systems in the control of body weight and describes the relevant pharmacologic characteristics of individual antipsychotic agents. By comparing the pharmacologic profiles of specific antipsychotic agents with their respective weight gain liabilities, this article attempts to gain an insight into the specific receptors underlying a drug's propensity to induce weight gain. However, there is still much to be learned concerning weight control mechanisms, and the role of many of the receptors at which antipsychotic agents are active remains unclear. In spite of this, an overview of current knowledge in the field may facilitate prediction of a potential novel antipsychotic agent's weight gain liability.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Eating; Humans; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Rats; Receptors, Neurotransmitter; Schizophrenia; Thiazoles; Weight Gain

Priapism is a prolonged, usually painful, and persistent penile erection not usually associated with sexual stimuli, resulting from a disturbance in the normal regulatory mechanisms that initiate and maintain penile flaccidity. This infrequent adverse event of antipsychotic medication use requires emergency evaluation and has potentially serious long-term sequelae including erectile dysfunction. Clinicians prescribing antipsychotic medications should be aware of this rare but serious adverse event.. A computerized search, using the MEDLINE database (1966-summer 2000), located cases of priapism associated with most conventional antipsychotics as well as with clozapine, risperidone, and olanzapine. The search included no restrictions on languages. Keywords included priapism combined with antipsychotic agents and the names of the currently available atypical antipsychotics. Twenty-nine publications were located using these parameters. Additional publications were reviewed for general background on pathophysiology, evaluation, and management. The quality of the evidence reviewed is limited by the observational and uncontrolled nature of case reports, case series. and review articles.. Psychotropic-induced priapism is currently believed to be caused by the alpha1-adrenergic antagonism of these medications. Detumescence is sympathetically mediated, and alpha1-adrenergic antagonism (within the corpora cavernosa) inhibits detumescence. The propensity of individual antipsychotics to induce priapism can presumably be estimated on the basis of alpha1adrenergic blockade affinities. Of the conventional antipsychotics, chlorpromazine and thioridazine have the greatest alpha1-adrenergic affinity and have been most frequently reported to be associated with priapism. Of the atypical antipsychotics, risperidone has greater alpha1-adrenergic affinity, although 3 of the 5 currently U.S. Food and Drug Administration (FDA)-approved atypicals have been reported to be associated with priapism.. Virtually all antipsychotic medications have been reported to rarely cause priapism due to their alpha-adrenergic antagonism. This adverse event should be considered a urologic emergency. Clinicians should be familiar with this infrequent serious adverse event of antipsychotic medications.

Topics: Antipsychotic Agents; Benzodiazepines; Circadian Rhythm; Clozapine; Erectile Dysfunction; Female; Forensic Psychiatry; Humans; Male; Olanzapine; Pirenzepine; Priapism; Psychotic Disorders; Risperidone

The number of elderly persons with psychosis will increase with the increasing geriatric population. Olanzapine is one of the newer atypical antipsychotics with efficacy for positive and negative symptoms and safer side effect profile compared to conventional antipsychotics. The manuscript describes the pharmacology, efficacy and tolerability studies, adverse effects and dosing considerations in the elderly. Further studies are needed to fully assess the efficacy and safety of olanzapine in the elderly. Current research supports a role for olanzapine in treating elderly patients with schizophrenia, schizoaffective disorder and behavioral and psychological symptoms of dementia.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome

Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs.. To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses.. The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), The Cochrane Schizophrenia Group's Register (September 1999), EMBASE (1980-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials.. All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses.. Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences.. Twenty trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0. 7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27), but trial data regarding negative symptoms are equivocal for this comparison. Dizziness and dry mouth were more common in the olanzapine-treated group, and, although not statistically significant, the olanzapine group gained more weight. Data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0. 86-1.02), the assumptions included in all continuous data are considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness.. For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia

Olanzapine, a serotonin-dopamine receptor antagonist, is one of the novel atypical antipsychotics that is effective against the positive and negative symptoms of schizophrenia with significantly fewer treatment-emergent extrapyramidal symptoms and less akathisia associated with traditional antipsychotics. Compared with traditional agents, olanzapine shows only a few adverse events such as dry mouth, sedation, and increase in appetite. Compared with risperidone, olanzapine causes greater increases in weight gain and body mass index but less hyperprolactinemia. Transient, non-dose-dependent, asymptomatic elevations in liver enzymes have also been noted in olanzapine-treated patients. Because of the comparative efficacy and improved side effect profiles of the atypical antipsychotics, consideration should be given to using the newer agents as preferred treatment for schizophrenia and related psychoses.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Mass Index; Clinical Trials as Topic; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Weight Gain

Risperidone and olanzapine are atypical antipsychotics that are now widely used in clinical practice.. A MEDLINE search (1966-1999) showed that, following the introduction of these agents in recent years, 26 cases of induced hypomanic and manic syndromes have been reported during standard olanzapine (N = 10) or risperidone (N = 16) treatment.. A critical analysis of these case reports reveals that the effects on mood were sometimes insufficiently documented and that in about half of them (N = 16) evidence is highly suggestive of a causative role of risperidone or olanzapine in the induction of (hypo)manic symptomatology.. Despite limitations, the available literature confirms intriguing effects of these 2 antipsychotics on mood. The risk factors as well as the mechanisms of action underlying these effects remain to be clarified.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia

For patients hospitalized with acute episodes of psychosis, rapid stabilization of intense positive symptoms, hostility, and agitation is typically a preeminent therapeutic goal. These goals often differ from those of the nonhospitalized patient with psychosis for whom long-term treatment goals such as improvement of negative symptoms, cognitive function, compliance, and reduction in side effect burden may be paramount. Therefore, when selecting an antipsychotic treatment for hospitalized patients, efficacy against positive symptoms and hostility as well as speed of therapeutic onset should strongly be considered. At the same time, selection of antipsychotic treatment in the inpatient setting should establish a definitive treatment that will address long-term goals effectively after discharge. This article presents the rationale and practical guidelines for selection of treatment regimens for patients hospitalized due to acute psychosis.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Haloperidol; Hospitalization; Hostility; Humans; Olanzapine; Pirenzepine; Practice Guidelines as Topic; Psychomotor Agitation; Psychotic Disorders; Risperidone; Treatment Outcome

Atypical neuroleptic agents are an excellent, safer, and more effective alternative to the widespread practice of maintenance adjunctive treatment with traditional neuroleptic agents in patients with bipolar disorder. Currently, a number of prospective studies are available with clozapine, risperidone, olanzapine, and quetiapine in the treatment of bipolar disorder. Most are short-term studies, although longer-term data are becoming available. Four double-blind studies of acute mania have been conducted with risperidone and olanzapine, leading to recent Food and Drug Administration approval for olanzapine in the indication of acute mania. Given the limited longer-term data, and the evidence for mostly adjunctive benefits with these agents, it seems unlikely that these agents will prove to be primary mood stabilizers in their own right. Nonetheless, they serve an important role as adjunctive treatments along with standard mood stabilizers in the rational polypharmacy of bipolar disorder. To date, differences in efficacy have not been established. However, differences in the side effect of weight gain may be even more relevant in bipolar disorder than in schizophrenia due to the need to use standard mood stabilizers that often potentiate such weight gain.

Topics: Acute Disease; Algorithms; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome; Valproic Acid

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Aggressive behavior of psychotic patients impacts all aspects of their clinical care. Better treatments to address this problem are needed, and atypical antipsychotics, such as clozapine, risperidone, and perhaps quetiapine, have shown promise. However, studying the psychopharmacology of aggression is difficult because of the many methodological problems that arise in the design of appropriate clinical trials. These include imprecise definitions of aggression, the difficulty of measuring outcome because of the relative rarity of aggressive events, bias in the selection of patients for study, inadequate and inappropriate control groups, and inattention to comorbidities and concomitant medications in analyzing results. Since the usual outcome measure is the aggressive event rate, a large sample size and lengthy baseline and trial periods are required when this rate is low. Furthermore, formidable practical and ethical obstacles interfere with the many sound techniques (e.g. randomization) used in typical designs of psychopharmacological clinical trials. Current research methods should be modified and new ones developed in order to progress in assessing the antiaggressive effects of treatments.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Disease Progression; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Research Design; Risperidone

Soon after the introduction of antipsychotic drugs into clinical practice, these agents were observed to be capable of producing not only acute extrapyramidal ("parkinsonian") side effects, but also later occurring abnormal involuntary movements that came to be called tardive dyskinesia. Since antipsychotic drugs are used in a variety of conditions that include psychotic features, studies have attempted to determine whether specific diagnostic subgroups may experience different degrees of vulnerability to drug-induced movement disorders. This issue is important not only to inform clinical practice, but also to provide clues to pathophysiology. A number of studies suggest that patients with affective disorders are at greater risk for developing tardive dyskinesia (controlling, to the extent possible, for other relevant variables such as age, sex, length of treatment). Encouraging preliminary data with new antipsychotic drugs such as olanzapine suggest that the risk of tardive dyskinesia associated with long-term antipsychotic drug use may be substantially reduced. This would go a long way toward improving the benefit-to-risk ratio of antipsychotic drug treatment, particularly in patients with affective disorders.

Topics: Adult; Affective Disorders, Psychotic; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Imidazoles; Indoles; Male; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Olanzapine is a novel antipsychotic agent displaying a unique and pleotrophic pharmacology, which distinguishes it from other existing treatments. Clinical investigations employing olanzapine have demonstrated a number of potential therapeutic advantages in reference not only to placebo but also to contemporary drug standards in the management of psychosis. This paper reviews data on the pharmacokinetics, efficacy and safety of olanzapine, its benefits for quality of life, and economic aspects to assist clinicians in determining where they can usefully employ it.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder; Drug Resistance; Humans; Olanzapine; Pirenzepine; Prolactin; Psychotic Disorders; Quality of Life; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

The recent introduction of the atypical antipsychotics into the treatment arena for psychoses and related disorders comes with justifiable excitement. These newer antipsychotics offer several clinical benefits over the conventional antipsychotics, which have been the mainstays of care thus far. The primary advantage of these atypical agents is their superior side effect profiles, particularly with regard to extrapyramidal side effects (EPS). The implications from a reduction in EPS touch on virtually every aspect of pathology in schizophrenic illness, including short- and long-term movement disorders, negative symptoms, noncompliance, cognitive dysfunction, and dysphoria. It should be emphasized that while atypical antipsychotics share many clinical attributes, there are also substantial differences among them. This review will examine the pharmacology, clinical efficacy, and side effect profiles of the atypical antipsychotics and attempt to relate the attributes observed in clinical practice and clinical trials to their basic pharmacologic profiles. There is a fair, but not perfect, correspondence between the pharmacologic profiles of the different atypical antipsychotics and their respective clinical attributes. After a comparative overview of their receptor-binding profiles, a brief pharmacokinetic summary will be provided. Finally, the clinical profiles of these agents will be summarized with regard to both their efficacy and adverse effects.

Topics: Animals; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dose-Response Relationship, Drug; Humans; Limbic System; Models, Biological; Olanzapine; Pirenzepine; Psychotic Disorders; Receptors, Neurotransmitter; Risperidone; Schizophrenia

Psychotic symptoms have become increasingly common in patients with idiopathic Parkinson's disease and other parkinsonian syndromes. This increased prevalence of psychoses is in part a reflection of the greater longevity of people with Parkinson's disease and, to a certain extent, is a consequence of our success in treating the motor symptoms of these syndromes. The psychotic symptoms associated with Parkinson's disease can be as varied as the motor symptoms. They stem from interactions between the underlying neuropathologies of the syndromes and the adverse effects associated with chronic antiparkinsonian drug administration. In patients with advanced Parkinson's disease, there is also a high prevalence of affective comorbidity. This increase in affective symptoms and the relatively high incidence of cognitive and affective side effects of the antiparkinsonian medications contribute to the increase in psychoses observed in these older patients. The most significant risk factors for developing psychosis in Parkinson's disease are (1) coexistence of dementia, (2) protracted sleep disturbances, and (3) nighttime use of long-acting dopaminomimetics. This article reviews the phenomenology, pathophysiology, and treatment of psychosis associated with parkinsonism and discusses how atypical antipsychotic medications have revolutionized the management of the symptoms and improved the quality of life of those affected.

Topics: Algorithms; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Clozapine; Comorbidity; Decision Trees; Dibenzothiazepines; Humans; Olanzapine; Parkinson Disease; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders; Quetiapine Fumarate

The management of agitation and aggression in psychiatric inpatients is a significant clinical dilemma. Establishing a clear diagnosis and distinguishing whether aggression is an acute manifestation or a long-standing or repetitive problem are fundamental antecedents of medication treatment. For acute aggression, either benzodiazepines or antipsychotic medications (typical and atypical) are recommended choices. Currently, on the basis of efficacy, ease of use, and availability in multiple (tablet, liquid, intramuscular) preparations, typical antipsychotics such as loxapine should be considered as first choice for acute aggression (in psychosis). On the other hand, atypical antipsychotics, particularly clozapine, should be considered when aggression in psychosis persists and/or is repetitive. Typical antipsychotics are indicated for persistent aggression in psychosis when medication noncompliance is the obstacle to effective treatment.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Loxapine; Mental Disorders; Olanzapine; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

Clinical studies with clozapine have clearly demonstrated its superior efficacy over that of conventional antipsychotics in treatment-resistant schizophrenic patients. In comparative trials with these drugs, considerably more patients respond to treatment with clozapine than to conventional antipsychotic medication. Recently, new antipsychotics, such as olanzapine, quetiapine, risperidone, sertindole, and zotepine, have been introduced, but extensive data on their effects in treatment-resistant patients are not yet available. Published studies have drawn criticism in terms of inappropriate titration schedules, nonequivalent dosing between treatment groups, short treatment duration, and inadequate sample sizes. Further research will be needed to determine whether novel antipsychotics may substitute for clozapine in the future or whether clozapine will retain its unique role in the management of patients suffering from difficult-to-treat schizophrenic disorders.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dibenzothiepins; Double-Blind Method; Drug Resistance; Humans; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Since the discovery of the neuroleptics in 1952, french psychiatrists have proposed a classification of neuroleptics taking into account the pharmalogical and therapeutic differences between these drugs. They distinguished three different clinical effects of neuroleptics: sedative effects, effects on the positive symptoms of schizophrenia and effects on the negative symptoms. However these agents have many side effects including the extrapyramidal syndrome (EPS), akathisia, dystonia and parkinsonism. These side effects occur in up to 75% of patients receiving typical neuroleptics and are the main cause of non-compliance. Since the eighties, clozapine was introduced for use in refractory patients because it has a better efficacy (than haloperidol) specifically on negative symptoms, a better tolerance and fewer effects. After clozapine, several new antipsychotic agents are now available, such as risperidone, olanzapine, sertindole, quietapine, ziprasidone ... Their therapeutical effects are probably linked with a dual antagonist effect on 5HT2 and D2 receptors. The present article reviews the evolution of the use of these new agents, their real efficacy, their adverse effects and their expanding indications. Future research will more clearly establish appropriate treatment guidelines for their use. These new antipsychotics should add a positive modification in schizophrenia care and in some mood disorders. The approach consisting on individualizing dimensions and clusters analysis might be useful to test the efficiency of each antipsychotic on a syndromic dimension.

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Sulpiride; Thiazoles

Antipsychotic agents have been used commonly in the treatment of bipolar disorder. This article reviews the evolution of the use of antipsychotic agents and their role in the acute and maintenance treatment of bipolar disorder. The focus is on neuroleptic drugs, the atypical antipsychotic drugs (risperidone and clozapine), and two fo the new atypical antipsychotic drugs that were recently approved.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Lithium; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Treatment Outcome

The author reviews the evolution of emergency psychiatric practice over the past 20 years--from the concept of high-dose antipsychotic medication to the more rational treatment approach for acute psychosis made possible by modern pharmacodynamic insight and the availability of new pharmacotherapeutic agents. A decision tree for current practice in the rapid tranquilization of agitated, apparently psychotic patients is described.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Clozapine; Decision Trees; Drug Administration Schedule; Emergency Services, Psychiatric; Emergency Treatment; Haloperidol; History, 20th Century; Humans; Lorazepam; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone

The incidence of acute extrapyramidal symptoms (EPS)--akathisia, dystonia, and parkinsonism--associated with traditional antipsychotics varies, but most researchers agree that neuroleptic-induced EPS occur in 50% to 75% of patients who take conventional antipsychotics. Atypical antipsychotics were developed to widen the therapeutic index and to reduce EPS. Although the mechanisms are unclear, the risk of EPS is less with the novel antipsychotics than with conventional drugs, and agents that produce low levels of acute EPS are likely to produce less tardive dyskinesia. Nevertheless, clinicians should exercise caution when comparing data from investigations of the novel antipsychotics and, until long-term data become available, should administer the new drugs at doses below the EPS-producing level.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Dystonia; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance Withdrawal Syndrome

Olanzapine is a thienobenzodiazepine derivative which displays efficacy in patients with schizophrenia and related psychoses. It has structural and pharmacological properties resembling those of the atypical antipsychotic clozapine and an improved tolerability profile compared with the classical antipsychotic haloperidol. In several large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine generally 5 to 20 mg/day was at least as effective as haloperidol (5 to 20mg) and more so than placebo, as assessed by overall rating scales for psychoses. Olanzapine improved negative symptoms to a greater extent than haloperidol in 2 of 3 comparative trials, including the largest trial. Efficacy of olanzapine has a rapid onset (within 1 to 2 weeks). Its clinical benefits appear to be maintained for treatment periods of up to 1 year, as shown by analysis of the extension phase of several trials demonstrating decreased probability of hospitalisation over this period compared with haloperidol. Preliminary data suggest the drug may also improve quality of life. Olanzapine was associated with significantly fewer adverse movement disorders (e.g. akathisia, dystonia, hypertonia, extrapyramidal symptoms) than haloperidol. There have been no reports of agranulocytosis (as occurs with clozapine) or any other haemotoxicity attributed to olanzapine, and the drug has shown minimal effect on prolactin levels. Transient increases in levels of hepatic transaminases seem to be clinically important. The only events recorded more frequently during olanzapine than during haloperidol therapy were weight gain, dry mouth and increased appetite. Although the antipsychotic activity of olanzapine has been well demonstrated. Its efficacy in refractory schizophrenia and its place relative to other atypical antipsychotics remain to be determined. Nevertheless, if the long term tolerability profile of olanzapine is confirmed, the drug should provide a valuable therapeutic alternative in the management of schizophrenia and related psychoses.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia

As the new generation of atypical antipsychotics becomes available, the limitations of the older typical agents become apparent. The new medications, which have benefits other than the alleviation of positive symptoms of schizophrenia, may also be beneficial for psychotic disorders that have responded poorly to conventional neuroleptics. This article will describe the potential use of the atypical antipsychotics, especially olanzapine, for affective mood disturbances in schizophrenia, psychotic depression and mania, first-break schizophrenia, comorbid schizophrenia and substance abuse disorders, dementia in the elderly and those with late-onset schizophrenia, and behavioral problems in patients with mental retardation or developmental delays.

Topics: Antipsychotic Agents; Benzodiazepines; Child; Comorbidity; Dementia; Depressive Disorder; Developmental Disabilities; Diagnosis, Dual (Psychiatry); Humans; Intellectual Disability; Mental Disorders; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Substance-Related Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Benzothiazoles; Clinical Trials as Topic; Dibenzothiazepines; Humans; Imidazoles; Indoles; Olanzapine; Piperazines; Pirenzepine; Pramipexole; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles

The unprecedented level of activity in the development of new antipsychotic medications can be traced to the 1989 approval of clozapine by the US Food and Drug Administration for treatment of refractory schizophrenia. This has encouraged the development of other new agents that share some of clozapine's receptor binding characteristics. A wide range of clinical trial designs are being used during the development of new antipsychotic medications. This article describes both basic designs and more innovative ones: flexible-dose designs that include placebo and conventional neuroleptic agents as controls; fixed-dose designs with multiple doses of experimental medication; and fixed-dose designs with multiple doses of the experimental and comparator medication. The strengths and weaknesses of each are identified. The need for long-term maintenance studies of newer agents is emphasized because psychotic disorders in general, and schizophrenia in particular, are chronic relapsing illnesses. The current status of four newer antipsychotic medications is considered: clozapine, risperidone, olanzapine, and sertindole. The importance of direct comparison among the newer antipsychotic medications in both short- and long-term trials is highlighted.

Topics: Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clinical Trials as Topic; Clozapine; Drug Administration Schedule; Drug Approval; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Recurrence; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; United States; United States Food and Drug Administration

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

Although neuroleptic drugs have become the mainstay of treating acute and chronic psychosis, they are substantially limited by troublesome side effects. The traditional neuroleptic drugs have a wide array of central nervous system and peripheral system side effects that often lead to problems in management or patient noncompliance. Of particular difficulty are the extrapyramidal symptoms and tardive dyskinesia. However, other side effects of seizures, sedation, neuroleptic malignant syndrome and cardiovascular, hematologic, endocrinological, and weight gain problems remain as clinical management challenges posed by existing antipsychotic drug therapy. Considerable progress has been made in improving the motor side effect profile with the advent of clozapine and risperidone. However, each of these drugs has its own dose-limiting side effect profile. Two new drugs, olanzapine and sertindole, are now added to the pharmacopeia for treating psychosis. They further improve the benefit/ risk ratio because they have even fewer EPS and other side effects. Overall, these new antipsychotic agents greatly improve the treatment of psychosis by reducing drug-induced morbidity and improving the quality of life for patients.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Humans; Imidazoles; Indoles; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Seizures; Sleep; Weight Gain

Advances in the neurosciences, concerns about cost containment, and a growing consumer advocacy movement are creating new hopes and challenges for the development of more effective and cost-effective treatments for persons with psychotic disorders. Using the development of new antipsychotic agents for the treatment of schizophrenia as a prototype, this article examines the assessment of outcomes of treatments for these patients. Psychotic disorders exert a broad range of negative effects on patients' lives. This requires a broad view of outcomes to assess the relative effectiveness of alternative pharmacotherapies. The outcomes of interest cover the clinical, rehabilitative, humanitarian, and public welfare domains. Most of our knowledge about the efficacy of antipsychotic agents focuses on improvements in and prevention of positive symptoms of schizophrenia. However, better antipsychotic medications must show advantages above and beyond symptom suppression. We need to know not only whether alternative medications offer advantages in these other dimensions of outcome, but also how they interact with psychosocial treatments to enhance outcomes, how effective they are with patients in usual practices settings, and how cost-effective they are relative to other treatments. A research agenda for evaluating these impacts must include longer term outcome studies that evaluate the wider range of outcomes of interest to practitioners, patients, families, and payers.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Costs; Health Care Reform; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Impaired insight into delusions is associated with a lower probability of remission of psychotic depression, independent of illness severity. The relationship between participant characteristics and impaired insight into delusions in remitted psychotic depression, and whether impaired insight is associated with risk of relapse of psychotic depression during continuation pharmacotherapy were examined.. Data were analyzed from 126 participants in the STOP-PD II study who experienced sustained remission of psychotic depression during 8-week stabilization treatment with sertraline plus olanzapine and were then randomized to 36 weeks of continuation treatment with sertraline plus either olanzapine or placebo. Insight into delusions was assessed with the Resolution of Delusions Scale (RODS). Linear regression analyses examined the associations between participant characteristics and insight into delusions. Cox proportional-hazards models examined whether i) change in RODS during stabilization treatment; or ii) RODS at the end of stabilization treatment predicted risk of relapse during 36 weeks of continuation treatment.. Severity of psychosis before initiation of treatment was the only participant characteristic associated with the change in insight during stabilization treatment. Neither change in insight during stabilization treatment nor insight at the end of stabilization treatment was associated with risk of relapse.. Insufficient statistical power and the lack of variability in RODS scores at the time of randomization may have contributed to the absence of a relationship between RODS and risk of relapse.. Residual or reemergent insight impairment following acute treatment does not preclude patients from sustaining remission of psychotic depression in a randomized placebo-controlled trial.

Topics: Antipsychotic Agents; Benzodiazepines; Delusions; Depression; Drug Therapy, Combination; Humans; Olanzapine; Psychotic Disorders; Sertraline; Treatment Outcome

Topics: Adolescent; Age of Onset; Antipsychotic Agents; Child; Female; Humans; Male; Molindone; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; United States

Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.. From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.. The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea.. Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Female; Follow-Up Studies; Haloperidol; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Young Adult

Some, but not all, studies have found longer duration of untreated psychosis (DUP) to be associated with poor response to treatment and more severe negative symptoms in schizophrenia. The aim of the current analysis was to investigate these parameters in a large cohort of patients in their first psychotic episode. The OPTiMiSE cohort included 446 patients with DUP up to two years, who were administered amisulpride for 4 weeks (Phase I). Patients who did not meet Andreasen remission criteria were randomized to double-blind continuation of amisulpride or olanzapine for 6 additional weeks in a blinded study (Phase II). Analyses showed that shorter DUP was associated with lower baseline CGI scores (p<0.001, r = 0.184), PANSS total (p = 0.025, r = 0.106) and PANSS negative subscale scores (p = 0.023, r = 0.107). Remitters had a significantly shorter mean DUP compared to non-remitters both in Phase I (24.5 weeks ±24.3 vs. 35 weeks ± 32.2, p = 0.01, t=-2.521) and in Phase II (24.3 weeks ± 26.4 vs. 38.3 weeks ± 31.3, p = 0.031, t=-2.194). Logistic regression analyses showed a significant effect of DUP on treatment response both in phase I (p = 0.008) and phase II (p = 0.041). Linear regression analyses found that DUP significantly affects PANSS Total change at the end of phase I (p = 0.028) but not at the end of phase II (p = 0.236). Based on these findings, it is possible to conclude that shorter DUP is associated with better response to treatment, particularly during the first weeks after treatment initiation. These findings highlight the need for early identification of the first psychotic episode.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Cohort Studies; Double-Blind Method; Europe; Female; Humans; Male; Olanzapine; Psychotic Disorders; Time Factors; Treatment Outcome; Young Adult

Prescriptions for antipsychotic medications continue to increase across many brain disorders, including off-label use in children and elderly individuals. Concerning animal and uncontrolled human data suggest antipsychotics are associated with change in brain structure, but to our knowledge, there are no controlled human studies that have yet addressed this question.. To assess the effects of antipsychotics on brain structure in humans.. Prespecified secondary analysis of a double-blind, randomized, placebo-controlled trial over a 36-week period at 5 academic centers. All participants, aged 18 to 85 years, were recruited from the multicenter Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). All participants had major depressive disorder with psychotic features (psychotic depression) and were prescribed olanzapine and sertraline for a period of 12 to 20 weeks, which included 8 weeks of remission of psychosis and remission/near remission of depression. Participants were then were randomized to continue receiving this regimen or to be switched to placebo and sertraline for a subsequent 36-week period. Data were analyzed between October 2018 and February 2019.. Those who consented to the imaging study completed a magnetic resonance imaging (MRI) scan at the time of randomization and a second MRI scan at the end of the 36-week period or at time of relapse.. The primary outcome measure was cortical thickness in gray matter and the secondary outcome measure was microstructural integrity of white matter.. Eighty-eight participants (age range, 18-85 years) completed a baseline scan; 75 completed a follow-up scan, of which 72 (32 men and 40 women) were useable for final analyses. There was a significant treatment-group by time interaction in cortical thickness (left, t = 3.3; P = .001; right, t = 3.6; P < .001) but not surface area. No significant interaction was found for fractional anisotropy, but one for mean diffusivity of the white matter skeleton was present (t = -2.6, P = .01). When the analysis was restricted to those who sustained remission, exposure to olanzapine compared with placebo was associated with significant decreases in cortical thickness in the left hemisphere (β [SE], 0.04 [0.009]; t34.4 = 4.7; P <.001), and the right hemisphere (β [SE], 0.03 [0.009]; t35.1 = 3.6; P <.001). Post hoc analyses showed that those who relapsed receiving placebo experienced decreases in cortical thickness compared with those who sustained remission.. In this secondary analysis of a randomized clinical trial, antipsychotic medication was shown to change brain structure. This information is important for prescribing in psychiatric conditions where alternatives are present. However, adverse effects of relapse on brain structure support antipsychotic treatment during active illness.. ClinicalTrials.gov Identifier: NCT01427608.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Cerebral Cortex; Depressive Disorder, Major; Diffusion Tensor Imaging; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Sertraline; White Matter; Young Adult

Patients with schizophrenia and comorbid alcohol use disorder remain understudied. This post hoc analysis evaluated data from Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness in Schizophrenia study (January 2001-December 2004).. Patients without substance abuse (except marijuana use) in the month before study entry were categorized into those with a history of alcohol use disorder (SZ + AUD) within 5 years before study entry and those without alcohol use disorder (SZ-only) per DSM-IV criteria. Time to first and recurrent exacerbations and hospitalizations were compared between disease states and between olanzapine and perphenazine, quetiapine, risperidone, and ziprasidone.. A total of 1,338 patients (SZ + AUD = 22.6%; SZ-only = 77.4%) were included. Time to first exacerbation of SZ was significantly shorter in the SZ + AUD versus SZ-only population (median = 5.4 vs 6.4 months; hazard ratio [HR] = 1.20 [95% CI, 1.01-1.42]; P = .039). Similar findings were observed for first hospitalization (HR = 1.63 [95% CI, 1.20-2.22]; P = .002) and recurrent hospitalizations (HR = 1.60 [95% CI, 1.18-2.15]; P = .002). The most common reasons leading to exacerbation in both groups were an increase in symptom severity and lack of efficacy. In patients with SZ + AUD related or unrelated to marijuana, perphenazine, quetiapine, risperidone, and ziprasidone were associated with significantly shorter time to first exacerbation versus olanzapine.. This post hoc analysis confirmed that patients with SZ + AUD had a worse illness course than patients with SZ-only and suggests that olanzapine may be associated with a longer time to first and recurrent exacerbations versus other antipsychotics in this difficult-to-treat population. Further research is needed to identify effective treatments for this important yet understudied patient population.. ClinicalTrials.gov identifier: NCT00014001.

Topics: Adult; Alcoholism; Antipsychotic Agents; Comorbidity; Female; Hospitalization; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Severity of Illness Index; Symptom Flare Up; Thiazoles; Time Factors

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.

Topics: Antipsychotic Agents; Benzodiazepines; Dopamine; Humans; Olanzapine; Piperazines; Piperidines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Treatment Outcome

Amisulpride, aripiprazole, and olanzapine are first-line atypical antipsychotics that have not previously been compared head-to-head in a pragmatic trial. We aimed to compare the efficacy and safety of these agents in a controlled trial.. This pragmatic, rater-blind, randomised controlled trial was done in three academic centres of psychiatry in Norway, and one in Austria. Eligible patients were aged 18 years or older, met ICD-10 criteria for schizophrenia-spectrum disorders (F20-29), and had symptoms of active psychosis. Eligible patients were randomly assigned to receive oral amisulpride, aripiprazole, or olanzapine. Treatment allocation was open to patients and staff, and starting dose, treatment changes, and adjustments were left to the discretion of the treating physician. Computer-generated randomisation lists for each study centre were prepared by independent statisticians. Patients were followed up for 52 weeks after random assignment, during which assessments were done 8 times by researchers masked to treatment. The primary outcome was reduction of the Positive And Negative Syndrome Scale (PANSS) total score at 52 weeks, and primary analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01446328.. Between Oct 20, 2011, and Dec 30, 2016, we assessed 359 patients for eligibility. 215 patients were excluded (107 did not meet inclusion criteria, 82 declined to participate, 26 other reasons). 144 patients (mean baseline PANSS total estimated score 78·4 [SD 1·4]) were randomly assigned 1:1:1 to receive amisulpride (44 patients), aripiprazole (48 patients) or olanzapine (52 patients). After 52 weeks, the patients allocated to amisulpride had a PANSS total score reduction of 32·7 points (SD 3·1) compared with 21·9 points reduction with aripiprazole (SD 3·9, p=0·027) and 23·3 points with olanzapine (2·9, p=0·025). We observed weight gain and increases of serum lipids and prolactin in all groups. 26 serious adverse events (SAEs) among 20 patients were registered (four [9%] of 44 patients allocated to amisulpride, ten [21%] of 48 patients allocated to aripiprazole, and six [12%] of 52 patients allocated to olanzapine), with no statistically significant differences between the study drugs. 17 (65%) of the 26 SAEs occurred during the use of the study drug, with readmission or protracted hospital admission accounting for 13 SAEs. One death by suicide, one unspecified death, and one life-threatening accident occurred during follow-up, after cessation of treatment.. Amisulpride was more efficacious than aripiprazole or olanzapine for reducing the PANSS total scores in adults with schizophrenia-spectrum disorders. Side-effect differences among the groups were generally small. This study supports the notion that clinically relevant efficacy differences exist between antipsychotic drugs. Future research should aim to compare first-line antipsychotics directly in pragmatic clinical trials that reflect everyday clinical practice.. The Research Council of Norway, the Western Norway Regional Health Trust, and participating hospitals and universities.

Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Aripiprazole; Female; Humans; Male; Middle Aged; Norway; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Treatment Outcome; Weight Gain; Young Adult

The study objective was to examine whether and when antipsychotic-induced weight gain in first episode psychosis (FEP) stabilizes over a 12-month exposure to the same antipsychotic in a sample of previously untreated FEP patients.. In this prospective naturalistic outcome study, 109 patients diagnosed with non-affective or affective psychosis (DSM-IV) were treated with the same antipsychotic medication (olanzapine n = 45, risperidone n = 39, or aripiprazole n = 25) throughout the first year of treatment. Body weight was measured and body mass index calculated at baseline and 1, 2, 3, 6, 9, and 12 months. Additional weight data over the second year were available, making extending the comparison for a second year possible.. Linear mixed model analysis showed a significant main effect of time (Type III test P < .001) after adjusting for baseline weight values. Post hoc pairwise comparisons showed that incremental weight changes subsequent to month 6 were insignificant, suggesting weight stabilization by month 9. No significant difference (P = .243) between groups or time × group interaction (P = .111) was observed. Similar findings were obtained with BMI. A follow-up analysis, of a subsample who continued treatment with the same antipsychotic for an additional 12 months (n = 57), confirmed weight stabilization in the second year. There was no significant main effect of time (P = .641), group (P = .539), or time × group interaction (P = .250).. Antipsychotic-induced weight gain occurs mostly in the first few months of treatment. Preventive interventions concurrent to second-generation antipsychotic treatment initiation in medication-naive FEP patients might be warranted.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Body Mass Index; Female; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Risperidone; Time Factors; Weight Gain; Young Adult

Antipsychotic induced weight gain is a frequent reason for treatment discontinuation in psychosis, subsequently increasing the risk of relapse and negatively affecting patient well-being. The metabolic effect of weight gain and the subsequent risk of obesity constitute a major medical problem on the long term. Despite its consequences, to date few risk factors have been identified (age, gender, body mass index at baseline), with some authors suggesting the implication of early life stressful events, such as perinatal conditions. We aim to describe if a surrogate marker of intrauterine environment (birth weight) might predict weight gain in a cohort of 23 antipsychotic naïve patients at the onset of the psychotic disease evaluated during 16 weeks with olanzapine treatment and in another cohort of 24 psychosis-resistant patients initiating clozapine assessed for 18 weeks. Two independent linear mixed model analyses were performed in each cohort of patients, with prospective weight gain as the dependent variable, age, gender, body mass index, duration of treatment and time as independent variables. Only in naïve patients, weight gain due to antipsychotics was significantly associated with birth weight, while male gender and body mass index at baseline were associated in both cohorts of patients. Treatment-resistant psychotic patients under clozapine were older, had previous antipsychotic treatment and more years of disease, confounders that might have influence a non significant association. Our results suggest that early environmental events might be playing a role in weight evolution in naïve patients treated with antipsychotics.

Topics: Adult; Antipsychotic Agents; Birth Weight; Body Mass Index; Clozapine; Cohort Studies; Female; Humans; Male; Models, Biological; Olanzapine; Pregnancy; Prenatal Exposure Delayed Effects; Psychotic Disorders; Sex Factors; Weight Gain; Young Adult

In patients with schizophrenia, medication adherence is important for relapse prevention, and effective adherence monitoring is essential for treatment planning. A digital medicine system (DMS) has been developed to objectively monitor patient adherence and support clinical decision making regarding treatment choices. This study assesses the acceptance and performance of the DMS in adults with schizophrenia, schizoaffective disorder or first-episode psychosis and in healthcare professionals (HCPs).. This is a multicentre, 8-week, single-arm, open-label pragmatic trial designed using coproduction methodology. The study will be conducted at five National Health Service Foundation Trusts in the UK. Patients 18-65 years old with a diagnosis of schizophrenia, schizoaffective disorder or first-episode psychosis will be eligible. HCPs (psychiatrists, care coordinators, nurses, pharmacists), researchers, information governance personnel, clinical commissioning groups and patients participated in the study design and coproduction. Intervention employed will be the DMS, an integrated system comprising an oral sensor tablet coencapsulated with an antipsychotic, non-medicated wearable patch, mobile application (app) and web-based dashboard. The coencapsulation product contains aripiprazole, olanzapine, quetiapine or risperidone, as prescribed by the HCP, with a miniature ingestible event marker (IEM) in tablet. On ingestion, the IEM transmits a signal to the patch, which collects ingestion and physical activity data for processing on the patient's smartphone or tablet before transmission to a cloud-based server for viewing by patients, caregivers and HCPs on secure web portals or mobile apps.. Approval was granted by London - City and East Research Ethics Committee (REC ref no 18/LO/0128), and clinical trial authorisation was provided by the Medicines and Healthcare products Regulatory Agency. Written informed consent will be obtained from every participant. The trial will be compliant with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines and the Declaration of Helsinki.. NCT03568500; EudraCT2017-004602-17; Pre-results.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Biosensing Techniques; Cloud Computing; Humans; Medical Informatics Applications; Medication Adherence; Mobile Applications; Multicenter Studies as Topic; Olanzapine; Pragmatic Clinical Trials as Topic; Psychiatry; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Tablets; United Kingdom

Topics: Adult; Antipsychotic Agents; Deprescriptions; Female; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Mental Status and Dementia Tests; Olanzapine; Perphenazine; Proportional Hazards Models; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Altered cortical brain morphology is observed in psychotic disorders. Despite the importance of lipid homeostasis for healthy brain functioning, knowledge about its role in cortical alterations in psychosis is limited. In a sample of patients with psychotic disorders, we investigated the relationship between treatment with olanzapine (OLZ), and cortical thickness and gray/white matter intensity contrast, and the association between these measures and serum lipid levels. We included 33 OLZ users, 19 unmedicated psychotic patients and 76 healthy controls (HC). Data on serum lipids and cortical measures based on MR brain images processed with FreeSurfer were analyzed with General Linear Models. We found that intensity contrast was similar in OLZ users as compared to HC and that the cortex (frontal, orbitofrontal, medial temporal) was thinner in OLZ users (p < 0.05, Bonferroni corrected). An OLZ-specific HDL interaction effect was further found for the pericentral cortical thickness measure (p < 0.05, Bonferroni corrected). Additionally, nominally significant findings indicated similar OLZ-specific interaction effects for cortical thickness in several regions, and an OLZ-specific interaction with LDL for occipital lobe contrast (p < 0.05, uncorrected). Our findings may suggest a drug-related lipid-effect on brain myelination. Experimental studies and replications in different study samples are needed to clarify these complex relationships further.

Topics: Adult; Antipsychotic Agents; Cerebral Cortex; Cholesterol; Cross-Sectional Studies; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Olanzapine; Psychotic Disorders; Treatment Outcome; White Matter

Acute akathisia is a neuropsychiatric syndrome with a negative effect on illness outcome. Its incidence in patients treated with antipsychotics has shown to be highly variable across studies.. Our goals were to investigate prevalence, risk factors for the development of acute akathisia, and differences in incidence between antipsychotics in a sample of 493 first episode non-affective psychosis patients.. This is a pooled analysis of three prospective, randomized, flexible-dose, and open-label clinical trials. Patients were randomized assigned to different arms of treatment (haloperidol, quetiapine, olanzapine, ziprasidone, risperidone, or aripiprazole). Akathisia was determined using the Barnes Akathisia Scale at 6 weeks after antipsychotic initialization. Univariate analyses were performed to identify demographic, biochemical, substance use, clinical, and treatment-related predictors of acute akathisia. Considering these results, a predictive model based of a subsample of 132 patients was constructed with akathisia as the dependent variable.. The overall incidence of akathisia was 19.5%. No differences in demographic, biochemical, substance use, and clinical variables were found. Significant incidence differences between antipsychotics were observed (Χ. Among second generation antipsychotics, only olanzapine and quetiapine should be considered as akathisia-sparing drugs. The type of antipsychotic, having been hospitalized, and a more severe symptomatology at intake seem to predict the development of acute akathisia.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Piperazines; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Thiazoles; Young Adult

The Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) compared the efficacy of risperidone, olanzapine, and molindone over 8 weeks in 119 youths age 8-19 years with early-onset schizophrenia or schizoaffective disorder. From this large dataset, we examined predictors of treatment response and drop out using stepwise regression and receiver operating characteristics curve (ROC) analysis. Treatment response was defined as having both a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) score and a Clinical Global Impression-Improvement (CGI-I) score < 3. More severe baseline symptoms, having a history of being in an early education program, and previous prescription of a mood stabilizer increased the likelihood of responding to treatment. Anhedonia and poor community functioning predicted a reduction in symptom severity on the PANSS. Random assignment to different antipsychotic treatment was not predictive of outcome. Parental report of aggressive behaviors at baseline and being African American were associated with a greater likelihood of drop out. Our results suggest youth with more severe psychotic symptoms are most likely to benefit from treatment with antipsychotics and that aggressive youth may require additional support to improve treatment adherence. Further investigation is needed to understand potentially modifiable predictors of response like early education programs.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Early Diagnosis; Female; Humans; Olanzapine; Patient Dropouts; Predictive Value of Tests; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Studies analyzing concentration-effect relationships in second-generation antipsychotics have reported contradictory results in chronic schizophrenia. No data are available for the early stages of the disease. The present study aims to evaluate the association between a single olanzapine plasma concentration, clinical response, and severity of adverse effects in first-episode psychosis (FEP); to test the utility of various plasma breakpoints as markers of early response to treatment; and to identify variables affecting olanzapine concentrations.. Data from 23 compliant FEP patients receiving olanzapine monotherapy (5-30 mg/d) were evaluated 2 months after beginning treatment. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg for Kliniske Undersøgelser scale. Plasma samples were drawn at 11 (SD, 1) hours after dosing and analyzed with high-performance liquid chromatography/tandem mass spectrometry.. Consistent with findings on chronic disease, dose, age, sex, weight, and cigarettes/day accounted for some of the variability in olanzapine concentrations. While no relationship was found between olanzapine concentrations and adverse effects or improvement of depressive symptoms, response of psychotic symptoms was associated with concentrations between 22.56 and 77.92 ng/mL. Plasma breakpoints did not show sufficiently high specificity, resulting in a large number of false-positive results.. Although olanzapine concentrations do not seem to be reliable indicators of early drug effect in FEP, they may still prove useful for detecting noncompliance, as well as pharmacokinetically relevant comorbidities or genetic particularities in drug metabolism.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Drug Monitoring; Humans; Middle Aged; Olanzapine; Pilot Projects; Psychotic Disorders; Young Adult

This study examined the effect of adjunctive telmisartan on psychopathology and cognition in olanzapine- or clozapine-treated patients with schizophrenia.. In a 12-week randomized, double-blind, placebo-controlled study, patients diagnosed with schizophrenia or schizoaffective disorder received either telmisartan (80 mg once per day) or placebo. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS), and a neuropsychological battery was used to assess cognitive performance. Assessments for psychopathology and cognition were conducted at baseline and week 12.. Fifty-four subjects were randomized, and 43 completed the study (22 in the telmisartan group, 21 in the placebo group). After 12-weeks of treatment, the telmisartan group had a significant decrease in PANSS total score compared withthe placebo group (mean ± SD: - 4.1 ± 8.1 vs. 0.4 ± 7.5, P = 0.038, SCohen's d = 0.57). There were no significant differences between the two groups in change from baseline to week 12 in PANSS subscale scores, SANS total score, or any cognitive measures (P > 0.100).. The present study suggests that adjunctive treatment with telmisartan may improve schizophrenia symptoms. Future trials with larger sample sizes and longer treatment durations are warranted.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Antipsychotic Agents; Benzimidazoles; Benzoates; Benzodiazepines; Clozapine; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Schizophrenia; Telmisartan

Biomarkers are now widely used in many fields of medicine, and the identification of biomarkers that predict antipsychotic efficacy and adverse reactions is a growing area of psychiatric research. Monoamine molecules of the peripheral bloodstream are possible prospective biomarkers based on a growing body of evidence indicating that they may reflect specific changes in neurotransmitters in the brain. The aim of this study was to detect peripheral biogenic amine indicators of patients with acute psychosis and to test the correlations between the biological measures studied and the psychopathological status of the patients.. This research included 60 patients with acute psychosis treated with olanzapine (n = 30) or haloperidol (n = 30). Here, we measured biogenic amine indicators, including mRNA levels of dopamine receptor D4 (DRD4) and the serotonin 2A receptor (5HTR2A), in peripheral blood mononuclear cells (PBMCs) using quantitative real-time polymerase chain reaction and serum dopamine concentrations by enzyme linked immunosorbent assay (ELISA). Psychopathological status was evaluated using psychometric scales. The assessments were conducted prior to and after 14 and 28 days of treatment.. The administration of haloperidol, but not olanzapine, up-regulated 5HTR2A mRNA in a linear manner, albeit without statistical significance (p = 0.052). Both drugs had non-significant effects on DRD4 mRNA levels. Nevertheless, a positive correlation was found between DRD4 and 5HTR2A mRNA levels over a longitudinal trajectory, suggesting co-expression of the two genes. A significant positive correlation was observed between 5HTR2A mRNA levels and total Positive and Negative Syndrome Scale (PANSS) scores in both groups of patients before treatment. A significant correlation between baseline 5HTR2A mRNA levels and PANSS scores on days 14 and 28 of treatment remained for patients treated with olanzapine only. Moreover, a significant positive correlation was observed between blood serum dopamine levels and scores on extrapyramidal symptom scales in the olanzapine group.. The DRD4 and 5HTR2A genes are co-expressed in PBMCs during antipsychotic administration. Despite a correlation between the studied biogenic amine indicators and the psychopathological status of patients, reliable biomarkers of treatment response could not be determined.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Dopamine; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D4; Treatment Outcome; Young Adult

Ziprasidone (ZIP) is often used with olanzapine (OLZ) in 'switch' and combination therapy but empirical evidence to support these strategies is limited.. This study was therefore designed to compare the efficacy and tolerability of switching from OLZ to ZIP, the combination of both medications, and OLZ and ZIP monotherapy, in patients with schizophrenia spectrum disorders (SSD).. In this 12 week open-label, assessor-blinded randomized trial, 148 patients with SSD who had not used antipsychotics for at least 3 months were assigned to ZIP (n = 49) or OLZ monotherapy (n = 31); OLZ for 4 weeks then a switch to ZIP (OLZ/ZIP, n = 35); or combination therapy (OLZ + ZIP, n = 33). The severity of psychosis and abnormal involuntary movements was evaluated at baseline, 1, 2, 4, 8, and 12 weeks using standard instruments. Baseline-to-endpoint changes in weight gain and metabolic measures were compared.. The efficacy of both OLZ/ZIP and OLZ + ZIP was comparable OLZ monotherapy and better than ZIP monotherapy in reducing overall psychotic and negative symptoms at most 8 and 12 week measurement points. Changes in weight gain, glucose, and lipid measures did not differ between OLZ/ZIP and OLZ + ZIP, but were markedly higher following OLZ monotherapy. The OLZ + ZIP group had the lowest overall incidence of adverse events and extrapyramidal symptoms of all the treatment regimens.. We conclude that combining ZIP and OLZ at the outset of treatment is superior to switching from OLZ to ZIP in terms of improving psychotic symptoms and limiting movement side effects without increasing the risk of metabolic syndrome.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Drug Substitution; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Male; Metabolic Syndrome; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Single-Blind Method; Thiazoles; Treatment Outcome; Weight Gain

To characterize cognitive function at baseline and investigate the relationship between change in cognition, depression, and psychosis after treatment among older adults with major depressive disorder with psychotic features.. This was a secondary analysis of a double-blind, randomized, controlled treatment trial at inpatient and outpatient settings at four academic health centers on "Young Old" (aged 60-71 years, N = 71) and "Older" (aged 72-86 years, N = 71) participants diagnosed with psychotic depression. Olanzapine plus sertraline or olanzapine plus placebo were given until week 12 or termination.. At baseline, Young Old and Older participants did not differ on measures of depression severity or global cognition, information processing speed, and executive function. Improvement in depressive and psychotic symptoms from baseline to treatment end was similar in both the Young Old and Older groups. However, improvement in depressive symptoms was significantly associated with improvement in global cognitive function in Young Old participants but not in Older participants.. Cognitive dysfunction was not a detriment to improvement in symptoms of psychotic major depression in our geriatric patients. Young Old and Older patients improved to a similar degree on measures of depression and delusions from baseline to treatment end. However, improvement in cognition over the course of treatment was more prominent in the Young Old group than in the Older group.

Topics: Aged; Aged, 80 and over; Aging; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cognition; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Humans; Late Onset Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Sertraline; Treatment Outcome

Patients with schizophrenia experience higher rates of obesity and related morbidity and mortality than the general population does. Given preclinical studies revealing the role of histamine H1 receptor in human eating behavior, and the potential of olanzapine to block with this system, we hypothesized that histamine H1 receptor agonists may be beneficial in reducing antipsychotic-associated weight gain. In the present study, 36 patients with a diagnosis of schizophrenia or schizoaffective disorder and treated with olanzapine were randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study outcomes were change in body weight from baseline and effect on antipsychotic efficacy of olanzapine. The patients in the betahistine group had less weight gain (-1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg, respectively). Positive and Negative Syndrome Scale Questionnaire showed improvement within each group and that subjects treated with betahistine enjoyed an improvement (reduction) by a mean of 35.7 points, higher when compared with placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal amount of subjects in both groups experienced adverse effects during the course of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects). Overall, there were no clinically marked differences in safety signals between both groups. A larger study addressing the weaknesses of this pilot study is warranted.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Betahistine; Double-Blind Method; Drug Therapy, Combination; Female; Histamine Agonists; Humans; Internationality; Male; Olanzapine; Pilot Projects; Psychotic Disorders; Schizophrenia; Weight Gain; Young Adult

While doctors often increase the dose of an antipsychotic when there is insufficient response, there is limited evidence that this intervention is any better than waiting longer on the lower dose. We put the proposition to test.. In this 4-week, double-blind, randomized controlled trial conducted in psychiatric care from September 2012 to March 2015, 103 patients with schizophrenia (ICD-10) who did not respond to olanzapine 10 mg/d or risperidone 3 mg/d were randomly allocated to a dose-increment or -continuation group. In the increment group, antipsychotic doses were doubled for 4 weeks, whereas in the continuation group, doses were not changed. Completion rate (primary outcome measure); changes in psychopathology, function, and extrapyramidal symptoms; and response rate were compared between the groups. The relationship between baseline plasma antipsychotic concentrations and changes in psychopathology was examined.. The completion rate was significantly lower in the increment group than in the continuation group (69.2% [36/52] vs 86.3% [44/51], P = .038). No significant superiority was observed in any of the outcome measures in the increment group compared to the continuation group, except the Positive and Negative Syndrome Scale (PANSS) positive subscale score change in intention-to-treat analysis. Those with lower plasma concentrations of olanzapine on their initial treatment showed a greater improvement on the PANSS positive subscale when their dose was increased (P = .042).. As a general strategy, patients with schizophrenia failing to respond to moderate antipsychotic doses may not benefit from an increase in dose. The possibility of benefit in those whose plasma antipsychotic concentrations at baseline are still low cannot be ruled out.. UMIN.ac.jp/ctr/index.htm identifier: UMIN000008667.

Topics: Adult; Aged; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Female; Humans; Japan; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology

The risk of persistent tardive dyskinesia (TD) was compared in patients with acute psychosis or agitation aged 55 years or older who were treated with olanzapine (OLZ) or conventional antipsychotic (CNV) drug therapy.. Patients without TD were randomized to treatment with OLZ (2.5-20 mg/d; n = 150) or CNV (dosed per label; n = 143). Following a 6-week drug tapering/initiation period, patients without TD were treated with OLZ or CNV for up to 1 year. The a priori defined primary outcome end point was persistent TD defined as Abnormal Involuntary Movement Scale (AIMS) scores = 2 on at least 2 items or ≥3 on at least 1 item (items 1-7) lasting at least for 1 month (Criterion A). Post hoc analyses assessed persistent TD meeting the criterion of moderate severity defined as AIMS score ≥3 on at least 1 item persisting for 1 month (Criterion B) and probable TD defined as elevated AIMS scores (Criterion A or B) not persisting for 1 month. Treatment groups were compared using Kaplan-Meier curve with log-rank exact test.. On average, patients were 78 years of age; the predominant diagnosis was dementia (76.7% in the OLZ group and 82.5% in the CNV group). Approximately, 40.6% of patients in the CNV group received haloperidol. No significant difference in time to developing persistent TD was observed during treatment with OLZ or CNV (cumulative incidence: OLZ, 2.5% [95% confidence interval [95% CI]: 0.5-7.0]; CNV, 5.5% [95% CI: 2.1-11.6], P = .193). The exposure-adjusted event rates per 100 person-years were not significantly different between treatment groups: OLZ (2.7) and CNV (6.3; ratio: 0.420; 95% CI: 0.068-1.969). Post hoc analyses revealed a significantly lower risk of at least moderately severe persistent TD persisting for 1 month (P = .012) and probable TD not persisting for 1 month (Criterion A, P = .030; Criterion B, P = .048) in OLZ-treated patients. For those patients without significant extrapyramidal symptoms at baseline, significantly more patients in the CNV treatment group developed treatment-emergent parkinsonism than for patients in the OLZ treatment group (CNV: 70%, 35 of 50 patients; OLZ 44%, 25 of 57 patients; P = .011). No significant difference between the groups was observed for treatment-emergent akathisia (CNV: 6%, 7 of 117 patients; OLZ: 10%, 13 of 130 patients; P = .351).. The cumulative incidence of persistent TD was low and the risk of persistent TD did not differ significantly among predominantly older adult patients having dementia with acute psychosis or agitation treated with OLZ or CNV.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Haloperidol; Humans; Incidence; Kaplan-Meier Estimate; Male; Movement Disorders; Olanzapine; Prospective Studies; Psychotic Disorders; Treatment Outcome; United States

To compare the efficacy and safety profile between intramuscular (IM) olanzapine and IM haloperidol plus IM lorazepam in acute schizophrenic patients with moderate to severe agitation.. This was a prospective, randomized, open-label study. Acutely agitated patients with schizophrenia or schizoaffective disorder (n = 67) were randomized to receive 10 mg IM olanzapine (n = 37) or 5 mg IM haloperidol plus 2 mg IM lorazepam (n = 30). Agitation was measured with Positive and Negative Syndrome Scale Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES) during the first 2 hours and at 24 hours after the first injection. Safety was assessed using the Simpson-Angus Scale and Barnes Akathisia Rating Scale and by recording adverse events at 24 hours following the first injection. The Clinical Global Impression-Severity scale was also rated.. The PANSS-EC scores decreased significantly at 2 hours after the first injection in both groups (olanzapine: -10.2, p < 0.001; haloperidol + lorazepam: -9.9, p < 0.001). Haloperidol plus lorazepam was not inferior to olanzapine in reducing agitation at 2 hours. There were no significant differences in PANSS-EC or ACES scores between the two groups within 2 hours following the first injection. The frequencies of adverse events and changes in Clinical Global Impression-Severity, Simpson-Angus Scale, and Barnes Akathisia Rating Scale scores from baseline to 24 hours showed no significant differences between the groups.. The findings suggest that IM haloperidol (5 mg) plus lorazepam (2 mg) is not inferior to IM olanzapine (10 mg) in the treatment of acute schizophrenic patients with moderate to severe agitation (ClinialTrials.gov identifier number NCT00797277).

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Haloperidol; Humans; Injections, Intramuscular; Lorazepam; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Taiwan; Treatment Outcome

We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested.. This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76).. BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01).. The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well.

Topics: Adult; Alleles; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Brain-Derived Neurotrophic Factor; Cholesterol, HDL; Cholesterol, LDL; Dyslipidemias; Female; Genotype; Glycated Hemoglobin; Humans; Insulin Resistance; Male; Middle Aged; Obesity; Olanzapine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prospective Studies; Psychotic Disorders; Risk Factors; Risperidone; Schizophrenia; Triglycerides

Clinical evidence and expert opinion support using a combination of an antipsychotic and an antidepressant when treating major depression with psychotic features. We characterized the impact of sertraline co-administration on olanzapine clearance in psychotic depression using population pharmacokinetic methods.. The Study of Pharmacotherapy for Psychotic Depression (STOP-PD) randomized 259 participants to olanzapine plus placebo or olanzapine plus sertraline. Olanzapine was started at 2.5-5 mg/day and sertraline at 25-50 mg/day. Doses were increased to a maximum of 20 mg/day for olanzapine and 200 mg/day for sertraline. Up to four olanzapine concentration samples were collected during the 12-week trial and 12-week continuation phase. We used NONMEM (Version VII) for population pharmacokinetic analysis, assessing effects of the covariates sex, African American origin, smoking, age, and sertraline co-administration.. Population pharmacokinetic analysis comprised 336 samples from 175 individuals. The structural model published by Bigos et al. was sufficient to describe the olanzapine data adequately: a one-compartment model with first-order absorption and elimination, using an additive residual error structure with the absorption rate constant fixed to 0.5. Sertraline co-administration significantly increased olanzapine apparent clearance (p < 0.005) by 25-35 % depending on the patient characteristics included. Male sex was associated with a significantly increased clearance. Age and race did not have a significant impact on clearance.. Contrary to expectations from the knowledge of cytochrome P450 interactions, sertraline increased olanzapine apparent clearance. Plausible explanations include patients treated with sertraline having poorer adherence to olanzapine, or the impact of sertraline inhibition of transporters resulting in increased intracellular concentrations and thus access to metabolizing enzymes.

Topics: Adult; Aged; Benzodiazepines; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Models, Biological; Olanzapine; Psychotic Disorders; Sertraline; Sex Factors

The purpose of this study was to assess differences in the outcomes of youth with schizophrenia-spectrum disorders (SCZ-S) and psychotic disorder not otherwise specified (PsyNOS) during early antipsychotic treatment.. The study was a prospective, naturalistic, inception cohort study of youth ≤19 years old with SCZ-S (schizophrenia, schizoaffective disorder, schizophreniform disorder) or PsyNOS (PsyNOS, brief psychotic disorder) and ≤24 months of lifetime antipsychotic treatment receiving clinician's choice antipsychotic treatment. Baseline demographic, illness and treatment variables, and effectiveness outcomes were compared at 12 weeks last-observation-carried-forward across SCZ-S and PsyNOS patients, adjusting for significantly different baseline variables.. Altogether, 130 youth with SCZ-S (n=42) or PsyNOS (n=88), mostly antipsychotic naïve (76.9%), were prescribed risperidone (47.7%), olanzapine (19.2%), aripiprazole (14.6%), quetiapine (11.5%), or ziprasidone (6.9%). Compared with those with PsyNOS, SCZ-S youth were older (16.4±2.1 vs. 14.8±3.2, p=0.0040), and less likely to be Caucasian (19.1% vs. 42.5%, p=0.009). At baseline, SCZ-S patients had significantly higher Clinical Global Impressions-Severity (CGI-S) scores (6.0±0.9 vs. 5.5±0.8, p=0.0018) and lower Children's Global Assessment Scale (CGAS) scores (29.6±9.2 vs. 36.1±8.9, p=0.0002) and were more likely to be in the severely ill CGAS group (i.e., CGAS≤40). SCZ-S and PsyNOS patients did not differ regarding all-cause discontinuation (40.5 vs. 40.3%. p=0.49), discontinuation because of adverse effects (12.2% vs. 12.4%, p=0.97), or nonadherence (29.3% vs. 30.9%, p=0.88), but somewhat more SCZ-S patients discontinued treatment for inefficacy (19.5% vs. 7.4%, p=0.063). CGI-S and CGAS scores improved significantly in both diagnostic groups (p=0.0001, each). Adjusting for baseline differences, PsyNOS patients experienced significantly better CGI-I improvement (CGI-I) scores (p=0.012) and more frequently reached higher categorical CGAS group status (p=0.021) than SCZ-S patients.. Both youth with SCZ-S and those with PsyNOS experienced significant improvements with clinician's choice antipsychotic treatment. However, treatment discontinuation was common within 12 weeks, with greater inefficacy-related discontinuation in the SCZ-S group, whereas CGI-I and CGAS score-based improvements were greater in the PsyNOS group.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Treatment Outcome

Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments.. Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures.. Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons.. Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Diagnostic and Statistical Manual of Mental Disorders; Drug Monitoring; Female; Humans; Lithium; Male; Olanzapine; Psychotic Disorders; Treatment Outcome

To examine whether cerebrovascular risk, executive function, and processing speed are associated with acute treatment outcome of psychotic depression in older adults.. The authors analyzed data from 142 persons aged 60 years or older with major depression with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo. The independent variables were baseline cerebrovascular risk (Framingham Stroke Risk Score), baseline executive function (Stroop interference score and the initiation/perseveration subscale of the Mattis Dementia Rating Scale), and baseline processing speed (color and word reading components of the Stroop). The outcome variable was change in severity of depression, measured by the 17-item Hamilton Depression Rating Scale total score, during the course of the RCT.. Greater baseline cerebrovascular risk was significantly associated with less improvement in depression severity over time, after controlling for pertinent covariates. Neither executive function nor processing speed predicted outcome.. This study suggests an association of cerebrovascular risk, but not executive function or processing speed, with treatment outcome of major depression with psychotic features in older adults.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cognition; Cognition Disorders; Depressive Disorder, Major; Double-Blind Method; Executive Function; Humans; Mental Processes; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Reaction Time; Risk; Sertraline; Severity of Illness Index; Stroop Test; Treatment Outcome; Young Adult

Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data.. This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables.. Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension.. Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

Topics: Adolescent; Adult; Antipsychotic Agents; Bayes Theorem; Benzodiazepines; Female; Haloperidol; Humans; Male; Marijuana Smoking; Middle Aged; Models, Psychological; Olanzapine; Prognosis; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Sex Factors; Time Factors; Treatment Outcome; Young Adult

Data on the long-term metabolic side-effects associated with antipsychotics are scarce. Prospective longitudinal studies in medication-naive patients with a first episode of psychosis are a valuable source of information as they provide an assessment prior to the antipsychotic exposure and minimize the effect of potential confounding factors. The aim of this study was to assess the course of weight gain and the incidence of metabolic abnormalities during the first 3 yr of antipsychotic treatment. Data were collected from a cohort of 170 first-episode psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine (32%) and risperidone (36%). The dose used was flexible. The initial antipsychotic treatment was changed when required, based on clinical response and tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the total mean weight gain) and then stabilized gradually over time. Total cholesterol, LDL-cholesterol and triglyceride levels followed a similar trajectory with a significant increase only during the first year. No significant changes were detected in the mean values of glycaemic parameters. Two patients with a family history of diabetes developed diabetes type II. At short-term the factors positively associated with weight gain were lower body mass index, male gender and olanzapine treatment. At long-term, functional status and clinical response were the main predictors. The results of our study indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic changes. Identification of weight gain patterns may help to inform studies that aim to prevent or mitigate the metabolic adverse events associated with antipsychotic therapy.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Male; Metabolic Diseases; Middle Aged; Olanzapine; Prospective Studies; Psychotic Disorders; Risk Factors; Risperidone; Time Factors; Weight Gain; Young Adult

Olanzapine (OLZ), a commonly prescribed second generation antipsychotic drug, is associated with obesity and metabolic syndrome and may contribute to increased cardiovascular morbidity and mortality. Opioidergic neurotransmission may be implicated in the development of these metabolic disturbances. The objective of this study was to assess the effects of opioid blockade on OLZ-treated patients' metabolic status. Patients with schizophrenia or schizoaffective disorder (n=30) on a stable dose of OLZ were randomized in a double-blind fashion to receive an opioid receptor antagonist, naltrexone (NTX), (n=14) or placebo (n=16). The primary outcome measure was the change in body mass index (BMI) at 12 weeks. Secondary measures included body fat and fat-free mass, along with homeostasis model assessment-estimated insulin resistance (HOMA-IR), plasma lipids and liver function tests (LFTs). There was no significant change in BMI between the treatment arms. However, in comparison to the OLZ + placebo combination, the OLZ + NTX group displayed a significant decrease in the fat and increase in fat-free mass along with a trend towards improvement in HOMA-IR values. There were no significant differences in plasma lipids and LFTs. These findings suggest that addition of NTX to OLZ may attenuate OLZ-induced body fat mass gain. A larger study of longer duration will be needed to confirm these results.

Topics: Adipose Tissue; Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Double-Blind Method; Female; Humans; Insulin Resistance; Lipids; Liver Function Tests; Male; Middle Aged; Naltrexone; Olanzapine; Pilot Projects; Psychotic Disorders; Schizophrenia; Young Adult

Agitation is a major problem in acute schizophrenia. Only a few studies have tested antipsychotic agents in severely agitated patients, mainly because of legal issues. Furthermore, most studies were limited to the first 24 hours. We aimed to investigate the efficacy of oral haloperidol, risperidone, and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospective, randomized, rater-blinded, controlled design within a naturalistic treatment regimen.. In total, 43 severely agitated patients at acute care psychiatric units were enrolled. Participants were randomly assigned to receive either daily haloperidol 15 mg, olanzapine 20 mg, or risperidone 2 to 6 mg over 5 days. Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable. A mixed-model analysis was applied.. All drugs were effective for rapid tranquilization within 2 hours. Over 5 days, the course differed between agents (P < 0.001), but none was superior. Dropouts occurred only in the risperidone and olanzapine groups. Men responded better to treatment than did women during the initial 2 hours (P = 0.046) as well as over the 5-day course (P < 0.001). No difference between drug groups was observed regarding diazepam or biperiden use.. Oral haloperidol, risperidone, and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders. Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study.

Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sex Factors; Switzerland; Time Factors; Treatment Outcome; Young Adult

There is no established psychometric instrument dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to investigate whether a new composite rating scale, the Psychotic Depression Assessment Scale (PDAS), covering both the psychotic and the depressive domains of PD, could detect differences in effect between two psychopharmacological treatment regimens.. We reanalyzed the data from the Study of Pharmacotherapy of Psychotic Depression (STOP-PD), which compared the effect of Olanzapine+Sertraline (n=129) versus Olanzapine+Placebo (n=130). The response to the two regimens was compared using both a mixed effects model and effect size statistics on the total scores of three rating scales: the 17-item Hamilton Depression Rating Scale (HAM-D17), its 6-item melancholia subscale (HAM-D6), and the 11-item PDAS consisting of the HAM-D6 plus five items from the Brief Psychiatric Rating Scale covering psychotic symptoms.. According to both statistical approaches, the PDAS, the HAM-D17 and the HAM-D6 were all able to detect significant differences in treatment effect between Olanzapine+Sertraline and Olanzapine+Placebo (Olanzapine+Sertraline being superior). Notably, 45% of the trial participants were at least "probable psychotic" at their last assessment in the trial.. The STOP-PD was not designed specifically to answer the research questions of the present study.. The Psychotic Depression Assessment Scale (PDAS) is a sensitive measure of treatment response in PD. The fact that 45% of the patients still experienced psychotic symptoms at their last trial assessment emphasizes the need to include items pertaining to psychotic symptoms in rating scales for PD.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Sertraline; Treatment Outcome

People with psychosis often experience weight gain, which places them at risk of cardiovascular disease, diabetes, and early death.. To determine the uptake, adherence, and clinical effectiveness of a healthy living intervention designed to reduce weight gain.. An exploratory randomized controlled trial, comparing the intervention with treatment as usual (TAU) in 2 early intervention services for psychosis in England. DSM-IV classification was the diagnostic criteria used to assign the psychiatric diagnoses. The primary outcome was change in body mass index (BMI) from baseline to 12-month follow-up. The study was conducted between February 2009 and October 2012.. 105 service users, with a BMI of ≥ 25 (≥ 24 in South Asians), were randomized to intervention (n = 54) or TAU (n = 51) after stratification by recent commencement of antipsychotic medication. Ninety-three service users (89%) were followed up at 12 months. Between-group difference in change in BMI was not significant (effect size = 0.11). The effect of the intervention was larger (effect size = 0.54, not significant) in 15 intervention (28%) and 10 TAU (20%) participants who were taking olanzapine or clozapine at randomization.. The healthy living intervention did not show a significant difference in BMI reduction compared to the TAU group.. www.isrctn.org identifier: ISRCTN22581937.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Diet; Drug Therapy, Combination; Female; Follow-Up Studies; Health Behavior; Humans; Male; Motor Activity; Olanzapine; Pilot Projects; Psychiatric Status Rating Scales; Psychotherapy; Psychotic Disorders; Single-Blind Method; Treatment Outcome; Young Adult

There are conflicting results on the impact of anxiety on depression outcomes. The impact of anxiety has not been studied in major depression with psychotic features ("psychotic depression").. We assessed the impact of specific anxiety symptoms and disorders on the outcomes of psychotic depression.. We analyzed data from the Study of Pharmacotherapy for Psychotic Depression that randomized 259 younger and older participants to either olanzapine plus placebo or olanzapine plus sertraline. We assessed the impact of specific anxiety symptoms from the Brief Psychiatric Rating Scale ("tension", "anxiety" and "somatic concerns" and a composite anxiety score) and diagnoses (panic disorder and GAD) on psychotic depression outcomes using linear or logistic regression. Age, gender, education and benzodiazepine use (at baseline and end) were included as covariates.. Anxiety symptoms at baseline and anxiety disorder diagnoses differentially impacted outcomes. On adjusted linear regression there was an association between improvement in depressive symptoms and both baseline "tension" (coefficient=0.784; 95% CI: 0.169-1.400; p=0.013) and the composite anxiety score (regression coefficient = 0.348; 95% CI: 0.064-0.632; p=0.017). There was an interaction between "tension" and treatment group, with better responses in those randomized to combination treatment if they had high baseline anxiety scores (coefficient=1.309; 95% CI: 0.105-2.514; p=0.033). In contrast, panic disorder was associated with worse clinical outcomes (coefficient=-3.858; 95% CI: -7.281 to -0.434; p=0.027) regardless of treatment.. Our results suggest that analysis of the impact of anxiety on depression outcome needs to differentiate psychic and somatic symptoms.

Topics: Antidepressive Agents; Antipsychotic Agents; Anxiety; Anxiety Disorders; Benzodiazepines; Depressive Disorder, Major; Female; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

The objective of this study was to assess the long-term safety and efficacy of olanzapine long-acting injection (LAI). A 6-year, single-arm, open-label extension study of olanzapine LAI was conducted at 127 sites in 25 countries. Patients were 18-76 years of age, were diagnosed with schizophrenia or schizoaffective disorder (N=931), and had been previously enrolled in one of three clinical trials of olanzapine LAI. Patients received flexibly dosed (45-405 mg) olanzapine LAI every 2-4 weeks. The mean duration of exposure was ∼3 years. A total of 393 (42.2%) patients completed the study. The mean weight change was +2.1 kg (P<0.001), with 40.6% of patients experiencing 7% or higher weight gain. Treatment-emergent categorical changes occurred in fasting glucose, total cholesterol, and triglyceride levels. Pharmacokinetic analyses revealed no systemic accumulation of olanzapine after long-term treatment. There were 36 occurrences of post-injection delirium/sedation syndrome, all resolving within 72 h. The mean Positive and Negative Syndrome Scale total and subscale scores did not change significantly over the course of the study, indicating clinical stability. Olanzapine LAI appeared effective as a long-term maintenance treatment, with a safety profile generally consistent with the known profile of oral olanzapine, except for injection-related events (including post-injection delirium/sedation syndrome).

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Cholesterol; Delayed-Action Preparations; Delirium; Double-Blind Method; Female; Humans; Injections, Intramuscular; International Cooperation; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quality of Life; Schizophrenia; Treatment Outcome; Triglycerides; Young Adult

To explore whether poor initial insight during a first episode of mania with psychotic features was predictive of poor psychosocial and clinical outcomes at 18 months.. Secondary analysis was performed on data collected during an 8-week RCT comparing the efficacy of olanzapine versus chlorpromazine as an adjunct to lithium, and at 18-month follow-up. 74 participants were divided into three groups (no insight, partial insight, and full insight) according to the insight item from the Young Mania Rating Scale (YMRS). Differences between these three groups were examined at baseline and at 18 months on measures of symptoms (YMRS, HAMD-21, and CGI-S), and social and occupational functioning (SOFAS). Baseline differences between the three groups were determined using general linear models and chi-squared analyses. Group differences from baseline to 18-month follow-up were determined using repeated measures general linear models.. At baseline there were significant differences between the three insight groups in terms of mania and functioning, but at 18 months all groups had improved significantly in terms of psychopathology, mania, depression and social and occupational functioning. There were no significant differences between the three groups at study completion with respect to these domains.. The study was limited by the lack of availability of a more detailed rating scale for insight, and it did not account for the duration of untreated psychosis (DUI).. Poor initial insight during a first episode of mania with psychotic features does not predict poor clinical and psychosocial outcome at 18 months.

Topics: Adult; Antipsychotic Agents; Awareness; Benzodiazepines; Bipolar Disorder; Chi-Square Distribution; Chlorpromazine; Depression; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Judgment; Linear Models; Lithium Compounds; Male; Middle Aged; Olanzapine; Predictive Value of Tests; Prognosis; Psychotic Disorders; Severity of Illness Index; Social Adjustment

This study was designed to investigate whether a preventive weight management program (WMP) reduces weight gain during olanzapine (OLZ) treatment. Moreover, we examined the effects of intervention on metabolic parameters.. Patients (N = 100) with schizophrenia or schizoaffective disorder (DSM-IV) who had commenced treatment with OLZ were recruited. Following a run-in period of 4 weeks, 74 patients who had gained at least 1.5 kg body weight were randomized to receive either 12 bi-weekly WMP sessions (prevention group (PG), n = 36), or usual care (control group (CG), n = 38). Anthropometric and metabolic parameters were assessed after the 24-week intervention phase and a 24-week follow-up.. Forty-two percent of 74 participants (PG: 36.1%, CG: 47.4%) finished the 24-week intervention phase while 34% of them (PG: 30.6%, CG: 36.8%) completed the 48-week study. There was no significant difference in weight gain between groups (PG: + 3.4 ± 4.2 kg vs. CG: + 4.5 ± 6.1 kg, P = 0.184) after 24 weeks. Nevertheless, PG showed a significantly smaller increase in waist circumference than CG (PG: + 4.6 ± 8.3 cm, CG: + 10.1 ± 7.3 cm, P = 0.019) after 48 weeks. Furthermore, PG showed a significantly smaller increase in fasting glucose (P = 0.031) and 2-h glucose after oral glucose load (P = 0.018) than CG.. These results suggest that preventive WMP may reduce the risk of abdominal obesity and deterioration of glucose metabolism in OLZ-treated patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Dyslipidemias; Early Medical Intervention; Female; Glucose Intolerance; Humans; Male; Middle Aged; Obesity; Olanzapine; Psychotic Disorders; Schizophrenia; Weight Reduction Programs

The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate.. A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis.. Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis.. The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Female; Follow-Up Studies; Haloperidol; Humans; Longitudinal Studies; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Risperidone; Schizophrenia; Time Factors; Treatment Outcome; Young Adult

To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies.. Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were randomized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study: (1) 40 mg/d for 2 weeks; (2) 40 mg/d for 1 week, increased to 80 mg/d on day 8 for week 2 (up-titration group); and (3) 80 mg/d for 2 weeks. Lurasidone was then flexibly dosed (40-120 mg/d) for the subsequent 4 weeks of the study. The preswitch antipsychotic agent was tapered by day 7 to 50% of the original dose and discontinued by the end of week 2. Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as "sedating" (olanzapine or quetiapine) or "nonsedating" (all other antipsychotics). The primary outcome measure was time to treatment failure, defined as any occurrence of insufficient clinical response, exacerbation of underlying disease, or discontinuation due to an adverse event. The study was conducted from June 2010 to May 2011.. Of 240 subjects treated in this study, 86 (35.8%) were treated with an antecedent sedating antipsychotic, and 154 (64.2%) were treated with an antecedent nonsedating antipsychotic. Nineteen (7.9%) of the 240 patients experienced treatment failure. No clinically relevant differences were observed when the 3 randomized switch groups were compared. Treatment failure rates were 10/86 (11.6%) versus 9/154 (5.8%) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication, respectively. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, glucose, insulin, lipids, or prolactin; mean improvements in weight and lipids were observed. Movement disorder rating scales did not demonstrate meaningful changes. The incidence of akathisia as an adverse event was 12.5%; only 1 subject (0.4%) discontinued due to akathisia.. Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks, or 80 mg/d for 2 weeks, or 40 mg/d for 1 week followed by 80 mg/d the second week.. ClinicalTrials.gov identifier: NCT01143077.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Isoindoles; Lurasidone Hydrochloride; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Time Factors; Treatment Failure; Treatment Outcome

Tardive dyskinesia (TD) is a debilitating adverse effect associated with antipsychotic treatment. Older age and the presence of mood disorder have been identified as risk factors for the development of TD. Thus, we assessed the incidence of TD in younger and older patients with major depressive disorder with psychotic features who participated in a 12-week clinical trial comparing olanzapine plus sertraline versus olanzapine plus placebo. All subjects (n = 259) were assessed with the Abnormal Involuntary Movement Scale at baseline and after 4, 8, and 12 weeks of treatment (or at termination). We used 7 different published criteria to estimate the prevalence of TD at baseline and the incidence over the duration of the trial. We compared the incidence of TD in subjects 60 years or older and those younger than 60 years. The overall prevalence and incidence of TD varied almost 10-fold, depending on the criteria (prevalence range, 1.2%-8.9%; incidence range, 0.0%-5.9%). Tardive dyskinesia was observed as a clinical adverse event in only 1 subject (0.4%). Whereas older subjects had a higher prevalence of TD at baseline, the incidence in younger and older subjects did not differ significantly. The incidence of TD was relatively low in both younger and older patients with major depressive disorder with psychotic features treated acutely with olanzapine. However, the estimate of the risk of TD varies widely, depending on the criteria used to define TD.

Topics: Age Factors; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Humans; Incidence; Middle Aged; Olanzapine; Prevalence; Psychotic Disorders; Risk Factors; Sertraline; Time Factors

In contrast to olanzapine, ziprasidone has been reported to cause minimal or no weight gain. This study aimed to compare the effects of ziprasidone and olanzapine on weight, body composition, appetite, resting energy expenditure, substrate oxidation, and metabolic parameters in adults with schizophrenia or other psychotic disorders.. Twenty adults with schizophrenia or other psychotic disorders were randomized 1:1 to ziprasidone 20-160 mg/day or olanzapine 5-20 mg/day for 12 weeks. The mean doses during the 12-week study period were 109(range: 65-140) mg/day for ziprasidone and 11.6(range: 8.2-15.5) mg/day for olanzapine. Body weight, appetite, body composition, resting energy expenditure, and metabolic parameters were measured before and after drug treatment. Outcome measurements before and after medication were compared, and ziprasidone- and olanzapine-treated patients were compared.. After 12 weeks, olanzapine-treated patients showed significant weight gain, particularly fat gain, with increased low density lipoprotein-cholesterol and decreased high density lipoprotein-cholesterol concentrations. In contrast, ziprasidone-treated patients showed no significant weight gain with increased high density lipoprotein-cholesterol concentration.. Ziprasidone was associated with a lower propensity for weight gain and central fat deposition than olanzapine. Studies in larger patient samples are required to confirm these results.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Appetite; Benzodiazepines; Body Composition; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Energy Metabolism; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Piperazines; Psychotic Disorders; Schizophrenia; Thiazoles; Weight Gain; Young Adult

We examined clinical characteristics including serum olanzapine concentrations for acute schizophrenia patients who required above conventional doses. We performed a rater-blinded, randomized clinical trial in 12 psychiatric emergency sites. Eligible patients were 18-64 years old and met diagnostic criteria for schizophrenia, acute schizophrenia-like psychotic disorder, or schizoaffective disorder. A total of 42 patients were randomly assigned by means of sealed envelopes to receive risperidone (3-12 mg/day; n=20) and olanzapine (10-40 mg/day; n=22), with follow-up at 8 weeks. The Negative score of the Positive and Negative Syndrome Scale was significantly higher in patients who required high doses than in patients who responded to conventional doses. Serum olanzapine concentrations at the time of oral 20mg/day could be obtained from 5 out of 7 patients who subsequently required high-dose olanzapine. All values were more than 30 ng/mL after 11-16 h from dosing to sample collection, and the mean value was 47.876 (S.D. 21.546) ng/mL. Such concentrations are appropriate with respect to a therapeutic range of 20-50 ng/mL. The present study has shown evidence that the reason for requiring high-dose olanzapine cannot be explained by pharmacokinetics in the treatment of acute-phase schizophrenia.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Emergency Services, Psychiatric; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Young Adult

Hallucinations are prevalent in schizophrenia and related psychotic disorders and may have severe consequences for the affected patients. Antipsychotic drug trials that specifically address the anti-hallucinatory effectiveness of the respective drugs in representative samples are rare. The aims of the present study were to investigate the rate and severity of hallucinations in acutely admitted psychotic patients at hospital admission and discharge or after 6 weeks at the latest, if not discharged earlier (discharge/6 weeks); and to compare the anti-hallucinatory effectiveness of risperidone, olanzapine, quetiapine, and ziprasidone with up to 2 years' follow-up.. Adult patients acutely admitted to an emergency ward for psychosis were consecutively randomized to risperidone, olanzapine, quetiapine, or ziprasidone and followed for up to 2 years in a pragmatic design. Participants were assessed repeatedly using the hallucinatory behavior item of the Positive and Negative Syndrome Scale (PANSS).. A total of 226 patients, 30.5% of those assessed for eligibility, were randomized and 68% were hallucinating at baseline. This proportion was reduced to 33% at discharge/6 weeks. In the primary analyses based on intention to treat groups of patients experiencing frequent hallucinations, the quetiapine and ziprasidone groups both had faster decreases of the mean hallucination scores than the risperidone group.. Hallucinations are fairly responsive to antipsychotic drug treatment and differential anti-hallucinatory effectiveness may be found among existing antipsychotic drugs. If replicated, this could pave the way for a more targeted pharmacotherapy based on individual symptom profiles, rather than on the diagnostic category.. ClinicalTrials.gov ID; NCT00932529.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Hallucinations; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Cognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis.. Adult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery.. A total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group.. Ziprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome; Young Adult

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease. All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures. PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment. The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Piperazines; Psychomotor Disorders; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles; Treatment Outcome; Young Adult

The mechanism underlying the weight gain due to treatment with olanzapine and other second generation antipsychotics has not been fully understood. To examine olanzapine's weight gain effects, we accepted first attack psychotic patients with no medication (pre-treatment) (n=22) and the healthy control group (n=26) in this study. After patientś diagnosis, they were hospitalized and then treated for four weeks with olanzapine (post-treatment). We used case-control association design to test body mass index (BMI) and biochemical changes in each group. We also investigated peripheral leptin and neuropeptides/hormones namely, pro-opiomelanocortin (POMC), cocaine and amphetaime regulated transcript (CART), and neuropeptide Y (NPY) levels. These neuropeptides which are synthesized/secreted from arcuate nucleus of hypothalamus affect food intake and therefore, body weight. After 4 weeks of olanzapine treatment; BMI (body mass index), waist circumference, blood triglyceride, total cholesterol, and very low density lipoprotein (VLDL) levels were increased significantly in patients compared to their pre-treatment baseline. In pre-treatment, patients' NPY levels were significantly lower while α-MSH, the anorexigenic product of POMC levels were significantly higher vs. control. Both leptin and NPY levels were significantly increased in patients after the treatment but the NPY levels were also significantly lower in post-treatment vs. the control group. The CART levels did not change after the treatment. We may presume that the antagonist effect of olanzapine on the serotonin (5HT2CR and 5HT1BR) receptors of the arcuate hypothalamic neurons may be a basis for a deregulation of the neurohormones secretion.

Topics: Adult; alpha-MSH; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cholesterol; Humans; Hypothalamus; Leptin; Male; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Olanzapine; Psychotic Disorders; Waist Circumference

The aim of the study was to identify predictors associated with a lower likelihood of achieving a clinical remission 1 year after the first break of the illness. Participants were 174 consecutive subjects included in a first episode programme with no prior treatment with antipsychotic medication. Patients were assigned to haloperidol, olanzapine or risperidone in a randomized, open-label, prospective clinical trial. The main outcome variable was the remission criteria developed by the Remission in Schizophrenia Working Group. Clinical variables were included in a logistic regression analysis in order to predict the remission state at 1 year. At 1 year, 31% of patients met criteria for remission. The logistic regression analysis revealed that the strongest predictors of achieving clinical remission 1 year away from a first episode of non-affective psychosis were the length of duration of untreated psychosis (DUP), the severity of negative symptomatology and the educational level attained at baseline. The results suggest that: (1) patients with a lengthy DUP, a greater severity of negative symptomatology at baseline and with a lower education level are in a higher risk of not achieving a clinical remission during the first year of treatment; and (2) early intervention clinical programs should aim to reduce the length of DUP in order to provide a better outcome for patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Educational Status; Female; Haloperidol; Humans; Logistic Models; Longitudinal Studies; Male; Olanzapine; Prognosis; Psychotic Disorders; Remission Induction; Risk Factors; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Time-to-Treatment; Young Adult

Constipation is a common and potentially fatal side effect of clozapine treatment. Another important side effect of clozapine may also be significant weight gain. Orlistat is a weight-control medication that is known to induce loose stools as a common side effect. This study aimed to explore whether orlistat used to control clozapine-induced weight gain can simultaneously tackle clozapine-related constipation. In this 16-week randomized-controlled study, clozapine-treated patients received add-on orlistat (n=30) or add-on placebo (n=24). Colonic function was measured using the Bristol Stool Form Scale. There was a significant (P=0.039) difference in the prevalence of constipation in favor of orlistat over placebo in completers (n=40) at the endpoint. A decrease in the prevalence of constipation within the orlistat group (P=0.035) was observed (vs. no statistically significant changes in the placebo group). In clozapine-treated patients, orlistat may be beneficial not only for weight control but also as a laxative. As no established treatments for clozapine-induced constipation exist, orlistat can be considered for this population, although more studies are required.

Topics: Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Colon; Constipation; Cross-Sectional Studies; Diarrhea; Double-Blind Method; Finland; Humans; Incidence; Lactones; Laxatives; Obesity; Olanzapine; Orlistat; Overweight; Patient Dropouts; Prevalence; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Weight Loss

To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria.. We used equipoise-stratified randomization (a hybrid of complete randomization and clinician's choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010.. Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events.. Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study.. Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients.. ClinicalTrials.gov identifier: NCT00245206.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Therapeutic Equipoise; Triglycerides; United States

This 22-week, open-label study, conducted between November 2006 and September 2008 in a community setting, was designed to determine if weight gain during olanzapine treatment can be prevented or mitigated with adjunctive treatment algorithms that include amantadine, metformin, and zonisamide.. Outpatients with schizophrenia or schizoaffective disorder (DSM-IV-TR criteria) were randomly assigned to olanzapine alone (n = 50), olanzapine plus algorithm A (olanzapine + A [amantadine 200 mg/d with possible switches to metformin 1,000-1,500 mg/d and then to zonisamide 100-400 mg/d; n = 76]), or olanzapine plus algorithm B (olanzapine + B [metformin 1,000-1,500 mg/d with possible switches to amantadine 200 mg/d and then to zonisamide 100-400 mg/d; n = 73]). Brief weight management education was provided at baseline. The primary outcome measure was comparison of mean weight gain between olanzapine and pooled olanzapine + A and olanzapine + B results.. Least squares mean ± SE weight gain was 2.76 ± 0.75 kg for olanzapine, 2.40 ± 0.65 kg for olanzapine + A, and 0.65 ± 0.63 kg for olanzapine + B. Mean weight gain during olanzapine treatment did not differ significantly from pooled results for olanzapine + A and olanzapine + B (P = .065). Participants treated with olanzapine + B experienced significantly less mean weight gain than olanzapine-treated participants (P = .036).. Pooled treatment algorithm results were not significantly different from olanzapine monotherapy in mitigating weight gain. However, participants who received treatment with metformin with possible progression to amantadine and then zonisamide had significantly less mean weight gain than participants treated with olanzapine alone. Progression of some participants through the algorithm indicated that a single therapy solution may not be adequate for every patient. Patients treated with olanzapine should receive regular weight monitoring.. clinicaltrials.gov Identifier: NCT00401973.

Topics: Adolescent; Adult; Aged; Algorithms; Amantadine; Antipsychotic Agents; Benzodiazepines; Clinical Protocols; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Isoxazoles; Male; Metformin; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Weight Gain; Zonisamide

To enhance the effectiveness of antipsychotics in first-episode psychosis is crucial in order to achieve the most favourable prognosis. Difference in effectiveness between antipsychotics is still under debate.. The purpose of this study is to determine the long-term (3-year) effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders.. This is a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention programme of first-episode psychosis. One hundred seventy-four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 3 years. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on per-protocol populations was conducted in the analysis for clinical efficacy.. The treatment discontinuation rate for any cause differed significantly between treatment groups (χ (2) = 10.752; p = 0.005), with a higher rate in haloperidol than in risperidone and olanzapine. The difference in the discontinuation rate between risperidone and olanzapine showed a tendency towards significance (χ (2) = 3.022; p = 0.082). There was a significant difference in the mean time to all-cause discontinuation between groups (log-rank χ ( 2 ) = 12.657;df = 2; p = 0.002). There were no significant advantages to any of the three treatments in reducing the psychopathology severity.. After 3 years of treatment, a lower effectiveness was observed in haloperidol compared to second-generation antipsychotics (SGAs). The use of SGAs for the treatment of early phases of nonaffective psychosis may enhance the effectiveness of antipsychotics.

Topics: Adult; Benzodiazepines; Cohort Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Haloperidol; Humans; Longitudinal Studies; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Risperidone; Time Factors; Treatment Outcome; Young Adult

Despite extensive experience with antipsychotic medications, we have limited capacity to predict which patients will benefit from which medications and for what symptoms. Such prediction is of particular importance for the proper treatment of violence. Our goal was to determine whether executive function predicts outcome of treatment for aggressive behavior and whether such prediction varies across medication groups.. Ninety-nine physically aggressive inpatients (aged 18-60 years) with schizophrenia or schizoaffective disorder (diagnosed according to DSM-IV) who completed tests of executive function were randomly assigned in a double-blind, parallel-group, 12-week trial to clozapine (n = 32), olanzapine (n = 32), or haloperidol (n = 35). The number and severity of aggressive events as measured by the Modified Overt Aggression Scale (MOAS) were the outcome measures. Psychopathology and medication side effects were also assessed. The study was conducted from 1999 to 2004.. Poor executive function predicted higher levels of aggression, as measured by MOAS scores over the 12-week period, in all 3 medication groups (F(1,98) = 222.2, P < .0001). There was, however, a significant interaction effect between medication grouping and executive function (F(1,98) = 15.32, P < .001): clozapine exerted an antiaggression effect even in the presence of executive dysfunction.. Executive function was a strong predictor of response to antiaggression treatment in all medication groups, but clozapine still retained clinical efficacy in the presence of poor executive functioning. Olanzapine was particularly efficacious in the absence of executive dysfunction. These findings have important implications for a targeted approach to the treatment of aggression in patients with schizophrenia.. clinicaltrials.gov Identifier: NCT01123408.

Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Executive Function; Female; Haloperidol; Humans; Male; Olanzapine; Predictive Value of Tests; Psychological Tests; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology

Although some previous studies have compared the 2 medicines, ziprasidone and olanzapine most selected chronic patients as subjects. Therefore, the present study was designed to compare the efficacy and safety of ziprasidone vs. olanzapine in naive first-episode schizophrenia.. 80 patients were randomly assigned to a 6-week treatment either with 80-160 mg/day of ziprasidone or 10-20 mg/day of olanzapine. The primary efficacy measurements were the Positive and Negative Syndrome Scale and Clinical Global Impression-severity scale scores. The second efficacy measurement was the response rate of treatment. Tolerability assessments were also performed.. 79 patients completed the trial. The average dose was 127.5 mg/day with ziprasidone and 19.1 mg/day with olanzapine. No significant differences were found between the 2 groups in primary or secondary efficacy measurements at each visit point (all p>0.05). Body weight significantly increased with olanzapine, and more extrapyramidal symptoms were observed with ziprasidone (all p<0.05). Both medicines were well tolerated, and no serious adverse events were observed.. Ziprasidone was as effective as olanzapine in short-term treatment for first-episode schizophrenia, and both medicines were well tolerated.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Comparative Effectiveness Research; Dose-Response Relationship, Drug; Drug Monitoring; Episode of Care; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Thiazoles; Time Factors; Treatment Outcome; Weight Gain

Patients with schizophrenia or related disorders often switch antipsychotic therapy, most commonly due to lack of efficacy and side effects. The differences in anticipated efficacy and tolerability among atypical antipsychotics may drive switching behaviours. Switching to long-acting antipsychotics may improve adherence. Improving adherence is essential as relatively short medication gaps significantly increase the risk of schizophrenia hospitalizations. Long-term treatment with risperidone long-acting injectable (RLAI), the first available long-acting atypical antipsychotic, versus oral atypical antipsychotics showed better adherence with RLAI. Stable patients with schizophrenia or related disorders treated with a stable dose of antipsychotic showed improved efficacy when switched to flexible doses of RLAI. The most common reason for patients to switch from olanzapine to another antipsychotic is excessive weight gain. Metabolic dysfunction also occurs more commonly with olanzapine than with risperidone. Patients switching from olanzapine to risperidone experienced significant decreases in body weight, body mass index and triglyceride levels, whereas patients switching from risperidone to olanzapine experienced significant increases in body weight and triglyceride levels. The efficacy, tolerability and safety of RLAI in non-acute patients with schizophrenia or schizoaffective disorder previously treated with oral olanzapine needs to be explored.. The objective of this study was to evaluate the efficacy, tolerability and safety of switching from oral olanzapine to RLAI.. This was a six-month, prospective, multicentre, non-randomized, single-arm, open-label trial. The trial evaluated non-acute adult patients with psychotic disorders treated with a stable olanzapine dose who required a treatment change. Three weeks after RLAI initiation, olanzapine was tapered off over 1 week or 3 weeks. Efficacy and safety measures included the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S), Global Assessment of Functioning (GAF) and treatment-emergent adverse events (TEAEs).. Among 96 patients analysed, significant endpoint efficacy changes versus baseline were observed for PANSS, CGI-S and GAF (all p<0.0001). PANSS total score improvement was ≥20% for 65.6% of patients and ≥50% for 31.3%. TEAEs were similar in the 1- and 3-week taper groups (40.0% and 46.5%, respectively). TEAEs were generally mild (34.5%) or moderate (49.0%) in intensity.. Switching non-acute patients with schizophrenia or schizoaffective disorder requiring a treatment change from a stable dose of oral olanzapine to RLAI improved psychiatric symptom control, functioning and patient treatment satisfaction. RLAI was generally well tolerated.. Clinicaltrials.gov identifier: NCT00216632.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Female; Humans; Injections; Male; Middle Aged; Olanzapine; Patient Satisfaction; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

Social cognition captures affect recognition, social cue perception, "theory of mind," empathy, and attributional style. The aim of our study was to assess social cognition in schizophrenia inpatients being treated with first-generation antipsychotic drugs (FGAs), n=28 (perphenazine and haloperidol, FGAs) or with second-generation antipsychotic drugs (SGAs), n=56 (olanzapine and clozapine, SGAs).. Eighty-four patients completed the Facial Expression Recognition Test, the Voice Emotion Recognition Test, the Short Recognition Memory Test for Faces, and the Reading the Mind in the Eyes Test. Patients also completed the Visual Object and Space Perception Test (VOSP) as a control task, which would not engage social cognition. The patients were compared with fifty healthy controls matched for age and gender.. There were no significant differences on social cognitive performance between the FGA- and SGA-treatment groups. Nor was olanzapine superior to clozapine, FGAs or both. However, patients treated with FGAs performed significantly worse on VOSP compared to both groups treated with SGAs, a 10% difference.. We cannot conclude that SGAs were associated with better social cognition than FGAs. However, there were small but significant advantages for SGAs in non-social visual processing function, as evaluated with the VOSP.

Topics: Adolescent; Adult; Affect; Antipsychotic Agents; Awareness; Benzodiazepines; Case-Control Studies; Clozapine; Cues; Discrimination, Psychological; Emotions; Facial Expression; Female; Haloperidol; Hospitalization; Humans; Linear Models; Male; Middle Aged; Olanzapine; Perphenazine; Psychotic Disorders; Retina; Schizophrenia; Schizophrenic Psychology; Social Behavior; Social Perception; Speech Perception; Theory of Mind; Visual Perception; Young Adult

Safety and efficacy results, collected in schizophrenia and schizoaffective disorder patients treated for up to nearly 3 years, are presented for asenapine and olanzapine.. Patients completing a 52-week randomized double-blind core study on flexible-dose asenapine (5 or 10 mg BID) or olanzapine (10 or 20 mg QD) could continue treatment until study blind was broken.290 patients on asenapine and 150 on olanzapine continued treatment for variable lengths of time [mean ± SD (range) 311.0 ± 146.1 (10 - 653) d and 327.4 ± 139.6 (15 - 631) d, respectively]. Adverse event (AE) incidence was lower during the extension (asenapine, 62%; olanzapine, 55%) than during the core study (78%, 80%). In both groups, body weight increase and incidence of extrapyramidal AEs were negligible during the extension. Mean PANSS total score changes during first year of treatment were - 37.0 for asenapine and - 35.3 for olanzapine, with further changes of 1.6 for asenapine and - 0.8 for olanzapine at the extension study endpoint.. Clinical stability on asenapine as well as olanzapine was maintained, with few recurrent or newly emerging AEs beyond 1 year of treatment.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Comparative Effectiveness Research; Diagnostic and Statistical Manual of Mental Disorders; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Drug Monitoring; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Pharmacovigilance; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Time; Treatment Outcome; Weight Gain

To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS).. Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated in a four-site, randomized, double-blind clinical trial comparing molindone, olanzapine, and risperidone. The primary outcomes were overall group change from baseline in neurocognitive composite and six domain scores after 8 weeks and continued treatment up to 52 weeks. Age and sex were included as covariates in all analyses.. Of 116 TEOSS participants, 77 (66%) had post-baseline neurocognitive data. No significant differences emerged in the neurocognitive outcomes of the three medication groups. Therefore, the three treatment groups were combined into one group to assess overall neurocognitive outcomes. Significant modest improvements were observed in the composite score and in three of six domain scores in the acute phase, and in four of six domain scores in the combined acute and maintenance phases. Partial correlation analyses revealed very few relationships among Positive and Negative Syndrome Scale (PANSS) baseline or change scores and neurocognition change scores.. Antipsychotic intervention in youth with early-onset schizophrenia spectrum disorders (EOSS) led to modest improvement in measures of neurocognitive function. The changes in cognition were largely unrelated to baseline symptoms or symptom change. Small treatment effect sizes, easily accounted for by practice effects, highlight the critical need for the development of more efficacious interventions for the enduring neurocognitive deficits seen in EOSS. Clinical trial registry information-Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS); http://www.clinicaltrials.gov; NCT00053703.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Molindone; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

Δ⁹-Tetrahydrocannabinol (THC) produces transient psychomimetic effects in healthy volunteers, constituting a pharmacological model for psychosis. The dopaminergic antagonist haloperidol has previously been shown to reduce these effects. This placebo-controlled, cross-over study in 49 healthy, male, mild cannabis users aimed to further explore this model by examining the effect of a single oral dose of olanzapine (with dopaminergic, serotonergic, adrenergic, muscarinergic and histaminergic properties) or two oral doses of diphenhydramine (histamine antagonist) on the effects of intrapulmonarily administered THC. Transient psychomimetic symptoms were seen after THC administration, as measured on the positive and negative syndrome scale (20.6% increase on positive subscale, p<0.001) and the visual analogue scale for psychedelic effects (increase of 10.7 mm on feeling high). Following the combination of THC and olanzapine, the positive subscale increased by only 13.7% and feeling high by only 8.7 mm. This reduction of THC effects on the positive subscale failed to reach statistical significance (p=0.066). However, one-third of the subjects did not show an increase in psychomimetic symptoms after THC alone. Within responders, olanzapine reduced the effects of THC on the positive subscale (p=0.005). Other outcome measures included pharmacokinetics, eye movements, postural stability, pupil/iris ratio, and serum concentrations of cortisol and prolactin.

Topics: Absorption; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cross-Over Studies; Double-Blind Method; Dronabinol; Drug Interactions; Drug Users; Hallucinogens; Histamine H1 Antagonists; Humans; Male; Metabolic Clearance Rate; Middle Aged; Netherlands; Neurotoxicity Syndromes; Olanzapine; Psychotic Disorders; Young Adult

The aim of this study was to compare the 12-month effectiveness of several second-generation antipsychotic drugs, with that of haloperidol in never-treated patients with first-episode psychosis. In total, 114 patients without life time exposure to any psychotropic medication were randomized to haloperidol, olanzapine, risperidone, quetiapine or ziprasidone. Primary outcome was time to all-cause discontinuation. Secondary outcomes included discontinuation rates and symptom change as measured by the Positive and Negative Syndrome Scale (PANSS). The overall discontinuation rate 64%. At 12 months, the proportion of patients discontinuing treatment was 40.0% for olanzapine, 56.5% for quetiapine, 64.0% for risperidone, 80.0% for ziprasidone and 85.7% for haloperidol. Mean time to antipsychotic discontinuation was higher in patients randomized to second-generation antipsychotics than in those taking haloperidol. Significantly lower discontinuation was noted in patients on olanzapine than on haloperidol, or ziprasidone. Our results suggest that olanzapine might lead to longer treatment continuation in treatment naïve FEP patients than haloperidol and, possibly ziprasidone. Global psychopathology was significantly less reduced by haloperidol than with each individual SGA in this earliest phase of treatment.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

Duration of untreated psychosis (DUP) has been significantly associated with poor clinical and social outcomes in First Episode Psychosis (FEP) patients, but an association with cognitive outcomes has not been clearly established.. Seventy-seven consecutively admitted, drug-naïve patients with FEP were assessed at baseline and at 1month and 6months. Underlying dimensions of DUP (general prodrome and positive, negative and disorganisation symptoms) were assessed using the Symptom Onset in Schizophrenia (SOS) inventory (Perkins et al., 2000). To assess the effect of DUP on the neuropsychological status of the patients, a linear mixed-effect model was fitted to each neuropsychological dimension. These models included a dichotomised version of DUP (short versus long duration) as a fixed effect, several adjusting variables to account for patient differences, and a random effect to incorporate the longitudinal structure of the data.. Patients with a short duration of untreated negative symptoms (DUNS) or a short duration of untreated positive symptoms (DUPS) outperformed patients with a long duration of untreated symptoms on memory tasks and a pre-attentional visual task but not on measures of verbal fluency, attention, reaction time, visual processing and executive functions.. This study provides additional support for an early intervention to shorten DUP to facilitate a better outcome in memory and attentional domains of FEP patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Humans; Longitudinal Studies; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Risperidone; Statistics, Nonparametric; Young Adult

This study was undertaken to examine if patients exhibit more pronounced metabolic abnormalities after 8-year treatment with clozapine or olanzapine than before, and also to investigate whether there exist any differences between long-term clozapine and olanzapine therapies regarding metabolic side- effects.. Fifty psychiatric outpatients diagnosed with schizophrenia or schizoaffective disorder and on treatment with clozapine or olanzapine were studied during 8 years. Fasting blood or serum samples for glucose, lipids, prolactin and antipsychotic drug concentrations were analyzed. In addition, body mass index was calculated.. More patients treated with olanzapine compared with those treated with clozapine ended with their medication, in most cases because of diabetes mellitus and/or hyperlipidemia, during the 8-year follow-up. Also more patients treated with olanzapine compared with those treated with clozapine developed manifest diabetes mellitus during the 8-year period. Prolactin levels were higher in the patients treated with olanzapine compared with in those treated with clozapine at study start, but there were no differences in the other parameters between the treatment groups at study start. In the patients remaining on their medication all 8 years, the glucose level increased over time in the clozapine group, but not in the olanzapine group, whereas body mass index and lipids were unchanged over time in both treatment groups.. Our findings point to that both olanzapine and clozapine long-term treatments cause development of hyperglycemia and/or hyperlipidemia. Furthermore, olanzapine long-term treatment seems to more often lead to development of manifest diabetes mellitus than long-term treatment with clozapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Hyperlipidemias; Male; Metabolic Diseases; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia

The main goal of this study was to assess the long-term effect of haloperidol, olanzapine, and risperidone on serum prolactin levels in a naturalistically treated first-episode psychosis population.. Patients included in this study were drawn from a prospective, randomized, open-label clinical trial. Prolactin levels were measured in 110 patients with medication-naive first-episode psychosis at baseline, 3 months, and 1 year.. A repeated-measures analysis of variance revealed a significant difference between treatments (F = 17.28, P < 0.001). At 1-year follow-up, most patients in the haloperidol and olanzapine arms had prolactin values that fell within the reference range. Patients treated with risperidone experienced a significant increase at 3 months resulting in prolactin levels above the reference range in 90% of men and 87% of women. The levels showed a tendency to decrease at 1 year, although still more than 70% of the values remained above the normative range. Sexual adverse drug reactions at 1 year assessed by the Udvalg for Kliniske Undersogelser scale showed that a higher percentage (39.3%) of patients had symptoms in the risperidone group compared to the olanzapine group (24%) or haloperidol group (20%), but the difference did not reach statistical significance (P = 0.281).. Olanzapine and haloperidol treatments do not significantly affect serum prolactin levels at long term. After 1 year, elevated prolactin levels persist in most patients treated with risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Female; Follow-Up Studies; Haloperidol; Humans; Male; Olanzapine; Prolactin; Prospective Studies; Psychotic Disorders; Risperidone; Time Factors; Treatment Outcome; Young Adult

Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia.. The study was an 8-week, double-blind, parallel-group, randomized, controlled multicenter trial (NCT00145444). Seventy-six patients with schizophreniform disorder, schizophrenia or schizoaffective disorder (diagnosis < 5 y), and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study. Efficacy of ziprasidone (80-160 mg/d) and olanzapine 10-20 mg was measured using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression (CGI) Scale, the Calgary Depression Scale for Schizophrenia (CDSS), and the Heinrich Quality of Life Scale (HQLS); tolerability assessments included laboratory assessments, body weight, and electroencephalogram.. Olanzapine (n = 34) and ziprasidone (n = 39) showed equal efficacy as measured by the PANSS, CDSS, CGI, and HQLS. However, mean weight gain was significantly higher in the olanzapine group (6.8 vs 0.1 kg, P < .001). Ziprasidone was associated with decreasing levels of triglycerides, cholesterol, and transaminases, while these parameters increased in the olanzapine group (all P values < .05). There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects. Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently (P < .05).. The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile. However, there is a risk of a type II error with this sample size. Clinically significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine, while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms.

Topics: Adult; Alanine Transaminase; Antipsychotic Agents; Aspartate Aminotransferases; Basal Ganglia Diseases; Benzodiazepines; Biperiden; Blood Glucose; Body Weight; Cholesterol; Chronic Disease; Electrocardiography; Female; Humans; Male; Muscarinic Antagonists; Olanzapine; Piperazines; Prolactin; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Thiazoles; Triglycerides; Young Adult

The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n =26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n =16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Neuropsychological Tests; Olanzapine; Psychometrics; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Spain; Treatment Outcome

Schizophrenia is a heterogeneous disorder in terms of patient response to antipsychotic treatment. Understanding the heterogeneity of treatment response may help to guide treatment decisions. This study was undertaken to capture inherent patterns of response to antipsychotic treatment in patients with schizophrenia, characterize the subgroups of patients with similar courses of response, and examine illness characteristics at baseline as possible predictors of response.. Growth mixture modeling (GMM) was applied to data from a randomized, double-blind, 12-week study of 628 patients with schizophrenia or schizo-affective disorder treated with risperidone or olanzapine.. Four distinct response trajectories based on Positive and Negative Syndrome Scale (PANSS) total score over 12 weeks were identified: Class 1 (420 patients, 80.6%) with moderate average baseline PANSS total score showing gradual symptom improvement; Class 2 (65 patients, 12.5%) showing rapid symptom improvement; Class 3 (24 patients, 4.6%) with high average baseline PANSS total score showing gradual symptom improvement; and Class 4 (12 patients, 2.3%) showing unsustained symptom improvement. Latent class membership of early responders (ER) and early non-responders (ENR) was determined based on 20% symptom improvement criteria at 2 weeks and ultimate responders (UR) and ultimate non-responders (UNR) based on 40% symptom improvement criteria at 12 weeks. Baseline factors with potential influence on latent class membership were identified.. This study identified four distinct treatment response patterns with predominant representation of responders or non-responders to treatment in these classes. This heterogeneity may represent discrete endophenotypes of response to treatment with different etiologic underpinnings.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Young Adult

The effectiveness of antipsychotics in preventing relapses and attaining symptomatic remission is a relevant topic of psychopharmacological research. The purpose of the present study was to compare the relapse and symptomatic remission rates during the first year of treatment between low doses of haloperidol and SGAs (olanzapine and risperidone) in drug-naïve first-episode non-affective psychosis individuals. This is a prospective, randomized, open-label study conducted from February 2001 to February 2006. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis (DSM-IV criteria) conducted at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred and seventy four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 1 year. Primary effectiveness measures were the time up to relapse and rates of relapse and symptomatic remission. There were no significant differences in the relapse rate between treatments (11.1% haloperidol; 18.5% olanzapine, and 13.8% risperidone) (χ(2) = 1.230; p = 0.541) or in the time up to relapse (Log Rank χ(2) = 0.308; p = 0.857). The rates of relapse for adherent (11.2%) and non-adherent (26.9%) patients were significantly different (χ(2) = 4.215; df = 1; p = 0.040). The remission rate did not differ significantly between treatment groups (χ(2) = 2.760; p = 0.252) and adherence to medication did not seem to significantly influence remission rates. We conclude that haloperidol, olanzapine and risperidone show a similar effectiveness in relapse prevention or in remission attainment during the first year of treatment.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Female; Follow-Up Studies; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Secondary Prevention; Treatment Outcome; Young Adult

The aim of this study was to investigate the long-term effectiveness and efficacy of haloperidol, risperidone and olanzapine in first-episode schizophrenia-spectrum disorders. This was a prospective, randomized, open-label study. Data for the present investigation were obtained from a large epidemiological and 3-year longitudinal intervention programme of first-episode psychosis conducted at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred and seventy-four patients were randomly assigned to haloperidol (N = 56), olanzapine (N = 55), or risperidone (N = 63) and followed up for 1 year. The primary effectiveness measure was all causes of treatment discontinuation. Effectiveness analyses were based on intend-to-treat populations. In addition, an analysis based on per protocol populations was conducted in the analysis for clinical efficacy. The treatment discontinuation rate for any cause was higher with haloperidol than with risperidone and olanzapine (χ(2) = 8.517; p = 0.014). The difference in discontinuation rate between risperidone and olanzapine was not significant (χ(2) = 0.063; p = 0.802). There were no significant advantages of any of the three treatments in reducing the severity of psychopathology. Risperidone and olanzapine demonstrated higher effectiveness relative to haloperidol, but the three antipsychotics were equally effective in reducing the severity of psychopathology. Specific clinical programmes and the use of second-generation antipsychotics may enhance the effectiveness of antipsychotic treatments.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Severity of Illness Index; Treatment Failure

To compare the blood lactate levels between patients with psychotic disorder receiving first- and those receiving second-generation antipsychotics.. The study was conducted at the psychiatric inpatient and outpatient clinics of the Split Clinical Hospital from June 6, 2008 to October 10, 2009. Sixty patients with psychotic disorder who were assigned to 6-month treatment were divided in two groups: 30 received haloperidol (first generation antipsychotic) and 30 received olanzapine (second generation antipsychotic). Blood lactate levels, other metabolic parameters, and scores on the extrapyramidal symptom rating scale were assessed.. Patients receiving haloperidol had significantly higher blood lactate levels than patients receiving olanzapine (P < 0.001). They also more frequently had parkinsonism, which was significantly correlated with both haloperidol treatment at 1 month (P < 0.001) and 6 months (P = 0.016) and olanzapine treatment at baseline (P = 0.016), 3 months (P = 0.019), and 6 months (P = 0.021). Also, patients receiving haloperidol had significant correlation between blood lactate and dystonia at 1 month (P < 0.001) and 6 months (P = 0.012) and tardive dyskinesia at 1 month (P = 0.032). There was a significant difference between the treatment groups in lactate levels at all points from baseline to month 6 (P < 0.001).. It is important to be aware of the potential effect of haloperidol treatment on increase in blood lactate levels and occurrence of extrapyramidal side effects. Therefore, alternative antipsychotics should be prescribed with lower risk of adverse side effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dopamine Antagonists; Drug Monitoring; Haloperidol; Humans; Lactic Acid; Male; Middle Aged; Movement Disorders; Olanzapine; Parkinson Disease, Secondary; Psychiatric Status Rating Scales; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Antipsychotic medications are associated with an increased risk of diabetes. Previous studies have also found an increased risk of type 2 diabetes mellitus in the relatives of schizophrenia probands. The aim of this study was to explore the metabolic adverse effects of olanzapine in a cohort of patients with newly diagnosed psychosis and minimal or no exposure to antipsychotics. Patients with newly diagnosed psychosis (n = 30) were enrolled in a 16-week open trial of olanzapine. Body mass index, fasting glucose, hemoglobin A1c, fasting insulin, IL-6, and a fasting lipid profile were measured at baseline and at 4-week intervals. There was a significant, linear increase over time in fasting glucose (P = 0.043), weight (P < 0.001), body mass index (P < 0.001), total cholesterol (P = 0.005), triglycerides (P = 0.003), and low-density lipoprotein (P = 0.013), but not hemoglobin A1c (P = 0.691), fasting insulin (P = 0.690), IL-6 (P = 0.877), or high-density lipoprotein (P = 0.446). An abnormal baseline IL-6 was a significant predictor of a greater increase in both total cholesterol (P < 0.01) and low-density lipoprotein (P < 0.01). Otherwise, neither parental history of type 2 diabetes mellitus nor baseline IL-6 predicted changes in metabolic measures. Changes in metabolic measures with olanzapine treatment can be detected early in the treatment of patients who are previously antipsychotic naive. The absence of a change in fasting insulin suggests a failure of pancreatic islet cells to compensate for the increase in fasting glucose.

Topics: Adolescent; Adult; Benzodiazepines; Blood Glucose; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Interleukin-6; Male; Middle Aged; Olanzapine; Predictive Value of Tests; Psychotic Disorders; Young Adult

In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine.. The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo.. Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine.. Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

Topics: Adrenergic Uptake Inhibitors; Adult; Antipsychotic Agents; Appetite Depressants; Atomoxetine Hydrochloride; Attention; Benzodiazepines; Body Mass Index; Body Weight; Brief Psychiatric Rating Scale; Clozapine; Combined Modality Therapy; Diet, Reducing; Double-Blind Method; Exercise; Female; Humans; Life Style; Male; Maryland; Middle Aged; Neuropsychological Tests; Obesity; Olanzapine; Propylamines; Psychotic Disorders; Schizophrenia

To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior.. One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage.. All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control.. Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Emergency Services, Psychiatric; Female; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Male; Midazolam; Olanzapine; Piperazines; Promethazine; Psychomotor Agitation; Psychotic Disorders; Thiazoles; Tranquilizing Agents

The authors conducted a multisite randomized controlled trial examining the strategy of switching from olanzapine, quetiapine, or risperidone to aripiprazole to ameliorate metabolic risk factors for cardiovascular disease.. Patients with schizophrenia or schizoaffective disorder with a body mass index ≥ 27 and non-high-density lipoprotein (non-HDL) cholesterol ≥ 130 mg/dl who were on a stable treatment dosage of olanzapine, quetiapine, or risperidone were randomly assigned to switch to ari-piprazole (N=109) for 24 weeks or stay on their current medication (N=106). All participants were enrolled in a behaviorally oriented diet and exercise program. Clinical raters were blinded to treatment assignment. The primary and key secondary outcomes were change in non-HDL cholesterol and efficacy failure, respectively.. The prespecified primary analysis included 89 switchers and 98 stayers who had at least one postbaseline non-HDL cholesterol measurement. The least squares mean estimates of non-HDL cholesterol decreased more for the switch group than for the stay group (-20.2 mg/dl and -10.8 mg/dl, respectively). Switching was associated with larger weight reductions (least squares mean=2.9 kg) and a net reduction of serum triglycerides of 32.7 mg/dl. Twenty-two switchers (20.6%) and 18 stayers (17.0%) experienced protocol-defined efficacy failure. Forty-seven switchers (43.9%) and 26 stayers (24.5%) discontinued the assigned antipsychotic medication before 24 weeks.. Switching to aripiprazole led to improvement of non-HDL cholesterol levels and other metabolic parameters. Rates of efficacy failure were similar between groups, but switching to aripiprazole was associated with a higher rate of treatment discontinuation. In the context of close clinical monitoring, switching from an antipsychotic with high metabolic risk to one with lower risk to improve metabolic parameters is an effective strategy.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Body Weight; Cholesterol; Cholesterol, LDL; Combined Modality Therapy; Dibenzothiazepines; Diet, Reducing; Drug Substitution; Exercise; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk; Risperidone; Schizophrenia; Treatment Outcome; Triglycerides

Longitudinal data comparing the metabolic effects of olanzapine and risperidone with or without valproic acid supplementation in schizophrenic and bipolar patients are lacking.. This study compares the metabolic effects of olanzapine and risperidone in a prospective, randomized, open-label trial in 160 patients with DSM-IV-TR schizophrenia, schizoaffective disorder, or bipolar disorder after 1, 3, 6, and 12 months' treatment. The study was conducted between 2000 and 2006. The primary analysis compared all patients randomized to olanzapine or risperidone; the primary outcome measure was changes in triglycerides (TG), and TG/high density lipoprotein cholesterol (HDL-C) ratio, a risk factor for ischemic cardiovascular disease. Secondary analyses included the effect of concomitant valproic acid.. Significantly greater increases in weight (F(4,434) = 4.7), body mass index (BMI) (F(4,424) = 5.1), glycosylated hemoglobin (HgbA1c) (F(4,427) = 4.3), total cholesterol (F(4,429) = 4.4), TG (F(4,426) = 5.9), and TG/HDL-C ratio (F(4,426) = 4.3) (P < .005 for all drug × time interaction effects) were observed at all but the initial time points in the olanzapine- compared to the risperidone patients. Olanzapine/+valproic acid produced significantly greater increases in HgbA1c, BMI, weight, TG, and TG/HDL-C than olanzapine/-valproic acid at 3 and 6 months, while risperidone/+valproic acid produced significantly smaller increases in HgbA1c, BMI, and weight at 1, 3, and 6 months than risperidone/-valproic acid. The olanzapine/+valproic acid group had significantly greater BMI, and weight at 1, 3, and 6 months, and greater HgbA1c at 3 and 6 months, compared with the risperidone/+valproic acid group. There were too few patients treated with mood stabilizers other than valproic acid to analyze effects of any other mood stabilizer separately. Metabolic effects did not differ significantly by diagnostic category (schizophrenia/schizoaffective disorder vs bipolar disorder).. Further study of the metabolic effects of adjunctive valproic acid is indicated, as valproic acid may produce markedly different metabolic effects when combined with various antipsychotic drugs.. clinicaltrials.gov Identifier: NCT00179062.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; GABA Agents; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychotic Disorders; Risperidone; Schizophrenia; Time Factors; Treatment Outcome; Valproic Acid; Young Adult

To compare the effects of haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on hostility in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder.. We used the data acquired in the European First-Episode Schizophrenia Trial, an open, randomized trial (conducted in 14 countries) comparing 5 antipsychotic drugs in 498 patients aged 18-40 years with first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. DSM-IV diagnostic criteria were used. Patients were assessed between December 23, 2002 and January 14, 2006. Most subjects joined the study as inpatients and then continued with follow-ups in outpatient clinic visits. The Positive and Negative Syndrome Scale (PANSS) was administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. We analyzed the scores on the PANSS hostility item in a subset of 302 patients showing at least minimal hostility (a score > 1) at baseline. We hypothesized (1) that the treatments would differ in their efficacy for hostility and (2) that olanzapine would be superior to haloperidol. Our primary statistical analysis tested the null hypothesis of no difference among the treatment groups in change in hostility over time. Secondary analysis addressed the question of whether the effects on hostility found in the primary analysis were specific to this item. All our analyses were post hoc.. The primary analysis of hostility indicated an effect of differences between treatments (F(4,889) = 4.02, P = .0031). Post hoc treatment-group contrasts for hostility change showed that, at months 1 and 3, olanzapine was significantly superior (P < .05) to haloperidol, quetiapine, and amisulpride in reducing hostility. Secondary analyses demonstrated that these results were at least partly specific to hostility.. Both hypotheses were supported. Olanzapine appears to be a superior treatment for hostility in early phases of therapy for first-episode schizophrenia, schizoaffective disorder, and schizophreniform disorder. This efficacy advantage of olanzapine must be weighed against its adverse metabolic effects and propensity to cause weight gain.. ISRCTN Register Identifier: ISRCTN68736636.

Topics: Adult; Aggression; Amisulpride; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Haloperidol; Hostility; Humans; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sulpiride; Thiazoles; Treatment Outcome

Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis.. Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale-Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS).. A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01).. There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis.. ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Benzodiazepines; Depression; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thiazoles

Schizophrenia patients have a potential increased risk of metabolic dysregulation during antipsychotic treatments. Our objective was to compare changes in prolactin and metabolic variables (glucose, lipids and weight) as a post-hoc analysis from a six-month, randomised, controlled study of olanzapine (OLZ, n = 171; 10-20 mg/day) or quetiapine (QUE, n = 175; 300-700 mg/day). No statistically significant treatment group differences for baseline to endpoint mean changes in body mass index (P = 0.209) or weight (P = 0.250) were observed. There was a greater incidence of clinically significant weight gain (defined as > or =7% increase from baseline) in OLZ (19.2%) compared to QUE (13.2%)-treated patients (P = 0.181). No statistically significant treatment group differences for lipids and glucose variables, either as mean change from baseline to endpoint or treatment-emergent (TE) categorical changes were found (P > or = 0.05). Incidence rates for TE diabetes were similar between treatment groups 2.5% (n = 4) in the OLZ-treatment group and 1.3% (n = 2) in the QUE-treatment group (P = 0.685). Hyperprolactinaemia was present at baseline in many patients (OLZ 32.9%; QUE 31.4%), but after 2 weeks of treatment prolactin values had reverted to normal for nearly all patients (OLZ 100%; QUE 99.4%). There were no significant treatment differences in any variable between cohorts.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lipid Metabolism; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Weight Gain

Our objective was to prospectively assess whether early (ie, 2 weeks) response to an antipsychotic predicts later (12-week) response and whether 'switching' early non-responders to another antipsychotic is a better strategy than 'staying'. This randomized, double-blind, flexible-dosed, 12-week study enrolled 628 patients diagnosed with schizophrenia or schizoaffective disorder. All initiated treatment with risperidone. Early response was defined as > or =20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score following 2 weeks of treatment. Early responders (ERs) continued on risperidone, whereas early non-responders (ENRs) were randomized (1 : 1) to continue on risperidone 2-6 mg/day or switch to olanzapine 10-20 mg/day for 10 additional weeks. Compared with ENRs, risperidone ERs showed significantly greater reduction in PANSS total score (end point; p<001). Early response/non-response was highly predictive of subsequent clinical outcomes. Switching risperidone ENRs to olanzapine at week 2 resulted in a small but significantly greater reduction in PANSS total score (end point; p=0.020) and in depressive symptoms (end point; p=0.004); the reduction in PANSS was greater among those who were still moderately ill at 2 weeks. Switching risperidone ENRs to olanzapine also resulted in significantly greater increases in triglycerides, a significantly greater decrease in prolactin, and significantly less treatment-emergent dyskinesia. This is the first study to prospectively show that early response/non-response to an antipsychotic (risperidone) is a reliable clinical marker of subsequent clinical outcomes and that a 'switching' strategy based on this information may lead to greater clinical improvement than staying on a drug for a longer period in some patients.

Topics: Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Olanzapine; Prolactin; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Sensitivity and Specificity; Statistics, Nonparametric; Triglycerides

We conducted a double-blind 1-year trial of asenapine in patients with schizophrenia or schizoaffective disorder.. Patients were randomized to asenapine (5 or 10 mg BID; n=913) or olanzapine (10-20 mg QD; n=312), and monitored regularly.. Trial completion rates were 38% with asenapine, 57% with olanzapine; main reasons for discontinuation were withdrawal of consent (22%, 16%) and insufficient response (25%, 14%); fewer discontinuations were due to adverse events (6%, 7%). Mean weight gain was 0.9 kg with asenapine, 4.2 kg with olanzapine. Extrapyramidal symptoms reported as adverse events were more common with asenapine. Mean reductions in PANSS total score with asenapine and olanzapine were -21.0 and -27.5 ( P<0.0001); the exclusion of patients who had previous poor experience with olanzapine may have biased the results in favor of olanzapine. Scores on the subjective well-being on neuroleptics scale and functionality measures were similar between groups.. Asenapine was well tolerated over 1 year of treatment, causing less weight gain than olanzapine but more frequent extrapyramidal symptoms. PANSS total score improved with both agents; the improvement was greater with olanzapine than with asenapine using last observations carried forward but not in an observed-case analysis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Double-Blind Method; Heterocyclic Compounds, 4 or More Rings; Humans; Longitudinal Studies; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Treatment Outcome; Young Adult

No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis. The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation, duration of index admission, time until readmission, change of psychopathology scores and tolerability outcomes.. Patients >or= 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively randomized to risperidone (n = 53), olanzapine (n = 52), quetiapine (n = 50), or ziprasidone (n = 58), and followed for up to 2 years.. A total of 213 patients were included, of which 68% were males. The sample represented a diverse population suffering from psychosis. At admittance the mean Positive and Negative Syndrome Scale (PANSS) total score was 74 points and 44% were antipsychotic drug naïve. The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug, until discharge from index admission, or until readmission. Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore. Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore; in decreasing the Clinical Global Impression - Severity of Illness scale score (CGI-S); and in increasing the Global Assessment of Functioning - Split version, Functions scale score (GAF-F). Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score, and in increasing the GAF-F score. The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone, and more galactorrhoea for risperidone compared to the other groups.. Quetiapine appears to be a good starting drug candidate in this sample of patients admitted to hospital for symptoms of psychosis.. ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Galactorrhea; Hospitalization; Humans; Length of Stay; Male; Olanzapine; Patient Readmission; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Thiazoles; Treatment Outcome

To compare the efficacy of risperidone and olanzapine in schizophrenic patients with tardive dyskinesia on treatment with first-generation antipsychotics.. We conducted a 24-week, rater-blinded, flexible-dose study. Sixty patients with DSM-IV schizophrenia (n = 58) or schizoaffective disorder (n = 2) met the DSM-IV research criteria for neuroleptic-induced tardive dyskinesia and were randomly assigned to a risperidone or olanzapine group. The primary outcome was a comparison of the change in the total scores on the Abnormal Involuntary Movement Scale (AIMS) from baseline to study end point between the groups. The study was conducted from July 2000 to June 2004.. The mean ± SD doses of risperidone and olanzapine from baseline to study end point were 1.9 ± 0.7 to 4.1 ± 1.4 mg/d and 8.1 ± 2.0 to 12.6 ± 5.4 mg/d, respectively. There were no statistically significant differences in demographic data, severity of tardive dyskinesia, or psychotic symptoms between risperidone and olanzapine groups at baseline assessment. Both groups showed significant improvement in mean ± SD AIMS total scores (risperidone: −7.4 ± 6.9, P < .0001; olanzapine: −6.2 ± 8.0, P = .0002). However, there was a more statistically significant change in the slope of AIMS total scores in the risperidone group than in the olanzapine group (P = .0001).. Our findings demonstrated that olanzapine may not have better potential for tardive dyskinesia improvement than risperidone did. Double-blinded, fixed dose studies with a larger sample size on schizophrenic patients with tardive dyskinesia from different ethnic groups are needed to confirm the results of our study.. clinicaltrials.gov Identifier NCT00621998

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Taiwan

The purpose of this study was to compare efficacy and safety among intramuscular olanzapine, intramuscular haloperidol, orally disintegrating olanzapine tablets, and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward.. Forty-two inpatients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled. They were randomly assigned to 1 of the 4 treatment groups (10-mg intramuscular olanzapine, 10-mg olanzapine oral disintegrating tablet, 3-mg oral risperidone solution, or 7.5-mg intramuscular haloperidol). Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation-Calmness Evaluation Scale, and the Clinical Global Impression--Severity Scale during the first 24 hours.. There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15, 30, 45, 60, 75, and 90 minutes after the initiation of treatment. More significant differences were found early in the treatment. In the post hoc analysis, the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15, 30, 45, 60, 75, and 90 minutes after injection.. These findings suggest that intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation. Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention. There is no significant difference in effectiveness among intramuscular olanzapine, orally disintegrating olanzapine tablets, and oral risperidone solution.

Topics: Acute Disease; Administration, Oral; Adult; Benzodiazepines; Disease Management; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pharmaceutical Solutions; Prospective Studies; Psychiatric Department, Hospital; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Risperidone; Solubility; Tablets; Taiwan; Treatment Outcome

To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders.. Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks.. Of the 116 youths randomized in the acute trial, 54 entered maintenance treatment (molindone, n = 20; olanzapine, n = 13; risperidone, n = 21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (n = 15), inadequate efficacy (n = 14), or study nonadherence (n = 8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment.. Only 12% of youths with early-onset schizophrenia spectrum disorders continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for early-onset schizophrenia spectrum disorders. Clinical trial registry information-Treatment of Schizophrenia and Related Disorders in Children and Adolescents; URL: http://www.clinicaltrials.gov, unique identifier: NCT00053703.

Topics: Adolescent; Akathisia, Drug-Induced; Benzodiazepines; Child; Double-Blind Method; Female; Humans; Long-Term Care; Male; Molindone; Olanzapine; Prolactin; Psychiatric Status Rating Scales; Psychotic Disorders; Psychotropic Drugs; Risk Factors; Risperidone; Schizophrenia; Schizophrenic Psychology; Weight Gain; Young Adult

Some preclinical and postmortem studies suggest that the effects of atypical antipsychotics could be mediated by brain-derived neurotrophic factor (BDNF). Olanzapine is an atypical antipsychotic with shown efficacy in psychosis treatment. The aim of this study was to compare plasma BDNF levels at baseline and after 1 year of olanzapine treatment in 18 drug-naive patients who experienced a first psychotic episode with those of 18 healthy control participants matched by age, sex, and socioeconomic level. Plasma BDNF levels were measured in patients at the index episode and at 1, 6, and 12 months of follow-up using an enzyme-linked immunosorbent assay. Symptoms and functioning of patients and controls were assessed with the Positive and Negative Symptom Scale and Global Assessment of Function Scale. BDNF levels of patients at onset were significantly lower than controls but increased toward control values during olanzapine treatment. There was a significant positive correlation between BDNF levels and functioning (Global Assessment of Function Scale). BDNF levels were also negatively correlated with positive symptoms, but not with negative symptoms or general psychopathology. Results suggest that olanzapine can offset the low BDNF levels at the onset of first psychotic episodes, and improving psychotic symptoms. The increase in BDNF levels may be its mechanism of action in improving positive symptoms.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Blood; Brain-Derived Neurotrophic Factor; Case-Control Studies; Humans; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Young Adult

Topics: Affective Symptoms; Antipsychotic Agents; Benzodiazepines; Humans; Marijuana Smoking; Medication Adherence; Olanzapine; Psychotic Disorders; Risperidone

We conducted exploratory analyses of the data from a multinational, randomised study to identify factors associated with weight change after 16 weeks of treatment with standard olanzapine tablets (SOT) or sublingual orally disintegrating olanzapine (ODO).. One hundred and forty nine outpatients who gained weight during prior SOT therapy were enrolled into the study and treated with ODO (N = 84) or SOT (N = 65). Exploratory analyses were conducted with the subset of compliant patients (ODO: n = 60; SOT: n = 47).. The decrease in the rate of weight gain at the end of study therapy (change from baseline) was greater in the ODO group than the SOT group (-0.59 kg/week vs. -0.38 kg/week, p = 0.0246). Age was negatively associated with weight change (p = 0.0203) in both treatment groups combined: patients gained 0.7 kg less for every 10 years of age. The least squares mean weight gain was lower with ODO than SOT in male patients (0.35 kg vs. 3.04 kg, p = 0.061), but not female patients and in American patients (0.55 kg vs. 6.21 kg, p < 0.0001), but not Canadian or Mexican patients.. Although not conclusive, these data suggest that ODO may be a reasonable treatment option for some patients who gain weight with SOT. Further research is required to confirm these findings.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Sex Distribution; Tablets; Weight Gain; Young Adult

Adaptive trial design applied to randomized clinical trials of psychiatric medicines offers the potential to make clinical trials more efficient. In the current analysis, we retrospectively applied Bayesian adaptive allocation methods to a case study in agitated patients with schizophrenia and related diseases. The original study used a randomized, double-blind, parallel design. The objective of this analysis was to demonstrate the potential benefits of Bayesian adaptive designs by shortening the study duration and therefore limiting patient exposure to ineffective placebo or an active comparator with a known side effect. Bayesian methods allowed us to fully leverage historical data along with data observed as the study was ongoing to calculate predictive probabilities of patient response to treatment without experiencing a specified side effect. Using the Bayesian adaptive approach would have required less than half the number of patients as the original study to draw the same conclusion. Sample size was reduced from 311 to 156 patients, thereby decreasing the number of patients exposed to placebo from 54 to 30 and the number exposed to the active control with a known side effect from 126 to 60.

Topics: Antipsychotic Agents; Bayes Theorem; Benzodiazepines; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Dystonia; Haloperidol; Humans; Monte Carlo Method; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Research Design; Retrospective Studies; Sample Size; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

The second generation antipsychotics clozapine and olanzapine are known to cause weight gain. However, only clozapine is associated with drug-induced fever. Cytokines have been linked to the induction of both weight gain and drug-induced fever. We investigated these potential side effects of clozapine and olanzapine and studied their differential effects on cytokine secretion. Thirty patients suffering from schizophrenia, schizophreniform disorder or schizoaffective disorder were treated with either clozapine (mean modal dose: 266.7+/-77.9mg) or olanzapine (21.2+/-2.5mg) in a randomized, double-blind, 6-week study. Body mass index (BMI), tympanic temperature, and plasma levels of leptin and cytokines (tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 and 2 (sTNFR-1/2), soluble interleukin-2 receptors (sIL-2R), interleukin-6) were determined weekly. BMI, leptin and cytokines significantly increased over time, except interleukin-6 and sTNFR-1 in the olanzapine group. All cytokines numerically increased compared to baseline already during the first week of treatment in both groups. Leptin, TNF-alpha, sTNFR-1, sTNFR-2 and sIL-2R levels correlated with the BMI. Five patients who received clozapine (33%) developed drug-induced fever (>/=38 degrees C). In these, interleukin-6 peak levels were significantly (p<0.01) higher than in those patients treated with clozapine who did not develop fever. In conclusion, increase of BMI appears to be related to clozapine's and olanzapine's similar effects on cytokine systems, whilst drug-induced fever appears to be related to clozapine's differential effects on interleukin-6.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Cytokines; Double-Blind Method; Female; Fever; Humans; Leptin; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Weight Gain

Hyperprolactinemia, an adverse effect associated with the use of typical antipsychotics and the atypical antipsychotic risperidone, has both acute and chronic clinical consequences. One option for clinical management is switching to an agent with a lower liability for inducing hyperprolactinemia. This post-hoc sub-analysis of an 8-week, open-label study in outpatients with schizophrenia (CN138-215) examined short-term effects on prolactin levels during a switch from risperidone or olanzapine to aripiprazole 30 mg/day. Three switch strategies were used: (I) immediate aripiprazole initiation with simultaneous immediate discontinuation of olanzapine/risperidone; (II) immediate aripiprazole initiation while tapering off olanzapine/risperidone over 14 days; (III) titrating aripiprazole upwards while tapering off olanzapine/risperidone over 14 days. Changes in prolactin levels from baseline to each last observation carried forward time point were compared with t-tests using Bonferroni correction for multiple comparisons. This sub-analysis included 269 subjects: 105 previously treated with risperidone; 164 previously treated with olanzapine. Mean baseline prolactin levels (ng/mL) were within normal range for the three olanzapine groups (Group-I, 11.7; Group-II, 13.2; Group-III, 11.2), but above normal for the risperidone groups (Group-I, 39.7; Group-II, 48.5; Group-III, 33.5). Following aripiprazole initiation, mean prolactin levels decreased significantly (p<0.001) at week-1 and were maintained to week-8 in all groups irrespective of prior treatment. Previously elevated prolactin levels in the risperidone groups were reduced to within normal range within 1 week, irrespective of switching strategy. Tolerability was good regardless of prior medication or switching strategy. Overall, rapid decreases of prolactin levels were achieved safely with all three aripiprazole switching strategies. Reversal of hyperprolactinemia during the crossover period indicates the safety and potential utility of aripiprazole addition in patients with elevated prolactin.

Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Piperazines; Prolactin; Psychotic Disorders; Quinolones; Risperidone; Schizophrenia; Sex Factors; Substance Withdrawal Syndrome; Young Adult

This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Early Diagnosis; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Prognosis; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Young Adult

It has been suggested that the family history of psychotic disorders is useful in defining homogeneous groups of bipolar patients. The plasma homovanillic acid (pHVA) concentrations have been related to the effect of antipsychotic treatment in psychotic patients. We have studied the influence of a positive family history of psychotic disorders both on the variation of pHVA levels and on the relation between pHVA concentrations and the clinical response to treatment. Clinical status and pHVA levels were assessed in 58 medication free patients before and after 4 weeks of treatment with olanzapine and lithium. Clinical improvement correlated positively with pHVA levels on the 28th day of treatment only in the patients having first degree relatives with psychotic disorders. The pHVA levels did not decrease after 28 days of treatment. Our results reinforce the idea that a positive family history of psychosis in psychotic bipolar disorders may constitute a good basis for sub-grouping these patients.

Topics: Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Family Health; Female; Homovanillic Acid; Humans; Lithium Compounds; Male; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

To compare the efficacy, safety, and tolerability of olanzapine and quetiapine in adolescents with first episode psychosis.. Fifty adolescents (age 16 +/- 1.25) with a first episode of psychosis were randomized to quetiapine or olanzapine in a 6-month open label study. Efficacy and side effect scales, as well as vital signs and laboratory data were recorded at baseline, 7, 15, 30, 90, and 180 days (end of study).. Out of the total sample included in the study, 32 patients completed the trial (quetiapine n = 16, olanzapine n = 16). Patients in both treatment groups had a significant reduction in all clinical scales with the exception of the negative scale of the Positive and Negative Symptom Scale (PANSS) for olanzapine and the general psychopathology scale of the PANSS for quetiapine. The only difference between treatment arms on the clinical scales was observed on the patients' strength and difficulties questionnaire (SDQ) scale, with greater improvement for olanzapine. Patients on olanzapine gained 15.5 kg and patients on quetiapine gained 5.5 kg.. Olanzapine and quetiapine reduced psychotic symptoms in this adolescent sample. Patients on olanzapine gained significantly more weight. Side effects with both drugs seemed to be more prevalent than those reported in adult studies.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Surveys and Questionnaires

To investigate the neurocognitive effectiveness of haloperidol, risperidone, and olanzapine in first-episode schizophrenia-spectrum disorders.. This prospective, randomized, open-label study was conducted from February 2001 to February 2005. Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis (DSM-IV criteria) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla, Santander, Spain. One hundred four patients randomly assigned to haloperidol (N = 35), olanzapine (N = 30), or risperidone (N = 39) who completed clinical and cognitive evaluations at baseline, 6 months, and 1 year were included in the final analysis. Thirty-seven healthy individuals were also longitudinally assessed. A neuropsychological battery that comprised 9 cognitive domains was used. The contribution of clinical changes, concomitant medications, and the severity of motor side effects to cognitive changes was controlled. The main outcome measure was cognitive changes at 1-year follow-up.. The 3 treatment groups showed a significant improvement in cognitive scores after 1 year. The differential cognitive effectiveness between antipsychotics was insignificant. The magnitude of cognitive changes was similar in the 3 treatment groups and controls, although a greater improvement on the Finger Tapping Test, Trail Making Test B, and Rey Complex Figure Test was found in the treatment groups. Clinical changes, use of concomitant medications, and the emergence of motor side effects did not significantly account for cognitive changes over time.. Haloperidol, olanzapine, and risperidone were equally effective in treating cognitive deficits of psychosis. The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics. Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implications for developing novel approaches for cognitive pharmacotherapy in schizophrenia.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Brain; Clozapine; Cognition Disorders; Female; Follow-Up Studies; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Perphenazine; Piperazines; Prospective Studies; Psychotic Disorders; Risperidone; Severity of Illness Index; Sulpiride; Thiazoles

Cognitive impairment in schizophrenia-spectrum disorders is highly prevalent and notably influences functional outcomes.. To characterise the cognitive effectiveness of second-generation antipsychotic drugs.. One hundred consecutive and previously unmedicated patients with first-episode schizophrenia-spectrum disorders were admitted. Seventy-seven completed baseline, 1-month and 6-month psychopathological and neuropsychological assessments. Patients were randomised to risperidone or olanzapine treatment. Four final treatment allocation groups were defined since patients continued treatment in their normal setting: risperidone, olanzapine, mixed and no-antipsychotic groups.. There were no differences in cognitive effectiveness between the four treatment groups. Reliable change index methods demonstrated that nearly a half of patients showed an improvement in Global Cognitive Score at the 6-month assessment. Improvement on the neuropsychological tests ranged from 17 to 54%. A strong predictor of cognitive response was poor performance on baseline neuropsychological tests; response was moderately influenced by a low premorbid scholastic performance and IQ.. Cognitive improvement related to second-generation antipsychotic drugs appeared within the first 4 weeks of treatment and persisted at 6 months irrespective of treatment group. Greater cognitive dysfunction at baseline and lower premorbid cognitive background predicted cognitive improvement in our sample.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cognition; Educational Status; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Statistics as Topic; Time Factors; Treatment Outcome; Young Adult

To examine the impact of medication nonadherence on treatment outcome in schizophrenia and potential risk factors for nonadherence.. A post hoc analysis of a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10, 20, and 40 mg/day for patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) with suboptimal response to current treatment (N = 599) was conducted between September 12, 2003, and November 3, 2005, at 55 study centers in the United States. Nonadherence was defined as not taking medication as prescribed based on daily pill counts. Because there was no significant difference in nonadherence between dose groups, effects of nonadherence on efficacy and safety outcomes were examined using all 3 groups combined. Baseline demographics and symptom severity were investigated as potential risk factors for nonadherence.. During the 8-week study, 34.5% of patients were nonadherent at least once. Nonadherent patients had significantly less improvement compared to adherent patients as measured by change in Positive and Negative Syndrome Scale total score (-22.57 vs. -26.84, p = .002). Longer duration of nonadherence was associated with reduced likelihood of treatment response (odds ratio = 0.94, 95% CI = 0.90 to 0.99, p = .008). The early treatment discontinuation rate was higher in nonadherent compared to adherent patients (40.8% vs. 24.5%, p < .001). Adherent and nonadherent patients had comparable outcomes in most safety measures, except for weight change, for which adherent patients had greater weight gain than nonadherent patients (2.63 kg vs. 1.96 kg, p = .02). Greater depression severity at baseline (p = .01) and greater hostility level during the study were significant risk factors for nonadherence (p = .02).. Medication nonadherence had a significantly negative impact on treatment response, highlighting the importance of adherence to achieve satisfactory treatment outcome. Findings may also help clinicians identify patients at risk for nonadherence and utilize interventions to improve adherence.. clinicaltrials.gov Identifier: NCT00100776.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Medication Adherence; Olanzapine; Patient Dropouts; Psychiatric Status Rating Scales; Psychotic Disorders; Recurrence; Schizophrenia; Severity of Illness Index; Treatment Outcome

To compare the effectiveness of a switch from haloperidol (N=99), olanzapine (N=82), or risperidone (N=104) to 12 weeks of treatment with 80-160 mg/day ziprasidone in patients with stable schizophrenia or schizoaffective disorder. Stable outpatients with persistent symptoms or troublesome side effects were switched using one of three 1-week taper/switch strategies as determined by the investigator. Efficacy was assessed using the Brief Psychiatric Rating Scale score, Clinical Global Impression, Positive and Negative Symptom Scale, Montgomery-Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale, and tolerability by using standard measures of weight change, extrapyramidal symptoms, and laboratory findings. Suboptimal efficacy was the primary reason for switching. The preferred switch strategy was immediate discontinuation, and the preferred dosing regimen was 120 mg/day. Completer rates were 68, 60, and 86% in the haloperidol, risperidone, and olanzapine pre-switch groups, respectively. At week 12, a switch to ziprasidone resulted in statistically significant improvement from baseline on the Brief Psychiatric Rating Scale score, Clinical Global Impression-Improvement, Positive and Negative Symptom Scale, and Global Assessment of Functioning scales, reduction in extrapyramidal symptoms and a neutral impact on metabolic parameters. Switch from olanzapine and risperidone resulted in weight reduction and from haloperidol in some weight increase. In conclusion, oral ziprasidone of 80-160 mg/day with food was a clinically valuable treatment option for stable patients with schizophrenia or schizoaffective disorder experiencing suboptimal efficacy or poor tolerability with haloperidol, olanzapine, or risperidone.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles

Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine (ODO) tablets. The primary objective of this study was to investigate the change in body mass index (BMI) in patients who had previously gained weight with SOT and continued with this therapy during the study period, compared with those patients who switched to ODO during the study period.. This was a 16-week, multicentre, randomized, double-blind, double-dummy, study of outpatients diagnosed with schizophrenia, schizoaffective disorder, related psychotic disorder or bipolar disorder, who were taking 5-20 mg SOT daily. Patients continued treatment with 5-20 mg olanzapine in a flexible single daily dose, and were randomized to either receive sublingual ODO plus an oral placebo, or sublingual placebo plus SOT.. No statistically significant between group differences in mean change from baseline in BMI, weight or waist circumference were observed. Analysis of change in body weight from baseline, by pre-specified category (no change, loss of >or=1.5 kg, gain of >or=1.5 kg), revealed a significant difference between groups, favoring ODO patients, who also experienced a significant reduction in subjective appetite and better treatment compliance, compared to patients in the SOT group.. In this study, patients treated with ODO experienced a similar mean change in BMI and weight from baseline, to those patients treated with SOT.

Topics: Administration, Oral; Administration, Sublingual; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Psychotic Disorders; Quality of Life; Waist Circumference; Young Adult

Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features.. To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age.. Twelve-week, double-blind, randomized, controlled trial.. Clinical services of 4 academic sites. Patients Two hundred fifty-nine subjects with MD with psychotic features randomized by age (<60 or > or =60 years) (mean [standard deviation (SD)], 41.3 [10.8] years in 117 younger adults vs 71.7 [7.8] years in 142 geriatric participants). Intervention Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day. Main Outcome Measure Remission rates of MD with psychotic features.. Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47; P < .001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy (chi(2)(1) = 9.53, P = .002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P = .02) and older (OR, 1.34; 95% CI, 1.09-1.66; P = .01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean [SD], 6.5 [6.6] kg vs 3.3 [4.9] kg, P = .001).. Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features. Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks.. clinicaltrials.gov Identifier: NCT00056472.

Topics: Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Humans; Olanzapine; Placebos; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

The present study explores sweet stimuli effects on hunger and negative alliesthesia in patients treated with antipsychotic drugs and controls. Those phenomena were examined in relation to previous weight gain, eating and weight-related cognitions and type of sweet stimuli: aspartame or sucrose. Alliesthesia is delayed in participants who gained weight regardless of cross group differences. A similar reduction of hunger was observed after the intake of two kinds of sweet stimuli (aspartame or sucrose) whereas alliesthesia measures were not affected. Whereas atypical antipsychotic drug-induced weight gain is linked to delayed satiety, the phenomenon is similar in magnitude in non-psychiatric controls who gained weight.

Topics: Adult; Antipsychotic Agents; Aspartame; Benzodiazepines; Carbonated Beverages; Clozapine; Dibenzothiazepines; Double-Blind Method; Food Preferences; Humans; Hunger; Male; Middle Aged; Olanzapine; Pleasure; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sucrose; Surveys and Questionnaires; Sweetening Agents; Taste; Time Factors; Young Adult

The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior.. The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals.. In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo.. In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.

Topics: Activities of Daily Living; Aged; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Cognition Disorders; Dibenzothiazepines; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Surveys and Questionnaires

The aim of this study was to evaluate metabolic and hormonal side effects in children and adolescents after 6 months of treatment with 3 different second-generation antipsychotics (SGAs).. 66 children and adolescents (44 male [66.7%], mean +/- SD age = 15.2 +/- 2.9 years) treated for 6 months with risperidone (N = 22), olanzapine (N = 20), or quetiapine (N = 24) composed the study sample. 34 patients (51.5%) suffered from schizophrenia or other psychosis (according to DSM-IV criteria). Patients were consecutively attending different programs from March 2005 to October 2006. Prior to enrollment in the study, patients were either antipsychotic-naive (37.9%, N = 25) or had been taking an antipsychotic drug for fewer than 30 days. Significant weight gain was defined as a > or = 0.5 increase in body mass index (BMI) z score (adjusted for age and gender) at 6 months. Based on recent criteria for pediatric populations, patients were considered "at risk for adverse health outcome" if they met at least 1 of the following criteria: (1) > or = 85th BMI percentile plus presence of 1 or more negative weight-related clinical outcomes, or (2) > or = 95th BMI percentile.. After the 6 months, BMI z scores increased significantly in patients receiving olanzapine and risperidone. At the 6-month follow-up, 33 patients (50.0%) showed significant weight gain. The number of patients at risk for adverse health outcome increased from 11 (16.7%) to 25 (37.9%) (p = .018). The latter increase was significant only in the olanzapine group (p = .012). Total cholesterol levels increased significantly in patients receiving olanzapine (p = .047) and quetiapine (p = .016). Treatment with quetiapine was associated with a significant decrease in free thyroxin (p = .011).. Metabolic and hormonal side effects of SGAs in children and adolescents should be carefully monitored when prescribing these drugs.

Topics: Adolescent; Benzodiazepines; Blood Glucose; Body Mass Index; Child; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Substance-Related Disorders; Thyroxine; Triglycerides

In clinical practice, physicians often need to change the antipsychotic medications they give to patients because of an inadequate response or the presence of unacceptable or unsafe side effects. However, there is a lack of consensus in the field as to the optimal switching strategy for antipsychotics, especially with regards to the speed at which the dose of the previous antipsychotic should be reduced. This paper assesses the short-term results of strategies for the discontinuation of olanzapine when initiating risperidone.. In a 6-week, randomized, open-label, rater-blinded study, patients with schizophrenia or schizoaffective disorder, on a stable drug dose for more than 30 days at entry, who were intolerant of or exhibiting a suboptimal symptom response to more than 30 days of olanzapine treatment, were randomly assigned to the following switch strategies (common risperidone initiation scheme; varying olanzapine discontinuation): (i) abrupt strategy, where olanzapine was discontinued at risperidone initiation; (ii) gradual 1 strategy, where olanzapine was given at 50% entry dose for 1 week after risperidone initiation and then discontinued; or (iii) gradual 2 strategy, where olanzapine was given at 100% entry dose for 1 week, then at 50% in the second week, and then discontinued.. The study enrolled 123 patients on stable doses of olanzapine. Their mean age was 40.3 years and mean (+/- standard deviation (SD)) baseline Positive and Negative Syndrome Scale (PANSS) total score of 75.6 +/- 11.5. All-cause treatment discontinuation was lowest (12%) in the group with the slowest olanzapine dose reduction (gradual 2) and occurred at half the discontinuation rate in the other two groups (25% in abrupt and 28% in gradual 1). The relative risk of early discontinuation was 0.77 (confidence interval 0.61-0.99) for the slowest dose reduction compared with the other two strategies. After the medication was changed, improvements at endpoint were seen in PANSS total score (-7.3; p < 0.0001) and in PANSS positive (-3.0; p < 0.0001), negative (-0.9; p = 0.171) and anxiety/depression (-1.4; p = 0.0005) subscale scores. Severity of movement disorders and weight changes were minimal.. When switching patients from olanzapine to risperidone, a gradual reduction in the dose of olanzapine over 2 weeks was associated with higher rates of retention compared with abrupt or less gradual discontinuation. Switching via any strategy was associated with significant improvements in positive and anxiety symptoms and was generally well tolerated.. ClinicalTrials.gov NCT00378183.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Single-Blind Method; Withholding Treatment

Major mental disorders are associated with an increased risk for obesity-related cardiovascular mortality, leading to interest in risk-reduction approaches that target weight and risk-related plasma lipids, including use of antipsychotic agents with low metabolic risk. This multicenter, randomized, double-blind study compared the metabolic effects of aripiprazole versus olanzapine in overweight persons with schizophrenia or schizoaffective disorder who were previously on olanzapine treatment.. In total, 173 subjects with DSM-IV-TR-defined schizophrenia or schizoaffective disorder were randomly assigned to receive aripiprazole (N = 88) or olanzapine (N = 85) for 16 weeks in a study conducted from March 30, 2004, to August 8, 2006. Primary and secondary endpoints were mean weight change from baseline and percentage change from baseline in fasting triglyceride levels, respectively.. At week 16, weight decreased significantly with aripiprazole versus olanzapine (-1.8 vs. +1.41 kg; p < .001). Significant differences in percentage change in triglyceride levels were observed with aripiprazole (decreases) versus olanzapine (increases) at all time-points. In addition, significantly more subjects receiving aripiprazole had clinically relevant (> or = 7%) weight loss versus olanzapine (11.1% vs. 2.6%; p = .038), and a lower percentage of subjects receiving aripiprazole had clinically relevant weight gain (2.5% vs. 9.1%; p = .082). Mean percentage changes in fasting total cholesterol and high-density lipoprotein cholesterol at week 16 were significantly different with aripiprazole versus olanzapine, with no significant effects on glycemic laboratory measures. Mean Clinical Global Impressions-Improvement (CGI-I) scores for both groups were in the range of "no change" to "minimal improvement." CGI-I endpoint scores were statistically significantly better with olanzapine (mean +/- SE = 3.09 +/- 0.16) versus aripiprazole (mean +/- SE = 3.74 +/- 0.15; p < .001), and more subjects discontinued aripiprazole (N = 32/88; 36%) than olanzapine (N = 22/85; 26%).. Significant improvements in weight and lipids observed during discontinuation of olanzapine and switch to aripiprazole treatment occurred with limited evidence of negative psychiatric effects, relative to uninterrupted continuation of olanzapine treatment. The results suggest that the potential value of therapeutic substitutions involving specific antipsychotic medications should be considered in overall efforts to reduce cardiovascular risk in this population.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Mass Index; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Administration Schedule; Electrocardiography; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Obesity; Olanzapine; Overweight; Piperazines; Psychotic Disorders; Quinolones; Schizophrenia; Triglycerides

The objective of this study was to assess the dose-response relationship of standard and higher doses of olanzapine in a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10 (n = 199), 20 (n = 200), and 40 mg/d (n = 200) for patients with schizophrenia or schizoaffective disorder and suboptimal response to current treatment. Patients meeting criteria for antipsychotic treatment resistance were excluded. Dose-response relationship was assessed by linear regression analysis with log-transformed dose (independent variable) and Positive and Negative Syndrome Scale (PANSS) total score (dependent variable). There were no significant dose group differences in patients completing the study (overall, 67.8%). All dose groups showed statistically significant improvement in PANSS total scores from baseline to end point without significant dose-response relationship (P = 0.295). Post hoc analysis of response showed significant interaction between baseline PANSS and dose (P = 0.023), indicating better response at higher doses for patients with higher baseline PANSS. There was a significant dose response for mean change in weight (P = 0.003) with significant difference between the 10- and 40-mg-dose groups (P = 0.002; 1.9 [10 mg/d], 2.3 [20 mg/d], and 3.0 kg [40 mg/d]). There was a significant dose response for change in prolactin (P < 0.001) with a significant difference between each group (-10.5 [10 mg/d], -1.7 [20 mg/d], and 4.9 ng/mL [40 mg/d]; P < or = 0.018). Over 8 weeks, non-treatment-resistant patients with schizophrenia or schizoaffective disorder responded to all 3 doses of olanzapine, without a statistically significant dose-response relationship, suggesting that for many patients with schizophrenia or schizoaffective disorder, particularly those who are mildly or moderately ill, 10 mg/d should be the initial dose of choice.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Prolactin; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Treatment Outcome; Weight Gain

The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a naturalistic longitudinal study of early-onset first psychotic episodes. This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months.. Participants were 110 patients, aged 9-17 years, with a first psychotic episode attended consecutively at six different centers. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions (CGI), Disability Assessment Schedule (DAS), and Global Assessment of Function (GAF) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale only at 6 months.. Diagnoses at baseline were 38.2% psychotic disorder not otherwise specified, 39.1% schizophrenia-type disorder, 11.8% depressive disorder with psychotic symptoms, and 10.9% bipolar disorder, manic episode with psychotic symptoms. The most frequently used antipsychotic agents were risperidone (n = 50), quetiapine (n = 18), and olanzapine (n = 16). Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms. Using the baseline score as covariate, no significant differences were found in the reductions on any scale in patients treated with risperidone, quetiapine, or olanzapine for 6 months. Weight increase was greater with olanzapine than with risperidone (p = 0.020) or quetiapine (p = 0.040). More neurological side effects appeared with risperidone than with olanzapine (p = 0.022). All side effects were mild or moderate.. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, are the most used in our context in first psychotic episodes in children and adolescents. These three obtain similar clinical improvement, but differ in their side effects.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Olanzapine; Practice Patterns, Physicians'; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Treatment Outcome; Weight Gain

Agitation is a common phenomenon in schizophrenia or acute mania. Because of the inability of patients to give informed consent in such situations, data from consenting studies are limited.. This observational prospective 5-day study evaluated the effectiveness of olanzapine in a sample of highly agitated patients with aggression. Primary endpoint was mean change of the PANSS-Excited Component (PANSS-EC) score.. Mean PANSS-EC score at baseline was 25.5 points, 60.2% were severely agitated and 41.6% severely aggressive. A significant decrease in PANSS-EC total score (-13.3 points) was observed with rapid dose escalation and an average daily dose of 21.2 mg/day of olanzapine. 40 patients (24.1%) required treatment with another antipsychotic and 21 patients (12.7%) were not treated with olanzapine at day 5. At endpoint, 64.2% of patients were in remission of agitation. PANSS-EC reduction was not significantly different in patients with or without concurrent benzodiazepine use.. Severe agitation with aggression may be well controlled with olanzapine in many cases, possibly by higher initial and overall doses of olanzapine. Controlled studies are needed to confirm these findings.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Time Factors; Treatment Outcome

The present study examined the ability of the International Suicide Prevention Trial (InterSePT) Scale for Suicidal Thinking (ISST) and the Calgary Depression Scale (CDS) to predict suicide attempts or hospitalizations to prevent attempts (referred to as Type 1 events) during the InterSePT trial [Meltzer, H.Y., Alphs, L., Green, A.I., Altamura, A.C., Anand, R., Bertoldi, A., Bourgeois, M., Chouinard, G., Islam, M.Z., Kane, J., Krishman, R., Lindenmayer, J.P., Potkin, S., 2003. Clozapine treatment for suicidality in schizophrenia. Archive of General Psychiatry 60, 82-91]. The primary goal of this analysis was to determine if the ISST and CDS ratings indicated that the raters, an unblinded (UP) and a blinded psychiatrist (BP) using the ISST, and a blinded rater using the CDS, were able to identify those patients who had a Type 1 event. The ratings of patients adjudged to have experienced a Type 1 event (Group 1) were compared with patients who did not (Group 2). The ISST and the CDS ratings obtained 2-8 weeks prior to a Type 1 event (Pre-1) and Pre-2, the rating immediately prior to Pre-1, obtained 2-12 weeks before Pre-1, were analyzed to test the hypothesis that the difference between Pre-2 and Pre-1 ratings for the Group 1 patients was significantly greater than the difference in the comparable ratings for Group 2 patients. The prediction that patients with Type 1 events would show greater worsening in ISST and CDS ratings between Pre-2 and Pre-1 than the Group 2 patients was confirmed. However, the sensitivity and specificity of a worsening in ratings was not sufficient to provide definitive warning of an impending Type 1 event. Other characteristics of the patients with Type 1 events provide additional warning: e.g. overall higher ratings on these scales, slower improvement in suicidality during treatment, and previous number of suicide attempts. These results indicate that the ISST and CDS may provide some additional information that can assist clinical decision making regarding suicidal risk in patients with schizophrenia or schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Observer Variation; Olanzapine; Personality Inventory; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Reproducibility of Results; Risk Assessment; Schizophrenia; Schizophrenic Psychology; Single-Blind Method; Suicide; Suicide Prevention; Suicide, Attempted; Thinking

Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder.. This double-blind multisite trial randomly assigned pediatric patients with early-onset schizophrenia and schizoaffective disorder to treatment with either olanzapine (2.5-20 mg/day), risperidone (0.5-6 mg/day), or molindone (10-140 mg/day, plus 1 mg/day of benztropine) for 8 weeks. The primary outcome was response to treatment, defined as a Clinical Global Impression (CGI) improvement score of 1 or 2 and >or=20% reduction in Positive and Negative Syndrome Scale (PANSS) total score after 8 weeks of treatment.. In total, 119 youth were randomly assigned to treatment. Of these subjects, 116 received at least one dose of treatment and thus were available for analysis. No significant differences were found among treatment groups in response rates (molindone: 50%; olanzapine: 34%; risperidone: 46%) or magnitude of symptom reduction. Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia.. Risperidone and olanzapine did not demonstrate superior efficacy over molindone for treating early-onset schizophrenia and schizoaffective disorder. Adverse effects were frequent but differed among medications. The results question the nearly exclusive use of second-generation antipsychotics to treat early-onset schizophrenia and schizoaffective disorder. The safety findings related to weight gain and metabolic problems raise important public health concerns, given the widespread use of second-generation antipsychotics in youth for nonpsychotic disorders.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Double-Blind Method; Female; Humans; Male; Molindone; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

To investigate potential changes and associations in clinical dimensions and cognitive functioning after the first 6 weeks of pharmacological treatment as the relation between cognitive and clinical change may have an impact in determining the importance of cognition as a treatment target.. Patients (n = 42) completed a brief battery of 5 neurocognitive tests within 72 hours of commencing, and 6 weeks after, standard pharmacological treatment. The cognitive testing comprised 5 domains: attention, visuomotor speed, declarative memory, working memory, and executive function. Volunteers (n = 43) were recruited to control for practice effects.. Patients and control subjects improved over time in the raw scores in cognitive tests. Patients' performance, at baseline and end point assessments, was below that of the control subjects in all cognitive variables, except the Stroop interference score. No interaction effect between time and group was found. Further, after controlling for practice effects and adjusting for multiple comparisons, patients' cognitive performance showed no significant improvement. Accordingly, there was no association between clinical improvement and cognitive change. This lack of association was also observed in the subgroup of people who showed decreased scores in negative symptoms.. Cognitive response is not clearly enhanced by antipsychotic drugs and it is not a by-product of clinical recovery during the acute phase (first 6 weeks) of a first-episode nonaffective psychosis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Risperidone; Schizophrenia; Statistics as Topic; Young Adult

This study aimed to evaluate the association of positive and negative symptoms, as well as of neurocognition to functional status in patients with schizophrenia. Participants were 309 veterans with DSM-IV-diagnosed schizophrenia or schizoaffective disorder who were enrolled in a 12-month double-blind clinical trial and randomized to receive either 5 to 20 mg/d of oral olanzapine or haloperidol. Patients were assessed at study entry and at 3, 6 and 12-months on the PANSS and measures of verbal memory, verbal fluency, fine motor coordination, visual sequencing/set shifting, and conceptual reasoning. Functional status was evaluated by the Heinrichs-Carpenter Quality of Life Scale (QLS) and by days of employment in the past 30. Hierarchical regression models examined the association of functional status with symptomatology and three neurocognitive factors (motor skills, memory and card sorting), controlling for demographics and visit number. A mixed effects model was used to adjust for repeated observations from the same subjects.. The PANSS explained 16% additional variance in QLS total score after accounting for demographics and visit number (p<.001), while the neurocognitive factors explained only 4% additional variance beyond the effect of symptoms. When neurocognition was entered before symptoms, it explained an additional 8% of the variance on the QLS total score, while the PANSS explained an additional 12% over and above neurocognition.. These findings suggest that symptoms may pose an equal or greater impediment to functional capacity independent of neurocognition, at least in younger non-institutionalized people with schizophrenia.

Topics: Activities of Daily Living; Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Employment; Female; Follow-Up Studies; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Veterans

The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, observational study of participants with bipolar I or schizoaffective disorder examining clinical, functional, and economic outcomes associated with naturalistic treatment.. Participants prescribed mood stabilisers were assessed using various measures, including the Young Mania Rating Scale (YMRS), 21-item Hamilton Depression Rating scale (HAMD21), Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), and the EuroQol instrument (EQ-5D).. 240 participants were recruited from two sites. On average, participants were 41.8+/-12.7 years of age (mean+/-SD), 58.3% were female, and 73.3% had a diagnosis of bipolar I disorder at study entry. The majority of participants were moderately ill, with an average CGI-BP Overall score of 3.8+/-1.3. Most participants had subthreshold mania and depression symptoms, indicated by HAMD21 Total 13.4+/-8.6, CGI-BP Depression 3.2+/-1.3, YMRS Total 8.2+/-8.5 and CGI-BP Mania 3.0+/-1.6 average scores. For bipolar participants, 94.6% of hospitalisations for psychiatric treatment in the past 3 months were single admissions (vs. 65.2% for schizoaffective participants, p=.002). Bipolar participants rated their overall health state higher (EQ-5D scores: 68.2+/-18.8 vs. 61.6+/-22.7, p=.023), had a higher mean weekly wage ($500-$999, 21.3% vs. 6.3%), lower unemployment (22.2% vs. 48.4%), and higher romantic relationship status (47.1% vs. 26.6%).. The observational design and small sample size may have limited the causal relationships and generalisability within the current findings.. Participants were characterised by social and occupational dysfunction at entry, but schizoaffective participants appeared to be more severely affected. Effective treatment is required to address both clinical and functional impairment.

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Australia; Benzodiazepines; Bipolar Disorder; Carbamazepine; Cohort Studies; Female; Health Status; Humans; Lithium Carbonate; Male; Olanzapine; Outcome Assessment, Health Care; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Severity of Illness Index; Social Adjustment; Treatment Outcome; Valproic Acid

Acute agitation is a common presentation in emergency departments and is often secondary to an underlying psychotic condition. The aim of this study was to compare the effectiveness of three second generation antipsychotics (risperidone, olanzapine, quetiapine) versus haloperidol in the treatment of psychotic agitation for up to 72 h.. We recruited 101 patients with acute psychosis who were admitted at the Mental Health Department 1 South of Turin, Psychiatric Emergency Service of San Giovanni Battista Hospital, from June 2004 to June 2005.. Aggressive behavior, as measured by Modified Overt Aggression Scale and Hostility-suspiciousness factor derived from the Brief Psychiatric Rating Scale, significantly improved in all groups, with no significant between-group differences. Extrapyramidal symptoms were more common in haloperidol treated patients compared with patients receiving risperidone, olanzapine or quetiapine.. Our results show that in the clinical practice setting of emergency psychiatry olanzapine, risperidone, quetiapine are as effective as haloperidol and better tolerated.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Haloperidol; Hostility; Humans; Italy; Male; Middle Aged; Olanzapine; Prospective Studies; Psychomotor Agitation; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To investigate the long-term weight loss outcomes during usual clinical practice after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT).. In this open-label prospective study, 26 patients with schizophrenia who were clinically stable on olanzapine SOT treatment were switched to olanzapine ODT. All other aspects of treatment remained constant. Weight was recorded at 3, 6, and 12 months.. Patients incurred an average weight loss of 2.7 +/- 0.7 kg (p = 0.001) after switching patients from olanzapine SOT to olanzapine ODT at 12 months. Peak weight loss was observed at 6 months; however, significant weight loss was achieved as early as 3 months. The majority (81.9%) of patients lost weight, while 18.1% had no weight change or weight gain. Body mass index (BMI) significantly decreased by 1.0 +/- 0.3 kg/m(2) (p = 0.001). Interestingly, patients treated with higher doses of olanzapine (> or = 20 mg) incurred a greater weight loss of their body weight (5.6%), compared to those treated with lower doses (< 20 mg), who lost 1.9% of their body weight (p = 0.04).. This study demonstrated that, in usual clinical practice, switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained over 12 months.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Chemistry, Pharmaceutical; Chronic Disease; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Overweight; Prospective Studies; Psychotic Disorders; Schizophrenia; Weight Loss

Clozapine, despite its side-effect burden, has been considered to be the drug of choice for patients with schizophrenia whose psychotic symptoms fail to respond adequately to other anti-psychotic drugs. There are conflicting data concerning the potential utility of olanzapine in treatment-resistant schizophrenia at doses beyond the 10- to 20-mg/day range that has proven to be effective for most nonrefractory patients with schizophrenia.. The main objective of this study was to compare the efficacy and tolerability of high-dose olanzapine (target dose, 25-45 mg/day) and clozapine (300-900 mg/day) in patients with schizophrenia or schizoaffective disorder who had failed to respond adequately to prior treatment with other antipsychotic drugs.. This 6-month, randomized, double-blind, parallel-group study compared the efficacy and tolerability of olanzapine (mean dose, 34 mg/day; N = 19) or clozapine (mean dose, 564 mg/day; N = 21) in patients with treatment-resistant schizophrenia or schizoaffective disorder, diagnosed according to DSM-IV criteria. Outcome measures included psychopathology, cognitive performance (as assessed with a comprehensive neuropsychological test battery), and tolerability. The study was conducted between May 2000 and December 2003.. Robust and significant (mostly p < .001) improvement in multiple measures of psychopathology, mainly between 6 weeks and 6 months of treatment, was found in both treatment groups, with no significant difference between the 2 treatments except for the Global Assessment of Functioning score, which favored clozapine (p = .01). Improvement in some domains of cognition was significant-and equivalent for both drugs, as well. Nonsignificantly different improvement in Verbal List Learning-Immediate Recall (p < .05), Controlled Word Association Test (p < .05), and Digit Symbol Substitution Test (p < .001) was found. There were no significant differences in extrapyramidal symptoms. Weight gain was significantly (p = .01) greater with olanzapine.. Olanzapine, at higher than customary doses, demonstrated similar efficacy to clozapine in treatment-resistant schizophrenia and schizoaffective disorder in this study. However, the small sample size precludes definitively concluding that the 2 treatments are equivalent, at these doses, in treatment-resistant schizophrenia. The metabolic side effects of olanzapine are a limitation in its use.. ClinicalTrials.gov identifier NCT00179231.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Serotonin Antagonists; Time Factors; Treatment Outcome; Weight Gain

An overactivation of the Th1 activity in schizophrenia had been described. Interleukin-12 (IL-12), a proinflammatory cytokine, plays a key role in the regulation of the Th1 response. The aims of this study were to investigate the effect of first and second generation antipsychotic drugs on IL-12 production during the acute phase of the illness and its association with clinical features. Participants comprised 56 drug-naïve first episode psychotic patients and 28 healthy volunteers. Patients were initially randomly assigned to risperidone (n=16), olanzapine (n=20) or haloperidol (n=20); subject were maintained on the same medication throughout the study. Clinical assessments were conducted at baseline and at 6 weeks. IL-12 plasma levels were assessed at baseline and after 6 weeks of antipsychotic treatment. IL-12 haplotypes were also analysed. Patients showed higher IL-12 plasma levels at baseline compared with controls, and had a significant increase in IL-12 plasma level after 6 weeks of antipsychotic treatment. No significant differences in IL-12 level increase were found among the three antipsychotic treatments. IL-12 plasma levels at week 6 were not significantly associated with the severity of psychopathology at week 6. Thus, patients with a first episode of psychosis have inflammatory-like immunological function during early phases of the illness that it is independent of the antipsychotic treatment used.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Demography; Diagnostic and Statistical Manual of Mental Disorders; Female; Haloperidol; Haplotypes; Humans; Interleukin-12; Male; Olanzapine; Psychotic Disorders; Risperidone; Time Factors

Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown.. We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function ("disposition index", DI) by intravenous glucose tolerance test.. At baseline, groups (risperidone: n=28; olanzapine: n=31) were overweight or obese by body mass index (risperidone: 28.4+/-5.4, olanzapine: 30.6+/-7.0kg/m2). Both drugs induced weight gain (p<0.004). Total adiposity was increased by olanzapine at 6 weeks (p=0.0006) and by both treatments at 24 weeks (p<0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p<0.003). S(I) did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and S(I), we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p<0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p=0.033), indicating inadequate pancreatic compensation for insulin resistance.. This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.

Topics: Absorptiometry, Photon; Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Brief Psychiatric Rating Scale; Double-Blind Method; Ethnicity; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Time Factors; Tomography, X-Ray Computed

To evaluate predictors of treatment discontinuation against medical advice and poor medication adherence among first-episode patients treated with olanzapine, quetiapine, or risperidone.. First-episode patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder (DSM-IV) were randomly assigned to olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) as part of a 52-week, randomized, double-blind, flexible-dose, multicenter study. Patients were enrolled from 2002 to 2004 at one of 26 sites in the United States and Canada. Survival analysis tested for predictors of treatment discontinuation against medical advice, while mixed models tested for predictors of poor medication adherence. Significant findings from the final models were replicated in sensitivity analyses.. Of the 400 patients randomly assigned to treatment, 115 patients who discontinued treatment against medical advice and 119 study completers were compared in this analysis. Poor treatment response (p < .001) and low medication adherence (p = .02) were independent predictors of discontinuation against medical advice. Ongoing substance abuse, ongoing depression, and treatment response failure significantly predicted poor medication adherence (p < .01). Higher cognitive performance at baseline and ethnicity (black) were also associated with lower medication adherence (p < .05). An association between poor medication adherence and illness insight at study entry was found at trend level (p = .059).. This study highlights the importance of treatment response in predicting discontinuation against medical advice and poor adherence to medication in first-episode patients. These results also support interventions to improve adherence behavior, particularly by targeting substance use disorders and depressive symptoms.. ClinicalTrials.gov identifier NCT00034892 (http://www.clinicaltrials.gov).

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Culture; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Surveys and Questionnaires; Treatment Refusal

The prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia is relatively high. Antipsychotics have been found to influence OCS.. To determine whether induction or severity of OCS differs during treatment with olanzapine or risperidone in young patients with early psychosis.. One hundred twenty-two patients with a Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder were randomized in a double-blind design to groups of 6 weeks' treatment with olanzapine (n = 59) or risperidone (n = 63), with a mean dose of 11.3 mg olanzapine and 3.0 mg risperidone at 6 weeks. Primary outcome measures were the mean baseline-to-endpoint change in total score on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS).. Treatment with olanzapine was associated with greater decreases in Y-BOCS total score than treatment with risperidone in total group (N = 122: -2.2 vs -0.3, z = -2.651, P < 0.01), in patients with baseline Y-BOCS total score greater than 0 (n = 58: -5.1 vs -0.4, z = -2.717, P < 0.01), and in patients with baseline Y-BOCS total score greater than 10 (n = 29: -7.1 vs -0.6, z = -2.138, P = 0.032).. In this randomized, 6-week, double-blind trial, we found a significant and clinically relevant difference in decrease in Y-BOCS scores favoring olanzapine compared with risperidone.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Capsules; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Severity of Illness Index; Time Factors; Treatment Outcome

Undesirable metabolic effects of modern antipsychotics, especially clozapine and olanzapine, merit development of new weight-control strategies, including pharmacologic ones. We investigated the feasibility of treatment with orlistat, a weight-control drug with no central effects, for overweight/obesity in clozapine- or olanzapine-treated male and female patients.. Add-on orlistat was prescribed for 16 weeks in a randomized, double-blind, placebo-controlled clinical trial to patients who were receiving stable clozapine or olanzapine medication and were aged 18 to 65 years, with no compliance with nonpharmacologic programs or hypocaloric diet required. The primary efficacy variable was body weight change. The study was conducted from 2004 through 2005.. Of 71 randomly assigned subjects, 63 were eligible for modified intent-to-treat analysis. While no statistically significant effect was observed in the whole population, male (but not female) patients benefited from treatment with orlistat (-2.36 kg vs. 0.62 kg on placebo, p = .011). There were 5 responders (16.1%) (those with >or= 5% weight loss) that received orlistat versus 2 responders (6.3%) that received placebo (number needed to treat = 11), but the difference was not statistically significant.. Without a hypocaloric diet, the effect of orlistat in overweight/obese clozapine-or olanzapine-treated patients is modest and may only be seen in men. More studies should define the optimal length of treatment and feasibility of combination of orlistat with behavioral programs in this population.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Double-Blind Method; Female; Humans; Lactones; Male; Middle Aged; Obesity; Olanzapine; Orlistat; Overweight; Psychotic Disorders

Weight gain has become one of the most common and concerning side effects of antipsychotic treatment. The mechanisms whereby antipsychotics induce weight gain are not known. It has been suggested that peptides related to food intake and energy balance could play a role in weight gain secondary to antipsychotic therapy. To better understand the pathophysiology of antipsychotic-induced weight gain, we studied the effects of 3 antipsychotic drugs (haloperidol, olanzapine, and risperidone) on peptides involved in energy balance (insulin, ghrelin, leptin, adiponectin, visfatin, and resistin) in a population of drug-naive patients with first episode of psychosis.A significant increase in weight (10.16 kg [SD, 8.30 kg]; P < 0.001), body mass index (3.56 kg/m [SD, 2.89 kg/m]; P < 0.001), and fasting insulin (3.93 muU/mL [SD, 3.93 muU/mL]; P = 0.028), leptin (6.76 ng/mL [SD, 7.21 ng/mL]; P < 0.001), and ghrelin (15.47 fmol/mL [SD, 47.90 fmol/mL]; P = 0.009) plasma levels were observed. The increments in insulin and leptin concentrations were highly correlated with the increment in weight and body mass index and seem to be a consequence of the higher fat stores. The unexpected increase in ghrelin levels might be related with the causal mechanism of weight gain induced by antipsychotics. Finally, the 3 antipsychotics had similar effects in all parameters evaluated.

Topics: Adiponectin; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Body Composition; Body Mass Index; Dose-Response Relationship, Drug; Energy Metabolism; Female; Ghrelin; Haloperidol; Humans; Insulin; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Olanzapine; Prospective Studies; Psychotic Disorders; Resistin; Risperidone; Schizophrenia; Weight Gain

Approximately 60% of patients with a first episode of psychosis will significantly reduce the severity of their positive symptomatology with antipsychotic drugs. The aim of this study was to investigate predictors of response to antipsychotic treatment during the first episode of non-affective psychosis. 172 patients (107 male) with a diagnosis of schizophreniform, schizophrenia, schizoaffective, brief reactive psychosis, schizotypal personality disorder or psychosis non-otherwise specified entered the study. Sociodemographic, premorbid and clinical data at baseline were evaluated. Unpaired t-test for continuous and chi2 for categorical data, respectively, were used to compare responders and non-responders selected variables. Multivariate logistic regression was used to establish a prediction model. 57.6% of study subjects (99 of 172) responded to antipsychotic treatment. The following variables were significantly associated with less likelihood of response: 1.--lower severity of general psychopathology, positive symptoms and disorganized symptoms at baseline; 2.--earlier age of onset; 3.--diagnosis of schizophrenia; 4.--longer DUP; 5.--poorer premorbid adjustment during adolescence, and 6.--hospitalization. Multivariate logistic regression demonstrated that differences between responders and non-responders were largely accounted for by BPRS total score, age of onset, premorbid adjustment at early adolescence, and diagnosis. Patients with an early age of onset of schizophrenia, a poor premorbid adolescent functioning, and with a lower severity of psychopathology at intake seem to have a decrease likelihood of responding to antipsychotic treatment. Helping clinicians to identify non-responders is meant as a first step to optimise therapeutic effort to benefit individuals in this vulnerable group.

Topics: Acute Disease; Adolescent; Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Comorbidity; Female; Haloperidol; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Prognosis; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Schizotypal Personality Disorder; Socioeconomic Factors; Spain; Treatment Outcome

A post-hoc analysis of the data from a randomised clinical trial involving prescription of antipsychotic treatment to never treated first-onset psychotic patients was used to compare the weight change after 6-week olanzapine treatment (standard tablets vs. orally disintegrating formulation).. In the subgroup of 38 patients randomised to olanzapine, standard olanzapine tablets were non-randomly and consecutively prescribed to the first 19 patients, with the orally disintegrating formulation being prescribed to the following 19 patients.. After 6-week treatment with olanzapine, a significant higher increase in weight was noted in those patients on standard tablets (mean weight increase 6.3 +/- 1.9 Kg) as compared to those on orally disintegrating olanzapine (mean weight increase 3.3 +/- 3.2 Kg) (F = 7.7; p = 0.009). BMI increase was also significantly higher in the olanzapine tablet group (mean increase of 2.1 Kg/m(2) as compared with 1.1 Kg/m(2) in the orally disintegrating group) (F = 4.7; p = 0.036). Substantial weight gain (SWG) (> or =7% increase from baseline weight) was noted in 84.2% (n = 16) of the olanzapine tablet patients and in 31.6% (n = 6) of the orally disintegrating olanzapine patients, with the olanzapine tablet group showing a significant increase in the mean percentage of weight gain (F = 4.0; p = 0.014).. Partial sublingual absorption occurring with orally disintegrating olanzapine may bypass gastrointestinal metabolisation and hence lead to differences in metabolite versus parent compound ratios. However, the need arises to replicate the present study with a longer follow-up.

Topics: Administration, Oral; Administration, Sublingual; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Dosage Forms; Female; Humans; Male; Olanzapine; Psychotic Disorders; Schizophrenia, Paranoid; Weight Gain

Thirteen outpatients with chronic but stable schizophrenia received donepezil and placebo augmentation of their maintenance antipsychotic medication regimen. Each subject received in a randomized, counterbalanced order 1) donepezil 5 mg for 6 weeks then donepezil 10 mg for six weeks and 2) placebo donepezil for 12 weeks. Serial ratings of the Positive and Negative Symptom Scale (PANSS) [Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13(2): 261-276] were performed by a trained rater blind to the donepezil order and condition: at baseline, 12 weeks and 24 weeks. On donepezil as compared to baseline or placebo, there was a significant improvement in PANSS negative scores (p=.018, n=13). These results are discussed with respect to other studies using cholinesterase inhibitors as an augmentation strategy in schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Clozapine; Cross-Over Studies; Donepezil; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indans; Male; Middle Aged; Nootropic Agents; Olanzapine; Piperidines; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This 52-week randomized, double-blind, flexible-dose, multicenter study evaluated the overall effectiveness (as measured by treatment discontinuation rates) of olanzapine, quetiapine, and risperidone in patients early in the course of psychotic illness.. Patients were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day) administered in twice-daily doses. Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks (primary outcome measure) based on a prespecified noninferiority margin of 20%.. A total of 400 patients were randomly assigned to treatment with olanzapine (N=133), quetiapine (N=134), or risperidone (N=133). The mean modal prescribed daily doses were 11.7 mg for olanzapine, 506 mg for quetiapine, and 2.4 mg for risperidone. At week 52, all-cause treatment discontinuation rates were 68.4%, 70.9%, and 71.4% for olanzapine, quetiapine, and risperidone, respectively. Reductions in total score on the Positive and Negative Syndrome Scale (PANSS) were similar for the three treatment groups, but reductions in PANSS positive subscale scores were greater in the olanzapine group (at 12 weeks and at 52 weeks or withdrawal from study) and the risperidone group (at 12 weeks). The most common elicited adverse events for olanzapine were drowsiness (53%), weight gain (51%), and insomnia (38%); for quetiapine, drowsiness (58%), increased sleep hours (42%), and weight gain (40%); and for risperidone, drowsiness (50%), menstrual irregularities in women (47%), and weight gain (41%).. Olanzapine, quetiapine, and risperidone demonstrated comparable effectiveness in early-psychosis patients, as indicated by similar rates of all-cause treatment discontinuation.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Dropouts; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sleep Stages; Sleep Wake Disorders; Treatment Outcome; Weight Gain

The authors sought to compare the effects of olanzapine, quetiapine, and risperidone on neurocognitive function in patients with early psychosis.. In a 52-week double-blind, multicenter study, 400 patients early in the course of psychotic illness (<5 years) were randomly assigned to treatment with olanzapine (2.5-20 mg/day), quetiapine (100-800 mg/day), or risperidone (0.5-4 mg/day). The mean modal daily dose was 11.7 mg (SD=5.3) for olanzapine, 506 mg (SD=215) for quetiapine, and 2.4 mg (SD=1.0) for risperidone. A total of 224 patients completed neurocognitive assessments at baseline and at 12 weeks, and 81 patients also completed them at 52 weeks. Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and from the Brief Assessment of Cognition in Schizophrenia.. At week 12, there was significant improvement in neurocognition for each treatment (p<0.01), but no significant overall difference between treatments. Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine, 0.33 for quetiapine, and 0.32 for risperidone. Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine, 0.34 for quetiapine, and 0.22 for risperidone. Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52.. Olanzapine, quetiapine, and risperidone all produced significant improvements in neurocognition in early-psychosis patients. Although cognitive improvements were modest, their clinical importance was suggested by relationships with improvements in functional outcome.

Topics: Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Least-Squares Analysis; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Treatment Outcome

Prepulse inhibition (PPI), whereby the startle eyeblink response is inhibited by a relatively weak non-startling stimulus preceding the powerful startle eliciting stimulus, is a measure of sensorimotor gating and has been shown to be deficient in schizophrenia patients. There is considerable interest in whether conventional and/or atypical antipsychotic medications can "normalize" PPI deficits in schizophrenia patients. 51 schizophrenia patients participated in a randomized, double-blind controlled trial on the effects of three commonly-prescribed antipsychotic medications (risperidone, olanzapine, or haloperidol) on PPI, startle habituation, and startle reactivity. Patients were tested at baseline, Week 4 and Week 8. Mixed model regression analyses revealed that olanzapine significantly improved PPI from Week 4 to Week 8, and that at Week 8 patients receiving olanzapine produced significantly greater PPI than those receiving risperidone, but not haloperidol. There were no effects of medication on startle habituation or startle reactivity. These results support the conclusion that olanzapine effectively increased PPI in schizophrenia patients, but that risperidone and haloperidol had no such effects. The results are discussed in terms of animal models, neural substrates, and treatment implications.

Topics: Acoustic Stimulation; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Electromyography; Female; Habituation, Psychophysiologic; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Reflex, Startle; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Although antipsychotic drugs control acute psychotic manifestations of schizophrenia, improving cognitive symptoms is also important for long-term prognosis.. Three hundred and seventy-seven adult patients with acute psychosis were randomised to either amisulpride (200-800 mg/d) or olanzapine (5-20 mg/d) for 6 months. Neuropsychological performance was assessed at inclusion and after 6 months in a subgroup of 26 subjects (11 treated with amisulpride and 15 with olanzapine) using the Auditory Verbal Learning Test (AVLT), the Trail Making Test (TMT) and the Controlled Oral Word Association Test (COWAT).. The improvement in BPRS score was similar in both treatment groups. No significant differences in test performance between groups were observed at inclusion. After 6 months, AVLT scores increased by 8.7 points in the amisulpride group and by 2.3 points in the olanzapine group (p = 0.049). Completion speed in the TMT increased by 17.4 s (amisulpride) and 15.4 s (olanzapine) for Part A and by 39.8 and 48.8 s, respectively for Part B. Performance in the COWAT improved little in both groups.. Both amisulpride and olanzapine produce sustained improvement in certain measures of neuropsychological performance in patients with schizophrenia; a significant improvement in score on the AVLT was observed only with amisulpride.

Topics: Acute Disease; Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Prognosis; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Sulpiride

The second generation antipsychotics clozapine and olanzapine frequently induce weight gain. Randomized studies investigating abnormal eating behavior (food craving, binge eating) possibly associated with weight gain are lacking. Thirty patients with schizophrenia, schizophreniform, or schizoaffective disorder were included in this randomized, double-blind, parallel study comparing abnormal eating behavior using a standardized scale, clinical efficacy using the Brief Psychiatric Rating Scale 0-6 and Clinical Global Impression-Severity scale, and tolerability of clozapine and olanzapine. In both treatment groups, the number of patients reporting food craving, binge eating, or both increased over time. The likelihood to experience food craving at any time during drug treatment showed a trend (P = 0.068) to be higher in the olanzapine group (48.9%) compared with the clozapine group (23.3%). The likelihood to experience binge eating at any time during drug treatment was numerically but not statistically significantly higher in the olanzapine group (16.7%) than in the clozapine group (8.9%). In both groups, significant baseline-to-end point improvements of clinical symptoms (Brief Psychiatric Rating Scale 0-6: clozapine, 36.6 +/- 8.8 to 15.9 +/- 13.7; olanzapine, 36.7 +/- 9.9 to 19.1 +/- 13.8) and severity of illness (Clinical Global Impression-Severity scale: clozapine, 4.7 +/- 0.6 to 2.5 +/- 1.5; olanzapine, 4.5 +/- 0.6 to 2.3 +/- 1.2) were observed. These improvements did not differ significantly between groups. Olanzapine was more tolerable than clozapine; adverse events occurred significantly (P < 0.01) less frequently than in the clozapine group. These results suggest that both clozapine and olanzapine can induce food craving and binge eating, however, olanzapine possibly to a greater extent. Findings on clinical efficacy and safety are in accordance with previous reports.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Appetite; Benzodiazepines; Blood Pressure; Body Mass Index; Bulimia; Clozapine; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue; Female; Heart Rate; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Sialorrhea; Treatment Outcome; Weight Gain

This study examined the main metabolic side effects induced by antipsychotic treatment in a cohort of first-episode drug-naive subjects.. A randomized, open-label, prospective clinical trial was conducted. Participants were 145 consecutive subjects included in a first-episode psychosis program (PAFIP) from February 2002 to February 2005, experiencing their first episode of psychosis (DSM-IV codes 295, 297, and 298), and never treated with antipsychotic medication. Patients were assigned to haloperidol, olanzapine, or risperidone treatment during 12 weeks. The main outcome measures were changes at 12 weeks in body weight; body mass index; and 12-hours-fasting morning levels of total cholesterol, tri-glycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, glucose, homeostasis model assessment (HOMA) index, and insulin.. At the endpoint, 128 patients were evaluated (88.3%). The mean doses were haloperidol = 4.2 mg/day, olanzapine = 12.7 mg/day, and risperidone = 3.6 mg/day. A significant weight gain was observed with the 3 antipsychotics: haloperidol = 3.8 (SD = 4.9) kg, olanzapine = 7.5 (SD = 5.1) kg, and risperidone = 5.6 (SD = 4.5) kg. Metabolic parameters showed a worsening lipid profile with the 3 treatments (statistically significant increase in total cholesterol and LDL cholesterol levels). Only the olanzapine group showed significant increases in triglyceride levels. After the 12-week study period, there were no significant changes in parameters involving glucose metabolism for any group.. Drug-naive patients experienced an extraordinary weight gain with first- and second-generation antipsychotics after the first 12 weeks of treatment. Significant increases in total cholesterol and LDL cholesterol levels are associated with the 3 treatments. Weight gain and metabolic disturbances induced by antipsychotics may increase the risk of developing cardiovascular disease.

Topics: Adolescent; Adult; Anthropometry; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Diagnostic and Statistical Manual of Mental Disorders; Dyslipidemias; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Prevalence; Prospective Studies; Psychotic Disorders; Risperidone; Severity of Illness Index; Weight Gain

Neurocognitive deficits are severe in first-episode psychosis.. Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.87 mg/day) for 104 weeks. A neurocognitive battery was administered at baseline (n = 246) and 12 (n = 167), 24 (n = 126), 52 (n = 89), and 104 (n = 46) weeks during treatment. Weighted principal component and unweighted composite scores were derived from individual tests.. Both treatment groups demonstrated significant improvement on both composite scores. On the basis of the weighted composite score, olanzapine had greater improvement than haloperidol only at 12 (p = .014) and 24 (p = .029) weeks. For the unweighted composite, olanzapine had significantly better improvement compared with haloperidol only at week 12 (p = .044). At week 12 only, olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol.. Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia. A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Principal Component Analysis; Psychotic Disorders; Statistics, Nonparametric

To describe patients included in the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study and to assess and clinically validate the presence of clinical subtypes of patients with acute mania.. The EMBLEM study is a 2-year prospective, observational study on the treatment and outcome of patients who are treated for a manic or mixed episode. Latent Class Analysis was used to define discrete groups of patients at baseline.. Three groups were identified: 'typical mania' (59% of patients); 'psychotic mania' (27%) with more severe mania and presence of psychotic symptoms; and 'dual mania' (13%) with a high proportion of substance abuse. Patient groups differed in age of onset, social functioning and service needs.. Dual mania represents a distinct and not infrequent subgroup of patients with mania. The exclusion of patients with comorbid substance problems from clinical trials creates a gap in our knowledge on treatment effectiveness.

Topics: Adult; Ambulatory Care; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Diagnosis, Dual (Psychiatry); Drug Therapy, Combination; Europe; Female; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Patient Admission; Prospective Studies; Psychotic Disorders; Substance-Related Disorders; Treatment Outcome

The authors examined cognitive changes associated with treatment with ziprasidone and olanzapine over a 6-month double-blind clinical trial, using normative standards for the cognitive measures. Sixty-two schizophrenia patients entered the study on ziprasidone treatment (39 completers), and 71 patients entered while receiving treatment with olanzapine (33 completers). From a larger set of cognitive domains assessed in the acute treatment study, we selected verbal learning, executive functioning, and verbal fluency for further analysis due to their functional relevance and extensive normative data. Standard scores were developed based on previously published age- and education-corrected norms. Baseline performance was impaired across all tests on average. The proportion of patients impaired on each of the tests at baseline ranged from 36% (letter fluency) to 89%. Performance was significantly improved by ziprasidone and olanzapine treatment for all cognitive variables and for the composite measure. A number of subjects met the a priori criteria for normalization in performance, ranging from 10% for Trail Making Test Part B to 37% for Word List Total Learning. There were no significant differences across medications in extent of change or likelihood of inducing normalization. Statistically significant improvements in cognitive performance over 6 months of treatment with atypical antipsychotic medications are associated with performance increasing into the normal range of cognitive functioning in a proportion of previously impaired patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Patient Admission; Piperazines; Psychometrics; Psychotic Disorders; Schizophrenia; Thiazoles

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Humans; Male; Olanzapine; Patient Dropouts; Psychotic Disorders; Risperidone

To determine how the use of the newer, so called atypical antipsychotic medications, effects the pharmacoeconomic treatment burden of schizophrenia and related conditions and to provide a clear comparison of the costs and risks associated with these atypical drugs.. In this 2-year, open-label, prospective study, resource utilization (RU) data were collected on 160 patients with these conditions. A comparison between risks and costs was performed by combining the generalized CNOMSS data on both economic factors and risk assessments.. The main findings of the study were that the total adjusted 1- and 2-year costs were lowest for quetiapine. Drug acquisition costs were lowest for risperidone for both the 1- and 2-year cohorts. Clozapine use was predictably associated with the highest overall and medication costs at both 1 and 2 years.. Treatment with risperidone or quetiapine was associated with the lowest overall costs when compared with olanzapine or clozapine.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Canada; Clozapine; Cohort Studies; Cost of Illness; Cost-Benefit Analysis; Dibenzothiazepines; Drug Costs; Female; Health Care Surveys; Health Resources; Humans; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risk Assessment; Risperidone; Schizophrenia

The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms.. This randomized, double-blind, 24-week, fixed-dose study compared olanzapine (n = 202) and ziprasidone (n = 192) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms. Outcome measures included change in Calgary Depression Scale for Schizophrenia (CDSS) score from baseline to 8 weeks (primary outcome) and changes in CDSS, Montgomery-Asberg Depression Rating Scales, Positive and Negative Syndrome Scale, and Global Assessment of Functioning (GAF) scores for 24 weeks. Statistical analyses included mixed-effects model repeated measures (primary analysis) and change from baseline to last observation carried forward (LOCF).. At baseline, patients had moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scales total score, 27.3). For 8 weeks, patients treated with olanzapine or ziprasidone had significant improvements on CDSS. Treatment group differences were not statistically significant (P = 0.493, mixed-effects model repeated measures; P = 0.497, LOCF). For 24 weeks, olanzapine-treated patients showed significantly greater improvements in depressive symptoms (results varied by depression measure and statistical approach) and GAF (P < 0.017, LOCF). A significantly higher proportion of olanzapine-treated patients completed the study (44.6% vs 29.7%; P = 0.003) and remained longer on medication (median, 163 vs 73 days, P < 0.001), compared with ziprasidone-treated patients. Olanzapine-treated patients experienced significantly (P < 0.05) greater increases in triglycerides, HgbA1c, and weight.. For 24 weeks, olanzapine-treated patients had greater and more sustained participation in treatment, during which time significantly greater improvements were observed in depressive symptoms and GAF scores, along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients.

Topics: Antipsychotic Agents; Benzodiazepines; Depression; Glycated Hemoglobin; Humans; Olanzapine; Patient Dropouts; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Thiazoles; Treatment Outcome; Triglycerides; United States; Weight Gain

The main objective was to assess the efficacy of a weight management program designed for outpatients taking olanzapine for schizophrenia or schizoaffective disorder and to compare these patients with a randomized control group. The effects of the weight management program were also assessed with regard to safety and quality of life.. Forty-eight patients were enrolled in a 12-week, randomized, multicenter weight management study. Thirty-three patients were randomly allocated to an intervention group in which they received olanzapine within a weight management program. Fifteen patients were allocated to a control group in which they were given olanzapine treatment as usual outpatients. Weight, body mass index (BMI), and measurements of safety and quality of life were evaluated. The study was conducted from January 7, 2003, to September 16, 2003.. Thirty-six patients (75%) completed this study. We found significant differences in weight (-3.94 +/- 3.63 kg vs. -1.48 +/- 1.88 kg, p = .006) and BMI (-1.50 +/- 1.34 vs. -0.59 +/- 0.73, p = .007) change from baseline to endpoint between the intervention and control groups, respectively. Significant differences in weight reduction were initially observed at week 8 (p = .040). No significant differences were found with regard to the safety outcomes. When the ratio of low-density lipoproteins to high-density lipoproteins was calculated, change from baseline was greater in the intervention group than the control group (-0.19 vs. -0.04), but the difference was not statistically significant (p = .556). After the completion of the weight management program, there was a trend toward statistical difference in the physical health score changes between the weight management and control groups (1.12 in the intervention group vs. -0.93 in the control group, p = .067).. The weight management program was effective in terms of weight reduction in patients with schizophrenia or schizoaffective disorder taking olanzapine and was also found to be safe in terms of psychiatric symptoms, vital signs, and laboratory data. In addition, such a weight management program might improve quality of life in patients with schizophrenia or schizoaffective disorder with respect to their physical well-being.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cognitive Behavioral Therapy; Diet, Reducing; Exercise Therapy; Female; Health Status; Humans; Male; Middle Aged; Obesity; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Schizophrenia; Treatment Outcome; Weight Loss

We conducted a naturalistic, multicenter, 24-hour, nonrandomized, observational study describing for the first time the effectiveness and safety of intramuscular (IM) olanzapine to control agitation and aggression in "real world" patients with psychosis. The data thus obtained was compared with that reported from randomized double-blind clinical trials.. 92 patients attending psychiatric emergency settings were enrolled. The study subjects were 44 male and 48 female patients with a mean age of 36.5+/-12 years and DSM-IV-TR diagnoses of schizophrenia (48.9%), psychotic disorder not specified (23.9%) or bipolar disorder (27.2%). 10 mg IM olanzapine was administered to all patients. An optional second injection was permitted> or =2 hours later in line with hospital policy. Evaluations (PANSS-EC and CGI-S) were performed at baseline and 2 and 24 hours following the IM injection.. Two hours after IM olanzapine was administered, a mean decrease of -9.6 in the PANSS-EC from a baseline score of 26.5 was recorded. At the 24-hour endpoint a statistically and clinically significant reduction in the PANSS-EC scores (11.6+/-5.3) was observed as compared with values at study entry (26.5+/-5.9) and at 2 hours endpoint (16.9+/-9.3), which represent a mean decrease of -14.9 and -5.3, respectively.. The present naturalistic study provides naturalistic data on the effectiveness of IM olanzapine in the treatment of acute agitation in patients with schizophrenia or bipolar mania that is in line the data obtained in randomized double-blind clinical trials.

Topics: Acute Disease; Adolescent; Adult; Aged; Aggression; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Time Factors; Treatment Outcome

We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol.. Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ).. Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups.. Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Topics: Adolescent; Adult; Antipsychotic Agents; Attitude to Health; Benzodiazepines; Brain; Cognition Disorders; Depressive Disorder, Major; Double-Blind Method; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Surveys and Questionnaires; Treatment Refusal

Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community. Finding appropriate treatment of violent behaviors is of primary importance.. To compare the efficacy of 2 atypical antipsychotic agents, clozapine and olanzapine, with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder.. Randomized, double-blind, parallel-group, 12-week trial. Physically assaultive subjects with schizophrenia or schizoaffective disorder who were inpatients in state psychiatric facilities were randomly assigned to treatment with clozapine (n = 37), olanzapine (n = 37), or haloperidol (n = 36).. Number and severity of physical assaults as measured by the Modified Overt Aggression Scale (MOAS) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score. Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS).. Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score. Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures. There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales.. Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior. This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications.

Topics: Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome; Violence

The objective of the study was to examine whether patients with schizophrenia who were judged to be stable on long-term treatment with conventional antipsychotic medications would further benefit from a switch to an atypical antipsychotic drug. Thirty-six subjects with schizophrenia spectrum disorder, on conventional antipsychotic medication therapy for at least 2 years, were randomized in double-blind fashion to risperidone versus olanzapine. Patients were titrated up to 6 mg risperidone or 15 mg olanzapine as tolerated, followed by tapering and discontinuation of conventional antipsychotic medication. Atypical antipsychotic agents were then administered alone (monotherapy) for 12 weeks. Efficacy and tolerability were assessed using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale, and Simpson Angus Scale. Body weight was measured at each visit. Both treatment groups exhibited marked and similar improvement in the total PANSS score from baseline to study endpoint (22 weeks) [risperidone: baseline=59.3 (SE 3.1), 22 weeks=44.3 (SE 2.3) (p<0.001); olanzapine: baseline=55.9 (SE 3.3), 22 weeks=46.9 (SE 3.2) (p<0.001). Both groups also exhibited significant reductions in PANSS factor scores for positive and negative symptoms and disorganized thoughts. Only risperidone-treated patients exhibited significant decreases in uncontrolled hostility/excitement and anxiety and depression. Of note, while positive factor scores exhibited the majority of change within the first 10 weeks, negative factor scores continued to decline significantly in both treatment groups throughout the study. Tolerability assessments did not differ between groups. The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Weight; Chronic Disease; Double-Blind Method; Female; Humans; Long-Term Care; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Creatine kinase is an important enzyme in the energy metabolism of many cell types, including muscle cells. Increased serum levels of creatine kinase may serve as a marker of enhanced creatine kinase synthesis in muscle cells or muscle cell membrane damage. The purpose of this study was to compare serum creatine kinase levels in chronic psychosis patients treated with either atypical or conventional antipsychotics. Forty-nine patients, receiving clozapine (n=18), or olanzapine (n=18), or conventional agents (n=13), were studied. Fasting serum samples were analyzed for creatine kinase. A significant difference in median creatine kinase level was found among the treatment groups (p=0.03), in that the creatine kinase level was higher both in the patients receiving clozapine and in the patients receiving olanzapine, compared to that in patients receiving conventional antipsychotics, p=0.001 and p<0.0001, respectively. In addition, elevated creatine kinase levels above the upper limit of normal were found in 6 (17%) of the patients treated with clozapine or olanzapine, but in none of the patients treated with conventional agents. In summary, the present results indicate that therapy with atypical antipsychotics like clozapine and olanzapine, in contrast to conventional agents, may be associated with serum creatine kinase elevation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chromatography, High Pressure Liquid; Clozapine; Creatine Kinase; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders

The use of olanzapine (OLZ) in the prevention of postpartum psychosis (PP) and mood episodes in women with bipolar disorder was investigated in a naturalistic, prospective study.. Eleven women received OLZ alone or in combination with an antidepressant or mood stabilizer, and 14 women received either antidepressants, mood stabilizers, or no medication for a minimum of 4 weeks after delivery.. Two (18.2%) of the women in the OLZ group experienced a postpartum mood episode, whereas eight (57.1%) of the women in the No-OLZ group did.. The role of OLZ in the prophylaxis of PP and mood episodes, particularly in women at high risk, clearly warrants further investigation.

Topics: Adult; Affect; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Olanzapine; Psychotic Disorders; Puerperal Disorders; Treatment Outcome

Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis. This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period. Two hundred and sixty-three patients were randomized to olanzapine or haloperidol in a doubleblind, multisite, international 2-year study. Clinical symptoms and side effects were assessed at baseline and longitudinally following randomization for the duration of the study. Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity (the primary outcome measure) over the course of the study. However, the treatment groups differed on two secondary efficacy measures. Patients were less likely to discontinue treatment with olanzapine than with haloperidol: mean time (in days) in the study was significantly greater for those treated with olanzapine compared to haloperidol (322.09 vs. 230.38, p<0.0085). Moreover, remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.25% vs. 43.94%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine. The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients, which must be weighed against those adverse effects that are more likely with olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Follow-Up Studies; Haloperidol; Humans; International Cooperation; Male; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Treatment Outcome

This study compared the effects of olanzapine (OLZ) with those of quetiapine (QUE) for improving negative symptoms in patients diagnosed with schizophrenia or schizoaffective disorder who had prominent negative symptoms and marked deficits in social or occupational functioning. In this 6-month, multicenter, double-blind clinical trial, patients were randomized to treatment with OLZ (n = 171, 10-20 mg/d) or QUE (n = 175, 300-700 mg/d). Patients were treated at community mental health centers and assigned case managers who developed individualized psychosocial treatment plans. The primary efficacy measure was the reduction in negative symptoms using the Scale for the Assessment of Negative Symptoms. Secondary measures assessed changes in functioning, psychopathology, and treatment tolerability. Treatment with OLZ or QUE led to a significant reduction in negative symptoms, with no between-group difference (P = 0.09). Both treatment groups also showed significant improvement on most efficacy measures. Olanzapine-treated patients showed significantly greater improvement on positive symptoms and on several measures of functioning including Global Assessment of Functioning Scale, Quality of Life Instrumental Role domain, and level of effort in psychosocial or occupational rehabilitation programs. Significantly more OLZ-treated patients completed the study (52.6% OLZ, 37.7% QUE, P = 0.007). Treatment differences in safety were relatively small and not thought to be clinically relevant. Patients with schizophrenia who manifest prominent negative symptoms and marked functional deficits demonstrated significant improvement in negative symptoms after treatment with OLZ or QUE. Greater improvement in positive symptoms and a greater study completion rate may hold relevance to enhanced functional outcomes observed after OLZ therapy.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Research Design; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Social Adjustment; Treatment Outcome

The aim of the study was to evaluate the efficacy of olanzapine (5 and 20 mg/day) over a 6-month period in chronic schizophrenic patients experiencing predominantly negative symptoms.. Two hundred and forty-four patients participated in a 6-month multicenter double-blind trial of placebo (n = 34), olanzapine 5 mg/day (n = 70), olanzapine 20 mg/day (n = 70), or amisulpride 150 mg/day (n = 70). Primary measure was the scale for the assessment of negative symptoms.. Olanzapine 5 mg/day showed significantly greater improvement than placebo in negative symptoms and in the Positive and Negative Syndrome Scale total score. Baseline positive symptoms were low at baseline and changed minimally. The neurological tolerance of olanzapine, amisulpride and placebo were comparable.. Olanzapine 5 mg/day was effective in treating negative symptoms in a group of schizophrenic with predominantly negative symptoms during the stabilization phase. Improvement in positive symptoms or extrapyramidal symptoms (EPS) was unlikely to explain this result while improvement in depression may have partially contributed.

Topics: Adult; Affect; Amisulpride; Antipsychotic Agents; Attention; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Chronic Disease; Depression; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Psychotic Disorders; Recurrence; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Sulpiride; Surveys and Questionnaires

Randomized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis. However, these results may not be generalizable to routine clinical practice. We evaluated the effectiveness, tolerability, and safety of olanza-pine, risperidone, and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical settings.. 172 patients participated in a practical clinical trial and were randomly assigned to haloperidol (N = 56), risperidone (N = 61), and olanzapine (N = 55). The mean modal daily doses were 5.4 mg/day for halo-peridol, 4 mg/day for risperidone, and 15.3 mg/day for olanzapine; 98.3% of subjects were drug naive at baseline. Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal (February 2001 to February 2005) intervention program of first-episode psychosis (schizophrenia spectrum disorders, DSM-IV criteria) are reported.. All 3 treatments showed similar effectiveness in reducing the severity of general, negative, and positive symptomatology after 6 weeks of treatment, as reported by mean change in total Clinical Global Impressions-Severity of Illness scale, Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks. The proportion of study subjects responding, defined as 40% or greater BPRS total score improvement from baseline, was 57.1% (N = 32 of 56) haloperidol, 52.5% (N = 32 of 61) risperidone, and 63.6% (N = 35 of 55) olanzapine, with no statistical differences among groups. The frequency of extrapyramidal symptoms (chi(2) = 24.519; p < .001) and concomitant anticholinergic medication use (chi(2) = 57.842; p < .0001) was greater with haloperidol than olanzapine or risperidone. Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups (p < .001).. Relatively low doses of haloperidol, risperidone, and olanzapine are equally effective for the acute treatment of first-episode nonaffective psychosis under usual conditions of real clinical practice.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Female; Haloperidol; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

To assess whether pharmacokinetic drug interactions occur when sertraline is added to antipsychotic medications.. Forty-eight patients with remitted DSM-IV schizophrenia and comorbid major depression were randomized to placebo for 6 weeks or sertraline 50 mg for 4 weeks followed by sertraline 50 mg to 100 mg for 2 weeks for nonresponders. Treatment with the patients' usual antipsychotic continued. Weekly clinical outcome assessments occurred for 6 weeks, and serum samples for drug monitoring were collected at Weeks 1, 5, and 6. Serum concentrations of sertraline and antipsychotics were measured with standard assays.. In both placebo- and sertraline-treated groups, most patients displayed minor fluctuations in antipsychotic serum levels over 6 weeks. There was no clinical evidence of drug interactions in the sertraline-treated group.. Clinically significant adverse effects did not occur despite variable antipsychotic serum levels with or without sertraline. Concern about pharmacokinetic interactions should not deter the use of sertraline for depression in individuals with schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Comorbidity; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Monitoring; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Sertraline

The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders.. One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day).. Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone.. Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Mass Index; Female; Follow-Up Studies; Humans; Male; Obesity; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain

Weight gain is commonly observed with olanzapine treatment and can increase the risk for obesity, cardiovascular disease, hypertension, and diabetes mellitus. This study examined the effectiveness of sibutramine, an approved weight loss agent, in overweight and obese subjects taking olanzapine for schizophrenia or schizoaffective disorder.. Each subject had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable dose of olanzapine for at least 4 months, and had a body mass index of >/=30 kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12-week double-blind, randomized, placebo-controlled study, 37 subjects received placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects participated in weekly group sessions focused on nutrition and behavioral modification.. The sibutramine and placebo groups had no significant baseline differences on age, gender, education, ethnicity, diagnosis, weight, body mass index, and blood pressure. At week 12 the sibutramine group had significantly greater losses than the placebo group in weight (mean=8.3 lb, SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and hemoglobin A(1c). There were no significant differences on most side effects, although the sibutramine group exhibited a mean increase in systolic blood pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep disturbances were at least twice as common in the sibutramine group.. Sibutramine was an effective and well-tolerated adjunct to behavior modification for weight loss in patients with schizophrenia and schizoaffective disorder being treated with olanzapine.

Topics: Adult; Antipsychotic Agents; Appetite Depressants; Behavior Therapy; Benzodiazepines; Combined Modality Therapy; Cyclobutanes; Double-Blind Method; Female; Humans; Male; Obesity; Olanzapine; Placebos; Psychotic Disorders; Schizophrenia; Sleep Wake Disorders; Treatment Outcome; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Haloperidol; Humans; Nursing Assessment; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Schizophrenia causes significant impairments of quality of life. As treatment approaches have advanced, more attention has been given to re-integrating patients into their psychosocial environments, rather than simply monitoring psychotic symptoms. The development of the second-generation antipsychotics raised hope that these medications would provide better quality of life improvement than conventional antipsychotics. This improvement is particularly relevant early in the course of schizophrenia.. To address these considerations, improvements in measures of general health and social function (determined using the SF-36) were assessed in 195 patients with first-episode schizophrenia for up to one year following randomization to either olanzapine or haloperidol in a double blind clinical trial. We hypothesized that olanzapine would demonstrate better improvement on these measures than haloperidol. In order to test this hypothesis, we used a repeated measure model with SF-36 scores as the outcome, and treatment group, time, time2, time-by-treatment group interaction, and time2-by-treatment group interaction as fixed effects.. Both treatments demonstrated similar changes on the SF-36. Independent of treatment, patients demonstrated significant improvements in most of the SF-36 subscales, which approached normative scores by the end of one year of treatment. Forty-six of 100 olanzapine-treated patients and 37 of 95 haloperidol-treated patients completed the one year of this study (p<.4).. These results suggest an important initial treatment goal for patients with new onset schizophrenic disorders, namely that they can expect to recover significant quality of life and social function at least initially in treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Disease Progression; Double-Blind Method; Female; Follow-Up Studies; Haloperidol; Humans; Male; Olanzapine; Pain; Pain Measurement; Psychotic Disorders; Quality of Life; Time Factors

The authors' goal was to compare the efficacy and tolerability of 6 months' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or schizoaffective disorder.. Brief Psychiatric Rating Scale (BPRS) scores and Clinical Global Impression (CGI) severity scores were obtained for 126 responders to a 6-week acute study of olanzapine and ziprasidone during a blinded 6-month continuation study and optional extension study.. Comparable improvements in BPRS and CGI severity scores were seen with both drugs. Olanzapine produced significant increases from acute-study baseline values in weight and body mass index and within-group increases in total cholesterol, low-density lipoprotein cholesterol, and fasting insulin. Between-group differences were not significant for lipids and insulin. Mean QTc values at endpoint were 407.1 msec (baseline mean=406.0 msec) and 394.4 msec (baseline mean=399.7 msec) for ziprasidone and olanzapine, respectively. No patient had a QTc interval > or =500 msec.. Ziprasidone and olanzapine had comparable long-term efficacy; olanzapine was associated with significant weight gain and metabolic alterations.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Humans; Obesity; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome; Weight Gain

To compare the efficacy of two atypical antipsychotic drugs, olanzapine and risperidone, in schizophrenic patients with post-psychotic depression.. A clinically significant decrease of MADRS scores occurred in patients treated with both drugs for 8 weeks.. Atypical antipsychotic drugs may be particularly appropriate when treating schizophrenic patients with depression.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Depression; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Severity of Illness Index

Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy.. Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment.. At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6).. These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Corpus Striatum; Dose-Response Relationship, Drug; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Raclopride; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The efficacy and tolerability of risperidone long-acting injectable were investigated in patients with schizophrenia or other psychotic disorders who had previously been symptomatically stable on olanzapine treatment. Patients received risperidone long-acting injectable, 25 mg, by intramuscular injection every 2 weeks; the dose could be increased to 37.5 or 50 mg if necessary. Patients were transferred directly from their previous medication to risperidone long-acting injectable without a run-in period of oral risperidone treatment. Of 192 patients recruited, 134 patients (70%) completed the study. The principal reasons for discontinuation were withdrawal of consent (8%), adverse events (6%), insufficient response (5%) and non-compliance (4%). Risperidone long-acting injectable produced a significant improvement (p = 0.0001) in Positive and Negative Syndrome Scale (PANSS) total scores, from 74.2+/-21.3 at baseline to 65.8+/-21.4 at endpoint. There were also significant reductions in PANSS subscales (positive symptoms, negative symptoms, general psycho-pharmacology) and Marder factor scores. The Clinical Global Impression increased significantly from baseline to endpoint (p = 0.0001), as reflected by the increase in the proportion of patients rated as 'not ill' or 'borderline ill' from 10% at baseline to 21% at endpoint. Risperidone long-acting injectable was also associated with significant improvements in Global Assessment of Function, patient satisfaction with treatment, and quality of life, measured on the SF-36 scale. Movement disorders, measured on the Extrapyramidal Symptom Rating Scale, were significantly reduced following the change to risperidone long-acting injectable. Treatment with risperidone long-acting injectable was well tolerated, and no significant weight gain occurred during the study. This open study suggests that risperidone long-acting injectable produces symptomatic improvement in schizophrenia patients previously considered symptomatically stable with olanzapine, along with improvement in movement disorders. The combination of improved efficacy and good tolerability may have important implications for patient adherence to therapy and subsequent long-term outcomes.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Body Weight; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Risperidone; Treatment Outcome

Risperidone and olanzapine are the 2 most widely prescribed second-generation anti-psychotics. The purpose of this study was to compare the efficacy of risperidone and olanzapine using duration of hospitalization as the primary outcome measure. This outcome was selected as it is an indirect measure of how well patients are responding to the medication and represents a "real world" endpoint relevant to practicing hospital psychiatrists.. The study was done at a large state psychiatric hospital in North Carolina from 2001 to 2003. Subjects were eligible for inclusion if they required treatment with an antipsychotic (e.g., positive symptoms) and were able to provide informed consent. Eighty-five patients entered the study and were randomly assigned to risperidone (N = 40) or olanzapine (N = 45) as their initial antipsychotic. Treatment was naturalistic, and dosing was based on the discretion of the treating physician.. There was no significant difference in the mean durations of hospitalization for the risperidone group (7.9 days) as compared to the olanzapine group (8.1 days). There were no significant differences in the demographics of either treatment group, but, during the study, risperidone-treated patients used more antihistamines (chi(2) = 4.0, p = .05). Eighty percent of each group (N = 36, olanzapine; N = 32, risperidone) remained on the study medication at discharge.. Risperidone and olanzapine were equally efficacious, suggesting that measures other than "efficacy" (e.g., side effects, cost) should be considered when determining overall "effectiveness" of treatment.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Hospitalization; Hospitals, Psychiatric; Humans; Length of Stay; Male; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Risperidone; Schizophrenia; Treatment Outcome

A major contributor to mortality inpatients with schizophrenia or schizoaffective disorder is cardiovascular disease, an important risk factor for which is the cluster of clinical abnormalities that define the metabolic syndrome (eg, abdominal/visceral obesity, hypertriglyceridemia, impaired glucose tolerance).. The aim of this article was to examine the effects of switching from the antipsychotic olanzapine to risperidone on the prevalence of the metabolic syndrome in high-risk overweight or obese patients with schizophrenia or schizoaffective disorder.. This post hoc analysis was based on data from a previous 2-phase, 20-week, multicenter (19 US sites), rater-blinded, open-label study. High-risk overweight or obese (body mass index [BMI], >26 kg/m(2)) patients aged 18 to 65 years with schizophrenia or schizoaffective disorder whose treatment was switched from olanzapine to risperidone were enrolled. Patients who entered the phase 1 switch from olanzapine to risperidone (6 weeks) and the phase 2 extension (14 weeks) were included in the assessment. The primary end point was the difference from baseline in the prevalence of the metabolic syndrome at week 20, determined using measurements of weight, BMI, waist circumference, and systolic and diastolic blood pressure (SBP/DBP).. Baseline assessments for the metabolic syndrome were available from 121 of 123 patients recruited for phase 1 of the study (61 men, 60 women; mean [SD] age, 41.1 [10.2] years; mean [SD] BMI, 33.9 [6.9] kg/m(2)); 71 patients entered phase 2 (29 men, 42 women; mean [SD] age, 40.2 [10.3] years; mean [SD] BMI, 35.1 [7.3] kg/m(2)), of whom 39 (54.9%) ere diagnosed with schizophrenia, and 32 (45.1%) with schizoaffective disorder. The metabolic syndrome was identified in 63 (52.1%) patients at study entry. In the 71 patients with data available from baseline and week 20 (using the last observation carried forward method), the prevalence of the metabolic syndrome was reduced from 38 (53.5%) patients at baseline to 26 (36.6%) at study end (McNemar chi(2) = 8.0, P < 0.005). Significant improvements at study end were seen in mean weight (P = 0.031), BMI (P = 0.002), waist circumference (P = 0.003), SBP (P = 0.006), and DBP (P = 0.010). There was no significant difference in the reduction in the prevalence of the metabolic syndrome between patients who did or did not receive the behavioral therapy for weight loss.. In this post hoc analysis of switching from the antipsychotic olanzapine to risperidone on the prevalence of the metabolic syndrome in high-risk overweight or obese patients with schizophrenia or schizoaffective disorder, the metabolic syndrome was highly prevalent at baseline. Switching from olanza- pine to risperidone was associated with a significant reduction in this prevalence.

Topics: Adult; Antipsychotic Agents; Behavior Therapy; Benzodiazepines; Blood Pressure; Body Mass Index; Body Weight; Female; Humans; Male; Metabolic Syndrome; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Risperidone; Schizophrenia; Systole; United States; Waist-Hip Ratio

This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population, in comparison to haloperidol, a conventional antipsychotic with established efficacy. Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth, but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied. Subjects, selected because of prominent positive psychotic symptoms, were randomly assigned to double-blind, parallel treatment with risperidone, olanzapine, or haloperidol for 8 weeks. The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination. An exploratory, descriptive analysis was done to compare the three treatments. A total of 50 patients, 8-19 years, participated. All treatments reduced symptoms significantly with p-values (corrected for multiple comparisons) of 0.0018 for each of the atypical agents and 0.012 for haloperidol. In all, 88% of subjects treated with olanzapine, 74% treated with risperidone, and 53% treated with haloperidol met response criteria. The primary side effects observed in all patients were mild to moderate sedation, extrapyramidal symptoms, and weight gain. Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample. Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol. However, youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Olanzapine; Pilot Projects; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Time Factors; Treatment Outcome

Newer antipsychotic medications have been reported to enhance cognitive functioning in schizophrenia. Head to head studies with double-blind methods are still relatively few in number.. To compare the relative cognitive enhancing effects of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.. In this 6-week, multicenter, double-blind, parallel-designed trial, patients were randomized to ziprasidone or olanzapine. No patient who had ever received a complete treatment trial with either of these medications previously was entered into the study. Cognitive testing measuring attention, motor speed, memory, executive functioning, and verbal skills were performed on all patients at baseline and endpoint.. Treatment with either ziprasidone or olanzapine was associated with statistically significant improvements from baseline in attention, memory, working memory, motor speed, and executive functions. Treatment with olanzapine was also associated with a statistically significant improvement in verbal fluency. No statistically significant differences between these medications were found in the magnitude of improvement from baseline on any of the cognitive measures (other than verbal fluency in an exploratory analysis). Observed changes were not associated with changes in clinical symptoms measured using the PANSS or changes in movement disorders.. During 6 weeks of treatment, ziprasidone and olanzapine demonstrated substantial and comparable cognitive-enhancing effects relative to previous treatment. These effects were noted in all aspects of cognitive functioning previously proven to predict functional outcome in schizophrenia. No overall differences were detected between the medications in terms of the extent of cognitive enhancement.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cognition; Double-Blind Method; Female; Hospitalization; Humans; Male; Memory; Middle Aged; Olanzapine; Piperazines; Psychotic Disorders; Schizophrenia; Thiazoles

The purpose of this study was to examine whether elderly chronic schizophrenia or schizoaffective disorder patients would clinically improve if switched to olanzapine from previous neuroleptic treatment. Twenty-one hospitalized patients, aged 6088 yr, with a diagnosis of chronic schizophrenia or schizoaffective disorder who were being treated with typical neuroleptic medication were switched to olanzapine. The Positive and Negative Symptom Scale (PANSS), Geriatric Depression Scale (GDS) and Clinical Global Impression Severity (CGI-S) Scale were completed while patients were on their previous medication regimen and again 6 months after the last patient had been started on olanzapine. The mean duration of treatment was 289 d (S.D.=139). Three patients discontinued the medication. Mean end dose of olanzapine was 12.9 mg (S.D.=5.7). Paired sample t tests were used to test change on PANSS Positive, Negative and Total scales, CGI, GDS and body weight. PANSS (Positive, p=0.002; Negative, p=0.003; General, p=0.003; and Total, p=0.000) and CGI (p=0.000) but not the GDS (p=0.67) demonstrated statistically significant improvement. There was no significant change in body weight (p=0.61). Elderly patients with aggravation of chronic schizophrenia showed improvement after being switched to olanzapine with no weight gain. Clinically meaningful change was observed in positive and negative psychotic symptomatology but not in depressive symptoms.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Chronic Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Treatment Outcome

Psychotic symptoms and behavioral disturbances are a concern in the care of elderly patients with Alzheimer's dementia (AD). This study was conducted to compare the efficacy of olanzapine versus placebo in patients with psychotic symptoms associated with AD in long-term or continuing-care settings.. Patients (n = 652) with AD and delusions or hallucinations were randomly assigned to 10 weeks of double-blind treatment with placebo or fixed-dose olanzapine (1.0, 2.5, 5.0, 7.5 mg/day).. Mean age was 76.6+/-10.4 years. Repeated-measures analysis showed significant improvement from baseline in NPI/NH Psychosis Total scores (sum of Delusions, Hallucinations items-primary efficacy measure) in all five treatment groups (p<0.001), but no pairwise treatment differences were seen at the 10-week endpoint. However, under LOCF analysis, improvement in the 7.5 mg olanzapine group (-6.2 +/- 4.9) was significantly greater than with placebo (-5.0 +/- 6.1, p = 0.008), while endpoint CGI-C scores showed the greatest improvement in the Olz 2.5 olanzapine group (2.8 +/- 1.4, p = 0.030) relative to placebo (3.2 +/- 1.4). There were significant overall treatment-group differences in increased weight, anorexia, and urinary incontinence, with olanzapine showing numerically higher incidences. However, neither the incidence of any other individual events, including extrapyramidal symptoms, nor of total adverse events occurred with significantly higher frequency in any olanzapine group relative to placebo. No clinically relevant significant changes were seen across groups in cognition or any other vital sign or laboratory measure, including glucose, triglyceride, and cholesterol.. While 1.0 mg olanzapine did not show significant differences from placebo, the 2.5 mg dose was a reasonable starting dose. Olanzapine at 7.5 mg/day significantly decreased psychosis and overall behavioral disturbances (NPI/NH, BPRS) and was well tolerated.

Topics: Adult; Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Delusions; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Psychiatric Status Rating Scales; Psychotic Disorders; Time Factors; Treatment Outcome

The purpose of the present paper was to investigate the effects of the dopamine agonist amantadine in those patients with weight gain induced by olanzapine. An open trial was conducted in those patients who gained >3 kg in weight induced by olanzapine use. All subjects were evaluated by weight, body mass index (BMI), the Brief Psychiatric Rating Scale (BPRS), and the Extrapyramidal Symptom Rating Scale (ESRS) before and after the use of amantadine in addition to olanzapine. Twenty-five of 30 enrolled patients completed the present study. Mean bodyweight and BMI was increased by 6.44 +/- 4.42 kg and 5.04 +/- 3.47 kg/m2 significantly with olanzapine alone (P < 0.001). When amantadine and olanzapine were used together, the average weight and BMI decreased by 1.07 +/- 3.19 kg and 0.84 +/- 2.5 kg/m2, but did not have statistical significance. The average values of BPRS showed a significant decrease (P < 0.001). No significant changes were present in ESRS. Amantadine did not have an effect on weight gain induced by olanzapine. Randomized placebo-controlled prospective studies are needed.

Topics: Adult; Amantadine; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Brief Psychiatric Rating Scale; Depressive Disorder, Major; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Psychotic Disorders; Schizophrenia; Treatment Outcome

Co-occurring substance use disorders, mostly involving alcohol, cannabis or cocaine, occur commonly in patients with schizophrenia and are associated with increased morbidity and mortality. Available but limited data suggest that substance use disorders (especially cannabis use disorders) may also be common in first-episode patients and appear linked to a poor outcome in these patients. Strategies to curtail substance use form an important dimension of the treatment program for both first-episode and chronic patients. We report on rates of co-occurring substance use disorders in patients within their first episode of schizophrenia-related psychosis from a multicenter, international treatment trial of olanzapine vs. haloperidol.. The study involved 262 patients (of 263 who were randomized and who returned for a post-randomization evaluation) within their first episode of psychosis (schizophrenia, schizoaffective disorder or schizophreniform disorder) recruited from 14 academic medical centers in North America and Western Europe. Patients with a history of substance dependence within 1 month prior to entry were excluded.. Of this sample, 97 (37%) had a lifetime diagnosis of substance use disorder (SUD); of these 74 (28% of the total) had a lifetime cannabis use disorder (CUD) and 54 (21%) had a lifetime diagnosis of alcohol use disorder (AUD). Patients with SUD were more likely to be men. Those with CUD had a lower age of onset than those without. Patients with SUD had more positive symptoms and fewer negative symptoms than those without SUD, and they had a longer duration of untreated psychosis. The 12-week response data indicated that 27% of patients with SUD were responders compared to 35% of those without SUD. Patients with AUD were less likely to respond to olanzapine than those without AUD.. These data suggest that first-episode patients are quite likely to have comorbid substance use disorders, and that the presence of these disorders may negatively influence response to antipsychotic medications, both typical and atypical antipsychotics, over the first 12 weeks of treatment.

Topics: Adolescent; Adult; Benzodiazepines; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Substance-Related Disorders

To examine the impact of smoking status on antipsychotic-associated weight gain.. In two double-blind studies, 552 adult and elderly patients with schizophrenia or schizoaffective disorder were randomly assigned to risperidone or olanzapine treatment for 8 weeks. Smoking status at baseline was recorded together with other background characteristics.. In both adult and elderly patients, olanzapine-treated smokers and nonsmokers gained weight at a similar rate, whereas risperidone-treated smokers gained less weight than did nonsmokers. Olanzapine was associated with significantly greater weight gain than was risperidone across all measures in both adult and elderly patients.. These findings support a quantitatively or qualitatively different effect of risperidone and olanzapine on the metabolic changes underlying antipsychotic-associated weight gain. Mechanisms responsible for olanzapine's effect on weight appear to counteract smokers' physiologic bias toward weight loss, an effect not seen among risperidone-treated patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Smoking; Weight Gain

Combat-related post-traumatic stress disorder (PTSD) is often complicated with other psychiatric comorbidities, and is refractory to treatment.. The aim of an open, comparative 6-week study was to compare olanzapine and fluphenazine, as a monotherapy, for treating psychotic combat-related PTSD.. Fifty-five male war veterans with psychotic PTSD (DSM-IV criteria) were treated for 6 weeks with olanzapine (n=28) or fluphenazine (n=27) in a 5-10 mg/day dose range, once or twice daily. Patients were evaluated at baseline, and after 3 and 6 weeks of treatment, using Watson's PTSD scale, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity Scale (CGI-S), Clinical Global Impression Improvement Scale (CGI-I), Patient Global Impression Improvement Scale (PGI-I) and Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS).. At baseline, patient's data (age, duration of combat experience and scores in all measurement instruments) did not differ. After 3 and 6 weeks of treatment, olanzapine was significantly more efficacious than fluphenazine in reducing symptoms in PANSS (negative, general psychopathology subscale, supplementary items), Watson's PTSD (avoidance, increased arousal) subscales, CGI-S, CGI-I, and PGI-I scale. Both treatments affected similarly the symptoms listed in PANSS positive and Watson's trauma re-experiencing subscales. Fluphenazine induced more extrapyramidal symptoms. Prolongation of the treatment for 3 additional weeks did not affect the efficacy of either drug.. Our data indicate that both fluphenazine and olanzapine were effective for particular symptom profile in psychotic combat-related PTSD. Olanzapine was better than fluphenazine in reducing most of the psychotic and PTSD symptoms, and was better tolerated in psychotic PTSD patients.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dose-Response Relationship, Drug; Fluphenazine; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Stress Disorders, Post-Traumatic

Results from the International Suicide Prevention Trial (InterSePT) indicate that clozapine is more effective than olanzapine in reducing suicidal behavior in schizophrenic and schizoaffective patients. However, because InterSePT allowed the uncontrolled use of concomitant psychotropic medications (CPMs), it is possible that the antisuicidal effect of clozapine may have been influenced by greater use of such agents. This article describes the use patterns of CPMs during InterSePT and examines whether CPM use may have affected study outcome.. In this study, 479 patients received clozapine and 477 patients received olanzapine. Concomitant psychotropic medications were grouped into 4 classes: antipsychotics, antidepressants, sedatives/anxiolytics, and mood stabilizers. The doses of each CPM were converted into dosage equivalents of standard reference drugs. An analysis of covariance was performed to compare mean daily doses of CPMs between the 2 groups over the 2-year treatment period. The duration of treatment for each patient was 2 years, with the first patient entering the study in March 1998 and the last patient completing treatment in February 2001.. Approximately 90% of patients in both treatment groups received at least 1 CPM. The mean +/- SD number of CPMs per patient was 3.8 +/- 2.90 in the clozapine group and 4.2 +/- 3.16 in the olanzapine group. For each CPM class, the mean daily dose was statistically significantly lower in the clozapine group (antipsychotics, p <.001; antidepressants, p <.01; sedatives/anxiolytics, p <.001; mood stabilizers, p <.05). Analyses of CPM use by study intervals, suicide attempters versus nonattempters, study completers versus noncompleters, and geographic region resulted in similar findings.. The results support the conclusion that the effects of clozapine in reducing the risk of suicidal behavior derive from its intrinsic pharmacology and not from the influence of concomitant psychotropic medications.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Olanzapine; Psychotic Disorders; Psychotropic Drugs; Schizophrenia; Schizophrenic Psychology; Suicide; Suicide Prevention; Treatment Outcome

The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis.. Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment.. An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine.. Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Principal Component Analysis; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The aim of this study was to assess the prevalence of weight gain during long-term treatment with olanzapine under routine conditions. Weight changes in a sample of 27 outpatients with schizophrenic or schizoaffective disorder were assessed over a mean duration of treatment of 22 months (6-42 months). Treatment with olanzapine was started anew or switched from a conventional antipsychotic drug. Eighteen (66.7%) patients gained more than 7% of their initial body weight. Mean weight gain was 9.2 kg over the study period for the first year 7.7 kg, and only 1.7 kg in the second year. Due to some patients losing weight in the second year, the latter finding obscures the fact that more than 50% of patients gained considerable weight also during the second year (4.8 kg). Weight gain per month was significantly higher in patients with lower body mass index, yet the highest weight gain was found in the most obese patient. Weight gain under olanzapine is a serious concern, and should be monitored closely and countered by active measures.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Weight Gain

The subjects were 157 treatment-resistant inpatients diagnosed with chronic schizophrenia or schizoaffective disorder. They were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol in a 14-week, double-blind trial. Incidents of overt aggression were recorded and their severity was scored. The Positive and Negative Syndrome Scale was administered. Atypical antipsychotics showed an overall superiority over haloperidol, particularly after the first 24 days of the study when the dose escalation of clozapine was completed. Once an adequate therapeutic dose of clozapine was reached, it was superior to haloperidol in reducing the number and severity of aggressive incidents. Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients. There was an interaction between aggressiveness, medication type, and antipsychotic response: risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior; the opposite was true for clozapine. Clozapine appears to have superior antiaggresive effects in treatment-resistant patients; this superiority develops after the patient has been exposed to an adequate dose regimen.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Haloperidol; Humans; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

Duration of untreated psychosis (DUP) may contribute to the observed heterogeneity of the treatment response in first-episode schizophrenia.. To examine the relationship of DUP and premorbid function with clinical outcomes following up to 2 years of antipsychotic treatment.. For a subsample (n=191) of subjects participating in a clinical trial, DUP and premorbid function were prospectively compared with clinical response to olanzapine or haloperidol.. Shorter DUP and good premorbid function each independently are associated with better clinical response, including improvement in overall psychopathology and negative symptoms. Premorbid function also is associated with positive symptom, social and vocational outcomes.. Earlier antipsychotic treatment is associated with better outcomes in first-episode schizophrenia. Poor premorbid function could indicate an illness subtype less likely to respond to antipsychotic treatment regardless of when it is instituted.

Topics: Adolescent; Adult; Age of Onset; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Prognosis; Psychiatric Status Rating Scales; Psychotic Disorders; Remission Induction; Schizophrenia; Treatment Outcome

The purpose of this study was to compare the efficacy and safety of olanzapine (OLZ) monotherapy and an olanzapine/fluoxetine combination (OFC) with placebo (PLA) for unipolar major depression with psychotic features. Under a single protocol, two 8-week, double-blind trials were conducted at 27 sites. Patients (n = 124 trial 1, n = 125 trial 2) were randomized to 1 of 3 treatment groups: OLZ (5 to 20 mg/d), PLA, or OFC (olanzapine 5 to 20 mg/d + fluoxetine 20 to 80 mg/d). The primary outcome measure was the 24-item Hamilton Depression Rating Scale total score. For trial 1, endpoint improvement for the OLZ group (-14.9) was not significantly different from the PLA or OFC groups. The OFC group had significantly greater endpoint improvement (-20.9) than the PLA group (-10.4, P = 0.001); this significant difference was present within 7 days of therapy and maintained at every subsequent visit. The OFC group also had significantly higher response rate (63.6%) than the PLA (28.0%, P = 0.004) or OLZ (34.9%, P = 0.027) groups. For trial 2, there were no significant differences among treatment groups on the 24-item Hamilton Depression Rating Scale total scores or response rates. The combination exhibited a comparable safety profile with OLZ monotherapy and no significant increases in extrapyramidal symptoms compared with placebo. Patients with major depression with psychotic features treated with OLZ monotherapy did not demonstrate significant depressive symptom improvement compared with placebo in either trial; however, an olanzapine/fluoxetine combination was associated with significant improvement compared with placebo in one trial and was well tolerated.

Topics: Adult; Analysis of Variance; Benzodiazepines; Chi-Square Distribution; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders

Limited randomized, controlled trial data exist on possible differences between atypical antipsychotics in efficacy, overall tolerability, and important indices of health status. The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill inpatients with schizophrenia or schizoaffective disorder.. In this 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, patients were randomly assigned to receive ziprasidone (N=136) or olanzapine (N=133). Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression (CGI) severity scale scores; secondary measures were scores on the CGI improvement scale, Positive and Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia. Tolerability assessments included fasting lipid profiles, fasting glucose and insulin measurements, electrocardiography, and monitoring of vital signs and body weight.. The overall mean daily doses were 129.9 mg (SD=27.3) for ziprasidone and 11.3 mg (SD=2.8) for olanzapine. Both antipsychotics were efficacious in improving symptoms and global illness severity. The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis. Both agents were well tolerated. Body weight, total cholesterol, triglycerides, and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone; all between-group comparisons of these variables were significant and favored ziprasidone. Olanzapine, but not ziprasidone, was associated with significant increases in fasting insulin level. No patient in either group exhibited a corrected QT interval >/=500 msec.. During 6 weeks' treatment, ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy. Differences favoring ziprasidone were observed in metabolic parameters.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lorazepam; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome; Weight Gain

The main objective of this study was to compare 1-year outcome on symptoms, extrapyramidal side effects (EPS) , positive and negative symptoms, and domains of cognition in first episode psychosis (FEP) patients. Drug-naive FEP patients, who were similar on a number of characteristics likely to affect outcome, were treated with only one antipsychotic (risperidone or olanzapine) for at least 1 year and compared at baseline and after 1 year of treatment. Differences in outcome were assessed using an analysis of co-variance with change scores between initial assessment and after 1 year of treatment on levels of psychotic, disorganization and psychomotor poverty symptoms, EPS (parkinsonism, akathesia and dyskineisa) and domains of cognition as the dependent variable, respective baseline scores as covariates, and drug group as the independent variable. While patients in both groups showed substantial improvement, there were no significant differences in the magnitude of change in reality distortion, disorganization and psychomotor poverty symptoms. Trends in change in EPS favouring olanzapine and on some domains of cognition (processing speed and executive functions) favouring risperidone failed to reach statistical significance. The failure to confirm previous claims of greater improvement on either risperidone or olanzapine in patients with a first episode of psychosis may be the result of methodological bias introduced by unequal dosing between the two drugs or the use of chronically ill and treatment-refractory patients in previous studies.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Olanzapine; Psychomotor Disorders; Psychotic Disorders; Risperidone; Severity of Illness Index

Suicidal behavior in patients with psychotic disorders represents a seriously undertreated life-threatening condition. The International Suicide Prevention Trial (InterSePT) is the first large-scale, prospective study designed to evaluate the potential of antipsychotic medications to reduce suicidal behaviors in patients with schizophrenia or schizoaffective disorder who are known to be at high risk for suicide. The unique challenges to study design and the solutions identified for the InterSePT study are described. These challenges included defining suicidal behavior in patients with psychosis, endpoint selection, determination of analytic strategy, and development of scales to assess suicidal behavior. Given the life-threatening nature of suicidal behavior, ethical considerations required that the design minimize suicide attempts and deaths. While the study focused primarily on treatment of suicide, opportunities were used to collect data in related areas of interest, including suicide risk factors, other efficacy measures (e.g., Positive and Negative Syndrome Scale, Covi Anxiety Scale, Calgary Depression Scale), adverse events, pharmacoeconomics, and pharmacogenetics. Because of the complexity of the design issues, a steering committee, suicide monitoring board, and publication committee were established to assist with their management.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Research Design; Risk Factors; Schizophrenia; Suicide Prevention; Treatment Outcome

Older individuals with dementia are highly sensitive to the effects of muscarinic receptor blockade.. This was a 6-week multisite, randomized clinical trial.. Eighty-six patients with probable Alzheimer's disease, vascular dementia, or mixed-etiology dementia (DSM-IV criteria) were randomly assigned to treatment with olanzapine or risperidone.. Anticholinergic activity was measured with a radioreceptor assay, and plasma levels of antipsychotic medications were determined. Primary outcomes were assessed with the Udvalg for Kliniske Undersogelser (UKU) scale and somnolence adverse events; secondary outcome measures included scores on the Neuropsychiatric Inventory (NPI) and other scales.. There were no between-treatment differences in the UKU scale or in somnolence adverse events. Statistically significant improvements (p < .001) from baseline were found for the NPI measures, with no between-treatment group differences. Olanzapine was associated with significant increases from baseline in anticholinergic activity, while risperidone was not; the between-treatment group differences were not statistically significant. Increase in anticholinergic activity was associated with an increase in anticholinergic side effects and slower performance on the Trail Making Test Part A. Higher endpoint anticholinergic activity was associated with higher endpoint scores on several items from the NPI, including delusions, anxiety, and aberrant motor behavior.. Efficacious doses of olanzapine increased anticholinergic activity in older patients with dementia, while similarly efficacious doses of risperidone did not. Patients whose anticholinergic activity increased were more likely to experience anticholinergic side effects and to have worsening in certain cognitive domains. These data suggest that certain patients may be vulnerable to the anticholinergic activity associated with antipsychotic treatment.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Delusions; Dementia; Double-Blind Method; Female; Hallucinations; Humans; Male; Middle Aged; Muscarinic Antagonists; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Radioligand Assay; Receptors, Muscarinic; Risperidone; Sleep Wake Disorders; Trail Making Test; Treatment Outcome

Approximately 50% of patients with schizophrenia or schizoaffective disorder attempt suicide, and approximately 10% die of suicide. Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients.. A multicenter, randomized, international, 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder, 26.8% of whom were refractory to previous treatment, who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation. To equalize clinical contact across treatments, all patients were seen weekly for 6 months and then biweekly for 18 months. Subsequent to randomization, unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts. Suicidal behavior was assessed at each visit. Primary end points included suicide attempts (including those that led to death), hospitalizations to prevent suicide, and a rating of "much worsening of suicidality" from baseline. Masked raters, including an independent suicide monitoring board, determined when end point criteria were achieved.. Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine (hazard ratio, 0.76; 95% confidence interval, 0.58-0.97; P =.03). Fewer clozapine-treated patients attempted suicide (34 vs 55; P =.03), required hospitalizations (82 vs 107; P =.05) or rescue interventions (118 vs 155; P =.01) to prevent suicide, or required concomitant treatment with antidepressants (221 vs 258; P =.01) or anxiolytics or soporifics (301 vs 331; P =.03). Overall, few of these high-risk patients died of suicide during the study (5 clozapine vs 3 olanzapine-treated patients; P =.73).. Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. Use of clozapine in this population should lead to a significant reduction in suicidal behavior.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Patient Dropouts; Pirenzepine; Psychotic Disorders; Risk Factors; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Suicide; Suicide Prevention; Suicide, Attempted; Treatment Outcome

The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies. The authors' goal was to assess the effects of clozapine, olanzapine, risperidone, and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a randomized double-blind 14-week trial.. One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were inpatients at four hospitals were originally included in the study. The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period. Planned assessments included fasting glucose and cholesterol, which were collected at baseline and at the end of the 8-week period and the following 6-week period.. One hundred eight of the 157 patients provided blood samples at baseline and at least at one point after random assignment to clozapine, olanzapine, risperidone, or haloperidol during the treatment trial. Seven of these patients had diabetes; their glucose levels were >125 mg/dl at baseline. Data from 101 patients were used for statistical analyses. During the initial 8-week period there was an overall significant increase in mean glucose levels. There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine (N=27) and those given haloperidol (N=25). The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period (N=22). Fourteen of the 101 patients developed abnormal glucose levels (>125 mg/dl) during the trial (six with clozapine, four with olanzapine, three with risperidone, and one with haloperidol). Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine (N=27) and those given olanzapine (N=26); cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine (N=22).. In this prospective randomized trial, clozapine, olanzapine, and haloperidol were associated with an increase of plasma glucose level, and clozapine and olanzapine were associated with an increase in cholesterol levels. The mean changes in glucose and cholesterol levels remained within clinically normal ranges, but approximately 14% of the patients developed abnormally high glucose levels during the course of their participation in the study.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Cholesterol; Clozapine; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Hospitalization; Humans; Hypercholesterolemia; Hyperglycemia; Male; Middle Aged; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Risperidone; Schizophrenia; Weight Gain

Elderly psychiatric patients often present with psychotic symptoms that need antipsychotic treatment. Olanzapine is one of the atypical antipsychotics with efficacy for psychotic symptoms and a safer side-effect profile than typical antipsychotics. This study was conducted to assess the efficacy and safety of olanzapine for treatment of geriatric psychosis. The sample population comprised 94 acute-ward patients who were 65 years of age or older. Clinical assessment was conducted at baseline and also at 4 weeks after commencement of olanzapine treatment, with use of the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments. A 4-week therapeutic evaluation was completed for 80 patients, 73 of whom (91.3%) experienced mild to substantial improvement as determined from the CGI-I. A mean 52.6% reduction from baseline was also determined from the BPRS. The mean daily dosage of olanzapine in the fourth week was 10.1 +/- 5.3 mg/d (range, 2.5-20.0). Higher olanzapine dosages were administered for patients with functional psychoses than for an analogous group with organic mental disorders. Adverse effects were monitored for all 94 patients, the most common of which were somnolence (18.1%), dizziness (18.1%), and weakness of legs or bradykinesia (16.0%). Body weight and fasting triglyceride and sugar levels were significantly elevated after olanzapine treatment (2.2, 39.9, and 8.9% from baseline, respectively). It seems reasonable to suggest that olanzapine is efficacious for geriatric patients with psychosis and that the dosage should be diagnosis-dependent.

Topics: Acute Disease; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Treatment Outcome

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Mood Disorders; Olanzapine; Pirenzepine; Psychomotor Disorders; Psychotic Disorders; Risk Factors; Schizophrenia; Schizophrenic Psychology; Sleep Wake Disorders; Speech Disorders

The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. This report presents the study rationale and design. Recent studies will be reviewed that have advanced our knowledge about the early course of schizophrenia and our ability to predict onset prospectively, advances that have rendered prodromal intervention research feasible and ethical. The study design has many novel features. It tests for prevention versus delay in psychosis onset, as well as for efficacy and safety in a newly defined clinical population. This has required the development of innovative clinical research assessment instruments and a new operational definition of psychosis onset. The integration of these novel elements into an otherwise typical clinical trial design is detailed. The companion report will address sample recruitment and the clinical phenomenology at baseline of this putative "prodromal" entity.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Child; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Feasibility Studies; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Preventive Health Services; Prospective Studies; Psychotic Disorders; Schizophrenia

Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial.. Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase.. Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%).. As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Treatment Outcome

Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide.. This study followed 980 patients at high risk for suicide in a multicenter prospective study for 2 years after randomization to clozapine or olanzapine. A priori predictors related to diagnosis, treatment resistance, and clinical constructs of disease symptoms were evaluated as possible predictors of subsequent suicide-related events.. Ten baseline univariate predictors were identified. Historical predictors were diagnosis of schizoaffective disorder, history or current use at baseline of alcohol or substance abuse, cigarette smoking, number of lifetime suicide attempts, and the number of hospitalizations in the previous 36 months to prevent suicide. Predictive clinical features included greater baseline scores on the InterSePT scale for suicidal thinking, the Covi Anxiety Scale, the Calgary Depression Scale (CDS), and severity of Parkinsonism. Subsequent multivariate analysis revealed the number of hospitalizations in the previous 36 months, baseline CDS, severity of Parkinson's, history of substance abuse, and lifetime suicide attempts. Clozapine, in general, was more effective than olanzapine in decreasing the risk of suicidality, regardless of risk factors present.. This is the first prospective analysis of predictors of suicide risk in a large schizophrenic and schizoaffective population judged to be at high risk for suicide. Assessment of these risk factors may aid clinicians in evaluating risk for suicidal behaviors so that appropriate interventions can be made.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Proportional Hazards Models; Prospective Studies; Psychotic Disorders; Research Design; Risk Assessment; Risk Factors; Schizophrenia; Schizophrenic Psychology; Suicide

The aim of the present study was to evaluate the objective and subjective efficacy as well as tolerability of olanzapine in acute treatment of schizophrenia spectrum disorders under naturalistic non-selective conditions. Inpatients with schizophrenia spectrum disorders, consecutively admitted over an 18-month period, treated with olanzapine, were included. Diagnoses were made according to ICD-10 criteria based on repeated clinical assessments. Efficacy and tolerability of olanzapine were assessed at baseline and at the end of inpatient acute treatment including Positive and Negative Symptom Scale (PANSS), Clinical Global Impression, subjective assessments, UKU and biological investigations. One hundred and twenty non-selected patients who met ICD-10 criteria for schizophrenia (73%), schizophreniform disorder (14%) or schizoaffective disorder (13%) were treated with olanzapine 15.3+/-5.2 mg/day. Baseline severity (PANSS total mean score 102.2) was higher compared to various admittance studies (PANSS total mean score 86-90). In 32% of patients (n=38), olanzapine treatment was discontinued, mainly because of inefficacy for positive (89%, n=34) and/or negative (95%, n=36) symptoms and/or because of adverse events (37%, n=14). Response rates as improvement in PANSS total score (after > or =3 weeks of treatment) of > or =20%, 30% or 40% were 68%, 55% and 35%, respectively. Response rates in post-hoc defined treatment resistant patients were not significantly different from non-refractory patients. Sedation (26%) was the most common side-effect, followed by weight gain (22%). With regards to subjective efficacy, 30% of the patients were not satisfied with the efficacy of olanzapine, while only 6% of the patients reported a not satisfying subjective tolerability. According to duration of olanzapine treatment, the results for patients, who remained in hospital, revealed a faster increase of weight compared to admittance studies (7 kg in 14 weeks versus 7 kg in 38 weeks). Olanzapine has been found to be effective and tolerable, also under naturalistic acute treatment conditions. Compared to previous double-blind admittance studies, patients had a higher severity of illness at entry and a lower > or =40% PANSS total score response rate. By contrast to previous results, mean dose of olanzapine was similar for multiple- and first-episode patients, and weight gain was more severe. The results underline the need of Phase IV studies for the assessment of clinical antipsy

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Patient Satisfaction; Pirenzepine; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Treatment Outcome

Atypical antipsychotics are the first-line treatment for psychosis and are commonly used for behavioural problems in people with intellectual disabilities (ID), but a comprehensive evidence base for this approach is lacking. We studied prescription trends and the clinical effectiveness of risperidone and olanzapine in people with ID in a clinical, naturalistic setting. The results suggest that both drugs are well tolerated and effective in treating target symptoms across a range of diagnoses and ID. Both risperidone and olanzapine appear to reach full efficacy within 3 months, after which improvement reaches a plateau, as reflected in the Clinical Global Impression-Improvement scale. Compliance with both drugs is high. Olanzapine tended to be prescribed mostly for psychotic disorders, and showed good rates of response, whereas risperidone was prescribed mostly for people with behavioural disturbance associated with a psychiatric diagnosis. Furthermore, approximately one-quarter of the risperidone group were prescribed the medication for a behavioural disorder associated with a pervasive developmental disorder. Again, the medication was broadly effective in treatment. Both medications were also used to effectively treat affective disorders in a small percentage of patients. This study appears to indicate that both medications could be of significant clinical benefit for people with ID across a wide range of diagnoses and level of ID, although further controlled trials are required.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Comorbidity; Disabled Persons; Female; Humans; Male; Middle Aged; Mood Disorders; Olanzapine; Pirenzepine; Practice Patterns, Physicians'; Psychotic Disorders; Risperidone; Treatment Outcome

Topics: Alcoholism; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cocaine-Related Disorders; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Substance-Related Disorders

In the present naturalistic study, the effectiveness and safety of quetiapine, risperidone and olanzapine were compared in the treatment of non selected acutely psychotic patients. It was observed that the rate of antipsychotic switch because of a lack of efficacy or side effects was higher in the quetiapine treated cases in comparison with the risperidone or olanzapine treated cases. The proportion of cases concomitantly treated with typical neuroleptics was significantly higher in the quetiapine group compared with the other two groups. In the outcome of non crossover cases, there were more improvements in the risperidone and olanzapine groups than in the quetiapine group. The results of this study suggest that quetiapine is not as efficacious as risperidone or olanzapine in the emergency psychiatric setting. Due to the methodological limitations of the study, these results must be considered preliminary and need confirmation.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Emergency Services, Psychiatric; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Sampling Studies; Treatment Outcome

To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder.. One hundred seventy-six elderly inpatients and outpatients with schizophrenia or schizoaffective disorder were enrolled in this multicenter, double-blind trial. After their antipsychotic medications were tapered for 1 week, patients were randomly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks. Performance on the Continuous Performance Test (CPT), Serial Verbal Learning Test (SVLT), TMT (Trail Making Test) Parts A and B, Wisconsin Card Sorting Test (WCST), and Verbal Fluency Examinations (VFE) was assessed at baseline and at end point.. Patients in the risperidone group had improved scores on at least one test of attention, memory, executive function, and verbal fluency, and those in the olanzapine group had improved scores on at least one test of attention and memory function. Scores on the TMT Part B, WCST total errors (executive function domain), and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group. No significant differences in change scores between the two groups were found. Higher baseline scores on each test predicted more improvement at endpoint.. Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder. Consistent with research in younger populations, these improvements occur in aspects of cognitive functioning related to functional outcome.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To determine whether patients with treatment-resistant schizophrenia or schizoaffective disorder would respond when switched to olanzapine and whether they could maintain their response on this atypical antipsychotic.. In this single-center, observational, 1-year open-label study, a cohort of patients was switched to olanzapine due to failure on previous treatment. The patients were followed up (retrospectively) for an additional 5 years. Patients had schizophrenia or schizoaffective disorder and all but one were treatment-resistant. The starting dose was 10 mg/day, with dosage adjustments based on physician judgment.. The CGI-S and CGI-I scales were the primary outcome measures. During the observation period, positive and negative symptoms, hospital readmission rates and duration of hospitalization were measured, and treatment-emergent adverse events recorded.. Mean age of patients (n = 25) was 39.7 years; 19 were male, and all were Caucasian. The mean number of antipsychotics used prior to olanzapine was 4.6 with risperidone (76%) being the most common. The mean duration of olanzapine therapy was 8.6 months. The average number of hospital admissions per patient dropped from 1.32 during the year prior to olanzapine therapy to 0.39 after starting olanzapine. Total number of hospital days was 1042 the year before and 258 the year after olanzapine treatment. The mean CGI-S score improved from markedly ill at baseline to borderline/mildly ill at study end. The mean CGI-I score was rated much improved at study end. Few adverse events occurred during the study. Twelve patients remained on olanzapine monotherapy after 5 years of treatment (mean duration of 62 months).. Olanzapine may be a treatment option for patients who fail to respond to treatment with other antipsychotics. Importantly, this is one of the first reports showing that patients with schizophrenia can be maintained on atypical antipsychotic monotherapy for at least 5 years.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Follow-Up Studies; Hospitalization; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Treatment Outcome

Minimum doses of haloperidol might show similar efficacy and side-effects compared to atypical antipsychotics. The objectives of this study were to compare the efficacy of minimum doses of haloperidol with standard doses of risperidone and olanzapine on a 6-month open trial in first psychotic episode patients and to examine the effect of compliance on their outcome. Forty-two patients were recruited and started on flexible doses of these drugs. Olanzapine was given with no cost to the patients. Efficacy and side-effects were monitored every 3 months using standardized assessments. Thirty patients completed the study. All treatment groups showed improvement in positive, negative and depressive symptoms. There were no differences in side-effects among them. The haloperidol group required higher doses of anticholinergics. The rate of treatment discontinuation was higher in the risperidone group due to the direct cost. Minimum doses of haloperidol might prove to be a good choice of treatment for patients with a first episode of psychosis.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cholinergic Antagonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Male; Mexico; Neurologic Examination; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Sustained response to antipsychotic therapy is an important outcome measure for patients with psychotic disorders. Placebo control in studies of relapse prevention contributes valuable information yet provokes much debate. This study, using placebo as a control, evaluated olanzapine's efficacy in preventing a psychotic relapse. Participants were stable minimally symptomatic outpatients with schizophrenia or schizoaffective disorder. The study included 4 phases: (1) 4-day to 9-day screening/evaluation (N = 583), (2) 6-week conversion to open-label olanzapine (N = 493; 10-20 mg/d), (3) 8-week stabilization on olanzapine (N = 458; 10-20 mg/d), and (4) 52-week randomized (2:1), double-blind maintenance with olanzapine (N = 224; 10-20 mg/d) or placebo (N = 102). Primary relapse criteria were clinically significant changes in the Brief Psychiatric Rating Scale (BPRS) positive item cluster or rehospitalization due to positive symptoms. Statistical methodology allowed sequential real-time estimation of efficacy across blinded treatment groups and multiple interim analyses, which permitted study termination when efficacy was significantly different between treatments. A significant between-treatment difference emerged 210 days after first patient randomization to double-blind treatment. Thus, 151 (46.3%) of the randomized patients were discontinued early and 34 (10.4%) of the planned patient enrollment were not required. The olanzapine group had a significantly longer time to relapse (P < 0.0001) than the placebo group. The 6-month cumulative estimated relapse rate (Kaplan-Meier) was 5.5% for olanzapine-treated patients versus 55.2% for placebo-treated patients. The design of this study enabled appropriate statistical testing of the primary hypothesis while minimizing exposure of patients to a less effective treatment than olanzapine. In remitted stabilized patients with schizophrenia or schizoaffective disorder, olanzapine demonstrated a positive benefit-to-risk profile in relapse prevention.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Secondary Prevention; Time Factors; Treatment Outcome

Side effect and health status changes were measured in 3 studies in which outpatients experiencing suboptimal efficacy or tolerability with their current antipsychotic were switched to 6 weeks of open-label ziprasidone. The studies differed only in the patient's prior antipsychotic; 1 study group was on olanzapine (n = 104), a second on risperidone (n = 58), and third on a conventional antipsychotic (n = 108). Baseline and end point health status measures included weight and height, nonfasting cholesterol, and triglyceride levels, prolactin levels, and extrapyramidal side effects. Improvements in health indices and side effects were seen among all 3 groups, but the specific benefits depended on the preswitch antipsychotic. For example, patients switched from olanzapine experienced a mean weight loss of 1.76 kg (P < 0.0001), those switched from risperidone had a lesser reduction in weight (-0.86 kg; P = 0.015), and those switched from conventionals had a nonsignificant increase (+0.27 kg; P = 0.3). Prolactin levels decreased among those switched from risperidone (P < 0.0001) or conventionals (P = 0.05), but not for patients switched from olanzapine. EPS improved among those switched from conventionals (P < 0.0001) and to a lesser extent among those switched from risperidone (P < 0.01), but not in those changed from olanzapine (NS). Thus, in these studies, switching to ziprasidone in patients with continuing symptoms or side effects on their current medication was often associated with improved health status indices, lowered prolactin levels, or less EPS, with the magnitude benefit consistent with the known side-effect profile of the preswitch antipsychotic.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Weight; Female; Health Status Indicators; Humans; Male; Middle Aged; Olanzapine; Piperazines; Prolactin; Psychotic Disorders; Risperidone; Schizophrenia; Thiazoles; Withholding Treatment

To determine the response of children with childhood-onset schizophrenia to a 1-year prospective, open-label trial of olanzapine.. Twenty children (age range 6-15 years) with childhood-onset Diagnostic and Statistical Manual of Mental Disorders (fourth edition) schizophrenia participated. The treating clinician was free to vary or discontinue dosing and use additional medications. Symptoms were assessed by the Brief Psychiatric Rating Scale-Child version (BPRS-C), Scale for the Assessment of Positive Symptoms, and Scale for the Assessment of Negative Symptoms. Extrapyramidal symptoms, akathisia, temperature, and weight were monitored.. BPRS-C subscales of thought disturbance and psychomotor excitation, and the Scale for the Assessment of Positive Symptoms demonstrated significant decreases by 6 weeks of treatment; BPRS-C anxiety and the Scale for the Assessment of Negative Symptoms (SANS) showed significant improvement after 1 year of treatment. Seventy-four percent of subjects were considered treatment responders, with a greater than 20% reduction in total BPRS-C score and overall impairment of mild or better. Weight gain (body mass index) was above that expected for normal development in every child. No child developed neuroleptic-related dyskinesias. Seventy-four percent (n = 14) of patients completed this 1-year, open-label trial. Of the 5 subjects who discontinued, weight gain was noted as the reason for 4 subjects.. Olanzapine appears useful in the treatment of childhood-onset schizophrenia, although there may be a delayed onset of benefit for anxiety and negative symptoms. Weight gain is problematic, but the emergence of dyskinesias may be rare. Additional controlled trials are indicated.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Drug Resistance; Female; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia, Childhood; Schizophrenic Psychology; Weight Gain

We examined the long-term consequences of switching patients from conventional to novel antipsychotic drugs, from a patient's perspective.. In a prospective, single-blinded, naturalistic study, a cohort of subjects (n=150) with schizophrenia or schizo-affective disorder (DSM-IV) were switched from conventional neuroleptic drugs to either risperidone (n=50), olanzepine (n=50) or quetiapine (n=50), and monitored for a period of 2 to 6 years. The ensuing natural history of transitions in treatments was charted, and the outcomes including symptoms, side effects, subjective tolerability of drugs and their impact on quality of life were documented with standardized rating scales.. Majority (85%) of the subjects benefited from a switch to the novel antipsychotic drugs, though some preferred to return to their original neuroleptic (8%), and others eventually required clozapine (7%) therapy. Novel antipsychotic drugs were significantly tolerated better, and had a positive impact on treatment-adherence, psychosocial functioning and quality of life. Among the novel drugs, risperidone was significantly better in improving negative symptoms, while olanzepine was particularly well tolerated and effective against comorbid anxiety and depressive symptoms. Patients treated with quetiapine reported fewer side effects, and showed a significantly greater improvement in neurocognitive deficits.. Novel antipsychotics emerged as the drug of choice in view of their overall effectiveness, though conventional neuroleptics and clozapine will continue to have a limited but distinct role in the management of schizophrenia. The challenge for clinicians lies in matching a patient's clinical and biochemical profile with that of a drug's pharmacological actions, in order to achieve optimum outcomes.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Humans; Male; Multivariate Analysis; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risperidone; Schizophrenia; Single-Blind Method

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = -0.86, p = 0.0001) and olanzapine (Pearson r = -0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t = -0.112, p = 0.911).

Topics: Adult; Aged; Antipsychotic Agents; Benzamides; Benzodiazepines; Contrast Media; Corpus Striatum; Dopamine D2 Receptor Antagonists; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Pyrrolidines; Receptors, Dopamine D2; Risperidone; Schizophrenia; Tomography, Emission-Computed, Single-Photon

Nine hundred and ten schizophrenic inpatients suffering from acute psychotic episodes were included in a naturalistic study. Patients were prescribed treatment with olanzapine (OLZ) or with typical antipsychotic (TYP) drugs. Patients receiving another atypical antipsychotic were excluded. Of the whole sample, 483 (53.4%) were treated with olanzapine and 421 (46.6%) with typical antipsychotics. Three specific subpopulations of greater severity were defined: patients with prominent psychotic symptoms, agitated patients, and patients initially treated with intramuscular (i.m.) medication because of their acute clinical condition. Severity of illness was assessed using the Clinical Global Impression (CGI) scale for severity, the Brief Psychiatric Rating Scale (BPRS) and the Nursing Observational Scale for Inpatient Evaluation. Baseline differences were adjusted per data analysis. The mean change from baseline to endpoint of overall symptomatology (total BPRS score) was significantly greater in the olanzapine group compared to the typical antipsychotic-treated group, both in the sample of patients with prominent positive symptoms (P < 0.001) and in the sample of agitated patients (P =0.015). Significant differences were also found in BPRS positive scores, BPRS negative scores and CGI scores in these two populations. Patients who had received previous i.m. drugs showed no statistically significant differences in symptomatic improvement between both treatments groups, except for a more favourable response of BPRS negative subscores in the olanzapine group (P =0.015). The results suggest that olanzapine may be considered as a first line treatment for severely psychotic inpatients with schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Treatment Outcome

When patients with schizophrenia fail to respond to an atypical antipsychotic, they are sometimes switched to another atypical compound. However, the benefits of such a switch have not been adequately studied. We present an open-label prospective 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder whose treatment resistance to clozapine, olanzapine, risperidone, and haloperidol had been determined prospectively.. The subjects were 45 inpatients with DSM-IV schizophrenia or schizoaffective disorder who failed to respond to treatment during a 14-week double-blind trial comparing clozapine, olanzapine, risperidone, and haloperidol. The patients had been selected for participation in the double-blind trial on the basis of a history of suboptimal response to previous treatment. Inclusion criteria for the present study were (1) completion of at least 8 weeks of the 14-week double-blind trial, (2) treatment resistance to 1 of the 4 compounds tested as evidenced by a decrease in total PANSS score of less than 20%, and (3) total PANSS score > or = 60. Subjects were cross-titrated from the previous double-blind treatment to open-label olanzapine, 10 to 40 mg/day, and were treated for 14 weeks without concomitant psychotropic medication. Patients were evaluated weekly with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions scale, and Extrapyramidal Symptom Rating Scale.. Open-label olanzapine treatment yielded no significant change in PANSS total, positive subscale, or negative subscale scores. There was a significant improvement for the PANSS cognitive factor (mean +/- SD change = 0.92 +/- 2.27; F = 7.5, df = 1,44; p <.009) and a marginally significant worsening for the excitement factor (mean change = -1.36 +/- 4.64; F = 4.0, df = 1,44; p < .053). Nine percent of patients (N = 4) were classified as responders using the Kane et al. criteria. The worsening in the PANSS excitement factor was significantly associated with the length of illness (t = -2.10, df = 44, p < .04). There was a nonsignificant decrease in extrapyramidal side effects and a significant increase in weight (mean increase = 3.5 +/- 6.2 kg [7.8 +/- 13.8 lb]; F = 5.29, df = 1,42; p <.0005).. Our results indicate that in patients with treatment-resistant schizophrenia, a switch to olanzapine after treatment failure with an atypical agent or haloperidol may not reduce psychopathology in general, but may improve symptoms related to cognitive function.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Hospitalization; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

Although atypical antipsychotic agents are commonly used in the treatment of psychotic depression, there are no published prospective studies on their use in this condition. The aim of this study was to assess, by interim analyses, the efficacy of the atypical antipsychotic agent olanzapine in combination with the selective serotonin reuptake inhibitor antidepressant agent fluoxetine.. We enrolled 27 patients (17 women [63.0%] and 10 men [37.0%]; mean +/- SD age: 41.2 +/- 14.7 years) with DSM-IV-defined major depressive disorder with psychotic features into an open trial of olanzapine, 5 to 20 mg/day, plus fluoxetine, 20 to 80 mg/day. Patients were assessed at each visit with the 17-item Hamilton Rating Scale for Depression and both the psychotic and mood modules of the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition. We are reporting the results of the first 6 weeks of treatment.. Twenty-two (81.5%) of the 27 enrolled patients completed the 6-week open trial, and 5 (18.5%) dropped out, with only 2 (7.4%) dropping out due to side effects. Of the 27 patients, 74.1% (N = 20) met criteria for melancholic features, 14.8% (N = 4) had delusions alone, 18.5% (N = 5) had hallucinations alone, and 66.7% (N = 18) reported both delusions and hallucinations. In addition, the overall rates of response for the intent-to-treat group were as follows: depression response rate, 66.7% (N = 18); psychosis response rate, 59.3% (N = 16); psychotic depression response rate, 55.6% (N = 15); and psychotic depression remission rate, 40.7% (N = 11).. The combination of olanzapine and fluoxetine appears to be a promising, safe, and effective treatment for psychotic depression. Double-blind studies are needed to confirm this impression.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Female; Fluoxetine; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders

To assess the cost and effectiveness of risperidone, olanzapine, and conventional antipsychotic medications under "usual practice" conditions in a large, public mental health system, 108 persons diagnosed with schizophrenia or schizoaffective disorder were randomly assigned to one of these three medication groups and followed prospectively over a 12-month period using standard instruments and procedures. Psychiatric medication costs increased more over time in both the olanzapine and risperidone groups than in the conventional medication group. Compliance with the prescribed medication was higher in the olanzapine group than in the conventional group. No differential effects by medication group were evident in this sample on the symptoms of schizophrenia, side effects, psychosocial functioning, time to discharge for index hospitalization, survival to initial rehospitalization, or client satisfaction with services. These results extend findings from previous efficacy and naturalistic studies in several ways but are limited chiefly by the small number of subjects who completed 6 to 12 months of the clinical trial, and the resulting power to detect differences in the statistical analyses.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Risperidone

To compare the effects of risperidone and olanzapine on cognition in elderly patients with dementia and psychosis, and to compare the side effects of these drugs.. Single-blind, multicenter, observational study.. Four rural nursing care facilities.. Nineteen elderly patients with dementia and psychosis.. Eleven patients were treated with risperidone, eight with olanzapine.. Rating assessments were completed at baseline, 1 month, and 2 months. Simple paired and unpaired t tests determined between- and within-group differences. Social functioning, including activities of daily living, improved over baseline in both groups (p=0.03). Cognition declined significantly (p<0.05) in the risperidone group; comparatively more side effects occurred and blood pressure decreased (p<0.05) in the olanzapine group. When compared with each group cross-sectionally at baseline and end point, however, the two groups did not differ significantly.. Improvements in social functioning in all 19 patients suggest that both risperidone and olanzapine may help improve functioning in elderly patients with dementia and psychosis. Cognitive and side effect profiles of these drugs may differ substantially. Further study is needed to determine patient subpopulations who may be able to tolerate one drug over another.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cognition; Dementia; Female; Humans; Iowa; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Single-Blind Method; Treatment Outcome

The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder.. In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period).. Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain.. The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Clozapine; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Patient Admission; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

This study sought to determine whether patients with dementia with Lewy bodies (DLB) and psychosis responded to treatment with olanzapine.. This was a post hoc analysis of a subgroup of patients with DLB included in a larger double-blind, placebo-controlled, randomized parallel group trial of olanzapine for the treatment of psychosis in patients with Alzheimer's disease. Patients meeting the consensus criteria for DLB and exhibiting parkinsonism and visual hallucinations were selected from the initial study. Psychosis was assessed with the Neuropsychiatric Inventory/Nursing Home (NPI-NH) version and the Brief Psychiatric Rating Scale (BPRS). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale.. Twenty-nine patients met the criteria for DLB; 10 were randomized to placebo, 5 received 5 mg of olanzapine, 7 received 10 mg of olanzapine and 7 received 15 mg of olanzapine. Patients with DLB treated with 5 mg of olanzapine showed significant reductions in delusions and hallucinations. Patients treated with 10 mg showed a significant reduction in the NPI-NH delusion subscale score. No significant differences were found between the 15-mg group and the placebo group. Confirmatory findings emerged from an analysis of the BPRS. Caregivers reported decreased disruptions in their occupational routines for the group receiving 5 or 10 mg of olanzapine. There was no significant exacerbation of parkinsonian symptoms in any study group, no decrement in Mini-Mental State Examination scores in any of the treatment groups, and symptoms suggestive of anticholinergic toxicity did not differ among treatment groups.. This preliminary analysis suggests that olanzapine (5 or 10 mg) reduces psychosis in patients with DLB without worsening parkinsonism.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Behavior; Benzodiazepines; Cognition; Delusions; Dose-Response Relationship, Drug; Double-Blind Method; Female; Hallucinations; Humans; Lewy Body Disease; Male; Olanzapine; Parkinsonian Disorders; Personality Inventory; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders

To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS.. We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter.. At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS.. There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Comorbidity; Female; Humans; Longitudinal Studies; Male; Netherlands; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia, but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents, particularly in patients who have had suboptimal response to prior treatments.. The authors examined the effects of clozapine, olanzapine, risperidone, and haloperidol on 16 measures of neurocognitive functioning in a double-blind, 14-week trial involving 101 patients. A global score was computed along with scores in four neurocognitive domains: memory, attention, motor function, and general executive and perceptual organization.. Global neurocognitive function improved with olanzapine and risperidone treatment, and these improvements were superior to those seen with haloperidol. Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments. Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol. Clozapine yielded improvement in motor function but not more than in other groups. Average effect sizes for change were in the small to medium range. More than half of the patients treated with olanzapine and risperidone experienced "clinically significant" improvement (changes in score of at least one-half standard deviation relative to baseline). These findings did not appear to be mediated by changes in symptoms, side effects, or blood levels of medications.. Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs, and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Double-Blind Method; Female; Haloperidol; Humans; Male; Neuropsychological Tests; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Elderly patients with Alzheimer's disease (AD) commonly exhibit psychotic symptoms, prompting clinicians to administer antipsychotics. This article compares the effects of olanzapine and placebo in the emergence of hallucinations or delusions in AD patients with symptoms of agitation/aggression but little or no psychotic symptomatology at baseline.. A multicenter, double-blind, placebo-controlled study was conducted in nursing home patients with AD according to DSM-IV criteria and symptoms of agitation/aggression and/or psychosis. Patients (N = 206) were randomly assigned to receive either placebo or fixed-dose olanzapine (5, 10, or 15 mg/day) for up to 6 weeks. This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH). Three subsets of patients were identified on the basis of their symptoms at baseline: those with no clinically significant hallucinations, those with no clinically significant delusions, and those with no clinically significant delusions or hallucinations.. Of the patients without hallucinations or delusions at baseline (N = 75), the placebo-treated patients showed significantly greater development of these symptoms compared with olanzapine-treated patients overall (NPI/NH hallucinations + delusions mean change score, +2.73 vs. +0.27, p = .006). Similarly, of the patients without baseline hallucinations (N = 153), the placebo-treated patients showed greater hallucinations score increases than did olanzapine-treated patients overall (+1.25 vs. +0.33, p = .026), whereas patients without baseline delusions (N = 87) showed no significant treatment effects. Olanzapine had a favorable safety profile in each patient subset.. These results suggest that, overall, olanzapine effectively attenuated emergence of psychosis in a short-term trial of patients with Alzheimer's disease.

Topics: Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Delusions; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hallucinations; Humans; Male; Nursing Homes; Olanzapine; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome

Weight change and the weight-related health factors of nonfasting serum glucose, serum cholesterol, and diastolic blood pressure levels were analyzed in patients with DSM-III-R schizophrenia and related disorders who received treatment with olanzapine for up to 3 years, and comparisons were made to patients treated with haloperidol. Baseline body mass index (BBMI; kg/m2) and dose (mg/day) were investigated as predictors of long-term weight change experienced during olanzapine treatment.. This analysis retrospectively examined 573 patients receiving olanzapine and 103 patients receiving haloperidol for 39 weeks or more from a study of 1,996 patients randomly assigned 2:1 to either olanzapine, 5 to 20 mg/day, or haloperidol, 5 to 20 mg/day. After 6 weeks of acute therapy, patients continued for 1 year or more with either double-blind or open-label olanzapine therapy or double-blind haloperidol therapy.. Mean weight gain for olanzapine-treated patients observed for a median of 2.54 years trended toward a plateau after the first 39 weeks of treatment with a last-observation-carried-forward mean weight change of 6.26 kg (13.8 lb) and a median of 5.90 kg (13.0 lb). This was significantly higher than that for haloperidol-treated patients, whose mean weight gain was 0.69 kg (1.5 lb) after 1.15 years (p < .001). Patients with higher BBMI (> 27.6) gained significantly less weight during treatment with olanzapine than their lighter counterparts (BBMI < 27.6) (p < .001). The effect of olanzapine dose on weight was not significant (p > or = . 183). Median serum glucose at endpoint was not significantly associated (p = .096) with weight change for olanzapine. Median serum cholesterol and diastolic blood pressure for olanzapine-treated patients at endpoint showed a relationship with weight change that was statistically (p < or = .001) but not clinically significant. The difference in incidence of elevated serum glucose, cholesterol, or diastolic blood pressure between olanzapine and haloperidol therapy groups was not different (p > .05).. Mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks of treatment with no further significant gain out to 3 years. Higher BBMI was predictive of a lower long-term weight gain, while dose was not a significant predictor of greater longer term weight change. The relationship between weight change and glucose was not statistically significant. The association between weight change and changes in cholesterol as well as changes in diastolic blood pressure was statistically significant but not considered clinically relevant based on the ranges observed.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Blood Pressure; Body Mass Index; Body Weight; Cholesterol; Diastole; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Longitudinal Studies; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain

Patients treated with olanzapine may gain weight, especially in the first months of therapy. Amantadine (100-300 mg/day) was started in 12 patients having a mean weight gain of 7.3 kg during olanzapine treatment. The patients' weight stabilised and over 3-6 months they lost an average of 3.5 kg. No clinical deterioration occurred and no adverse effects were reported. These observations merit confirmation in randomised, controlled trials.

Topics: Adult; Amantadine; Antipsychotic Agents; Benzodiazepines; Dopamine Agents; Female; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Weight Gain

Cognitive impairment in multiple domains is common in patients with schizophrenia and may be a powerful determinant of poor functional ability and quality of life. We report a double-blind, placebo-controlled, cross-over study of donepezil augmentation in a schizoaffective disorder patient stabilized on olanzapine pharmacotherapy. The patient showed significant improvements in several cognitive measures and increased activation of prefrontal cortex and basal ganglia on functional MRI during the donepezil augmentation. In addition, the donepezil augmentation resulted in a reduction of depressive symptoms and in significant improvements in functional abilities and quality of life. Further studies of donepezil augmentation of neuroleptics in schizophrenia are warranted.

Topics: Adult; Basal Ganglia; Benzodiazepines; Brain; Brain Mapping; Cognition Disorders; Cross-Over Studies; Donepezil; Double-Blind Method; Drug Therapy, Combination; Humans; Indans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Olanzapine; Piperidines; Pirenzepine; Prefrontal Cortex; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life

The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice.. Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks.. The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants.. Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain

Recent studies suggest a role for the atypical antipsychotic olanzapine in the acute treatment of psychotic mood disorders, but long-term data are unavailable. The purpose of this naturalistic study was to determine the long-term effectiveness and tolerability of olanzapine as add-on therapy in psychotic mood disorders.. Hospital records were reviewed for 125 inpatients at the state psychiatric hospital in Buffalo, N.Y., who received at least 6 weeks of add-on olanzapine treatment for psychotic mood disorders (schizoaffective disorders [bipolar and depressive type], bipolar disorders [I, II, and NOS], and major depressive disorder). A group of schizophrenic patients served as a control group (N = 50). Baseline measures, including age, gender, number of hospitalizations in the 2 years prior to olanzapine treatment, concomitant medications, the Clinical Global Impressions scale (CGI), and the Global Assessment of Functioning-Equivalent (GAF-EQ) and Kennedy Axis V psychological impairment, violence, social skills, and activities of daily living subscale scores, were obtained. Follow-up information was obtained from the patients at least 6 months after initiation of olanzapine or by chart review and discussion with the treating psychiatrist. Patients with a diagnosis of psychotic mood disorders were compared with patients with the non-affective psychotic disorder (schizophrenia) on a variety of outcome measures.. Follow-up information was available on 102 patients (82%). Mean follow-up was 15 months; 50 (49%) of the 102 patients remained on olanzapine treatment at follow-up (32 psychotic mood disorder, 18 schizophrenic). The primary reason for discontinuation in both groups was lack of response. Both the psychotic mood disorder and schizophrenic groups had comparable outcomes on the CGI and GAF-EQ. Improvement on the Kennedy Axis V psychological impairment and social skills subscales was seen only in the psychotic mood disorders group (p < .01); both groups showed significant (p < .02) improvement in the violence subscale. Sustained mood-stabilizing effect was evident in only 7/27 (26%) of the psychotic mood disorders patients continuing on add-on olanzapine treatment at follow-up.. Lack of response was the primary reason for discontinuation of add-on olanzapine in both groups. Mood symptoms predicted a better response to add-on olanzapine in patients with psychotic mood disorders on selective outcome measures. However, only 26% of the patients with psychotic mood disorders sustained a clinically meaningful mood-stabilizing effect with add-on olanzapine treatment at follow-up.

Topics: Adult; Affective Disorders, Psychotic; Aged; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brief Psychiatric Rating Scale; Cohort Studies; Depressive Disorder; Drug Therapy, Combination; Female; Follow-Up Studies; Hospitalization; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Treatment Outcome; Valproic Acid

This study compared the specific antiaggressive effects of clozapine with those of olanzapine, risperidone, and haloperidol.. A total of 157 inpatients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were randomly assigned to receive clozapine, olanzapine, risperidone, or haloperidol in a double-blind 14-week trial. The trial was divided into two periods: eight weeks during which the dosage was escalated and then fixed, and six weeks during which variable dosages were used. The hostility item of the Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure. Covariates included the items that reflect positive symptoms of schizophrenia (delusions, suspiciousness or feelings of persecution, grandiosity, unusual thought content, conceptual disorganization, and hallucinations) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation (NOSIE).. Patients differed in their treatment response as measured by the hostility item of the PANSS. The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone. The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking, a formal thought disorder, or hallucinations and independent of sedation as measured by the NOSIE. Neither risperidone nor olanzapine showed superiority to haloperidol.. Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Double-Blind Method; Emotions; Female; Haloperidol; Hostility; Humans; Linear Models; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Statistics, Nonparametric; Survival Analysis

The authors describe the development of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) protocol for Alzheimer disease (AD), a trial developed in collaboration with the National Institute of Mental Health (NIMH), assessing the effectiveness of atypical antipsychotics for psychosis and agitation occurring in AD outpatients. They provide an overview of the methodology utilized in the trial as well as the clinical-outcomes and effectiveness measures that were implemented.

Topics: Aged; Algorithms; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Citalopram; Cost-Benefit Analysis; Humans; Olanzapine; Patient Compliance; Pirenzepine; Psychomotor Agitation; Psychotic Disorders; Risperidone; Treatment Outcome

Psychotic symptoms and behavioral disturbances are a leading cause of institutionalization in elderly patients with Alzheimer's disease (AD).. Elderly nursing home patients (n=105) with possible or probable AD were entered into a multicenter study to determine the long-term efficacy and safety of olanzapine in treatment of psychotic symptoms and behavioral disturbances due to AD.. Following a double-blind, 6-week exposure to fixed-dose olanzapine (5, 10, or 15 mg/d), patients entered an additional 18-week, open-label, flexible-dose treatment. Baseline was defined from the start of the extension phase.. Patients improved significantly on the primary efficacy measure, defined a priori, which consisted of the sum of the Agitation/Aggression, Delusions, and Hallucinations items ('Core':) of the NPI/NH. Olanzapine also significantly improved scores for the NPI/NH total and the Core item-associated Occupational Disruptiveness of the NPI/NH, as well as the BPRS total and CGI Severity-of-Alzheimer's scores. Barnes Akathasia scores improved significantly from baseline, while Simpson-Angus and AIMS scores were not significantly changed. Treatment-emergent symptoms included somnolence, accidental injury, and rash. No significant changes were seen in ECGs, including QT(c) interval, nor in weight or vital signs, including orthostasis.. Low-dose olanzapine appears to be effective and well tolerated for treatment of behavioral disturbances and psychotic symptoms due to AD in elderly patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Behavioral Symptoms; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Homes for the Aged; Humans; Long-Term Care; Male; Neuropsychological Tests; Nursing Homes; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

Compared to major depression without psychosis, psychotic depression often responds poorly to treatment with tricyclic antidepressants alone. Atypical antipsychotics, which appear to possess thymoleptic properties, may represent a new treatment alternative for patients with psychotic mood disorders. This open-label, pilot study evaluated the efficacy of olanzapine monotherapy in patients with psychotic depression. Seven inpatients who met DSM-IV criteria for a major depressive episode (unipolar) with psychotic features participated in a 10-week open-label trial of olanzapine 10-20 mg/day. The Hamilton Rating Scale for Depression (HRSD), the Scale for the Assessment of Positive Symptoms (SAPS), and the Clinical Global Impression Scale (CGI) were performed at each visit to evaluate clinical response. Four out of the 5 study completers responded during the trial. Overall, there was a statistically significant change between baseline and final visit on the SAPS, HRSD, and the CGI Scale (p < .001). The results of this pilot study suggest that olanzapine may be an effective treatment for some patients with unipolar psychotic depression. However, these observations require replication in randomized, controlled trials.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Female; Humans; Male; Olanzapine; Pilot Projects; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Treatment Outcome

The present analysis was performed on data from a subsample of patients with schizoaffective disorder, bipolar type, who participated in a multicenter, double-blind study comparing olanzapine to haloperidol.. Patients with schizoaffective disorder bipolar type, characterized as currently manic, mixed, depressed, or euthymic, were assessed weekly for 6 weeks during treatment with either olanzapine or haloperidol. Manic symptoms were measured using the sum of six items of the BPRS, and depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale. In addition, cognitive functioning was measured using the sum of seven items from the PANSS. Repeated measures analyses were performed using random coefficients regression of the serial measurement of manic, cognitive, and depressive symptoms.. A significant treatment difference was detected overall, indicating that olanzapine was significantly more effective than haloperidol in reducing symptoms of depression and improving patients' cognitive symptoms. The superiority of olanzapine over haloperidol in the reduction of manic symptoms did not reach statistical significance (P=.052). The greatest improvement in both manic and cognitive symptoms was seen in the olanzapine-treated 'currently manic' subgroup, and least improvement in the haloperidol-treated 'euthymic' subgroup. Depressive symptoms were most improved in the olanzapine-treated 'depressed' subgroup, and least improved in the corresponding haloperidol subgroup.. Overall, olanzapine was superior to haloperidol with respect to thymoleptic effects in patients with schizoaffective disorder, bipolar type.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Severity of Illness Index; Treatment Outcome

Olanzapine is a novel antipsychotic effective in reducing positive and negative symptoms of schizophrenia and with a safe side-effect profile. Premarketing trials, however, included only a few elderly patients. Further data are needed regarding the effects of olanzapine in the elderly and those with comorbid medical illness. In this pilot study, 11 hospitalized patients (age range 60-85 years) who manifested symptoms of psychosis related to schizophrenia and schizoaffective disorders were treated with olanzapine (dose range, 5-20 mg/day). Efficacy and safety were assessed by the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Extrapyramidal Symptom Rating Scale (ESRS), Mini-Mental State Examination (MMSE), Calgary Depression Scale For Schizophrenia (CDSS), EKG, physical examination, and various laboratory tests. Seven patients responded to treatment and all of them showed improvement in both positive and negative symptoms, with greater reduction in positive symptoms. Treatment was discontinued in 2 patients whose symptoms showed no improvement or worsened. The CGI showed significant improvement in 9 patients, remained the same in 1, and worsened in 1 patient. ESRS showed significant reduction from baseline to final visit. Of the 10 patients who cooperated for MMSE, 9 had improved scores. The CDSS showed significant reduction in scores from baseline to final visit. No significant changes were noted in laboratory tests, prolactin levels, EKG, and physical examination. Concomitant administration of lorazepam, carbamazepine, divalproex sodium, and lithium carbonate caused no adverse consequences. The reduction of positive and negative symptoms, lack of significant extrapyramidal symptoms and other side effects, and lack of any significant drug interaction suggest that olanzapine may be a safe and effective antipsychotic medication in the elderly.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Treatment Outcome

This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p < 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.

Topics: Adult; Antipsychotic Agents; Atropine; Autonomic Nervous System Diseases; Benzodiazepines; Cholinergic Antagonists; Clozapine; Female; Humans; Male; Muscarinic Antagonists; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Radioligand Assay; Receptors, Muscarinic

Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregiver distress, and lead to institutionalization. This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and/or agitation/aggression in patients with AD.. A multicenter, double-blind, placebo-controlled, 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and/or behavioral symptoms. Patients were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression, Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric Inventory-Nursing Home version.. Low-dose olanzapine (5 and 10 mg/d) produced significant improvement compared with placebo on the Core Total (-7.6 vs -3.7 [P<.001] and -6.1 vs -3. 7 [P =.006], respectively). Core Total improvement with olanzapine, 15 mg/d, was not significantly greater than placebo. The Occupational Disruptiveness score, reflecting the impact of patients' psychosis and behavioral disturbances on the caregiver, was significantly reduced in the 5-mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P =.008). Somnolence was significantly more common among patients receiving olanzapine (25.0%-35.8%), and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%, respectively). No significant cognitive impairment, increase in extrapyramidal symptoms, or central anticholinergic effects were found at any olanzapine dose relative to placebo.. Low-dose olanzapine (5 and 10 mg/d) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nursing Homes; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Treatment Outcome

This study compared the efficacy and safety of 4 therapeutically relevant strategies for switching clinically stable patients from a conventional antipsychotic drug or risperidone to olanzapine.. Two hundred nine outpatients with a DSM-IV diagnosis of schizophrenia or schizo-affective disorder who were clinically stable while being treated with a conventional antipsychotic drug or risperidone were openly randomly assigned to either abrupt or gradual discontinuation of their prior antipsychotic drug. Patients were further randomly assigned in a double-blind fashion to immediate olanzapine initiation (olanzapine, 10 mg q.d. for 3 weeks) or stepwise initiation (a sequence of 1 week each on placebo; olanzapine, 5 mg q.d.; and olanzapine, 10 mg q.d.). The efficacy of these 4 switching paradigms was assessed using the Clinical Global Impressions (CGI)-Improvement scale, Patient's Global Impressions (PGI)-Improvement scale, and Positive and Negative Syndrome Scale (PANSS). Safety assessments included ratings for extrapyramidal symptoms, cognitive impairment, adverse events, laboratory parameters, weight change, and vital signs.. The paradigm of gradual antipsychotic drug discontinuation combined with an initial full dose of olanzapine, 10 mg/day, had the most favorable efficacy and tolerability profile overall. By week 3, the majority of completing patients on all 4 switching paradigms were either improved or clinically unchanged (> 90%). No clinically significant differences between switching paradigms were seen in laboratory values or vital signs.. In this study, switching clinically stable outpatients with a diagnosis of schizophrenia or schizoaffective disorder to olanzapine was most successful when a full therapeutic dose of olanzapine was immediately initiated while gradually discontinuing prior conventional antipsychotic drug or risperidone treatment. Overall, switching was achieved without increased vulnerability to relapse or to occurrence of clinically burdensome antipsychotic drug withdrawal symptoms in the majority of patients.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The aim of this study was to compare the degree of striatal dopamine D2 receptor availability in patients treated with recommended (5-20 mg, mean dose 11.9 +/- 6.3 mg daily) and higher doses (25-40 mg, mean 32.1 +/- 5.6 mg daily) of the novel antipsychotic drug olanzapine by means of [123I] IBZM Single photon emission computed tomography (SPECT). The results were compared to those of a group of 10 untreated, healthy, age- and sex-matched controls. The degree of dopamine D2 receptor occupancy in the patient group was correlated with the presence of extrapyramidal symptoms (EPS). A total of 20 patients who met the DSM III R criteria for schizophrenia or schizoaffective disorder received a clinically effective antipsychotic monotherapy with olanzapine. The mean daily dose of olanzapine ranged from 0.05-0.6 mg/kg body weight. The dopamine D2 receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding expressed as the [STR-BKG]/BKG ratio ranged from 0.13-0.61 (healthy controls 0.95). The D2 receptor availability revealed an exponential dose-response relationship (r = - 0.85, p < 0.001). The frequency of EPS induced by olanzapine was considerably lower. Only one patient, treated with 40 mg olanzapine, suffered from severe EPS symptoms and had to be given biperiden. There were no significant differences in the presence of EPS symptoms between patients with recommended doses and those with higher doses of olanzapine.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzamides; Benzodiazepines; Brain; Brain Chemistry; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Pyrrolidines; Radiopharmaceuticals; Receptors, Dopamine D2; Schizophrenia; Tomography, Emission-Computed, Single-Photon

Clozapine is an atypical antipsychotic indicated for the management of severely ill patients with schizophrenia who have failed to respond adequately to standard drug treatment. The significant risk of agranulocytosis and seizure associated with clozapine has led to the restrictions in its use. Additionally, drug-induced sedation, sialorrhea, enuresis, and weight gain are often cited as problematic consequences of clozapine treatment. Our primary objective was to determine the effectiveness and safety of a method of slow cross-titration from clozapine to olanzapine among patients responsive to clozapine treatment but experiencing medication-induced adverse events.. Changes in symptomatology, mood, subjective response, and safety were examined in 20 outpatients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder who converted from clozapine to olanzapine. Patients were considered clozapine-responsive as evidenced by improved social function and decreased symptoms with clozapine therapy; however, they were interested in alternative pharmacologic treatment because of clozapine-related side effects.. Equivalent efficacy of olanzapine to clozapine was found in 90% of the patients (18/20) in the study group, without rehospitalization or suicidal behavior in any of the patients. Also notable was a reduction in drug-induced side effects and improved subjective response to pharmacotherapy.. The successful conversion from clozapine to olanzapine has the potential to provide great benefits for the patient, including reducing drug-induced side effects while maintaining symptom control. These preliminary results suggest that further research on converting clozapine responders to olanzapine is warranted.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

It has been hypothesized that the morbidity and mortality associated with schizophrenia can be prevented by providing effective treatment during the first episode of psychosis. Hence, the authors examined patients with first-episode psychosis to determine the efficacy and safety of olanzapine and haloperidol treatment.. A subpopulation of first-episode patients (N=83) from a large prospective, multicenter, international, double-blind, 6-week acute treatment study was evaluated. These patients were selected from a pool of 1,996 patients who had a DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder and who also met the following criteria: 1) the length of their current psychotic episode had to be 5 or fewer years, and 2) patients had to be 45 years of age or younger at onset of first psychotic symptoms.. Compared to haloperidol, olanzapine showed a statistically significantly greater reduction in the Brief Psychiatric Rating Scale (BPRS) total and negative scores and in the Positive and Negative Syndrome Scale total and positive scores. Clinical response (defined as 40% or greater improvement in BPRS total score from baseline) was also statistically significantly higher in olanzapine-treated patients (67.2%) than in haloperidol-treated patients (29.2%). Olanzapine-treated patients further showed statistically significant improvements in the Simpson-Angus scale and Barnes Akathisia Scale scores, while haloperidol-treated patients showed a worsening on both measures. Compared to olanzapine-treated multiple-episode patients in the parent study, olanzapine-treated first-episode patients achieved an even statistically significantly higher response. Haloperidol-treated first-episode patients experienced statistically significantly more extrapyramidal symptoms than haloperidol-treated multiple-episode patients.. In patients experiencing first-episode psychosis, olanzapine had a risk-benefit profile significantly superior to that of haloperidol. The study results suggest that novel antipsychotic agents such as olanzapine should be considered as a preferred option in first-episode psychosis, on the basis of both safety and efficacy advantages.

Topics: Age of Onset; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Haloperidol; Humans; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Time Factors; Treatment Outcome

Olanzapine's structural similarities to clozapine and the results of premarketing clinical trials suggested potential usefulness in treating patients with treatment-refractory psychoses. Sixteen inpatients from the state hospital with severe, refractory schizophrenic or schizoaffective psychoses received olanzapine in a prospective, 12-week, open-label trial. The olanzapine dose was 10 mg/day for at least the first 6 weeks and never exceeded 20 mg/day. Mood stabilizers and other antipsychotic agents were discontinued before olanzapine was started. Patients frequently became more agitated within the first several weeks of initiating treatment, requiring the increased use of benzodiazepines and often leading to the discontinuation of olanzapine. Two patients improved significantly. Overall, significant clinical improvement was noted only for motor side effects. This study concluded that olanzapine was not effective in this heterogeneous group with chronic, severe, treatment-resistant psychosis when used in this manner. Further research is needed to explain the tendency toward agitation upon transition to olanzapine, which is reminiscent of reported risperidone complications. Clinicians should be alert for this complication and should minimize concomitant medication changes that might add to the risk of emergent agitation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Monitoring; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Prospective Studies; Psychomotor Performance; Psychotic Disorders; Treatment Outcome

The effectiveness of antipsychotic monotherapy in schizoaffective disorder is limited, and further constrained by safety concerns.. We aimed to compare the efficacy, tolerability and safety profile of the new pharmaceutical, olanzapine, with haloperidol.. Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospective international study. Subjects were randomly allocated to six weeks of olanzapine (5-20 mg) or haloperidol (5-20 mg) treatment; responders were followed for up to one year of double-blind, long-term maintenance therapy.. Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy, including clinical response. Significantly fewer olanzapine patients left the study early, and fewer adverse events were observed among those receiving olanzapine. During maintenance, olanzapine-treated patients continued to experience additional improvement, with fewer EPS but more weight gain than those on haloperidol.. Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia

Psychosis is a defining feature of schizophrenia consisting of formal thought disorder, delusions, and hallucinations. Although psychosis is present in the majority of patients with schizophrenia, the prevalence, responsiveness to atypical antipsychotic drug therapy, and prediction of outcome of individual psychotic symptoms in a population of well-diagnosed patients with schizophrenia have not been conclusively established.. This paper examined the prevalence, responsiveness to the atypical antipsychotic olanzapine, and relationship to outcome of individual psychotic symptoms using data from a previously reported large multicenter, double-blind clinical trial of olanzapine (mean daily dose at endpoint = 13.6 +/- 6.9 mg/day).. The most frequently reported psychotic symptoms at baseline were delusions (65%), conceptual disorganization (50%), and hallucinations (52%), and the majority of patients (68%) experienced from one to three symptoms. Additionally, with olanzapine treatment there were significant improvements (p < .001) in baseline to endpoint Positive and Negative Symptom Scale (PANSS) psychotic item scores, with the largest effect sizes observed for hallucinatory behavior, unusual thought content, suspiciousness/persecution, and delusions. During the acute phase of the trial, quality of life was correlated significantly with baseline conceptual disorganization (p = .038) and unusual thought content (p = .023), and time spent in the hospital was correlated with unusual thought content (p = .005).. The implications of these for the clinical management of schizophrenia are discussed.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Olanzapine; Pirenzepine; Prevalence; Prognosis; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

Topics: Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Tablets

Previous studies have suggested that clozapine is associated with increases in both weight and serum triglyceride (but not cholesterol) levels. Because of the pharmacologic similarities between clozapine and olanzapine, we decided to evaluate if olanzapine use was associated with an increase in triglycerides.. Twenty-five inpatients (21 men, 4 women) were treated with olanzapine, and their outcomes were tracked prospectively in a medication utilization evaluation study.. After 12 weeks on a mean +/- SD dose of 13.8+/-4.4 mg/day, weight increased a mean of 12 lb (5.4 kg; from 190+/-37 lb [85.5+/-16.7 kg] to 202+/-30 lb [90.9+/-13.5 kg]), while fasting triglycerides increased a mean of 60 mg/dL (from 162+/-121 mg/dL to 222+/-135 mg/dL). Both increases were significant at p < .05. Fasting total cholesterol did not increase. The triglyceride increase was even larger when we excluded 8 patients who received various interventions to lower lipid levels (e.g., pravastatin, low-fat diet) during the olanzapine trial. There was a strong association between weight change and triglyceride change (p < .02); after controlling for weight, analysis of covariance showed no independent increase in triglycerides.. These results suggest olanzapine has significant effects on weight and serum triglyceride levels. Clinical implications are discussed.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Female; Hospitalization; Humans; Hypertriglyceridemia; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Triglycerides; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Research Design; Risperidone; Schizophrenia; Treatment Outcome

Olanzapine is a recently introduced atypical neuroleptic agent for which little information is available on its use in children. Open clinical trials of olanzapine treatment were conducted on five hospitalized children (ages 6 to 11 years) with varying diagnoses including bipolar disorder, psychosis not otherwise specified, schizophrenia, and attention-deficit/ hyperactivity disorder. Each patient had failed previous psychotropic medication trials, with a mean of four prior trials. The mean length of olanzapine treatment was 32 days (range, 2 to 7 weeks), and mean daily dose was 7.5 mg/day (range, 2.5 to 1.0 mg/day) or 0.22 mg/kg/day (range, 0.12 to 0.29 mg/kg/day). All children experienced adverse effects, including sedation (N = 3), weight gain of up to 16 pounds (N = 3), and akathisia (N = 2). Three patients showed some clinical improvement, but olanzapine treatment was discontinued in all five children within the first 6 weeks of treatment because of adverse effects or lack of clinically significant therapeutic response, although higher (or lower) doses, slower titration of dosage, or a longer duration of treatment might have produced more favorable results. Psychotic symptoms did not respond in the two patients with evidence of overt hallucinations and paranoid ideation. Improvement was observed in sleep in all five patients and in control of aggression in three. Before controlled trials of olanzapine in children are undertaken, further exploration of dose range and increased duration of treatment on an open basis are warranted. Until more encouraging data are available, clinicians should be cautious and conservative in their predictions about the potential value of olanzapine in treating preadolescent psychiatric disorders.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Benzodiazepines; Child; Female; Humans; Impulsive Behavior; Male; Mental Disorders; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine; Psychotic Disorders; Self-Injurious Behavior; Tourette Syndrome

This international, multicenter double-blind trial was designed to compare the therapeutic profile of an atypical antipsychotic, olanzapine, with that of a conventional dopamine D2 antagonist, haloperidol.. A total of 1,996 patients at 174 sites in Europe and North America were randomly assigned to treatment with olanzapine (N = 1,336) or haloperidol (N = 660) over 6 weeks. The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale (BPRS). Secondary analyses included comparisons of the mean change in positive and negative symptoms, comorbid depression, extrapyramidal symptoms, and overall drug safety.. Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure, including depression. Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events. Substantially more olanzapine-treated patients (66.5%) than haloperidol-treated patients (46.8%) completed 6 weeks of therapy. Statistically significant advantages of olanzapine treatment were related to 1) change in negative symptoms, 2) extrapyramidal symptom profile, 3) effect on prolactin levels, and 4) response rate.. Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology, with a substantially more favorable safety profile, than haloperidol. It meets several of the criteria for a novel atypical antipsychotic agent.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Comorbidity; Depressive Disorder; Double-Blind Method; Europe; Female; Haloperidol; Humans; Male; North America; Olanzapine; Patient Dropouts; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Tardive dyskinesia is a serious and common complication of neuroleptic treatment. Olanzapine is a novel antipsychotic agent exhibiting regional mesolimbic dopaminergic selectivity and a broad-based pharmacology encompassing serotonin, dopamine, muscarinic, and adrenergic receptor binding affinities. The authors' goal was to compare the incidence of tardive dyskinesia among patients receiving olanzapine and those receiving the conventional dopamine 2 antagonist haloperidol.. Data were analyzed from three actively controlled and blind long-term responder studies of subjects meeting DSM-III-R criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder treated with olanzapine (N = 707, up to 20 mg/day, 237 median days of exposure) or haloperidol (N = 197, up to 20 mg/day, 203 median days of exposure) who did not have evidence of tardive dyskinesia at baseline. All of the subjects had a chronic disease course (mean greater than 10 years), and there were no significant between-treatment group differences in demographic or disease characteristics. The Abnormal Involuntary Movement Scale and research diagnostic criteria for tardive dyskinesia were used to define the comparative incidence rates of long-term treatment-emergent tardive dyskinesia.. The incidence of newly emergent tardive dyskinesia at any visit after baseline, at the final visit, and at the final two clinical assessments was statistically significantly lower among olanzapine-treated patients than among haloperidol-treated patients.. These findings support an atypical extrapyramidal symptom profile and the potential of a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol among patients requiring maintenance antipsychotic treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Schizophrenia; Severity of Illness Index; Treatment Outcome

Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Risperidone; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Psychotic Disorders; Schizophrenia; Weight Loss

Pseudotumor cerebri or idiopathic intracranial hypertension (IIH) secondary to psychotropic drugs is a very rare occurrence. Lithium is typically the culprit agent. Here, authors report on an interesting case of an adolescent with early-onset schizophrenia that develops a reversible IIH putatively related to olanzapine-induced weight gain. This is followed by discussion of purported pharmacodynamic mechanisms and brief review of literature. Clinicians should be cognizant to this serious complication given the propensity of the majority of atypical antipsychotics to induce significant weight gain especially in younger population.

Topics: Adolescent; Antipsychotic Agents; Humans; Olanzapine; Pseudotumor Cerebri; Psychotic Disorders; Weight Gain

Previous studies have shown mixed evidence on ethnic disparities in antipsychotic prescribing among patients with psychosis in the UK, partly due to small sample sizes. This study aimed to examine the current state of antipsychotic prescription with respect to patient ethnicity among the entire population known to a large UK mental health trust with non-affective psychosis, adjusting for multiple potential risk factors.. This retrospective cohort study included all patients (N = 19,291) who were aged 18 years or over at their first diagnoses of non-affective psychosis (identified with the ICD-10 codes of F20-F29) recorded in electronic health records (EHRs) at the South London and Maudsley NHS Trust until March 2021. The most recently recorded antipsychotic treatments and patient attributes were extracted from EHRs, including both structured fields and free-text fields processed using natural language processing applications. Multivariable logistic regression models were used to calculate the odds ratios (OR) for antipsychotic prescription according to patient ethnicity, adjusted for multiple potential contributing factors, including demographic (age and gender), clinical (diagnoses, duration of illness, service use and history of cannabis use), socioeconomic factors (level of deprivation and own-group ethnic density in the area of residence) and temporal changes in clinical guidelines (date of prescription).. The cohort consisted of 43.10 % White, 8.31 % Asian, 40.80 % Black, 2.64 % Mixed, and 5.14 % of patients from Other ethnicity. Among them, 92.62 % had recorded antipsychotic receipt, where 24.05 % for depot antipsychotics and 81.72 % for second-generation antipsychotic (SGA) medications. Most ethnic minority groups were not significantly different from White patients in receiving any antipsychotic. Among those receiving antipsychotic prescribing, Black patients were more likely to be prescribed depot (adjusted OR 1.29, 95 % confidence interval (CI) 1.14-1.47), but less likely to receive SGA (adjusted OR 0.85, 95 % CI 0.74-0.97), olanzapine (OR 0.82, 95 % CI 0.73-0.92) and clozapine (adjusted OR 0.71, 95 % CI 0.6-0.85) than White patients. All the ethnic minority groups were less likely to be prescribed olanzapine than the White group.. Black patients with psychosis had a distinct pattern in antipsychotic prescription, with less use of SGA, including olanzapine and clozapine, but more use of depot antipsychotics, even when adjusting for the effects of multiple demographic, clinical and socioeconomic factors. Further research is required to understand the sources of these ethnic disparities and eliminate care inequalities.

Topics: Antipsychotic Agents; Clozapine; Electronics; Ethnicity; Humans; Minority Groups; Olanzapine; Psychotic Disorders; Retrospective Studies

Expert consensus-based clinically equivalent dose estimates and dosing recommendations can provide valuable support for the use of drugs for psychosis in clinical practice and research.. This second International Consensus Study of Antipsychotic Dosing provides dosing equivalencies and recommendations for newer drugs for psychosis and previously reported drugs with low consensus.. We used a two-step Delphi survey process to establish and update consensus with a broad, international sample of clinical and research experts regarding 26 drug formulations to obtain dosing recommendations (start, target range, and maximum) and estimates of clinically equivalent doses for the treatment of schizophrenia. Reference agents for equivalent dose estimates were oral olanzapine 20 mg/day for 15 oral and 7 long-acting injectable (LAI) agents and intramuscular haloperidol 5 mg for 4 short-acting injectable (SAI) agents. We also provide a contemporary list of equivalency estimates and dosing recommendations for a total of 44 oral, 16 LAI, and 14 SAI drugs for psychosis.. Survey participants (. As randomized, controlled, fixed, multiple-dose trials to optimize the dosing of drugs for psychosis remain rare, expert consensus remains a useful alternative for estimating clinical dosing equivalents. The present findings can support clinical practice, guideline development, and research design and interpretation involving drugs for psychosis.

Topics: Antipsychotic Agents; Delayed-Action Preparations; Haloperidol; Humans; Olanzapine; Psychotic Disorders; Schizophrenia

Whilst antipsychotic medication reduces risk of relapse following a first episode of psychosis (FEP), some individuals can discontinue medication and remain relapse free. We aimed to identify patient and service-specific factors which influence clinical outcome following antipsychotic discontinuation. The outcomes 'admission to hospital' and 'remaining free from psychotic symptoms', both within one year from discontinuation, were explored retrospectively in an established naturalistic cohort of 354 patients with FEP. Logistic regression analysis was used to explore influence of routinely available baseline and treatment course variables on these outcomes. Seventy-seven individuals (22 %) fully discontinued antipsychotic treatment within a year, at mean 102 days from initiation. Only antipsychotic type had significant association with discontinuation; aripiprazole was discontinued more than olanzapine (p = 0.028). Seventeen individuals required admission to hospital; significantly associated with prior admission at first illness onset (p = 0.004), and prior legal detention to hospital (p = 0.001). Admission was less likely in those discontinuing aripiprazole vs olanzapine (p = 0.044). Twenty-four patients remained psychosis symptom free and were most significantly likely to have received clinician support in discontinuation; this group had no association with either initial duration of untreated psychosis or prior duration of antipsychotic treatment. Future studies exploring outcomes following antipsychotic discontinuation require consistency of choice of outcome measures and sample stratification by vulnerability factors including severity of first illness episode, whether remaining symptom free after first episode, which medication switched from and baseline functioning. The impact and nature of clinician support to discontinue requires further exploration alongside its association with abruptness of discontinuation.

Topics: Antipsychotic Agents; Aripiprazole; Hospitalization; Humans; Olanzapine; Psychotic Disorders; Retrospective Studies

The Zinc finger protein 804A (ZNF804A) is a potential schizophrenia candidate gene that has emerged from genome-wide association studies. The aim of the study is to investigate whether this gene variant influences the response of positive or negative symptoms to antipsychotic drug olanzapine in North Indian schizophrenia patients.. Our study involved 184 unrelated schizophrenia cases (114 males and 70 females; mean age: 52.8 ± 11.6 years) and 300 normal controls (168 males and 132 females; mean age: 54.9 ± 6.9 years). At the start of treatment and after four weeks, we assessed the response of positive and negative symptoms by positive and negative syndrome scale (PANSS). Olanzapine drug level was estimated using HPLC Method and Genotyping was performed using PCR-Snap Shot technique.. Significant differences were observed in the genotype distribution (. Our findings indicate that ZNF804A gene polymorphism plays a significant role in the treatment of schizophrenia, suggesting that ZNF804A may be an effective marker for schizophrenia treatment.

Topics: Adult; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Kruppel-Like Transcription Factors; Male; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; Psychotic Disorders; Schizophrenia; Zinc Fingers

Many psychotic patients are treated with antipsychotic medications during acute agitation and aggressive behavior episodes in an attempt to achieve a rapid calming effect. Those medications include olanzapine, zuclopenthixol acetate, and haloperidol intramuscular administration. This study compared the effectiveness of these injections in reducing the need for restraint during agitated-psychotic episodes that include aggression. Sociodemographical and clinical data were retrieved from the electronic medical records of 179 patients who needed rapid calming while hospitalized in a mental health center with acute psychosis. The treatments administered were olanzapine intramuscular, zuclopenthixol acetate intramuscular, and haloperidol intramuscular. The assessed outcomes were rate of restraint and violent behavior. Olanzapine was found significantly more effective in reducing the need for restraint compared to zuclopenthixol acetate. No significant differences were found between haloperidol and the other two with regard to restraint. Neither were other significant differences found between the groups with regard to violent or self-harming behaviors. No significant differences were found in the rate of violent behavior and antipsychotic dosage at discharge. In conclusion, in inpatients with acute agitated psychosis, olanzapine intramuscular shows better efficacy in reducing the need for restraint, at least as compared to zuclopenthixol acetate intramuscular.

Topics: Antipsychotic Agents; Benzodiazepines; Clopenthixol; Haloperidol; Humans; Injections, Intramuscular; Olanzapine; Psychomotor Agitation; Psychotic Disorders

We report a case of refractory psychosis after carbon monoxide poisoning in a 65-year-old woman who attempted suicide by charcoal burning in 2018. On discharge from hospital, she was bedbound, tube-fed, and had limited verbal output. In early 2019, she was able to resume oral feeding and her physical condition improved. However, she started to have paranoid ideas and auditory hallucinations. She was diagnosed as having organic brain syndrome and was prescribed with quetiapine 300 mg every night. Because of the poor clinical response, quetiapine was switched to olanzapine 20 mg every night and augmented with amisulpride and valproate sodium. However, she remained distressed, psychotic, and suicidal. She was then prescribed with clozapine 300 mg every night. Her symptoms improved despite residual auditory hallucinations remained, but she was less distressed about them.

Topics: Aged; Carbon Monoxide Poisoning; Female; Hallucinations; Humans; Olanzapine; Psychotic Disorders; Quetiapine Fumarate

Antipsychotics (APs) can cause weight gain. Little is known about changes in weight when APs are combined with other psychotropics. This study examines the weight change in patients undergoing long-term treatment with APs or with AP combined with other psychotropics.. Patients with non-affective psychotic disorder from the GROUP study were divided into three groups: AP medication group (APm) (n = 100), AP in combination with other psychotropics (APc) (n = 73), and medication-free (Meds-free) (n = 100). Weight change was examined at inclusion and after three years using a paired-sample t-test. An Independent-sample t-test was performed to evaluate weight change among patients taking clozapine, olanzapine, and quetiapine and individuals not taking these medications. Linear regression was performed to evaluate the association between covariates and weight.. Patients in the APm group [mean = 1.800 kg, t(99)=2.849, 95% CI(0.546, 3.054), p = 0.005] and the APc group [mean = 1.877 kg, t(72)=2.688, 95% CI(0.485, 3.268), p = 0.009] showed significant weight gain. Patients taking clozapine, olanzapine or quetiapine showed significant weight gain compared to those not taking these medications [mean difference=1.707 kg, t(271)= 2.061, 95% CI(0.077, 3.337), p = 0.040)].. Patients receiving APs and APs with other psychotropics gain weight during long-term treatment. It is possible that weight gain is mainly driven by APs.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Longitudinal Studies; Olanzapine; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Risperidone; Weight Gain

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Mania; Olanzapine; Psychotic Disorders; Risperidone

Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2 years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit-risk assessment.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Female; Humans; Male; Mental Disorders; Middle Aged; Mirtazapine; Off-Label Use; Olanzapine; Psychiatry; Psychotic Disorders; Psychotropic Drugs; Quetiapine Fumarate; Retrospective Studies; Risperidone; Valproic Acid

The authors sought to determine whether antipsychotic use, compared with nonuse, is associated with lower work disability in first-episode nonaffective psychosis, and if so, for how long.. A within-subject design was used to study the risk of sickness absence or disability pension during antipsychotic use compared with nonuse during a maximum of 11 years of follow-up (2006-2016) in a Swedish nationwide cohort of patients with first-episode nonaffective psychosis (N=21,551; age range, 16-45 years). The within-subject analyses were conducted with stratified Cox regression models, adjusted for time-varying factors, using each individual as her or his own control to eliminate selection bias. The primary outcome was work disability (sickness absence or disability pension).. Overall, 45.9% of first-episode patients had work disability during the median length of follow-up of 4.8 years. The risk of work disability was lower during use compared with nonuse of any antipsychotic (adjusted hazard ratio [aHR]=0.65, 95% CI=0.59-0.72). The lowest adjusted hazard ratios emerged for long-acting injectable antipsychotics (aHR=0.46, 95% CI=0.34-0.62), oral aripiprazole (aHR=0.68, 95% CI=0.56-0.82), and oral olanzapine (aHR=0.68, 95% CI=0.59-0.78). Long-acting injectables were associated with lower risk than olanzapine, the most commonly used oral antipsychotic (aHR=0.68, 95% CI=0.50-0.94). Adjusted hazard ratios were similar during the periods of <2 years, 2-5 years, and >5 years since diagnosis.. Among individuals with first-episode nonaffective psychosis, antipsychotic treatment (with long-acting injectables in particular) was associated with about 30%-50% lower risk of work disability compared with nonuse of antipsychotics in the same individuals, which held true beyond 5 years after first diagnosis. These findings are informative regarding the important topic of early discontinuation of antipsychotic treatment after a first episode of nonaffective psychosis, but they need replication.

Topics: Adolescent; Adult; Antipsychotic Agents; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Sweden; Young Adult

This paper aims to examine how existing mental health within the city of Chennai, India manages first-episode psychosis, to determine lacunae and barriers in providing effective early intervention and to make appropriate recommendations to improve the care of first-episode psychosis patients.. Interviews were held with 15 health professionals to capture information on current practices and facilities available for the management of first-episode psychosis.. No specialized clinic or services were available for individuals with first-episode psychosis in Chennai, except one. Pharmacotherapy was the main treatment modality with psychological support to patients and families. Most common drugs used were Risperidone, Olanzapine, and Haloperidol in their recommended doses. General practitioners and paediatricians, due to inadequate training in mental health, referred patients with psychosis to mental health professionals.. Equipping the existing mental health services to manage FEP and training all health professionals on psychosis will improve FEP management in Chennai.

Topics: Haloperidol; Humans; India; Olanzapine; Psychotic Disorders; Risperidone

Coordinated specialty care (CSC) has become the standard of care for first-episode psychosis (FEP). The gap between CSC best practices and the actual care delivered is unknown. This longitudinal study aimed to measure that gap by using a large Medicaid claims database and 10 quality indicators (QIs) reflecting aspects of CSC and to study the relationship between these QIs and future health care utilization.. Individuals with FEP were identified in a Missouri Medicaid claims database. Participants were required to have been eligible for Medicaid benefits for at least 10 months in the year prior to and the year after their first episode of psychosis and to have had no evidence of a prior psychosis diagnosis. Descriptive statistics were generated for each of the QIs, and a stratified Cox regression was used to identify predictors of subsequent health care utilization.. Data were obtained for 6,246 participants, and follow-up lasted a mean of 4.24 years. Significant practice gaps were found in the use and monitoring of antipsychotic medications. Of those prescribed antipsychotic medication, 5% received prescriptions above recommended daily doses, 16% received two or more antipsychotics, and 20% were treated with olanzapine or clozapine. Among the QIs, lack of monitoring for smoking (hazard ratio [HR]=2.71, 95% confidence interval [CI]=2.47-2.97) and lack of integrated care delivery in treatment (HR=2.00, 95% CI=1.92-2.08) were most associated with psychiatric hospitalization.. In most cases, treatment was far from meeting CSC recommendations, suggesting that implementation of CSC requires substantial modifications to delivery of care for individuals with FEP.

Topics: Antipsychotic Agents; Humans; Longitudinal Studies; Missouri; Olanzapine; Psychotic Disorders

The role of Olanzapine therapeutic drug monitoring is controversial. The present study explores the associations of Olanzapine plasma concentrations with clinical response and metabolic side effects in first episode psychosis (FEP) after 2 months of treatment.. Forty-seven patients were included. Improvement in clinical symptomatology was assessed using the PANSS. Metabolic assessment included weight, blood pressure, waist circumference, blood glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides.. The Olanzapine plasma concentrations after 2 months of treatment were positively correlated with weight gain (r = 0.49, p = 0.003), and a concentration > 23.28 ng/mL was identified as a positive predictor of weight gain (≥ 7%). The Olanzapine concentration to dose (C/D) ratio was positively correlated with the percentage of improvement in the total PANSS (r = 0.46, p = 0.004), and a C/D ratio > 2.12 was identified as a positive predictor of a good response (percentage of improvement > 30%) after 2 months of treatment. We also identified several factors that could alter Olanzapine pharmacokinetics: gender (p = 0.03), diagnosis (p = 0.05), smoking habit (p = 0.05), and co-medications such as valproic acid (p = 0.05) and anxiolytics (p = 0.01).. In conclusion, our results suggest that therapeutic drug monitoring of Olanzapine could be helpful to evaluate therapeutic efficacy and metabolic dysfunction in FEP patients treated with Olanzapine.

Topics: Adult; Antipsychotic Agents; Blood Glucose; Blood Pressure; Drug Monitoring; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Smoking; Treatment Outcome; Weight Gain

Non-compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first-episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group.. We evaluated a large sample of patients with FEP for 2 years to compare the time to all-cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded.. A total of 310 FEP patients were assessed across seven early intervention teams (mean age = 30.2 years; SD = 11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non-compliance. There were no differences in the relapse rates between different APs. Patients treated with long-acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs.. Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Humans; Olanzapine; Prescriptions; Psychotic Disorders; Risperidone

Guidelines for antipsychotic use in first-episode psychosis (FEP) recommend that medication be chosen initially on the basis of side effect profile with doses at the lower end of the range. Our objective was to describe the pattern of antipsychotic use in FEP over a period of 21 years in the context of changing clinical guidelines and the development of specialist early intervention in psychosis (EIP) services.. A community-based mental health service in South County Dublin (population 187 000) and a large private hospital.. Participants included 465 patients with FEP (146 from an epidemiological study (1995-1999) and 319 from a specialist EIP service (2005-2016)). Treatment with antipsychotic medication did not exceed 30 days at study entry.. This is a descriptive study of prescribing practices in the context of service development and changing guidelines.. First-generation antipsychotics were prescribed for 65% of the early cohort compared with 4.3% of the EIP cohort. Olanzapine was initially prescribed for 79.7% of EIP patients. Initial doses of medication were frequently low (≤50% British National Formulary (BNF) maximum) in both cohorts (71% and 78.6%). The demographic and clinical factors investigated did not influence the initial choice of antipsychotic medication significantly. Univariate logistic regression analysis suggested inpatient treatment setting was associated with a higher initial dose (>50% BNF maximum) of antipsychotic medication. Increasing dose requirements over the first month of engagement with an EIP service was associated with poorer global functioning at baseline, greater positive symptoms at baseline and the inpatient treatment setting. However, these associations were not seen in the multivariable model.. Second-generation antipsychotic prescribing predominates, but guidelines are often overlooked when choosing olanzapine notwithstanding lower initial dosages. EIP services should include proactive support for optimising medicines in line with evidence-based guidelines.

Topics: Antipsychotic Agents; Hospitalization; Humans; Olanzapine; Psychotic Disorders; Retrospective Studies

Topics: Aggression; Clozapine; Conduct Disorder; Haloperidol; Humans; Olanzapine; Psychotic Disorders; Schizophrenia; Violence

The COVID-19 outbreak has affected millions of people globally and it also has a huge psychological impact. The objective of this case report is to outline the possible effect of the COVID-19 pandemic to the content of delusions in patients with psychosis. Α 34-year-old male with no history of mental disorder, involuntarily hospitalized due to agitation and aggression towards others, experienced grandiose delusions, referential delusions and delusions of passivity. The content of all his delusions was related to the COVID-19 pandemic. His symptoms were not proven to be caused by any physical condition or substance use disorder. He was prescribed olanzapine 10mg bd and lorazepam 2,5mg td and demonstrated significant improvement with a complete subsidence of his symptoms within a week. He was discharged after a total of 13 days with an ICD-10 diagnosis of brief psychotic disorder. At his 6 months follow-up, he reported no psychiatric symptoms. Existing literature indicates a strong relationship between life experiences and the content of delusions. This case report highlights how the stressful life event of the COVID-19 outbreak affected the content of our patient's delusions.

Topics: Adult; Aggression; Anti-Anxiety Agents; Antipsychotic Agents; COVID-19; Delusions; Humans; Involuntary Commitment; Life Change Events; Lorazepam; Male; Olanzapine; Pandemics; Psychomotor Agitation; Psychotic Disorders; Stress, Psychological

The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES).. We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" remitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period.. Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR) = 4.186, 95% confidence interval (CI) = 2.082-8.416, p < 0.001) and older age (OR = 1.081, 95% CI = 1.026-1.138, p = 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019).. Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population.. ClinicalTrials.gov identifier: NCT01248195, https://clinicaltrials.gov/ct2/show/NCT01248195.

Topics: Adolescent; Adult; Antipsychotic Agents; Depression; Female; Humans; Male; Olanzapine; Psychotic Disorders; Schizophrenia; Treatment Outcome; Young Adult

Atypical or second-generation antipsychotics are used in the treatment of psychosis and behavioral problems in older persons with dementia. However, these pharmaceutical drugs are associated with an increased risk of stroke in such patients. In this study, we evaluated the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients (mean age >88 years). The results showed that the levels of dihydroceramides, very-long-chain ceramides, and lysophosphatidylcholines decreased in PBMCs of the risperidone-treated group compared with untreated controls. These findings were confirmed by in vitro assays using human THP-1 monocytes. The reduction in the levels of very-long-chain ceramides and dihydroceramides could be due to the decrease in the expression of fatty acid elongase 3, as observed in THP-1 monocytes. Moreover, risperidone disrupted lipid raft domains in the plasma membrane of PBMCs. These results indicated that risperidone alters phospholipid and sphingolipid composition and lipid raft domains in PBMCs of older patients, potentially affecting multiple signaling pathways associated with these membrane domains.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Cell Membrane; Ceramides; Female; Humans; Leukocytes, Mononuclear; Lipid Metabolism; Lysophospholipids; Male; Olanzapine; Psychotic Disorders; Risperidone; Sphingolipids

Topics: Administration, Oral; Adult; Antipsychotic Agents; Drug Interactions; Humans; Male; Olanzapine; Opioid-Induced Constipation; Opioid-Related Disorders; Psychotic Disorders; Psyllium; Treatment Failure

Gut microbiota plays an important role in host metabolism. Antipsychotic drugs can result in metabolic abnormalities. Probiotics may ameliorate the antipsychotic drug-induced metabolic abnormalities by regulating gut microbiota.. To determine whether Bifidobacterium intervention can ameliorate olanzapine-induced weight increase.. Enrolled patients were assigned to either the olanzapine or olanzapine plus Bifidobacterium group. The following were assessed: body weight, body mass index (BMI), appetite, latency to increased appetite, and baseline weight increase of more than 7%. All assessments were conducted at baseline and at 4, 8, and 12 weeks of treatment.. We enrolled 70 patients with schizophrenia or schizophrenic affective disorder, and 67 completed the study. Treatment for 4 weeks led to between-group differences in weight change (2.4 vs. 1.1 kg, p < 0.05) and BMI (0.9 vs. 0.4, p < 0.05). However, this difference disappeared at 8 and 12 weeks of treatment (both p > 0.05). The two groups did not differ in appetite increase at any time point (p > 0.05). The mean time from olanzapine initiation to appetite increase was also not significantly different between the two groups (t = 1.243, p = 0.220).. Probiotics may mitigate olanzapine-induced weight gain in the early stage of treatment and delay olanzapine-induced appetite increase.

Topics: Antipsychotic Agents; Appetite; Benzodiazepines; Bifidobacterium; Body Mass Index; Body Weight; Humans; Olanzapine; Psychotic Disorders

Topics: Administration, Oral; Adolescent; Cannabis; Humans; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Tomography, X-Ray Computed

Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration.. All patients (. At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia.. Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.

Topics: Adult; Benzodiazepines; Female; Humans; Male; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Substance-Related Disorders; Thiazoles

The relationship between a daily dose of olanzapine, its serum concentration, and the genotype of young nonsmoking men treated for schizophrenia or schizophreniform disorder was investigated in day-to-day clinical practice. Pharmacogenetics was also examined for the selected patients.. A total of 49 participants were recruited as in-patients at the Mental Health Research Center (Moscow, Russia). Inclusion criteria were patients who had been diagnosed with schizophrenia or schizoaffective disorder (following DSM-IV guidelines) and were being treated with OLZ. A prospective, observational, open-study design was implemented. In line with the literature, patients were only included if they attained steady-state OLZ concentrations lasting for at least 8 days. A liquid chromatographic-tandem mass spectrometric method was developed for analyzing OLZ in human serum. The single cytochrome P450 polymorphisms were genotyped using an amplifier real-time polymerase chain reaction system following standard protocols.. Evidence indicating that CYP2D6 polymorphism has a significant (P = 0.046) effect on the pharmacokinetics of olanzapine was obtained, confirming the beneficial effects of therapeutic drug monitoring (TDM) for olanzapine.. TDM should therefore be used as a standard care during olanzapine therapy. TDM is also useful in assessing adherence and may have a role in limiting olanzapine dosage geared at minimizing the risk of long-term toxicity.

Topics: Adult; Antipsychotic Agents; Chromatography, Liquid; Cytochrome P-450 CYP2D6; Drug Monitoring; Genotype; Humans; Male; Non-Smokers; Olanzapine; Prospective Studies; Psychotic Disorders; Real-Time Polymerase Chain Reaction; Schizophrenia; Tandem Mass Spectrometry; Young Adult

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Australia; Drug Prescriptions; Evidence-Based Medicine; Female; Guideline Adherence; Humans; Male; Olanzapine; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Retrospective Studies; Schizophrenia; Young Adult

Topics: Antipsychotic Agents; Delusions; Female; Humans; Middle Aged; Olanzapine; Pregnancy; Premenopause; Psychotic Disorders; Treatment Outcome

Antipsychotic medication, stress, gender, and age are factors that influence prolactin levels in patients with psychosis. The aim of the study was to investigate the level of prolactin response to antipsychotic treatment in acute patients, taking into account the total duration of psychosis.. The study was conducted on 170 acute patients with schizophrenia spectrum disorders and bipolar disorder. Subjects were divided into three subgroups according to the duration of the psychosis (less than 5 years, between 5 and 10 years and more than 10 years of disorder duration). The initial prolactin response under antipsychotic treatment was measured, while the severity of the psychiatric symptoms was assessed with the BPRS (Brief Psychiatric Rating Scale). Hyperprolactinemia was found in 120 (70.6%) patients, amongst which 80 (66.7%) were females and 40 (33.3%) were males. The average increase in prolactinemia was 2.46 times the maximum value in women, and 1.59 times in men. Gender (β = 0.27, p<0.0001), type of antipsychotic medication according to potency of inducing hyperprolactinemia (β = -0.23, p<0.003), and the duration of psychosis over 10 years (β = -0.15, p = 0.04) significantly predicted prolactin levels, when age, diagnosis, antipsychotic category (conventional/atypical/combinations of antipsychotics), and BPRS total scores were controlled for.. Prolactin levels in patients treated with antipsychotic medication appeared to depend on patients' gender, on the type of antipsychotic medication according to potency of inducing hyperprolactinemia, and on the duration of the psychosis. An increase in prolactin levels was associated with female gender, while the use of prolactin sparing antipsychotics and a duration of psychosis over 10 years were associated with lower prolactin levels.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Hyperprolactinemia; Inpatients; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Risperidone; Schizophrenia; Sex Factors; Time Factors

Topics: Adult; Adult Survivors of Child Abuse; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major; Desvenlafaxine Succinate; Eye Movement Desensitization Reprocessing; Female; Humans; Olanzapine; Paranoid Disorders; Psychotic Disorders; Stress Disorders, Post-Traumatic

A 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. He was sexually disinhibited with pressured speech and grandiose ideas. His behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. Investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neuroimaging and a lumbar puncture were normal. Initial screening for SARS-CoV-2 in the cerebrospinal fluid was negative although no validated assay was available. The patient's mental state remained abnormal following stepdown from intensive care. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid.

Topics: Adult; Affective Symptoms; Betacoronavirus; Cerebrospinal Fluid; Clonazepam; Coronavirus Infections; COVID-19; Diagnosis, Differential; Emergency Medical Services; Headache; Humans; Male; Neuroimaging; Olanzapine; Pandemics; Pneumonia, Viral; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Psychotropic Drugs; SARS-CoV-2; Treatment Outcome

Topics: Antipsychotic Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Health Personnel; Humans; Male; Middle Aged; Olanzapine; Pandemics; Pneumonia, Viral; Psychotic Disorders; SARS-CoV-2

The aim of this paper is to determine clinical factors related to hostility and disturbing and aggressive behaviour and to examine the effect of medication on these behaviours in FEP.. Data from phase I and II of the OPTiMiSE trial are used. Outcome measures are the hostility item of the Positive and Negative Syndrome Scale (PANSS P7) and the disturbing and aggressive behaviour domain of the Personal and Social Performance scale (PSP-D).. Moderate, severe or extreme hostility (PANSS P7 > 3) was present in 42 patients (9.4%). The PANSS P7 and PSP-D were low to moderate but significantly associated with the selected PANSS items: delusions, hallucinatory behaviour, excitement, tension, uncooperativeness, unusual thought content, impulsivity, and lack of judgement and insight. In a subsample of 185 patients (41.5%) with baseline PANSS P7 > 1, the PANSS P7 and PSP-D scores improved in the first 4 weeks of amisulpride treatment. This effect remained significant after controlling for baseline positive symptoms (PANSS P1-P6). No significant differences were found between olanzapine and amisulpride in the second phase of the trial.. Clinical risk factors such as poor impulse control, uncooperativeness and excitement could help clinicians in detecting and treating hostile and aggressive behaviour in FEP. Amisulpride could be an effective antipsychotic choice in the treatment of FEP patients who express hostile or aggressive behaviour. Future research is needed to compare the effects of amisulpride and olanzapine on hostility in FEP during the first weeks of treatment.

Topics: Antipsychotic Agents; Hostility; Humans; Olanzapine; Psychotic Disorders; Schizophrenia

Topics: Adult; Antipsychotic Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Delusions; Haloperidol; Humans; Involuntary Treatment; Lorazepam; Male; Olanzapine; Pandemics; Paranoid Behavior; Pneumonia, Viral; Psychotic Disorders; SARS-CoV-2; Social Isolation; Treatment Outcome

Topics: Antipsychotic Agents; Asymptomatic Infections; COVID-19; Delusions; Female; Hallucinations; Haloperidol; Humans; India; Olanzapine; Psychotic Disorders; Puerperal Disorders; Restraint, Physical; Self-Injurious Behavior; Trihexyphenidyl; Young Adult

Clozapine treatment may have beneficial effects on behavioral outcomes in psychotic disorders, including violent offending. Although clozapine and other antipsychotics have been linked to lower levels of violent behavior, these have been primarily in small selected samples, and population-based estimates have been limited and imprecise. We aimed to assess the effect of clozapine treatment on the rate of violent and nonviolent offending. We carried out a within-person mirror-image study of the Swedish population with linked prescription, hospitalization, and sociodemographic registers. Outcomes were violent, nonviolent, and overall offences occurring before and after clozapine, or olanzapine, initiation. Comparison of effects of clozapine and olanzapine on key variables was modeled with interaction terms. We found periods of mirror-image observation time with clozapine treatment were associated with a much lower rate of violent offending compared to periods before treatment (rate ratio [RR]: 0.13 (95% CI: 0.05, 0.34). Reductions in nonviolent offences were smaller in magnitude (RR: 0.37, 95% CI: 0.17, 0.80). There was a statistically greater rate reduction effect on violent offences for clozapine than olanzapine (RR for interaction: 4.84, 95% CI: 1.56, 14.86, P = .002). In patients with psychotic disorders, clozapine treatment is associated with a lower rate of violent offending compared to olanzapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Clozapine; Criminals; Drug Prescriptions; Female; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Registries; Sweden; Violence; Young Adult

Topics: Adult; Antipsychotic Agents; Delusions; Hallucinations; Humans; Male; Olanzapine; Psychotic Disorders

Topics: Depression; Depressive Disorder, Major; Humans; Olanzapine; Psychotic Disorders; Recurrence

Antipsychotic (AP) medications are the first line of treatment for schizophrenia. However, most conferr a risk of antipsychotic-induced weight gain (AIWG). The objective of this investigation was to conduct a genome-wide association study (GWAS) of AIWG, followed by comprehensive, post-GWAS approaches.. We investigated n = 201 schizophrenia or schizoaffective disorder patients of European and African American ancestry who were treated primarily with clozapine or olanzapine. We conducted a genome-wide association analysis for AIWG, defined primarily as a percentage of weight change from baseline.. When examining Europeans (n = 147), we noticed an association between rs62097526 (β = 0.39, p = 3.59 × 10-6, CADD = 2.213) variant, located downstream of the CIDEA gene, which is considered a risk factor for AIWG. In the entire sample, we observed a significant association between rs1525085 (β = 0.411, p = 3.15 × 10-9) variant of the DGKB gene and AIWG. The association was nominally significant in Europeans (β = 0.271, p = 0.002) and African Americans (β = 0.579, p = 5.73 × 10-5) with the same risk allele. Our top genes (p < 5 × 10-5) were enriched in the GWAS catalog for the risk of obesity and interacted with the known risk factors for obesity (G6PD) and diabetes (IRS1). In addition, these genes are targeted by miRNAs related to schizophrenia (mir-34a) and obesity (mir-19b). However, our polygenic risk score analyses did not provide support for major genetic overlap between obesity and the risk of AIWG.. In summary, we propose that the CIDEA and DGKB genes are risk factors for AIWG in transethnic populations. Additionally, our evidence suggests that the G6PD and IRS1 gene-related pathways might be involved in AIWG.

Topics: Adolescent; Adult; Antipsychotic Agents; Black or African American; Chronic Disease; Clozapine; Diacylglycerol Kinase; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Middle Aged; Multifactorial Inheritance; Obesity; Olanzapine; Psychotic Disorders; Schizophrenia; Weight Gain; White People; Young Adult

A man in his 40s was brought to the accident and emergency department in an acute psychotic state, 3 weeks after the European Union referendum results in the UK were declared. His mental health had deteriorated rapidly following the announcement of the results, with significant concerns about Brexit. He presented as agitated, confused and thought disordered. He had auditory hallucinations, and paranoid, referential, misidentification and bizarre delusions. He recovered completely within 2 weeks after a brief admission and treatment with olanzapine. He had experienced a similar episode of much less severity 13 years previously after major work related stress which resolved completely within a few days. He was experiencing stress related to work and family prior to the current episode which could potentially have been a contributory factor. Political events can act as major psychological stressors and have a significant impact on the mental health of people, especially those with a predisposition to develop mental illness.

Topics: Adjustment Disorders; Adult; Antipsychotic Agents; Delusions; Diagnosis, Differential; European Union; Hallucinations; Humans; Male; Olanzapine; Psychotic Disorders; Treatment Outcome; United Kingdom

In this commentary we discuss the findings of the recently published OPTiMiSE trial. In terms of design, important advantages of the trial are the naturalistic, open label set-up that allowed the authors to assess the efficacy of the sequential use of amisulpride followed by olanzapine and clozapine. In terms of results, we highlight the efficacy of amisulpride, while we disagree with the authors of OPTiMiSE when they claim clozapine should be tried in the clinic after one unsuccessful trial of amisulpride. We also show how the actual percentages of those complaining of sexual side effects during amisulpride use are higher than computed by the authors. On a general note, we suggest that whenever symptoms of patients allow it - and gradual improvement is observed - clinicians may wish to wait several weeks before considering a switch to amisulpride.

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Drug Monitoring; Drug Substitution; Humans; Olanzapine; Patient Selection; Psychotic Disorders; Schizophrenia

Topics: Antipsychotic Agents; Brain; Diagnosis, Differential; Female; Humans; Huntington Disease; Middle Aged; Olanzapine; Psychotic Disorders

Topics: Adolescent; Akathisia, Drug-Induced; Antipsychotic Agents; Aripiprazole; Autism Spectrum Disorder; Delusions; Dystonia; Female; Hallucinations; Humans; Hypnotics and Sedatives; Intellectual Disability; Lorazepam; Loxapine; Olanzapine; Paranoid Disorders; Psychotic Disorders; Quetiapine Fumarate; Tourette Syndrome

Topics: Antipsychotic Agents; Depression; Humans; Olanzapine; Psychotic Disorders; Recurrence

Early clinical response predicts symptomatic remission and recovery in the maintenance treatment phase of first-episode schizophrenia (FES). However, little is known about predictors of symptomatic remission during acute treatment of severely ill patients with FES. Here, we conducted a secondary analysis of our retrospective observational study, which examined response, remission and treatment-resistance rates in seriously ill patients with FES spectrum disorders involuntarily hospitalized and treated with algorithm-based pharmacotherapy.. We performed a retrospective chart review of 131 involuntarily admitted patients with schizophrenia or schizoaffective disorder. Our algorithm aimed to delay olanzapine treatment, standardize medications and suggest initiation of clozapine after failure of third-line antipsychotic treatment. The duration of each adequate antipsychotic treatment at an optimal dosage was 4 weeks or more. Remission was defined using the symptom-severity component of consensus remission criteria. A logistic regression model was applied to identify significant predictors of remission at discharge.. Overall, 74 patients (56%) were in remission at discharge. Non-remitters were hampered from becoming remitters mainly by the presence of negative symptoms. There were no differences in first-line antipsychotics, dosage of antipsychotics at time of response and adherence rates to algorithm-based pharmacotherapy between remitters and non-remitters. Shorter duration of untreated psychosis, favourable early response and less negative symptoms at baseline were identified as independent predictors of remission at discharge.. The importance of early intervention and specific and adequate treatments of negative symptoms is highlighted.

Topics: Administration, Oral; Adult; Algorithms; Antipsychotic Agents; Clozapine; Commitment of Mentally Ill; Drug Therapy, Combination; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Methotrimeprazine; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

Previous studies suggest immunological alterations in patients with first-episode psychosis (FEP). Some studies show that antipsychotic compounds may cause immunomodulatory effects. To evaluate the immunological changes and the possible immunomodulatory effects in FEP, we recruited patients with FEP (n = 67) and matched controls (n = 38), aged 18-40 years, from the catchment area of the Helsinki University Hospital and the City of Helsinki, Finland. Fasting peripheral blood samples were collected between 8 and 10 a.m. in 10 ml PAXgene tubes. We applied the NanoString nCounter in-solution hybridization technology to determine gene expression levels of 147 candidate genes reflecting activation of the immune system. Cases had higher gene expression levels of BDKRB1 and SPP1/osteopontin compared with controls. Of the individual medications used as monotherapy, risperidone was associated with a statistically significant upregulation of 11 immune system genes, including cytokines and cytokine receptors (SPP1, IL1R1, IL1R2), pattern recognition molecules (TLR1, TLR2 and TLR6, dectin-1/CLEC7A), molecules involved in apoptosis (FAS), and some other molecules with functions in immune activation (BDKRB1, IGF1R, CR1). In conclusion, risperidone possessed strong immunomodulatory properties affecting mainly innate immune response in FEP patients, whereas the observed effects of quetiapine and olanzapine were only marginal. Our results further emphasize the importance of understanding the immunomodulatory mechanisms of antipsychotic treatment, especially in terms of specific compounds, doses and duration of medication in patients with severe mental illness. Future studies should evaluate the response pre- and post-treatment, and the possible role of this inflammatory activation for the progression of psychiatric and metabolic symptoms.

Topics: Adolescent; Adult; Antipsychotic Agents; Cytokines; Female; Gene Expression; Gene Expression Regulation; Humans; Immunity, Innate; Immunologic Factors; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Receptors, Cytokine; Risperidone; Up-Regulation; Young Adult

Psychiatric care has entered a new era in which care for treatment-resistant psychiatric disorder has attained priority status. Addressing treatment resistance involves 1) alleviating symptoms and signs of the diagnostic condition, 2) returning the patient to functional capacity, and 3) preventing subsequent recurrence. This approach has achieved considerable momentum in regard to major depressive disorder, as evidenced by early recognition and timely treatment, medication augmentation strategies, mind-body training for the populace at large, effective and efficient psychotherapies, and new biomedical interventions. This report proposes a pharmacotherapy that may qualify for treatment-resistant psychosis, that is, high-dose olanzapine. Considerable thought, planning, resources, and effort would be necessary to test this intervention. This proposal includes suggestions for developing an affordable means of assessing this and future candidates for treatment-resistant psychosis.

Topics: Adult; Antipsychotic Agents; Humans; Male; Olanzapine; Psychotic Disorders; Treatment Failure

Agmatine is an endogenous NMDA (N-methyl-d-aspartate) antagonist which is synthesized from l-Arginine and described as a novel neurotransmitter. Agmatine is considered to play an important role for the development of schizophrenia. The aim of the present study is to explore the role of agmatine and l-arginine metabolism in medication-naive first-episode psychosis (FEP). We conducted a case control study in medication-naive patients with FEP (n = 40). The healthy volunteers with no family history of schizophrenia (n = 35) matched for age, gender and education level were selected as a control group. The patients were recruited to the study and followed up for 10 weeks. The plasma l-arginine, l-citrulline, l-ornithine and agmatine levels were measured using modified liquid chromatography/mass spectrometry. The plasma levels of l-arginine, l-citrulline and agmatine (p < 0.0001), but not l-ornithine and agmatinase (p > 0.05), were significantly increased during baseline analysis. After 10 weeks of treatment, plasma l-arginine and l-citrulline levels were still significantly increased (p < 0.05) while l-ornithine and agmatinase levels remained unchanged (p > 0.05). Conversely, plasma agmatine levels were significantly decreased after the treatment (p < 0.0001). Positive and negative predictive values of agmatine used for evaluating the diagnostic accuracy were 95.1% and 97.1%, respectively (p < 000.1). This is the first study of arginine metabolism and agmatine in medication-naive first-episode patients and provides evidence of increased levels of an endogenous NMDA antagonist which decreases following antipsychotic treatment.

Topics: Agmatine; Antipsychotic Agents; Arginine; Case-Control Studies; Citrulline; Female; Humans; Male; Olanzapine; Ornithine; Psychotic Disorders; Receptors, N-Methyl-D-Aspartate; Risperidone; Young Adult

Topics: Adult; Antipsychotic Agents; Ghrelin; Humans; Meta-Analysis as Topic; Olanzapine; Psychotic Disorders; Weight Gain

Topics: Antidepressive Agents; Antipsychotic Agents; Child; Female; Humans; Lithium Compounds; Mood Disorders; Olanzapine; Psychotic Disorders; Schizophrenia, Childhood

Erotomania is a delusional phenomenon in which patient believes that some celebrity is in love with her. It is associated with various psychiatric illnesses. We herein present a report of a young woman with erotomanic delusion diagnosed with recurrent depression, current episode being severe with psychotic features. A 22-year woman, previously treated for a depressive episode three years ago, was brought by the mother for evaluation. The woman presented with symptoms of depression for the past six months along with the delusion that famous singer SY is in love with her for the past two months. This has resulted in a gross decline in social and academic functioning. Psychometrics revealed Beck's depression inventory (BDI) score of 36 and brief psychiatric rating scale (BPRS) score of 41. A diagnosis of recurrent depression with current severe episode with psychotic features, was made at our psychiatric facility. This case report highlights that psychotic depression can present with a rare mood incongruent delusion of erotomanic content and accurate diagnosis and management require adequate knowledge about this phenomenon.

Topics: Bipolar Disorder; Delusions; Depression; Depressive Disorder; Emotions; Female; Fluoxetine; Humans; Love; Olanzapine; Psychotic Disorders; Young Adult

Despite benefits, atypical antipsychotics produce troublesome metabolic adverse effects particularly hyperphagia, weight gain, dyslipidemia, hyperglycemia and insulin resistance which further develop metabolic and cardiac complications. The animal models studied for antipsychotic-induced weight gain only focused on metabolic alteration in antipsychotics treated animals but none has considered psychosis as a predisposing factor which mimics the clinical condition. The present study was aimed to rule out the impact of pharmacologically induced psychosis-like phenotype on metabolic alterations induced by antipsychotics. Female BALB/c mice (weighing 18-23 g) exhibiting schizophrenia-like behavior after 5 days of MK-801 treatment (0.1 mg/kg, i.p.) were administered olanzapine (3 and 6 mg/kg, per oral) and risperidone (2 and 4 mg/kg, per oral) for six weeks. Acute as well as chronic treatment with olanzapine and risperidone treatment significantly reduced locomotion, increased feed intake and body weight in a time-dependent manner, which confirms the face validity of the animal model. Olanzapine (6 mg/kg) treatment significantly altered glucose and lipid homeostasis which was further accompanied by elevated levels of proinflammatory cytokines, ghrelin and leptin. These metabolic and biochemical alterations have demonstrated construct validity. Further, no significant difference was observed in the metabolic parameters in control and schizophrenic mice treated with olanzapine which confers that antipsychotic-induced metabolic alterations are independent of psychosis. Our study concluded that six-week olanzapine (6 mg/kg) treatment in control mice induced most of the clinically relevant physiological, biochemical and metabolic alterations (clinically relevant), that is independent of pharmacologically-induced psychosis.

Topics: Animals; Antipsychotic Agents; Body Weight; Female; Ghrelin; Hyperglycemia; Leptin; Mice; Mice, Inbred BALB C; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Combined Modality Therapy; Drug Therapy, Combination; Female; Humans; Medication Adherence; Olanzapine; Personality Disorders; Psychometrics; Psychotherapy; Psychotic Disorders; Relaxation Therapy; Young Adult

Antipsychotic drug use among children and adolescents is increasing, and there is growing concern about off-label use and adverse effects. The present study aims to investigate the incidence, psychiatric co-morbidity and pharmacological treatment of severe mental disorder in Norwegian children and adolescents.. We obtained data on mental disorders from the Norwegian Patient Registry on 0-18 year olds who during 2009-2011 were diagnosed for the first time with schizophrenia-like disorder (International Classification of Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled prescriptions for psychotropic drugs were obtained from the Norwegian Prescription Database.. A total of 884 children and adolescents (25.1 per 100 000 person years) were first time diagnosed with schizophrenia-like disorder (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years), or severe depressive episode with psychotic symptoms (3.3 per 100 000 person years) during 2009-2011. The most common co-morbid mental disorders were depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%), aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%).. When a severe mental disorder was diagnosed in children and adolescents, the patient was usually also prescribed antipsychotic medication. Clinicians must be aware of the high prevalence of depressive and anxiety disorders among early psychosis patients.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Comorbidity; Depressive Disorder, Major; Female; Humans; Incidence; Infant; Male; Mental Disorders; Norway; Olanzapine; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Some atypical antipsychotics are associated with metabolic side effects, which are risk factors for gestational diabetes. The authors examined the risk of developing gestational diabetes associated with the continuation of treatment with aripiprazole, ziprasidone, quetiapine, risperidone, and olanzapine during pregnancy compared with discontinuation of these antipsychotic drugs.. Nondiabetic pregnant women who were linked to a live-born infant and enrolled in Medicaid (2000-2010) and who received one or more prescriptions dispensed for an antipsychotic drug during the 3 months before pregnancy were included in the analyses. Among 1,543,334 pregnancies, some expectant mothers at baseline were receiving treatment with aripiprazole (N=1,924), ziprasidone (N=673), quetiapine (N=4,533), risperidone (N=1,824), or olanzapine (N=1,425). For each antipsychotic drug, women with two or more dispensings ("continuers") were compared with women with no dispensings ("discontinuers") during the first half of pregnancy. A generalized linear model and propensity-score stratification were used to obtain absolute and relative risks of developing gestational diabetes, with adjustment for confounders.. Women who continued antipsychotic treatment during pregnancy generally had higher comorbidity and longer baseline antipsychotic use. The crude risk of developing gestational diabetes among continuers compared with discontinuers, respectively, was 4.8% and 4.5% for aripiprazole, 4.2% and 3.8% for ziprasidone, 7.1% and 4.1% for quetiapine, 6.4% and 4.1% for risperidone, and 12.0% and 4.7% for olanzapine. The adjusted relative risks were 0.82 (95% CI=0.50-1.33) for aripiprazole, 0.76 (95% CI=0.29-2.00) for ziprasidone, 1.28 (95% CI=1.01-1.62) for quetiapine, 1.09 (95% CI=0.70-1.70) for risperidone, and 1.61 (95% CI=1.13-2.29) for olanzapine.. Compared with women who discontinued use of an atypical antipsychotic medication before the start of pregnancy, women who continued treatment with olanzapine or quetiapine had an increased risk of gestational diabetes that may be explained by the metabolic effects associated with these two drugs.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Diabetes, Gestational; Female; Humans; Olanzapine; Piperazines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Thiazoles; Young Adult

This case report aims to highlight the challenges faced by mental health clinicians in managing complex medical and psychiatric presentation, with a particular interest in intravenous (IV) olanzapine use outside the emergency department (ED) and intensive care unit setting.. There is no current prescribing guideline regarding the use of IV olanzapine for acute agitation associated with schizophrenia and bipolar disorder. Most of the literature available regarding the use of IV olanzapine has originated from studies performed in the ED setting, with the majority of studies reporting a favourable efficacy and safety profile for IV olanzapine. Further research on the utilization of IV olanzapine in the general medical ward is required. Until more data is available, use of IV olanzapine in the acute arousal setting on a general medical ward remains off-label.

Topics: Administration, Intravenous; Antipsychotic Agents; Humans; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Psychotic Disorders

We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD).. Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination.. The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change.. Continuation of acute treatment was associated with stability of remission.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Blood Glucose; Body Weight; Cholesterol; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Placebos; Psychotic Disorders; Remission Induction; Sertraline; Triglycerides

Topics: Antipsychotic Agents; Edema; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders

Topics: Amisulpride; Clozapine; Humans; Olanzapine; Psychotic Disorders; Schizophrenia

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Humans; Olanzapine; Psychotic Disorders; Schizophrenia

Topics: Amisulpride; Antipsychotic Agents; Clozapine; Humans; Olanzapine; Psychotic Disorders; Schizophrenia

Antipsychotics produce electroencephalogram (EEG) modifications and increase the risk of epileptic seizure. These modifications remain sparsely studied specifically for atypical antipsychotics. In this context, our study focuses on EEG modifications associated with atypical strict antipsychotic monotherapies.. Electroencephalogram recordings of 84 psychiatric patients treated with atypical antipsychotics in strict monotherapy (clozapine, n = 22; aripiprazole, n = 22; olanzapine, n = 17; risperidone, n = 9; quetiapine, n = 8; risperidone long-acting injection, n = 4; and paliperidone long-acting injection, n = 2) were analyzed. The modifications were ranked according to both slowing and excitability scores.. Electroencephalogram modifications (in 51 subjects, 60.71%) were graded according to 4 stages combining general slowing and sharp slow waves and/or epileptiform activities. The presence of sharp or epileptiform activities was significantly greater for clozapine (90.9%) compared with other second-generation antipsychotics (aripiprazole, 50%; olanzapine, 58.8%; quetiapine, 37.5%; risperidone, 44.4%). Age, duration of disease progression, and diagnosis were not associated as risk factors. Electroencephalogram modifications were associated with lower doses for treatment with quetiapine but not for specific antipsychotics. Electroencephalogram modifications and severe excitability were associated with higher chlorpromazine equivalent doses.. Atypical antipsychotics (clozapine, aripiprazole, quetiapine, olanzapine, and risperidone) induce EEG modifications, and these are significantly greater for clozapine and appear dependent on chlorpromazine equivalent dose. No encephalopathy was observed in these antipsychotic monotherapies, whatever dose.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Cerebral Cortex; Clozapine; Depressive Disorder, Major; Electroencephalography; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

A positive correlation between antipsychotic-induced weight gain (AIWG) and the antagonist effect of antipsychotic drugs at the histamine H1 receptor (HRH1) as well as the agonist effect at the histamine H3 receptor (HRH3) in the brain has been consistently demonstrated. We investigated the potential impact of single-nucleotide polymorphisms (SNPs) in HRH1 and HRH3 genes on AIWG.. We analysed 40 tagSNPs in HRH1 (n = 34) and HRH3 (n = 6) in schizophrenia/schizoaffective disorder patients (n = 193) primarily treated with clozapine or olanzapine for up to 14 weeks. Linear regression was used to evaluate the association between SNPs and AIWG, with baseline weight and treatment duration as covariates.. In HRH1, a nominal association of rs7639145 with AIWG was observed in patients of European ancestry treated with either clozapine or olanzapine (P. The current study suggests that SNPs in HRH1 and HRH3 may not have a major role in AIWG.

Topics: Adult; Antipsychotic Agents; Clozapine; Female; Humans; Male; Olanzapine; Polymorphism, Single Nucleotide; Psychotic Disorders; Receptors, Histamine H1; Receptors, Histamine H3; Schizophrenia; Weight Gain

The relationship between daily dose, serum concentrations, and clinical outcomes of olanzapine as well as the influencing factors thereof in children and adolescents treated for different psychiatric disorders were investigated in daily clinical practice. In addition, it was examined whether the current recommended therapeutic range (TR) for adult patients with psychotic disorders is valid for minors.. The Competence Network for Therapeutic Drug Monitoring (www.tdm-kjp.com) routinely collects demographic and clinical outcome data as well as serum concentrations of children and adolescents treated with psychotropics. The therapeutic effect is documented using the Clinical Global Impression Scale subscale for Global Improvement. Adverse drug reactions (ADRs) are assessed using the Udvalg for Kliniske Undersogelser-Side Effect Rating Scale.. One hundred fifteen patients (mean age = 15.9 years; range = 10.4-18.8 years; 40.9% male) were included. The majority (72.1%) was cotreated with other psychotropic drugs. A positive medium linear relationship (r = 0.619; P < 0.001) between olanzapine dose (mean = 11.64 mg/d) and serum concentration (mean = 35.65 ng/mL) was found with a marked interindividual variability of serum concentrations. Neither relationship between olanzapine serum concentration and treatment response (clinical benefit documented in 80%) nor ADRs (documented in 53.3%, in 7.5% judged as severe) was detected. Most of the patients with psychotic and eating disorders (68.8% and 71.8%, respectively) had an olanzapine serum concentration within the TR suggested for adults.. There are several limitations of this study because of the naturalistic design, and our results should therefore be interpreted with caution. As most of the patients showed a clinical benefit under olanzapine concentrations within the TR for adults and only a minority had severe ADRs, it is reasonable to conclude a similar TR for children, adolescents, and adults.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Olanzapine; Psychotic Disorders; Psychotropic Drugs

Studies on treatment outcome in mania had been many. A few studies from the west address the issue of outcome in mood congruent and mood incongruent manias. None could be found from India.. To compare the treatment response in three groups of patients with mania- Nonpsychotic, psychotic with mood congruent and psychotic with mood incongruent features.. All consecutive manic patients admitted during 2013 to 2014, meeting inclusion and exclusion criteria were taken up. 28 patients with nonpsychotic Mania, 10 with mood congruent psychotic symptoms (MIC-) & 12 with mood incongruent psychotic features (MIC+). Diagnosis was confirmed using SCID. Mood stabilizers and Olanzapine or equivalent doses of antipsychotics were administered. Semi structured proforma was used for Socio Demographic & clinical details. YMRS, HDRS, Semi structured proforma to assess response (ISBD recommendations), CGI -BP & SAPS were used. Last 5 tools to assess the response to treatment at every 2 weeks, for 8 weeks.. Statistical Package for Social Sciences, version 17.0 was used.. These three groups did not show statistically significant difference in the socio-demographic variables. Severity of Mania was higher in Psychotic Mania. Psychotic Manias (group 2 and 3 combined) showed longer response time. However, mood incongruent psychotic manias when compared against the other 2 groups clubbed together did not differ significantly.. All patients were from a tertiary referral centre and were hospitalized. Majority of them had a past history. The sample sizes were small. Treatment could not be fully matched.. Our findings support the view that psychotic manias on the whole take significantly longer time than mania without psychotic symptoms to respond, and also scored higher on indices of severity. Mood Incongruent Psychotic Manias and Mood Congruent Psychotic Manias did not differ in severity & response time.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Follow-Up Studies; Humans; India; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Young Adult

Topics: Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antipsychotic Agents; Catatonia; Diagnosis, Differential; Female; Humans; Methylprednisolone; Olanzapine; Plasmapheresis; Psychotic Disorders

Olanzapine, an atypical antipsychotic, is associated with glucoregulatory abnormalities, but the nature of this link is not fully elucidated. This is the first olanzapine oral glucose tolerance test (oGTT) study to consider treatment dose and duration, and to compare complementary indices respectively assessing insulin sensitivity (Matsuda index) and resistance (homeostasis model assessment).. Body mass index (BMI), body composition, plasma lipids, and oGTT were measured in olanzapine-treated nondiabetic patients with DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder (n = 35).. While only one previously undiagnosed participant met diabetes criteria based on fasting plasma glucose alone (≥126 mg/dL), seven were diagnosed with oGTT (2-hr plasma glucose ≥200 mg/dL). Multiple regression analyses revealed that the Matsuda index correlated with BMI (p < 0.0001) and plasma triglycerides (p = 0.01), but not with age, olanzapine dose, olanzapine treatment duration, or plasma cholesterol. Homeostasis model assessment and fasting plasma glucose correlated with triglycerides only (p < 0.0001 for both).. Our data suggest that BMI and triglycerides may be implicated in olanzapine-related glucoregulatory abnormalities. The lack of correlation between glucoregulatory abnormalities and olanzapine dose or treatment duration suggests preexisting metabolic disturbances and/or disturbances arising early in the course of treatment. Clinicians prescribing antipsychotics should consider oGTT, especially in patients with obesity and/or hypertriglyceridemia.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Dose-Response Relationship, Drug; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin Resistance; Male; Middle Aged; Olanzapine; Psychotic Disorders; Regression Analysis; Schizophrenia; Triglycerides

Parkinson's disease psychosis (PDP) is a frequent complication of idiopathic Parkinson's disease (iPD) with significant impact on quality of life and association with poorer outcomes. Atypical antipsychotic drugs (APDs) are often used for the treatment of PDP; however, their use is often complicated by adverse drug reactions (ADRs). In this study, we present patients with PDP who were treated with the most commonly used atypical antipsychotic agents and review their respective ADRs.. A retrospective study was carried out to include a total of 45 patients with iPD who visited a movement disorders clinic between 2006 and 2015. All PDP patients treated with atypical APDs were included in the analysis for their specific ADRs.. Forty-five iPD patients (mean age of onset: 62.67 ± 9.86 years) were included, of those 10 patients had psychosis (mean age of onset: 76.80 ± 4.61 years). Of the 45 patients, 22.2% were found to have psychotic symptoms, of whom 70% had hallucinations, 20% had delusions, and 10% illusions. Seventy percent of psychotic symptoms occurred after ten or more years from diagnosis of iPD. PDP patients were treated with quetiapine, olanzapine, and risperidone separately or in combination, all of which were found to have certain ADRs.. This study was limited by its retrospective study design and small sample size and with likely selection bias.. The prevalence of PDP is relatively high in older patients with iPD. The uses of the currently available atypical APDs in this patient population are often complicated by ADRs. The selective 5-HT

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Olanzapine; Outcome and Process Assessment, Health Care; Parkinson Disease; Piperidines; Psychological Techniques; Psychotic Disorders; Quality of Life; Retrospective Studies; Urea

Topics: Adolescent; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Antipsychotic Agents; Autoantibodies; Clonazepam; Diagnosis, Differential; Female; Humans; Olanzapine; Psychotic Disorders; Receptors, N-Methyl-D-Aspartate

A 50-year-old man with known multidrug resistant coexistent focal and generalised epilepsy was commenced on ethosuximide, with normalisation of his electroencephalogram and cessation of absence seizures. Within 3 weeks, he developed a rapidly worsening paranoid psychosis with visual and olfactory hallucinations. A month after the cessation of ethosuximide and concurrent treatment with olanzapine, his psychosis resolved and permitted reinitiation of ethosuximide at a lower dose without recurrence of psychotic symptoms.

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Diagnosis, Differential; Electroencephalography; Epilepsy; Ethosuximide; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders

Populations exposed to humanitarian emergencies are particularly vulnerable to mental health problems, including new onset, relapse and deterioration of psychotic disorders. Inadequate care for this group may lead to human rights abuses and even premature death. The WHO Mental Health Gap Action Programme Intervention Guide (mhGAP-IG), and its adaptation for humanitarian settings (mhGAP-HIG), provides guidance for management of mental health conditions by non-specialised healthcare professionals. However, the pharmacological treatment of people with non-affective psychosis who do not improve with mhGAP first-line antipsychotic treatments is not addressed. In order to fill this gap, UNHCR has formulated specific guidance on the second-line pharmacological treatment of non-affective psychosis in humanitarian, non-specialised settings.. Following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, a group of international experts performed an extensive search and retrieval of evidence on the basis of four scoping questions. Available data were critically appraised and summarised. Clinical guidance was produced by integrating this evidence base with context-related feasibility issues, preferences, values and resource-use considerations.. When first-line treatments recommended by mhGAP (namely haloperidol and chlorpromazine) are not effective, no other first-generation antipsychotics are likely to provide clinically meaningful improvements. Risperidone or olanzapine may represent beneficial second-line options. However, if these second-line medications do not produce clinically significant beneficial effects, there are two possibilities. First, to switch to the alternative (olanzapine to risperidone or vice versa) or, second, to consider clozapine, provided that specialist supervision and regular laboratory monitoring are available in the long term. If clinically relevant depressive, cognitive or negative symptoms occur, the use of a selective serotonin reuptake inhibitor may be considered in addition or as an alternative to standard psychological interventions.. Adapting scientific evidence into practical guidance for non-specialised health workers in humanitarian settings was challenging due to the paucity of relevant evidence as well as the imprecision and inconsistency of results between studies. Pragmatic outcome evaluation studies from low-resource contexts are urgently needed. Nonetheless, the UNHCR clinical guidance is based on best available evidence and can help to address the compelling issue of undertreated, non-affective psychosis in humanitarian settings.

Topics: Antipsychotic Agents; Benzodiazepines; Guidelines as Topic; Humans; Olanzapine; Psychotic Disorders; Relief Work; Risperidone; United Nations

To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D. Open-label prospective PET [. A tertiary care center outpatient setting.. Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months.. Gradual reduction in their olanzapine or risperidone daily dose of up to 40%.. Clinical and cognitive assessments, and [. Reducing the antipsychotic dose resulted in an increase in D. Our findings suggest that optimizing D

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cognitive Dysfunction; Corpus Striatum; Female; Humans; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Raclopride; Receptors, Dopamine D2; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Delusions; Female; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Parasitic Diseases; Psychotic Disorders; Referral and Consultation; Shared Paranoid Disorder

Thioredoxin is a serum antioxidant that has been investigated in the etiology of schizophrenia. The aim of this study is investigating the relationship between serum thioredoxin levels and cognitive functions in acute psychotic episode and remission state patients with schizophrenia; and examining whether there were differences between patients using clozapine and other atypical antipsychotics; including risperidone, olanzapine and amisulpride. This research was performed in schizophrenia patients hospitalized with acute psychotic episode (n=57), reevaluated patients after the initiation of treatment (mean 16 weeks) (n=46), and healthy controls (n=41). Positive and Negative Syndrome Scale, Clinic Global Impressions Scale, Neuropsychologic test battery to assess cognitive performance, and serum thioredoxin levels measured by ELISA were used in this research. Serum thioredoxin levels were highest in acute psychotic episode, lower in the remission state and the lowest in healthy controls. Significant correlation has been established between serum thioredoxin levels and Trail Making Test-A performance in remission state patients. In conclusion, serum thioredoxin levels were increased in acute psychotic episode and decreased in remission state, and its relationship with attention is worth to consider in schizophrenia patients.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Sulpiride; Thioredoxins; Young Adult

This study aims to determine the optimal tolerability dose ranges of risperidone (RIS) and olanzapine (OLZ) administered during schizophrenia maintenance phase.. Two-year continuation rates of prescription at discharge were examined using a retrospective cohort study method. Adult patients with schizophrenia and related psychotic disorders, receiving antipsychotic monotherapy with RIS or OLZ at discharge, were included. The primary outcome measures were the time to treatment discontinuation and 2-year continuation rates at 4 modal dose ranges of each drug. We estimated the optimal tolerability dose ranges by comparing the continuation rates at various modal doses.. Of 648 patients, 344 received RIS and 304 received OLZ. The RIS 2-year continuation rates at 4 daily modal dose ranges were significantly different (0.5-2.5 mg: 46.0%, 3.0-5.0 mg: 40.0%, 5.5-7.5 mg: 30.0%, and 8.0-10.0 mg: 28.0%), with the difference favoring RIS at lower doses (0.5-5.0 mg) more than higher doses (5.5-10.0 mg). In contrast, there were no significant differences among OLZ 4 modal dose ranges (2.5-7.5 mg: 49.1%, 10.0-15.0 mg: 42.6%, 17.5-22.5 mg: 40.9%, and 25.0-30.0 mg: 39.0%). The time to treatment discontinuation significantly favored OLZ over RIS. However, it did not significantly differ between RIS and OLZ at lower doses.. It is suggested that the optimal tolerability dose range during maintenance treatment is 0.5 to 5.0 mg/d for RIS and 2.5 to 30 mg/d for OLZ, and that RIS at lower doses is comparable with OLZ at lower doses.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Psychotic Disorders; Retrospective Studies; Risperidone; Schizophrenia; Young Adult

Objective Despite many women suffering from psychosis in their childbearing years, limited data exist about the use of atypical antipsychotic agents in pregnancy. Atypical antipsychotic agents are often used to treat bipolar disorder, instead of lithium or valproate because of the known teratogenicity of those agents. As well, atypical antipsychotics are often prescribed in anxiety disorders and depression. This study sought to describe pregnancy outcomes for women prescribed atypical antipsychotics during pregnancy. Methods This retrospective review included all cases treated by Auckland Maternal Mental Health services in which atypical antipsychotic agents were utilized during pregnancy over three years. Results Over the three years, 45 pregnant women were prescribed atypical antipsychotic agents, most commonly quetiapine or olanzapine. Two-fifths (40%) were diagnosed with bipolar disorder and almost one-third (31%) with a psychotic disorder. Two-thirds (64%) were prescribed multiple psychotropic medications during their pregnancy. Instrumental delivery rates were elevated at 38%. A minority (13%) of the women developed gestational diabetes mellitus. Although 7% of infants were born premature, all were born after 35 weeks. Two major malformations were noted, similar to baseline community rates. Conclusions This naturalistic study adds to the limited literature about treatment with atypical antipsychotic agents in pregnancy, though not adequately powered to detect small differences in malformations or obstetrical outcomes. It also highlights the myriad of indications for which pregnant women are prescribed atypical antipsychotics, and the multiple other risk factors seen in this population.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Maternal Health Services; Mental Health Services; Olanzapine; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Young Adult

Topics: Benzodiazepines; Female; Humans; Middle Aged; Olanzapine; Prednisolone; Psychotic Disorders; Tuberous Sclerosis

Ischemic colitis (IC) is an uncommon adverse event associated with antipsychotic agents, more commonly found with phenothiazine drugs and atypical neuroleptics such as clozapine. The risk of developing ischemic colitis increases when anticholinergic drugs are associated. We report the case of a 38-year-old woman with a history of schizoaffective disorder who had been on chronic quetiapine for 3 years, and presented to the ER because of diarrhea for 5 days. Four months previously, olanzapine had been added to her psychiatric drug regimen. Physical examination revealed abdominal distension with abdominal tympanic sounds and tenderness. Emergency laboratory tests were notable for increased acute phase reagents. Tomography revealed a concentric thickening of the colonic wall in the transverse, descending and sigmoid segments, with no signs of intestinal perforation. Colonoscopy demonstrated severe mucosal involvement from the sigmoid to the hepatic flexure, with ulcerations and fibrinoid exudate. Biopsies confirmed the diagnosis of ischemic colitis. The only relevant finding in her history was the newly added drug to her baseline regimen. An adverse effect was suspected because of its anticholinergic action at the intestinal level, and the drug was withdrawn. After 6 months of follow-up clinical, laboratory and endoscopic recovery was achieved. Therefore, antipsychotic medication should be considered as a potential cause of ischemic colitis, particularly atypical antipsychotics such as clozapine and olanzapine; despite being uncommon, this adverse event may result in high morbidity and mortality.

Topics: Adult; Benzodiazepines; Colitis, Ischemic; Colonoscopy; Female; Humans; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Tomography, X-Ray Computed

Topics: Adult; Age of Onset; Benzodiazepines; Central Nervous System Cysts; Female; Humans; Olanzapine; Prosencephalon; Psychotic Disorders; Treatment Outcome

We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depression. Contrary to knowledge of cytochrome p450 interactions sertraline increased apparent clearance of olanzapine by 30%. Here we examined the pharmacokinetics of sertraline in the same population. Existing studies suggest that sertraline apparent clearance is significantly increased in male subjects and suggested an age/sex interaction.. We studied subjects undergoing combination of sertraline/olanzapine treatment for psychotic depression in the Study of the Pharmacotherapy of Psychotic Depression. Nonlinear mixed effect modelling software was used to examine the sertraline pharmacokinetics, evaluating age, sex, race, and olanzapine exposure as covariates.. Eighty-seven subjects (median age 62 years, 28 male subjects, 11 African-Americans) provided 138 samples for sertraline concentration. Olanzapine exposure had a 14.8-fold range. A one compartment model with combined residual error described the sertraline concentration data adequately. Half-life and sex effect on sertraline apparent clearance (males averaging 50% higher (p < 0.005); 96.6 l/h vs 64.8 in female subjects) were similar to previous reports. No other covariate (age, race or olanzapine exposure) had a significant impact on apparent clearance, and no age/sex interaction emerged.. Sertraline pharmacokinetics were similar to historical descriptions in populations not taking antipsychotics. Unlike our unexpected finding that sertraline increases olanzapine apparent clearance, olanzapine exposure had no impact on sertraline pharmacokinetics. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Female; Half-Life; Humans; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Sertraline; Sex Factors

Early antipsychotic response predicts outcomes for psychotic patients, but recent evidence suggests that this may not be true for patients treated with olanzapine. In this study, we assessed the predictive value of early response to olanzapine or haloperidol in 75 antipsychotic-naive, first-episode psychosis inpatients. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Young Mania Rating Scale (YMRS). Regression analyses were used to determine whether improvement at week 2 or week 3 predicted improvement at hospital discharge. The majority of patients in both groups experienced a decrease in symptom severity of ≥50% at week 2. In the haloperidol group, week 2 improvement predicted improvement at discharge for all measures except the HAM-A. In the olanzapine group, week 2 improvement only predicted improvement at discharge for HAM-D scores. However, week 3 improvement in the olanzapine group predicted improvement at discharge for all measures except the HAM-A. Olanzapine non-responders at week 3 (but not week 2) benefited from having olanzapine switched to another antipsychotic. These results suggest that a 2 week trial of haloperidol is sufficient to predict treatment outcomes, while a 3 week trial is required for olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Haloperidol; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Prognosis; Psychiatric Status Rating Scales; Psychotic Disorders; Young Adult

We present a patient with topiramate-induced psychosis who developed alternative psychosis following temporal lobectomy. The number of surgical candidates for temporal lobectomy is increasing as is the frequency of psychiatric co-morbidities. Preoperative planning should take account of these psychiatric co-morbidities. In particular, precautions should be taken when antiepileptic drug-induced psychosis occurs, as this could predict the occurrence of alternative psychosis following lobectomy.

Topics: Adult; Anterior Temporal Lobectomy; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Female; Fructose; Humans; Neuroprotective Agents; Olanzapine; Psychoses, Substance-Induced; Psychotic Disorders; Topiramate

A major medical problem for patients undergoing electroconvulsive therapy (ECT) is the occurrence of postictal agitation (PIA). This phenomenon is associated with confusion and disorientation that can have severe clinical implications for the safety of the patient and health care professionals. Many different pharmacological strategies have been used to prevent PIA. We present data on 40 patients who suffered from PIA after a course of ECT and evaluate the prophylactic use of orally disintegrating olanzapine in the prevention of PIA in subsequent ECT treatments.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Treatment Outcome; Young Adult

The aim was to determine distribution and trends in the outpatient utilization of antipsychotics to evaluate the rationality of antipsychotic drug prescribing during the ten year period.. The epidemiological method of descriptive and analytical observation was used. Data on drug utilization from Zagreb Municipal Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the World Health Organization Anatomical-Therapeutic-Chemical methodology. The ratio of typical versus atypical antipsychotics served as an indicator on assessing the rationality of the utilization. Data on the use of anticholinergics in the treatment of neuroleptic side effects were also included.. Outpatient utilization of antipsychotics showed a declining pattern from 14.17 in 2001 to 8.42 DDD/TID in 2010. The utilization of atypical antipsychotics increased by 60% (from 3.68 to 5.89 DDD/TID), while the utilization of typical antipsychotics decreased by 76% (from 10.49 to 2.53 DDD/TID). The drugs showing the largest increase were olanzapine (from 1.21 to 2.78 DDD/TID) and quetiapine (from 0 to 0.68 DDD/TID). The typical/atypical antipsychotic ratio changed from 1:0.4 in 2001 to 1:2.3 in 2010. A 2.3-fold decrease was recorded in the utilization of anticholinergics (from 2.05 to 0.91 DDD/TID).. Total consumption of neuroleptics significantly decreased. A decrease was also recorded in the utilization of anticholinergics. Study results pointed to two favorable features, i.e. low use of typical antipsychotics and the ratio of typical and atypical antipsychotics. Implementation of the new clinical guidelines for nervous system disorders and updating of the list of reimbursable drugs with the addition of new ones contributed to the observed improvement in the prescribing patterns during the study period. Using the WHO ATC/DDD methodology and rationality indicators in the assessment of trends in the outpatient utilization of psychopharmaceuticals over a ten-year period proved efficient in the evaluation of prescribing rationality.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cholinergic Antagonists; Croatia; Drug Prescriptions; Drug Utilization; Humans; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Diabetes Mellitus; Diagnostic and Statistical Manual of Mental Disorders; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Statistics as Topic; Triglycerides

In 2004, the American Diabetes Association (ADA) released treatment guidelines recommending metabolic screening for children and adolescents before and after initiation of second-generation antipsychotics. Prior studies showed that the guidelines coincided with a small increase in glucose testing of children and adults but had limited follow-up. This study sought to evaluate changes in metabolic screening of children initiating second-generation antipsychotics around the time of the 2004 guidelines and in the following eight years.. Study patients (N=52,407) were identified in a large nationwide commercial insurance claims database for the period January 1, 2003, through December 31, 2011. The study population was a cohort of nondiabetic new users of second-generation antipsychotics who were ages 5-18. Glucose and HbA1c tests completed before and after second-generation antipsychotic initiation were identified with Current Procedural Terminology-4 codes. Metabolic screening was also examined by second-generation antipsychotic agent prescribed and psychiatric diagnosis.. The proportion of patients receiving a glucose test preinitiation increased from 17.9% in 2003 to 18.9% in 2004, and testing postinitiation increased from 14.7% to 16.6% in the same period. The slight increase in glucose testing was not sustained; the proportion tested dropped in the following years before rising again in 2008. Glucose screening was most common for patients taking aripiprazole. Patients with a diagnosis of hyperkinetic disorder were less likely to be tested. HbA1c testing was less frequent but had a similar usage pattern.. The small improvement in metabolic screening immediately after the 2004 ADA guidelines were issued was not sustained. Overall, metabolic screening rates remained suboptimal throughout the study period.

Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Anxiety Disorders; Aripiprazole; Benzodiazepines; Blood Glucose; Child; Child, Preschool; Cohort Studies; Conduct Disorder; Databases, Factual; Depressive Disorder; Diabetes Mellitus; Female; Glycated Hemoglobin; Guideline Adherence; Humans; Hyperkinesis; Male; Mass Screening; Mental Disorders; Olanzapine; Piperazines; Practice Guidelines as Topic; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Thiazoles

Topics: Adolescent; Affective Disorders, Psychotic; Antipsychotic Agents; Antithyroid Agents; Benzodiazepines; Bipolar Disorder; Delirium; Diagnosis, Differential; Female; Graves Disease; Humans; Methimazole; Olanzapine; Psychotic Disorders; Radionuclide Imaging; Thyroid Gland; Thyroidectomy

Guidelines for the treatment of psychoses recommend antipsychotic monotherapy. However, the rate of antipsychotic polytherapy has increased over the last decade, reaching up to 60% in some settings. Studies evaluating the costs and impact of antipsychotic polytherapy in the health system are scarce.. To estimate the costs of antipsychotic polytherapy and its impact on public health costs in a sample of subjects with psychotic disorders living in residential facilities in the city of Sao Paulo, Brazil.. A cross-sectional study that used a bottom-up approach for collecting costs data in a public health provider's perspective. Subjects with psychosis living in 20 fully-staffed residential facilities in the city of Sao Paulo were assessed for clinical and psychosocial profile, severity of symptoms, quality of life, use of health services and pharmacological treatment. The impact of polytherapy on total direct costs was evaluated.. 147 subjects were included, 134 used antipsychotics regularly and 38% were in use of antipsychotic polytherapy. There were no significant differences in clinical and psychosocial characteristics between polytherapy and monotherapy groups. Four variables explained 30% of direct costs: the number of antipsychotics, location of the residential facility, time living in the facility and use of olanzapine. The costs of antipsychotics corresponded to 94.4% of the total psychotropic costs and to 49.5% of all health services use when excluding accommodation costs. Olanzapine costs corresponded to 51% of all psychotropic costs.. Antipsychotic polytherapy is a huge economic burden to public health service, despite the lack of evidence supporting this practice. Great variations on antipsychotic costs explicit the need of establishing protocols for rational antipsychotic prescriptions and consequently optimising resource allocation. Cost-effectiveness studies are necessary to estimate the best value for money among antipsychotics, especially in low and middle income countries.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brazil; Cost-Benefit Analysis; Cross-Sectional Studies; Drug Therapy, Combination; Female; Humans; Male; Mental Health Services; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Public Health; Quality of Life

A 25-year-old Thai woman with ovarian germ cell tumour presented with behavioural changes after receiving an intensive dose of neoadjuvant chemotherapy with bleomycin, etoposide and cisplatin, for a relapse. Her initial symptoms of mood fluctuation and insomnia were noticed while hospitalised for the third cycle, and became more severe. She was very irritable, highly distracted and forgetful. She exhibited flights of ideas and hyperactivity, including compulsive shopping. She also had paranoid ideations, auditory hallucinations, and thoughts of being wealthy and close to the prime minister. She was not depressed. She was diagnosed with axis I psychotic disorder not otherwise specified. The incremental dosage of olanzapine from 5 to 20 mg/day was given but failed to control her psychotic symptoms during the first week, and was therefore switched to risperidone. At 4 mg/day, her symptoms were dramatically controlled. This novel evidence suggests the rare possibility of an association between chemotherapy and the development of psychotic attacks.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antipsychotic Agents; Benzodiazepines; Chemotherapy, Adjuvant; Female; Humans; Neoplasm Recurrence, Local; Neoplasms, Germ Cell and Embryonal; Olanzapine; Ovarian Neoplasms; Psychotic Disorders; Risperidone; Treatment Outcome

Altered expression of transcription factor specificity protein 4 (SP4) has been found in the postmortem brain of patients with psychiatric disorders including schizophrenia and bipolar disorder. Reduced levels of SP4 protein have recently been reported in peripheral blood mononuclear cells in first-episode psychosis. Also, SP4 levels are modulated by lithium treatment in cultured neurons. Phosphorylation of SP4 at S770 is increased in the cerebellum of bipolar disorder subjects and upon inhibition of NMDA receptor signaling in cultured neurons. The aim of this study was to investigate whether SP4 S770 phosphorylation is increased in lymphocytes of first-episode psychosis patients and the effect of lithium treatment on this phosphorylation.. A cross-sectional study of S770 phosphorylation relative to total SP4 immunoreactivity using specific antibodies in peripheral blood mononuclear cells in first-episode psychosis patients (n = 14, treated with lithium or not) and matched healthy controls (n = 14) by immunoblot was designed. We also determined the effects of the prescribed drugs lithium, olanzapine or valproic acid on SP4 phosphorylation in rat primary cultured cerebellar granule neurons.. We found that SP4 S770 phosphorylation was significantly increased in lymphocytes in first-episode psychosis compared to controls and decreased in patients treated with lithium compared to patients who did not receive lithium. Moreover, incubation with lithium but not olanzapine or valproic acid reduced SP4 phosphorylation in rat cultured cerebellar granule neurons.. The findings presented here indicate that SP4 S770 phosphorylation is increased in lymphocytes in first-episode psychosis which may be reduced by lithium treatment in patients. Moreover, our study shows lithium treatment prevents this phosphorylation in vitro in neurons. This pilot study suggests that S770 SP4 phosphorylation could be a peripheral biomarker of psychosis, and may be regulated by lithium treatment in first-episode psychosis.

Topics: Adolescent; Adult; Animals; Antipsychotic Agents; Benzodiazepines; Cells, Cultured; Cross-Sectional Studies; Female; Humans; Lithium; Male; Models, Biological; Neurons; Olanzapine; Phosphorylation; Pilot Projects; Psychotic Disorders; Rats; Serine; Sp4 Transcription Factor; Valproic Acid; Young Adult

Topics: Adult; Antipsychotic Agents; Antithyroid Agents; Benzodiazepines; Female; Graves Disease; Humans; Methimazole; Olanzapine; Periventricular Nodular Heterotopia; Psychotic Disorders

New Zealand's Pharmaceutical Management Agency (PHARMAC) manages the list of medicines available for prescribing with government subsidy, within a fixed annual medicines budget. PHARMAC achieves this through a mix of pricing strategies including reference pricing. In 2011, PHARMAC applied generic reference pricing to olanzapine tablets.. This study sought to evaluate change in outcome measures of patients switching from originator to generic olanzapine consequent to the introduction of the policy.. A retrospective study using national health data collections was conducted. Outcome measures included medicines indicators (change in dosage, concomitant therapy and treatment cessation), health care service indicators (use of emergency departments, hospitals and specialist services), surveillance reports of adverse events, and mortality.. Subsequent to the removal of funding for originator brand olanzapine tablets, 99.7% of patients meeting the inclusion criteria switched to using generic olanzapine. Limited case reports of suspected therapeutic loss were received in the study time period. No increase in use of additional oral or injectable antipsychotic medication was observed after switching, nor any increase in other unique, non-antipsychotic prescription items. However, a high incidence of multiple switching between available brands was found. No net impact of switching brands on health service utilisation or mortality was found.. The study shows that a switch can be made safely from originator olanzapine to a generic brand, and suggests that switching to generics should generally be viewed more positively. Generic reference pricing achieves considerable savings and, as a pricing policy, could be applied more widely.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cost Savings; Drug Substitution; Drugs, Generic; Female; Humans; Male; Medical Audit; New Zealand; Olanzapine; Psychotic Disorders; Retrospective Studies

The pharmacological self-management of novel psychoactive substance (NPS)-induced psychopathological consequences represents a fast growing phenomenon. This is facilitated by the frequent sharing of NPS intake experiences online and by the ease of access to a range of psychotropic medications from both the online and street market. Olanzapine is anecdotally reported by Web users to be the most frequent self-prescribed medication to cope with NPS-induced psychoses. Hence, we aimed here at better assessing olanzapine use/misuse for this purpose.. Exploratory qualitative searches of 163 discussion fora/specialized websites have been carried out in four languages (English, German, Spanish, and Italian) in the time frame November 2012-2013.. Most NPS-users allegedly self administer with olanzapine to manage related psychotic crises/"bad trips". This may be typically taken only for a few days, at a dosage range of 5-50 mg/day.. Only a few research studies have formally assessed the effectiveness of olanzapine and indeed of other second-generation antipsychotics to treat NPS-induced psychosis. Olanzapine was suggested here from a range of pro drug websites as being the "ideal" molecule to terminate "bad trips". Health professionals should be informed about the risks related to olanzapine misuse.

Topics: Antiemetics; Benzodiazepines; Female; Humans; Male; Olanzapine; Online Systems; Psychotic Disorders; Psychotropic Drugs; Substance-Related Disorders

To identify the frequency and characteristics of eating disorders in patients with schizophrenia treated with second generation antipsychotics.. A sample included 56 patients (48 women and 8 men, mean age 28 ± 4.5 years) with schizophrenia and schizoaffective disorder. Patients received risperidone, quetiapine and olanzapine. The study employed clinical-anamnestic, endocrinological methods and assessment of eating behavior with DEBQ (The Dutch Eating Behavior Questionnaire). All of the patients had extra Body mass or obesity: extra Body mass of the 1st grade was found in 18 patients (BMI<30 kg/m²) and obesity grade 2-3 in 38 patients (BMI>30 kg/m²).. Authors identified different types of eating disorders: external, restrictive and emotiogenic as well as the relationship of their prevalence and severity with sex, drug, presence and grade of obesity. Based on these. we developed recommendations for management of patients treated with second generation antipsychotics.. Цель исследования - установление частоты и особенностей пищевого поведения у больных шизофренией при лечении антипсихотиками второго поколения. Материал и методы. Выборку составили 56 пациентов, 48 женщин и 8 мужчин, с диагнозами 'шизофрения' и 'шизоаффективное расстройство'. Их средний возраст был 28±4,5 года. Больные лечились рисперидоном, кветиапином и оланзапином. Исследование включало клинико-анамнестический, эндокринологический методы и тестирование стереотипа пищевого поведения с помощью специального опросника DEBQ. У всех обследованных были выявлены избыточная масса тела или ожирение: избыточная масса тела 1-й степени - у 18 пациентов (ИМТ до 30 кг/м2) и ожирение 2-3-й степени - у 38 (ИМТ более 30 кг/м2). Результаты и заключение. Выявлены разные типы нарушений пищевого поведения - экстернальный, ограничительный и эмоциогенный и зависимость их частоты и выраженности от пола, лечебного препарата, наличия и степени ожирения. На основе полученных данных были сформулированы рекомендации в отношении тактики ведения пациентов, находящихся на терапии антипсихотиками второго поколения.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Feeding and Eating Disorders; Female; Humans; Male; Obesity; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Young Adult

We present the case of a 19-year-old who developed psychotic symptoms after exposure to a potentially rabid animal and post-exposure prophylactic treatment. This case serves to remind physicians to fully explore the possibility of a nonpsychiatric origin of de novo psychotic symptoms and provides indirect evidence in favor of the possible involvement of the immune system in the development of psychotic disorders.

Topics: Adult; Anti-Anxiety Agents; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Clonazepam; Diagnosis, Differential; Dibenzothiazepines; Female; Haloperidol; Humans; Lorazepam; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Rabies; Rabies Vaccines; Young Adult

In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units.. The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population.. The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death.. Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System; Denmark; Depression, Chemical; Drug Overdose; Electrocardiography; Female; Hospitals, Psychiatric; Humans; Inpatients; Long QT Syndrome; Male; Neuroleptic Malignant Syndrome; Olanzapine; Psychotic Disorders; Retrospective Studies; Risk Assessment

Depot antipsychotic injections are an important tool for the management of patients with schizophrenia who have difficulty with adherence to oral medication. However, pain and discomfort at the injection site can be a potential impediment to the use of these long-acting formulations. We report here the results of a pooled analysis of injection site-related adverse events (AEs) collected during treatment with the olanzapine long-acting injection (olanzapine LAI).. Unsolicited injection site-related AEs were pooled from 7 olanzapine LAI clinical trials conducted in patients between March 2001 and December 2010. All patients had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of schizophrenia or schizoaffective disorder and were between the ages of 18 and 75. Doses ranged from 45 to 405 mg olanzapine LAI, and injection intervals were 2, 3, or 4 weeks. Events were evaluated for severity, timing, possible risk factors, and outcome. A criterion of p < .05 for statistical significance was used for all tests.. A total of 1752 patients received at least 1 olanzapine LAI injection. Of these, 92 patients (5.3%) reported at least 1 injection site-related AE, with "pain" being the most common type (2.9%). Most events were mild (81.4%) and the median duration was 3 days. Four patients (0.2%) discontinued due to injection site-related AEs. Dose volume and body mass index did not appear to affect the probability of injection site-related AEs. However, patients who experienced a post-injection delirium/sedation syndrome event (n = 37) were more likely to have or have had an injection site-related AE at some time during the study. Incidence of injection site-related AEs appeared to decrease over time. In 94.2% of the injection site-related AEs, no specific treatment or concomitant medication was reported; in 9 cases, patients received pharmacologic treatment for reaction, mass, abscess, rash, or pain.. Injection site-related AEs with olanzapine LAI were generally mild. The incidence and nature of these injection site-related AEs were generally similar to those occurring during treatment with other injectable antipsychotics.. ClinicalTrials.gov ID; URL: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Incidence; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Pain; Psychotic Disorders; Risk Factors; Schizophrenia; Young Adult

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Electroconvulsive Therapy; Emergency Services, Psychiatric; Fatigue Syndrome, Chronic; Female; Humans; Olanzapine; Psychotic Disorders; Suicidal Ideation; Treatment Outcome

Neuroleptic malignant syndrome (NMS) can be caused by various drugs. We report a case of a 60-year-old woman who presented with high-grade fever, muscular rigidity, tachycardia, tachypnoea and altered sensorium along with seizures. She had been taking olanzapine for the past 2 years for psychosis. For the last month valproate was added to her treatment. Her blood investigations revealed hyponatraemia and raised serum ammonia and creatinine phosphokinase (CPK) levels. In view of hyperthermia, muscular rigidity, autonomic disturbances, altered mental status and raised CPK, a diagnosis of NMS was made. Valproate could have probably precipitated NMS; although the patient was taking antipsychotics for a long time, it was only with the addition of valproate that she developed these symptoms. Raised serum ammonia levels also indicated the presence of valproate toxicity. Seizures were probably due to electrolyte disturbances. Offending drugs were withdrawn. The patient improved with treatment by dopamine agonist and other supportive treatments.

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Benzothiazoles; Dopamine Agonists; Drug Therapy, Combination; Female; Fluid Therapy; Humans; Levetiracetam; Lorazepam; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Piracetam; Pramipexole; Psychotic Disorders; Valproic Acid

Although the number of patients admitted for psychiatric emergency care is increasing according to data from various countries, there are no large-scale studies assessing clinical emergency practice and in several countries no national guidelines have been published concerning emergency care in psychiatry. The aim of our study was to assess practice related to emergency care of agitated-psychotic patients in Hungary.. Anonymous survey questionnaire with questions related to care of an agitated patient showing psychotic symptoms was dispatched to 210 institutions providing psychiatric care in Hungary in 2013.. The overwhelming majority of the 155 participating clinicians would use haloperidol (92.9%) and benzodiazepines (81.3%), 74.8% in a dual combination. 18.7% would apply monotherapy and 5.2% a triple combination of medications. 59.4% would use i.v. and 23.9% i.m. therapy, and 9% would apply the combination of these two. In case of failure of first-line therapy, 76.8% of participants would repeat the previous medication.. The aim of our study was to assess emergency interventions in psychiatry focusing on different psychopharmacological approaches. Our results provide a cross-sectional view on current practice in Hungary, and therefore may contribute to outlining practice-coherent guidelines and also provide the opportunity for a comparison with international trends.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Clopenthixol; Droperidol; Drug Prescriptions; Drug Therapy, Combination; Emergency Treatment; Female; Haloperidol; Humans; Hungary; Male; Middle Aged; Olanzapine; Piperazines; Practice Patterns, Physicians'; Promethazine; Psychiatry; Psychomotor Agitation; Psychotic Disorders; Quinolones; Surveys and Questionnaires

Antipsychotics are effective in treating schizophrenia symptoms. However, the use of clozapine and olanzapine in particular are associated with significant weight gain. Mouse and human studies suggest that the protein kinase cAMP-dependent regulatory type II beta (PRKAR2B) gene may be involved in energy metabolism, and there is evidence that it is associated with clozapine's effects on triglyceride levels. We aimed at assessing PRKAR2B's role in antipsychotic-induced weight gain in schizophrenia patients.. DNA samples from adult schizophrenia or schizoaffective disorder patients of mixed ancestry were genotyped, and weight gain was assessed. We analyzed 16 tag single-nucleotide polymorphisms across the PRKAR2B gene in a Caucasian subset treated either with clozapine or olanzapine (N = 99). Linear regression based on an additive model was performed with the inclusion of relevant covariates.. Normalized per cent weight change was analyzed, revealing that patients with the minor allele at rs9656135 had a mean weight increase of 4.1%, whereas patients without this allele had an increase of 3.4%. This association is not significant after correcting for multiple testing.. Because of limited power, PRKAR2B's role in antipsychotic-induced weight gain is unclear, but biological evidence suggests that PRKAR2B may be involved. Further research in larger sample sizes is warranted.

Topics: Adolescent; Adult; Aged; Alleles; Antipsychotic Agents; Benzodiazepines; Clozapine; Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; Female; Genetic Predisposition to Disease; Genotyping Techniques; Humans; Linkage Disequilibrium; Male; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; Psychotic Disorders; Schizophrenia; Weight Gain; White People; Young Adult

Olanzapine is an atypical antipsychotic drug, whose chronic use has been associated with the development of potential adverse effects such as weight gain and cardio-metabolic disorders like hypercholesterolemia and diabetes. To circumvent these side effects, the controlled release of olanzapine is a promising approach to improve adhesion of schizophrenic patients to the treatment. An innovative strategy to prolong drug release consists of loading the drug into biodegradable polymeric lipid-core nanocapsules. In this study, particle size, polydispersity, pH, zeta potential and drug loading of olanzapine-loaded lipid-core nanocapsules were analyzed. Weight gain, biochemical parameters and antipsychotic activity were evaluated in male Wistar rats. The lipid-core nanocapsules had a mean diameter of 156 +/- 13 nm, a polydispersity index lower than 0.1, a pH value of 6.12 +/- 0.14, zeta potential of -17 +/- 2.40 mV and encapsulation efficiency close to 100%. The animals treated with olanzapine-loaded lipid-core nanocapsules showed significantly lower weight gain (63.4 +/- 19.6 g) and total cholesterol levels (66.2 +/- 3.5 g x dl(-1)), compared to those administered with free olanzapine (112.6 +/- 10.3 g and 90.4 +/- 2.4 g x dl(-1)), respectively. Additionally, a more prolonged antipsychotic action was observed in the stereotyped behavior animal model induced by D,L-amphetamine, which affords to conclude that nanoencapsulation is a promising alternative to treat schizophrenic patients.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Diffusion; Drug Synergism; Male; Mental Disorders; Nanocapsules; Olanzapine; Particle Size; Psychotic Disorders; Rats; Rats, Wistar; Surface Properties; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Female; Humans; Movement Disorders; Olanzapine; Psychotic Disorders; Young Adult

Lack of insight is predominant in schizophrenia though the causes are still unclear. The present study was carried on to investigate the effect of three Second Generation Antipsychotics (SGAs) and Haloperidol on insight and the associations among different clusters of symptoms and insight. Fifty-five patients have been recruited at the moment of pharmacological switch needed for psychotic exacerbation, from other antipsychotic drugs to Olanzapine, Aripiprazole, Ziprasidone and Haloperidol. Patients have been followed for 6 months and evaluated at baseline, after 3 months and after 6 months. Regarding the insight improvement, all SGAs resulted more effective than Haloperidol, while no difference was detected among different SGAs. Concerning psychopathology, all SGAs showed a better efficacy than Haloperidol, positive symptoms apart. All SGAs showed a similar efficacy on all domains, except for negative symptoms which resulted less responsive to ziprasidone and haloperidol. An association between improvement of insight and psychopathology was detected. Furthermore, insight appears to be related to psychopathology severity, particularly to negative symptoms. However, the observed different effectiveness of Ziprasidone on negative symptoms and insight suggests that these psychopathological features may be not strictly related and, thus, they may be sustained by different psychopathological processes.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Awareness; Benzodiazepines; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Piperazines; Psychotic Disorders; Quinolones; Schizophrenia; Schizophrenic Psychology; Thiazoles

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Chemical Analysis; Breast Feeding; Female; Humans; Infant; Milk, Human; Olanzapine; Pregnancy; Psychotic Disorders; Schizophrenia, Paranoid; Umbilical Veins

Antipsychotics frequently cause changes in glucose metabolism followed by development of weight gain and/or diabetes. Recent findings from our group indicated an influence of glucose-related genes on this serious side effect. With this study, we aimed to extend previous research and performed a comprehensive study on the peroxisome proliferator-activated receptor gamma (PPARG) and the adiponectin (ADIPOQ) genes. In 216 schizophrenic patients receiving antipsychotics for up to 14 weeks, we investigated single-nucleotide polymorphisms in or near PPARG (N=24) and ADIPOQ (N=18). Statistical analysis was done using ANCOVA in SPSS. Haplotype analysis was performed in UNPHASED 3.1.4 and Haploview 4.2. None of the PPARG or ADIPOQ variants showed significant association with antipsychotic-induced weight gain in our combined sample or in a refined subsample of patients of European ancestry treated with clozapine or olanzapine after correction for multiple testing. Similarly, no haplotype association could withstand multiple test correction. Although we could not find a significant influence of ADIPOQ and PPARG on antipsychotic-induced weight gain, our comprehensive examination of these two genes contributes to understanding the biology of this serious side effect. More research on glucose metabolism genes is warranted to elucidate their role in metabolic changes during antipsychotic treatment.

Topics: Adiponectin; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Haplotypes; Humans; Male; Middle Aged; Olanzapine; Overweight; Polymorphism, Single Nucleotide; PPAR gamma; Psychotic Disorders; Weight Gain; White People; Young Adult

Topics: Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Drug Combinations; Drug Resistance; Humans; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Psychotic Disorders

The complex aetiology of most mental disorders involves gene-environment interactions that may operate using epigenetic mechanisms particularly DNA methylation. It may explain many of the features seen in mental disorders including transmission, expression and antipsychotic treatment responses. This report deals with the assessment of DNA methylation in response to an antipsychotic drug (olanzapine) on brain (cerebellum and hippocampus), and liver as a non-neural reference in a rat model. The study focuses on the Cadherin/protocadherins encoded by a multi-gene family that serve as adhesion molecules and are involved in cell-cell communication in the mammalian brain. A number of these molecules have been implicated in the causation of schizophrenia and related disorders.. The results show that olanzapine causes changes in DNA methylation, most specific to the promoter region of specific genes. This response is tissue specific and involves a number of cadherin genes, particularly in cerebellum. Also, the genes identified have led to the identification of several pathways significantly affected by DNA methylation in cerebellum, hippocampus and liver. These included the Gα12/13 Signalling (p = 9.2E-08) and Wnt signalling (p = 0.01) pathways as contributors to psychosis that is based on its responsiveness to antipsychotics used in its treatment.. The results suggest that DNA methylation changes on the promoter regions of the Cadherin/protocadherin genes impact the response of olanzapine treatment. These impacts have been revealed through the identified pathways and particularly in the identification of pathways that have been previously implicated in psychosis.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Cadherins; Cerebellum; DNA Methylation; Hippocampus; Immunoprecipitation; Liver; Male; Olanzapine; Promoter Regions, Genetic; Psychotic Disorders; Rats, Sprague-Dawley

Schizophrenia is a chronic illness with a progressive course that can be marked by resistance to antipsychotic treatment. This can make therapeutic support challenging for the practitioner, with results that are partial and unsatisfactory. In the literature, treatment with high-dose olanzapine (>20mg/day) appears to be a good alternative to clozapine, the gold standard for treatment-resistant schizophrenia. In the present observational prospective study, we studied the clinical and biological profiles of patients treated with olanzapine doses up to 100mg/day. In total, 50 patients were clinically and biologically assessed. We found a linear relationship between oral dose and serum concentration (Pearson's r=0.83, p<0.001) with effects of tobacco (p<0.05) and of coffee and tea consumption (p<0.01). Tolerance seemed to be good regardless of dose. No link was found between concentration and efficiency. Despite a nonexhaustive assessment of pharmacokinetic parameters, not least pharmacogenetic data (e.g., genotyping of cytochrome P450-1A2 or glycoprotein P Abcb1a), pharmacokinetic aspects alone cannot account for why the disease may sometimes be resistant to 20mg of olanzapine but respond to higher doses. A nuclear imaging study exploring brain occupancy by high-dose olanzapine, coupled with the abovementioned pharmacokinetic assessment, may prove a relevant experimental paradigm for studying the pathophysiological mechanisms of resistant schizophrenia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Resistance; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Treatment Outcome; Young Adult

Anecdotal evidence tends to favour olanzapine in the treatment of hallucinations in patients with schizophrenia spectrum disorders; however, no conclusive evidence is available on this topic. We report here a clinical case in which a 46-year-old man, suffering from a schizoaffective disorder (depressed type), underwent olanzapine treatment (20 mg/day). After inducing an initial amelioration, the patient had a re-exacerbation of auditory hallucinations and a clinical and psychosocial worsening, which subsided after olanzapine discontinuation. Olanzapine may induce a worsening of hallucinations in a psychotic disorder with substantial affective component and therefore its use should be carefully evaluated in such cases.

Topics: Antipsychotic Agents; Benzodiazepines; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Recurrence

In Italy, even though olanzapine has been discouraged for treatment of behaviour disorders in older patients affected by dementia, some physicians chose to prescribe for them. In response to this situation, the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) promulgated a cautionary note.. This study examined epidemiological indices for olanzapine prescriptions between 2004 and 2007 in the Marche Region of central Italy and in its provinces, to assess physician compliance with the AIFA note, and to determine whether there were differences in drug prescription between populations of the same territory, or differences based on gender or age group.. Our analyses revealed high olanzapine use among young men and mature women, suggesting that these groups are most prone to psychotic symptoms. Analysis revealed that olanzapine prescription in elderly patients was reduced in some provinces, in line with the AIFA note.. Prudent use of olanzapine prescription, in compliance with the AIFA note, was noted throughout the Region. Furthermore, this work offers details that may be useful in future studies of adverse drug reactions.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Drug Prescriptions; Female; Humans; Italy; Male; Middle Aged; Olanzapine; Pharmacoepidemiology; Psychotic Disorders; Young Adult

The association between the use of antipsychotics and diabetes mellitus (DM) is still unclear, as depicted by several conflicting reports. Our study aims to assess the risk of DM in new users of antipsychotics.. Our nested case-control study used the Quebec Health Insurance Board databases. People in the source cohort were DM-free and had initiated an antipsychotic treatment. Subjects were cohort members who initiated an antidiabetic or had a diagnosis of DM during their follow-up period. Three variables were used to assess antipsychotic exposure: the antipsychotic used (any typical, clozapine, olanzapine, quetiapine, risperidone, or more than 1 drug); the number of 30-day periods of use; and antipsychotic use at index date (current or past). A paired multivariate logistic regression model was used to calculate adjusted odds ratios.. Among the 88 467 people included in the cohort, 6109 subjects with DM were identified and were matched to 61 090 control subjects. New users of quetiapine were less likely to develop DM than new users of typical antipsychotics (OR, 0.89; 95% CI 0.81 to 0.99). The risk of DM was not statistically different across the atypical antipsychotics. A longer exposure to any antipsychotic (for each 30-day period, OR 1.009; 95% CI 1.006 to 1.011) and current use of antipsychotics (OR 1.26; 95% CI 1.17 to 1.36) were associated with DM.. These results suggest that metabolic parameters of people exposed to antipsychotics should be monitored, irrespective of the drug taken, among the drugs available at the time of analysis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Clozapine; Cohort Studies; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Time Factors; Young Adult

Topics: Administration, Oral; Adolescent; Antipsychotic Agents; Arthritis, Juvenile; Benzodiazepines; Delayed-Action Preparations; Exanthema; Humans; Male; Olanzapine; Psychotic Disorders

Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine) have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines), particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results.. A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS) in new users of risperidone compared to new users of FGAs.. After controlling for potential confounders (demographics, comorbidity and medication use), risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22-0.67; 0.45, 95% CI: 0.28-0.73; 0.50, 95% CI: 0.33-0.77; 0.65, 95% CI: 0.45-0.94, respectively). At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54-1.05.. In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Canada; Dementia; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Phenothiazines; Proportional Hazards Models; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone

With this paper we aimed to describe a case of a woman affected by Anorexia Nervosa Restricting subtype (AN-R) with delusional symptoms, visual hallucinations and severe body image distortion. We discussed the main AN diagnosis and whether delusional symptoms could be related to severity of AN describing also the use of olanzapine in such a severe clinical condition. The use of olanzapine was found to be effective to reduce both delusions and body distortions, and to improve compliance to treatments. We found a severe delusional symptomatology with mystic, omnipotence and persecution features. The psychotic structure seemed preceding the eating disorder and was also found to be worsened by emaciation. The use of antipsychotic helped reducing delusional symptoms and improving compliance to treatments. Finally, the dynamically oriented therapeutic relationship helped the patient to gain weight and to achieve a full recovery from psychotic symptoms.

Topics: Adult; Anorexia Nervosa; Antipsychotic Agents; Benzodiazepines; Body Image; Female; Humans; Olanzapine; Patient Compliance; Psychotic Disorders; Treatment Outcome

Treatment guidelines suggest antipsychotic monotherapy in the treatment of psychosis. 20-40% of patients take combination therapy in clinical practice due to inadequate treatment response to monotherapy. First-generation antipsychotic monotherapy was ineffective in case of our patient who had severe psychotic symptoms. Switching to a second generation antipsychotic had partial therapeutic effect, the severe psychotic condition was persistent. For this reason the therapy was changed to olanzapine-clozapine combination. Due to this combination the patient's psychotic symptoms disappeared. He was able to maintain the relationship with psychiatrist. During this therapy we observed good compliance, no more drug abuse and no relapse.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Marijuana Abuse; Medication Adherence; Olanzapine; Psychotic Disorders; Treatment Outcome

Metabolic abnormalities are serious adverse effects of atypical antipsychotic treatment. This study aims to determine the effects of adjunctive aripiprazole on metabolic profiles among patients receiving treatment with atypical antipsychotics, and to examine whether these effects are different from that of pre-existing atypical antipsychotics. In the 8-week open-label trial, aripiprazole was added to patients who were receiving treatment with atypical antipsychotics and had experienced weight gain or dyslipidemia. The dosage of pre-existing atypical antipsychotics was fixed, while the dosage of aripiprazole ranged from 5 to 20 mg/day during the study period. Metabolic profiles, including body weight, body mass index (BMI), plasma levels of fasting glucose, triglycerides, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and adiponectin, were measured at baseline and week 8. As a result, 43 subjects (16 males and 27 females, mean age: 37.8±10.8 years) completed the study. The pre-existing antipsychotics were olanzapine (n=12), risperidone (n=19), quetiapine (n=6) and amisulpiride (n=6). The mean dosage of adjunctive aripiprazole was 9.9±3.2 mg/day. After the aripiprazole-augmented regimen for 8 weeks, patients treated with olanzapine had significant decreases in body weight, BMI and triglyceride levels, and had significant increases in adiponectin levels. For patients treated with other atypical antipsychotics, none of the metabolic parameters significantly changed after administering aripiprazole. In conclusion, aripiprazole-augmented treatment might be beneficial for the metabolic regulation of patients being treated with a stable dose of olanzapine, but not for those treated with other atypical antipsychotics. A long-term, randomized, double-blind controlled design is suggested to confirm these findings.

Topics: Adiponectin; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Female; Humans; Lipids; Male; Middle Aged; Obesity; Olanzapine; Piperazines; Prospective Studies; Psychotic Disorders; Quinolones; Weight Gain

Acute catatonia is a non-specific, relatively frequent syndrome, which manifests itself through characteristic motor signs that enables its diagnosis. It occurs in association with mood disorders, psychotic disorders and several somatic or toxic diseases. Its short-term prognosis is of paramount importance. Without effective treatment, it is associated with high mortality. Despite the vital risk inherent in this disorder, it is not recognized as an independent diagnostic category by international rankings, which makes its diagnostic detection difficult and consequently does not allow adequate therapeutic care. However, if benzodiazepines and electroconvulsive therapy have proved effective in the treatment of acute catatonia, the role of atypical antipsychotics remains controversial. In fact, despite the progress made by the DSM-IV-TR and CIM 10 by the recognition of the etiologic diversity of catatonia, we deplore the absence to date of a consensus on clinical management and therapy of catatonia, which constitutes a source of confusion for practitioners in their approach to catatonic patients. To illustrate the difficulty in supporting these patients, we report here a clinical vignette.. Mr. M. aged 21, without psychiatric history, has shown a functional acute psychotic episode involving a delirious and hallucinatory syndrome associated with a marked catatonic dimension. Olanzapine was initiated at a dose of 10mg/d on the nineth day of hospitalization; the clinical picture was complicated by a malignant catatonia justifying the halt of olanzapine and the institution, in intensive units, of 15mg per day of lorazepam. After 72hours, the patient has not responded to this treatment. ECT was expected, but the patient died on the 12th day.. This case raises a threefold question: the crucial issue of immediate vital prognosis, that of the truthfulness of the positive diagnosis of this psychotic table and finally the issue of therapeutic care, primarily the well-founded or otherwise use of an atypical antipsychotic for the treatment of this type of psychotic disorder. For Mr. M., the clinical diagnosis that he has shown, according to the DSM IV-TR, is brief psychotic disorder "temporary diagnosis". This diagnosis - brief psychotic disorder - does not actually allow for a specific clinical approach to this type of psychotic table. The immediate vital prognosis inherent in the catatonic dimension may not be properly evaluated and the therapeutic conduct may miss the application of the specific treatment of the catatonic syndrome. The proper diagnosis for this type of psychotic disorder would be "catatonia" as proposed by Taylor and Fink, instead of "brief psychotic disorder" if the international rankings have included this disorder as a separate and independent diagnosis. The identification by international rankings of the catatonic syndrome as an independent diagnostic category seems essential for clinicians to allow: its clinical detection, the establishment of a syndromic diagnosis of catatonic disorder, appropriate prognostic evaluation and finally, the application of a suitable therapeutic strategy. Conventional treatment, benzodiazepine- and/or ECT-based, can solve the catatonic episode in a few days, irrespective of its etiology and its severity. Moreover, while all authors agree that conventional antipsychotics may induce a catatonic state or worsen a preexisting catatonia into a malignant catatonia and should thus be avoided for catatonic patients or with prior catatonic episodes, recent data from the literature emphasize the frequent and successful use of atypical antipsychotics, including olanzapine, in various clinical forms of benign catatonia. However, our patient did not respond to treatment with olanzapine and got even more complicated. Was the malignant catatonia that this patient has shown induced by olanzapine ? The answer to this question seems difficult since some authors report the efficacy of olanzapine in malignant catatonia. We wonder if we should have kept olanzapine and strengthen its dosage like Cassidy et al. in 2001 and Suzuki et al. in 2010 for the treatment of the malignant form constituted in this patient rather than having stopped it and used lorazepam as indica. The non-recognition of catatonia as an independent entity, the lack of a therapeutic consensus and the pending issue on the safety and efficacy of atypical antipsychotics in the treatment of catatonia are at the origin of the difficulties of therapeutic support of catatonic patients.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Catatonia; Fatal Outcome; Hospitalization; Humans; Male; Olanzapine; Prognosis; Psychotic Disorders; Treatment Failure; Young Adult

Scant information exists to guide pharmacological treatment of early-onset schizophrenia. We examine variation across commonly prescribed second-generation antipsychotic medications in medication discontinuation and psychiatric hospital admission among children and adolescents clinically diagnosed with schizophrenia. A 45-state Medicaid claims file (2001-2005) was analyzed focusing on outpatients, aged 6-17 years, diagnosed with schizophrenia or a related disorder prior to starting a new episode of antipsychotic monotherapy with risperidone (n = 805), olanzapine (n = 382), quetiapine (n = 260), aripiprazole (n = 173), or ziprasidone (n = 125). Cox proportional hazard regressions estimated adjusted hazard ratios of 180-day antipsychotic medication discontinuation and 180-day psychiatric hospitalization for patients treated with each medication. During the first 180 days following antipsychotic initiation, most youth treated with quetiapine (70.7%), ziprasidone (73.3%), olanzapine (73.7%), risperidone (74.7%), and aripirazole (76.5%) discontinued their medication (χ(2) = 1.69, df = 4, P = .79). Compared with risperidone, the adjusted hazards of antipsychotic discontinuation did not significantly differ for any of the 4-comparator medications. The percentages of youth receiving inpatient psychiatric treatment while receiving their initial antipsychotic medication ranged from 7.19% (aripiprazole) to 9.89% (quetiapine) (χ(2) = 0.79, df = 4, P = .94). As compared with risperidone, the adjusted hazard ratio of psychiatric hospital admission was 0.96 (95% CI: 0.57-1.61) for olanzapine, 1.03 (95% CI: 0.59-1.81) for quetiapine, 0.85 (95% CI: 0.43-1.70) for aripiprazole, and 1.22 (95% CI: 0.60-2.51) for ziprasidone. The results suggest that rapid antipsychotic medication discontinuation and psychiatric hospital admission are common in the community treatment of early-onset schizophrenia. No significant differences were detected in risk of either adverse outcome across 5 commonly prescribed second-generation antipsychotic medications.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Dibenzothiazepines; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Medication Adherence; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Thiazoles; Treatment Outcome

To investigate the influence of a single episode of psychiatric inpatient treatment on metabolic parameters.. A total of 294 consecutive patients of an Upper Austrian psychiatric department were assessed at admission and discharge regarding bodyweight, body mass index (BMI), high density cholesterol (HDL), low density cholesterol (LDL), triglycerides (TG) and fasting glucose (FG), and the TG/HDL ratio.. Patients showed an increase of BMI of 0.35 kg/m² (+ 1.3%) during a mean duration of inpatient stay of 25.8 days. LDL rose by 10.7 mg/dl (+ 8.1%), triglycerides by 23.0 mg/dl (+ 17%), HDL decreased by 4.4 mg/dl (-7.4%). Fasting glucose decreased by 3.6 mg/dl (-3.8%), yet the TG/HDL ratio, as a marker for insulin resistance, increased significantly from 2.86 to 3.58 (+ 25.2%) on average. Patients with psychotic disorders gained about three times more weight than patients with other diagnoses. Negative alterations of serum lipids were to be found in all diagnostic groups but were especially pronounced in patients with psychotic disorders who were treated with second-generation antipsychotics clozapine, olanzapine and quetiapine.. Psychiatric inpatient treatment leads to clinically relevant deterioration of metabolic parameters within a short time, most pronouncedly in patients with psychotic disorders.

Topics: Antipsychotic Agents; Austria; Benzodiazepines; Biomarkers; Body Mass Index; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Clozapine; Dibenzothiazepines; Female; Glucose; Hospitalization; Humans; Insulin Resistance; Length of Stay; Lipid Metabolism; Male; Mental Disorders; Middle Aged; Multivariate Analysis; Olanzapine; Polypharmacy; Prospective Studies; Psychiatric Department, Hospital; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Triglycerides; Weight Gain

Olanzapine is an atypical antipsychotic drug that infrequently has been reported to cause seizures and myoclonus despite a small proconvulsant risk. This is the first report of generalized myoclonus induced in a patient who had been maintained on low dose olanzapine for over seven years without any change in her dose. Olanzapine was discontinued, and the myoclonic jerks completely resolved within 48 h.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Electroencephalography; Female; Humans; Myoclonus; Olanzapine; Psychotic Disorders

: The use of antipsychotic medications is associated with an increased risk of death in older adults with dementia. The risk of death in patients with preexisting parkinsonism who receive antipsychotic drugs is not known.. : Using a nested case-control design, we examined the risk of death within 30 days of newly starting antipsychotic medications among people with Parkinsonism aged 70 years and older in Ontario, Canada. Data were obtained from Ontario's healthcare administrative databases.. : Among 5,391 individuals with parkinsonism who died during the study period (2002-2008) and a matched comparison group of 25,937 who were still alive, individuals exposed to atypical antipsychotic drugs had a higher risk of death (unadjusted odds ratio [OR] = 2.8, 95% CI: 2.1-3.8, adjusted OR: 2.0, 95% CI: 1.4-2.7). Results were similar for quetiapine use compared with no antipsychotic use (unadjusted OR: 2.5, 95% CI: 1.6-4.0, adjusted OR = 1.8, 95% CI: 1.1-3.0). Typical antipsychotics were associated with an increased odds of death compared with atypical antipsychotics (unadjusted OR = 2.4, 95% CI 1.1-5.2, adjusted OR = 2.4, 95% CI: 1.1-5.7).. : Individuals with parkinsonism who are newly prescribed antipsychotic medications have a higher risk of death within 30 days than those who do not start these medications. Although it is not possible to establish causality, the results suggest an increased risk. It is important to be vigilant for accompanying serious medical conditions that may increase mortality in individuals requiring treatment with antipsychotics and to consider alternative approaches to treating psychosis, agitation, and aggression in this population.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cohort Studies; Dibenzothiazepines; Female; Humans; Male; Olanzapine; Ontario; Parkinsonian Disorders; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk; Risperidone

Several factors may contribute to increase in duration of untreated psychosis (DUP). In most cases, early intervention, namely psychopharmacological or psychosocial intervention, is done after first-episode psychosis. It is important to know what factors can contribute to duration of untreated psychosis. During this phase, patients often display unspecific symptoms such as anxiety and depression, personality disorders, and abuse of alcohol or drugs. These symptoms could go unrecognized and, hence, cause a delay in seeking treatment. In addition, functional and social decline frequently occurs in the prodromal phase or in the early course of schizophrenia. The purpose of this paper is to highlight barriers that cause delay in treatment and to review early detection and specific treatment strategies that may help to improve outcomes leading to psychosocial recovery.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delayed Diagnosis; Diagnosis, Differential; Early Medical Intervention; Health Services Accessibility; Humans; Male; Medication Adherence; Olanzapine; Prognosis; Psychotic Disorders; Recurrence; Treatment Refusal

Topics: Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Molindone; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology

Objective of this observational trial is to examine the effects of quetiapine in comparison with olanzapine and risperidone on clinical outcomes and quality of life in patients with schizophrenia and schizoaffective disorder in routine care. 374 adult persons with schizophrenia or schizoaffective disorder prescribed antipsychotic maintenance therapy with quetiapine, olanzapine, or risperidone at discharge from inpatient treatment were included. Clinical and psychosocial outcomes were assessed before discharge and at 6, 12, 18, and 24 months. Statistical analyses were conducted by mixed-effects regression models for longitudinal data. The propensity score method was used to control for selection bias. Patients discharged on olanzapine had significantly lower hospital readmissions than those receiving quetiapine or risperidone. The average chlorpromazine equivalent dose of quetiapine was higher than in patients treated with olanzapine or risperidone. No further significant differences between treatment groups were found. Quetiapine and risperidone are less effective in preventing the need for psychiatric inpatient care than olanzapine, and higher chlorpromazine equivalent doses of quetiapine are needed to obtain clinical effects similar to those of olanzapine and risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Hospital Administration; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Selection Bias; Survival Analysis; Time Factors; Treatment Outcome

Topics: Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Drug Monitoring; Haloperidol; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Retrospective Studies; Schizophrenia; Severity of Illness Index; Time Factors; Young Adult

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Drug Substitution; Humans; Male; Olanzapine; Psychotic Disorders

Postpartum psychosis is a rare, however severe mood disorder in the perinatal period. It is most commonly associated with postpartum bipolar disorder. The author reports a case where a male patient with psychosis was admitted to the psychiatric unit 5 days after his wife gave birth to their male child. The patient was very concerned about the well being of his child and was afraid that something bad would happen to his child. The patient was diagnosed with an acute manic episode with psychotic symptoms and treated with olanzapine and lithium. The patient has been continued on therapeutic dose of lithium without any relapse of the symptoms, 3 months after the initial episode. The role of psychological stress in precipitating such a severe mood or psychotic disorder needs to be highlighted.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Fathers; Humans; Lithium Compounds; Male; Olanzapine; Postpartum Period; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delusions; Epilepsy, Temporal Lobe; Female; Hallucinations; Humans; Olanzapine; Psychotic Disorders

The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with 'real-world' treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.. Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale - Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.. On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts.. Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Australia; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Outpatients; Practice Patterns, Physicians'; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Recurrence; Valproic Acid

In the healthy population, several pathways are known to exert an effect on basal metabolic factors. Previous studies have found associations between single nucleotide polymorphisms in clock genes or downstream hormone receptors such as the leptin receptor (LEPR) or glucocorticoid receptor (NR3C1) and obesity in the healthy population, but this association remains to be examined in patients with schizophrenia treated with antipsychotics.. To assess anthropomorphic parameters in patients taking second-generation antipsychotics (SGA) as a function of nine polymorphisms in three core genes of the clock pathway, and two genes of downstream hormone receptors.. Clinical parameters were evaluated in 261 patients with schizophrenia spectrum disorder. Polymorphisms in LEPR, MC3R, NR3C1, PER2 and SDC3 were genotyped. In order to control for multiple testing, permutation tests were used to generate corrected empirical p-values using the Max(T) procedure in PLINK.. A significant effect of the rs6196 polymorphism in the NR3C1 on weight (β=-4.18; SE=2.02; p=0.018), BMI (β=-1.88; SE=0.64; p=0.004), waist (β=-5.77; SE=1.75; p=0.001) and waist/hip ratio (β=-0.03; SE=0.012; p=0.009) was found. Permutation tests confirmed the findings for BMI (p=0.037) and waist (p=0.024). Carriers of the G allele consistently displayed better parameters than patients with the wild type allele. A weak effect of rs4949184 in SDC3 on BMI was found, but this did not sustain permutation testing (β=-1.27; SE=0.58; p=0.030, p=0.270 after permutations).. Variations in genes implicated in circadian regulation or its related downstream pathways may be important in the regulation of antropomorphic parameters in patients with schizophrenia during long-term treatment with SGA.

Topics: Adult; Age Factors; Alleles; Amisulpride; Anthropometry; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Body Composition; Body Mass Index; CLOCK Proteins; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Female; Genetic Association Studies; Genetic Carrier Screening; Genotype; Humans; Long-Term Care; Male; Middle Aged; Mutation, Missense; Olanzapine; Period Circadian Proteins; Piperazines; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptor, Melanocortin, Type 3; Receptors, Glucocorticoid; Receptors, Leptin; Risperidone; Schizophrenia; Sex Factors; Sulpiride; Syndecan-3

Dopamine D2 receptors, encoded by DRD2, play a role in regulating serum prolactin concentration. Single nucleotide polymorphisms (SNPs), rs2734842(C), rs6275(T), and rs6279(C) located within DRD2, have been shown to be associated with prolactin increase in olanzapine/fluoxetine combination (OFC)-treated women. The present analyses seek to replicate these results and test other SNPs in DRD2 and neighboring gene ANKK1 for associations with prolactin increase in women, using data from 3 pooled studies of olanzapine, and 2 previously examined studies OFC. An ANCOVA was used to test whether change from baseline in the natural log of prolactin concentration (ln[prolactin]) was associated with SNPs in the pooled olanzapine studies. A meta-analysis was also performed using the inverse chi-square method, pooling p-values from the 2 previously examined studies and the 3 olanzapine studies. Negative strand alleles rs2734842(C), rs6275(T), and rs6279(C) were significantly associated with increased prolactin in olanzapine-treated women, replicating previous results. These SNPs also showed moderate association with increased prolactin in olanzapine-treated and OFC-treated women in the meta-analysis, as did rs4938016, rs2734848, rs2734841, rs1124493, and rs1076562. Five of these SNPs fall in or are adjacent to an LD block spanning DRD2 intron 7, exon 7, 5' untranslated region and ANKK1.. www.clinicaltrial.gov.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Drug Combinations; Female; Fluoxetine; Gene Frequency; Genome-Wide Association Study; Genotype; Humans; Meta-Analysis as Topic; Middle Aged; Olanzapine; Pharmacogenetics; Polymorphism, Single Nucleotide; Prolactin; Protein Serine-Threonine Kinases; Psychotic Disorders; Receptors, Dopamine D2; Sex Characteristics

The primary aim of the present study was to investigate the relationship between steady state serum and cerebrospinal fluid (CSF) concentrations of olanzapine (OLA) and its metabolite 4'-N-desmethylolanzapine (DMO) in patients with schizophrenia or schizoaffective disorder treated with oral OLA as the only antipsychotic drug. The influence of smoking, gender, age, as well as polymorphisms in cytochrome P450 CYP2D6, CYP1A2, and ABCB1 genes on the serum and CSF drug levels was also analyzed. Thirty-seven white outpatients (10 smokers and 27 nonsmokers) were included. From 29 of them, CSF was collected successfully. A strong correlation (Spearman rank correlation [rs] = 0.93; P < 0.05) was found between serum and CSF concentrations of OLA and a somewhat weaker correlation (rs = 0.5; P < 0.05) between those of DMO. The CSF concentrations of OLA and DMO were on average 12% and 16% of those in serum. Extensive metabolizers of CYP2D6 had higher (P < 0.05) daily doses than poor metabolizers when the influence of smoking was taken into account. Smokers had lower (P < 0.01) concentration-to-dose ratios of OLA in serum (mean, 2.23 ng/mL per mg vs 3.32 ng/mL per mg) and CSF (0.27 ng/mL per mg vs 0.41 ng/mL per mg) than nonsmokers. The concentration-to-dose ratio for serum DMO decreased with increasing age (rs = -0.41; P < 0.05). Carriers of ABCB1 1236T/2677T/3435T haplotype had higher serum (mean, 37.7 ng/mL vs 22.5 ng/mL; P = 0.035) and CSF (4.7 ng/mL vs 2.6 ng/mL; P = 0.018) OLA concentrations than patients without this haplotype. The present study shows a strong correlation between serum and CSF concentrations of OLA, indicating that concentrations of OLA in serum reflect those in CSF.

Topics: Administration, Oral; Adult; Antipsychotic Agents; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Benzodiazepines; Biomarkers; Cytochrome P-450 CYP1A2; Female; Humans; Male; Middle Aged; Olanzapine; Polymorphism, Genetic; Psychotic Disorders; Schizophrenia; Young Adult

Blockade of dopamine D(2) receptors is thought to mediate the therapeutic effects of antipsychotic medication but may also induce social indifference. As antipsychotic drugs differ in D(2) receptor binding, "tight" and "loose" binding drugs may be hypothesized to differentially affect emotional experience. The present study investigates the differential effects of relatively tight versus looser binding drugs on the experience of emotions in the realm of daily life.. We assessed positive and negative affect in the daily life of 109 patients with a DSM-IV diagnosis of psychotic disorder who were currently taking antipsychotic medication by using the experience sampling method (a structured diary technique). Antipsychotic medication was classified as loose (olanzapine; n = 35) or tight (haloperidol, risperidone; n = 74) binding, based on the drug's dissociation constants at the D(2) receptor. The study was conducted from 2007 to 2008.. Multilevel analyses showed a significant interaction between binding group (loose vs tight) and D(2) receptor occupancy estimates with regard to the experience of positive (P = .008) and negative (P = .019) affect. For tight-binding-agent users, a significant association was found between D(2) receptor binding estimates and both positive affect (P = .040) and negative affect (P = .0001) in the flow of daily life, with increasing levels of estimated D(2) receptor occupancy being associated with decreased feelings of positive affect and increased feelings of negative affect. For loose-binding-agent users, no such association was apparent. These associations were only partly mediated by clinical symptoms.. These findings add ecological validity to previous laboratory findings showing an association between D(2) receptor occupancy and emotional experience.

Topics: Adolescent; Adult; Affect; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Receptors, Dopamine D2; Risperidone; Schizophrenia; Self Report; Severity of Illness Index; Young Adult

Treatment of shared delusional disorder (folie à deux) often involves separation and use of antipsychotic medication, with uncertain outcomes and potential risks.. We report on two highly interdependent and chronically psychotic sisters with shared systematic delusion, followed by psychiatrists over several years.. The dominant patient was diagnosed with schizoaffective disorder and her non-dominant sister with paranoid schizophrenia. Both received antipsychotics and supportive therapy as outpatients and allowed to continue conjoint therapy with individual psychiatrists-therapists. They returned for follow-up visits for 20 months, when the dominant decided to continue treatment alone, as her sister gradually improved symptomatically and functionally. After separation, the dominant became increasingly anxious. She impulsively ingested an overdose of the non-dominant sister's medicines and died of cardiac arrest, despite her sister's efforts to seek medical assistance. The surviving non-dominant sister developed anxiety and increasing agitation requiring psychiatric hospitalization and increased pharmacotherapy. She improved gradually, but continued to be dysfunctional and required placement in a psychiatric inpatient unit for several months, eventually doing better in a community-based rehabilitative program with regular psychiatric follow-up.. Combined treatment of patients with folie à deux may encourage continuous pathological interactions, but separation may increase risk of adverse outcomes.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Clozapine; Combined Modality Therapy; Epilepsy; Fatal Outcome; Female; Haloperidol; Humans; Nordazepam; Olanzapine; Patient Compliance; Psychotherapy; Psychotic Disorders; Schizophrenia, Paranoid; Shared Paranoid Disorder; Sibling Relations; Suicide; Valproic Acid

Topics: Adolescent; Agranulocytosis; Antipsychotic Agents; Benzodiazepines; Humans; Male; Olanzapine; Psychotic Disorders

When treating schizophrenia, improving patients' productivity level is a major goal considering schizophrenia is a leading cause of functional disability. Productivity level has been identified as the most preferred treatment outcome by patients with schizophrenia. However, little has been done to systematically investigate productivity levels in schizophrenia. We set out to better understand the change in productivity level among chronically ill patients with schizophrenia treated with olanzapine compared with other antipsychotic medications. We also assessed the links between productivity level and other clinical outcomes.. This post hoc analysis used data from 6 randomized, double-blind clinical trials of patients with schizophrenia or schizoaffective disorder, with each trial being of approximately 6 months duration. Change in productivity level was compared between olanzapine-treated patients (HGBG, n = 172; HGHJ, n = 277; HGJB, n = 171; HGLB, n = 281; HGGN, n = 159; HGDH, n = 131) and patients treated with other antipsychotic medications (separately vs. haloperidol [HGGN, n = 97; HGDH, n = 132], risperidone [HGBG, n = 167; HGGN, n = 158], quetiapine [HGJB, n = 175], ziprasidone [HGHJ, n = 271] and aripiprazole [HGLB, n = 285]). Productivity was defined as functional activities/work including working for pay, studying, housekeeping and volunteer work. Productivity level in the prior 3 months was assessed on a 5-point scale ranging from no useful functioning to functional activity/work 75% to 100% of the time.. Chronically ill patients treated with olanzapine (OLZ) experienced significantly greater improvement in productivity when compared to patients treated with risperidone (RISP) (OLZ = 0.22 ± 1.19, RISP = -0.03 ± 1.17, p = 0.033) or ziprasidone (ZIP) (OLZ = 0.50 ± 1.38, ZIP = 0.25 ± 1.27, p = 0.026), but did not significantly differ from the quetiapine, aripiprazole or haloperidol treatment groups. Among first episode patients, OLZ therapy was associated with greater improvements in productivity levels compared to haloperidol (HAL), during the acute phase (OLZ = -0.31 ± 1.59, HAL = -0.69 ± 1.56, p = 0.011) and over the long-term (OLZ = 0.10 ± 1.50, HAL = -0.32 ± 1.91, p = 0.008). Significantly more chronically ill and first episode patients treated with olanzapine showed moderately high (>50%-75% of the time) and high levels of productivity (>75%-100% of the time) at endpoint, when compared to risperidone or haloperidol-treated patients (p < .05), respectively. Higher productivity level was associated with significantly higher study completion rates and better scores on the positive, negative, disorganized thoughts, hostility and depression subscales of the Positive and Negative Symptom Scale (PANSS).. Some antipsychotic medications significantly differed in beneficial impact on productivity level in the long-term treatment of patients with schizophrenia. Findings further highlight the link between clinical and functional outcomes, showing significant associations between higher productivity, lower symptom severity and better persistence on therapy.. clinicaltrials.gov identifier NCT00088049; NCT00036088.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Efficiency; Female; Humans; Male; Medication Adherence; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index

We report about a woman of 60 years who received psychiatric inpatient treatment for an affective disorder with psychotic symptoms on several occasions. As time elapsed symptoms of dementia became more and more obvious. Despite a comprehensive workup with neuroimaging methods (SPECT, PET) the correct diagnosis of Huntington's Chorea was not attained until the characteristic movements appeared. Up till then pathologic movements had hardly occurred and there were no known cases of Huntington's Chorea in the family. This case is remarkable as the patient was not only treated with different antidepressants and antipsychotics but with a course of ECT too. Beyond this it shows the enormous stress this illness imposes on patients and their caregivers.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Brain; Combined Modality Therapy; Dementia; Depressive Disorder, Major; Diagnosis, Differential; Disease Progression; Electroconvulsive Therapy; Female; Humans; Huntington Disease; Middle Aged; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Suicidal Ideation; Tomography, Emission-Computed, Single-Photon; Treatment Failure

Topics: Adult; Airway Obstruction; Anesthetics, Intravenous; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Dystonia; Fracture Fixation; Humans; Laryngeal Muscles; Male; Olanzapine; Propofol; Psychotic Disorders; Spinal Fractures

To measure the changes in subcutaneous and intra-abdominal fat and other metabolic parameters in patients with psychotic disorders, who were newly started on olanzapine treatment and in drug-free controls. The correlation between changes in visceral fat and other metabolic parameters were also studied.. Using a longitudinal open-label design, the 2 studied groups included patients with psychoses (n = 23) [diagnosed as per the 10th edition of the International Classification of Diseases criteria] and drug-free controls (n = 11). Fasting sugar, lipid profile and glycosylated haemoglobin levels were collected at baseline and follow-up. Computed tomographic scans were used to determine changes in the various abdominal fat parameters.. The patients were significantly younger than the controls, and the former had higher mean subcutaneous fat at baseline. There were statistically significant increases in the subcutaneous fat, intraabdominal fat, weight, waist circumference, hip circumference and body mass index in patients but not in controls. The mean dose of olanzapine (mg/day) correlated significantly with change of intraabdominal fat at follow-up. The change in intra-abdominal fat did not correlate significantly with any of the metabolic parameters studied.. Olanzapine produced significant increase in weight and fat parameters. This increase correlated with the dose of olanzapine.

Topics: Abdominal Fat; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Follow-Up Studies; Glycated Hemoglobin; Humans; India; Intra-Abdominal Fat; Lipids; Longitudinal Studies; Middle Aged; Olanzapine; Psychotic Disorders; Tomography, X-Ray Computed; Waist Circumference; Waist-Hip Ratio; Young Adult

This study consisting of two subprojects was undertaken to evaluate the effects of hyperprolactinemia on cardiovascular disease (CVD) risk parameters such as anthropometric measures, insulin sensitivity and blood lipids in patients with schizophrenia or related psychoses on long term treatment with antipsychotics.. In subproject Ι, 45 patients receiving the 2nd generation antipsychotics risperidone, clozapine or olanzapine were compared regarding prolactin (PRL), body mass index (BMI), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood lipids. In subproject Π, 24 patients receiving 1st or 2nd generation antipsychotics were investigated with diurnal profile of PRL and oral glucose tolerance test (OGTT).. Elevated PRL levels were found in about 45% of the patients and occurred more often in patients receiving risperidone or haloperidol, compared to patients receiving clozapine or olanzapine. In contrast, in subproject Ι, insulin and HOMA-IR were higher and high density lipoprotein cholesterol was lower in patients receiving clozapine or olanzapine, compared with patients receiving risperidone. However, PRL levels did not correlate to BMI, insulin, HOMA-IR or lipids in any of these three treatment groups. In subproject Π, OGTT showed impaired glucose tolerance in 25% and new-onset diabetes in 4% of the 24 patients investigated. Additionally, the PRL (median 24 h) levels correlated positively to the 2 h glucose level at OGTT (rs=0.42, p=0.04).. Our findings point to that hyperprolactinemia due to 1st and 2nd generation antipsychotics may decrease insulin sensitivity, whereas other mechanisms probably underlie insulin resistance induced by PRL-sparing antipsychotics such as clozapine and olanzapine.

Topics: Adult; Anthropometry; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Clozapine; Female; Glucose Intolerance; Humans; Hyperprolactinemia; Insulin Resistance; Lipids; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Risperidone; Schizophrenia; Young Adult

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Substitution; Humans; Hypercholesterolemia; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia

The present study aims to evaluate effectiveness of antipsychotics in a cohort of chronic outpatients affected by schizophrenia and related disorders.. Three hundred chronic patients affected by schizophrenia (n=173), schizoaffective (n=117) and delusional (n=60) disorder who were in treament with antipsychotics on 1.3.2008 were considered in the study; effectiveness of antipsychotic treatment was evaluated by means of rates of all cause discontinuation in a 12 months period (31.3.2008-31.3.2009) and of "overall duration of treatment" (DT) (duration of treatment retrospectively evaluated on the basis of clinical records+duration of treatment prospectively evaluated during the 12-months follow up).. Discontinuation of treatment was registered in 25% of patients (29% due to side effects, 14% due to scarce adherence, 11% due to lack of efficacy, 22% due to more causes). Clozapine (7%), Risperidon Long-acting (10%), Typical Antipsychotics depot (11%) and Olanzapine were associated to lower rates of all causes discontinuation. Overall mean duration of antipsychotic treatment was 18± 32 months, with statistically significant differences between drugs (F=4.65, p=0.000). Clozapine (65 mo), Olanzapine (50 mo), butyrophenones (49 mo), typical antipsychotics depot (48 mo), and risperidone (47.5 mo) were the antipsychotics with a longer duration of treatment. Only Clozapine showed a significantly longer DT than any other antipsychotic medication excluding buthyrrohenones.. Rates of all cause discontinuation of antipsychotics appear to be somewhat lower than expected on the basis of pragmatic studied published in the last years; similarly overall duration of treatment seems to be longer. Clozapine is associated to a higher overall effectiveness respect to any other atypical antipsychotic.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Butyrophenones; Clozapine; Delayed-Action Preparations; Delusions; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Patient Dropouts; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Young Adult

To identify the factors associated with newly prescribed, first-line, second-generation antipsychotics (SgAs) associated with weight gain-olanzapine, risperidone, and quetiapine.. Retrospective medical record review.. Outpatient and inpatient psychiatry services at a tertiary care, academic medical center.. Three hundred forty consecutive adults who had major depressive disorder with psychotic features, bipolar I, bipolar II, bipolar not otherwise specified, or schizoaffective disorder over two time periods (August 30-October 30, 2009, and April 1-May 31, 2010).. Clinical and sociodemographic variables associated with newly prescribed olanzapine, risperidone, and quetiapine were identified by using univariate and multivariate logistic regression. Several clinical factors were individually associated with initiation of these SgAs: mania (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.2-10.8, p=0.02), psychosis (OR 3.3, 95% CI 1.5-6.9, p=0.002), and inpatient treatment (OR 3.8, 95% CI 1.8-7.9, p=0.0005). Prevalent use of lithium (OR 0.3, 95% CI 0.1-0.9, p=0.03) and being married (OR 0.3, 95% CI 0.1-0.8, p=0.02) were inversely associated with new use of an SgA. Mania, psychosis, married status, and lithium use remained independently associated on multivariate analysis. Factors related to metabolic or vascular risk were not associated with SgA initiation.. Psychiatric clinicians were influenced heavily by clinical features related to mental status and acuity when determining whether to prescribe SgAs. However, factors related to vascular risk were not associated. Future observational studies should consider current clinical status as an important factor in determining propensity to receive antipsychotics or other short-term treatments for bipolar and related disorders.

Topics: Academic Medical Centers; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

The aim of our study was to assess the time to 'first improvement' associated with specific atypical (AAP) and typical (TAP) antipsychotic drugs in patients with early-onset schizophrenia and other related psychotic disorders.. This study involved a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs and TAPs, for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 296 teenage patients (141 males, 155 females; mean age 16.0 ± 1.5 years). The time to first improvement could be estimated in 258 patients; of these, 195 patients (76%) had been treated with AAPs and 63 patients (24%) with TAPs. We found that most patients were taking risperidone (N = 96), followed by olanzapine (64 patients). Other patient numbers were as follows: ziprasidone (16 patients), quetiapine (12 patients), clozapine (7 patients), haloperidol (15 patients), perphenazine (28 patients), and sulpiride (20 patients).. The mean time to first improvement was 6.9 (± 4.2) days in the AAP group and 5.8 (± 3.5) days in the TAP group; the difference was significant at the trend level (p=0.063). With respect to individual drugs, the mean time to first improvement was 7.1 (± 4.1) days for risperidone, 6.7 (± 4.2) days for olanzapine, 6.5 (± 5.2) days for ziprasidone, 6.1 (± 4.4) days for quetiapine, 7.4 (± 3.0) days for clozapine, 5.2 (± 2.4) days for haloperidol, 5.9 (± 3.8) days for perphenazine, and 6.0 (± 3.9) days for sulpiride. Differences among drugs were not significant (p=0.680).. Analysis revealed a significant group level trend indicating that typical antipsychotic drugs have faster onsets of action than atypical antipsychotic drugs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Female; Haloperidol; Humans; Male; Medical Records; Olanzapine; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride; Thiazoles; Time Factors; Treatment Outcome

We here report on a psychotic mother and her breast-fed infant who was treated with olanzapine. Consecutively olanzapine concentrations in the milk and plasma of the mother and in the infant were measured with tandem mass spectroscopy over a period of five month. The results show a relatively high plasma level in the infant aged four month, probably referring to an immature hepatic transformation system, especially CYP1A2. In the following four months plasma levels of olanzapine decreased to very low, even undetectable concentrations in the infant. The infant developed normally and showed no side effects during the treatment period.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Breast Feeding; Cytochrome P-450 CYP1A2; Depression, Postpartum; Female; Humans; Infant; Male; Milk, Human; Olanzapine; Psychotic Disorders; Tandem Mass Spectrometry

Measles virus is a highly prevalent neurotropic virus capable of causing persistent infections within the central nervous system.. We measured IgG class antibodies to measles in 820 individuals including 138 with recent onset psychosis, 378 with persistent schizophrenia, and 304 non-psychiatric controls. Levels of antibodies among the groups were compared by bivariate and by multivariate analyses and correlated with clinical and demographic variables.. The level of measles antibodies in individuals with a recent onset of psychosis was greater than the level of antibodies in individuals with persistent schizophrenia or individuals without a history of a psychiatric disorder (p<.00001). The level of measles antibodies in the individuals with persistent schizophrenia was greater than the level of measles antibodies in the controls (p<.001). Recent onset of psychosis was associated with having elevated levels of measles antibodies, defined as the 90th percentile of the levels of the controls, with an odds ratio of 8.0 (95% CI 4.6, 14.0); persistent schizophrenia was associated with having this level with an odds ratio of 2.3 (95% CI 1.4, 3.7). Within the psychiatric groups, measles antibody levels were associated with age, race, and current treatment with the antipsychotic medication, olanzapine.. The reasons for elevated levels of measles antibodies in the psychiatric groups are not known with certainty and should be studied in prospective investigations.

Topics: Adolescent; Adult; Age Factors; Antibodies, Viral; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Female; Humans; Immunoglobulin G; Male; Measles virus; Middle Aged; Odds Ratio; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Reference Values; Schizophrenia; Schizophrenic Psychology; Sex Factors; Young Adult

Topics: Adult; Age Factors; Benzodiazepines; Humans; Male; Olanzapine; Psychotic Disorders; Severity of Illness Index; Subacute Sclerosing Panencephalitis

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diagnosis, Differential; Dose-Response Relationship, Drug; Drug Hypersensitivity; Humans; Male; Myocarditis; Olanzapine; Psychotic Disorders; Retreatment

Although it is a troublesome side effect, information on antipsychotic-induced sexual dysfunction is limited.. To evaluate the frequency of sexual dysfunction and its impact on treatment adherence in patients with a psychotic disorder treated with various antipsychotics under routine clinical conditions.. Subjects included were sexually active male and female patients 18 years of age or older with a diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or other psychotic disorder. This was a multicenter, cross-sectional, and naturalistic study conducted by 18 investigators. In addition to sexual functioning, we recorded demographic data, psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), and medication history.. Pyschotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SalSex).. All the analyses were performed in the 243 evaluable patients. Most patients were males (71%), and the most common diagnosis was schizophrenia (71%). Overall, 46% of the patients exhibited sexual dysfunction according to the assessment with the SalSex (50% of the males and 37% of the females). Only 37% of the patients with sexual dysfuntion spontaneously reported it. Among the patients exhibiting sexual dysfunction, 32% reported to have poor tolerance to the disturbance. With the exception of conventionals depot, which had a very important and greater effect on females' sexual funtioning, the severity and tolerance of sexual dysfunction were worse in males than in females regardless of the antipsychotic studied. In the univariate logistic regression analysis, using olanzapine as a reference category, risperidone (odds ratio [OR] 7.45, 95% confidence interval [CI] 3.73-14.89) and conventionals, depot (OR 4.57, 95% CI 1.72-12.13) and nondepot (OR 4.92, 95% CI 1.43-16.93), showed a significant increased risk of sexual dysfunction.. Our results show that sexual dysfunction is very common in patients receiving long-term treatment with antipsychotics, and it is associated with a great impact in a substantial proportion of patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Confidence Intervals; Cross-Sectional Studies; Delayed-Action Preparations; Female; Humans; Logistic Models; Male; Odds Ratio; Olanzapine; Psychotic Disorders; Risk Factors; Risperidone; Schizophrenia; Severity of Illness Index; Sex Factors; Sexual Dysfunction, Physiological

Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders.. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups.. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p < 0.001 for all comparisons), total cholesterol increased in the bipolar (p = 0.02) and psychotic (p = 0.01) disorder groups, low-density lipoprotein cholesterol increased in the bipolar group (p = 0.02), and free T4 decreased in the psychotic disorder group (p = 0.05). More patients with bipolar disorder presented overweight plus > or = 1 obesity-related complication at follow-up.. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Biomarkers; Bipolar Disorder; Body Mass Index; Child; Cholesterol, LDL; Chromatography, High Pressure Liquid; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Obesity; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thyroxine; Treatment Outcome; Weight Gain

Topics: Amisulpride; Antipsychotic Agents; Benzodiazepines; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Magnetic Resonance Imaging; Middle Aged; Olanzapine; Pituitary Gland; Pituitary Neoplasms; Prolactinoma; Psychotic Disorders; Remission, Spontaneous; Sulpiride; Thyrotropin-Releasing Hormone

Topics: Antipsychotic Agents; Australia; Benzodiazepines; Commitment of Mentally Ill; Delayed-Action Preparations; Health Services Misuse; Humans; Injections, Intramuscular; Inservice Training; Monitoring, Physiologic; New Zealand; Olanzapine; Patient Care Team; Patient Compliance; Psychiatric Department, Hospital; Psychiatric Nursing; Psychotic Disorders; Resuscitation

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Drug Therapy, Combination; Humans; Male; Memory Disorders; Olanzapine; Piperazines; Psychotic Disorders; Quinolones; Treatment Outcome

Sydenham chorea (SC) is a complication of a group A beta-haemolytic streptococcal infection which is characterised by involuntary, choreatic movements. There is a definitive link between SC and psychoses. Furthermore, patients with SC seem to run a greater risk of developing neuroleptic-induced movement disorders. In this case-study of a 19-year-old psychotic male with a history of SC, the authors illustrate that this complicates the treatment of a psychotic episode.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Carbamazepine; Chorea; Humans; Male; Olanzapine; Psychotic Disorders; Streptococcal Infections; Streptococcus pyogenes; Young Adult

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Receptors, Dopamine D2; Severity of Illness Index

Acute psychosis is diagnosed by clearly defined operational criteria embedded into international classification systems. Many studies have tried to determine the role of gender in psychosis but mainly in terms of epidemiology and course of illness, most often schizophrenia. There are however also important gender-specific differences in clinical symptoms of acute psychosis. No guidelines or treatment recommendations suggest gender as an important factor in the choice of antipsychotic treatment, which is true for all treatment modalities (antipsychotic, dose, duration). We will review shortly available literature and present some of our own research data on gender differences in clinical presentations of acute psychosis. When the diagnosis of an illness depends almost entirely on symptoms and their presentations as in the case of acute psychosis, important gender specific differences might challenge the diagnostic process as well as treatment choice and course of psychosis. Our as well as other data confirm that acute psychosis manifest itself differently in males and females. To define further the impact of observed differences we need further research into gender specific clinical and not just epidemiological variables.

Topics: Acute Disease; Adult; Affect; Amisulpride; Antipsychotic Agents; Benzodiazepines; Brain; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Hospitalization; Humans; Internal-External Control; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Sex Factors; Sulpiride; Thinking

Offering a new perspective on sleep state misperception, we discuss a patient who presented with sleep state misperception and was ultimately diagnosed with delusional disorder. A 60-year-old woman with chief complaints of insomnia, agitation, and suicidal ideation, was admitted to an inpatient psychiatric ward. Based on information from her family and a mental state examination, her primary diagnosis was sleep state misperception. She was treated with Trazodone. Because she was unresponsive to the treatment, a full psychiatric evaluation and wrist actigraphy report were undertaken, resulting in a revised diagnosis of delusional disorder. She was started on Olanzapine and, after 6 weeks was discharged with good improvement. Sleep state misperception might be considered not just as a sleep disorder, but also as a psychiatric disorder with psychotic symptoms. Further research is recommended.

Topics: Antipsychotic Agents; Benzodiazepines; Female; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Sleep Initiation and Maintenance Disorders

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Huntington Disease; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychotic Disorders; Quinolones; Treatment Outcome

Clinically significant weight gain has been reported during treatment with atypical antipsychotics. It has been suggested that weight changes in patients treated with olanzapine may be associated with increased appetite.. Data were used from adult patients for whom both appetite and weight data were available from 4 prospective, 12- to 24-week clinical trials. Patients' appetites were assessed with Eating Behavior Assessment (EBA, Study 1), Platypus Appetite Rating Scale (PARS, Study 2), Eating Inventory (EI, Study 3), Food Craving Inventory (FCI, Study 3), and Eating Attitude Scale (EAS, Study 4).. In Studies 1 (EBA) and 4 (EAS), patients who reported overall score increases on appetite scales, indicating an increase in appetite, experienced the greatest overall weight gains. However, in Studies 2 (PARS) and 3 (EI, FCI), patients who reported overall score increases on appetite scales did not experience greater weight changes than patients not reporting score increases. Early weight changes (2-4 weeks) were more positively correlated with overall weight changes than early or overall score changes on any utilized appetite assessment scale. No additional information was gained by adding early appetite change to early weight change in correlation to overall weight change.. Early weight changes may be a more useful predictor for long-term weight changes than early score changes on appetite assessment scales.. This report represents secondary analyses of 4 clinical studies. Studies 1, 2, and 3 were registered at http://clinicaltrials.gov/ct2/home, under NCT00190749, NCT00303602, and NCT00401973, respectively. Study 4 predates the registration requirements for observational studies that are not classified as category 1 observational studies.

Topics: Adult; Aged; Antipsychotic Agents; Appetite; Appetite Regulation; Benzodiazepines; Clinical Trials, Phase IV as Topic; Feeding Behavior; Female; Humans; Life Style; Male; Middle Aged; Olanzapine; Probability; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Weight Gain

Topics: Adult; Benzodiazepines; Clozapine; Drug Interactions; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone; Thiophenes; Young Adult

Topics: Benzodiazepines; Body Mass Index; Cholecystokinin; Ghrelin; Humans; Leptin; Lipids; Lipoproteins, LDL; Male; Olanzapine; Psychotic Disorders; Time Factors; Treatment Outcome; Triglycerides

Eating disorders in early childhood are the same frequency in boys and girls. During adolescence eating disorders are ten (10) times more frequent in girls than in boys. Worrying is the fact that eating disorders are the third chronic illness among adolescents after obesity and asthma. Depicting this adolescent we tried to show difficulty of treatment of this disorder, where in the beginning is important to stabilize body weight and prevent somatic damages such as: heart damage, amenorrhoea, changes in EKG (electrocardiogram) and electrolyte dysbalance that could endanger the life of patient. Simultaneously it is important to recognize and treat comorbid psychological disturbances such as in this case: depression, delusions with occasional psychotic reactions combined with unrealistic thinking about the layout of her own body. There is still no cure for the treatment of eating disorders which are in growing number of reports among male adolescents.

Topics: Adolescent; Anorexia Nervosa; Antipsychotic Agents; Benzodiazepines; Female; Humans; Olanzapine; Psychotic Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Movement Disorders; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Severity of Illness Index

The objective of the study was to investigate the change of body mass index (BMI), waist circumference, lipid profile, leptin, ghrelin, orexin, visfatin, agouti-related protein, and cholecystokinin levels during 6 weeks of olanzapine treatment in newly diagnosed first-episode drug naive, young adult, nonobese male patients with psychosis. Twenty male participants who were all first-episode drug naive psychotic patients without prominent affective signs and symptoms and 22 healthy male controls of similar age were included. BMI, waist circumference, fasting glucose, and lipid profiles were measured, and Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores were obtained at baseline, during the second and sixth week of treatment, and the aforementioned neuropeptide levels were measured at baseline and during the sixth week of treatment. Treatment was associated with significant increases in BMI, waist circumference, serum triglyceride, and low-density lipoprotein levels. BMI levels increased more than 7% in over 75% of the patients. Leptin increased, and ghrelin and orexin decreased significantly with olanzapine treatment, whereas cholecystokinin, visfatin, and agouti-related protein levels did not change significantly. In conclusion, consistent with previous studies, we found increased BMI, leptin and lipids during olanzapine treatment. Association of neuropeptide level changes with symptom improvement might be mediated by the dopaminergic and serotonergic systems.

Topics: Agouti-Related Protein; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholecystokinin; Disease Progression; Ghrelin; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Lipids; Male; Neuropeptides; Nicotinamide Phosphoribosyltransferase; Olanzapine; Orexins; Psychiatric Status Rating Scales; Psychotic Disorders; Time Factors; Waist Circumference; Young Adult

We discussed a neurosyphilis case who had a risky sexual intercourse history nearly 10 years ago. After the neurosyphilis diagnosis, the patient has clinical symptoms of a demential case starting as a typical manic episode and Jarisch-Herxheimer reaction because of intravenous penicillin treatment that has improved with olanzapine treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dementia; Humans; Male; Neurosyphilis; Olanzapine; Penicillins; Psychotic Disorders

Comparative effectiveness analyses using retrospective databases may be highly sensitive to common design decisions employed by researchers.. To test the sensitivity of statistical results to common research methods in retrospective database analyses. Comparisons of time to all-cause discontinuation (TTAD) across antipsychotic drug therapies are used to illustrate these effects.. Data from the California Medicaid Program were used to identify 231,635 episodes of antipsychotic drug therapy. Four sequential analyses of TTAD were performed on all patients, patients with 1 year of post-treatment data, and patients with schizophrenia and using models that included variables documenting drug treatment history.. Patients using atypical antipsychotics consistently achieve longer TTAD than patients treated with conventional antipsychotics. Nevertheless, estimated differences narrowed when analyses included only patients with schizophrenia. Risperidone performed better than olanzapine when diagnosis was not limited to schizophrenia, and quetiapine outperformed olanzapine and risperidone when the analysis did not control for treatment history. This latter result reflects the disproportionate use of quetiapine in long-duration augmentation episodes. There were no statistical differences across alternative atypical antipsychotics once the analysis excluded patients without a diagnosis of schizophrenia and included patient treatment history in the analysis.. Comparative effectiveness analyses of alternative drug therapies are sensitive to diagnosis and patient drug treatment history. Data on these factors can be derived from paid claims data and should be used to provide more accurate comparisons of effectiveness across drugs and to provide results that cover the full range of clinical scenarios that clinicians face.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; California; Databases, Factual; Decision Making; Dibenzothiazepines; Female; Humans; Male; Medicaid; Middle Aged; Olanzapine; Patient Selection; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone; Schizophrenia; United States; Young Adult

Progression of metabolic illness in a patient with schizophrenia who was stabilized on an atypical antipsychotic is described using a case study framework. Risks and benefits of staying on current treatment versus switching to another agent and switching strategies are described.. Switching an antipsychotic with more favorable side effects may improve metabolic parameters if other weight loss strategies have failed. Switching or stopping medications too quickly may exacerbate psychiatric symptoms. There is little evidence to support which is the best switching strategy.. The psychiatric mental health nurse practitioner carries a significant responsibility of discussing risks and benefits of switching and closely monitoring the patient during a switch of medications. Ensuring that the patient decides and agrees upon the treatment plan will improve the overall outcome.

Topics: Antipsychotic Agents; Benzodiazepines; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Follow-Up Studies; Humans; Hypercholesterolemia; Hypertriglyceridemia; Long-Term Care; Male; Middle Aged; Olanzapine; Paroxetine; Psychotic Disorders; Risk Assessment; Schizophrenia; Thioridazine

Few cases of seizures associated with olanzapine therapy and even fewer with mirtazapine have been published, most of them in patients with confounding risk factors. Our objective was to report a case of Status epilepticus in a patient receiving olanzapine and mirtazapine, with no previous history of seizure and no confirmed underlying cause for seizure.. A 48-year-old white, psychotic woman developed generalized tonic-clonic seizures that progressed to Status epilepticus during hospitalization. 4 days before the incident, mirtazapine (30 mg) was added to the treatment, while 2 days before the incident, the treatment switched from quetiapine to olanzapine, and mirtazapine was increased to 60 mg. No other toxic, metabolic, electrolyte or anatomic abnormality was identified. After discontinuation of olanzapine, the patient remained seizure-free.. To our knowledge, this is the second reported case of Status epilepticus that has been associated with the use of olanzapine, while only one report of seizures, but none of Status epilepticus connected to mirtazapine is found in the literature. Although olanzapine has infrequently been associated with epileptogenic risk, it should be used cautiously especially when concomitant medication or other predisposing factors exist.

Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Drug Interactions; Female; Humans; Mianserin; Middle Aged; Mirtazapine; Olanzapine; Psychotic Disorders; Status Epilepticus

We explored the subjective effects associated with olanzapine, risperidone and older antipsychotics.. We conducted a content analysis of an Internet database of comments about prescribed medications.. We analysed 223 comments on risperidone, 170 on olanzapine and 46 relating to three older antipsychotics. The predominant subjective effects produced by all drugs consisted of sedation, cognitive impairment and emotional flattening or indifference. Connections appeared between these effects and Parkinsonian-like symptoms with the older drugs, sexual impairment with risperidone and metabolic effects with olanzapine. The experience of akathisia was frequently linked to suicidal thoughts. Some respondents described how the drugs' subjective effects helped to reduce symptoms of mania, psychosis and anxiety.. The generalisability of Internet data is uncertain. However, the data suggest that adverse subjective effects play a central role in the experience of taking antipsychotic drugs and may be related to the drugs' desired benefits.

Topics: Adult; Affect; Akathisia, Drug-Induced; Antipsychotic Agents; Anxiety Disorders; Attitude to Health; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Female; Health Behavior; Humans; Internet; Male; Middle Aged; Olanzapine; Parkinsonian Disorders; Psychotic Disorders; Risperidone; Sexual Dysfunction, Physiological

The necessary evidence of new therapies of clinical interest extends beyond clinical trials in a less controlled population and closer to clinical practice justified since several years the need of conducting observational, noninterventional studies. Observational studies must include epidemiological (quantitative observational) data to define prevalence and natural history of the target conditions. Moreover, pharmacological interventions in "naturalistic" patients populations, selected by clinicians as per clinical judgment within the scope of the target disease will allow to generate data to complement clinical trials. Clinical trials designed to show robust data on efficacy and tolerability particularly during registration trials must be complemented by robust observational research to confirm and better describe clinical effectiveness in the target population. A noninterventional, observational trial is a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorization. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnosis or monitoring procedures shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data. Olanzapine is a new antipsychotic therapy registered in Europe for the treatment of schizophrenia since 1996.. The primary objective of this observational research was to study the evolution of the olanzapine dosage under naturalistic settings. Secondary objectives included patients characteristics, severity of disease, therapeutic evolution and coprescriptions, in a patient's cohort, suffering from schizophrenia, adult patients, diagnosis based on ICD-10; patients were followed during a total of 12 months.. The cohort study was conducted in France. Between the period of June 2000 and February 2001, 407 psychiatrics randomized to participate in the study had consolidated the patient's cohort.. A total of 1810 patients were included, 1093 (60, 4%) male, 717 (39, 6%) females. Age was recorded for a total of 1802 (99, 6%) patients, mean age was 37.8 years as per inclusion criteria and patients consent according to current regulations. Patients entered in the cohort as per clinicians decision underwent a treatment with olanzapine during an outpatient's consultation or at hospitalization. More than two thirds of the patients were followed up during 12 months after onset of this treatment. Clinical outcome was assessed at three, six, nine and 12 months following cohort inclusion using the following tools: CGI, PANSS, Calgary and GAF; as per CGI 78% of the patients cohort were severely ill, the mean PANSS score was 94.1. At second month of treatment clinicians were requested to very well document any changes in olanzapine dosage as well as reasons for the dosage modifications and potential coprescriptions.. The daily mean dosage of olanzapine was 9.5mg at initiation of treatment, 10.5mg after one month and 11.2mg after 12 months of follow-up. The increase of the dosage after one month was associated with factors such as younger age, schizophrenia diagnosis and severity of the symptoms as measured by CGI and PANSS scores evolution, low initial dosage and hospitalization at treatment initiation. Within the 1810 participants included in the cohort, 1383 (76.5%) received a coprescrition of a psychotropic, for example, 811 (44.8%) a benzodiazepine, 506 (28.0%) an antidepressant. Among the patients cohort that were followed during 12 months, all the clinical and patient-functioning indicators progressed in the direction of a significant improvement.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; France; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Young Adult

Atypical antipsychotics interfere with central and peripheral neurotransmitter systems and with hormonal production. In this study we compared the effect of olanzapine and risperidone on hormonal state and sexual function (by using the Questionnaire for Sexual Dysfunction, QSD) in 40 patients with a first episode psychosis. Results were compared to those of 34 healthy controls. Patients using risperidone had significant higher prolactin levels than patients using olanzapine. Patients using olanzapine had significantly higher 17beta-estradiol levels than patients using risperidone. Overall satisfaction with sexuality was less in patients compared to controls, but not different between patients using olanzapine and those using risperidone. Problems with sexual arousal were significantly higher in patients using olanzapine compared to patients using risperidone. A significantly higher frequency of problems with ejaculation and problems with insensibility of genitals were found in patients compared to healthy controls. We found no relation between medication, prolactin and 17beta-estradiol levels, frequency of sexual activity, overall satisfaction with sexuality and any of the 18 sexual dysfunctions we investigated. Our results suggests that sexual dysfunction in patients with first episode psychosis might occur despite normal prolactin levels. Also, sexual dysfunction is highly prevalent in healthy controls. Awareness should be raised of potential sexual problems in young adults.

Topics: Antipsychotic Agents; Benzodiazepines; Case-Control Studies; Cross-Sectional Studies; Estradiol; Female; Humans; Male; Olanzapine; Prolactin; Psychotic Disorders; Risperidone; Sexual Dysfunction, Physiological; Young Adult

The objective of this study was to examine the predictors associated with adherence to atypical antipsychotic medication following discharge from hospital for children and adolescents with first-episode psychosis. Sixty-five children and adolescents, age 15.35 +/- 2.08 years, 59% boys, who had participated in a longitudinal cohort study examining relapse following first hospitalization for episode of psychosis were included in this study. All those studied were discharged on one of three atypical antipsychotics, risperidone, quetiapine, or olanzapine between January 1999 and October 2003. Time 1 data were collected retrospectively from medical charts using a standardized questionnaire; time 2 data were obtained using questionnaire mailed to participants' parents a minimum of 2 years post-discharge, mean 3.9 +/- 1.3 years. Variables examined as predictors of adherence fell into broad categories of biological, social and treatment variables. Discharge on concurrent pharmacologic agent for affective symptoms in addition to atypical antipsychotic, OR = 10.5 [95% confidence interval (CI) = 2.06-53.19] was a strong predictor of medication adherence in adolescents. The results indicated that children and adolescents discharged from their first hospitalization following a psychotic episode may be more likely to stay on prescribed antipsychotic medication if they are prescribed concurrent medication for affective symptoms.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Cohort Studies; Dibenzothiazepines; Epidemiologic Studies; Female; Humans; Length of Stay; Male; Olanzapine; Patient Compliance; Patient Discharge; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Treatment Outcome; United States

Asenapine, a novel psychopharmacologic agent in the development for schizophrenia and bipolar disorder, has high affinity for serotonergic, alpha-adrenergic, and dopaminergic receptors, suggesting potential for antipsychotic and cognitive-enhancing properties.. The effects of asenapine in rat models of antipsychotic efficacy and cognition were examined and compared with those of olanzapine and risperidone.. Amphetamine-stimulated locomotor activity (Amp-LMA; 1.0 or 3.0 mg/kg s.c.) and apomorphine-disrupted prepulse inhibition (Apo-PPI; 0.5 mg/kg s.c.) were used as tests for antipsychotic activity. Delayed non-match to place (DNMTP) and five-choice serial reaction (5-CSR) tasks were used to assess short-term spatial memory and attention, respectively. Asenapine doses varied across tasks: Amp-LMA (0.01-0.3 mg/kg s.c.), Apo-PPI (0.001-0.3 mg/kg s.c.), DNMTP (0.01-0.1 mg/kg s.c.), and 5-CSR (0.003-0.3 mg/kg s.c.).. Asenapine was highly potent (active at 0.03 mg/kg) in the Amp-LMA and Apo-PPI assays. DNMTP or 5-CSR performance was not improved by asenapine, olanzapine, or risperidone. All agents (P < 0.01) reduced DNMTP accuracy at short delays; post hoc analyses revealed that only 0.1 mg/kg asenapine and 0.3 mg/kg risperidone differed from vehicle. All active agents (asenapine, 0.3 mg/kg; olanzapine, 0.03-0.3 mg/kg; and risperidone, 0.01-0.1 mg/kg) significantly impaired 5-CSR accuracy (P < 0.05).. Asenapine has potent antidopaminergic properties that are predictive of antipsychotic efficacy. Asenapine, like risperidone and olanzapine, did not improve cognition in normal rats. Rather, at doses greater than those required for antipsychotic activity, asenapine impaired cognitive performance due to disturbance of motor function, an effect also observed with olanzapine and risperidone.

Topics: Amphetamine; Animals; Antipsychotic Agents; Apomorphine; Attention; Benzodiazepines; Cognition; Dibenzocycloheptenes; Disease Models, Animal; Dose-Response Relationship, Drug; Heterocyclic Compounds, 4 or More Rings; Male; Olanzapine; Psychotic Disorders; Rats; Rats, Sprague-Dawley; Risperidone

The objective of this study was to illustrate the implications of using standardised psychotic relapse definitions by comparing published clinical trial relapse and drop-out rates for patients with schizophrenia.. Relapse definitions from three published placebo-controlled clinical trials were standardised to facilitate pair-wise retrospective comparison of relapse outcomes in patients with schizophrenia receiving extended-release quetiapine fumarate (quetiapine XR), paliperidone extended release (paliperidone ER) and olanzapine. Relapse definitions were based on changes in the Positive and Negative Syndrome Scale score, Clinical Global Impression-Severity score and predefined Brief Psychiatric Rating Scale positive items. Economic implications of relapse outcomes were also calculated. A limitation of this study is that this was not a head-to-head comparison. In addition, patient-level data were lacking for the paliperidone ER and olanzapine studies.. When the relapse definition from the paliperidone study was applied to the quetiapine XR clinical trial data, 14 quetiapine XR patients (15%) relapsed compared with 23 (22%) in the paliperidone ER study. According to the olanzapine relapse definition, three quetiapine XR patients (3.2%) experienced a relapse compared with nine patients (4.0%) in the olanzapine study. An illustrative calculation of potential economic impact associated with these standardised relapse rates implied incremental expenditures ranging from 74.8 million pound sterling to 373.9 million pound sterling (2006 pound sterling) for paliperidone ER versus quetiapine XR treatment and no material difference with olanzapine.. The results show that the definition of relapse has a significant impact on relapse outcomes, and associated economic implications, and that relative drug efficacy can only be considered when results are based on standardised relapse criteria.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Controlled Clinical Trials as Topic; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Isoxazoles; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Placebos; Psychotic Disorders; Pyrimidines; Quetiapine Fumarate; Recurrence; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cognitive Behavioral Therapy; Combined Modality Therapy; Early Diagnosis; Female; Humans; Male; Olanzapine; Outpatients; Psychotic Disorders; Randomized Controlled Trials as Topic; Risk; Risperidone; Time Factors; Young Adult

Topics: Anti-Inflammatory Agents; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Ataxia; Benzodiazepines; Depressive Disorder, Major; Doxepin; Female; Humans; Middle Aged; Olanzapine; Opioid-Related Disorders; Prednisone; Psychotic Disorders; Treatment Outcome; Vasculitis, Central Nervous System

To assess the effects of olanzapine and risperidone on metabolic factors in children and adolescents admitted to an inpatient psychiatric hospital.. The study was a retrospective chart review of hospitalized patients younger than 18 years of age treated with olanzapine or risperidone. Data collected from medical charts were analyzed to assess weight gain, lipid profiles, blood pressure, and glucose levels in patients prescribed olanzapine or risperidone.. A total of 49 patients (25 receiving olanzapine and 24 receiving risperidone) with a mean age of 13 years were included in the study; the mean duration of treatment was 27 days. A significant increase in body mass index (BMI) from baseline to endpoint in both treatment groups was found (P<0.001); however, the change in BMI was not significantly different between the olanzapine and risperidone groups (P=0.425). Seven new cases (28%) in the olanzapine group and 4 new cases (17%) in the risperidone group met criteria for being overweight or at risk for being overweight. A significant increase in mean systolic blood pressure was found in subjects receiving olanzapine compared with those receiving risperidone (+5.4 mm Hg vs. -3.2 mm Hg; P=0.044), while diastolic blood pressure did not differ between the treatment groups. A significant increase in risk factors for diabetes mellitus (P=0.008) and in overall risk factors for metabolic syndrome (P=0.013) was found in the olanzapine group over the course of treatment, whereas no significant effect on risk factors for diabetes or metabolic syndrome was found in the risperidone group.. Inpatient treatment with both olanzapine and risperidone was correlated with a significant increase in BMI. Olanzapine also resulted in increased risk factors for diabetes and metabolic syndrome.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Child; Diabetes Mellitus, Type 2; Female; Hospitalization; Hospitals, Psychiatric; Humans; Male; Metabolic Syndrome; Olanzapine; Psychotic Disorders; Retrospective Studies; Risperidone

The effect of valproate on the steady-state plasma concentrations of olanzapine was investigated in 18 patients with bipolar or schizoaffective disorder. Additional valproate, at a dose ranging from 600 to 2000 mg/d, was administered for 4 weeks to patients stabilized on olanzapine (5-20 mg/d). During valproate coadministration, mean plasma olanzapine concentrations decreased significantly from 32.9 +/- 9.7 ng/mL at baseline to 27.4 +/- 9.8 ng/mL at week 2 (P = 0.02), and to 26.9 +/- 9.2 ng/mL at week 4 (P = 0.001). Smoking also decreased plasma olanzapine concentrations. Valproate coadministration with olanzapine was well tolerated and no patient showed a worsening of his or her psychopathological condition. These findings indicate that valproate, at doses of up to 2000 mg/d, is associated with a minimal, presumably not clinically significant, decrease in plasma olanzapine concentrations, possibly as a result of induction of olanzapine metabolism. New studies are needed to confirm that valproate could have mild inductive effects.

Topics: Adult; Aging; Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Smoking; Time Factors; Valproic Acid; Young Adult

Stuttering is a vocal phenomenon, which manifests itself as disturbances in speech fluency. While stuttering is most commonly treated with speech therapy and psychotherapy, a number of antipsychotic agents have been investigated as possible treatments. We present the case of a 37-year-old man who developed a post-concussive syndrome with psychosis and associated stuttering after his second exposure to a blast from an improvised explosive device (IED). After treatment with olanzapine, both his psychosis and his stuttering showed significant improvement. We also discuss stuttering and review previous studies that have investigated antipsychotic use in stuttering.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blast Injuries; Brain Concussion; Humans; Iraq War, 2003-2011; Male; Olanzapine; Psychotic Disorders; Stuttering; Warfare

The noradrenergic (NE) system mediates cognitive dysfunction in schizophrenia patients, and the NE transporter represents a putative target for cognitive enhancing therapy. In a double-blind placebo-controlled study we evaluated the effect of add-on reboxetine (4 mg/day), a selective norepinephrine reuptake inhibitor (NRI), co-administered with atypical antipsychotic olanzapine (10 mg/day) on cognitive functioning in DSM-IV schizophrenia patients. The Automated Neuropsychological Assessment Metrics battery and Wisconsin Card Sorting Test were used to assess selective cognitive functions at baseline and endpoint (6 weeks). Clinical assessment was also performed. No between-group differences were found in neurocognitive tests, suggesting that reboxetine did not significantly change patients' cognitive performance compared to placebo. Reboxetine was well-tolerated and did not interfere with the therapeutic effect of olanzapine. Long-term studies using higher reboxetine dosages and alternative NRIs (e.g., atomoxetine) are needed to determine the role of NRIs as cognitive enhancers in patients with schizophrenia and other disorders associated with cognitive impairments.

Topics: Adrenergic Uptake Inhibitors; Adult; Antipsychotic Agents; Benzodiazepines; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Reboxetine; Schizophrenia; Schizophrenic Psychology; Young Adult

This naturalistic study aims to compare discontinuation rates for low-dose first-generation versus second-generation antipsychotics in first-episode psychotic patients.. The prescription of antipsychotic medication in 301 consecutively admitted patients with first-episode psychosis from four catchment areas is described. For the first year of inclusion a first-generation antipsychotic in low dose was recommended as the first medication. From the second year a second-generation antipsychotic was recommended as first choice. Switching was allowed when any drug was judged to be ineffective or to have serious side-effects. Switching during the first 2 years after inclusion is described.. Switching from a low-dose first-generation antipsychotic was more frequent than from a second-generation antipsychotic (90.7 vs. 58.4%). Lack of therapeutic effect and side-effects were the more frequently recorded reasons for changing in the first-generation group. Akathisia, parkinsonism, dyskinesias, dystonia and dysphoria were more often reported in patients on first-generation drugs. Weight gain and sedation were more often reported in patients on second-generation drugs.. The findings suggest a better adherence to and tolerability for second-generation antipsychotics than for low-dose first-generation antipsychotics in first-episode psychosis.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Chi-Square Distribution; Clopenthixol; Clozapine; Female; Humans; Imidazoles; Indoles; Kaplan-Meier Estimate; Male; Middle Aged; Olanzapine; Perphenazine; Psychotic Disorders; Risperidone; Statistics, Nonparametric; Time Factors; Young Adult

In comparison to metabolic syndrome, edema seems to be a rare occurrence in antipsychotic treatment.. In this paper, we report on two subjects with psychotic disorders who were found to have peripheral edema during olanzapine therapy.. The theoretical background and the relevance of this observation are examined. Furthermore, edema as a side effect of antipsychotic treatment is reviewed. In particular, the importance of olanzapine, a commonly used neuroleptic drug, as a possible causative substance is evaluated.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Therapy, Combination; Edema; Female; Humans; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Facial Muscles; Humans; Male; Olanzapine; Psychotic Disorders; Syndrome; Tremor

To make well informed treatment decisions for their patients, clinicians need credible information about potential risk for substantial weight gain. We therefore conducted a post-hoc analysis of clinical trial data, examining early weight gain as a predictor of later substantial weight gain.. Data from 669 (Study 1) and 102 (Study 2) olanzapine-treated patients diagnosed with schizophrenia, schizophreniform, or schizoaffective disorder were analyzed to identify and validate weight gain cut-offs at Weeks 1-4 that were predictive of substantial weight gain (defined as an increase of > or = 5, 7, 10 kg or 7% of baseline weight) after approximately 30 weeks of treatment. Baseline characteristics alone, baseline characteristics plus weight change from baseline to Weeks 1, 2, 3 or 4, and weight change from baseline to Weeks 1, 2, 3, or 4 alone were evaluated as predictors of substantial weight gain. Similar analyses were performed to determine BMI increase cut-offs at Weeks 1-4 of treatment that were predictive of substantial increase in BMI (1, 2 or 3 kg/m2 increase from baseline).. At Weeks 1 and 2, predictions based on early weight gain plus baseline characteristics were more robust than those based on early weight gain alone. However, by Weeks 3 and 4, there was little difference between the operating characteristics associated with these two sets of predictors. The positive predictive values ranged from 30.1% to 73.5%, while the negative predictive values ranged from 58.1% to 89.0%. Predictions based on early BMI increase plus baseline characteristics were not uniformly more robust at any time compared to those based on early BMI increase alone. The positive predictive values ranged from 38.3% to 83.5%, while negative predictive values ranged from 42.1% to 84.7%. For analyses of both early weight gain and early BMI increase, results for the validation dataset were similar to those observed in the primary dataset.. Results from these analyses can be used by clinicians to evaluate risk of substantial weight gain or BMI increase for individual patients. For instance, negative predictive values based on data from these studies suggest approximately 88% of patients who gain less than 2 kg by Week 3 will gain less than 10 kg after 26-34 weeks of olanzapine treatment. Analysis of changes in BMI suggests that approximately 84% of patients who gain less than .64 kg/m2 in BMI by Week 3 will gain less than 3 kg/m2 in BMI after 26-34 weeks of olanzapine treatment. Further research in larger patient populations for longer periods is necessary to confirm these results.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Female; Humans; Male; Obesity; Olanzapine; Psychotic Disorders; Risk Factors; Schizophrenia; Time Factors; Treatment Outcome; Weight Gain

Analyses of smooth pursuit eye movement parameters in patients with schizophrenia provide information about the integrity of neural networks mediating motion perception, sensorimotor transformation, and cognitive processes such as prediction. Although pursuit eye tracking deficits have been widely reported in schizophrenia, the integrity of discrete components of pursuit responses and the effect of second-generation antipsychotic medication on them are not well established.. To examine different components of smooth pursuit performance in antipsychotic-naive patients with schizophrenia before and after treatment with second-generation antipsychotic medication.. Thirty-three antipsychotic-naive patients with schizophrenia performed 3 different smooth pursuit paradigms designed to evaluate specific components of the pursuit response. All of the patients were retested after 6 weeks of treatment with risperidone or olanzapine. Testing was also performed with 39 matched healthy individuals. Thirteen patients and 21 healthy participants were retested after 26 and 52 weeks.. Pursuit initiation, maintenance gain (ratio of eye velocity over target velocity), and frequency of catch-up saccades during pursuit maintenance.. Prior to treatment, pursuit gain when tracking less predictable ramp targets tended to be reduced, latency of pursuit initiation was speeded, and catch-up saccade frequency was increased during predictive pursuit. After antipsychotic treatment initiation, pursuit gain decreased with ramp targets, indicating treatment-emergent impairments in sensorimotor processing. No changes were observed for predictive pursuit. Exploratory analyses in the subgroup with follow-up to 1 year revealed that these effects continued through long-term follow-up with some partial normalization at 1 year. Deficits were unrelated to drug dosage and clinical ratings.. Impaired sensorimotor function was observed after initiation of second-generation antipsychotic medications, which may be explained by their serotonergic antagonism of brainstem sensorimotor systems. Predictive mechanisms supported by frontostriatal-cerebellar circuitry were not affected by treatment initiation and appear able to compensate for treatment-emergent sensorimotor impairments during predictive tracking.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Follow-Up Studies; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Pursuit, Smooth; Reaction Time; Risperidone; Saccades; Schizophrenia

In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The underlying mechanism, however, is poorly understood. Adiponectin is a recently identified adipocyte-derived protein, with low adiponectin levels being associated with metabolic abnormalities such as obesity, insulin resistance and type 2 diabetes.. Fasting adiponectin levels were assessed in a cross-sectional sample of 386 patients with schizophrenia or schizoaffective disorder. All patients were on monotherapy of second-generation antipsychotics (SGA) and underwent an extensive metabolic screening including an oral glucose tolerance test (OGTT).. Adiponectin plasma levels were inversely correlated with BMI, and differed significantly between patients with normal weight, overweight or obesity (p<0.05). Patients who met criteria for the metabolic syndrome, according to adapted National Cholesterol Educational Program - Adult Treatment Panel criteria (NCEP-ATP III) (29.3%), had significantly lower adiponectin levels than patients not meeting metabolic syndrome criteria (p<0.0001). Patients without glucose abnormalities (78%) had significantly higher adiponectin levels than patients with diabetes (5.7%) (p<0.05). After controlling for components of metabolic syndrome and sex, antipsychotic medication independently influenced adiponectin levels (p<0.0001), with the lowest mean levels in patients on clozapine and olanzapine.. Adiponectin levels in schizophrenic patients mirror what is observed in the general population, with the lowest levels in the most metabolically comprised subjects. However, antipsychotic medication may also influence adiponectin regulation independently, a finding that should be confirmed in longitudinal studies.

Topics: Adiponectin; Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Humans; Male; Metabolic Syndrome; Olanzapine; Psychotic Disorders; Risk Factors; Schizophrenia

Septo-optic dysplasia, a variable combination of abnormalities of cerebral midline structures, is a clinically heterogeneous syndrome in which the midline defects may be implicated in psychiatric disturbances.. To describe a case of septo-optic dysplasia associated with depression and psychosis and to discuss the role of these developmental abnormalities in psychiatric disturbances.. The patient's clinico-anamnestic, neuroradiologic, neuropsychiatric, endocrinologic, ophthalmologic, and genetic profile was evaluated.. Developmental abnormalities due to disruption of the complex neural network linking the septum pellucidum with other limbic structures may have been involved in the affective and psychotic disturbances observed in our patient.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Septo-Optic Dysplasia; Tomography, X-Ray Computed; Valproic Acid; Visual Fields; Wechsler Scales

The goal of this study was to select some genes that may serve as good candidates for future studies of the direct effects (not explained by obesity) of some antipsychotics on hyperlipidemia. A search for single-nucleotide polymorphisms (SNPs) that may be associated with these direct effects was conducted. From a published cross-sectional sample, 357 patients on antipsychotics were genotyped using a DNA microarray with 384 SNPs. A total of 165 patients were taking olanzapine, quetiapine or chlorpromazine which may directly cause hypertriglyceridemia or hypercholesterolemia. Another 192 patients taking other antipsychotics were controls. A two-stage statistical analysis that included loglinear and logistic models was developed to select SNPs blindly. In a third stage, physiological knowledge was used to select promising SNPs. Known physiological mechanisms were supported for 3 associations found in patients taking olanzapine, quetiapine or chlorpromazine [acetyl-coenzyme A carboxylase alpha SNP (rs4072032) in the hypertriglyceridemia model, and for the neuropeptide Y (rs1468271) and ACCbeta, (rs2241220) in the hypercholesterolemia model]. These genes may be promising candidates for studies of the direct effects of some antipsychotics on hyperlipidemia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Cross-Sectional Studies; Dibenzothiazepines; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Lipids; Male; Olanzapine; Oligonucleotide Array Sequence Analysis; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Following the presentation of a case study and an overview of current data highlighting the need for further research into the use of antipsychotic medication during pregnancy, the aim of the present paper was to outline the establishment of, and present preliminary data from, the National Register of Antipsychotic Medication in Pregnancy (NRAMP).. Australian women with a history of psychosis, including schizophrenia, bipolar affective disorder with psychosis, schizoaffective disorder and first-episode psychosis, who are pregnant, are currently being invited to participate. The confluence of speculated national pregnancy rates and epidemiological data regarding child-bearing-age women with psychosis suggested an enrollment target of 100 women over a 24 month period. Details of antipsychotic medication are recorded throughout the pregnancy and for 1 year postnatally. Interviews with the mother are conducted 6 weekly antenatally, and then at 6 and 12 weeks, and 6 and 12 months postnatally, to assess symptoms of psychosis and depression, and attitudes towards parenting. In addition, consultations are conducted with the women's health-care providers to collate information regarding pharmacology and related side-effects, obstetric outcomes, psychiatric diagnoses and symptoms during pregnancy and for 1 year after delivery, and the provision of details on the baby's health and well-being.. NRAMP was launched in 2005. Ethics approvals have been gained at 14 sites nationally. Thirty women have consented, and 11 have completed. Data including demographics, health-care provision and medication for the first 30 participants are presented.. The establishment of NRAMP is an important strategy in improving the management of serious mental illness such as schizophrenia and related disorders, in women who are pregnant. This project involves extensive collaboration between many different clinical groups and industry, and shall culminate in an important resource to improve the quality of life for both patients and future generations.

Topics: Adult; Antipsychotic Agents; Australia; Benzodiazepines; Chlorpromazine; Cross-Sectional Studies; Data Collection; Female; Humans; Infant, Newborn; Olanzapine; Phenytoin; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications; Psychotic Disorders; Registries; Risk Factors; Substance Withdrawal Syndrome; Suicide

The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related.. To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5-20 mg/day), or patients with schizophrenia who received olanzapine (N = 172, 10-20 mg/day), we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW) methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i) stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii) stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses.. While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect.". While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Probability; Psychotic Disorders; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Selection Bias; Treatment Outcome

Problems with the voluntary control of behavior, such as those leading to increased antisaccade errors, are accepted as evidence of prefrontal dysfunction in schizophrenia. We previously reported that speeded prosaccade responses, i.e., shorter response latencies for automatic shifts of attention to visual targets, were associated with higher antisaccade error rates in schizophrenia. This suggests that dysregulation of automatic attentional processes may contribute to disturbances in prefrontally mediated control of voluntary behavior.. Twenty-four antipsychotic-naïve schizophrenia patients and 30 healthy individuals completed three tasks: a no-gap prosaccade task in which subjects shifted gaze toward a peripheral target that appeared coincident with the disappearance of a central fixation target and separate prosaccade and antisaccade tasks in which a temporal gap or overlap of the central target offset and peripheral target onset occurred. Sixteen patients were retested after 6 weeks of antipsychotic treatment.. Patients' prosaccade latencies in the no-gap task were speeded compared with healthy individuals. While patients were not atypical in the degree to which response latencies were speeded or slowed by the gap and overlap manipulations, those patients with diminished attentional engagement on the prosaccade task (i.e., reduced overlap effect) had significantly elevated antisaccade error rates. This effect persisted in patients evaluated after antipsychotic treatment.. This study provides evidence that a reduced ability to engage attention may render patients more distracted by sensory inputs, thereby further compromising impaired executive control during antisaccade tasks. Thus, alterations in attentional and executive control functions can synergistically disrupt voluntary behavioral responses in schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Attention; Benzodiazepines; Electrooculography; Female; Fixation, Ocular; Humans; Male; Neural Inhibition; Olanzapine; Orientation; Pattern Recognition, Visual; Prefrontal Cortex; Psychotic Disorders; Reaction Time; Risperidone; Saccades; Schizophrenia; Signal Processing, Computer-Assisted

This study examined the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly in the United States.. The study involved analysis of household and prescription files of the Medical Expenditure Panel Survey (MEPS) data from 1996 to 2004. The analysis focused on the use of six atypical antipsychotic agents namely, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole among the elderly of 60 years or older. Multiple logistic regression analysis within the conceptual framework of Andersen's Behavioral Model was used to examine the determinants of atypical antipsychotic use among antipsychotic users in community-dwelling elderly.. An average of 0.62 million elderly received antipsychotic agents annually during the study period. A majority of the elderly using antipsychotic agents were female (70%), white (86%), non-Hispanic (95%), and living in metropolitan statistical areas (79%). Frequently reported diagnoses among the elderly taking antipsychotic agents were dementia (26.12%), anxiety (20.42%), and schizophrenia (6.62%). Of the elderly receiving antipsychotic agents, 50.39% received atypical agents and 51.88% received typical agents during the study period. The most frequently used atypical agents were risperidone, olanzapine, and quetiapine. Multivariate logistic regression analysis revealed that need (perceived mental health, p < 0.01) and enabling (time, p < 0.01) factors were significantly associated with atypical antipsychotic use after controlling for predisposing factors. The study found that elderly patients with relatively poor perception of mental health (need) and utilization of antipsychotic agents after 1998 (enabling) were more likely to involve the use of atypical agents.. This study was limited to the use of antipsychotic agents in community settings and cannot be extrapolated to other settings. Correlates examined in this study were limited to variables available from the data source and those used by previous researchers.. Need and enabling factors play a vital role in the use of atypical agents in the elderly. The findings have important implications in understanding the use and outcomes of atypical agents in the elderly. Future pharmacoepidemiological research can use these variables to control for confounding and selection bias when evaluating health care outcomes in observational studies.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Anxiety; Benzodiazepines; Cross-Sectional Studies; Dementia; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Residence Characteristics; Risperidone; Schizophrenia; Serotonin Antagonists; United States

Topics: Acute Kidney Injury; Antipsychotic Agents; Benzodiazepines; Electroencephalography; Female; Fluphenazine; Humans; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Psychotic Disorders

The aim of this study was to assess effectiveness and tolerability of oral olanzapine treatment of adolescents with schizophrenic disorders.. Adolescent patients (12-19 years) with schizophrenia, schizoaffective, or schizophreniform disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) were enrolled in a multicenter, prospective, open-label study. Following a 2- to 9-day washout period, patients initially received 10 mg/day olanzapine. Dose modification was allowed during week 2 (dose range 5-15 mg/day) and during weeks 3-6 (dose range, 5-20 mg/day). Responders (improvement > or =30% on the Brief Psychiatric Rating Scale, BPRS) continued olanzapine for additional 18 weeks. Psychopathology was assessed using BPRS and Clinical Global Impressions (CGI) scales; side effects were assessed by adverse event reporting.. Out of 96 patients enrolled at 10 sites, 60 (62.5%) met response criteria at week 6. Mean BPRS total scores decreased significantly (p < 0.001) from baseline (39.2 +/- 13.4) to week 6 last observation carried forward (LOCF) (22.2 +/- 14.7). The rate of patients considered markedly ill or worse (CGI-S) decreased from 83.3% (baseline) to 37.5% (week 6, LOCF). The most common reported adverse event was weight gain (30.2%, 29/96). Three patients (3.1%) discontinued due to adverse events.. In this study of young patients with schizophrenia, schizoaffective, or schizophreniform disorders, olanzapine treatment was associated with marked symptom improvement. As changes in weight and prolactin levels may be greater in adolescent than in adult patients, potential risks and benefits of olanzapine treatment in adolescents should be considered carefully.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Child; Electrocardiography; Electroencephalography; Female; Humans; Male; Olanzapine; Prolactin; Prospective Studies; Psychotic Disorders; Schizophrenia; Weight Gain

To test association of dopamine receptor D3 (DRD-3) gene polymorphisms with olanzapine response in genetic samples from a registration phase clinical trial.. Eighty-eight acutely ill patients with schizophrenia or schizoaffective disorder were genotyped for ser-9-gly (rs6280) and 23 other polymorphisms within the DRD-3 gene. Allelic association of clinical response (mean baseline- to-endpoint reduction in Positive and Negative Syndrome Scale [PANSS] total and subscores) over 6 weeks of olanzapine treatment was assessed using repeated measures analysis of variance.. Ser-9-gly genotypes were associated with differences in PANSS total score improvement from baseline to 6 weeks (p = 0.021). This association was most notable for improvement in positive symptoms (p = 0.0001), with patients with gly/gly genotype significantly more responsive. More patients with the gly/gly genotype had greater positive symptom remission (endpoint rating of minimal or none on all PANSS positive items, 39.1%) compared with patients with gly/ser and ser/ser genotypes (13.8%; p = 0.033). DRD-3 polymorphisms in disequilibrium with ser-9-gly were also significantly associated with greater positive symptom improvement (p = 0.0009-0.021), and one not in complete linkage disequilibrium, with lesser improvement (p = 0.027).. Gly/gly DRD-3 genotype predicted statistically and clinically significantly better acute positive symptom reduction compared with other ser-9-gly genotypes in patients treated with olanzapine.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Double-Blind Method; Female; Genotype; Humans; Male; Olanzapine; Polymorphism, Genetic; Psychotic Disorders; Randomized Controlled Trials as Topic; Receptors, Dopamine D3; Schizophrenia; Treatment Outcome; White People

Topics: Adolescent; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Climate; Clonazepam; Dehydration; Delusions; Depressive Disorder; Fluoxetine; GABA Modulators; Greenhouse Effect; Humans; Male; Olanzapine; Psychotic Disorders; Water Supply

Antipsychotic (AP) treatment, in particular with some second-generation drugs, is associated with weight gain and other metabolic side effects. However, the relationship between drug-induced weight gain and dyslipidemia is not well understood. We investigated how cardiometabolic risk factors were related to body mass during treatment with different APs under real-life conditions.. This cross-sectional naturalistic study included 242 subjects with severe mental disorders who were on monotherapy with olanzapine (OLZ) or clozapine (CLZ) (n = 80), monotherapy with other APs (n = 80), or unmedicated (n = 82). Groups were adjusted for age and compared for prevalence of the metabolic syndrome and its components. Groups were further adjusted for body mass and compared for mean values of blood pressure, lipids, and fasting glucose.. There was no significant intergroup difference in the prevalence of metabolic syndrome, obesity, hypertension, or hyperglycemia. Despite similar body mass index, OLZ/CLZ-treated subjects had significantly higher prevalence of dyslipidemia (high triglyceride and low HDL cholesterol levels) than unmedicated subjects. They also had higher mean values of triglycerides (P = 0.003) and lower mean values of HDL cholesterol (P < 0.001). Patients treated with other APs had intermediate values.. Intergroup differences in body mass index were minimal in this naturalistic setting, probably because of awareness of this treatment hazard among clinicians. However, independently of body mass, dyslipidemia was significantly associated with AP treatment, in particular with OLZ and CLZ. These findings indicate a primary effect of APs on lipid regulation, important in understanding their mechanism of action, and with clinical implications.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cholesterol, HDL; Clozapine; Cross-Sectional Studies; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Hypertension; Male; Metabolic Syndrome; Middle Aged; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Schizophrenia; Sex Factors; Triglycerides; Weight Gain

To investigate 3-month changes in glucose metabolism in a naturalistic sample of patients with schizophrenia newly started on or switched to specific atypical antipsychotic medication therapy.. One hundred eighty-three patients were evaluated before initiation and 3 months after with a 75-g glucose load oral glucose tolerance test (OGTT). Data were collected between November 2003 and January 2007.. Eight patients (4.4%) developed new-onset diabetes within 3 months. Initiation of clozapine resulted in a significantly higher risk for new-onset glucose abnormalities than initiation of aripiprazole (odds ratio = 67.29, 95% CI = 5.23 to 866.49). Significant drug x time interactions were found for all OGTT glucose assessments (fasting: F = 6.79, df = 5,177; p < .0001; 30 minutes: F = 3.89, df = 5,177; p = .0023; 60 minutes: F = 5.03, df = 5,177; p = .0002; 120 minutes: F = 3.78, df = 5,177; p = .0028), with the evolution of plasma glucose levels being significantly worse in patients initiated on clozapine therapy (fasting, 30 minutes, and 60 minutes), olanzapine therapy (fasting, 60 minutes, and 120 minutes), and quetiapine therapy (fasting and 60 minutes) than in patients initiated on aripiprazole therapy (p < .05). Clozapine was also significantly more deleterious than risperidone and amisulpride for fasting plasma glucose level changes (p < .05). Type of initiation (start or switch) did not affect any of the metabolic parameters.. The incidence of new-onset glucose abnormalities, including diabetes, in the first 3 months after newly starting or switching atypical antipsychotic medication is high and may be markedly influenced by type of prescribed antipsychotic. The importance of accurately screening for new-onset glucose abnormalities after initiation of an atypical antipsychotic is emphasized.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Blood Glucose; Body Mass Index; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Fasting; Feeding Behavior; Female; Glucose; Glucose Tolerance Test; Humans; Incidence; Insulin; Male; Middle Aged; Olanzapine; Piperazines; Prevalence; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Time Factors

Second-generation atypical antipsychotics improve the outcome of patients with schizophrenia, although studies of their cost efficacy in comparison to first-generation conventional antipsychotics have yielded mixed results.. This study examines the cost effectiveness outcome of olanzapine treatment in veterans with schizophrenia (n 5 22) or schizoaffective disorder (n 5 4).. Health-care utilization and costs associated with prospective olanzapine treatment were compared with those of retrospective first-generation neuroleptic treatment in a mirror-image design.. The analysis of variance with repeated measures for the Positive and Negative Syndrome Scale (PANSS; n 5 22) showed a significant main effect of olanzapine treatment (p , .025), and the effect was of medium-to-large size (h2 5 .13). The PANSS-positive subscale (p , .005) and the PANSS general subscale (p , .005) significantly decreased, but the PANSS negative subscale did not change. The quality of life survey (n 5 21) significantly increased (p , .025), and the effect size was large (h2 5 .14). For VA outpatient and inpatient care, study patients incurred an average cost difference of 2$1,289 (NS) and 2$6,682 (NS), respectively. Combining inpatient and outpatient VA care, patients incurred an annual difference of 2$7,971 per patient (NS). These numerically lower costs were due, in part, to a slower growth rate in outpatient encounters (p 5 .013), lower overall cost per outpatient encounter (p 5 .008), and a lower overall inpatient encounter rate (p 5 .005).. Olanzapine treatment resulted in improvements in positive and general psychiatric symptoms, as well as quality of life. Negative symptoms did not change significantly. Though not statistically significant, the postbaseline health-care costs and utilization declined.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Cost-Benefit Analysis; Economics, Pharmaceutical; Female; Health Care Costs; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quality of Life; Retrospective Studies; Schizophrenia; Veterans

To report a case of rapidly occurring hyperglycemia that occurred in a geriatric patient 3 days after treatment with olanzapine.. An 89-year-old man was admitted for dementia with behavioral disturbance and psychosis and was started on olanzapine 2.5 mg twice daily. Due to paranoia and agitation, the dose was increased to 5 mg twice daily after 2 days. Subsequently, he developed hyperglycemia (fasting blood glucose 138 mg/dL) that resolved when olanzapine was stopped and recurred (fasting blood glucose 150 mg/dL) after 2 days of rechallenge with olanzapine 2.5 mg twice daily. In addition, his overall medical status worsened, as he developed concurrent acute renal failure and became more confused and lethargic. The hyperglycemia once again resolved with discontinuation of the drug.. We postulate that the rapid onset of hyperglycemia and the resulting medical sequelae were due to olanzapine. An objective causality assessment revealed that the adverse drug event was probable. There have been numerous case reports of hyperglycemia with olanzapine in the literature, but none reported hyperglycemia within days of initiation of the medication. Although weight gain often coincides with hyperglycemia in patients taking atypical antipsychotics, it does not seem to be a necessary causal factor. Recent data in animal studies have indicated that olanzapine and clozapine rapidly impair whole-body insulin sensitivity in a dose-dependent manner.. Clinicians treating elderly patients with olanzapine should be aware of the potential for rapidly developing hyperglycemia and monitor such patients accordingly.

Topics: Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Humans; Hyperglycemia; Male; Olanzapine; Psychotic Disorders

The number of electrical injuries are rising in proportion to the increased use of electricity in both domestic and industrial sectors. There are multiple ways in which electricity can cause tissue damage, which can be due to direct effects, electroporation and thermal effects. However, these mechanisms fail to explain the enigmatous occurrences of diffuse and delayed neurological and psychological manifestations, especially those remote to the theoretical current pathway and in absence of any gross neurological abnormalities. Immediate neuropsychological sequelae have been well reported in the literature in the form of transient anxiety, emotional instability and memory disturbances. Among psychiatric manifestations, neurotic disorders like post-traumatic stress disorder, conversion and adjustment disorders have been appreciated many a times as a frequent accompaniment of these injuries. Occasional reports of occurrence of mania have also been recorded.. This study reports a case of schizophrenia like illness following a low voltage electrical injury. A discussion regarding the ways in which electrical injury and schizophrenia like illness could be related has been put forth. A brief review of the literature regarding the occurrence of psychiatric disorders in such injuries is also presented.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Electric Injuries; Electroencephalography; Humans; Male; Olanzapine; Psychotic Disorders; Schizophrenic Psychology; Treatment Outcome

Antipsychotics have long been used to treat agitation and psychosis related to Alzheimer's disease, but in a limited fashion because of troubling adverse effects. The new atypical antipsychotics are thought to be at least as effective as first-generation drugs and to cause fewer adverse effects. These drugs, however, are currently not US FDA-approved for use among elderly demented subjects due to a slight increase in the risk of death and serious cardiovascular events within this population. However, their favourable adverse effect profile has led many physicians to prescribe these drugs as first-line therapy for behaviourally disturbed patients with Alzheimer's disease. Clinical trials to evaluate the use of atypical antipsychotics have produced varying results, and clarity has not yet been achieved. Thus, a quantitative summary of the risks and benefits may help inform complex decisions that must be made in this area. In this study we set out to compare the expected costs and outcomes for a community-dwelling cohort of patients with Alzheimer's disease with agitation and/or psychosis who are (a) untreated, or (b) treated with olanzapine.. We constructed a Markov state-transition model using the best published data from several sources for Alzheimer's disease patient progression and treatment. This model allowed us to compare the expected costs and outcomes associated with olanzapine treatment compared with no treatment for a synthetic cohort of US adults aged > or =65 years. The model cycles every 6 months and continues until all patients die from Alzheimer's disease progression or from co-morbid conditions. Outcome estimates included the incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. The robustness of the estimates was examined by sensitivity analyses of key parameters, including cost of care, olanzapine effectiveness and Alzheimer's disease progression rates.. Results indicated that olanzapine was a cost-effective treatment for agitation and psychosis related to Alzheimer's disease when compared with no treatment (ICER <$US50,000). In addition, sensitivity analyses demonstrated that olanzapine remained cost effective despite multiple variations of several parameters, both alone and concurrently.. Olanzapine treatment for agitation and psychosis related to Alzheimer's disease is cost effective when compared with no treatment. Further analysis should be performed as atypical antipsychotics become generic, as more information on health utilities in the Alzheimer's disease population becomes available, and to compare atypical antipsychotics with first-generation antipsychotics.

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Cost-Benefit Analysis; Drug Costs; Ethnicity; Humans; Markov Chains; Mortality; Olanzapine; Proportional Hazards Models; Psychomotor Agitation; Psychotic Disorders; Quality-Adjusted Life Years; Treatment Outcome; United States

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Health Care Costs; Humans; Informed Consent; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy; Haloperidol; Humans; Olanzapine; Perphenazine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles

Topics: Aged; Alzheimer Disease; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Delirium; Depressive Disorder; Diagnosis, Differential; Dibenzothiazepines; Hallucinations; Humans; Male; Olanzapine; Oxazepam; Psychotic Disorders; Quetiapine Fumarate; Tachycardia

The behavioral and psychological symptoms of dementia present a major challenge in the management of these patients. There is no Food and Drug Administration-indicated medication for the management of these symptoms. Even though atypical antipsychotics are considered safer than conventional antipsychotics, safety concerns have emerged.. The FDA has issued warnings regarding the cardiac and metabolic side effects, cerebrovascular events, and, most recently, mortality risk. This study was conducted in 2003 when physicians were notified of the cerebrovascular risks of risperidone. Since then, similar warnings have been issued for olanzapine and aripiprazole.. The medical records of 58 elderly dementia patients who were taking risperidone and were abruptly switched to olanzapine were reviewed. Clinical Global Impressions scale at assigned retrospectively at switch, and weeks 4-6 assessed treatment.. Baseline and follow-up Clinical Global Impressions scale scores were essentially unchanged. Adverse events were mild to moderate in severity. Mean risperidone dose at switch was 1.54 mg/day (range: 0.25-6 mg/day). Mean olanzapine dose after the switch was 5.69 mg/day (range: 2.52-27.5 mg/day).. Most of the 58 patients were switched from risperidone to olanzapine without any deterioration in their clinical status. Even though it is generally not recommended in elderly patients, abrupt switching did not have any negative consequences in this group of patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Benzodiazepines; Comorbidity; Dementia, Vascular; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Homes for the Aged; Humans; Male; Nursing Homes; Olanzapine; Psychotic Disorders; Retrospective Studies; Risk Factors; Risperidone; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Thiazoles

Significant weight gain is a serious side effect of many antipsychotic medications, yet successful strategies for significant weight loss are lacking. The transtheoretical model for weight management can be used to identify people who are ready to change (contemplation-preparation group) their eating habits and physical activity. This study compared characteristics of patients in Canada who had a psychotic disorder and were ready to make lifestyle changes with characteristics of patients who were not considering lifestyle changes.. Participants were surveyed to determine their stages of change for eating habits and physical activity, and various characteristics were measured, including body mass index, body image, nutritional intake, and level of physical activity.. A total of 101 participants (64 men) (mean+/-SD age 35+/-11 years) were taking antipsychotic medications. Seventy-one percent had schizophrenia spectrum disorders, and 15% had affective psychosis. The prevalence of patients identified as being ready for change was higher than expected: 68% for eating habits and 54% for physical activity. Participants who were ready to change eating habits were also ready to change physical activity habits (p<.04). Stages of change for eating habits were associated with body mass index (p<.004), whereas stages of change for physical activity were associated with self-reported vigorous (p<.001) and moderate (p<.005) physical activity but not mild physical activity.. Clinicians may help patients develop healthier eating and physical activity habits by using the transtheoretical model, because it identifies patients who are ready to change to healthier lifestyle strategies and may help patients with antipsychotic-induced weight gain.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Exercise; Feeding Behavior; Female; Health Knowledge, Attitudes, Practice; Humans; Life Style; Male; Middle Aged; Nutrition Surveys; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Weight Gain

The authors describe three patients with foreign accent syndrome during psychotic episodes which resolve with improvement of psychotic symptoms. Psychotic symptoms were worse during the times patients had foreign accents, suggesting a relationship between the presence of the accent and the severity of the psychosis.

Topics: Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Electroencephalography; Female; Humans; Language; Lithium Carbonate; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenic Psychology; Tomography, Emission-Computed, Single-Photon; Valproic Acid; Verbal Behavior

Schizophrenia is a neurodevelopmental disorder associated with persistent symptomatology, severe functional disability, and residual morbidity characteristic of neurodegenerative brain diseases. The illness begins with genetic susceptibility and generally expresses itself after puberty through subtle changes that begin during the prodromal stage. Symptoms get progressively worse and tend to become more resistant to treatment with each relapse. Evidence for a neuroprotective effect of some forms of early treatment is beginning to emerge. While the underlying mechanisms remain uncertain, atypical antipsychotics may counteract some of the progressive deteriorative effects by enhancing synaptic plasticity and cellular resilience. However, identifying and treating patients in the earliest disease states presents methodological challenges as there is no consensus on the best methods of intervention and differences in at-risk children are not readily detectable or substantial enough to predict which ones will develop schizophrenia. In this expert roundtable supplement, Jeffrey A. Lieberman, MD, reviews the historical context of progressive deterioration in schizophrenia. Next, Diana O. Perkins, MD, MPH, reviews some of the challenges to early identification of illness as well as the impact of early versus delayed treatment. Finally, L. Fredrik Jarskog, MD, focuses on the neurobiology of functional progression in schizophrenia as well as pharmacology and the potential for neuroprotection.

Topics: Adolescent; Adult; Antipsychotic Agents; Atrophy; Benzodiazepines; Cerebral Cortex; Child; Cognition Disorders; Disease Progression; Haloperidol; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Neurodegenerative Diseases; Neuroprotective Agents; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Schizotypal Personality Disorder

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delusions; Edema; Eyelid Diseases; Humans; Male; Olanzapine; Psychotic Disorders; Suicide, Attempted

This article provides an introduction to the complex issues surrounding the management of women who have a history of psychosis and who become pregnant. Balancing the mental wellbeing of the woman and the safety and wellbeing of the baby is a complex task for both the expectant mother and the health professionals involved in her care.. Within this article the complexity of the issues will be outlined as a case report of a woman with a history of psychotic related disorders, who was also pregnant.. The woman was being case managed by a Mental Health Service in Victoria, Australia, and was included on the National Register of Antipsychotic Medications in Pregnancy Register (NRAMP) recently established at the Alfred Psychiatry Research Centre (APRC).. The profile of women with a history of previous mental illness, and who are pregnant, often includes a poor psychosocial history and involvement with child protection agencies with regard to custody of the children. Well meant but poorly coordinated decisions by health professionals result in sub-optimal outcomes for both mother and infant.. There is a need for the exploration of the management and experiences of women who have a history of psychosis and who are pregnant. This case example highlights the complexity of issues surrounding the management of this vulnerable group of women and their babies.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Case Management; Child Custody; Cooperative Behavior; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hyperbilirubinemia, Neonatal; Infant, Newborn; Infant, Small for Gestational Age; Interprofessional Relations; Olanzapine; Pregnancy; Pregnancy Complications; Psychotic Disorders; Puerperal Disorders; Risperidone; Schizophrenia; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Psychotic Disorders

The author relates the case study of a 38-year-old man with schizoaffective disorder (bipolar type) refractory to multiple medications. This patient had a long history of psychiatric illness and had been hospitalized at least 15 times because of aggression, hostility, and psychosis. Two separate trials of risperidone and olanzapine resulted in adverse effects, including possible neuroleptic malignant syndrome. Quetiapine, as part of combination therapy, led to substantial reductions in the patient's schizoaffective disorder symptoms and problematic behaviors. The patient tolerated quetiapine and did not experience any adverse effects. Quetiapine may be a suitable treatment option in patients with schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Humans; Male; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Violence

Following our report of a linkage at 12q24 with a phenotype of obesity under antipsychotics, we tested the pro-melanin-concentrating hormone (PMCH) candidate gene for a possible association in humans with the body mass index (BMI; kg/m2) in unrelated schizophrenic patients (SZ) receiving antipsychotics (N = 300) and in controls (CTL; N = 150). Subjects were classified in obese (OB) (BMI > or = 30 kg/m2), overweight (25 < or = BMI < 30 kg/m2), and normal weight (BMI < 25 kg/m2) groups. Single nucleotide polymorphisms (SNP) rs7973796 and rs11111201, located 5' at -4.5 kb and 3' at +1.8 kb, respectively, of PMCH were genotyped. Interaction effects of genotypes and antipsychotic treatment on BMI were tested in a covariance analysis with age and gender as covariates. Interaction effects on the prevalence of obesity were tested in a logistic regression analysis. For subjects under 50 years, the effect of the rs7973796 genotype on BMI differed between the SZ patients taking olanzapine and CTL group (interaction P = 0.025). Olanzapine-treated SZ patients carrying the ancestral homozygote genotype showed a higher BMI for rs7973796 (P = 0.016 with the LSMeans t-test) than the variant homozygotes. Accordingly, the ORs for obesity associated with rs7973796 genotypes differed in the SZ patients taking olanzapine compared to the CTL group (interaction P = 0.0094). The G allele was associated with an increase in the odds of obesity in SZ patients taking olanzapine. No association was observed for those over 50 years, or for rs11111201. These results suggest that the common allele of PMCH rs7973796 may be associated with a greater BMI in olanzapine-treated SZ patients.

Topics: Adult; Age Distribution; Aged; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Case-Control Studies; Female; Genetic Linkage; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Hypothalamic Hormones; Male; Middle Aged; Obesity; Olanzapine; Polymorphism, Single Nucleotide; Protein Precursors; Psychotic Disorders; Schizophrenia; Sex Distribution; Weight Gain

We acquired Positron emission tomography with 18-F-deoxyglucose (FDG-PET) and anatomical MRI in 30 never-previously medicated psychotic adolescents (ages 13-20). (FDG-PET) was obtained at baseline and after 8-9 weeks of a randomized double-blind trial of either olanzapine or haloperidol. Neuropsychological tests of executive function were also obtained. Patients carried out the serial verbal learning task, a modification of the California Verbal Learning Test, during the uptake of the FDG. PET scans were coregistered with spoiled gradient MRI (TR=24, TE=5, flip angle 40 degrees, slice thickness 1.2 mm, field of view 230 mm) for accurate anatomical identification of regions of interest traced on the MRI. Twenty-two of the thirty patients completed the second PET and clinical evaluation. Individuals treated with olanzapine increased relative metabolic rates in the frontal lobe more than the occipital lobe while patients treated with haloperidol failed to increase frontal metabolic rates and did not show an anteroposterior gradient in medication response. Haloperidol increased striatal metabolic rate more than olanzapine. Both drugs increased thalamic metabolic rates and this increase was significantly larger in younger (age 13-15) than older (16-21) patients.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Brain; Cognition Disorders; Female; Fluorodeoxyglucose F18; Frontal Lobe; Haloperidol; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Occipital Lobe; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Radiopharmaceuticals; Temporal Lobe

Weight gain is common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate plasma lipids, lipoproteins and some hormones levels during olanzapine treatment in patients with psychosis. The study population comprised twenty nine patients (29) diagnosed with psychosis and eleven patients (11) with endogenous depression. Plasma cholesterol, triglicerides, phospholipids, high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (ApoA-I) and apolipoprotein B (Apo B), and hormones - prolactin, cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and estradiol were measured by auto-analyzer and by classic photometric methods. All measurements were performed before and during one-year treatment with olanzapine and antidepressant. Treatment of the schizophrenic patients with olanzapine caused a great metabolic impact that is primarily expressed in body mass, cholesterol increase and statistically significant rise of BMI, respectively. Body mass increase could be explained by the fact that olanzapine blocked not only dopaminergic, serotonergic, cholinergic, alpha-adrenergic but histaminergic receptors as well.

Topics: Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Hormones; Humans; Lipids; Lipoproteins; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Weight Gain

Although most patients treated for first-episode schizophrenia will experience considerable improvement with initial antipsychotic therapy, a subgroup experiences significant ongoing positive symptoms. Clozapine has unique efficacy in improving treatment-resistant patients with chronic schizophrenia, but its role in the treatment of first-episode patients remains unclear. A standardized treatment algorithm was implemented in our First Episode Psychosis Program, with patients receiving 2 trials with 2 second-generation antipsychotics (olanzapine, quetiapine, or risperidone at low, medium, and high doses), followed by a trial of clozapine as early as 25 weeks into the start of their treatment. Patients progress along the algorithm according to their response as defined by clinical rating scales. To date, 123 patients with first-episode schizophrenia have been treated according to the algorithm. Of these, 93 (76%) responded to the first trial of an antipsychotic. Only 7 (23%) of the remaining 30 patients responded to a second antipsychotic trial; 13 of the remaining 23 individuals agreed to a trial of clozapine. We compared the clozapine-treated group with a group of 9 patients who refused clozapine and chose to continue the same antipsychotic treatment as before. Subjects who received clozapine experienced a mean Brief Psychiatric Rating Scale change of 19 points (from 53.5 to 34.5) and a change in the Clinical Global Inventory severity rating from 5.4 to 3.5 (from severely ill to mildly ill); those who refused clozapine had a 2-point increase in mean Brief Psychiatric Rating Scale (from 53 to 55) and a 0.6-point increase in the mean Clinical Global Inventory severity rating from 5.4 to 6 (remaining markedly to severely ill). In clinical practice, there is a hesitancy to switch individuals to clozapine given its side effect profile and position as treatment of "last resort." The present findings suggest that clozapine may have an important role in the early treatment of first-episode patients whose psychosis does not remit with other second-generation antipsychotics during the first months of treatment.

Topics: Adolescent; Adult; Algorithms; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Resistance; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Chylomicrons; Humans; Male; Olanzapine; Pancreatitis; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Haloperidol; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Retrospective Studies; Risperidone

To study the prescribing practices of atypical antipsychotic drugs in French psychiatric hospitals.. A 1-day cross-sectional observational survey was performed in seven psychiatric hospitals to study prescribing practices of the four atypical antipsychotics (AAP) marketed in France. These hospitals are members of the PIC network, a pharmacists' working group based in southwestern France.. Type and dosages of prescribed atypical antipsychotics, indication and concomitant prescriptions.. The study included 1475 adult inpatients' prescriptions with an antipsychotic drug; 647 prescriptions included an AAP with risperidone and olanzapine accounting for about 70% cases. AAP prescriptions concerned psychotic patients in 65% of cases. Patients receiving an AAP in this indication were more likely to be male, were younger, and received higher daily doses than patients treated for other troubles. They were also more likely to receive associated neuroleptic and anticholinergic antiparkinsonian agents. There were 59 prescriptions (9.1%) for bipolar disorders. Clozapine wasn't used in this indication. In 76.3% of cases, mood stabilizers were associated to the AAP prescribed in this indication.. This observational survey underlines the significant place taken by AAP for the treatment of psychiatric diseases in hospital prescribing practices. They show usage patterns of these drugs: dose, indications and concomitant medications, in line or not with current recommendations and reference guidelines. In bipolar disorders, AAPs seem more likely to be associated to an ongoing therapy using mood stabilizer than to replace it.

Topics: Adult; Age Factors; Amisulpride; Antimanic Agents; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; France; Hospitals, Psychiatric; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Risperidone; Sex Factors; Sulpiride

There are limited data regarding the use of atypical antipsychotic medications in pregnancy. The objectives of the current study were to quantify placental permeability to antipsychotic medications and to document obstetrical outcomes for women taking these agents proximate to delivery.. The authors conducted a prospective observational study of women treated with an atypical antipsychotic or haloperidol during pregnancy. Maternal and umbilical cord plasma samples collected at delivery were analyzed for medication concentrations. Placental passage was defined as the ratio of umbilical cord to maternal plasma concentrations (ng/ml). Obstetrical outcome was ascertained through maternal reports and reviews of obstetrical records.. Fifty-four pregnant women with laboratory-confirmed antipsychotic use proximate to delivery were included in the analysis. Complete maternal-infant sample pairs were available for 50 participants. Placental passage ratio was highest for olanzapine (mean=72.1%, SD=42.0%), followed by haloperidol (mean=65.5%, SD=40.3%), risperidone (mean=49.2%, SD=33.9%), and quetiapine (mean=23.8%, SD=11.0%). There were tendencies toward higher rates of low birth weight (30.8%) and neonatal intensive care unit admission (30.8%) among neonates exposed to olanzapine.. All four antipsychotics demonstrated incomplete placental passage. Quetiapine demonstrated the lowest placental passage of the medications studied. These novel data provide an initial quantification of the placental passage of antipsychotics and fetal exposure in humans, demonstrating significant differences between individual medications.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Fetal Blood; Haloperidol; Humans; Infant, Low Birth Weight; Infant, Newborn; Intensive Care Units, Neonatal; Maternal-Fetal Exchange; Olanzapine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Olanzapine; Pregnancy; Pregnancy Complications; Psychotic Disorders

Assessing treatment effectiveness in longitudinal observational data is complicated as patients may change medications at any time. To illustrate, three general statistical strategies were utilized to assess treatment effectiveness in an observational schizophrenia study: ignoring, eliminating, and modeling the switching. Differential switching rates produced dramatic differences in estimates of treatment effectiveness across the strategies, with p-values ranging from nearly 0 to almost 1. Ignoring the treatment switching by utilizing intent-to-treat approaches resulted in treatment effect estimates of near zero. Various methods of eliminating the switching, such as epoch analyses and on-drug subset analyses, along with use of marginal structural models generated reasonably consistent non-zero treatment effect estimates. When analyzing longitudinal observational data, researchers must understand the options, key concepts and assumptions behind the various statistical methods available. Marginal structural models are a promising approach to estimation of causal treatment effects in such data.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Data Interpretation, Statistical; Female; Humans; Longitudinal Studies; Male; Models, Statistical; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Schizophrenic Psychology

This study examined the short-term effects of first- and second-generation antipsychotic medications on social cognition and basic cognition.. One hundred patients with schizophrenia or schizoaffective disorder participated in an 8 week, double-blind study of risperidone, olanzapine, and haloperidol. Participants were administered multiple measures of social cognition, basic cognition, and clinical symptoms at baseline, the end of week 4, and the end of week 8. Seventy-three patients completed the baseline assessment and at least one other assessment. Data were analyzed with mixed-effects analyses of covariance. For data reduction, the social cognitive measures were clustered into a summary score, and the cognitive measures were clustered into two summary scores: general cognitive ability and processing speed.. There were no treatment-related differences on any of the three summary scores. Social cognition did not show within-group changes over time either by itself or after control for the cognitive clusters. One cognitive score (general cognitive ability) increased during the study period for all three medication groups.. The present study included a rather thorough assessment of social cognition and did not find any evidence of between-group or within-group effects of antipsychotic medication on social cognition.

Topics: Ambulatory Care; Antipsychotic Agents; Benzodiazepines; Cognition; Cognition Disorders; Emotions; Facial Expression; Female; Haloperidol; Humans; Male; Middle Aged; Neuropsychological Tests; Olanzapine; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Social Perception; Treatment Outcome

Risperidone and olanzapine are second-generation antipsychotics that are increasingly used in child and adolescent psychiatry. So far, little is known about plasma concentrations and concentration-to-dose (C/D) ratios of these agents in children and adolescents compared to adults.. This study investigated whether age and gender influence risperidone and olanzapine plasma concentration by determining risperidone and olanzapine plasma levels by tandem mass spectrometry in 162 Caucasian patients (98 risperidone and 64 olanzapine).. For risperidone and 9-hydroxyrisperidone, the C(total)/D ratio was almost identical in both age groups (10-18 and 19-45 years, respectively). In the younger age group, females exhibited significantly higher total plasma levels than males while receiving similar doses of risperidone. For olanzapine, in adolescents significantly higher C/D ratios were detected by an average of 43% (after adjustment for weight: 34%) compared to adults.. This study demonstrates an age effect for olanzapine but not for risperidone resulting in higher olanzapine plasma levels in younger patients. For risperidone, we found a gender effect as female adolescent patients had significantly higher risperidone plasma concentrations than male adolescent patients. Future prospective studies are necessary to clarify whether the prescribed dosage should be different in young and older patients.

Topics: Adolescent; Adult; Aging; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Body Weight; Child; Dose-Response Relationship, Drug; Drug Interactions; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Retrospective Studies; Risperidone; Sex Characteristics; Smoking; Tandem Mass Spectrometry; Valproic Acid

Statistical models based on item response theory were used to examine (a) the performance of individual Positive and Negative Syndrome Scale (PANSS) items and their options, (b) the effectiveness of various subscales to discriminate among individual differences in symptom severity, and (c) the appropriateness of cutoff scores recently recommended by Andreasen and her colleagues (2005) to establish symptom remission.. Option characteristic curves were estimated using a nonparametric item response model to examine the probability of endorsing each of 7 options within each of 30 PANSS items as a function of standardized, overall symptom severity. Our data were baseline PANSS scores from 9205 patients with schizophrenia or schizoaffective disorder who were enrolled between 1995 and 2003 in either a large, naturalistic, observational study or else in 1 of 12 randomized, double-blind, clinical trials comparing olanzapine to other antipsychotic drugs.. Our analyses show that the majority of items forming the Positive and Negative subscales of the PANSS perform very well. We also identified key areas for improvement or revision in items and options within the General Psychopathology subscale. The Positive and Negative subscale scores are not only more discriminating of individual differences in symptom severity than the General Psychopathology subscale score, but are also more efficient on average than the 30-item total score. Of the 8 items recently recommended to establish symptom remission, 1 performed markedly different from the 7 others and should either be deleted or rescored requiring that patients achieve a lower score of 2 (rather than 3) to signal remission.. This first item response analysis of the PANSS supports its sound psychometric properties; most PANSS items were either very good or good at assessing overall severity of illness. These analyses did identify some items which might be further improved for measuring individual severity differences or for defining remission thresholds. Findings also suggest that the Positive and Negative subscales are more sensitive to change than the PANSS total score and, thus, may constitute a "mini PANSS" that may be more reliable, require shorter administration and training time, and possibly reduce sample sizes needed for future research.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Defense Mechanisms; Delusions; Depression; Double-Blind Method; Dyskinesias; Female; Hallucinations; Humans; Individuality; Male; Middle Aged; Models, Statistical; Olanzapine; Personality Inventory; Psychiatric Status Rating Scales; Psychometrics; Psychotic Disorders; Randomized Controlled Trials as Topic; Reproducibility of Results; Schizophrenia; Schizophrenic Psychology; Statistics, Nonparametric; Treatment Outcome

We examined the reliability and construct validity of the 5-Item Arizona Sexual Experience Scale (ASEX) in patients with schizophrenia or schizoaffective disorder. In addition, we assessed the performance of two 1-item screening questions to detect sexual dysfunction as defined by a cut-off scoring criteria of sexual dysfunction for the ASEX. One question was a general question about any side effects. The second question asked specifically about sexual dysfunction. Altogether 247 participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder provided data at a single interview. Results indicated that the ASEX has good internal consistency and construct validity for the patients with schizophrenia and schizoaffective disorder. The point-biserial correlations and logistic regression found a high degree of agreement between the one-item specific screening question for sexual dysfunction and the ASEX. Overall, sensitivity (85%), specificity (63.7%), and positive (83%) and negative (67.1%) predictive values for the specific one-item screening question were satisfactory. The single general side effect question performed poorly (sensitivity=11.3%; specificity=92.5%; positive predictive value=76%; negative predictive value=33%). The current findings demonstrate the highly acceptable psychometric properties of the ASEX in patients with schizophrenia or schizoaffective disorder. In addition, a specific one-item screening question is of clinical utility in patients with schizophrenia or schizoaffective disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cross-Sectional Studies; Dibenzothiazepines; Female; Humans; Interview, Psychological; Male; Middle Aged; Olanzapine; Psychometrics; Psychotic Disorders; Quetiapine Fumarate; Reproducibility of Results; Risperidone; Schizophrenia; Sexual Dysfunction, Physiological

We studied a sample of schizophrenia out-patients to test the hypotheses that serum homocysteine concentrations would correlate positively with measures of glucose metabolism.. Subjects underwent a nutritional assessment and fasting plasma, serum insulin and homocysteine tests.. Males had a significantly higher homocysteine levels than females (7.69 +/- 1.42 microM vs. 6.63 +/- 1.40 microM; P = 0.02). Comparing subjects with normal fasting glucose (NFG) (glucose < 100 mg/dl) and impaired fasting glucose (IFG) (> or = 100 mg/dl) subjects with IFG (mean 8.2 +/- 1.5 microM) had significantly higher homocysteine levels than those with NFG (mean 7.2 +/- 1.4 microM, P = 0.03). IFG was also associated with greater mean values for a Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.002) and diastolic blood pressure (P = 0.045).. The group with IFG had higher fasting serum homocysteine concentrations than those with NFG which supports a connection to an important cardiovascular risk factor.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Blood Pressure; Chronic Disease; Clozapine; Community Mental Health Centers; Female; Folic Acid; Homeostasis; Homocysteine; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Nutrition Assessment; Olanzapine; Prediabetic State; Psychotic Disorders; Reference Values; Risk Factors; Risperidone; Schizophrenia; Sex Factors; Statistics as Topic; Waist-Hip Ratio

To determine whether atypical antipsychotic polytherapy is a risk factor for drug treatment for extrapyramidal side-effects (anti-EPS drugs) and whether the risk is attributable to antipsychotic dose.. We studied Iowa Medicaid beneficiaries aged 18-64 years with an active atypical and no conventional antipsychotic on January 1, 2001. The association of atypical antipsychotic polytherapy with anti-EPS drug treatment was determined. Multiple logistic regression was utilized to adjust for covariates in two models, the first adjusting for age, sex and the specific antipsychotic(s) prescribed, and the second also adjusting for doses.. Among 4400 patients, the unadjusted odds of anti-EPS treatment were increased two-fold with polytherapy. Polytherapy remained a risk factor in the first model (OR 1.5, 95% CI 1.1-2.0), but not after adjusting for doses (OR 1.0, 95% CI 0.7-1.4).. Atypical antipsychotic polytherapy is a risk factor for anti-EPS drug treatment, apparently because of higher cumulative doses.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cross-Sectional Studies; Delayed-Action Preparations; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Iowa; Male; Mathematical Computing; Medicaid; Middle Aged; Models, Statistical; Olanzapine; Product Surveillance, Postmarketing; Psychotic Disorders; Quetiapine Fumarate; Regression Analysis; Risk Factors; Risperidone; Statistics as Topic

Topics: Antipsychotic Agents; Benzodiazepines; Cohort Studies; Dibenzothiazepines; Drug Administration Schedule; Drug Resistance; Humans; Mental Disorders; Olanzapine; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Selection Bias; Thiazoles; Treatment Outcome

We report a case of recurrent psychosis, spanning decades, with full inter-episode recovery and minimal functional impairment. While it is difficult to classify this disorder using DSM IV-TR criteria, Leonhard and others have described a 'cycloid psychosis' that correlates well with the phenomenology and course of this case. We believe this may represent a subset within the ICD-10 category of 'acute and transient psychotic disorders'. While this disorder, of unknown incidence, is not well reported in the U.S., it is worthy of further investigation and clinical attention given its generally favorable prognosis and potentially distinct pathophysiology and treatment.

Topics: Acute Disease; Aged; Benzodiazepines; Cognition Disorders; Delusions; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Hallucinations; Hospitalization; Humans; Lorazepam; Male; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Recurrence

Massive elevations of serum creatine kinase (CK) can occur in a significant number of patients treated with neuroleptics in the absence of neuroleptic malignant syndrome (NMS). We report two cases of CK-elevations associated with quetiapine treatment, which disappeared after drug discontinuation. To our knowledge, case number one is the first case of quetiapine-induced CK elevation in a neuroleptic-naïve patient. We thus suggest CK assessment when myalgia occurs with neuroleptic treatment.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Creatine Kinase; Depressive Disorder, Major; Dibenzothiazepines; Humans; Male; Mianserin; Mirtazapine; Olanzapine; Pain; Psychotic Disorders; Quetiapine Fumarate

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Male; Olanzapine; Psychotic Disorders; Severity of Illness Index; Stevens-Johnson Syndrome; Surveys and Questionnaires; Treatment Outcome

There is retrospective evidence of a correlation between psychosis in multiple sclerosis (MS) patients and temporal lobe pathology. A 35-year-old woman with MS presented with psychosis. There was no concurrent history of medication/substance use or family history. Comparison with previous MRI scans showed significant progression of lesions within the periventricular white matter of the left temporal lobe. This case highlights the association of psychosis and MS progression with worsening of left temporal lobe lesions. Prospective studies are required to ascertain the extent to which left temporal lobe lesions are predictive of future psychosis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delusions; Excitatory Amino Acid Antagonists; Female; Hallucinations; Humans; Lamotrigine; Magnetic Resonance Imaging; Multiple Sclerosis; Olanzapine; Pain; Psychotic Disorders; Risperidone; Temporal Lobe; Triazines; Weight Gain

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cause of Death; Controlled Clinical Trials as Topic; Dementia, Vascular; Humans; Olanzapine; Psychotic Disorders; Risk; Risperidone; Statistics as Topic; Stroke; Survival Analysis

The BEACH program, a continuous national study of general practice activity in Australia, gives us an overview of consultations involving the management of psychoses. In this analysis we have included schizophrenia, affective disorders/bipolar, organic psychoses, and senile psychoses, with undefined psychosis and chronic brain syndrome grouped as 'other'. This synopsis provides a backdrop against which the theme articles in this issue of Australian Family Physician can be further considered.

Topics: Adolescent; Adult; Age Factors; Aged; Antimanic Agents; Antipsychotic Agents; Australia; Benzodiazepines; Directive Counseling; Female; Fluphenazine; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Psychotic Disorders; Referral and Consultation; Sex Factors

The activity of catechol-O-methyltransferase (COMT) may be related to psychosis susceptibility. The Val108/158Met polymorphism of the COMT gene influences its enzymatic activity and may result in altered concentrations of monoamine metabolites and different clinical responses of patients to pharmacological treatments.. We examined in a sample of 42 bipolar patients if the Val108/158Met polymorphism influences: (a) the presence of psychosis in type I bipolar patients; (b) the blood plasma concentration of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), which are metabolites of dopamine and noradrenaline respectively and (c) the severity of the clinical characteristics of these patients and their response to pharmacological treatment.. No significant associations were found between the studied COMT genotypes and the studied parameters. However, a non-significant aggregation of bipolar patients presenting with psychosis was found in the homozygous Val-Val group. Clinical improvement was found to significantly correlate with the levels of plasma MHPG prior to treatment. Moreover, a significant difference was found between the standard deviations of the concentrations of HVA in the three genotypes, but not in their mean values. Significant associations were not detected between COMT polymorphisms and the initial severity of the disorder, or the clinical response to pharmacological treatment.. The size of the studied sample is somewhat small and comparisons have been made with a previously studied control group.. The Val108/158Met polymorphism does not appear to be a crucial determinant in type I bipolar disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biogenic Monoamines; Bipolar Disorder; Catechol O-Methyltransferase; Drug Therapy, Combination; Female; Gene Expression; Genetic Predisposition to Disease; Genotype; Homovanillic Acid; Humans; Lithium Carbonate; Male; Methoxyhydroxyphenylglycol; Middle Aged; Olanzapine; Polymorphism, Genetic; Prevalence; Psychotic Disorders; Severity of Illness Index; Treatment Outcome

Hypersalivation has been reported as a side effect of atypical antipsychotics such as clozapine and olanzapine. As it is very common for antipsychotics to cause dry mouth due to anticholinergic effects, hypersalivation seems to be paradoxical. We present the case of a 34-year-old Japanese man with delusional disorder, somatic type (DSM-IV). He had chronic neck pain as well as somatic hallucination with hypochondriacal delusion for 4 years. Since combination therapy with atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) has been introduced in the treatment of refractory psychiatric disorders such as schizophrenia, olanzapine (10 mg/day) was added to fluvoxamine treatment (200 mg/day) in this case. Subsequently, hypersalivation was induced without any extrapyramidal symptoms. It is suggested that hypersalivation was an adverse effect of olanzapine. Possible interaction olanzapine with fluvoxamine might increase the risk of the adverse effect. When combination therapy of atypical antipsychotics and SSRI is introduced, it should be used cautiously with careful observation. Underlying pharmacological and clinical problems will be discussed.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Fluvoxamine; Humans; Male; Olanzapine; Psychotic Disorders; Sialorrhea

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Benztropine; Dementia; Drug Resistance; Humans; Muscarinic Antagonists; Olanzapine; Psychotic Disorders; Risperidone

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Clopenthixol; Humans; Male; Olanzapine; Psychotic Disorders; Valproic Acid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Restraint, Physical

Agitation is relatively common among Borderline Personality Disorder (BPD) patients in Psychiatric Emergency Services (PES). New injectable atypical antipsychotics are indicated for treatment in agitated psychotic or maniac patients but not for agitated BDP patients. Twenty agitated BPD patients were treated with intramuscular atypical antipsychotics (olanzapine or ziprasidone). Results suggest intramuscular atypical antipsychotics may be effective, fast and safe for treating acute BPD patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Emergency Services, Psychiatric; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Thiazoles; Treatment Outcome

Evaluate sexual dysfunction, as measured by the Arizona Sexual Experience Scale (ASEX), in olanzapine-, quetiapine-, and risperidone-treated outpatients with schizophrenia or schizoaffective disorder.. The sexual functioning of 238 outpatients (age> or =18 years) with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine (n=57), olanzapine (n=94), or risperidone (n=87) was evaluated with a one-time rating of the ASEX. The dose range for each treatment group was 5 to 40 mg/day (M=16.6 mg/day, SD=7.4) for olanzapine; 1 to 8 mg/day (M=3.9 mg/day, SD=1.6) for risperidone; and 50 to 900 mg/day (M=376.8 mg/day, SD=213.4) for quetiapine. Antipsychotic group designation was based on medication treatment at study entry (i.e., non-random assignment). Participant characteristics were collected to test for treatment group differences and for potential associations with severity of sexual dysfunction. The primary data analysis was a mixed linear model analysis of covariance with age, gender, and presence/absence of antidepressant known to cause sexual dysfunction included as covariates.. There was a significant treatment effect on severity of sexual dysfunction, as measured by ASEX total scores (p=.04). The adjusted average ASEX total scores were lower in the quetiapine (M=17.80) than in the risperidone (M=19.69) or olanzapine (M=20.34) groups. Individual comparisons of the treatments on adjusted average ASEX total scores indicated a significant difference between olanzapine and quetiapine (p=.04), but no difference between risperidone and quetiapine (p=.17) or olanzapine and risperidone (p=.76).. Quetiapine was associated with less severe sexual dysfunction than olanzapine and risperidone (albeit the effect between risperidone and quetiapine was not statistically significant). Olanzapine and risperidone were associated with a comparable degree of sexual dysfunction. Patients in all three treatment groups, nonetheless, experienced a moderately high degree of sexual dysfunction. Because the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Outpatients; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia; Severity of Illness Index; Sexual Dysfunction, Physiological

This is a case report of a 33 year old woman with a history of psychosis, who presented to the women's mental health clinic for consultation at the 12(th) week of gestation, having already received olanzapine throughout the first trimester. She was followed from that point on at our clinic and remained on small doses of olanzapine for the rest of her pregnancy, which was uncomplicated. She gave birth to a healthy female, which at the age of three months was diagnosed with developmental dysplasia of the hip and subsequently received appropriate treatment with favorable outcome. The possibility of the association of this congenital dysplasia with the use of olanzapine during pregnancy is further discussed in this paper.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Hip Dislocation, Congenital; Humans; Infant, Newborn; Olanzapine; Pregnancy; Pregnancy Complications; Prenatal Care; Prenatal Exposure Delayed Effects; Psychotic Disorders; Treatment Outcome

Weight gain is a common adverse effect associated with the use of most typical and atypical antipsychotic. Aim of this study was to investigate serum prolactin, leptin, cholesterol, triglyceride, lipoproteins, such high density lipoprotein (HDL), and low density lipoprotein (LDL) levels in patients with Parkinson's disease (PD)-related psychosis during long-term medication with atypical antipsychotic. The study population comprised 40 patients, who were divided into 4 groups: olanzapine (n=10), risperidone (n=10), seroquel (n=10) monotherapy, a group of 10 patients receiving only antiparkinson drugs and a control group of 8 healthy persons. The patients were evaluated at baseline and at the sixth and twelfth week according to the Positive and Negative Syndrome Scale (PANSS), body mass index (BMI), and fasting serum prolactin, leptin, lipids and lipoproteins levels. Treatment of patients with olanzapine caused marked increase of serum LDL, cholesterol, triglyceride, and leptin levels (p<0,02). No changes in HDL concentrations. There was positive relationship between serum leptin, lipid levels and BMI. However, treatment of patients with seroquel did not cause changes in serum prolactin, leptin, lipids, and lipoproteins levels. Our results suggest that treatment of patients with PD-related psychosis with seroquel appears to have minimal influence on serum leptin, prolactin, lipids, lipoproteins and BMI compared with olanzapine and risperidone.

Topics: Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Dibenzothiazepines; Humans; Leptin; Lipids; Lipoproteins; Olanzapine; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Antipsychotic Agents; Antiviral Agents; Benzodiazepines; Hepatitis C; Humans; Interferon-alpha; Male; Middle Aged; Olanzapine; Psychotic Disorders

Monosymptomatic hypochondriacal psychosis (MHP) is a form of psychosis characterized by the delusional idea that there is a serious problem in the skin or other body parts. Because MHP patients believe that their complaint is dermatological, not psychiatric, they often admit to several other medical disciplines before coming to a psychiatry clinic. This leads to a series of time-consuming examinations and treatment interventions. In this case report, we emphasize the importance of diagnosing the illness correctly and referring the patient to a psychiatrist. The patient presented in this report has been treated with a new generation neuroleptic, olanzapine. This treatment has led to complete resolution of delusional symptoms. Therefore, we conclude that knowing that MHP is a psychiatric illness allows early establishment of diagnosis and successful treatment.

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Hypochondriasis; Male; Middle Aged; Olanzapine; Oral Ulcer; Psychotic Disorders; Recurrence; Remission Induction; Skin Diseases

This paper describes a case of co-morbid panic disorder and psychosis with a focus on the successful treatment of the panic disorder via a CBT approach. The patient has had only one episode of psychosis. The cognitive model of panic disorder is used as a template to consider this young man's psychotic experiences, in the context of some types of delusional beliefs, especially those involving the catastrophic and atypical misinterpretation of the physiological sensations associated with anxiety. This case emphasises the therapeutic value for certain patients of focussing therapy on the non-psychotic symptoms once the acute psychotic state has been managed.

Topics: Adult; Agoraphobia; Antipsychotic Agents; Atenolol; Benzodiazepines; Cognitive Behavioral Therapy; Combined Modality Therapy; Desensitization, Psychologic; Diazepam; Hospitalization; Humans; Male; Olanzapine; Panic Disorder; Paroxetine; Psychotic Disorders; Reality Testing; Socialization

Topics: Adolescent; Amnesia; Antipsychotic Agents; Benzodiazepines; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Psychotic Disorders

Reversible schizophrenia-like syndromes have been reported to occur with small-cell carcinoma of the lung, thymoma, and hematological disorders.. A 56-year-old man was admitted due to an acute psychosis characterized by delusions, agitation, and aggressive outbursts. His medical and psychiatric history was unremarkable. On treatment with olanzapine, valproic acid, and perazine there was only moderate improvement. Extensive checkup revealed an isolated mediastinal metastasis of an undifferentiated carcinoma. A primary tumor was not found. After removal of the metastasis, the psychosis remitted rapidly and completely, and the patient remained well on follow-up.. Paraneoplastic syndromes may clinically present as acute psychoses and, in late-onset schizophreniform disorders with an atypical presentation, performing a tumor search should always be considered.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Humans; Male; Mediastinal Neoplasms; Middle Aged; Olanzapine; Paraneoplastic Syndromes, Nervous System; Perazine; Psychotic Disorders; Valproic Acid

Weight gain is a commonly observed adverse effect of atypical antipsychotic medications, but associated changes in energy balance and body composition are not well defined. The authors report here the effect of olanzapine on body weight, body composition, resting energy expenditure, and substrate oxidation as well as leptin, insulin, glucose, and lipid levels in a group of outpatient volunteers with first-episode psychosis.. Nine adults (six men and three women) experiencing their first psychotic episode who had no previous history of antipsychotic drug therapy began a regimen of olanzapine and were studied within 7 weeks and approximately 12 weeks after olanzapine initiation.. After approximately 12 weeks of olanzapine therapy, the median increase in body weight was 4.7 kg, a significant increase of 7.3% from first observation. Body fat, measured by dual-energy x-ray absorptiometry, increased significantly, with a propensity for central fat deposition. Lean body mass and bone mineral content did not change. Resting energy expenditure, measured by indirect calorimetry, did not change. Respiratory quotient significantly increased 0.12 with olanzapine and was greatest in those who gained >5% of their initial weight. Fasting insulin, C-peptide, and triglyceride levels significantly increased, but there were no changes in glucose levels; total, high density lipoprotein, or low density lipoprotein cholesterol levels; or leptin levels.. Olanzapine appears to have induced an increase in central body fat deposition, insulin, and triglyceride levels, suggesting the possible development of insulin resistance. The decrease in fat oxidation may be secondary or predispose patients to olanzapine-induced weight gain.

Topics: Adipose Tissue; Adult; Antipsychotic Agents; Benzodiazepines; Body Composition; Body Weight; C-Peptide; Energy Metabolism; Female; Humans; Insulin; Male; Obesity; Olanzapine; Oxidation-Reduction; Psychotic Disorders; Respiratory Physiological Phenomena; Schizophrenia; Triglycerides

Antipsychotic drugs may contribute to weight gain in children and adolescents.. We used Medline's PubMed in the pediatric age using key words 'weight gain' and 'obesity', for each newer antipsychotic drug.. We found 21 articles linking weight gain and obesity with newer antipsychotic drugs among youths. Risperidone was the most commonly cited agent. Weight gain from olanzapine was the largest among the more commonly prescribed newer agents. All studies reported absolute weight gain. Only a few studies used the better measure of body mass index (BMI). None incorporated growth charts to allow for changes in weight and height over time because of growth.. Weight gain may be a major problem when prescribing newer antipsychotic drugs in the pediatric population. Risperidone is associated with less weight gain than olanzapine. Published reports and studies have not utilized state-of-the-art techniques using BMI with readily available growth charts.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Child; Child, Preschool; Humans; Infant; Obesity; Olanzapine; Prospective Studies; Psychotic Disorders; Risperidone; Weight Gain

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bromocriptine; Drug Therapy, Combination; Female; Galactorrhea; Hormone Antagonists; Humans; Hyperprolactinemia; Olanzapine; Prolactin; Psychotic Disorders

Despite the advances in antipsychotic pharmacotherapy over the past decade, many atypical antipsychotic agents are not readily accessible by patients with major psychosis or in developing countries where the acquisition costs may be prohibitive. Olanzapine is an efficacious and widely prescribed atypical antipsychotic agent. In theory, olanzapine therapeutic dose requirement may be reduced during concurrent treatment with inhibitors of drug metabolism. In vitro studies suggest that smoking-inducible cytochrome P450 (CYP) 1A2 contributes to formation of the metabolite 4'-N-desmethylolanzapine. The present prospective study tested the hypothesis that olanzapine steady-state doses can be significantly decreased by coadministration of a low subclinical dose of fluvoxamine, a potent inhibitor of cytochrome P450 1A2. The study design followed a targeted "at-risk" population approach with a focus on smokers who were likely to exhibit increased cytochrome P450 1A2 expression. Patients with stable psychotic illness (N = 10 men, all smokers) and receiving chronic olanzapine treatment were evaluated for steady-state plasma concentrations of olanzapine and 4'-N-desmethylolanzapine. Subsequently, olanzapine dose was reduced from 17.5 +/- 4.2 mg/d (mean +/- SD) to 13.0 +/- 3.3 mg/d, and a nontherapeutic dose of fluvoxamine (25 mg/d, PO) was added to regimen. Patients were reevaluated at 2, 4, and 6 weeks during olanzapine-fluvoxamine cotreatment. There was no significant change in olanzapine plasma concentration, antipsychotic response, or metabolic indices (eg, serum glucose and lipids) after dose reduction in the presence of fluvoxamine (P > 0.05). 4'-N-desmethylolanzapine/olanzapine metabolic ratio decreased from 0.45 +/- 0.20 at baseline to 0.25 +/- 0.11 at week 6, suggesting inhibition of the cytochrome P450 1A2-mediated olanzapine 4'-N-demethylation by fluvoxamine (P < 0.05). In conclusion, this prospective pilot study suggests that a 26% reduction in olanzapine therapeutic dose requirement may be achieved by coadministration of a nontherapeutic oral dose of fluvoxamine.

Topics: Benzodiazepines; Drug Interactions; Drug Therapy, Combination; Fluvoxamine; Humans; Middle Aged; Olanzapine; Pilot Projects; Prospective Studies; Psychotic Disorders

This retrospective study aimed to compare differences in hepatic enzyme elevation during treatment with either risperidone or olanzapine alone in patients with psychotic disorders. The charts were reviewed for six hundred and sixty-seven (667) inpatients with psychotic disorders who were treated with either risperidone (n=289) or olanzapine (n=145) alone at a university-affiliated hospital between 1998 and 2002. Frequencies of elevation greater than the reference level in any enzyme among aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphotase (ALP) were higher in the olanzapine-treated group (26.9%) than in the risperidone-treated group (14.2%) [odds ratio (OR)=2.225, 95% confidence interval (CI)=1.362-3.638, P=0.002]. Frequencies of elevation greater than the reference level in ALT were higher in the olanzapine-treated group than in the risperidone-treated group (OR=2.182, P=0.004), as were frequencies with two-fold (OR=3.064, P=0.017) and three-fold (OR=2.883, P=0.039) elevation. Recovery time was longer in the olanzapine-treated group than in the risperidone-treated group (P=0.0059), as was latency time (P=0.0044). These results suggest that there are potential differences in antipsychotic-associated hepatic enzyme alterations between risperidone and olanzapine treatment. Controlled, prospective studies should be conducted to identify the risk factors associated with an alteration in hepatic enzymes related to treatment with risperidone and olanzapine.

Topics: Adult; Alanine Transaminase; Alkaline Phosphatase; Antipsychotic Agents; Aspartate Aminotransferases; Benzodiazepines; Female; Humans; Inpatients; Liver; Liver Function Tests; Male; Olanzapine; Psychotic Disorders; Retrospective Studies; Risperidone; Schizophrenia

Although pharmacologic treatments are available for patients with schizophrenia, little is known about how prescription patterns of atypical antipsychotic agents are related to patient characteristics. In this study, we examined the association between patient characteristics and the likelihood of being initiated on olanzapine or risperidone, two of the most frequently prescribed atypical agents for schizophrenia. We selected patients who were diagnosed with schizophrenia or schizoaffective disorder based on > or = 1 inpatient or > or = 2 outpatient ICD-9-CM codes (> or = 7 days apart) between 7/1/98 and 6/30/99 from the Veterans Health Administration (VA). We classified patients into one of three types of initiation: (a) not on olanzapine or risperidone, (b) not on any atypical agents, or (c) not on any antipsychotic agents for 6 months, and then subsequently being prescribed the target drugs. Using logistic regression, we examined whether the odds ratio of being initiated on olanzapine versus risperidone are related to patient sociodemographic and clinical characteristics. Compared to risperidone initiators, olanzapine initiators used more drugs for psychiatric conditions (including antiparkinsonian agents, typical antipsychotics, and mood stabilizers) than risperidone initiators. On the other hand, risperidone initiators had more medical comorbidities and more non-psychiatric hospitalizations. Olanzapine and risperidone appear to be prescribed to patients with different characteristics. Initiation of risperidone was more common among patients who presented with more medical comorbid conditions, whereas initiation of olanzapine was more common among patient who presented with more mental comorbid conditions. Future research needs to determine the reasons for those differences.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Comorbidity; Female; Humans; Likelihood Functions; Logistic Models; Male; Mental Health Services; Middle Aged; Multivariate Analysis; Olanzapine; Patient Selection; Psychotic Disorders; Retrospective Studies; Risperidone; Schizophrenia; Socioeconomic Factors; United States

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Citalopram; Delusions; Depressive Disorder, Major; Diagnosis, Differential; Drug Therapy, Combination; Hospitalization; Humans; Male; Marijuana Abuse; Olanzapine; Patient Readmission; Psychotic Disorders; Spouses

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delusions; Drug Therapy, Combination; Humans; Hypochondriasis; Male; Olanzapine; Pimozide; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Adult; Benzodiazepines; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Hyperlipidemias; Male; Olanzapine; Prospective Studies; Psychotic Disorders; Weight Gain

There are few real life independent comparative studies of atypical antipsychotics. We prospectively examined five commonly used atypical antipychotics in the UK, without support from the pharmaceutical industry.. Prospective naturalistic systematic clinical evaluation. Patients being newly prescribed atypical anti-psychotics over a one year period were assessed by psychiatrists at initiation and after six months treatment using five outcome measures: clinical global impression; positive and negative psychotic symptoms; drug related side effects; and quality of life.. 373 patients participated in total. Olanzapine and risperidone produced statistically significant reductions in all ratings at six months. Amisulpride, clozapine, and quetiapine were also studied. There was limited variance between the different drugs, although some sample sizes were small.. Atypical anti-psychotics were found to be clinically effective, and produced similar outcomes. Routine monitoring of outcomes in psychiatry is feasible.

Topics: Adolescent; Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Patient Compliance; Probability; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Risk Assessment; Risperidone; Severity of Illness Index; Statistics, Nonparametric; Sulpiride; Treatment Outcome

Atypical antipsychotics, especially clozapine and olanzapine, have been increasingly associated with weight gain and other adverse metabolic events (diabetes mellitus, hyperlipidemia) in non-mentally retarded populations. This report explores the incidence of this phenomenon in an institution-dwelling population of individuals with developmental disabilities.. A retrospective longitudinal analysis was performed for a sample of 41 adults with developmental disabilities and comorbid psychiatric and/or behavioral syndromes for whom treatment was converted from typical antipsychotics to olanzapine or risperidone for a minimum period of 2 years. Data were collected from October 1998 to September 2002. Among parameters analyzed were chlorpromazine equivalent dosage of antipsychotic, metabolic parameters, body mass index (BMI), level of concurrent medications, and concomitant dietary restrictions.. Thirty-two study subjects (78.0%) were men. The mean age of the study subjects was 43.6 years (at the end of the study). Thirty-seven (90.2%) had severe-to-profound mental retardation. Eight (19.5%) were on a restricted diet. Twenty-three subjects (56.1%) were switched from a typical antipsychotic to olanzapine, and 18 subjects (43.9%) were switched from a typical antipsychotic to risperidone. Of the subsample of subjects who were switched from a typical antipsychotic to risperidone, 12 (66.7%) went on to be switched to olanzapine because of either emergent side effects or lack of efficacy. For the overall sample (N = 41), there was a 19.3% increase in chlorpromazine-equivalent antipsychotic dosage from baseline to the 2-year endpoint along with a 5.6% decrease in fasting blood glucose from baseline to the 2-year endpoint. There were no significant differences between baseline and endpoint values for BMI, total cholesterol, low-density lipoprotein cholesterol, or triglycerides.. The findings of this 2-year evaluation suggest that clinically or statistically significant BMI increases as well as blood glucose and lipid elevations are not unavoidably correlated with the use of the atypical antipsychotic agents olanzapine and risperi-done and may be minimized by careful monitoring, a regimen of dietary control, and a moderate activity level in a residential population of individuals with mental retardation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholesterol; Comorbidity; Diabetes Mellitus; Female; Humans; Hyperlipidemias; Intellectual Disability; Longitudinal Studies; Male; Metabolic Syndrome; Middle Aged; Motor Activity; Olanzapine; Psychotic Disorders; Retrospective Studies; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Creatine Kinase, MM Form; Humans; Male; Myoglobin; Olanzapine; Psychotic Disorders; White People

The possibility that low-dose antipsychotic treatment is associated with increased risk of cerebrovascular events (CVEs) in elderly patients with dementia has been raised. The objective was to determine whether risperidone is associated with an increased risk of CVEs relative to other commonly considered alternative treatments.. An analysis of Medicaid data from 1999 to 2002, representing approximately 8 million enrollees from multiple states, was conducted. The primary outcome was the incidence of acute inpatient admission for a CVE within 3 months following initiation of treatment with atypical antipsychotics (risperidone, olanzapine, quetiapine, or ziprasidone), haloperidol, or benzo-diazepines.. Descriptive analyses found similar rates of incident CVEs across evaluated agents. Multivariate analyses found no differences in comparisons of risperidone with olanzapine or quetiapine. Risperidone and other antipsychotics as a group were also not associated with a higher odds ratio (OR) of incident CVE than either haloperidol or benzodiazepines. With risperidone as the reference group: olanzapine, OR = 1.05, 95% CI 0.63-1.73; quetiapine, OR = 0.66, 95% CI 0.23-1.87; haloperidol, OR = 1.91, 95% CI 1.02-3.60; benzodiazepines, OR = 1.97, 95% CI 1.30-2.98. With benzodiazepines as the reference group, the OR of incident CVE for all antipsychotics as a class was 0.49, 95%CI 0.35-0.69.. This study found no significant difference in the incidence of CVEs between patients taking risperidone and those taking other atypical antipsychotics. Risperidone and all atypical antipsychotics were not associated with higher risk than two common treatment alternatives (haloperidol and benzodiazepines). These findings do not support the conclusion that risperidone is associated with a higher risk of CVE than other available treatment alternatives. The data also suggest that patient characteristics other than antipsychotic use are more significant predictors of CVEs. Given the relatively low rates of incident CVEs, a larger sample of patients with groups closely balanced on a wide spectrum of potential risk factors could provide a more precise assessment of risk.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cerebrovascular Disorders; Cohort Studies; Dementia; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Haloperidol; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Patient Admission; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Thiazoles

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Fluvoxamine; Humans; Olanzapine; Psychotic Disorders

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Humans; Olanzapine; Piperazines; Psychomotor Agitation; Psychotic Disorders; Quinolones; Risperidone; Thiazoles

Topics: Antidepressive Agents; Antipsychotic Agents; Azabicyclo Compounds; Benzodiazepines; Clonazepam; Cyclohexanols; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Love; Olanzapine; Piperazines; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Wit and Humor as Topic

Plasma prolactin concentration was measured in patients with schizophrenia and schizoaffective disorders receiving therapy with risperidone, olanzapine, and quetiapine and compared with the corresponding parameter in patient receiving typical neuroleptic drug haloperidol. We evaluated the specific effects of the test drugs on prolactin concentration in men and women.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Dibenzothiazepines; Female; Haloperidol; Humans; Immunoenzyme Techniques; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sex Factors

In patients with schizophrenia, risperidone and olanzapine are the two most commonly used atypical anti-psychotics. A recent meta-analysis based on randomized trials suggests that, in the long term, olanzapine can have a lower frequency of treatment discontinuation (or dropout) in comparison with risperidone. To better test this hypothesis, our observational study was aimed at assessing whether or not this advantage of olanzapine versus risperidone could be confirmed in a patient series examined in an observational setting.. Our study was based on a retrospective multi-centre observational design. We collected the following information from each patient: demographic characteristics; current anti-psychotic treatment (olanzapine or risperidone, under the condition of a stable therapy over months -1 to -4); cumulative dose of the drug; previous anti-psychotic treatment (during months -5, -6, -7 and/or, when available, also before month -7); daily dose and treatment duration. Our primary analysis traced back the patient's history from the date of enrollment retrospectively up to month -7. The secondary analysis followed-up the patient's history prior to month -7, thus extending this retrospective recording as long as possible (depending on what information was actually available for individual patients).. The patients were enrolled from 31 institutions. In our primary analysis (months -1 to -7), a total of 144 patients were included; in this subgroup treated with olanzapine or risperidone as initial drug ( n=94), we observed 4 of 54 switches from olanzapine to risperidone and 11 of 40 switches from risperidone to olanzapine ( P=0.01). A total of 454 patients were enrolled in our secondary analysis (from month -1 up to month -73); the same comparison showed 9 of 236 switches from olanzapine to risperidone and 17 of 150 switches from risperidone to olanzapine ( P=0.004).. Our analysis confirms the results of a recent meta-analysis and shows that olanzapine might imply a lower risk of dropout than risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Meta-Analysis as Topic; Multicenter Studies as Topic; Olanzapine; Patient Dropouts; Pharmacoepidemiology; Psychotic Disorders; Retrospective Studies; Risperidone

Topics: Adult; Benzodiazepines; Breast Feeding; Chromatography, Gas; Drug Therapy, Combination; Female; Haloperidol; Humans; Infant, Newborn; Lactation; Methotrimeprazine; Milk, Human; Olanzapine; Psychotic Disorders; Puerperal Disorders

Although olanzapine is known as a widely used atypical antipsychotic there have been very few studies about its use in children and adolescents. Eight adolescent patients who were diagnosed as having schizophrenia or schizoaffective disorder, and treated with olanzapine are reported in this case series. The patients were followed-up for 17.5 weeks in the range 4-26 weeks. According to the CGI improvement assessment at the end of the follow-up period, three of eight cases were rated as very much or much improved, three as minimally improved and two as not improved. Olanzapine was well tolerated by the adolescents in this case series except for weight gain. Our results suggest that olanzapine may be an effective antipsychotic for some psychotic adolescents and during olanzapine trials weight gain. Should be monitored.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Female; Humans; Male; Olanzapine; Psychotic Disorders; Schizophrenia; Treatment Outcome; Weight Gain

Treatment-resistant schizophrenia often leads to combined application of antipsychotic drugs. We report first experience with the combination of olanzapine and amisulpride. Improvement of psychopathological state and side effects could be achieved, and drug doses were lower than under monotherapy. We thus conclude that this approach represents a useful therapeutic option.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Retrospective Studies; Schizophrenia; Sulpiride

Topics: Adult; Benzodiazepines; Female; Galactorrhea; Humans; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors

The introduction of new antipsychotics has resulted in the availability of drugs with improved safety and tolerability as well as proven efficacy compared to the older antipsychotics. New compounds might show new or different adverse effects that arise in the post-marketing phase when a greater number of patients are treated. One goal of the drug safety program in psychiatry AMSP ( Arzneimittelsicherheit in der Psychiatrie) is the detection and description of severe, new, or rare adverse drug reactions (ADRs). Between 1993 and 2000, 122,562 patients were monitored in 35 psychiatric institutions, 86,349 patients of which received antipsychotics. Hyperglycemia related to antipsychotics was observed in association with only two compounds so far: clozapine and olanzapine (clozapine 2 cases, olanzapine 7 cases). In 6 of 9 patients, weight gain preceded hyperglycemia. The relative frequency of these adverse drug related events was 0.013 % for clozapine and 0.075 % for olanzapine. The symptomatology included reversible hyperglycemia, worsening of existing diabetes, and new-onset diabetes. Control for glycemic dysregulation should be maintained in clinical practice with these drugs.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Product Surveillance, Postmarketing; Prospective Studies; Psychotic Disorders; Retrospective Studies; Risk Factors

As a follow-up to our previous study of clozapine, medical records of a state psychiatric hospital were reviewed for patients who were prescribed an atypical antipsychotic. From that sample, demographic and clinical data were obtained for individuals with an initial score of 35 or greater on the Brief Psychiatric Rating Scale (BPRS), and at least two additional successive monthly BPRS ratings. A total of 100 patients met the criteria. Most received either olanzapine (46%) or risperidone (36%), with few administered quetiapine (11%) or clozapine (7%). Most also received adjunctive medications, including conventional antipsychotics, anticonvulsants/mood stabilizers, antidepressants, and antiparkinsonian agents. The number of patients whose BPRS total scores decreased by 20% or more from baseline was significantly greater for those who received olanzapine than those who received risperidone. However, there was no difference between the two antipsychotics in the number of patients who maintained that degree of improvement, in the average latency to achieve that decrease (1.67 and 1.47 months, respectively), or the average length of stay (LOS; 332 and 376 days, respectively). These results indicate a modest therapeutic advantage of olanzapine compared to risperidone, and a substantial degree of polypharmacy in the use of atypical antipsychotics. This uncontrolled "real-world" evaluation supports data from controlled clinical trials, showing that either risperidone or olanzapine would be a reasonable first choice in patients with treatment-resistant schizophrenia, with the decision based on the least adverse side effect profile and economic constraints. When compared to our previous clozapine study, we confirm a slight advantage for the effectiveness of clozapine in the treatment of this refractory population.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Female; Hospitals, Psychiatric; Hospitals, State; Humans; Length of Stay; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome

In spite of conflicting reports, there is emerging evidence that at least two of the atypical antipsychotics, clozapine and olanzapine, are associated with an increased risk of developing glucose dysregulation or new onset diabetes mellitus. We report on the management of six patients who developed diabetes mellitus following treatment with olanzapine, five of whom had independent risk factors for diabetes. Olanzapine was changed to quetiapine in all patients with improvement in glycaemic control in two patients. In view of the uncertainty of the size and mechanism of the link between olanzapine and diabetes, we discuss issues surrounding routine clinical management and monitoring of patients on antipsychotics and the clinical implications.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders

Olanzapine is an atypical antipsychotic with proven therapeutic effect, though it is rarely used in agitated patients. This study was to assess the effectiveness and safety of a 20-mg initial dose of olanzapine to control agitation of hospitalized patients with schizophrenia and schizoaffective and schizofreniform disorders.. A group of 95 patients aged 18-65 years was observed for 7 days. Effectiveness was assessed according to the CGI and PANSS (including the positive and negative symptoms and excitement subscale PANSS-EC) scales. Adverse events were also recorded.. Two therapeutic groups were distinguished: patients treated with olanzapine alone (OLZ) and those whose condition necessitated at least one administration of benzodiazepines (OLZ + BZ). Although these groups differed with respect to baseline symptom severity, improvement was similar. In the OLZ group, improvement according to the CGI scale was observed after 2 h and persisted to the end of the study. In the OLZ + BZ group there was improvement after 1 h, but not after 2 h. Significant improvement reappeared after 6 h and persisted. Improvement measured by the PANSS-EC scale was noted in the OLZ group after 2 h and in the OLZ + BZ group after 6 h, persisting in both groups from the 12th hr to the end of the observation.. Olanzapine is an antipsychotic which, used alone or in combination with benzodiazepines, is effective and well tolerated in treatment of agitation in schizophrenic patients. Further studies are warranted.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Time Factors

It is important to assess cardiovascular risk factors to properly verify the potential consequences of atypical antipsychotic-related weight gain. The objective of the present study was to evaluate whether 2 atypical antipsychotics differ regarding their impact on the cardiovascular disease risk profile compared with a reference group.. We conducted a cross-sectional, multicenter study to assess anthropometric indices of obesity and to obtain a comprehensive fasting metabolic risk profile. Either risperidone or olanzapine had to be prescribed as the first and only antipsychotic for a minimum of 6 months. Patients were compared with a reference group of nondiabetic men. Data were collected from August 1999 to August 2001.. Eighty-seven patients treated with olanzapine (N = 42) or risperidone (N = 45) were evaluated. Olanzapine-treated patients had significantly higher plasma triglyceride concentrations (2.01 +/-1.05 vs. 1.34 +/-0.65 mmol/L, p < or =.05), lower high-density lipoprotein (HDL)-cholesterol levels (0.92 +/-0.17 vs. 1.04 +/- 0.21 mmol/L, p < or =.05), higher cholesterol/HDL-cholesterol ratios (5.62 +/-1.70 vs. 4.50 +/- 1.44, p < or =.05), higher apolipoprotein B levels (1.07 +/- 0.35 vs. 0.92 +/- 0.27 g/L, p < or =.05), smaller low-density lipoprotein peak particle diameters (252.6 +/-4.1 vs. 255.2 +/-4.3 A, p <.01), and higher fasting insulin concentrations (103.9 +/- 67.6 vs. 87.5 +/- 56.1 pmol/L, p < or =.05) than risperidone-treated patients. Moreover, 33% of olanzapine-treated patients were carriers of 3 atherogenic features of the metabolic syndrome as opposed to a prevalence of only 11% of risperidone-treated patients.. These results suggest that olanzapine-treated patients are characterized by a more deteriorated metabolic risk factor profile compared with risperidone-treated patients. These observations raise concerns about the potential differential long-term deleterious effects of some antipsychotics, such as olanzapine, on cardiovascular health.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biomarkers; Carrier State; Cholesterol, HDL; Coronary Artery Disease; Cross-Sectional Studies; Factor Analysis, Statistical; Fasting; Health Surveys; Humans; Hypertriglyceridemia; Insulin; Male; Metabolic Syndrome; Obesity; Olanzapine; Prevalence; Psychotic Disorders; Risk Factors; Risperidone; Weight Gain

The exponential growth in the prevalence of cognitive impairment of old patients leads the physicians to deal with a larger incidence of behavioral disorders (such as excitement,aggressiveness), and psychotic symptoms (such as delirium and visual hallucinations). The presence of psychotic troubles in dementia causes a remarkable distress to caregivers and involves higher difficulties in the patient management. The estimates of such troubles range between 15 and 75 %. Geriatric assessment and the management of behavioral troubles require a prompt evaluation of all their possible causes. As a matter of fact, their appearance often reveals a physical disturbance (pain, fever, etc.), or adverse environmental conditions, or it could also be a consequence of a multiple drug therapy. For this reason,the use of antipsychotics should always be preceded by an accurate clinical diagnosis.Anxiolytic, anti-depressive, anti-convulsive and anti-psychotic drugs are among the therapeutic strategies for the management of the psychogeriatric patient. Atypical antipsychotics seem to be able to decrease the psychotic symptoms, with low levels of therapeutic failure. They also reduce extrapyramidal effects and the growth of prolactine hormone, which is quite useful when dealing with very old patients. Risperidone and olanzapine are two atypical anti-psychotics, which already proved to be adequate and well tolerated during the treatment of schizophrenia and of acute maniacal disorders. Our experience, with a population of patients followed by our Alzheimer Evaluation Unit (AEU), confirms that a low dose of olanzapine (5mg/day) and risperidone (0.5-1.0 mg/day) are effective in lowering behavioral disturbances, and psychotic symptoms due to dementia. Even in the long run,low doses of these drugs are still well tolerated. Higher levels of risperidone (> 1 mg/die)often caused extra-pyramidal symptoms such as rigidity and dyskinesia, whereas higher levels of olanzapine (> 5 mg/day) lead to an exceeding sedation. The management of behavioral disturbances is one of the most important goals in the global treatment of patients affected by dementia, to the extent of improving the quality of life. Atypical antipsychotics are preferable compared to old-generation drugs, therefore, they are the key therapeutic strategy we cannot renounce.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Aggression; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition Disorders; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Psychotic Disorders; Risperidone

Olanzapine has a U.S. Food and Drug Administration-approved dosing range of 10 to 20 mg/day but is often used at doses exceeding this range. Olanzapine is largely metabolized by cytochrome P450 (CYP) 1A2. Smoking, which induces CYP1A2, is expected to increase clearance of olanzapine by 40%; however, dosage adjustment in smokers is not currently recommended. Additionally, female gender is expected to reduce clearance by 30%. Many institutions target high-dose olanzapine prescribers in an effort to reduce unnecessary drug costs. However, factors such as smoking or gender may necessitate increased doses.. A retrospective review of all patients receiving olanzapine during an inpatient stay at a state psychiatric hospital in Kentucky during 2001 was conducted. Demographic information and smoking status were collected for all patients. Olanzapine doses of > 20 mg/day were considered high doses.. Nine percent (48/522) of olanzapine patients were prescribed high doses. The percentages were similar in women and men (10% vs. 9%, p =.69) and in smokers and nonsmokers (9% vs. 9%, p =.82). Moreover, the mean maximum olanzapine dose was also similar in men and women (15.4 +/- 7.2 vs. 14.9 +/- 7.3 mg/day, p =.51). The odds of receiving a high dose of olanzapine were increased 2.1 for patients with a schizophrenia spectrum diagnosis (DSM-IV schizophrenia or other psychotic disorder). The odds of receiving a high dose of olanzapine were increased with each incremental increase in length of stay (intermediate length of stay [8-60 days], OR = 5.6; long-term length of stay [> 60 days], OR = 12.0, relative to acute length of stay [< 8 days]).. Neither gender nor smoking status was associated with receiving a high dose of olanzapine. The association of increased length of stay with high dose suggests that treatment resistance may be an important factor in receiving high daily doses of olanzapine.

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Benzodiazepines; Comorbidity; Cytochrome P-450 CYP1A2; Drug Administration Schedule; Drug Therapy, Combination; Drug Utilization; Female; Hospitalization; Hospitals, Psychiatric; Hospitals, State; Humans; Male; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Retrospective Studies; Schizophrenia; Sex Factors; Smoking

Clozapine, the prototype of atypical antipsychotics, remains unique in its efficacy in the treatment of refractory schizophrenia. Its affinity for dopamine D(4) receptors, serotonin 5-HT(2A) receptor antagonism, effects on the noradrenergic system, and its relatively moderate occupancy of D(2) receptors are unlikely to be the critical mechanism underlying its efficacy. In an attempt to elucidate the molecular/synaptic mechanism underlying clozapine's distinctiveness in refractory schizophrenia, the authors studied the in vivo D(1) and D(2) receptor profile of clozapine compared with other atypical antipsychotics.. Positron emission tomography with the radioligands [(11)C]SCH23390 and [(11)C]raclopride was used to investigate D(1) and D(2) receptor occupancy in vivo in 25 schizophrenia patients receiving atypical antipsychotic treatment with clozapine, olanzapine, quetiapine, or risperidone.. Mean striatal D(1) occupancies ranged from 55% with clozapine to 12% with quetiapine (rank order: clozapine > olanzapine > risperidone > quetiapine). The striatal D(2) occupancy ranged from 81% with risperidone to 30% with quetiapine (rank order: risperidone > olanzapine > clozapine > quetiapine). The ratio of striatal D(1)/D(2) occupancy was significantly higher for clozapine (0.88) relative to olanzapine (0.54), quetiapine (0.41), or risperidone (0.31).. Among the atypical antipsychotics, clozapine appears to have a simultaneous and equivalent occupancy of dopamine D(1) and D(2) receptors. Whether its effect on D(1) receptors represents agonism or antagonism is not yet clear, as this issue is still unresolved in the preclinical arena. This distinctive effect on D(1)/D(2) receptors may be responsible for clozapine's unique effectiveness in patients with schizophrenia refractory to other typical and atypical antipsychotics.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzazepines; Benzodiazepines; Carbon Radioisotopes; Clozapine; Corpus Striatum; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Raclopride; Receptors, Dopamine D1; Receptors, Dopamine D2; Risperidone; Schizophrenia; Tomography, Emission-Computed; Treatment Outcome

We report the case of a euglycaemic woman whose glucose control rapidly decompensated following olanzapine initiation leading to diabetic coma. Hyperglycaemia has been associated with chronic psychotic disorders and antipsychotics for many years. However, it is unusual to see such rapid and life-threatening changes associated with treatment. The case highlights that changes in antipsychotic treatment may be associated with large changes in glucose tolerance, and that it is possible to continue antipsychotic treatment with appropriate diabetic care.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 1; Diabetic Coma; Diabetic Ketoacidosis; Dose-Response Relationship, Drug; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Olanzapine; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blepharospasm; Delusions; Diagnostic and Statistical Manual of Mental Disorders; Humans; Male; Olanzapine; Psychotic Disorders; Severity of Illness Index

We report the case of a 62-year-old man with monosymptomatic hypochondriacal psychosis who failed to respond to paroxetine treatment. Olanzapine addition brought about dramatic improvement in the patient's condition and thereafter paroxetine withdrawal further eliminated his psychosis. These findings suggest that olanzapine itself may be effective for the treatment of monosymptomatic hypochondriacal psychosis. Further controlled studies are required, but this is the first report describing an olanzapine effect in a male patient with monosymptomatic hypochondriacal psychosis.

Topics: Benzodiazepines; Humans; Hypochondriasis; Male; Middle Aged; Olanzapine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Despite most studies of antipsychotic efficacy and safety having been conducted in young patients with schizophrenia, antipsychotic agents are often prescribed in elderly subjects with psychotic symptoms. The aim of this study was to document and describe the level of antipsychotic exposure among elderly subjects. We used the Regional Administrative Database of Lombardy, a region of northern Italy with more than 1.6 million elderly inhabitants, to extract all antipsychotic prescriptions dispensed during 2001 to subjects aged 65 years or above. Prevalence data were calculated by dividing antipsychotic users by the total number of male and female residents in each age group. During the 12 months surveyed 35 363 subjects received at least one antipsychotic prescription, yielding a prevalence of use of 2.18 subjects per 100 inhabitants (95% confidence interval 2.16-2.20). Almost two-thirds were prescribed first-generation agents only, and thioridazine, a first-generation agent associated with prolonged QTC interval, and which is restricted in most European countries, was the most prescribed agent. However, risperidone and olanzapine accounted for 30% of antipsychotic use for all subjects. The majority of patients were also prescribed agents for medical disorders. Because the population of Lombardy is approximately one-sixth of the entire Italian population, it can be assumed that there are over 200 000 elderly subjects annually exposed to these agents in Italy. This generates particular concern because elderly patients are vulnerable to the adverse effects of antipsychotics, and recent warnings have indicated that there are cerebrovascular risks associated with risperidone and olanzapine therapy.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Data Collection; Drug Prescriptions; Drug Utilization; Female; Humans; Italy; Male; Olanzapine; Psychotic Disorders; Risperidone; Thioridazine

Recently, atypical antipsychotic agents have largely replaced traditional agents as first-line drugs for the treatment of schizophrenia and psychotic mood disorders. Considering the increase in atypical antipsychotics prescriptions and the increased risk of suicide in this patient population, the number of reported cases of antipsychotic drugs may be expected to increase. This paper describes the clinical course of atypical antipsychotic agents intoxication, chiefly clozapine, risperidone and olanzapine. Clozapine was the ingestant in 11 cases of atypical antipsychotics overdose in our material. The major observed effects in this group included deep coma, tachycardia, hypersalivation, delirium and shock. Clozapine has a small therapeutic index; in our patients the mortality rate was 27%. Ten patients with risperidone overdose were identified. Our data show that risperidone toxicity manifests mainly as mild central nervous system effects: somnolence, vertigo and tardive dyskinesia. Olanzapine has been considered to be similar to clozapine, but olanzapine intoxication appeared to have a relatively benign clinical course as compared with clozapine intoxication. In olanzapine intoxications deep coma, myosis and mild cardiovascular effects (hypotonia) were observed.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Male; Middle Aged; Olanzapine; Poland; Psychotic Disorders; Risperidone

Neuroleptic malignant syndrome (NMS) is an uncommon potentially fatal side effect of neuroleptic drugs, characterized by movement disorder, altered mental status and autonomic instability. A single dose of clotiapine was administered to an 11-year old male with acute psychosis. The previously healthy child had signs consistent with NMS including hyperthermia, hypertension, motor and mental changes. Repeat examination performed two weeks later, demonstrated that while his hyperthermia subsided, his mental status deteriorated. Olanzapine was administered, after which the child had hyperthermia, dystonia and more pronounced restlessness, once again consistent with NMS. He developed respiratory failure and was intubated and mechanically ventilated. Lorazepam, dantrolene and bromocriptine were administered as treatment of possible NMS. His mental condition, movement disorder and autonomic dysfunction improved significantly. Two weeks later, the patient was discharged in good general condition without the need for any ongoing medical treatment. There are only few case reports of NMS in children treated with olanzapine, an atypical antipsychotic. In children, caution must be exercised when prescribing antipsychotics, particularly atypical antipsychotics as these drugs may cause NMS. Because of the low incidence of NMS, a high index of suspicion is needed to identify cases so prompt treatment can be undertaken.

Topics: Acute Disease; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Blood Cell Count; Child; Dibenzothiazepines; Electroencephalography; False Positive Reactions; Humans; Magnetic Resonance Imaging; Male; Neuroleptic Malignant Syndrome; Neurologic Examination; Olanzapine; Phenytoin; Prion Diseases; Psychotic Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Humans; Hyperprolactinemia; Middle Aged; Olanzapine; Psychotic Disorders; Thromboembolism; Venous Thrombosis

Therapeutic drug monitoring (TDM) has been established at BKH Augsburg (psychiatric district hospital) since January 2001. According to Olanzapine product information the following illustration shows the evaluation (n = 216) of various parameters of the TDM requirements of Olanzapine.. Items examined include "classification according to diagnoses", "reason for requirement", "severity of disease", "therapeutic effect" and "side-effects". In addition, serum concentration, daily dosage, clinical assessment (Brief Psychiatric Rating Scale), age, height and weight of patients will be presented.. Clearly sick patients, 52 % of them between 20 and 30 years old, were less compliant and achieved only a moderate therapeutic effect.. TDM is mainly assessed to control compliance. However, more specific and more personalized TDM would be more useful.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Treatment Outcome

Three patients with Parkinson's disease developed psychosis. None of the three showed any other somatic cause for the psychosis except the Parkinson's disease. The first patient, a 73-year-old male, was initially treated with olanzapine and rivastigmine, without any effect. While treating the second patient, a 75-year-old male who had been suffering from Parkinson's disease for years, the Parkinson medication was first reduced and later on olanzapine and rivastigmine were prescribed, without a lasting effect on the psychotic symptoms. In the third patient, an 85-year-old male, medication reduction was unsuccessful. Finally, all three were treated effectively with clozapine. Psychosis in Parkinson's disease is a serious disorder that is often difficult to treat. In most cases, antipsychotic medication is needed. The atypical antipsychotic clozapine is effective without aggravation of the motor symptoms. Despite the side effects, such as the risk of agranulocytosis, drowsiness and weight gain, clozapine should be considered as a possible treatment.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clozapine; Female; Humans; Male; Neuroprotective Agents; Olanzapine; Parkinson Disease; Phenylcarbamates; Psychotic Disorders; Rivastigmine; Treatment Outcome

We attempt to demonstrate the association between neuroleptic-induced hyperprolactinemia and sexual dysfunction in schizophrenic patients treated with prolactin-elevating antipsychotics. Our findings indicate that sexual function improved with euprolactinemia in patients switched from treatment with prolactin-elevating antipsychotics to olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Ejaculation; Female; Humans; Hyperprolactinemia; Male; Olanzapine; Prolactin; Psychotic Disorders; Risperidone; Sex Characteristics; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological

Topics: Aged; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Cerebral Infarction; Dementia, Vascular; Humans; Olanzapine; Psychotic Disorders; Randomized Controlled Trials as Topic; Risk Factors; Risperidone; Treatment Outcome

Acute manic episodes in bipolar disorder require rapid and effective relief. Bipolar depression is a major component of the bipolar disorder spectrum. Existing treatment options for bipolar depression include lithium, lamotrigine and conventional antidepressants. However, lithium is more effective in treating mania or hypomania than depression, both acutely and prophylactically, lamotrigine has only been demonstrated to be effective in one adequately powered study in acute bipolar I depression, and conventional antidepressants have been associated with emergent mania and cycle acceleration. Symptomatic outpatients can expect to spend, on average, 33% of their time in the depressive phase compared with 11% in the manic phase. Consequently, there is a need for additional agents to effectively treat bipolar depression. The atypical agents olanzapine, risperidone and quetiapine have demonstrated efficacy against the manic phase of bipolar disorder and appear also to have potential in the depressive phase. Olanzapine monotherapy significantly improved depressive symptoms compared with placebo in patients with bipolar disorder in an 8-week randomized, controlled clinical study, but the magnitude of the clinical effect was small. The observed improvement in depressive symptoms became moderately large when olanzapine was combined with the antidepressant fluoxetine. Quetiapine monotherapy also resulted in significant improvements compared with placebo in patients with either bipolar I or bipolar II disorder in another 8-week randomized, controlled clinical study, but the effect size was large. A 6-month open-label study of risperidone added to ongoing therapy demonstrated improvements in depressive symptoms in patients with bipolar and schizoaffective disorders experiencing a manic, hypomanic, mixed or depressive episode. The receptor-binding profile of these agents supports a role in the treatment of depressive symptoms and clinical data are beginning to emerge of their efficacy in both the acute and maintenance setting.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Tolerance; Follow-Up Studies; Humans; Olanzapine; Psychotic Disorders; Risperidone; Time Factors

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Haloperidol; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Research Design; Risperidone; Schizophrenia; Treatment Outcome

Risperidone and olanzapine are thought to have broadly similar clinical effects. This study was designed as a cost analysis study comparing costs and basic clinical outcomes of treatment with risperidone or olanzapine in a naturalistic setting.. The U.K. Risperidone Olanzapine Drug Outcomes Studies in Schizophrenia (RODOS-UK) program consisted of a retrospective review of medical notes and prescription charts for 501 patients with schizophrenia or schizoaffective disorder who had been admitted to the hospital for the treatment of psychosis. The main outcome measure was cost of inpatient drug treatment. Clinical outcomes (clinician-assessed and -documented effectiveness, time to discharge) were also evaluated. Data were collected and verified between June and September 2000.. Clinical outcomes were similar for risperidone and olanzapine. Clinician-assessed effectiveness was similar for both treatments (78% risperidone, 74% olanzapine; p =.39), but mean time to documented onset of effectiveness was significantly shorter for those treated with risperidone versus olanzapine (17.6 vs. 22.4 days; p =.01). Risperidone-treated patients stayed a mean of 9 fewer days in the hospital compared with olanzapine-treated patients (49 vs. 58 days; p =.007). The possibility that these observed differences were a result of different baseline characteristics could not be entirely discounted. Mean +/- SD doses of risperidone and olanzapine were 5.5 +/- 2.4 mg/day and 14.1 +/- 4.7 mg/day, respectively. The mean daily cost of all inpatient drugs was significantly higher for olanzapine than for risperidone (pound 5.63 vs. pound 3.92; p <.0001). Mean total costs of all inpatient drugs were significantly higher for olanzapine than for risperidone (pound 164 vs. pound 96; p <.0001), which partly reflected the longer mean treatment duration for olanzapine compared with risperidone (44 vs. 37 days). Concomitant antipsychotic use was similar for both groups (66% risperidone, 67% olanzapine). The number of patients documented as experiencing adverse events was not different between groups (22% risperidone, 19% olanzapine; p =.32).. Risperidone and olanzapine produced broadly comparable clinical outcome in this cohort of hospitalized patients, but the use of risperidone was associated with significantly lower drug treatment costs.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Cost-Benefit Analysis; Costs and Cost Analysis; Drug Administration Schedule; Drug Costs; Drug Therapy, Combination; Drug Utilization; Female; Hospitalization; Humans; Male; Olanzapine; Outcome Assessment, Health Care; Pirenzepine; Psychotic Disorders; Retrospective Studies; Risperidone; Schizophrenia; Treatment Outcome

The increasing use of olanzapine for treating adolescent patients has brought with it greater awareness of the recognized side effects of this medication, especially weight gain. Of the reports of glucose dysregulation related to olanzapine therapy, only a few pertain to adolescents. We present five cases: two youths who consequently suffered from overt diabetes and three who responded with glucose dysregulation. According to the Naranjo probability scale, the relation of this phenomenon to olanzapine therapy is "probable." We consider the findings of the presented case series as justification for regular metabolic follow-up for apparently healthy adolescents receiving olanzapine therapy.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemia; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Weight Gain

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Female; Health Status; Humans; Long QT Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Severity of Illness Index

Topics: Antipsychotic Agents; Behavior, Addictive; Benzodiazepines; Cocaine-Related Disorders; Comorbidity; Diagnosis, Dual (Psychiatry); Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Secondary Prevention; Treatment Outcome

Orally disintegrating olanzapine is a recently marketed form of olanzapine that dissolves rapidly on contact with saliva. We describe six demented patients resistant to treatment with common oral antipsychotic medications who were successfully treated with the formulation. The importance of these case reports is to make physicians aware that orally disintegrating olanzapine may be useful for the management of psychobehavioral disturbances in demented patients who resist or have difficulty taking standard oral medications.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Benzodiazepines; Biological Availability; Brain Injury, Chronic; Dementia; Dementia, Vascular; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Mental Disorders; Mental Status Schedule; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

Elevations in prolactin plasma concentration occur with antipsychotics due to their dopamine D2 receptor antagonism. Hyperprolactinemia may be associated with both acute (galactorrhea, amenorrhea, decreased libido etc.) and chronic (predisposition to osteoporosis and cardiovascular disease) treatment emergent effects in both men and women associated with apparently impaired compliance. The aim of our study was to investigate these supposed effects regarding clinically relevant endocrinologic symptoms under routine treatment conditions with newer, atypical antipsychotics. Our findings confirm that amisulpride frequently leads to a remarkable elevation of prolactin plasma concentration, same--in minor degree--for risperidone. Under treatment with quetiapine and olanzapine just temporary elevated prolactin levels were registered. However, no correlation between prolactin levels and dosage could be found. In females treated with amisulpride acute hormonal side effects were seen in a clinically relevant manner. Features of illness itself, stress factors, concomitant medication or other patient's conditions are supposed to be relevant factors for acute endocrine symptomatology.

Topics: Adult; Amisulpride; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Male; Middle Aged; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Prolactin; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

Hallervorden-Spatz disease is a rare autosomal recessive condition, with early onset of predominantly extrapyramidal dysfunction. The symptoms of the disease are dystonia, rigidity, choreoathetosis, pyramidal signs, and intellectual decline. Recent genetic studies mapped the disease to chromosome 20p12.3-p13, and identified mutations in the pantothenate kinase gene. This report describes a childhood onset case of Hallervorden-Spatz disease with schizophreniform psychotic symptoms. Former reports about the psychiatric comorbidity generally included depressive disorder.. A single case report.. A 14-year-old boy with Hallervorden-Spatz disease presented a psychotic episode with prominent auditory hallucinations. Symptoms were relieved after neuroleptic treatment.. To the authors' knowledge, this is the first published report of the disease with psychotic symptoms. The contribution of basal ganglia, with their wide projections, to the emergence of psychotic symptoms was discussed.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Benzodiazepines; Comorbidity; Dementia; Dominance, Cerebral; Globus Pallidus; Humans; Magnetic Resonance Imaging; Male; Neurologic Examination; Olanzapine; Pantothenate Kinase-Associated Neurodegeneration; Psychotic Disorders

Recently concern regarding the cause or worsening of diabetes mellitus by some of the second-generation antipsychotics and their adverse affects on lipid metabolism has caused growing concern amongst physicians and patients. This study aims to assess these effects in elderly patients with schizophrenia.. In a prospective 6-month follow-up study of elderly inpatients experiencing an acute psychotic exacerbation and exposed to olanzapine for the first time, patients underwent physical and psychiatric assessments including: routine laboratory tests (including serum cholesterol and triglycerides levels), and bodyweight and clinical rating scale measurement. All tests and evaluations were performed at baseline and at the end of study.. Twenty-one elderly patients with schizophrenia (15 women and six men) mean age 71.7 +/- 8.2 years were included. All were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (4th edition) as patients with schizophrenia or schizoaffective disorder. Mean duration of olanzapine treatment was 289 days (SD +/- 139) and the mean olanzapine dosage at the end of the study was 12.9 mg/day. At the end of the study, no significant change from baseline serum lipid levels were found for triglycerides (paired differences = -12.8 [SD +/- 38.5], 95% CI -30.3 to +4.7, t = -1.5, df = 20, p = 0.143) or cholesterol (paired differences = -9.0 [SD +/- 43.5], 95% CI = -28.8 to +10.8, t = -0.95, df = 20, p = 0.355).. The association between olanzapine exposure and lipid abnormalities may not hold true for older patients. Larger studies with elderly patients are needed to support the present report.

Topics: Aged; Aged, 80 and over; Benzodiazepines; Cholesterol; Female; Follow-Up Studies; Humans; Lipids; Male; Middle Aged; Olanzapine; Prospective Studies; Psychotic Disorders; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Triglycerides

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cholesterol; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Triglycerides; Weight Gain

This analysis compares the efficacy of risperidone and olanzapine in controlling negative and positive symptoms of chronic psychosis in older patients.. Post hoc assessments were made in a subset of risperidone-treated (N = 19) and olanzapine-treated (N = 20) older patients (aged 50 to 65 years) from a large international, multicenter, parallel, double-blind, 28-week study of patients aged 18 to 65 years (N = 339) randomly assigned to receive risperidone (4-12 mg/day) or olanzapine (10-20 mg/day). Assessments were made using repeated-measures analysis.. At both 8 weeks and 28 weeks, the magnitude of changes in Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores did not differ between treatment groups (8 weeks: risperidone, -6.5; olanzapine, -6.8, p = .866; 28 weeks: risperidone, -6.5; olanzapine, -7.0; p = .804). However, by the 8-week timepoint, olanzapine had reduced PANSS negative subscale scores significantly more than risperidone (-8.8 vs. -4.9, p = .032). By the 28-week endpoint, olanzapine had continued to maintain significantly greater reduction in baseline-to-endpoint PANSS negative scores (-8.1 vs. -3.5, p = .032) and led to significantly greater reduction in scores on the Scale for the Assessment of Negative Symptoms (SANS) dimensions of affective flattening (-5.2 vs. -0.6, p = .033) and alogia (-3.8 vs. -0.3, p = .007). Patients in the olanzapine treatment group also demonstrated numerically greater reduction of both SANS summary (-3.7 vs. -1.0, p = .078) and SANS composite scores (-14.1 vs. -4.1, p = .075).. These data demonstrate that, in older patients with schizophrenia and related psychotic disorders, risperidone and olanzapine have approximately equal efficacy in controlling positive symptoms. However, olanzapine appears to be more efficacious in maintaining control over negative symptoms.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Depression; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Increasingly alarmed by the health risks (that is, weight gain, elevated lipids, and poor glucose tolerance) posed by novel antipsychotic medications, clinicians who treat schizophrenia are attempting to help patients improve lifestyle factors. Unfortunately, schizophrenia research has neglected exercise as a legitimate adjunctive treatment for schizophrenia.. To assess the extent to which stable patients with schizophrenia would adhere to an exercise program if offered access to a fitness facility.. Ten of 20 stable patients with schizophrenia or schizoaffective disorder who were treated with olanzapine for at least 4 weeks had the opportunity to receive access to a Young Men's Christian Association (YMCA) fitness facility, based on random allocation. The intervention included a free membership to the YMCA for 6 months, with access to all the fitness amenities and equipment. The mean dosage of olanzapine was 11.5 mg daily for the YMCA group.. Of the 10 subjects, 2 did not attend at all. One subject met criteria for full attendance for each of the 6 months and lost 15 Kg. Dropout rates were as follows: 90% at 6 months, 70% at 5 months, and 40% at 4 months. The main reason they gave for poor attendance was lack of motivation. The mean weight gain was 2 kg in the YMCA group.. Most subjects did not regularly exercise or attend. They cited poor motivation as the main reason. The subject who exercised regularly lost a significant amount of weight.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Exercise; Female; Fitness Centers; Health Services Accessibility; Humans; Male; Middle Aged; Motivation; Olanzapine; Physical Fitness; Pilot Projects; Pirenzepine; Prospective Studies; Psychotic Disorders; Random Allocation; Schizophrenia

This study evaluates whether high-dose olanzapine is associated with elevation of serum prolactin levels.. Twenty-four patients taking daily doses of olanzapine of 20, 25, 30, and 40 mg for DSM-IV schizophrenia or schizoaffective disorder had serum prolactin levels measured. The patients were all from one author's (J.L.K.'s) clinical practice. The mean duration of olanzapine therapy was 15.3 months at a dose of at least 20 mg/day. Data were gathered in 2000 and 2001.. There was no significant correlation between olanzapine dose and prolactin level (Pearson product moment correlation coefficient = 0.09). No significant differences were found between mean prolactin values in each dose group.. There was no significant elevation of prolactin with higher doses of olanzapine. Thus, preliminary evidence suggests that using higher doses of olanzapine is generally safe with regard to prolactin levels.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Prolactin; Psychotic Disorders; Reference Values; Schizophrenia

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Pulmonary Embolism

During the last few years there have been numerous publications concerning glucose dysregulation and antipsychotic treatment with new-onset diabetes and exacerbation of existing disease being reported. At the same time three anecdotal reports describing decrease of blood glucose level during clozapine and olanzapine treatment were published. Here we report two cases of clinically significant dose-related reductions in glucose levels in schizophrenic and schizoaffective patients suffering from pre-existing type 2 diabetes during high dose (40 mg/day) olanzapine treatment. To the best of our knowledge, this is a first report of decreasing glucose blood levels in association with olanzapine therapy in pre-existing type 2 diabetes. Antipsychotic treatment with high doses of olanzapine showed that the relationship between olanzapine and glucose regulation is more unambiguous than usually assumed.. There is a need for further studies in order to define the influence of high dose olanzapine for schizophrenic and schizoaffective patients suffering from type 2 diabetes.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Comorbidity; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Middle Aged; Olanzapine; Psychotic Disorders; Schizophrenia; Treatment Outcome

The influence of carbamazepine on the glucuronidation of the antipsychotic olanzapine was studied in a group of psychiatric patients. Steady-state serum concentrations of free and glucuronidated olanzapine were measured in 31 psychiatric patients in monotherapy (dose range, 2.5-30 mg/d; median, 15 mg/d) and in 16 patients being comedicated with carbamazepine (dose range, 5-50 mg/d; median, 20 mg/d). The concentrations were determined by HPLC with and without acid hydrolysis of glucuronidated olanzapine. For the monotherapy group, the concentrations of free and glucuronidated olanzapine ranged from 0 nmol/L to 292 nmol/L (median, 94 nmol/L) and from 0 nmol/L to 180 nmol/L (median, 27 nmol/L), respectively. The serum concentrations of the carbamazepine-treated group ranged from 21 nmol/L to 310 nmol/L (median, 81 nmol/L) and from 0 to 376 nmol/L (median, 57 nmol/L) for free and glucuronidated olanzapine, respectively. Two patients with outlying values were excluded from further analysis. The median concentration-to-daily dose ratios (C/D) of free and glucuronidated olanzapine in the monotherapy group were 5.8 nmol/L/mg and 2.2 nmol/L/mg, respectively (n =30). The corresponding values for the group comedicated with carbamazepine were 3.6 and 3.1 nmol/L/mg (n =15). Thus, the median C/D of free olanzapine in the carbamazepine group was 38% lower than that of the monotherapy group (P <0.01), confirming that carbamazepine accelerates the metabolism of olanzapine. Further, for the carbamazepine group the median glucuronidated olanzapine fraction constituted 79% of the free fraction compared with 43% for the monotherapy group (P <0.01), which suggests that an increased rate of olanzapine glucuronidation contributes to the increased rate of metabolism of olanzapine induced by carbamazepine.

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Carbamazepine; Chromatography, High Pressure Liquid; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Glucuronides; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders

Patients with a Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) diagnosis of schizophrenia or psychotic disorder not otherwise specified with onset of psychosis before the age of 13 participated in 6- to 8-week open or double-blind trials of haloperidol (n = 15, mean dose 15.4 +/- 8.1 mg/day [0.27 +/- 0.15 mg/kg/day]), clozapine (n = 30, mean dose 269.9 +/- 173.3 mg/day [4.4 +/- 2.6 mg/kg/day]), or olanzapine (n = 12, mean dose 17.5 +/- 2.8 mg/day [0.30 +/- 0.13 mg/kg/day]). Blood samples were obtained at 6 weeks for evaluation of haloperidol, reduced haloperidol, clozapine, desmethylclozapine, and olanzapine plasma concentrations and serum prolactin concentrations. No gender differences were noted for antipsychotic dose or concentration within each treatment group. Correlations between antipsychotic plasma concentration and serum prolactin concentration were significant only for the olanzapine treatment group (r = 0.80, p = 0.002). Separate correlations for gender were significant only for females receiving olanzapine (r = 0.91, p = 0.03); the patient with the highest serum prolactin experienced galactorrhea. Further studies evaluating the prolactin-elevating properties of antipsychotics are warranted in this population.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Child; Clozapine; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Prolactin; Psychotic Disorders; Schizophrenia

Although olanzapine therapy has been associated with fewer extrapyramidal side effects than the traditional antipsychotic medications, reported side effects include dystonia, tardive dyskinesia, hypotension, diabetes mellitus, seizures and neuroleptic malignant syndrome. There are no previous published reports of hyperventilation associated with olanzapine therapy, but we present the case of a male patient who developed dyspnea and hyperventilation while taking olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Hyperventilation; Male; Olanzapine; Pirenzepine; Psychotic Disorders

The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels.. The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses.. Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations.. It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Mass Index; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Clozapine; Diabetes Mellitus, Type 2; Dibenzothiazepines; Female; Haloperidol; Humans; Hyperlipidemias; Lipids; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Triglycerides; Weight Gain

Case series suggest that some antipsychotics may induce or exacerbate type 2 diabetes. This study measured the association of antipsychotic treatments with diabetes at a population level.. Claims data for psychosis patients (ICD-CM-9 290.xx-299.xx) within health plans encompassing 2.5 million individuals were analyzed. Patients reporting preexisting type 2 diabetes up to 8 months prior to observation were excluded. The frequency of newly reported type 2 diabetes in untreated patients and among patients treated with antipsychotics from 5 categories (risperidone, olanzapine, clozapine, and high-potency and low-potency conventionals) was compared. Logistic regression models compared the odds of diabetes based on exposure to each of the antipsychotic categories.. Based on 12 months of exposure, the odds of type 2 diabetes for risperidone-treated patients (odds ratio = 0.88, 95% CI = 0.372 to 2.070) was not significantly different from that for untreated patients, whereas patients receiving other antipsychotics had a significantly greater risk of diabetes than untreated patients (p < .05): olanzapine, 3.10 (95% CI = 1.620 to 5.934); clozapine, 7.44 (95% CI = 0.603 to 34.751); high-potency conventionals, 2.13 (95% CI = 1.097 to 4.134); and low-potency conventionals, 3.46 (95% CI = 1.522 to 7.785). Older age and greater use of non-antipsychotic psychotropic medications also contributed to risk of type 2 diabetes. Olanzapine also showed significantly higher (p < .01) odds of diabetes associated with increasing dose.. Consistent with previously published literature, these data suggest that olanzapine, clozapine, and some conventional antipsychotics appear to increase the risk of acquiring or exacerbating type 2 diabetes and that the effect may vary by drug. In contrast to these agents, risperidone was not associated with an increased risk of type 2 diabetes.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Comorbidity; Confidence Intervals; Databases as Topic; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Insurance Claim Review; Logistic Models; Male; Middle Aged; Odds Ratio; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Risperidone; United States

The relative risk of diabetes among patients undergoing risperidone treatment was compared with that of patients receiving olanzapine.. A cohort was formed of 33,946 patients with at least 1 prescription for either olanzapine (N = 19,153) or risperidone (N = 14,793) between January 1, 1997, and December 31, 1999, recorded in the Régie de l'Assurance Maladie du Québec database. Patients were excluded if clozapine was dispensed to them during the study period or if they were diagnosed with diabetes before beginning antipsychotic therapy. New diabetes diagnoses made after the first antipsychotic prescription during the period were tabulated until December 31, 1999; censoring occurred at this date or at the last service date, if there was no record of using services during the last 6 months of follow-up. Crude hazard ratio and proportional hazard analyses were carried out.. 319 patients developed diabetes on olanzapine treatment, and 217 developed diabetes on risperidone treatment; a crude hazard ratio of 1.08 (95% CI = 0.89 to 1.31, p =.43) was determined. When age, gender, and haloperidol use were controlled for using proportional hazard analysis, there was a 20% increased risk of diabetes with olanzapine relative to risperidone (95% CI = 0% to 43%, p =.05). Proportional hazard analyses adjusted for duration of olanzapine exposure indicated that the first 3 months of olanzapine treatment was associated with an increased risk of diabetes of 90% (95% CI = 40% to 157%, p <.0001), after adjusting for age, gender, and haloperidol use.. Compared with risperidone, olanzapine was associated with an increased risk of developing diabetes. More studies are required to further investigate this association.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Cohort Studies; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Retrospective Studies; Risk Factors; Risperidone

Topics: Affect; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Depressive Disorder; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Hypochondriasis; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia, Paranoid; Treatment Outcome

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Eosinophilia; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors

To provide evidence that olanzapine can cause glucose dysregulation by a mechanism other than weight gain.. I report a case of a diabetic patient who developed glucose dysregulation soon after initiation of olanzapine treatment, occurring in the absence of weight gain. I compare this case to previous case reports.. Our patient developed persistent hyperglycaemia within 3 weeks of initiating treatment with olanzapine. Weight recorded just prior to commencement and soon after discontinuation of olanzapine were not significantly different.. Controlled studies are necessary to elucidate the mechanism by which olanzapine can cause dysregulation of glucose homeostasis, and to develop guidelines for the use of olanzapine in patients with known diabetes as well as in patients with risk factors for diabetes.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hyperglycemia; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Female; Humans; Hyperglycemia; Olanzapine; Pirenzepine; Psychotic Disorders; Weight Gain

The comparatively high acquisition costs of the newer antipsychotic medications have caused the mental health community to look closely at their potential benefits.. The purpose of this study was to perform a naturalistic analysis of changes in mental health service utilization, economic costs, and clinical outcomes after the initiation of olanzapine therapy for psychotic symptoms in an indigent patient population from a large county-operated mental health care system.. This was a prospective, uncontrolled investigation using a mirror-image cohort design. All captured costs from patients who began olanzapine therapy between November 1, 1996, and April 30, 1998, were analyzed in an intent-to-treat fashion to compare resource utilization in the 12 months immediately before and after the intervention. Clinical function was assessed at baseline and 6 months using the Positive and Negative Syndrome Scale (PANSS). In a subgroup analysis, the baseline characteristics of patients who completed 12 months of olanzapine treatment were compared with those of patients who (1) changed medication or (2) changed pay or source or were lost to follow-up.. One hundred eighty-nine patients were started on olanzapine treatment during the 18-month study entry phase. Patients were primarily male (63.5%) and had a mean age of 35.9 years. Most (66.3%) had a formal diagnosis of thought disorder. Fifty-six patients received olanzapine for 12 consecutive months, and 22 were switched to other psychotropic medications. Of the remaining 111 patients, 70 changed payors (ie, qualified for Medicaid), and 41 were lost to follow-up. In the subgroup analysis, patients who completed 12 months of treatment (ie, responders) had significantly lower mean PANSS total scores at baseline compared with those who changed payors or were lost to follow-up (P = 0.047), and were significantly more likely to have a formal diagnosis of thought disorder (P = 0.039). Responders demonstrated a significant reduction in PANSS total and negative subscale scores at 6-month follow-up (both measures, P < 0.001). In the intent-to-treat analysis of resource utilization in all patients with complete data sets (n = 78), hospitalization costs and crisis costs decreased significantly during the 12-month follow-up period (P = 0.003 and P = 0.009, respectively), and both outpatient and medication costs increased significantly (P = 0.035 and P < 0.001, respectively). Overall, the change in total annual resource utilization during the 12 months after initiation of olanzapine was not statistically significant (mean decrease per patient, $1,991; 95% CI, -$5,258 to $1,122).. Initiation of olanzapine therapy was associated with favorable clinical outcomes in this population, particularly in patients with a formal diagnosis of thought disorder. Overall, there was a cost shift away from hospital and crisis costs toward medication and outpatient services costs. The decline in total resource utilization was not statistically significant, although it may be of practical importance.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; California; Community Mental Health Services; Cost-Benefit Analysis; Economics, Pharmaceutical; Female; Humans; Male; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Severity of Illness Index

This study examined one-year rehospitalization rates for patients who were discharged from Austin State Hospital between August 1, 1997, and July 31, 1998, while taking olanzapine, risperidone, or a conventional antipsychotic. Time to readmission was measured by the product-limit formula. Although conventional antipsychotics were associated with a lower rehospitalization rate, no significant difference in the one-year rehospitalization rate was observed between the groups. At 180 days after initial discharge, the patients who received olanzapine had a higher rate of rehospitalization than patients who were taking conventional antipsychotics. Conventional antipsychotics were associated with a lower one-year rehospitalization rate than risperidone or olanzapine.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Humans; Middle Aged; Olanzapine; Patient Readmission; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia; Time Factors

The aim of this study was to evaluate the mechanisms underlying weight gain induced by the atypical antipsychotic, olanzapine. We performed euglycemic, hyperinsulinemic clamp combined with indirect calorimetry on a 48-year-old male with antisocial personality disorder, alcohol dependence and paranoid ideation before and after one month of olanzapine (10 - 15 mg/day) therapy. The patient gave his informed, written consent for this study. The results were a weight gain of 6 kg and a decrease in both basal (from 1673 to 1613 kcal/24 h) and 3-hour (from 22.8 to 20.2 cal/kg fat free mass/min) energy expenditure. Serum thyroid hormone and high-density lipoprotein cholesterol levels decreased, and the triglyceride and low-density lipoprotein cholesterol levels increased. Insulin sensitivity did not change. We conclude that decreased basal energy expenditure may contribute to weight gain in olanzapine treatment.

Topics: Antipsychotic Agents; Benzodiazepines; Calorimetry, Indirect; Energy Metabolism; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Weight Gain

This report focuses on the case of a pregnant woman with a bad obstetric history who developed psychosis at the 23 rd week of gestation. She was treated with olanzapine from the 24th week until 10 days prior to delivery. No adverse events occurred during pregnancy or delivery. The Apgar score was 8/10 at one minute and 9/10 at 5 minutes.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Olanzapine; Pirenzepine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Psychotic Disorders

Acute, high-dose loading strategies (rapid neuroleptization) with the first-generation antipsychotics administered orally or parenterally, alone or combined with benzodiazepines, have been a commonly used treatment paradigm for controlling acutely agitated psychotic patients. The rationale was to achieve high plasma levels of drug within a shorter time period, resulting in rapid symptom mitigation. However, studies have shown that rapid neuroleptization with first-generation antipsychotics is associated with a greater incidence of side effects. To our knowledge, loading strategies with second-generation antipsychotics have not been investigated, primarily owing to a need for dose titration. Olanzapine, a second-generation antipsychotic, is well tolerated in doses ranging from 5 to 20 mg. The objective of this report was to determine experience with the use of up to 20 mg of an oral loading dose of olanzapine administered within 4 hours in the treatment of patients early in an acute psychotic phase of their illness. In the reported case series of 57 patients, olanzapine initiated at 15 to 20 mg/day was a safe and effective medication for rapidly calming the agitation of acutely agitated psychotic patients (rapid tranquilization). Furthermore, dose reduction over 2 to 3 weeks was achieved in a number of patients without appreciable loss of efficacy.

Topics: Acute Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Drug Administration Schedule; Humans; Incidence; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Administration Schedule; Drug Approval; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; United States; United States Food and Drug Administration

The hypothesis provides the justification for the clinical trial. It is antecedent to the trial and establishes the trial's direction. Hypothesis testing is the most widely employed method of determining whether the outcome of clinical trials is positive or negative. Too often, however, neither the hypothesis nor the statistical information necessary to evaluate outcomes, such as p values and alpha levels, is stated explicitly in reports of clinical trials. This article examines 5 recent studies comparing atypical antipsychotics with special attention to how they approach the hypothesis and hypothesis testing. Alternative approaches are also discussed.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Dibenzothiazepines; Humans; Olanzapine; Periodicals as Topic; Pirenzepine; Psychotic Disorders; Publishing; Quetiapine Fumarate; Reproducibility of Results; Research Design; Risperidone; Schizophrenia; Terminology as Topic

The assumption that psychotic patients assigned to placebo in clinical trials of antipsychotics are exposed to substantial morbidity and mortality is not based on data about what actually happens to such patients. This study assesses symptoms and risks of suicide and suicide attempts in psychotic patients assigned to receive placebo in clinical trials.. The authors used the Food and Drug Administration database to assess suicides, suicide attempts, and psychotic symptom reduction in clinical trials of three new antipsychotics.. Among 10,118 participating patients, 26 committed suicide and 51 attempted suicide. Rates of suicide and attempted suicide did not differ significantly between the placebo-treated and the drug-treated groups. Annual rates of suicide and attempted suicide based on patient exposure years were 1.8% and 3.3%, respectively, with placebo; 0.9% and 5.7% with an established antipsychotic; and 0.7% and 5.0% with a new antipsychotic. Symptom reduction was 16.6% with new antipsychotics (N=1,203), 17.3% with established antipsychotics (N=261), and 1.1% with placebo (N=462).. These data may help inform discussions about the use of placebo in antipsychotic clinical trials.

Topics: Antipsychotic Agents; Benzodiazepines; Brief Psychiatric Rating Scale; Clinical Trials as Topic; Databases as Topic; Dibenzothiazepines; Drug Approval; Humans; Incidence; Olanzapine; Pirenzepine; Placebos; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Suicide; Suicide, Attempted; Treatment Outcome; United States; United States Food and Drug Administration

We present here clinical case reports of three adolescents, aged 14-17 years, who were treated with olanzapine. The daily dose was 10 mg. Prior to olanzapine, the patients were unsuccessfully treated with other antipsychotic drugs. The response to olanzapine for psychotic symptoms was clinically significant in all three patients. The major adverse effect was excessive weight gain. The increases in body mass index (BMI) were 9, 8 and 5 kg/m2. One of the patients later lost the additional weight. Especially in adolescents obesity is a serious side effect and potential consequences include numerous health problems.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia, Paranoid; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Blood Glucose; Diabetes Mellitus, Type 2; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Infant, Newborn; Male; Olanzapine; Pirenzepine; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Psychotic Disorders

We performed a retrospective analysis of data involving 121 inpatients to examine the rate of weight gain during antipsychotic-free periods and during treatment with various antipsychotic drugs.. Data were analyzed to determine differences in weekly weight change during antipsychotic-free (N = 65), typical antipsychotic (N = 51), or atypical antipsychotic (N = 130) treatment periods. Atypical antipsychotic treatment periods were further subdivided into olanzapine (N = 45), clozapine (N = 47), or risperidone (N = 36) treatment periods. A paired comparison was conducted on 65 patients who had an antipsychotic-free treatment period preceding or following a neuroleptic drug treatment period. In addition, patients were classified as either non-obese (with a body mass index [BMI] < or = 29.9 kg/ml) or obese (BMI > or = 30.0 kg/m2) to test whether the rate of weight gain during treatment periods was related to initial BMI.. Across all treatment periods, weekly weight gain was as follows: 0.89 lb/wk (0.40 kg/wk) on atypical antipsychotic medication, 0.61 lb/wk (0.27 kg/wk) on typical antipsychotic medication, and 0.21 lb/wk (0.09 kg/wk) on no antipsychotic medications. The atypical antipsychotic versus antipsychotic-free comparison was significant (F = 3.51; df = 2,231; p = .031), while the typical antipsychotic versus antipsychotic-free comparison was not. Among the individual atypical antipsychotic medications, significantly more weight gain occurred during olanzapine treatment (1.70 lb/wk) (0.76 kg/wk) than with either clozapine (0.50 lb/wk) (0.22 kg/wk) or risperidone (0.34 lb/wk) (0.15 kg/wk) treatments (F = 7.77; df = 2,117; p = .001). In the paired analysis with patients serving as their own controls, the difference between weekly weight gain during atypical antipsychotic treatment and antipsychotic-free treatment was significant (t = -3.91; df = 44; p = .001), while the difference between weight gain during typical antipsychotic treatment and antipsychotic-free treatment was not significant. With the individual drugs. treatment with both olanzapine and clozapine caused significantly higher weekly weight gain than antipsychotic-free treatment (p = .001 and p = .036, respectively). while treatment with risperidone did not. Non-obese patients (BMI < 29.9 kg/m2) and obese patients (BMI > 30.0 kg/m2) did not differ significantly in their weight gain during typical or atypical antipsychotic treatment.. Treatment with atypical antipsychotics was associated with more weight gain than treatment with typical antipsychotics. Among the atypical drugs, olanzapine was associated with more weight gain than either clozapine or risperidone. The patient's admission BMI was not associated with the amount of weight gained during subsequent antipsychotic treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Clozapine; Drug Administration Schedule; Female; Hospitalization; Humans; Male; Obesity; Olanzapine; Pirenzepine; Psychotic Disorders; Regression Analysis; Research Design; Retrospective Studies; Risperidone; Schizophrenia; Weight Gain

To study the usage, efficacy, and side effects patterns of atypical neuroleptics (atypicals) in adolescents and young adults with developmental disabilities (DDs) (mental retardation).. We undertook a chart review of adolescents and young adults (under age 25 years) seen by our specialized mental health team.. Risperidone and olanzapine were by far the most frequently prescribed atypicals. Robust clinical effects were noted for both psychotic and nonpsychotic disorders. Most patients tolerated atypicals well, although a significant minority did experience neuroleptic induced movement disorders (NIMDs), particularly dystonias and dyskinesias. Female patients with DDs appear to be at particular risk of NIMDs.. Atypicals are useful in treating various conditions associated with DDs. This population, however, seems particularly sensitive to NIMDs, hence caution and close monitoring are required.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Intellectual Disability; Male; Movement Disorders; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Sex Factors

Topics: Adult; Benzodiazepines; Erectile Dysfunction; Humans; Male; Olanzapine; Pirenzepine; Priapism; Psychotic Disorders; Recurrence; Reoperation

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Hepatolenticular Degeneration; Humans; Male; Muscle Rigidity; Olanzapine; Parkinsonian Disorders; Pirenzepine; Psychotic Disorders; Risperidone

Topics: Antipsychotic Agents; Benzodiazepines; Body Weight; Female; Humans; Insulin; Leptin; Male; Metabolic Syndrome; Obesity; Olanzapine; Pirenzepine; Psychotic Disorders

Atypical antipsychotics are widely used in psychotic disorders, refractory to conventional neuroleptic agents. They induce minimal extra pyramidal side effects, probably due to their greater affinity for certain dopaminergic receptors. However, this polyreceptor affinity may be responsible for the development of other side effects. We report a 48 years old male drinker and addicted to cocaine, that after two months of Olanzapine use, developed a severe diabetes mellitus with fasting blood glucose values reaching 514 mg/dl. When he was admitted to the hospital, physical examination was normal and his body mass index was 28 kg/m2. Olanzapine was discontinued and blood glucose values gradually returned to normal. After two months of follow up, the patient is on dietary treatment and with a fasting glucose of 132 mg/dl.

Topics: Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Overdose; Humans; Insulin; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Suicide, Attempted

Topics: Antipsychotic Agents; Autobiographies as Topic; Benzodiazepines; Commitment of Mentally Ill; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Sick Role

Neuroleptic-induced tardive dyskinesia, which often appears in middle-aged and older adults early in the course of treatment with low doses of conventional antipsychotics, is 5 to 6 times more prevalent in elderly than in younger patients. In addition to age, other risk factors for tardive dyskinesia include early extrapyramidal symptoms (EPS), cumulative amounts of neuroleptics, duration of neuroleptic treatment, and history of alcohol abuse and/or dependence. The atypical antipsychotics, which have a low liability for EPS, are likely to also have low potential for tardive dyskinesia, despite the paucity of controlled studies. Starting and maintenance doses of the atypical antipsychotics should generally be lower in older than in younger adults.

Topics: Adult; Age Factors; Aged; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Incidence; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone

To evaluate the efficacy and safety of olanzapine in a hospitalized geriatric population that had previously failed to respond to, or tolerate, numerous trials with other antipsychotic medications.. A retrospective chart analysis was conducted on 58 elderly patients with psychotic symptoms who were given a trial on olanzapine. Data was collected regarding patients' psychiatric diagnoses, duration of illness, duration of hospitalization, prior response to psychotropic therapies, concomitant psychotropic agents, side effects, and clinically determined changes over time.. Results indicated that 60.3% of this refractory group of patients improved on olanzapine. Side effects were reported for 38% of the patients, with delirium, extrapyramidal symptoms (EPS), and drowsiness or lethargy being the most common.. The reported level of improvement in this group of refractory elderly psychotic patients indicates that olanzapine can make an important contribution to the mental health of elderly patients with similar characteristics.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Retrospective Studies

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Interactions; Humans; Male; Olanzapine; Pirenzepine; Priapism; Psychotic Disorders

The present study was designed to monitor the use of atypical antipsychotics in adults with intellectual disability and to evaluate the clinical effectiveness of these drugs. Twenty-one patients were commenced on an atypical antipsychotic: 12 on Olanzapine and nine on Risperidone. The ICD-10 diagnoses of the subjects were mild (13 cases) or moderate (8 cases) mental retardation, and psychiatric disorders (17 cases) with significant impairment of behaviour in 10 cases. Tolerability was good for 15 patients experiencing minimum or no side-effects, and medication was only stopped as a result of side-effects in one case. Clinical global outcome was rated as minimally improved or better for 16 cases. The present findings suggest that the atypical antipsychotics Olanzapine and Risperidone are well tolerated by patients with intellectual disability and psychiatric disorders, and are broadly effective against target symptoms.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Intellectual Disability; Male; Middle Aged; Mood Disorders; Olanzapine; Pirenzepine; Prospective Studies; Psychotic Disorders; Risperidone; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Topics: Adult; Benzodiazepines; Female; Humans; Obesity; Olanzapine; Pirenzepine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors; Weight Gain

Olanzapine is similar in structure and pharmacology to clozapine. An increased incidence of electroencephalogram (EEG) abnormalities and seizures has been associated with clozapine but not with olanzapine, although isolated cases of seizures under olanzapine have been observed in high-risk patients.. To evaluate the frequency of epileptic and non-epileptiform EEG abnormalities during treatment with olanzapine.. Using a rating scale of demonstrated reliability, 43 EEGs of patients receiving 10-25 mg/day olanzapine in routine treatment were blindly rated and compared with EEG registrations from the same 43 patients with a different medication.. There was no difference in epileptiform activity between the conditions with and without olanzapine. However, EEG slowing was significantly more frequent with olanzapine than under the other condition. This difference could not be attributed to concomitant medication.. Although epileptiform activity did not increase under olanzapine, unspecific EEG abnormalities may be more frequent than with use of other neuroleptics. Careful surveillance of patients with risk factors for seizures is advisable. Further studies addressing the frequency and clinical relevance of EEG changes under olanzapine are necessary.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Electroencephalography; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Seizures; Statistics, Nonparametric

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Esotropia; Female; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Dopamine Antagonists; Dyskinesia, Drug-Induced; Flupenthixol; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Remission Induction; Selective Serotonin Reuptake Inhibitors

Atypical anti-psychotic drugs (APDs) are widely used in psychotic disorders refractory to conventional neuroleptic agents.. Three cases of new-onset diabetes are reported in Caucasian men who were on clozapine (one) or olanzapine (two) for 3-6 months. They had a distinct presentation: weight loss, ketosis (one ketoacidosis), severe hyperglycaemia requiring insulin therapy, and relative insulin deficiency as reflected by glucagon stimulatory tests. In all cases, insulin was stopped within 1 month after the APD was discontinued.. Novel APDs not only induce diabetes as a result of weight gain in predisposed patients, but can also lead to a reversible state of insulin deficiency, and sometimes ketoacidosis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Depressive Disorder; Diabetes Mellitus; Glyburide; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Polypharmacy; Psychotic Disorders; Treatment Outcome

The aim of this study was to investigate the influence of the antipsychotic agent olanzapine on glucose-insulin homeostasis to explain possible mechanisms behind olanzapine-associated weight gain.. Fourteen patients on treatment with olanzapine (all meeting DSM-IV criteria for schizophrenia or related psychoses) were studied. Fasting blood samples for glucose, insulin, the growth hormone (GH)-dependent insulin-like growth factor I, and the insulin-dependent insulin-like growth factor binding protein-1 (IGFBP-1) were analyzed, as well as GH, leptin, and blood lipid levels and the serum concentrations of olanzapine and its metabolite N-desmethylolanzapine. In addition, body mass index (BMI) was calculated. Moreover, weight change during olanzapine treatment was determined.. Twelve of the 14 patients reported weight gain between 1 and 10 kg during a median olanzapine treatment time of 5 months, whereas data were not available for the other 2 patients. Eight patients (57%) had BMI above the normal limit. Eleven patients were normoglycemic, and 3 showed increased blood glucose values. Most patients (10/14; 71%) had elevated insulin levels (i.e., above the normal limit). Accordingly, the median value of IGFBP-1 was significantly lower for the patients in comparison with healthy subjects. Moreover, 8 (57%) of 14 patients had hyperleptinemia, 62% (8/13) had hypertriglyceridemia, and 85% (11/13) hypercholesterolemia. Weight change correlated positively to blood glucose levels and inversely to the serum concentration level of N-desmethylolanzapine. Additionally, the levels of blood glucose, triglycerides, and cholesterol correlated inversely to the serum concentration of N-desmethylolanzapine.. Olanzapine treatment was associated with weight gain and elevated levels of insulin, leptin, and blood lipids as well as insulin resistance, with 3 patients diagnosed to have diabetes mellitus. Both increased insulin secretion and hyprleptinemia may be mechanisms behind olanzapine-induced weight gain. Moreover, it is suggested that the metabolite N-desmethylolanzapine, but not olanzapine, has a normalizing effect on the metabolic abnormalities.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Body Weight; Chromatography, High Pressure Liquid; Female; Humans; Insulin; Leptin; Lipids; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Triglycerides

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Leukocyte Count; Male; Middle Aged; Neutropenia; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Time Factors

Because risperidone and olanzapine have similar efficacy and tolerability in the treatment of schizophrenia, costs, physician experience, and preference become relevant considerations in making treatment decisions. The purpose of this paper is to compare daily treatment costs of risperidone and olanzapine, and to examine psychiatrists' clinical preferences.. Dosage information was obtained from a national Ministry of Health registry and a national survey of psychiatrists. In addition, psychiatrists' clinical preference of antipsychotic medication and dosage for patient subtypes were examined by the national survey.. Data from the registry and national survey estimated the mean daily dose of risperidone to be one-third that of olanzapine, irrespective of patient subtype. Taking into account drug costs and dosage requirements, the average daily retail price was US $6.85 for risperidone and US $13.60 for olanzapine. Psychiatrists preferred risperidone for first-episode psychosis and elderly psychosis, and olanzapine for patients sensitive to EPS. They rated the drugs equally effective on positive and negative symptoms, for chronic patients, for treatment-refractory patients and relapse prevention.. Risperidone has a substantial cost advantage over olanzapine, and was preferred by psychiatrists for more indications.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Utilization; Humans; Israel; Olanzapine; Pirenzepine; Practice Patterns, Physicians'; Psychiatry; Psychotic Disorders; Risperidone; Surveys and Questionnaires

To emphasize the availability of safer alternatives to currently standard therapy for monosymptomatic hypochondriacal psychosis (MHP).. We report a case of treatment of monosymptomatic hypochondriacal psychosis in an elderly woman with the atypical neuroleptic olanzapine.. Treatment with rather low doses of olanzapine led to complete resolution of delusional symptoms.. Olanzapine, like other atypical neuroleptic agents, shows promise as a treatment for this syndrome, and it offers considerable safety and side-effect advantages over older agents.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Hypochondriasis; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

Four days after swallowing lithium and amitriptyline tablets with suicidal intent, a 48-year-old man was admitted. He was known to be suffering from recurrent depression which had led to 7 previous hospital admissions. At psychiatric assessment he appeared to be depressed with reduced ability of affective changes and impaired formal reasoning. He exhibited delusions of guilt and reference. His sleep was impaired and appetite diminished.. Serum lithium level was 1.98 mmol/l (therapeutic range 0.8-1.0 mmol/l). An ECG demonstrated sinus tachycardia, the EEG showed theta waves with mild general changes.. He was diagnosed as suffering from severe depressive syndrome with psychotic symptoms. He was given both antidepressive and neuroleptic drugs: mirtazapine 30 mg daily (p.d.) and halperidol 10 mg p.d.. When both the depressive and psychotic symptoms were treatment-resistant, even after a change from mirtazapine to venlafaxine (300 mg p.d.), the drug regimen was changed to sertraline, 150 mg p.d., and olanzapine, 20 mg p.d.. While this brought about improvement, his condition deteriorated when olanzapine was withdrawn. But all symptoms completely disappeared when olanzapine was again given. Spontaneous remission in the future thus seems unlikely to occur.. This case illustrates that the atypical antipsychotic drug olanzapine has some advantages over such typical antipsychotic drug olanzapine has some advantages over such typical antipsychotic medication as butyrophenone. The underlying mechanism for this greater efficacy is probably the difference in receptor-binding capacity between these drugs, the former inhibiting some serotonin receptors so that it is synergistic with antidepressives that inhibit serotonin transport.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Sertraline; Treatment Outcome

Four patients affected by severe Parkinson's disease developed leucopenia (900-1200 WBC) during treatment of psychosis (3) or untreatable insomnia (1) with clozapine (37.5-75 mg/day). Clozapine withdrawal was followed by recovery of leucopenia (4000-6000 WBC) in two weeks with no need for the administration of leucokines. After 1-6 months olanzapine was administered (increasing the dose from 2.5 to 10 mg/day) to treat persisting disturbances, but the drug induced severe worsening of parkinsonism and also this drug had to be withdrawn.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Leukopenia; Male; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Sexual Dysfunctions, Psychological; Sleep Initiation and Maintenance Disorders

Topics: Adult; Alcoholism; Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

We recorded steady state serum concentrations of olanzapine in 56 psychiatric patients under routine conditions. Twenty-two patients (39%) underwent monotherapy; the rest received additional psychotropic drugs. Doses were given once daily in the evening, and serum olanzapine levels were measured 12 hours later. For the whole group, the concentration-to-dose ratio (C/D) varied 26-fold, with a median value of 4.8 (nmol/L)/(mg/24 hours), but 80% of the patients had C/D values within the range 2 to 10 (nmol/L)/(mg/24 hours). All but three patients received standard doses (5-20 mg/24 hours), of whom 80% had serum concentrations of olanzapine within the range 22 to 146 nmol/L. Patients comedicated with potential inhibitors of CYP2D6 and other drugs displayed a median C/D approximately 40% higher than the group undergoing monotherapy. Patients comedicated with carbamazepine had a median C/D 36% lower than that of the monotherapy group. Therefore, the serum concentration range (12-hour values) of 25 to 150 nmol/L can be expected for patients receiving a standard daily dose.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Cytochrome P-450 CYP2D6 Inhibitors; Drug Interactions; Drug Monitoring; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Administration Schedule; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Treatment Outcome

Olanzapine acutely induced disabling hypofrontal symptoms in a 31-year-old male. This occurred after 13 years of exposure to typical neuroleptics without such symptoms. Presumably, hypofrontal symptoms should limit the dose of atypical neuroleptics in some patients. Milder expressions of hypofrontal symptoms should be more common.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D(2)/D(3) receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [(123)I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [(123)I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrence of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [(123)I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D(2)/D(3) receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR-BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D(2)/D(3) receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D(2)/D(3) receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D(2)/D(3) availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D(2)/D(3) striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D(2)/D(3) receptor affinity and a similar 5HT(2) receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D(2)/D(3) receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. t

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzamides; Benzodiazepines; Case-Control Studies; Corpus Striatum; Dopamine Antagonists; Female; Humans; Iodine Radioisotopes; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Pyrrolidines; Receptors, Dopamine; Risperidone; Schizophrenia; Tomography, Emission-Computed, Single-Photon

Twenty-one patients with Parkinson's disease and psychosis were included in an open-label 8-week trial of olanzapine. Eight subjects had dementia. Six subjects (29%) discontinued treatment prematurely because of drowsiness. Delusions and hallucinations improved significantly, and 80% were rated as much or very much improved. There was no worsening of parkinsonism or cognition.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dementia; Dose-Response Relationship, Drug; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Parkinson Disease; Pirenzepine; Prospective Studies; Psychotic Disorders; Severity of Illness Index; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Substance Withdrawal Syndrome; Treatment Outcome

Antipsychotic polypharmacy is a surprisingly frequent occurrence that can be both justified and unjustifed, depending on how it is used. To the extent that this phenomenon has been unrecognized and is not being studied, it is a "dirty little secret." To the extent that careful clinicians have uncovered a useful strategy for boosting the effectiveness of available antipsychotic monotherapies, it represents an opportunity to improve the outcomes of patients with psychotic illnesses.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Polypharmacy; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Dystonia; Facial Muscles; Humans; Male; Middle Aged; Neck Muscles; Olanzapine; Pirenzepine; Psychotic Disorders; Recurrence; Risperidone

There is paucity of published data regarding controlled trials with risperidone and olanzapine in elderly psychotic patients. Medical records of 151 hospitalized geropsychiatric patients (risperidone patients n = 114 and olanzapine patients n = 37) were analyzed for demographic data, target symptoms, doses, effects, side effects, comorbid medical conditions and concurrent medications. The mean age of the patients was 71 years. The male: female ratio was essentially the same for both groups. The mean daily dose was 3 mg for risperidone and 10 mg for olanzapine. 78% of the risperidone group and 75% of the olanzapine group appear to have responded to treatment. The discontinuation rates of medication was the same in both groups (22%). Adverse events were reported in 16-17% in both groups. It appears from this study that both risperidone and olanzapine are relatively safe and effective in geropsychiatric patients with comorbid medical illnesses. Controlled studies and head-to-head comparison studies are recommended.

Topics: Aged; Aged, 80 and over; Aging; Antipsychotic Agents; Benzodiazepines; Comorbidity; Female; Geriatric Psychiatry; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Retrospective Studies; Risperidone

Topics: Benzodiazepines; Female; Humans; Leukopenia; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Selective Serotonin Reuptake Inhibitors

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders

This is a report of two cases with schizophrenia in which a good response to olanzapine in an acute 6-week treatment phase was obtained, followed by early relapse without any clear contributing factors. Referring to a few other case reports of early relapse after an initial response to atypical antipsychotics other than olanzapine, the possibility is discussed that rapid displacement of these drugs due to loose binding could play a role in early relapse.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Binding, Competitive; Brief Psychiatric Rating Scale; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Patient Compliance; Pirenzepine; Psychotic Disorders; Receptors, Dopamine D2; Recurrence; Time Factors

Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). Weight gain occurs no matter what the patient's age, sex, or race and is seen with both oral and depot drug formulations. Numerous studies have found that patients gain weight when treated with a conventional antipsychotic, such as chlorpromazine, fluphenazine, and haloperidol. The newer, novel antipsychotics offer advantages over conventional antipsychotics, especially a relative lack of extrapyramidal symptoms, but some still have the disadvantage of causing weight gain. Clozapine and olanzapine in particular appear to cause substantial weight gain, much more so than do most conventional neuroleptics and novel agents such as risperidone. Given the risks to health and treatment compliance associated with weight gain and obesity, clinicians should monitor weight during the course of antipsychotic therapy and consider switching agents if excessive weight gain occurs.

Topics: Administration, Oral; Antipsychotic Agents; Benzodiazepines; Clozapine; Delayed-Action Preparations; Humans; Obesity; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Weight Gain

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorprothixene; Clopenthixol; Female; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Recurrence

We report a female patient with a diagnosis of a not otherwise specified psychotic disorder (DSM-IV) who developed hypomania shortly after the introduction of olanzapine treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

The aim of this paper is to survey patterns of use of new generation and conventional antipsychosis and adjunctive drugs by an inner urban community psychiatric service.. All prescriptions for antipsychosis medications and all patients receiving these drugs in May 1998 were identified. Case record review yielded demographic and diagnostic data. Information was also obtained directly from prescribers.. Of 859 patients, 77% received antipsychosis medication; 53% of prescriptions for antipsychotics were for new generation drugs: risperidone (42%), olanzapine (37%) and clozapine (21%). Mean doses were 4.1+/-2.5 mg (risperidone), 14.7+/-8.2 mg (olanzapine) and 377.4+/-178.9 mg (clozapine). Doses for men tended to be higher than those for women, but the differences were not significant. DSM-IV diagnosis was schizophrenia for 74% of patients on atypicals, but patients with other diagnoses were also being treated with these drugs. Risperidone was more commonly used in combination with benzodiazepines and anticholinergics than olanzapine and clozapine, while clozapine was less likely to be combined with antidepressants and mood stabilisers. Of the conventionals, 66% were in depot form, mostly because of non-compliance. Combinations of antipsychotics were prescribed to 13% of patients.. New generation antipsychosis medications were prescribed more commonly than conventional drugs in this service for a wide range of diagnoses. Adjunctive medications were commonly utilised. These findings underline the clinical complexity of antipsychotic treatment in a changing environment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Community Mental Health Services; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Utilization; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Urban Population

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Olanzapine; Paranoid Disorders; Pirenzepine; Psychotic Disorders; Schizophrenia; Stress, Psychological

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Schizophrenia

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Retrospective Studies; Weight Gain

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Dystonia; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia, Paranoid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Therapy, Combination; Female; Humans; Hypothermia; Olanzapine; Pirenzepine; Prader-Willi Syndrome; Psychotic Disorders; Risperidone

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Risperidone; Schizophrenia; Schizophrenic Psychology

The new antipsychotics induce minimal extrapyramidal side effects, probably due to their relatively greater affinity for certain nondopaminergic receptors than their older, conventional counterparts; however, this polyreceptor affinity may be responsible for the development of other adverse effects. One serious adverse effect that may be linked to these effects is non-insulin-dependent diabetes mellitus.. We summarize 6 new cases of clozapine- and olanzapine-associated diabetes that we have documented in our clinic. We compare our cases to previous reports and tabulate the pertinent similarities among cases.. Two of the cases were olanzapine-associated and 4 were clozapine-associated diabetes. Five of our 6 patients had risk factors for diabetes, as have 7 of the 9 previously reported in the literature. Four of our 6 patients, and 2 of the 4 prior cases in which such data were reported, experienced substantial weight gain after starting their antipsychotics.. Novel antipsychotics should be administered with great care to patients with risk factors for diabetes. Although the precise mechanism of the novel antipsychotic-associated diabetes is unclear, we hypothesize that histaminic and possibly serotonergic antagonism induces weight gain, which in turn leads to changes in glucose homeostasis. Additionally, serotonin1A antagonism might decrease pancreatic beta-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clozapine; Diabetes Mellitus, Type 2; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Syndrome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Treatment Outcome

Olanzapine is a relatively new antipsychotic agent which appears to be effective in the treatment of both the positive and negative symptoms of schizophrenia. Reported here is the case of a patient who developed symptoms of mania secondary to treatment with olanzapine. Physicians prescribing olanzapine should be aware of this potential complication.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders

Three studies compared olanzapine and haloperidol given orally in maintenance therapy for schizophrenia and related psychoses.. Data were from double-blind extensions of acute studies. The subjects met criteria for schizophrenia, schizophreniform disorder or schizoaffective disorder. Subjects had responded to acute therapy (Brief Psychiatric Rating Scale total score decreased > or = 40% from baseline (Studies 1, 2, and 3) or was < or = 18 (Studies 1 and 2)) and were out-patients at their last acute phase visit. Relapse was defined as hospitalisation for psychopathology. Subjects treated with olanzapine in the three studies were pooled to form the olanzapine group and subjects treated with haloperidol were pooled to form the haloperidol group.. Olanzapine-treated subjects experienced less relapse (P = 0.034). The Kaplan-Meier estimated one-year risk of relapse was 19.7% with olanzapine and 28% with haloperidol.. Olanzapine was superior to haloperidol in the maintenance therapy of schizophrenia and related psychoses.. This work was sponsored by Eli Lilly and Company.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Life Tables; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Randomized Controlled Trials as Topic; Recurrence; Schizophrenia; Survival Analysis; Treatment Outcome

Topics: Adult; Amenorrhea; Antipsychotic Agents; Benzodiazepines; Female; Humans; Menstruation; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Recurrence

The aim of the present paper is to report a case of Neuroleptic Malignant Syndrome (NMS) occurring 2 days after olanzapine was added to the treatment regimen of an elderly patient with Schizoaffective Disorder. The patient had a previous history of NMS associated with risperidone.. Two days after commencement of olanzapine, the patient presented in a stuporous state with dysarthria and increased muscle tone with cogwheeling. His level of consciousness fluctuated over the following 24 h with worsening rigidity, the onset of a mild fever, tachycardia and elevated blood pressure. Biochemical screening revealed markedly elevated creatine kinase.. Olanzapine was ceased and intravenous fluid replacement commenced. Hourly physical observations were instigated, as was regular serum monitoring of creatine kinase level.. Over the subsequent 48 h, there was gradual clinical improvement with resolution of dysarthria, ataxia, rigidity and fever. The patient was returned to the psychiatric ward 3 days after his admission to the medical ward.. Olanzapine therapy can be associated with NMS. To our knowledge, there are no previous reports of this in the literature.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Diagnosis, Differential; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Receptors, Dopamine D2; Receptors, Serotonin; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Clozapine; History, 20th Century; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Disease Management; Drug Costs; Humans; Mental Health Services; New York City; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Treatment Outcome

We studied the effect of olanzapine (1 to 15 mg/d) in 15 nondemented parkinsonian patients with drug-induced psychosis. Psychotic symptoms decreased significantly during treatment, and there was no worsening of extrapyramidal symptoms. These results suggest that olanzapine is a well-tolerated and effective treatment for drug-induced psychosis in nondemented patients with Parkinson's disease.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Parkinson Disease; Pirenzepine; Psychotic Disorders; Time Factors

Topics: Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine; Pirenzepine; Psychotic Disorders