olanzapine and Basal-Ganglia-Diseases

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

Topics: Aged; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Diagnosis, Differential; Female; Humans; Metabolic Syndrome; Middle Aged; Olanzapine; Pain; Patient Compliance; Peripheral Nervous System Diseases; Piperazines; Quinolones; Schizophrenia, Paranoid; Skin Diseases, Parasitic; Sleep Wake Disorders

Early-onset schizophrenia-spectrum (EOSS) disorders (onset of psychotic symptoms before 18 years of age) represent a severe variant associated with significant chronic functional impairment and poor response to antipsychotic treatment. All drugs with proven antipsychotic effects block dopamine D(2) receptors to some degree. The ongoing development of the dopamine and other neurotransmitter receptor systems during childhood and adolescence may affect clinical response and susceptibility to side effects in youth. A literature search was conducted of clinical trials of antipsychotics in children and adolescents with EOSS disorders between 1980 and 2007 from the Medline database, reference lists, and conference proceedings. Trials were limited to double-blind studies of duration of 4 or more weeks that included 15 or more patients. Ten clinical trials were identified. Antipsychotic medications were consistently found to reduce the severity of psychotic symptoms in children and adolescents when compared with placebo. The superiority of clozapine has been now demonstrated relative to haloperidol, standard-dose olanzapine, and "high-dose" olanzapine for EOSS disorders. However, limited comparative data are available regarding whether there are differences among the remaining second-generation antipsychotics (SGAs) in clinical effectiveness. The available data from short-term studies suggest that youth might be more sensitive than adults to developing antipsychotic-related adverse side effects (eg, extrapyramidal side effects, sedation, prolactin elevation, weight gain). In addition, preliminary data suggest that SGA use can lead to the development of diabetes in some youth, a disease which itself carries with it significant morbidity and mortality. Such a substantial risk points to the urgent need to develop therapeutic strategies to prevent and/or mitigate weight gain and diabetes early in the course of treatment in this population.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Disorders of Excessive Somnolence; Haloperidol; Humans; Olanzapine; Prolactin; Schizophrenia, Childhood; Treatment Outcome; Weight Gain

Topics: Antidepressive Agents, Second-Generation; Basal Ganglia Diseases; Benzodiazepines; Clinical Trials, Phase I as Topic; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Risperidone; Schizophrenia; Thiazoles

Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.. We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with a special reference to trial duration.. In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5-6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6-12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6-12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of >or=7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.. Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Humans; Lamotrigine; Olanzapine; Prevalence; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Surveys and Questionnaires; Treatment Outcome; Triazines

Topics: Adrenergic alpha-Antagonists; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Mass Index; Cytochrome P-450 Enzyme System; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Drug Interactions; Histamine H1 Antagonists; Humans; Muscarinic Antagonists; Olanzapine; Psychopharmacology; Receptor, Muscarinic M1; Retinoic Acid 4-Hydroxylase; Schizophrenia

Previous research on pharmacotherapy with conventional antipsychotics has suggested that patients with affective disorders have higher rates of treatment-emergent extrapyramidal symptoms (EPS) than patients with schizophrenia. It is not known whether this differential vulnerability holds true for treatment with atypical antipsychotics such as olanzapine. The present analysis retrospectively examined olanzapine clinical trial data for incidence of treatment-emergent EPS in patients with either schizophrenia or bipolar disorder.. Study participants were 4417 patients meeting DSM-III or DSM-IV criteria for either schizophrenia or bipolar mania participating in olanzapine clinical trials through July 31, 2001. Data were pooled across haloperidol-controlled trials and separately across placebo-controlled trials. Measures of EPS included rates of treatment-emergent EPS adverse event by type (i.e., dystonic, parkinsonian, or residual), Simpson-Angus Scale score mean change, rates of treatment-emergent parkinsonism, and rates of anticholinergic use.. Consistent with prior research, haloperidol-treated patients with bipolar disorder appeared to be more vulnerable to the development of EPS than those with schizophrenia. However, olanzapine-treated patients with bipolar disorder were no more likely to develop EPS than those with schizophrenia.. Results support previous research regarding conventional antipsychotics and suggest that olanzapine therapy does not increase the risk of EPS for patients with bipolar disorder.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Brief Psychiatric Rating Scale; Cholinergic Antagonists; Databases, Bibliographic; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Randomized Controlled Trials as Topic; Schizophrenia

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Comorbidity; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Haloperidol; Humans; Middle Aged; Obsessive-Compulsive Disorder; Olanzapine; Patient Dropouts; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Tic Disorders; Treatment Outcome

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cognition Disorders; Drug Tolerance; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Piperazines; Quinolones; Risperidone; Schizophrenia; Sulpiride; Time Factors

A key goal of the pharmacologic treatment of acute bipolar mania is rapid symptom improvement. Medications commonly used to attain this goal include lithium, several anticonvulsants, and both first- and second-generation antipsychotics. Second-generation antipsychotics, which are associated with substantially lower rates of extrapyramidal side effects than first-generation agents, are becoming a mainstay in the treatment of acute mania. Although their efficacy appears to be comparable, second-generation antipsychotics may differ in time to onset and in their side effect profiles. Therefore, selecting a second-generation antipsychotic requires consideration of how an agent's efficacy, onset of action, and adverse events profile influence its appropriateness for each patient.

Topics: Acute Disease; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Double-Blind Method; Humans; Lithium; Olanzapine; Piperazines; Placebos; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Pharmacotherapy in patients with dementia aims to improve distressing behavioral and psychological signs of dementia after nonpharmacologic interventions fail, without causing unacceptable side effects or exacerbating underlying cognitive impairment. We review data describing risperidone (3 published placebo-controlled trials), olanzapine (1 abstract regarding a placebo-controlled trial and a published placebo-controlled trial), quetiapine (1 published open-label trial and an abstract regarding a placebo-controlled trial), and aripiprazole (1 abstract regarding a placebo-controlled trial). For example, a 12-week study of risperidone in patients with Alzheimer's disease showed a dose-related improvement in psychosis and agitation. The frequency of extrapyramidal symptoms (EPS) was also significantly greater in patients receiving the highest doses. A 6-week study of olanzapine showed greater improvement than placebo in agitation/aggression and psychosis with doses of 5 and 10 mg/day, but not 15 mg/day, with side effects including gait disturbance and sedation at all doses. A 52-week, open-label trial of quetiapine (median dose = 138 mg/day) in elderly patients with psychosis suggested good tolerability with apparent behavioral benefit; EPS improved or remained unchanged in most patients. Limited data describing aripiprazole have shown inconclusive evidence regarding relief of psychosis in elderly patients with Alzheimer's disease-related dementia, with apparently good tolerability over the short term. It appears that, in the aggregate, atypical antipsychotics are efficacious for treatment of agitation in dementia, with less clear impact on psychosis, but their tolerability profiles clearly differ. The National Institute of Mental Health-funded Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease project will provide the first head-to-head comparisons of atypicals in dementia and will examine possible drug-drug differences between efficacy and effectiveness.

Topics: Aged; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Controlled Clinical Trials as Topic; Dementia; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Treatment Outcome

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

Although life prevalence of substance use disorders among patients with schizophrenia is close to 50%, few studies have been carried out to date to identify an integrated pharmacological treatment for this comorbidity. So far, the most promising results, that we report here, have been obtained with clozapine. To a lesser extent, quetiapine and olanzapine, both clozapine analogues, have also shown promising results. Further to these observations, the present paper critically reviews the advantages associated with clozapine, quetiapine and olanzapine, and their relevance to the treatment of addiction among schizophrenic patients. Six characteristics seem to distinguish clozapine, quetiapine and olanzapine from the first-generation antipsychotics: (1) acting preferentially on the reward system, these second-generation antipsychotics (mainly clozapine and quetiapine) induce almost no extrapyramidal symptoms; (2) quickly dissociating from D(2), theses drugs (mainly clozapine and quetiapine) seem not to induce dysphoria, unlike conventional antipsychotics like haloperidol;(3) these drugs (mainly clozapine) seem more effective in the treatment of negative symptoms than conventional antipsychotics; (4) because of a diversified activity on several serotoninergic and noradrenergic receptors, these drugs positively alter mood, which does not seem to be the case with conventional antipsychotics, except for flupenthixol; (5) these drugs have a positive impact on cognition, which is not the case with the first-generation antipsychotics; (6) unlike conventional antipsychotics, these drugs seem to have a moderate affinity for 5-HT(3), the receptor on which ondansetron, an anti-craving medication, acts.

Topics: Affect; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Cognition; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Schizophrenia; Substance-Related Disorders; Treatment Outcome

Pharmacological treatment remains the mainstay of the management of schizophrenia. Older, "typical" antipsychotics carry a significant burden of side effects, notably extrapyramidal and neurocognitive side effects. Newer, "atypical" agents carry a lower risk of extrapyramidal side effects. They appear to have added benefit for treating negative and cognitive symptoms of schizophrenia, and hence can enhance the quality of life of some patients. The choice of particular agents for individual patients requires a balancing of efficacy and side effects. Medication is only one element of what should be an individualised comprehensive treatment plan for people with schizophrenia.

Topics: Amisulpride; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia; Sulpiride

The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (- 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database.. This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and akathisia events were compared using treatment-emergent adverse-event data. Categorical analyses of Simpson-Angus Scale and Barnes Akathisia Scale (BAS) scores, use of anticholinergic medications, and baseline-to-endpoint changes in Simpson-Angus Scale and BAS scores were compared.. A significantly smaller percentage of olanzapine-treated patients experienced dystonic events than did haloperidol- (p <.001) or risperidone-treated patients (p =.047). A significantly greater percentage of haloperidol-treated patients experienced parkinsonian (p <.001) and akathisia (p <.001) events than did olanzapine-treated patients. Categorical analysis of Simpson-Angus Scale scores showed significantly more haloperidol- (p <.001) or risperidone-treated patients (p =.004) developed parkinsonism than did olanzapine-treated patients. Olanzapine-treated patients experienced significantly greater reductions in Simpson-Angus Scale scores than did haloperidol- (p <.001), risperidone- (p <.001), or clozapine-treated (p =.032) patients. Categorical analysis of BAS scores showed significantly more haloperidol-treated patients experienced treatment-emergent akathisia versus olanzapine-treated patients (p <.001). Significantly greater reductions in BAS scores were experienced during olanzapine treatment versus placebo (p =.007), haloperidol (p <.001), and risperidone (p =.004) treatments. A significantly smaller percentage of olanzapine-treated patients received anticholinergic medications compared with that of haloperidol- (p <.001) or risperidone-treated patients (p =.018). Compared with that in olanzapine-treated patients, the duration of anticholinergic cotreatment was significantly longer among haloperidol- (p <.001) or risperidone-treated patients (p =.040) and significantly shorter among clozapine-treated patients (p =.021).. This analysis of available data from olanzapine clinical trials lends additional support to olanzapine's favorable EPS profile.

Topics: Acute Disease; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cholinergic Antagonists; Clozapine; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Placebos; Randomized Controlled Trials as Topic; Retrospective Studies; Risperidone; Schizophrenia

The atypical antipsychotics have a low incidence of extrapyramidal side effects (EPS), have improved tardive dyskinesia profiles, and have a broad range of therapeutic efficacy. These agents offer important therapeutic advantages that extend beyond their initial regulatory approval in several conditions and patient groups. The use of atypical antipsychotics is most relevant in the treatment of mood disorders, where these medications are being used increasingly for acute mood stabilization and in patients who are resistant to other treatments. Similar circumstances and clinical advantages pertain to the use of atypical antipsychotics in the treatment of behavioral disturbances in patients with dementia and in the management of personality disorders-both circumstances where conventional antipsychotics were initially poorly tolerated because of EPS. The low incidence of EPS associated with atypical antipsychotics is highly beneficial in several neuropsychiatric conditions. The extent to which endocrine and metabolic dysregulations associated with atypical antipsychotics will influence antipsychotics' role remains to be determined. As therapeutic opportunities evolve and diversify, atypical antipsychotics, because of favorable adverse-effect profiles, will have enhanced patient tolerability and use in nonpsychiatric conditions.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child Development Disorders, Pervasive; Clozapine; Dementia; Dibenzothiazepines; Humans; Mood Disorders; Olanzapine; Personality Disorders; Pirenzepine; Quetiapine Fumarate; Risperidone

The most frequent problems associated with the older generation of antipsychotic agents are extrapyramidal side effects (EPS) and tardive dyskinesia. Neuroleptic-induced EPS are thought to be caused by blockade of nigrostriatal dopamine tracts resulting in a relative increase in cholinergic activity; tardive dyskinesia is less well understood but is thought to be a supersensitivity response to chronic dopamine blockade. The leading hypothesis for the mechanism of action of the newer generation of atypical antipsychotics is the presence of a high serotonin-to-dopamine receptor blockade ratio in the brain. When serotonergic activity is blocked-as is the case with atypical antipsychotics-dopamine release increases and balances out the dopamine blockade effect at postsynaptic receptor sites, which results in few or no EPS. Prospective data indicate that the risk of tardive dyskinesia in patients taking atypical antipsychotics is less than that for those taking typical antipsychotics. This article reviews the mechanisms of neuroleptic-induced EPS and tardive dyskinesia and discusses the relationship between these movement disorders and atypical antipsychotic agents.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brain; Clozapine; Dibenzothiazepines; Humans; Movement Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Receptors, Dopamine; Receptors, Serotonin; Risk Factors; Risperidone

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

The objective of this meta-analysis is to summarize the efficacy and tolerability of the new antipsychotics risperidone, olanzapine, sertindole and quetiapine in schizophrenia compared to placebo and conventional antipsychotics. The main results are: (1) All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate [mean effect size, r, of all antipsychotics vs. placebo = 0.25, with a 95% confidence interval (CI) = 0.22-0.28, n = 2477]. (2) According to the studies published to date, sertindole and quetiapine are as effective as haloperidol, and risperidone and olanzapine are slightly more effective than haloperidol in the treatment of global schizophrenic symptomatology. (3) With respect to negative symptoms, all new antipsychotics are more effective than placebo. However, contrary to widespread opinion, so is the 'conventional' antipsychotic haloperidol. Risperidone and olanzapine are slightly superior, sertindole is as effective and--according to the only study fully published to date--quetiapine is even slightly less effective than haloperidol in this regard. (4) All new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol, with risperidone appearing to have a slightly less favourable EPS-profile than the other new antipsychotics. The methodological limitations of this review, the generalizability of the results and expectations from future research are discussed.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzothiazepines; Double-Blind Method; Haloperidol; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Typical antipsychotic agents produce central nervous system effects, especially extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Nearly every patient who receives neuroleptic therapy has one or more identifiable risk factors for TD, among the most significant of which are older age, female gender, presence of EPS, diabetes mellitus, affective disorders, and certain parameters of neuroleptic exposure (i.e. dose and duration of therapy). The typical course of TD is a gradual onset after several years of drug therapy, followed by slow improvement or remission, but a large number of patients have persistent TD with irreversible symptoms. In the management of TD, the patient's mental status is of primary concern. Currently, no uniformly safe and effective therapies for TD exist, though a variety of therapeutic agents, including some of the atypical neuroleptics, have been reported to treat TD successfully in some patients. Because TD liability is so much lower with novel antipsychotic therapy, all patients who have TD or are at risk for TD, as well as EPS, should be considered candidates for switching to these new drugs.

Topics: Adult; Age Factors; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone; Schizophrenia; Sex Factors

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

Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System Diseases; Clozapine; Dibenzothiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Health Status; Humans; Hypotension, Orthostatic; Olanzapine; Pirenzepine; Quality of Life; Quetiapine Fumarate; Receptors, Cholinergic; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Sleep Wake Disorders; Treatment Refusal; Weight Gain

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 new antipsychotic agent with serotonin/dopamine antagonism action. Efficacy in treating overall psychopathology in acute schizophrenia as measured by the BPRS0-6 total score was demonstrated at 10 mg/day versus placebo; at doses in a 5-20 mg/day range, olanzapine was comparable or superior to haloperidol. Superior efficacy for negative and depressive symptoms was shown in comparison to haloperidol. Olanzapine has a favorable acute and tardive extrapyramidal symptom profile relative to haloperidol and caused substantially less elevation of serum prolactin. Dose-related weight gain and asymptomatic mild transaminase elevations occurred in olanzapine-treated patients.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Prolactin; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology

Most traditional neuroleptics have a narrow therapeutic-to-toxic index, and thus, the novel antipsychotics are the result of a search to substantially widen the distance between the dose that treats psychosis and the one that produces adverse effects. In vitro binding profiles have been created for the atypical antipsychotics that have been approved by the U.S. Food and Drug Administration (FDA)-clozapine, olanzapine, and risperidone and those that are under FDA review-quetiapine and sertindole. These profiles, which were compared with that of the typical neuroleptic haloperidol, provide guidance for predicting the adverse effects produced by these drugs. Most conventional antipsychotics have central nervous system effects, particularly extrapyramidal symptoms (EPS) and tardive dyskinesia, sedation, and dulling of cognition. Other adverse effects of the typical antipsychotics include the neuroleptic malignant syndrome, orthostatic hypotension, changes in liver function, anticholinergic and antiadrenergic side effects, sexual dysfunction, and weight gain. The newer agents have a lower incidence of EPS and tardive dyskinesia, while weight gain and changes in blood pressure and liver function tests are adverse effects that have been associated with the use of the newer agents. The favorable side effect profile of these new antipsychotics is likely to make patients more willing to continue treatment, and thus these agents represent a step forward in the treatment of patients with severe, chronic mental illness.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Haloperidol; Humans; Olanzapine; Parkinson Disease, Secondary; Pirenzepine; Receptors, Neurotransmitter; Seizures; Sleep; Weight Gain

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

Evaluate the efficacy and safety of asenapine 2.5 mg twice daily (bid; n=97) or 5 mg bid (n=113) versus placebo (n=101) in adults with acute exacerbation of schizophrenia.. Adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) schizophrenia diagnosis were randomized to asenapine 2.5 mg bid, 5 mg bid, placebo, or olanzapine 15 mg once daily. The primary objective was to test superiority of asenapine versus placebo as measured by the change from baseline to day 42 in the Positive and Negative Syndrome Scale (PANSS) total score. The key safety objective was to evaluate weight change in asenapine versus olanzapine at day 42.. The primary efficacy endpoint was met; the difference in least squares mean change from baseline to day 42 in PANSS total score between asenapine 5 mg bid and placebo was -5.5 points (unadjusted 95% CI: -10.1, -1.0; multiplicity adjusted P=0.0356). Neither asenapine 2.5 mg bid nor olanzapine 15mg were superior to placebo. Both asenapine groups demonstrated significantly less weight gain than olanzapine at day 42. Significantly higher incidences of oral hypoesthesia and dysgeusia (combined) for asenapine 2.5 mg bid (5.2% vs 0.0%; P=0.0217) and 5 mg bid (7.1% vs 0.0%; P=0.0033) were observed versus placebo. There were no significant differences between asenapine and placebo for insomnia, extrapyramidal symptoms, akathisia, dizziness, or combination of somnolence/sedation/hypersomnia.. This study supports previous efficacy and safety findings of asenapine; asenapine 5 mg bid is the lowest effective dose in adults with schizophrenia. Asenapine was associated with significantly less weight gain than olanzapine at day 42.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzocycloheptenes; Disease Progression; Disorders of Excessive Somnolence; Dizziness; Double-Blind Method; Dysgeusia; Europe; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Hypesthesia; Least-Squares Analysis; Male; Mouth Diseases; Olanzapine; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Weight Gain

This analysis of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (NCT01157351) compared outcomes after administration of once-monthly paliperidone palmitate (PP) vs conventional oral antipsychotics (COAs) or atypical oral antipsychotics (AOAs).. PRIDE was a 15-month study of 444 individuals with schizophrenia and a history of incarceration. They were randomly assigned to PP or to 1 of 7 commonly prescribed OAs. Primary endpoint was time to first treatment failure (TF). Event-free probabilities were estimated using the Kaplan-Meier method; treatment group differences (PP vs COAs, PP vs AOAs, and PP vs oral paliperidone/risperidone) were assessed using a log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. No adjustment was made for multiplicity.. Compared with PP, risk for first TF was 34% higher with COAs (HR: 1.34; 95% CI: 0.80-2.25), 41% higher with AOAs (HR: 1.41; 95% CI: 1.06-1.88), and 39% higher with paliperidone/risperidone (HR: 1.39; 95% CI: 0.97-1.99). Incidences of extrapyramidal symptom-related adverse events (AEs) were 45.7%, 13.7%, and 10.6% in the COA, AOA, and oral paliperidone/risperidone groups vs 23.9% in the PP group. Incidences of prolactin-related AEs were 5.7%, 3.8%, and 3.5% vs 23.5%, and incidences of ≥7% weight increase were 11.4%, 14.9%, and 16.0% vs 32.4%.. Results suggest a lower risk of TF but a higher rate of some AEs after treatment with PP vs COAs, AOAs, and paliperidone/risperidone. Deselection of specific OAs and low patient-compliance rates with OAs likely biased the safety results.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Female; Haloperidol; Humans; Hyperprolactinemia; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Perphenazine; Proportional Hazards Models; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Failure; Treatment Outcome

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

The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Catechol O-Methyltransferase; Dopamine Plasma Membrane Transport Proteins; Female; Genotype; GluK3 Kainate Receptor; Humans; Male; Middle Aged; Monoamine Oxidase; Olanzapine; Overweight; Perazine; Piperazines; Polymorphism, Genetic; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Receptors, Kainic Acid; Schizophrenia, Paranoid; Serotonin Plasma Membrane Transport Proteins; Thiazoles; Weight Gain; Young Adult

Two randomized, double-blind, 26-week core studies (Eastern [EH] and Western Hemisphere [WH]) tested the hypothesis that asenapine is superior to olanzapine for persistent negative symptoms of schizophrenia; 26-week extension studies assessed the comparative long-term efficacy and safety of these agents. In the core studies, 949 people were randomized to asenapine (n = 241 and 244) or olanzapine (n = 240 and 224); 26-week completion rates with asenapine were 64.7% and 49.6% (olanzapine, 80.4% and 63.8%) in the EH and WH, respectively. In the EH and WH extensions, respectively (asenapine, n = 134 and 86; olanzapine, n = 172 and 110), 52-week completion rates were 84.3% and 66.3% with asenapine (olanzapine, 89.0% and 80.9%). Asenapine was not superior to olanzapine in change in the 16-item Negative Symptom Assessment Scale total score in either core study, but asenapine was superior to olanzapine at week 52 in the WH extension study. Olanzapine was associated with modest, but significantly greater, changes in PANSS positive subscale score at various assessment times in both core studies and the WH extension study. Incidence of treatment-emergent adverse events was comparable between treatments across studies. Weight gain was consistently lower with asenapine. Extrapyramidal symptom-related adverse event incidence was higher with asenapine (EH: 8.3%; 95% confidence interval [CI], 5.1%-12.5%; WH: 16.4%; 95% CI, 11.9%-21.6%) than olanzapine (EH: 3.3%; 95% CI, 1.4%-6.4%; WH: 12.1%; 95% CI, 8.1%-17.0%), but Extrapyramidal Symptom Rating Scale-Abbreviated total score changes did not significantly differ between treatments. In conclusion, asenapine superiority over olanzapine was not observed in the core studies. Both treatments improved persistent negative symptoms, but discontinuation rates were higher with asenapine.

Topics: Adult; Affect; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzocycloheptenes; Double-Blind Method; Drug Resistance; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Interpersonal Relations; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Psychomotor Performance; Schizophrenia; Schizophrenic Psychology; Social Behavior; Young Adult

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

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

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

Early response to antipsychotic medication has been shown to accurately predict later response to continued use of the same treatment in patients with chronic schizophrenia. This study examines whether this predictive pattern exists for patients with first-episode psychosis. We used a data-driven threshold for early response of ≥ 26.2% improvement from baseline on the Positive and Negative Syndrome Scale (PANSS(0-6)) Total score to determine whether response at Week 2 of treatment may predict response at Week 12 in a randomized, double-blind trial of olanzapine versus haloperidol for treatment of patients with first-episode psychosis (N=225). Later response was defined as a ≥ 40% and ≥ 50% improvement in PANSS Total(0-6) score and as remission. At Week 2, 43% (97/225) of patients were identified as early responders. At a threshold for later response of ≥ 50% improvement in PANSS(0-6) Total score, early non-response most strongly predicted later non-response, demonstrating high specificity (74%) and high negative predictive value (80%). As had been seen in the treatment of patients with chronic schizophrenia, early non-response was a robust predictor of subsequent non-response in the treatment of patients with first-episode psychosis.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Double-Blind Method; Female; Follow-Up Studies; Haloperidol; Humans; International Cooperation; Male; Mental Disorders; Olanzapine; Predictive Value of Tests; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome; Weight Gain; Young Adult

The concepts of partial recovery and remission have become increasingly important for the evaluation of the effectiveness of schizophrenia therapeutics. The relationship of baseline symptoms and changes in symptoms to remission of psychosis was evaluated. Fifty-six outpatients with residual schizophrenia completed a double-blind trial of olanzapine versus haloperidol and were then enrolled into a one-year open-label trial of olanzapine. Out of these 56 subjects, 13 (23%) met remission criteria at the beginning of the open-label treatment and were excluded. During the one-year study, 7/43 (16%) subjects met remission criteria. These subjects had significantly lower baseline ratings for tardive dyskinesia (TD) than subjects who did not achieve remission (1.8 +/- 1.5 vs. 4.2 +/- 4.6, P = 0.03). As expected, remitted subjects had significantly greater improvements in Brief Psychiatric Rating Scale total scores, positive subscale scores and scale for the Assessment of Negative Symptoms total scores. Remitted subjects also experienced a significantly greater improvement in depressive symptoms (P = 0.001), activation (P = 0.005), and Clinical Global Impressions scores (P < 0.001), as well as greater improvements in extrapyramidal symptoms (P = 0.007) and TD (P < 0.001). These results suggest that the relationship of depressive symptoms and improved side effects to the construct of remission in schizophrenia may deserve special attention. Future studies should aim to relate remission criteria to functional outcomes, cognition, and other important symptom domains.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Depression; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Quality of Life; Remission Induction; Schizophrenia; Severity of Illness Index

An open-label study was performed to investigate the clinical efficacy and tolerability of olanzapine orally disintegrating tablets (Zyprexa Zydis) in ameliorating excitement symptoms in the acute phase of schizophrenia. Fifty-three patients meeting DSM-IV criteria for first-episode schizophrenia and treated with olanzapine monotherapy were evaluated with regard to their clinical improvement, behavioural response to medication, and extrapyramidal side effects using the Positive and Negative Syndrome Scale Excited Component (PANSS-EC), Nursing Assessment of Medication Acceptance (NAMA), and Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), respectively. Scores of PANSS-EC were significantly reduced after 3 days of olanzapine administration. A reduction in NAMA scores was also observed 7 days after administration of olanzapine. The DIEPSS score was unaffected by olanzapine administration. These results suggest that olanzapine orally disintegrating tablets are effective and well-tolerated for treatment excitement in the acute phase of schizophrenic patients. In addition, it is possible that adherence to medications is improved by using olanzapine orally disintegrating tablets.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Male; Middle Aged; Mouth; Olanzapine; Patient Compliance; Prospective Studies; Psychomotor Agitation; Schizophrenia; Severity of Illness Index; Solubility; Young Adult

This multicenter, double-blind, randomized, controlled study conducted in China examined the efficacy and safety of olanzapine versus lithium in the treatment of patients with bipolar manic/mixed episodes.. Patients with bipolar manic or mixed episode (DSM-IV criteria) and Young Mania Rating Scale (YMRS) score> or =20 at screening received olanzapine (5-20 mg/day, n=69) or lithium carbonate (600-1800 mg/day, n=71) for 4 weeks. The primary outcome was mean change from baseline in Clinical Global Impressions-Bipolar Version Overall Severity of Illness (CGI-BP) score. Secondary efficacy measures included YMRS, Brief Psychiatric Rating Scale (BPRS), and Montgomery-Asberg Depression Rating Scale (MADRS) scores. Safety was also assessed.. A significantly greater mean change was observed in olanzapine versus lithium patients in CGI-BP (Overall Severity) (P=0.009), YMRS (P=0.013), BPRS (P=0.032), and CGI-BP (Severity of Mania) (P=0.012) scores. More olanzapine than lithium patients experienced at least one adverse event possibly related to study drug (P=0.038). More olanzapine patients had a clinically significant weight increase (> or =7% of baseline weight) compared to lithium patients (P=0.009). More olanzapine patients completed the study than lithium patients, although this difference was not statistically significant (olz, 91.3%; lith, 78.9%; P=0.057).. No placebo arm was included; however both treatments have previously been reported to be more effective than placebo.. These results suggest that olanzapine has superior efficacy to lithium in the acute treatment of patients with bipolar mania over a 4-week period. However, adverse events were experienced by a greater number of olanzapine patients than lithium patients.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Brief Psychiatric Rating Scale; Depressive Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Lithium Carbonate; Male; Obesity; Olanzapine; Psychiatric Status Rating Scales; Severity of Illness Index; Weight Gain

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

This was a randomized, flexible-dose, rater-blind, parallel-group, quasi-naturalistic trial comparing the efficacy, safety, and tolerability of quetiapine, risperidone, and olanzapine in patients with schizophrenia hospitalized for severe psychotic symptoms. Seventy-five patients were randomized to quetiapine (n=25), risperidone (n=25), or olanzapine (n=25). Mean doses at Week 8 were: 590.0 mg/day quetiapine; 5.1 mg/day risperidone; 15.1 mg/day olanzapine. Four quetiapine, five risperidone, and five olanzapine patients discontinued prior to Week 8. There were no significant differences between groups in the primary efficacy measures of improvement from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 8 in the per protocol (PP) population and the number of completers who experienced >or=40% improvement on the same scale. PP and intent-to-treat analyses showed significant improvement from baseline in each component of a PANSS-derived battery, without significant differences between treatments. No quetiapine patients, one risperidone, and four olanzapine patients reported an adverse event (AE) of moderate intensity; no severe AEs were reported. A linear mixed model for repeated measures showed an effect of treatment on body weight, with significant differences favoring quetiapine over risperidone and olanzapine. Simpson-Angus Scale scores were significantly worse with risperidone compared with both olanzapine and quetiapine at Week 3 and compared with quetiapine thereafter. Use of concomitant medications for anxiety or tension was significantly less frequent with quetiapine. In conclusion, quetiapine, risperidone, and olanzapine have similar efficacy in schizophrenia, but there are drug-specific differences for some AEs and in the use of concomitant medication that differentiate these agents.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

To evaluate the efficacy of olanzapine compared with risperidone in negative symptoms, after 1 year of treatment, in schizophrenic outpatients with prominent negative symptoms.. This was a multicenter, randomized, monitored, open-label, parallel, dose-flexible, 1-year study of outpatients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) with prominent negative symptoms (Scale for the Assessment of Negative Symptoms [SANS] summary score > or =10) previously treated with conventional antipsychotics. Patients were randomly assigned to treatment with an initial dose of olanzapine 10 mg/d or more (n = 120) or risperidone 3 mg/d or more (n = 115). The primary efficacy measure was the SANS summary score. Secondary efficacy measures included Scale for the Assessment of Positive Symptoms, Clinical Global Impression of Severity Scale, Calgary Depression Scale, and Social Functioning Scale. The response rate was defined as 30% or more of improvement in the SANS summary score.. The mean dose throughout the study was 12.2 mg/d (+/-5.8 mg/d) for olanzapine and 4.9 mg/d (+/-2.0 mg/d) for risperidone. At 1 year, olanzapine patients showed significantly higher improvement than risperidone patients on the SANS summary (P = 0.015) and on the affective flattening (P = 0.007) and avolition/apathy (P = 0.028) SANS subscales. There were also significant improvements in favor of olanzapine in the Scale for the Assessment of Positive Symptoms summary (P = 0.021), Clinical Global Impression of Severity (P = 0.008), and Social Functioning Scale total (P < 0.001) scores. The response rate was greater (P = 0.001) in the olanzapine cohort (69.2%) than in the risperidone cohort (48.7%). Olanzapine patients reported less extrapyramidal side effects but a higher incidence of clinically important body weight increase than risperidone patients.. Long-term treatment with olanzapine was associated with significantly better improvement in negative symptoms as compared with risperidone-treated schizophrenic outpatients with prominent negative symptoms.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Mass Index; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Olanzapine; Outpatients; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Weight Gain

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

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

Olanzapine has been hypothesized to have superior efficacy in patients with treatment-resistant schizophrenia. The authors examined the comparative efficacy and safety of olanzapine and haloperidol in outpatients with partially responsive schizophrenia.. Sixty-three outpatients with schizophrenia who met retrospective and prospective criteria for either residual positive or residual negative symptoms entered a 16-week double-blind, parallel-groups comparison of olanzapine and haloperidol.. There were no significant differences between the two drugs in their effect on positive or negative symptoms. There were no significant differences between the two treatment groups on measures of social and functional outcome. Olanzapine-treated patients had a significant reduction in extrapyramidal symptoms and subjective measures of stiffness and dry mouth, but the increases in systolic blood pressure and weight in olanzapine-treated patients were significantly greater than they were in haloperidol-treated patients.. Olanzapine has limited differential benefit for either positive or negative symptoms in patients with treatment-resistant schizophrenia. Although olanzapine is associated with fewer extrapyramidal symptoms, other side effects may offset this benefit.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Weight; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Obesity; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Comorbid cocaine abuse adversely affects clinical outcomes in schizophrenia. Using a prospective, randomized, parallel group design (N = 24), we tested the hypothesis that patients with schizophrenia treated with olanzapine have reduced cocaine craving and abuse compared with those treated with haloperidol. In addition, we examined whether this differential effect correlated with reductions in extrapyramidal symptoms, positive and negative symptoms, and/or depression. There were no significant differences overall in proportions of positive drug screens between treatment groups; no differences in positive, negative, or depressive symptoms; and few differences between treatment conditions in extrapyramidal symptoms. However, craving for cocaine was rated significantly lower by patients treated with haloperidol compared with patients treated with olanzapine. Important study limitations include a small sample size and high attrition rates. Larger controlled studies are necessary to determine optimal antipsychotic therapy for patients with schizophrenia and comorbid cocaine abuse.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Behavior, Addictive; Benzodiazepines; Cocaine-Related Disorders; Comorbidity; Depressive Disorder; Female; Haloperidol; Hospitals, Veterans; Humans; Male; Middle Aged; Olanzapine; Philadelphia; Research Design; Schizophrenia; Schizophrenic Psychology; Substance Abuse Detection

This study investigated safety and effectiveness of olanzapine in monotherapy compared with conventional antipsychotics in treatment of acute inpatients with schizophrenia.. This was a prospective, comparative, nonrandomized, open-label, multisite, observational study of Spanish inpatients with an acute episode of schizophrenia. Data included safety assessments with an extrapyramidal symptoms (EPS) questionnaire and the report of spontaneous adverse events, plus clinical assessments with the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate methodology was used to more adequately determine which factors can influence safety and effectiveness of olanzapine in monotherapy.. 339 patients treated with olanzapine in monotherapy (OGm) and 385 patients treated with conventional antipsychotics (CG) were included in the analysis. Treatment-emergent EPS were significantly higher in the CG (p<0.0001). Response rate was significantly higher in the OGm (p=0.005). Logistic regression analyses revealed that the only variable significantly correlated with treatment-emergent EPS and clinical response was treatment strategy, with patients in OGm having 1.5 times the probability of obtaining a clinical response and patients in CG having 5 times the risk of developing EPS.. In this naturalistic study olanzapine in monotherapy was better-tolerated and at least as effective as conventional antipsychotics.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Demography; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Prospective Studies; Risk; Schizophrenia; Severity of Illness Index; Treatment Outcome

The authors compared efficacy of olanzapine versus placebo and risperidone as measured by the Neuropsychiatric Inventory and Clinical Global Impression-Severity of Psychosis scale in patients with dementia-related psychosis.. Patients with moderate-to-severe psychotic symptoms associated with dementia were recruited from outpatient or residential settings and randomly assigned to 10-week, double-blind, flexible-dose treatment with olanzapine (N=204; 2.5 mg-10 mg/day; mean: 5.2 mg/day), risperidone (N=196; 0.5 mg-2 mg/day; mean: 1.0 mg/day) or placebo (N=94).. Most measures of neuropsychiatric functioning improved in all treatment groups, including the placebo group, and no significant treatment differences occurred. Overall discontinuation was lowest in the placebo group, and the olanzapine group had a significantly higher incidence of discontinuation due to adverse events (16.2%) relative to placebo (3.2%) and risperidone (8.7%) groups. Treatment-emergent extrapyramidal symptoms were more numerous for risperidone- than placebo- or olanzapine-treated patients. Abnormally high prolactin levels occurred in 78.0% of risperidone patients, compared with 16.7% for olanzapine and 5.0% for placebo. The incidence of weight gain greater than 7% from baseline was higher in the olanzapine group relative to risperidone, but neither active-treatment group showed a statistical difference from placebo (1.1%). No other statistically significant and clinically relevant differences were seen for any other vital sign, electrocardiographic measure, or laboratory hematology and chemistry, including glucose, except for cholesterol, which decreased from baseline to endpoint in both active-treatment groups.. Patients' neuropsychiatric functioning improved with olanzapine, risperidone, and placebo treatment. There was a substantial response in the placebo group, and no significant differences emerged among treatments.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Comorbidity; Conduct Disorder; Dementia, Vascular; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Neuropsychological Tests; Olanzapine; Psychomotor Agitation; Risperidone; Treatment Outcome

In this pilot study, we have investigated the effects of switching from olanzapine or risperidone treatment to low-dose perphenazine combined with buspirone in six schizophrenic patients who had experienced weight gain. We found no relapse as to psychotic symptoms measured by the CGI-S scale and no exacerbation of extrapyramidal side-effects as measured by the Simpson-Angus Scale. In addition, we observed a medium weight reduction of 10.5 kg (range 1-20 kg).

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Buspirone; Denmark; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Perphenazine; Pilot Projects; Risperidone; Schizophrenia; Schizophrenic Psychology; Serotonin Receptor Agonists; Weight Loss

The efficacy and safety of olanzapine were compared with those of ziprasidone.. This was a multicenter randomized, double-blind, parallel-group, 28-week study of patients with schizophrenia. Patients were randomly assigned to treatment with 10-20 mg/day of olanzapine or 80-160 mg/day of ziprasidone. The primary efficacy measure was the Positive and Negative Syndrome Scale total score. Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood, quality of life, and extrapyramidal symptom scales. Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight.. The study was completed by significantly more olanzapine-treated patients (165 of 277, 59.6%) than ziprasidone-treated patients (115 of 271, 42.4%). At 28 weeks, the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement. The responder rate was higher for olanzapine than for ziprasidone. Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses, but results favored olanzapine on baseline-to-maximum changes. Weight change was significantly greater with olanzapine (mean=3.06 kg, SD=6.87) than with ziprasidone (mean=-1.12 kg, SD=4.70). Fasting lipid profiles were significantly superior in the ziprasidone group; there was no significant difference in fasting glucose level.. Olanzapine treatment resulted in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment, while ziprasidone was superior for weight change and lipid profile.

Topics: Adult; Age of Onset; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Blood Glucose; Double-Blind Method; Drug Administration Schedule; Fasting; Female; Humans; Lipids; Male; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Thiazoles; Treatment Outcome

To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.. Prospective randomized trial.. Tertiary care university affiliated critical care unit.. All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.. Patients were randomized to receive either enteral olanzapine or haloperidol.. Patient's delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.. Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.. Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Delirium; Haloperidol; Humans; Infusions, Parenteral; Intensive Care Units; Middle Aged; Olanzapine; Prospective Studies

Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Weight; Clozapine; Double-Blind Method; Drug Resistance; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia

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

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

Several recent studies, albeit limited in sample number, design and generalizability, have suggested that augmentation of atypical antipsychotic medication (such as clozapine and olanzapine) with sulpiride, a substituted benzamide antipsychotic medication, may play a role in the management of treatment-resistant psychotic conditions. The objective of this study was to investigate any change in clinical symptomatology or side-effect profile in treatment-resistant schizophrenia patients receiving sulpiride in addition to olanzapine. Seventeen patients with treatment-resistant chronic schizophrenia, who were receiving olanzapine monotherapy for at least 6 months before study commencement, were randomized in a 1:1 fashion to receive either adjunctive treatment with sulpiride (study group) or to continue their pre-study treatment with olanzapine with no medication augmentation (control group), each for a period of 8 weeks. Changes in measures of positive and negative symptoms, anxiety, depression and extrapyramidal symptoms were assessed at baseline and at 8 weeks. Study observations indicated no significant differences in the changes in positive or negative symptomatology between patients receiving a combined regimen of olanzapine with sulpiride (600 mg/ day) augmentation and controls. However, a significantly greater improvement of depressive symptomatology (P < 0.05; as assessed by the Hamilton Scale for Depression) was noted in the sulpiride augmentation group. These data indicate improvement in depressive symptomatology with sulpiride augmentation of olanzapine in treatment-resistant chronic schizophrenia patients.

Topics: Adolescent; Adult; Affect; Antipsychotic Agents; Anxiety; Basal Ganglia Diseases; Benzodiazepines; Chronic Disease; Depressive Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sulpiride

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

This open-label study investigated the strategy of switching patients who had gained excessive weight on olanzapine to quetiapine, with assessments of safety and continued efficacy as well as weight change. Patients who were psychiatrically stable on olanzapine but had gained >20% in weight and had body mass index >25 mg/kg(2) were switched to quetiapine over a 4-week period and followed for 6 weeks, the total study duration being 10 weeks. Assessments included weight change, antipsychotic efficacy using the Positive and Negative Symptom Syndrome Scale (PANSS), extrapyramidal adverse events using the Simpson-Angus Scale (SAS), and laboratory studies for metabolic measures. Of 16 enrolled patients, 12 completed the study. Mean weight loss was 2.25 kg (Cohen's d = 0.12; P = 0.03). There were no significant changes in PANSS total scores, SAS scores, or metabolic parameters. Switching patients to quetiapine, appears to be a viable strategy for managing olanzapine-induced weight gain as indicated by this 10-week open-label study. Prospective controlled trials of longer duration and larger number of subjects are needed.

Topics: Basal Ganglia Diseases; Benzodiazepines; Body Weight; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Quetiapine Fumarate; Weight Loss

The aim of this study was to examine the effects of olanzapine on aggressive behaviour and tic severity in children with Tourette's Syndrome (TS).. Ten (10) subjects (aged 7-13 years) with a primary diagnosis of TS and a history of aggressive behaviour were treated in a single-blind, 2-week placebo run-in, 8-week treatment phase trial. The starting dose of olanzapine was 1.25-2.5 mg/day and was titrated at biweekly intervals, as tolerated. The mean dosage at the end of the trial was 14.5 mg/day.. All 10 subjects completed the study. Olanzapine produced clinically and statistically significant reductions of aggression and tic severity from baseline to trial completion, as measured by the Achenbach Child Behavior Checklist (CBCL) and Yale Global Tic Severity Scale (YGTSS). Weight gain during the treatment period was the most common adverse effect (range 2-20 lbs: group mean 12.0 lbs +/- 5.71). No other significant adverse effects were observed during the 10-week trial.. The results of this trial confirm clinical observations that olanzapine may be an effective treatment for aggression and tics in children with Tourette's syndrome. Olanzapine was generally well tolerated, although significant weight gain was observed throughout the trial.

Topics: Adolescent; Affect; Aggression; Antipsychotic Agents; Anxiety; Basal Ganglia Diseases; Benzodiazepines; Child; Family; Female; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Pilot Projects; Prospective Studies; Psychiatric Status Rating Scales; Single-Blind Method; Social Behavior; Surveys and Questionnaires; Tics; Tourette Syndrome; Weight Gain

A follow-up study of patients with schizophrenia was conducted to examine change in striatal volumes and extrapyramidal symptoms after a change in medication.. Thirty-seven patients with schizophrenia and 23 healthy volunteers were examined. Patients at baseline receiving typical antipsychotics (N=10) or risperidone but exhibiting limited response (N=13) were switched to treatment with olanzapine. Patients receiving risperidone and exhibiting a good response (N=14) continued treatment with risperidone. Caudate, putamen, and pallidal volumes were assessed with magnetic resonance imaging. The Extrapyramidal Symptoms Rating Scale was used to assess clinical signs and symptoms.. At baseline, basal ganglia volumes in patients treated with typical antipsychotics were greater than in healthy subjects (putamen: 7.0% larger; globus pallidus: 20.7% larger). After the switch to olanzapine, putamen and globus pallidus volumes decreased (9.8% and 10.7%, respectively) and did not differ from those of healthy subjects at the follow-up evaluation. Akathisia was also reduced. In the patients receiving risperidone at baseline, basal ganglia volumes did not differ between those exhibiting good and poor response, and no significant volume changes were observed in subjects with poor risperidone response after the switch to olanzapine treatment.. Olanzapine reversed putamen and globus pallidus enlargement induced by typical antipsychotics but did not alter volumes in patients previously treated with risperidone. Changes in striatal volumes related to typical and atypical antipsychotics may represent an interactive effect between individual medications and unique patient characteristics.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia; Basal Ganglia Diseases; Benzodiazepines; Caudate Nucleus; Cross-Over Studies; Female; Follow-Up Studies; Globus Pallidus; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Putamen; Risperidone; Schizophrenia; Severity of Illness Index; Treatment Outcome

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

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

The superiority of olanzapine to haloperidol with respect to a decreased incidence of treatment-emergent extrapyramidal syndromes (EPS) in patients with schizophrenia was demonstrated in studies conducted in both Japan and Western countries. EPS measurements used in Western countries included the Simpson-Angus, Barnes akathisia and the Abnormal Involuntary Movement Scale, while the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) was used in Japan. The aim of this study was to clarify how the DIEPSS captures EPS profiles. The baseline prevalence and treatment-emergent incidence of EPS in Japanese schizophrenic patients treated with olanzapine or haloperidol were retrospectively compared as assessed by the DIEPSS to the prevalence and incidence of EPS in primarily Caucasian schizophrenic patients who were treated with olanzapine or haloperidol. Specifically, the prevalence and incidence of dyskinesia, akathisia and parkinsonism were compared between the Japanese trial and an international trial to examine if appropriate definitions using the DIEPSS can be derived assuming that a comparable prevalence and incidence of the syndromes would be observed when any differences in residual antipsychotic exposure at the initiation of study treatment were accounted for. For the incidence of all EPS syndromes, odds ratios were observed to be similar between the two studies, indicating that appropriate criteria for the clinical diagnosis of the EPS syndromes could be established based on the DIEPSS. This preliminary and retrospective work suggests that the DIEPSS can be used to operationally define the presence or absence, and make the clinical diagnosis, of specific EPS syndromes.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Diagnosis, Differential; Female; Haloperidol; Humans; Incidence; Male; Middle Aged; Odds Ratio; Olanzapine; Pirenzepine; Prevalence; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia

The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol.. Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography.. The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group.. A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Corpus Striatum; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Haloperidol; Humans; Iodobenzenes; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

This study evaluated the effectiveness, safety, and quality of life (Qol) offered by olanzapine in first-episode schizophrenia.. One hundred and eighty-two patients with first-episode schizophrenia (ICD-10) drawn from a larger, naturalistic, study were evaluated after 6 months of treatment with olanzapine, risperidone, or conventional antipsychotics (CA). Clinical status was assessed using the Clinical Global Impression-Severity (CGI-S) and Global Assessment of Function (GAF). AWAD and EuroQol scales were used to evaluate patients' attitude towards medication and Qol, respectively.. Subjects treated with olanzapine, risperidone, and CA showed similar improvements on CGI-S and GAF. Treatment-emergent, extrapyramidal symptoms were significantly lower in olanzapine-treated patients (17.8%) than in the risperidone (46.4%) and CA (62.2%) groups. Compared to CA, olanzapine and risperidone showed significantly greater improvement on the visual analog scale of EuroQol. Olanzapine-treated patients also showed significantly improved AWAD scores.. In first-episode schizophrenia, atypical antipsychotics were effective, and improved Qol. Olanzapine had a lower incidence of extrapyramidal symptoms and better subjective acceptance of medication.

Topics: Adult; Antipsychotic Agents; Attitude to Health; Basal Ganglia Diseases; Benzodiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Quality of Life; Schizophrenia; Severity of Illness Index; Treatment Outcome

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

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 antipsychotic efficacy and extrapyramidal safety of intramuscular (i.m.) olanzapine and i.m. haloperidol during the first 24 hours of treatment of acute schizophrenia.. Patients (n = 311) with acute schizophrenia were randomly allocated (2:2:1) to receive i.m. olanzapine (10.0 mg, n = 131), i.m. haloperidol (7.5 mg, n = 126), or i.m. placebo (n = 54).. After the first injection, i.m. olanzapine was comparable to i.m. haloperidol and superior to i.m. placebo for reducing mean change scores from baseline on the Brief Psychiatric Rating Scale (BRPS) Positive at 2 hours (-2.9 olanzapine, -2.7 haloperidol, and -1.5 placebo) and 24 hours (-2.8 olanzapine, -3.2 haloperidol, and -1.3 placebo); the BPRS Total at 2 hours (-14.2 olanzapine,-13.1 haloperidol, and -7.1 placebo) and 24 hours (-12.8 olanzapine, -12.9 haloperidol, and -6.2 placebo); and the Clinical Global Impressions (CGI) scale at 24 hours (-0.5 olanzapine, -0.5 haloperidol, and -0.1 placebo). Patients treated with i.m. olanzapine had significantly fewer incidences of treatment-emergent parkinsonism (4.3% olanzapine vs 13.3% haloperidol, P = 0.036), but not akathisia (1.1% olanzapine vs 6.5% haloperidol, P = 0.065), than did patients treated with i.m. haloperidol; they also required significantly less anticholinergic treatment (4.6% olanzapine vs 20.6% haloperidol, P < 0.001). Mean extrapyramidal symptoms (EPS) safety scores improved significantly from baseline during i.m. olanzapine treatment, compared with a general worsening during i.m. haloperidol treatment (Simpson-Angus Scale total score mean change: -0.61 olanzapine vs 0.70 haloperidol; P < 0.001; Barnes Akathisia Scale global score mean change: -0.27 olanzapine vs 0.01 haloperidol; P < 0.05).. I.m. olanzapine was comparable to i.m. haloperidol for reducing the symptoms of acute schizophrenia during the first 24 hours of treatment, the efficacy of both being evident within 2 hours after the first injection. In general, more EPS were observed during treatment with i.m. haloperidol than with i.m. olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Injections, Intramuscular; Male; Olanzapine; Schizophrenia; Severity of Illness Index; Time Factors; Treatment Outcome

Previous clinical trials have clearly shown the superiority of olanzapine to haloperidol in the improvement of extrapyramidal symptoms (EPS) in schizophrenic patients. The primary purpose of this study was to compare EPS profiles in Japanese schizophrenic patients treated with an atypical antipsychotic, olanzapine, or a typical antipsychotic, haloperidol, as measured by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The DIEPSS, which consists of eight individual parameters and one global assessment (overall severity), was used to evaluate 182 patients enrolled in this 8-week study. The primary safety analysis was maximum change (that could be either a decrease or increase) from baseline in DIEPSS total score. Secondary analyses included change from baseline to maximum in DIEPSS total score, change from baseline to endpoint (LOCF) in DIEPSS total score, and the rank sum of the maximum change (that could be either a decrease or increase) from baseline in the DIEPSS individual items. Incidence of treatment-emergent EPS adverse events using the DIEPSS scale was also analyzed. The olanzapine group showed statistically significant superiority to the haloperidol group on the primary analysis (p<0.001). Secondary analyses also demonstrated olanzapine's superiority in DIEPSS total, parkinsonism, akathisia and overall severity scores (all p< or =0.014). Categorical analysis of treatment-emergent akathisia and parkinsonism syndromes at endpoint showed improvement in the olanzapine group but worsening in the haloperidol group. The results from this study suggest that olanzapine, as in Caucasian populations, is a safe treatment in Japanese patients chronically ill with schizophrenia.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Double-Blind Method; Female; Haloperidol; Humans; Incidence; Japan; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Statistics, Nonparametric

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

The aim of this study is to provide long-term data on the effectiveness and safety of olanzapine in a group of patients with severe refractory schizophrenia.. Twenty patients who had previously received treatment with typical antipsychotic agents and who met the DSM-IV criteria of schizophrenia and refractoriness to treatment were evaluated in a 1-year prospective study after switching to olanzapine. The Positive and Negative Symptoms Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) were used to measure effectiveness. The extrapyramidal symptoms were also recorded. Serial laboratory tests, electrocardiograms and body weight measurements were also performed. Longitudinal statistical analyses were performed on the global changes in the scores of the scales by means of a repeated measures analysis of variance.. Significant reductions in the global scores from baseline in the PANSS, as well as in the BPRS, were observed. Furthermore, these reductions were also significant when considered only from Week 12. Olanzapine was, in general, well tolerated; a weight gain was observed between baseline and Month 4.5, but, interestingly, it decreased again from this time point to Month 12.. Olanzapine was shown to be a suitable treatment for refractory schizophrenia in this series of seriously ill patients. Although most of the effects were observed before Week 12, improvement persisted after 1 year. Weight gain stopped or even regressed when the treatment was prolonged. Large controlled clinical trials to define the role of atypical antipsychotics for the management of treatment-refractory schizophrenia are necessary.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Body Weight; Chronic Disease; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia

This study was conducted to prospectively examine the effect of switching from risperidone to olanzapine on female schizophrenia patients who experienced menstrual disturbances, galactorrhea, and/or sexual dysfunction.. Twenty female patients with DSM-IV schizophrenia who were taking risperidone and were suffering from menstrual disturbances, galactorrhea, and/or sexual dysfunction were enrolled. Patients were switched from risperidone to olanzapine over a 2-week period, then treated with olanzapine for 8 additional weeks. The serum prolactin concentrations were examined every 2 weeks. The Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), and questions from the Dickson-Glazer Sexual Functioning Scale were administered to evaluate efficacy, extrapyramidal side effects, and sexual and reproductive functioning at baseline and the endpoint of 10 weeks.. Serum prolactin levels decreased significantly (p < .01) following the switch from risperidone to olanzapine. Scores of PANSS, AIMS, and SAS at the endpoint were also significantly decreased (p < .01) compared to those of baseline. Patients experienced improvements in menstrual functioning and perceptions of sexual side effects.. Olanzapine reversed hyperprolactinemia in risperidone-treated female schizophrenic patients. This was associated with a decrease in amenorrhea, improved cycle regularity, and a decrease in sexual side effects that the women attributed to antipsychotic medication. This study suggests that switching to olanzapine is a safe and effective alternative method for patients with antipsychotic-induced hyperprolactinemia associated sexual and/or reproductive dysfunction. Long-term follow-up studies are warranted, with particular attention to the course of sexual and reproductive dysfunction.

Topics: Adolescent; Adult; Amenorrhea; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Galactorrhea; Humans; Hyperprolactinemia; Menstruation Disturbances; Middle Aged; Olanzapine; Pirenzepine; Prolactin; Prospective Studies; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Treatment Outcome

Treatment-resistant depression is a significant public health concern; drug switching or augmentation often produce limited results. The authors hypothesized that fluoxetine could be augmented with olanzapine to successfully treat resistant depression.. An 8-week double-blind study was conducted with 28 patients who were diagnosed with recurrent, nonbipolar, treatment-resistant depression without psychotic features. Subjects were randomly assigned to one of three groups: olanzapine plus placebo, fluoxetine plus placebo, or olanzapine plus fluoxetine.. Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression. The benefits of olanzapine monotherapy were modest. Olanzapine plus fluoxetine produced significantly greater improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week. There were no significant differences between treatment groups on extrapyramidal measures nor significant adverse drug interactions.. Olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared to either agent alone.

Topics: Ambulatory Care; Basal Ganglia Diseases; Benzodiazepines; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

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

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cross-Sectional Studies; Drug Resistance; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Time Factors

Atypical antipsychotic medications have generally been found to be more effective than conventional antipsychotics in the treatment of negative symptoms. Whether the benefits derived from the atypical agents are the result of improvements in primary versus secondary negative symptoms is unclear. The authors examined the effects of olanzapine on primary and secondary negative symptoms for patients with severe negative symptoms who did or did not have the deficit syndrome.. Thirty-nine outpatients with schizophrenia and severe negative symptoms were assessed for the presence of the deficit syndrome and entered into a 12-week, open-label study of olanzapine. Positive and negative symptoms, extrapyramidal side effects, quality of life, and level of functioning of the patients were assessed at baseline and endpoint.. All 39 patients completed the 12-week protocol; 13 of the patients had deficit negative symptoms, and 26 had nondeficit negative symptoms. Patients who had nondeficit negative symptoms demonstrated improvements in positive and negative symptoms, level of functioning, and extrapyramidal side effects over baseline. In contrast, patients meeting criteria for the deficit syndrome improved significantly over baseline only in extrapyramidal side effects.. The results of this study suggest that olanzapine is efficacious for secondary negative symptoms in schizophrenia but fail to support the contention that olanzapine has a direct beneficial effect on primary negative symptoms.

Topics: Adult; Age of Onset; Ambulatory Care; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Social Adjustment; Treatment Outcome

Results of controlled clinical trials should be confirmed through safety and effectiveness studies in nonselected patient cohorts treated according to routine clinical practice.. Outpatients with schizophrenia (ICD-10 criteria) entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Safety was evaluated through the collection of spontaneous adverse events and a specific questionnaire for extrapyramidal symptoms. Global clinical status was measured through the Clinical Global Impressions-Severity (CGI-S) and the Global Assessment of Functioning (GAF) scales.. From the 2967 patients included, 2128 patients were treated with olanzapine as monotherapy or combined with other drugs (olanzapine group), and 821 were treated with other antipsychotic drugs as monotherapy or combined with other drugs (control group). There were no statistical differences between treatment groups at baseline regarding age, gender, disease duration, or severity of symptoms. Olanzapine was well tolerated and effective in this study. Overall incidence of adverse events was significantly lower in the olanzapine group compared with the control group (p < .001). Somnolence and weight gain were significantly more frequent in the olanzapine group, and akathisia, dystonia, extrapyramidal syndrome, hypertonia, hypokinesia, and tremor were significantly higher in the control group. Clinical improvement at endpoint, measured through the mean change in the CGI-S and the GAF, was significantly higher in the olanzapine group compared with the control group (p = .004).. These results show that olanzapine is safe and effective in nonselected schizophrenic outpatients and are consistent with the efficacy and safety profile that olanzapine has shown in previous controlled clinical trials.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Drug Therapy, Combination; Humans; Middle Aged; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome

This open-label clinical study was conducted for patients with schizophrenia in order to investigate the efficacy, safety and optimal dose of olanzapine. One hundred and fifty-six of the 159 enrolled patients were included in the analysis set. For the primary efficacy measure, the Final Global Improvement Rating (FGIR) score, 15.4% of patients had remarkable improvement, 58.3% of patients had moderate improvement or more, 79.5% of patients had slight improvement or more, and 10.3% of patients had increase in disease symptomatology (worsening). Results from the Brief Psychiatric Rating Scale (BPRS) in all individual items were improved from baseline. Olanzapine was effective not only against positive psychotic symptoms but also against negative symptoms. This was consistent with results from the Positive and Negative Syndrome Scale (PANSS). For the majority of patients, a dose range of 7.5-10.0mg/day, as a lower bound on the minimally effective dose, was suggested by the results of the dose to first response based on improvement in Global Improvement Rating (GIR) analyses. The ratio of olanzapine dose to equivalent haloperidol dose was estimated at 1.2 :1. The most commonly reported treatment-emergent signs and symptoms (TESS) occurring at a frequency of 10% or more were insomnia, weight increase, excitement, sleepiness, anxiety, malaise and dull headaches. There was a low incidence of extrapyramidal treatment-emergent signs and symptoms; the most commonly reported were akathisia (6.4%), tremor (5.8%) and muscle rigidity (2.6%).

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Treatment Outcome; Weight Gain

Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I.. A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication.. Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine.. These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Body Weight; Clozapine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Treatment Outcome; Valproic Acid

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

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

Atypical neuroleptics present a unique opportunity to examine confounding by neuroleptic-induced extrapyramidal symptoms (EPS) in the assessment of negative signs of schizophrenia. EPS, such as facial bradykinesia and akinesia, involve some of the same response systems and phenomena as emotional display channels. EPS are attributed to the blockade of dopamine receptors in the striatum by traditional neuroleptics. Newer atypical neuroleptics target primarily mesolimbic and mesocortical areas, and receptors for other transmitters such as serotonin. Olanzapine has been reported as less likely to cause EPS and may improve some negative signs. We investigated the relationship between measures of EPS and negative symptoms in patients with schizophrenia treated with haloperidol or olanzapine. Patients were rated with the Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale EPS scale. Results show that the two agents have comparable efficacy but different safety outcomes. A positive correlation between EPS and PANSS negative score was detected in the haloperidol group only. Stepwise multiple regression analysis shows that a big proportion of variability in PANSS negative symptoms is predicted by EPS in the haloperidol group, but not in the olanzapine group, even though EPS increased in patients treated with haloperidol but not in olanzapine patients.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

The purpose of this study was to compare the efficacy of olanzapine with that of chlorpromazine plus benztropine in patients with treatment-resistant schizophrenia.. One hundred three previously treatment-resistant patients with schizophrenia diagnosed according to the DSM-III-R criteria were given a prospective 6-week trial of 10-40 mg/day of haloperidol. Eighty-four of them failed to respond to that trial and agreed to be randomly assigned to an 8-week fixed-dose trial of either 25 mg/day of olanzapine alone or 1200 mg/day of chlorpromazine plus 4 mg/day of benztropine mesylate.. Fifty-nine (70%) of the 84 subjects completed the trial. The primary outcome measures were Brief Psychiatric Rating Scale total score and positive symptom score, Scale for the Assessment of Negative Symptoms global score, and Clinical Global Impression score. An analysis of variance for the subjects who completed the study showed no difference in efficacy between the two drugs. Seven percent of the olanzapine-treated patients responded according to a priori criteria; no chlorpromazine-treated patients responded. The olanzapine-treated patients had fewer motor and cardiovascular side effects than the chlorpromazine-treated patients. Extrapyramidal symptoms and akathisia were similar in the two groups, although no antiparkinsonian drugs were used in the olanzapine group.. Olanzapine and chlorpromazine showed similar efficacy, and the total amount of improvement with either drug was modest. Olanzapine-treated patients had fewer side effects than chlorpromazine-treated patients.

Topics: Adult; Akathisia, Drug-Induced; Analysis of Variance; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Chlorpromazine; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Headache; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sleep Stages; Treatment Outcome; Xerostomia

Hallucinosis is a dopaminergic dose limiting complication of the treatment of idiopathic Parkinson's disease. Typical neuroleptic medications cannot be used for suppressing hallucinosis because the extrapyramidal side effects worsen parkinsonian motor control. Olanzapine is a novel atypical antipsychotic drug with few reported extrapyramidal side effects which may be more suitable for controlling hallucinosis in these patients.. Olanzapine was given to five patients with idiopathic Parkinson's disease and the dosage was titrated until a clinically meaningful reduction in hallucinosis was achieved. The commercially available 5 mg, 7.5 mg and 10 mg tablets were used.. After an initial 9 days of treatment, hallucinosis frequency was significantly reduced, an effect which was maintained with continued treatment. However, during this early phase of treatment, parkinsonian motor disability increased, which resulted in two of the patients discontinuing medication.. Olanzapine is effective in the suppression of hallucinosis in patients with idiopathic Parkinson's disease but the currently available dose increments may result in an unacceptable exacerbation of motor disability.

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Male; Middle Aged; Olanzapine; Parkinson Disease; Pirenzepine; Severity of Illness Index

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

A relative lack of extrapyramidal symptoms (EPS, i.e., the syndromes of dystonia, parkinsonism, akathisia, dyskinesia) is one criterion used to determine whether an antipsychotic is "atypical." The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospective clinical trials.. Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine (5 to 20 mg/day) and 810 patients treated with haloperidol (5 to 20 mg/day) for up to 6 weeks of therapy. Patients were monitored weekly by three methods of extrapyramidal symptom assessment: (1) detection of extrapyramidal adverse events (signs and symptoms) by casual observation, nonprobing inquiry, and spontaneous report; (2) objective rating scale scores: and (3) use of concomitant anticholinergic medications. Emergence of EPS was assessed by (1) analysis of the incidence of extrapyramidal syndrome categories based on adverse events, (2) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores, (3) analysis of mean maximum change in rating scale scores, and (4) categorical analysis of anticholinergic medication use. Outcome of EPS was assessed by (1) analysis of mean change in rating scale scores at endpoint and (2) mean anticholinergic use at endpoint.. Olanzapine was statistically significantly (p = .014, p < .001) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome. Furthermore, during acute treatment, statistically significantly fewer patients treated with olanzapine (0.3%) discontinued the study because of any extrapyramidal adverse event than patients treated with haloperidol (2.7%, p < .001).. Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile than the conventional antipsychotic haloperidol at comparably effective antipsychotic doses. The lower extrapyramidal symptom profile with olanzapine was evident despite statistically significantly more frequent use of anticholinergic drugs among haloperidol-treated patients. Fewer olanzapine-treated than haloperidol-treated patients discontinued because of EPS, suggesting that olanzapine should contribute to better compliance with longer term maintenance treatment, with minimal anticholinergic-associated events.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Double-Blind Method; Drug Administration Schedule; Drug Tolerance; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Patient Compliance; Patient Dropouts; Pirenzepine; Schizophrenia; Treatment Outcome

Clozapine is currently the treatment of choice for neuroleptic-resistant schizophrenia. Olanzapine is a new antipsychotic drug that has shown efficacy against positive and negative symptoms of schizophrenia, with minimal extrapyramidal side effects. However, the effectiveness of olanzapine has not yet been reported among treatment-refractory schizophrenic patients.. A total of 25 schizophrenic patients (DSM-IV criteria) with documented lack of response to two conventional antipsychotic drugs entered this 6-week prospective, open-label treatment trial with olanzapine 15 to 25 mg/day. An optional extension up to 6 months was provided.. As a group, the olanzapine-treated patients showed statistically significant improvement (p < .05) in both positive and negative symptoms by the end of 6 weeks of therapy. Overall, 9 of the patients (36%) met the a priori criteria for treatment-response (> or = 35% decrease in Brief Psychiatric Rating Scale [BPRS] total score, plus posttreatment Clinical Global Impression-Severity < or = 3 or BPRS total < 18). Only one patient discontinued treatment because of an adverse event during the study. Despite the relatively high dosages of olanzapine used, there were no reports of parkinsonism, akathisia, or dystonia, and no patients required anticholinergic medication.. This open study suggests that olanzapine may be effective and well tolerated for a substantial number of neuroleptic-resistant schizophrenic patients. Further blinded, controlled trials are needed to confirm our results.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brief Psychiatric Rating Scale; Drug Administration Schedule; Female; Hospitalization; Humans; Male; Olanzapine; Pilot Projects; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Driving motorized vehicles is an integral part of individual mobility and a key parameter for employment and social integration. This naturalistic, cross-sectional study investigated the associations between driving fitness, residual symptomatology, olanzapine equivalent, and extrapyramidal symptoms (EPS) in long term stable outpatients with schizophrenia.. Beside sociodemographic data, and driving habits, residual symptoms, and EPS were assessed using the Positive and Negative Syndrome Scale (PANSS), and the Modified Simpson Angus Scale (MSAS). PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. MSAS cut-off scores ≥3 were defined as positive for EPS. Driving skills were assessed using the Vienna Test System and an expert evaluation.. 50 patients were included into the study. Mean PANSS total scores indicated mild residual symptomatology and EPS were not present in 48% of study participants. 44% passed the driving fitness assessment and were considered as competent to drive, 20% were judged to be partially competent and 36% to be incompetent to drive. With the exception of disorganization (r = -0·287, p = 0·048) residual symptoms of schizophrenia did not correlate with driving fitness. However, moderate negative correlations were detected between driving fitness and the severity of EPS (r = -0·554, p = 0·000), age (r = -0·413, p = 0·003) as well as olanzapine equivalent doses (r = -0·432, p = 0·002). These results were not corrected for multiple comparison.. The present findings indicate that up to two thirds of clinically stable outpatients with chronic schizophrenia may be (partially) competent to drive. Both the presence of EPS as well as the dosage of antipsychotic medication seem to be of particular relevance in this regard.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cross-Sectional Studies; Humans; Olanzapine; Outpatients; Schizophrenia; Treatment Outcome

Fahr disease, also known as familial idiopathic basal ganglia calcification, is a rare neurodegenerative disorder, the etiology of which remains unknown. Given its various presentations, Fahr disease is presumed to be underdiagnosed and its prevalence underestimated. We present a case of Fahr disease that presented mainly with pure psychiatric symptoms. Isolated psychiatric symptoms without neurological manifestations are rarely seen in patients diagnosed with Fahr disease. Psychiatrists should consider Fahr disease as a differential diagnosis in the evaluation of psychiatric illness.

Topics: Basal Ganglia; Basal Ganglia Diseases; Calcinosis; Depression; Diagnosis, Differential; Female; Humans; Mental Disorders; Middle Aged; Neurodegenerative Diseases; Olanzapine; Paroxetine; Psychiatric Status Rating Scales; Psychotropic Drugs; Tomography, X-Ray Computed; Treatment Outcome

To compare rates of specific adverse outcomes between patients starting quetiapine, olanzapine, or risperidone use in the Netherlands.. Observational study using the PHARMO Database Network, including patients starting quetiapine (4658), olanzapine (5856), or risperidone (7229) in 2000-2009, comparing rates of all-cause mortality, failed suicide attempts, extrapyrimidal symptoms (EPS), diabetes mellitus (DM), hypothyroidism, and acute myocardial infarction (AMI).. Median follow-up until discontinuation/end of follow-up was 0.6 years. Prescribed doses were generally lower than the approved defined daily doses, especially for quetiapine. Quetiapine was significantly associated with lower EPS rates (HR 0.18; 95% CI 0.13-0.24), but higher failed suicide attempt rates (HR 2.07; 95% CI 1.35-3.16) compared to risperidone. Quetiapine was significantly associated with lower EPS rates (HR 0.59; 95% CI 0.42-0.84) and DM rates (HR 0.66; 95% CI 0.44-0.97) compared to olanzapine. Rates for all-cause mortality, hypothyroidism, and stroke were similar between groups. AMI events were too infrequent to draw conclusions.. Quetiapine was associated with lower EPS, but higher failed suicide attempt rates compared to risperidone. Quetiapine was associated with lower EPS and DM rates compared to olanzapine. The results should be interpreted with caution because of possible channelling and residual confounding. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality; Netherlands; Olanzapine; Product Surveillance, Postmarketing; Quetiapine Fumarate; Retrospective Studies; Risperidone; Schizophrenia

The purpose of the study was to determine the downstream implications of atypical antipsychotic (AAP) prescribing in the intensive care unit (ICU), including discharge prescribing practices, monitoring, and attributable adverse drug events.. This retrospective cohort study included patients at least 18 years of age admitted to an ICU that received at least 2 doses of an AAP for documented delirium or avoidance of a deliriogenic medication. Exclusion criteria were documentation of an AAP as a home medication or initiation for a psychiatric indication unrelated to delirium (eg, schizophrenia).. During the 8-month study period, 156 patients were included and 133 (85.2%) patients survived to hospital discharge. Of the survivors, AAP therapy was continued for 112 (84.2%) patients upon ICU transfer and for 38 (28.6%) patients upon hospital discharge. A majority of these patients had evidence of delirium resolution or no indication for continuation documented at discharge. Of the 127 patients with an electrocardiogram ordered during AAP therapy, QTc prolongation occurred in 49 (31.4%) patients. An adverse drug event leading to drug discontinuation was documented in 16 (10.2%) patients.. Because of significant patient-centered implications, AAPs initiated in the ICU require continued evaluation for indication to avoid prolonged and possibly unnecessary use.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Delirium; Disorders of Excessive Somnolence; Female; Humans; Inappropriate Prescribing; Intensive Care Units; Male; Middle Aged; Olanzapine; Patient Discharge; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Survivors; Thiazoles

Patients with late-life schizophrenia (LLS) are highly susceptible to antipsychotic adverse effects. Treatment guidelines endorse lower antipsychotic doses. However, the optimal dose of antipsychotics and associated dopamine D2/3 receptor (D2/3R) occupancies remain largely unexplored in patients with LLS.. To evaluate effects of antipsychotic dose reduction on striatal dopamine D2/3R occupancies, clinical variables, and blood pharmacokinetic measures in patients with LLS.. An open-label, single-arm prospective study with a 3- to 6-month follow-up period (January 10, 2007, to October 21, 2013) was conducted at an academic tertiary care center with practice for ambulatory care. Participants included 35 outpatients with clinically stable LLS (patients aged ≥ 50 years receiving olanzapine or risperidone monotherapy at the same dose for 6 to 12 months). Follow-up was completed on October 21, 2013, and analysis was conducted from October 22, 2014, to February 2, 2015.. Carbon 11-labeled raclopride positron emission tomography, clinical measures, and blood pharmacokinetic measures performed before and after gradual dose reduction by up to 40% from the baseline dose and at least 3 months after dose reduction.. Striatal dopamine D2/3R occupancies with antipsychotics, clinical measures (Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, Targeted Inventory on Problems in Schizophrenia, Simpson-Angus Scale, Barnes Rating Scale for Drug-Induced Akathisia, Udvalg for Kliniske Undersøgelser Side Effect Rating Scale), and blood pharmacokinetic measures (prolactin and antipsychotic blood levels).. Dopamine D2/3R occupancy of the entire sample decreased by a mean (SD) of 6.2% (8.2%) following dose reduction (from 70% [12%] to 64% [12%]; P < .001). The lowest D2/3R occupancy associated with clinical stability was 50%. Extrapyramidal symptoms (EPSs) were more likely to occur with D2/3R occupancies higher than 60%: 90.5% (19 of 21) of the participants with baseline EPSs and 76.9% (10 of 13) of the participants with postreduction EPSs had striatal D2/3R occupancies higher than 60%. The baseline D2/3R occupancies were lower in patients with clinical deterioration (n = 5) than in those whose condition remained stable (n = 29) (58% [15%] vs 72% [10%]; P = .03). Following dose reduction, Targeted Inventory on Problems in Schizophrenia score increased (P = .046) and Positive and Negative Syndrome Scale (P = .02), Brief Psychiatric Rating Scale (P = .03), Simpson-Angus Scale (P < .001), Barnes Rating Scale for Drug-Induced Akathisia (P = .03), and Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (P < .001) scores and prolactin (P < .001) and blood antipsychotic (olanzapine, P < .001; risperidone plus the metabolite 9-hydroxyrisperidone, P = .02) levels all decreased.. Antipsychotic dose reduction is feasible in patients with stable LLS, decreasing adverse effects and improving illness severity measures. The results of the present study suggest a lower therapeutic window of D2/3R occupancy in patients with LLS (50%-60%) than previously reported in younger patients (65%-80%).

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brain; Carbon Radioisotopes; Female; Humans; Male; Middle Aged; Neostriatum; Olanzapine; Positron-Emission Tomography; Prolactin; Prospective Studies; Raclopride; Receptors, Dopamine D2; Receptors, Dopamine D3; Risperidone; Schizophrenia; Treatment Outcome

The incidence of extrapyramidal symptoms (EPS) has been shown to be generally low among patients with schizophrenia receiving oral olanzapine. A long-acting injection (LAI) of olanzapine has recently been approved for the treatment of schizophrenia in a number of countries. Accordingly, the objective of the current analyses was to compare the incidences of EPS during treatment with olanzapine LAI versus oral olanzapine.. The incidences of treatment-emergent EPS were examined in adults with schizophrenia receiving olanzapine LAI or oral olanzapine for up to 3 years. Short-term data were obtained from two double-blind studies of olanzapine LAI: one included a placebo comparator, and the other included oral olanzapine as an active comparator. Long-term data were obtained from an open-label extension study for olanzapine LAI and from an integrated database for oral olanzapine.. The short-term incidence of EPS was 5.6% during treatment with olanzapine LAI (45-405 mg every 2-4 weeks) and 5.0% with oral olanzapine (5-20 mg/day). Akathisia (2.6% LAI, 1.2% oral), and Parkinson-like symptoms (1.8% LAI, 3.7% oral) were similar between treatment groups. The incidence of EPS for long-term treatment was 9.2% for olanzapine LAI. Incidences of EPS events were not significantly different between patients receiving olanzapine LAI or oral olanzapine for up to 3 years.. These findings suggest that EPS profiles are similar for olanzapine LAI and oral olanzapine.

Topics: Administration, Oral; Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Dystonia; Humans; Incidence; Middle Aged; Olanzapine; Parkinsonian Disorders; Schizophrenia; 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

Many patients with Lewy body dementia develop visual hallucinations and other psychiatric symptoms. These patients are hypersensitive to antipsychotic drugs. Although patients tolerate atypical better than typical antipsychotics, both types can cause major extrapyramidal side effects. The anticonvulsant mood stabilizer topiramate, which does not cause parkinsonism, has been used as adjuvant therapy for both the positive and negative symptoms of schizophrenia; these symptoms can resemble those of Lewy body dementia. This report documents a 65-year-old woman with a 3-year history of progressive dementia that over the past 2 years had become complicated by severe extrapyramidal symptoms and agitated hallucinations. Her hallucinations became daily and were disrupting to her family. She was given a clinical diagnosis of Lewy body dementia after imaging and laboratory studies ruled out other etiologies. Treatment with olanzapine relieved her psychotic symptoms but caused severe dystonias, daily myoclonic jerks, and tremors. Stopping the olanzapine and starting topiramate 25 mg daily eliminated the hallucinations and agitation without worsening her extrapyramidal side effects. However, the topiramate was stopped because the patient reportedly developed anorexia and significant weight loss. Her hallucinations returned. When topiramate was reinstated at 12.5 mg a day, her agitation resolved, although her hallucinations continued. After 6 months on this dose, her agitation was still fairly well controlled without serious side effects or worsening of her parkinsonian symptoms.

Topics: Aged; Anticonvulsants; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Fructose; Hallucinations; Humans; Lewy Body Disease; Neuroprotective Agents; Olanzapine; Psychomotor Agitation; Schizophrenia; Topiramate; Treatment Outcome

The frequency of severe adverse drug reactions (ADRs) from psychotropic drugs was investigated in hospitalised psychiatric patients in relation to their age. Specifically, the incidence of ADRs in patients up to 60 years was compared to that of patients older than 60 years.. Prescription rates of psychotropic drugs and reports of severe ADRs were collected in psychiatric hospitals in Switzerland between 2001 and 2010. The data stem from the drug surveillance programme AMSP.. A total of 699 patients exhibited severe ADRs: 517 out of 28,282 patients up to 60 years (1.8%); 182 out of 11,446 elderly patients (1.6%, ns). Logistic regression analyses showed a significantly negative relationship between the incidence of ADRs and patients' age in general and in particular for weight gain, extrapyramidal motor system (EPMS) symptoms, increased liver enzymes and galactorrhoea. A significantly negative relationship was observed for age and the dosages of olanzapine, quetiapine, risperidone, valproic acid and lamotrigine. When comparing age groups, frequency of ADRs was lower in general for antipsychotic drugs and anticonvulsants, in particular for valproic acid in the elderly. Weight gain was found to be lower in the elderly for antipsychotic drugs, in particular for olanzapine. For the group of mood-stabilising anticonvulsants (carbamazepine, lamotrigine and valproic acid) the elderly exhibited a lower incidence of reported allergic skin reactions.. The results suggest that for psychiatric inpatients the incidence of common severe ADRs (e.g., weight gain or EPMS symptoms) arising from psychotropic medication decreases with the age of patients.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Aged, 80 and over; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Carbamazepine; Causality; Dibenzothiazepines; Drug-Related Side Effects and Adverse Reactions; Female; Galactorrhea; Humans; Lamotrigine; Logistic Models; Male; Middle Aged; Neuroleptic Malignant Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Switzerland; Triazines; Valproic Acid; Weight Gain; Young Adult

The association of antipsychotics is a widespread therapeutic resource in clinical practice. The purpose of the present work was to evaluate the efficacy and safety of amisulpride augmentation in patients responding at least partially to olanzapine.. In this observational 3-months open-label investigation, we evaluated the effectiveness of the addition of amisulpride to 49 subjects, after having scored at least 25 on the brief psychiatric rating scale (BPRS) following olanzapine monotherapy for 6 weeks. Patients were assessed at baseline, 1 and 3 months using the BPRS, the clinical global impression severity of illness (CGI-S) scale and the Udvalg for Kliniske Undersogelser side effect rating scale (UKU).. In subjects who were at least partially responsive to monotherapy with olanzapine, coadjuvant treatment with amisulpride achieved a statistically significant improvement in mental status over a 3 month period as measured by the BPRS, CGI and UKU scales. The response rate (>20% reduction in BPRS score) was 75.51%.. Amisulpride augmentation, in a group of patients partially or non-responsive to olanzapine, may lead to an improvement in schizophrenic symptoms. However, these results are subject to several limitations making it difficult to derive firm clinical recommendations, and underscoring the need for future research into the value of these therapeutic alternatives in poor responders.

Topics: Adolescent; Adult; Amisulpride; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Dopamine Antagonists; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Sulpiride; Young Adult

To examine the safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania.. Subjects (n = 18) who were acutely manic, did not respond to lithium, anticonvulsants, and neuroleptics, and/or had intolerable side effects to them in previous manic episodes were openly treated with olanzapine monotherapy (5-40 mg/d) for 12 weeks. The primary and secondary outcomes included the change from baseline to endpoint in Young Mania Rating Scale (YMRS) total score, Clinical Global Impression for Bipolar Disorder-Severity Scale (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D) and Positive and Negative Syndrome Scale (PANSS), and response and remission rate.. The mean change in YMRS total score from baseline to endpoint was -23.3 ± 8.4 (p < 0.001). Fifteen (88.5%) patients achieved response (≥50% reduction in YMRS total score) and 14 (77.8%) achieved remission (YMRS total score ≤9 at endpoint). Mean changes from baseline to endpoint in CGI-S for mania and PANSS total score were significant, but not the changes in HAM-D total score or CGI-S for depression. The most common adverse events were sedation, self-reported weight gain, ≥7% increase in body weight, dizziness, and akathisia.. These preliminary results suggest that olanzapine monotherapy is effective and relatively safe in patients with treatment-resistant bipolar mania. Randomized, double-blind, placebo-controlled study is warranted.

Topics: Adult; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Middle Aged; Olanzapine; Time Factors; Treatment Outcome

This Schizophrenia Outcome Survey compared medical costs, psychopathology and adverse events in outpatients for 2 years following hospitalisation for an acute schizophrenic episode.. Adults stabilised with haloperidol, olanzapine or risperidone entered this observational study or=1 EPS; 69% (p<0.013), 40 and 44%, respectively, had >or=1 sexual problem (NS). Mean weight gain was 0.4 (NS), 2.6 (p<0.05) and 2.6 kg (p<0.05), respectively.. In this naturalistic study, treatment allocation might have introduced a bias in the interpretation of efficiency results, but olanzapine and risperidone caused less EPS than haloperidol during 2 years of outpatient follow-up.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Belgium; Benzodiazepines; Brief Psychiatric Rating Scale; Dyskinesia, Drug-Induced; Female; Haloperidol; Health Care Costs; Hospitalization; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Weight Gain

To compare the effectiveness of intramuscular (IM) olanzapine and typical IM antipsychotics in naturalistically treated acutely agitated patients with schizophrenia or acute mania.. During the acute phase, 2011 inpatients (including emergency settings) were assessed at 2, 24 and 72 h, and 7 days following initial injection and on oral antipsychotic transition. Mean change in agitation was assessed via Positive and Negative Symptom Scale-Excited Component (PANSS-EC) and Clinical Global Impressions-Severity (CGI-S) scores. Response (> or = 40% reduction in baseline PANSS-EC score) was analysed using logistic regression.. Significantly greater decreases in PANSS-EC and CGI-S scores were observed in patients receiving IM olanzapine (n = 1294) as their first injection compared with patients receiving other IM antipsychotics (n = 717) (P<0.05; 2 h: effect size 0.1); IM haloperidol treatment (all assessments, P<0.05); and IM zuclopenthixol treatment (2 h, P<0.001). Higher response rates were observed with IM olanzapine compared with other IM antipsychotics at 24 and 72 h, and 7 days (P<0.05). IM olanzapine was associated with fewer extrapyramidal side effects compared with other assessed IM antipsychotics.. IM olanzapine provided somewhat more effective control of acute agitation than other assessed IM antipsychotics.

Topics: Acute Disease; Administration, Oral; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Clopenthixol; Cross-Cultural Comparison; Female; Haloperidol; Hospitalization; Humans; Injections, Intramuscular; Male; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Aripiprazole has been used effectively to treat schizophrenia in the clinic; however, its mechanisms of action are not clear. This study examined how short- and long-term aripiprazole treatment affects dopaminergic transmission in mesolimbic and nigrostriatal pathways. For comparison, the effects of haloperidol and olanzapine treatment were also examined. Aripiprazole significantly increased D2 receptor mRNA expression and decreased tyrosine hydroxylase (TH) mRNA expression in the ventral tegmental area (VTA) after 1- and 12-wk treatment, but had no effect in substantia nigra (SN) and nucleus accumbens (NAc). Aripiprazole also decreased dopamine transporter (DAT) binding density in NAc (for 1- and 12-wk treatment) and VTA (1-wk treatment). In contrast, haloperidol significantly increased D2 receptor binding density and decreased DAT binding density in NAc and caudate putamen (CPu) after 1- and 12-wk treatment, and it also decreases DAT binding in VTA after 12-wk treatment. Olanzapine had less widespread effects, namely an increase in D2 receptor mRNA in VTA after 12-wk treatment and decreased DAT binding in NAc after 1-wk treatment. These results suggest that aripiprazole has selective effects on the mesolimbic dopaminergic pathway. Selectively reducing dopamine synthesis in VTA is a possible therapeutic mechanism for the long-term efficacy of aripiprazole in controlling schizophrenia symptoms with reduced extrapyramidal side-effects.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Brain; Caudate Nucleus; Dopamine; Dopamine Plasma Membrane Transport Proteins; Gene Expression Regulation, Enzymologic; Haloperidol; Limbic System; Nucleus Accumbens; Olanzapine; Piperazines; Putamen; Quinolones; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; RNA, Messenger; Substantia Nigra; Time Factors; Tyrosine 3-Monooxygenase; Up-Regulation; Ventral Tegmental Area

We report the case of a 16-year-old male with Mucopolysaccharidosis III type A (Sanfilippo syndrome) who was commenced on risperidone for behaviour management. He rapidly developed extrapyramidal symptoms that have not resolved.. The medication histories of 20 patients with Mucopolysaccharidosis III seen at a Lysosomal Storage Diseases Clinic were reviewed to determine the incidence of extrapyramidal side effects.. Six patients had been treated with risperidone, olanzapine, or lamotrigine. Five of these patients developed extrapyramidal side effects.. The incidence of extrapyramidal side effects was considerably higher than expected. We suggest that these medications be used with considerable caution in these patients.

Topics: Adolescent; Adult; Anticonvulsants; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child, Preschool; Cohort Studies; Female; Humans; Incidence; Lamotrigine; Male; Mental Disorders; Mucopolysaccharidosis III; Olanzapine; Risperidone; Triazines; Young Adult

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Brain; Calcinosis; Capgras Syndrome; Female; Humans; Olanzapine; Tomography, X-Ray Computed; Treatment Outcome

The receptor binding affinities of the three drug candidates 1 (SLV310), 2 (SLV313), and 3 (SLV314) were positioned against the results from nine (a)typical antipsychotic drugs. The receptor binding data from sixteen monoaminergic receptors served as the input in a principal component analysis (PCA). The PCA outcome revealed a unique binding profile of 1, 2, and 3 as compared with the reference compounds 4-8 and 10-12. The weight gain inducing antipsychotics 6-8 clustered in the PCA by scoring strongly negative for factor 1. The hyperprolactinaemia related antipsychotics 4, 5, 10, and 12 clustered by their negative scores for factor 2.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzoxazines; Biogenic Monoamines; Humans; Hyperprolactinemia; Indoles; Metabolic Diseases; Phthalimides; Piperazines; Principal Component Analysis; Pyridines; Radioligand Assay; Receptors, Biogenic Amine; Weight Gain

We have previously shown that the orexin-1 antagonist SB-334867 blocks the electrophysiological effects of haloperidol and olanzapine on the activity of A9 and A10 dopamine neurons. To evaluate if orexin-1 antagonists might block other effects of antipsychotic drugs in animals, we examined the effects of SB-334867 on behavioral, neurochemical, and neuroendocrine effects of antipsychotic drugs. Pretreatment with SB-334867 (0.01-10 mg/kg, intraperitoneal [IP]) significantly decreased the catalepsy produced by the administration of haloperidol (1 mg/kg, subcutaneous [SC]), risperidone (2 mg/kg, SC), and olanzapine (10 mg/kg, SC). Administration of SB-334467 also reversed catalepsy after it had been established in animals pretreated 2 hours earlier with haloperidol. However, pretreatment with SB-334867 (1-10 mg/kg, IP) did not block the decreases in exploratory locomotor activity produced by administration of haloperidol (0.1 mg/kg, SC) or risperidone (0.3 mg/kg, SC). In addition, pretreatment with SB-334867 (1-10 mg/kg, IP) neither blocked the increased levels of dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens or striatum nor the elevation in serum prolactin produced by administration of haloperidol (0.1 mg/kg, SC) and risperidone (1 mg/kg, SC). Administration of SB-334867 alone neither changed locomotor activity and DOPAC or prolactin levels nor produced catalepsy. These results show that orexin-1 antagonists block the catoleptogenic effects of antipsychotics but do not block other locomotor, neurochemical, or neuroendocrine effects of antipsychotics. Because catalepsy is thought to be a good predictor of extrapyramidal symptoms in humans, treatment with orexin-1 antagonists might decrease the occurrence or severity of antipsychotic treatment-emergent extrapyramidal symptoms in humans.

Topics: Animals; Antipsychotic Agents; Basal Ganglia Diseases; Behavior, Animal; Benzodiazepines; Benzoxazoles; Catalepsy; Haloperidol; Intracellular Signaling Peptides and Proteins; Locomotion; Male; Naphthyridines; Neuropeptides; Olanzapine; Orexins; Prolactin; Rats; Rats, Sprague-Dawley; Risperidone; Urea

The International Schizophrenia Outpatient Health Outcomes study, IC-SOHO is a three-year international observational study that investigates clinical and health outcomes of antipsychotic treatments. 7658 outpatients treated for schizophrenia were enrolled in the study, who needed an antipsychotic therapy to initiate or switch. The primary analysis compared the group taking olanzapine with the group taking any other antipsychotics, while the secondary comparison was performed between those treated with olanzapine and those with risperidone. Efficacy analysis was carried out based on changes in Clinical Global Impression of Severity scale (CGI-S), which was performed at a global symptom level, as well as with respect to the patients' positive, negative, cognitive and depressive symptoms. In addition, adverse events were also evaluated. Results of the analysis of the 3- and 6-month data from Hungary are disclosed in this publication. 200 patients were enrolled in the country. Demographics of the treatment groups were not significantly different. At 3 and 6 months after treatment initiation, there were no significant between-group differences in improvement of global symptomatology, however, cognitive symptoms improved more in the Olanzapine-group compared to those taking other antipsychotics (p<0.05). In patients showing Extrapyramidal Symptoms (EPS) at baseline, these symptoms finished to a greater extent among those receiving olanzapine than in those receiving other antipsychotics (after 6 months D<0.0001). Half a year later, significantly less patients showed extrapyramidal adverse events (p=0,0007), and the previous EPS terminated to a greater extent (p=0.0016) in the olanzapine group, as compared to those taking risperidone. No between-group differences were found in changes of sexual functions, as well as of weight and Body Mass Index measures. Switching antipsychotic initiated at study baseline, and adding-on one or more other antipsychotic to the initial one, were significantly less frequent in the Olanzapine-group compared to those initiated other antipsychotics. In the first 3 months, treatment compliance was significantly higher with olanzapine therapy than with other antipsychotic treatments, and with risperidone respectively. Results from the Hungarian sample correspond with results from higher analysis levels of wider patient populations of IC-SOHO study. Olanzapine showed outstanding efficacy in lessening cognitive disturbances and global cli

Topics: Adult; Aggression; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Erectile Dysfunction; Female; Galactorrhea; Gynecomastia; Haloperidol; Humans; Hungary; International Cooperation; Libido; Male; Menstruation Disturbances; Middle Aged; Olanzapine; Outpatients; Patient Admission; Patient Compliance; Prospective Studies; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index

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

To examine clinical outcomes in Asian patients with schizophrenia receiving monotherapy with olanzapine, risperidone or typical antipsychotics in naturalistic settings.. In this report, data from the first 12 months of the prospective, observational, 3-year Intercontinental Schizophrenia Outpatient Health Outcomes study are presented for patients from participating Asian countries (Korea, Taiwan and Malaysia) who were started on, or switched to, monotherapy with olanzapine (n = 484), risperidone (n = 287) or a typical antipsychotic drug (n = 127) at baseline.. At 12 months, overall reduction in the score of Clinical Global Impressions-Severity of Illness rating scale was greatest with olanzapine (p < 0.001 vs typical agents), followed by risperidone (p = 0.007 vs typical agents) treatment. Olanzapine treatment was found to have significantly better effects than typical agents on negative and depressive symptom scores, and significantly greater improvements than risperidone on negative and cognitive symptoms. The occurrence of extrapyramidal symptoms was least likely with olanzapine (p < 0.001 vs typical agents, and p = 0.012 vs risperidone), while the estimated odds of tardive dyskinesia were greatest in the typical treatment group (p = 0.046 vs olanzapine, and p = 0.082 vs risperidone). Mean weight increase was greater for olanzapine-treated patients compared with the other agents (p = 0.030 vs typical agents and p < 0.001 vs risperidone). The risk of menstrual disturbance was relatively high with risperidone when compared with olanzapine treatment (p < 0.001).. The results of this observational study indicate that, in Asian patients with schizophrenia, olanzapine may offer benefits when compared with typical agents or risperidone. However, the significantly greater odds of weight gain should be considered in the clinical management of olanzapine-treated patients.

Topics: Adult; Antipsychotic Agents; Asian People; Basal Ganglia Diseases; Benzodiazepines; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Korea; Malaysia; Male; Obesity; Olanzapine; Risperidone; Schizophrenia; Severity of Illness Index; Taiwan

The aim of the study was to investigate whether the most recent introduced atypical antipsychotics olanzapine and risperidone were preferentially prescribed to patients susceptible to develop extrapyramidal side effects (EPS) and those not responding adequately to typical antipsychotics.. Data were obtained from the Dutch PHARMO system that includes complete medication and hospital admission records of 675 000 residents of 14 Dutch cities. A total number of 129 new users of olanzapine and 142 new users of risperidone as well as 507 new users of typical antipsychotic drugs were identified from our database in the period of 1996-1998. The prevalence of markers of EPS, therapy resistance and therapy non-compliance were assessed in the period of 1 year prior to a new start of an antipsychotic.. New use of olanzapine and risperidone was significantly associated with previous use of other antipsychotics (odds ratio 4.0, 95%CI: 2.5-6.7 and odds ratio 3.0, 95%CI: 2.0-4.7, respectively). New use of olanzapine and risperidone was also associated with previous use of anticholinergic drugs compared to users of typical antipsychotics (over three and two times more, respectively). This effect diminished when adjusted for previous use of antipsychotics.. In particular olanzapine and also risperidone were selectively prescribed to patients formerly treated with other antipsychotics and to those susceptible for EPS. If not recognised or controlled for, observational studies comparing different antipsychotic drugs may produce biased results on efficacy or frequency of side effects for the different types of antipsychotics.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cholinergic Antagonists; Clozapine; Delayed-Action Preparations; Disease Susceptibility; Drug Administration Schedule; Drug Monitoring; Drug Utilization Review; Female; Humans; Male; Medical Records, Problem-Oriented; Middle Aged; Netherlands; Olanzapine; Patient Selection; Pharmacoepidemiology; Risperidone; Treatment Outcome

Common adverse effect measures in psychiatric trials are typically analysed with repeated measures ANOVA, despite having distributions which violate key assumptions of that method; moreover, some adverse effects may be concentrated in vulnerable subgroups of participants. For testing treatment differences in adverse effects, we propose use of Kendall's taub as a summary measure of within-participant trends in adverse events, in conjunction with a weighted modification of a rank test proposed by Conover and Salsburg. Data on extrapyramidal side effects from a controlled clinical trial conducted in persons with treatment resistant schizophrenia was used to compare the proposed analysis to repeated measures ANOVA using mixed models and alternate tests for treatment differences in taub trend scores.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Chlorpromazine; Computer Simulation; Data Interpretation, Statistical; Double-Blind Method; Humans; Olanzapine; Psychiatry; Randomized Controlled Trials as Topic; Schizophrenia

The Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) was examined for its usefulness as a subjective measure of drug-induced parkinsonism and akathisia. Eighty-three subjects were assessed using the LUNSERS, the Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS), before and after a 6-week treatment with olanzapine. Significant correlations were found between the changes in scores of parkinsonism items of LUNSERS and SAS. The changes in scores of akathisia item (restlessness), extrapyramidal side effects (EPS) subscale and psychic side-effects subscale of LUNSERS were significantly correlated with those of the BARS. 'Shakiness', one item of the EPS subscale of LUNSERS, correctly classified between parkinsonism and non-parkinsonism groups with 81.0% accuracy. A combination of four items included in EPS and psychic side-effect subscales of LUNSERS identified akathisia and non-akathisia groups with 76.2% accuracy. These results suggest that the EPS and psychic side-effect subscales of LUNSERS may be useful in screening for drug-induced parkinsonism and akathisia.

Topics: Adult; Akathisia, Drug-Induced; Basal Ganglia Diseases; Benzodiazepines; Comorbidity; Drug Administration Schedule; Female; Humans; Male; Olanzapine; Parkinson Disease, Secondary; Patient Participation; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome

Topics: Antipsychotic Agents; Athetosis; Basal Ganglia Diseases; Benzodiazepines; Brain; Chorea; Diffusion Magnetic Resonance Imaging; Drug Overdose; Fatal Outcome; Humans; Male; Middle Aged; Olanzapine

Treatment of schizophrenia with antipsychotics is often associated with extrapyramidal symptoms (EPS), a disorder involving involuntary muscle movement. Because EPS are often associated with the use of antipsychotics, anticholinergic agents are often indicated.. In this observational, retrospective study, we examined whether the initiation of olanzapine or risperidone, the two most widely prescribed atypical antipsychotics, is related to the adjunctive use of anticholinergic agents.. We identified patients with schizophrenia from outpatient clinics in the Veterans Health Administration (VA) and defined initiation of olanzapine or risperidone as patients who were not on any antipsychotics for 6 months and subsequently initiated on the target drug between 1/4/1999 and 31/3/2000. The data were analysed using tests of means or chi-square tests.. The study yielded two major findings. First, compared with risperidone initiators, there were significantly fewer olanzapine initiators who used at least one anticholinergic agent adjunctively. Secondly, among olanzapine or risperidone initiators, patients who used at least one anticholinergic agent adjunctively tended to stay on the target drug significantly longer than those who did not use any anticholinergic agent adjunctively with the target drug.. As the use of anticholinergics is a proxy for the presence of EPS, these findings suggest that risperidone may be more associated with EPS than olanzapine. However, to assess the benefits and side effects associated with olanzapine or risperidone, future research needs to examine various patient outcomes resulting from the initiation of each drug.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cholinergic Antagonists; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitals, Veterans; Humans; Male; Olanzapine; Outpatients; Patient Selection; Retrospective Studies; Risperidone; Schizophrenia; Time Factors; Treatment Outcome; United States

We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic (PK-PD) model based on the receptor occupancy. We collected the data for EPS induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a typical antipsychotic, haloperidol from literature and analyzed the following five indices of EPS, the ratio of patients obliged to take anticholinergic medication, the occurrence rates of plural extrapyramidal symptoms (more than one of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.), parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e., a model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition and a model not considering the endogenous dopamine release, and used them to examine the relationship between the D2 receptor occupancy of endogenous dopamine and the extent of drug-induced EPS. The model incorporating endogenous dopamine release better described the relationship between the mean D2 receptor occupancy of endogenous dopamine and the extent of EPS than the other model, as assessed by the final sum of squares of residuals (final SS) and Akaike's Information Criteria (AIC). Furthermore, the former model could appropriately predict the risks of EPS induced by two other atypical antipsychotics, clozapine and ziprasidone, which were not incorporated into the model development. The developed model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition may be useful for the prediction of antipsychotics-induced EPS.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Controlled Clinical Trials as Topic; Dibenzothiazepines; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Risperidone; Schizophrenia; Thiazoles

Cognitive deficits are a fundamental feature of the schizophrenic disorder, but the effect of antipsychotic treatment is still debated. The study assesses the effect of olanzapine on neurocognitive functioning and symptomatology of patients with schizophrenic disorder residual type. Executive function evaluation by the Wisconsin card sorting test (WCST) was performed on 39 patients treated with olanzapine (5-20 mg/day); the efficacy of drug in improving symptomatology, safety and quality of life was also evaluated. After 7 months of treatment, the mean number of WCST categories tended to increase. Correct responses increased with a statistically significant change from the baseline. The total and unique errors decreased significantly. At all post-baseline visits a decrease from baseline in the PANSS total, positive and negative scores was seen. The proportion of patients with less severe illness (CGI), increased over the course of the study with a corresponding decrease of patients with more severe illness. The quality of life scores also tended to improve during treatment. The Simpson Angus scale, Barnes-akathisia and abnormal involuntary movement scale scores decreased consistently. The most common treatment emergent drug related adverse events were weight gain, insomnia, agitation and anxiety. Neurocognitive functioning in terms of executive performance and symptomatology improved in people with schizophrenia residual type.

Topics: Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cognition; Female; Humans; Male; Middle Aged; Olanzapine; Quality of Life; Schizophrenia; Schizophrenic Psychology

The extent to which atypical antipsychotics have a lower incidence of extrapyramidal symptoms than typical antipsychotics has not been well-evaluated in community practice.. To examine the effects of switching antipsychotics on antiparkinsonian medication use among individuals with schizophrenia in UK general practices.. We included those switched from typical to atypical antipsychotics (n=209) or from one typical antipsychotic to another (n=261) from 1994 to 1998.. Antiparkinsonian drug prescribing dropped by 9.2% after switching to atypical antipsychotics (P<0.0001). Switching to olanzapine decreased the rate by 19.2% (P<0.0001), but switching to risperidone had no impact. After switching from one typical antipsychotic to another, antiparkinsonian drug prescribing increased by 12.9% (P<0.0001).. Reduction in antiparkinsonian medication use after switching to atypical antipsychotics was substantial in community practice but not as large as in randomised controlled trials. The rate of reduction varied according to the type of medication.

Topics: Adult; Age Factors; Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Chlorpromazine; Dopamine Antagonists; Drug Administration Schedule; Family Practice; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Risperidone; Schizophrenia; Sex Factors

We report an elderly patient who developed severe delirium and extrapyramidal signs after initiation of lithium-olanzapine combination. On hospital admission, serum levels of lithium were found to be 3.0 mM/L which were far above toxic level. Immediate discontinuation of both drugs resulted in complete resolution of most of the symptoms except for perioral dyskinesia which persisted for three more months. We critically discussed the differential diagnosis of lithium intoxication and assessed confounding factors which induce delirium and extrapyramidal signs related with combination therapy of lithium and olanzapine.

Topics: Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Delirium; Drug Therapy, Combination; Female; Humans; Lithium; Middle Aged; Olanzapine

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

Topics: Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Dementia; Humans; Olanzapine; Risperidone; Stroke; Treatment Outcome; United Kingdom; United States

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; Male; Neurologic Examination; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Treatment Outcome

To evaluate the safety and tolerability of olanzapine in the treatment of elderly patients with schizophrenia.. A total of 135 outpatients with schizophrenia > or =60 years of age were treated with olanzapine (n = 105) or another antipsychotic (n = 30) and followed up for 6 months. Safety measures included the recording of spontaneous adverse events and extrapyramidal symptoms (EPS). Clinical status and effectiveness of the medications were measured using the Clinical Global Impressions-Severity of Illness and the Global Assessment of Function (GAF) scales. Quality of life was assessed by means of the Spanish version of the EuroQol. The Awad scale was applied to evaluate patients' subjective attitude towards medication.. The incidence of overall adverse events and EPS was non-significantly lower in patients treated with olanzapine than in patients treated with other antipsychotics. The use of anticholinergic drugs was significantly lower (P = 0.04) in patients treated with olanzapine. Both groups of patients experienced similar improvements in Clinical Global Impressions-Severity and GAF scores. Non-significantly greater improvement in the acceptance of medication occurred at endpoint in olanzapine-treated patients than in control patients as measured by the Awad scale. The improvement in the EuroQol quality of life scale achieved at the end of study did not differ between both treatment groups.. Results from this naturalistic study showed that olanzapine was as safe and effective as other antipsychotic drugs in the treatment of elderly patients with schizophrenia.

Topics: Aged; Antipsychotic Agents; Attitude to Health; Basal Ganglia Diseases; Benzodiazepines; Drug Tolerance; Drug Utilization; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Quality of Life; Risperidone; Schizophrenia; Severity of Illness Index; Surveys and Questionnaires

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

Atypical antipsychotic medications are increasingly prescribed for child and adolescent patients. Relatively little information on adverse events (AEs), specifically in children or adolescents taking atypical antipsychotics, is available.. The Food and Drug Administration spontaneous AE reporting postmarketing surveillance database was queried for olanzapine until March 31, 2000. Patient exposure estimates as of the same date were provided by the manufacturer. AE complaints and exposure estimates were divided by age: children (birth-9 years), adolescents (10-19), and adults (20+). AE complaint risks per 10,000 patients exposed were calculated along with risk ratios across age groups and their 95% confidence intervals.. Extrapyramidal syndrome complaint risks were similar across development, and tardive dyskinesia complaint risks were comparable in adolescents and adults. Overrepresented AE complaints in children included sedation, weight gain, liver function abnormalities, and tardive dyskinesia. Overrepresented AE complaints in adolescents included sedation, weight gain, liver function abnormalities, and prolactin increase.. Extrapyramidal syndromes may be no more common in children and adolescents with olanzapine than in adults. The frequency of some other AEs may differ across development. Caution is warranted because of the likelihood of reporting bias. Similar analyses should be conducted with other atypical antipsychotics.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Child, Preschool; Dyskinesia, Drug-Induced; Female; Humans; Infant; Infant, Newborn; Male; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; United States

Plasma levels of clozapine and olanzapine are lower in smokers than in nonsmokers, which is mainly due to induction of cytochrome P4501A2 (CYP1A2) by some smoke constituents. Smoking cessation in patients treated with antipsychotic drugs that are CYP1A2 substrates may result in increased plasma levels of the drug and, consequently, in adverse drug effects. Two cases of patients who smoked tobacco and cannabis are reported. The first patient, who was receiving clozapine treatment, developed confusion after tobacco and cannabis smoking cessation, which was related to increased clozapine plasma levels. The second patient, who was receiving olanzapine treatment, showed important extrapyramidal motor symptoms after reducing his tobacco consumption. The clinical implication of these observations is that smoking patients treated with CYP1A2 substrate antipsychotics should regularly be monitored with regard to their smoking consumption in order to adjust doses in cases of a reduction or increase in smoking.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Confusion; Cytochrome P-450 CYP1A2; Humans; Male; Marijuana Smoking; Olanzapine; Pirenzepine; Smoking; Smoking Cessation

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

The role of olanzapine in treatment-resistant schizophrenia is still unresolved. This article presents an open-label, prospective, 14-week trial with olanzapine in patients with schizophrenia and schizoaffective disorder selected for unambiguous resistance to either clozapine or risperidone and to typical antipsychotics. Forty-three inpatients (mean age, 41.6 years; mean duration of illness, 21.7 years) were enrolled and treated after cross-titration from their previous antipsychotic treatment with olanzapine 10 to 40 mg daily without any concomitant antipsychotic medication. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale, and the Extrapyramidal Symptom Rating Scale. The change with olanzapine treatment was associated with a PANSS total score improvement of 3.7 (SD = 15.6; not significant). There was a significant improvement for the PANSS cognitive and depression/anxiety factors, whereas the PANSS excitement factor worsened. The improvement rate was superior in patients receiving olanzapine doses higher than 20 mg. A total of 16.7% of patients reached response criteria set forth by a previous study. There was a significant decrease in extrapyramidal side effects (t = 2.04; p < 0.05) and statistically significant, yet modest, weight gain. These results indicate that olanzapine is only modestly effective in these severely treatment-resistant patients with schizophrenia. However, a trial with olanzapine can be recommended in these patients before moving to augmentation strategies, given the lack of proven alternatives and the observation that 16.7% of patients reached the response criteria.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Drug Resistance; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Weight Gain

Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting.. This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart.. Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001).. Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Length of Stay; Male; Middle Aged; Neurologic Examination; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Risperidone; Treatment Outcome

To compare the risk of extrapyramidal syndrome (EPS) between risperidone, olanzapine, and haloperidol, taking into account patients' past antipsychotic drug use and past EPS.. Data were obtained from the PHARMO-database, containing filled prescriptions of 450,000 community-dwelling people in the Netherlands from 1986 through 1999. We defined cohorts of first-time users of haloperidol, risperidone, or olanzapine aged 15 to 54 years. In the first 90 days of treatment, we assessed the occurrence of EPS, defined as first use of any antiparkinsonian agent. We estimated relative risks of EPS for risperidone and olanzapine versus haloperidol using a Cox proportional hazards model. Patients were subdivided according to prior use of antipsychotic and antiparkinsonian drugs.. We identified 424 patients starting treatment with haloperidol, 243 with risperidone, and 181 with olanzapine. Prior use of antipsychotic plus antiparkinsonian medication was significantly more frequent among users of risperidone and olanzapine than in those using haloperidol (36.2%, 40.3%, and 4.5%, respectively; p < 0.001). Within most subgroups of comparable treatment history, patients using risperidone and olanzapine showed reduced risks of EPS compared with haloperidol, although some of these findings did not reach statistical significance (RR 0.03-0.22). However, this was not observed for patients using risperidone who had experienced EPS in the past (RR 1.30; 95% CI 0.24 to 7.18).. In general, we observed reduced risks of EPS for risperidone and olanzapine compared with haloperidol within subgroups of patients with a similar treatment history. However, the added value of risperidone in patients who have experienced EPS in the past needs further study.

Topics: Adolescent; Adult; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Drug Interactions; Female; Haloperidol; Humans; Male; Middle Aged; Netherlands; Olanzapine; Pirenzepine; Risk Factors; Risperidone

In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice.. Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale.. A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients.. Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS.

Topics: Adult; Antipsychotic Agents; Attitude to Health; Basal Ganglia Diseases; Benzodiazepines; Female; Haloperidol; Humans; Incidence; Male; Olanzapine; Patient Compliance; Prospective Studies; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

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

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Patient Compliance; Pirenzepine; Practice Patterns, Physicians'; Quality of Life; Quetiapine Fumarate; Risperidone

The authors' goal was to study the relationship between subjective experience during treatment with olanzapine or risperidone and dopamine D(2) receptor occupancy in stabilized patients with schizophrenia.. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed, and D(2) receptor occupancy was determined with [(123)I]iodobenzamide single photon emission computed tomography, in 22 patients whose schizophrenia was stabilized by olanzapine or risperidone.. Subjective experience, depression, and negative symptoms were related to dopamine D(2) receptor occupancy, but extrapyramidal symptoms were not.. These results provide preliminary evidence that negative subjective experience is related to high D(2) receptor occupancy. Longitudinal study is required because this relationship may have implications for dosing strategies.

Topics: Adolescent; Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzamides; Benzodiazepines; Corpus Striatum; Female; Health Status; Humans; Iodine Radioisotopes; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Pyrrolidines; Receptors, Dopamine D2; Risperidone; Schizophrenia; Schizophrenic Psychology; Tomography, Emission-Computed, Single-Photon

The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications.. The present study involved a subset of patients from a 6-month, open-label, prospective observational study. Data were collected by 293 psychiatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score < or = 4.. A total of 2657 patients were included in the analysis. The initial and overall mean daily doses for the 3 groups were as follows: OLZ, 12.2 and 13.0 mg, respectively; RIS, 5.2 and 5.4 mg; and HAL, 13.9 and 13.6 mg. Initial and overall median daily doses were the same in each group: OLZ, 10 mg; RIS, 6 mg; and HAL, 10 mg. A significantly lower proportion of OLZ-treated patients (36.9%) experienced EPS compared with RIS-treated (49.6%) and HAL-treated (76.0%) patients (P < or = 0.001). A significantly lower proportion of patients in the OLZ group (47.8%) experienced adverse events compared with patients in the RIS (57.2%) and HAL (79.8%) groups (P < or = 0.001). A significantly greater proportion of OLZ-treated patients (37.3%) were responders compared with RIS-treated patients (31.5%) (P < 0.05). In all 3 groups, patients who had an initial CGI score > or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6) compared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001).. The mean daily doses recorded in this analysis based on data from a naturalistic setting are consistent with recommendations based on clinical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and less likely to use concomitant anticholinergic medications. OLZ-treated patients were also more likely to respond to treatment than were RIS-treated patients.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Drug Utilization; Female; Haloperidol; Humans; Male; Olanzapine; Pharmacoepidemiology; Pirenzepine; Practice Patterns, Physicians'; Prospective Studies; Risperidone; Schizophrenia

Topics: Acute Disease; Affect; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Bipolar Disorder; Drug Monitoring; Dyskinesia, Drug-Induced; Humans; Olanzapine; Pirenzepine

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Female; Haloperidol; Humans; Mouth Diseases; Olanzapine; Pirenzepine; Schizophrenia; Stereotypic Movement Disorder; Syndrome; Treatment Outcome

Previously, we have shown that the atypical antipsychotics clozapine and risperidone, unlike haloperidol, decreased the firing rate of substantia nigra reticulata (SNR) neurons. As the SNR receives substantial input from the striatum, an area where motoric side-effects of antipsychotics are thought to be mediated, the SNR might be an interesting brain structure with regard to motor side-effects.. The newly developed atypical antipsychotic olanzapine was studied for its effects on the firing rate of SNR cells. In addition, to gain insight in the implications of our experimental setup for clinical use, responses upon clozapine, olanzapine and haloperidol were studied after chronic treatment.. In chloralhydrate-anaesthetized male Wistar rats, extracellular recordings were made from SNR neurons upon intravenously (i.v.) administered cumulative doses of the antipsychotics. Naive rats and rats that were subcutaneously (SC) injected for 21 days with an antipsychotic were used.. Olanzapine (50-1600 mg/kg; i.v.), significantly inhibited the firing rate of the SNR neurons. Upon 21 days of treatment with a daily SC injection of 20 mg/kg clozapine, the challenge on day 22 with cumulative injections of clozapine (200 6400 mg/kg; i.v.) significantly inhibited the firing rate of the SNR neurons. Olanzapine (50-1600 mg/kg; i.v.) also significantly inhibited the SNR activity when pretreated with olanzapine in an SC administered dose of 1 mg/kg, but not 5 mg/kg. Haloperidol (12.5-800 microg/kg; i.v.) did not significantly affect the SNR activity in rats pretreated with SC administered 0.5 mg/kg haloperidol.. Upon acute and chronic administration of clozapine and olanzapine versus haloperidol, differential effects on SNR neuronal firing could be obtained. The experimental setup seem to be valid for further studies into the mechanism of action of typical versus (relatively low doses of) atypical antipsychotics. The implications of the inhibitory effect of atypical antipsychotics on the SNR firing rate are presently unknown, but could be associated with the lower propensity to induced motoric side-effects. On the other hand, the SNR activity might also reflect non-motoric activity possibly related to negative symptoms.

Topics: Animals; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Haloperidol; Male; Neurons; Olanzapine; Pirenzepine; Rats; Rats, Wistar; Substantia Nigra

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

The atypical antipsychotic drug olanzapine has been proposed for treatment of dopaminergic psychosis in Parkinson's disease (PD). We report on a 68-year-old patient who developed a severe akinetic-rigid extrapyramidal syndrome, accompanied by additional paranoid symptoms, following olanzapine treatment of optic hallucinosis in PD. Olanzapine may also induce clinically relevant extrapyramidal side effects in PD patients.

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Clozapine; Drug Therapy, Combination; Hallucinations; Humans; Levodopa; Male; Olanzapine; Paranoid Disorders; Parkinson Disease; Piperidines; Pirenzepine; Selegiline; Severity of Illness Index

Topics: Acute Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Drug Overdose; Humans; Male; Olanzapine; Pirenzepine; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Chronic Disease; Drug Administration Schedule; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Treatment Outcome

Iloperidone (HP 873; 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy] -3- methoxyphenyl]ethanone) is a compound currently in clinical trials for the treatment of schizophrenia. Iloperidone displays affinity for dopamine D2 receptors and for 5-HT2A receptors and has a variety of in vivo activities suggestive of an atypical antipsychotic. Here we present an examination of the affinity of iloperidone to a variety of human and rat homologs of dopamine and 5-HT receptor subtypes. We employed receptor binding assays using membranes from cells stably expressing human dopamine D1, D2S, D2L, D3, D4 and D5 and 5-HT2A and 5-HT2C receptors and rat 5-HT6 and 5-HT7 receptors. Iloperidone displayed higher affinity for the dopamine D3 receptor (Ki = 7.1 nM) than for the dopamine D4 receptor (Ki = 25 nM). Iloperidone displayed high affinity for the 5-HT6 and 5-HT7 receptors (Ki = 42.7 and 21.6 nM, respectively), and was found to have higher affinity for the 5-HT2A (Ki = 5.6 nM) than for the 5-HT2C receptor (Ki = 42.8 nM). The potential implications of this receptor binding profile are discussed in comparison with data for other antipsychotic compounds.

Topics: Animals; Antipsychotic Agents; Basal Ganglia Diseases; CHO Cells; Cricetinae; Humans; Isoxazoles; Kinetics; Piperidines; Rats; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Dopamine D4; Receptors, Dopamine D5; Receptors, Serotonin