olanzapine and Bipolar-Disorder

People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population.. Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age).. Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES).. Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Fluoxetine; Glycated Hemoglobin; Humans; Longevity; Olanzapine; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors

Are antipsychotic dose equivalents between acute mania and schizophrenia the same?. Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre-post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia.. We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: -022, 95% CI -0.41 to -0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, -8.1%) and risperidone (p<0.001, -15.8%).. Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.

Topics: Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Haloperidol; Humans; Mania; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia

Antipsychotic medications are increasingly used for difficult-to-treat depression in young people. However, the evidence-base for this is unclear. Our aim was to assess the evidence for the efficacy of atypical antipsychotics in treating unipolar and bipolar depression in adolescents and young adults.. We conducted a comprehensive systematic review and meta-analysis of randomized-control-trial studies (RCTs) of antipsychotic medications for 10- to 25-year-olds with unipolar and bipolar depression. The primary outcome of interest was change in depressive symptoms from baseline to trial endpoint.. No studies were identified that evaluated the use of antipsychotics in the treatment of unipolar depression. However, we identified four studies, of quetiapine, lurasidone and olanzapine/fluoxetine combination, comprising a total of 866 randomized patients, that evaluated treatment of bipolar depression. All studies used the Children's Depression Rating Scale-Revised (CDRS-R). Our meta-analysis revealed the weighted mean difference (WMD) was -4.58 (95 % CI, -6.59 to -2.57) between antipsychotic and placebo-treated groups. Response and remission rates were also significantly in favor of antipsychotic treatment.. There were few studies, several did not address risk-of-bias domains and there was a lack of non-industry sponsored studies.. There is an absence of evidence for the use of antipsychotic medications in treatment of youth unipolar depression, and no recommendations can be made. There is some evidence for the efficacy of antipsychotics, specifically lurasidone and olanzapine/fluoxetine combination, in the treatment of young people with bipolar depression. However, this evidence is limited and more studies investigating the use of these medications in young people are needed.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Fluoxetine; Humans; Lurasidone Hydrochloride; Olanzapine; Young Adult

Bipolar depression constitutes a major public health problem due to its substantial burden of disease. Although pharmacological interventions are available, guidelines required updated evidence synthesis to improve their current recommendations. In order to inform evidence-based prescribing, we investigated the comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression.. We conducted a systematic review and network meta-analysis. We searched for randomised controlled trials comparing pharmacological interventions with each other or placebo in adults with acute bipolar depression (type I, type II, or not otherwise specified), excluding those with substance misuse, unipolar depression, or schizophrenia, in MEDLINE, Embase, PsycINFO, Google Scholar, Cochrane Library, Web of Knowledge, CINAHL, and LILACS from database inception up to April 13, 2023. Criteria for eligibility were a duration of 2-16 weeks with masked outcome assessments, and we included combination, add-on design, and monotherapy studies. The co-primary outcomes were depressive symptoms, examined with standardised mean differences (SMDs), and manic switch, examined with odds ratios (ORs). We also investigated dropouts due to any reason, inefficacy, adverse events, and important side-effects as secondary outcomes. The confidence in the evidence was evaluated using Confidence-In-Network-Meta-Analysis (CINeMA). The study was registered with PROSPERO, CRD42020171726.. We analysed data from 101 randomised controlled trials covering 20 081 participants, 8063 men (41·7%) and 11 263 women (58·3%; sex not available in four studies), mean age 41·0 years (range of means 28·7-53·6 years), and 68 medications and placebo. Ethnicity data were not available. With moderate confidence in the evidence, olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were more efficacious than placebo in reducing depressive symptoms, with SMDs ranging from 0·41 (95% CI 0·19-0·64) for olanzapine plus fluoxetine to 0·16 (0·03-0·29) for lamotrigine. Several other drugs might also be efficacious, but the confidence in the evidence was very low to low. Antidepressants as a class seem to be efficacious, but had a higher risk for manic switch compared to antipsychotics. Medications differed in their side-effect profiles.. This is, to our knowledge, the largest network meta-analysis of pharmacotherapy for bipolar depression to date. Olanzapine plus fluoxetine, quetiapine, olanzapine, lurasidone, lumateperone, cariprazine, and lamotrigine were found to be more efficacious than placebo in adults with acute bipolar depression, with good confidence in the evidence, and to differ in their side-effect profiles. These findings can inform evidence-based care and the development of treatment guidelines internationally.. None.

Topics: Adult; Bipolar Disorder; Depression; Drug-Related Side Effects and Adverse Reactions; Female; Fluoxetine; Humans; Lamotrigine; Lurasidone Hydrochloride; Male; Middle Aged; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p<0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19-0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25-0.55, p<0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone

A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Female; Haloperidol; Humans; Lithium; Male; Mania; Network Meta-Analysis; Olanzapine; Paliperidone Palmitate; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Tamoxifen; Valproic Acid

To describe the approval of olanzapine/samidorphan, compare the clinical trial data, and summarize key findings, with a focus on impact to clinical practice.. A literature search of PubMed was performed (March 2006 to November 2021) using the following search terms:. Relevant English-language studies conducted in humans were considered. Primary use of Phase III clinical drug approval trials preferred; supplementary trial analysis evaluated to provide context.. This review details the pharmacologic, pharmacokinetic, associated dosing and indications, and adverse effects for the drug combination olanzapine/samidorphan. Better understanding of novel drug mechanisms will help to expand on the potential role and place for use in clinical practice.. When treating complex patients with schizophrenia, the olanzapine/samidorphan combination has limited effect on medication-induced weight gain often associated with antipsychotic olanzapine monotherapy. Additional studies are needed to further define the role of olanzapine/samidorphan in bipolar I disorder and clinical practice.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Naltrexone; Olanzapine; Schizophrenia

Although olanzapine remains one of the most efficacious antipsychotic medications for the treatment of schizophrenia, there are significant tolerability concerns related to its weight and metabolic profile. Olanzapine-samidorphan combination tablets (OLZ/SAM), branded as Lybalvi, is a newly FDA approved formulation aimed at attenuating antipsychotic induced weight gain via modulation of the endogenous opioid system with samidorphan, while retaining the robust antipsychotic efficacy of olanzapine.. We reviewed the published literature of OLZ/SAM for the management of schizophrenia using the US National Library of Medicine's PubMed.gov resource. Topics covered in this narrative review include the pharmacokinetics, pharmacodynamics, efficacy, and tolerability of OLZ/SAM.. OLZ/SAM is an effective and well-tolerated pharmacologic option in mitigating olanzapine induced weight gain while retaining olanzapine's efficacy. OLZ/SAM cumulatively tends to attenuate weight gain rather than promote weight loss. Effect on metabolic laboratory variables appears limited. Additional research will be needed to determine its effectiveness compared to alternative strategies to attenuate antipsychotic induced weight gain.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Naltrexone; Narcotic Antagonists; Olanzapine; Schizophrenia; Tablets; Weight Gain

Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.. A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.. Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.. Small sample sizes, different index episodes and variety of outcome measures.. Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.

Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Valproic Acid

Olanzapine is a second-generation antipsychotic with established efficacy in several psychiatric disease states, but its use is limited because of weight gain and metabolic side effects. Samidorphan is a novel opioid antagonist that binds to mu-opioid, kappa-opioid, and delta-opioid receptors and is hypothesized to reduce cravings for high-calorie foods thus attenuating antipsychotic-induced weight gain. The combination product olanzapine/samidorphan was approved by the US Food and Drug Administration in June 2021 for the treatment of schizophrenia and bipolar I disorder; this article reviews the pharmacological properties of oral olanzapine/samidorphan and its clinical efficacy and tolerability with a focus on mitigation of olanzapine-induced weight gain in these patient populations. In clinical trials, the combination of olanzapine/samidorphan was associated with significantly less weight gain and smaller increases in waist circumference as compared with olanzapine monotherapy. Olanzapine/samidorphan demonstrated similar efficacy as olanzapine monotherapy and was well tolerated. Weight gain and metabolic side effects associated with olanzapine monotherapy can result in tolerability issues and potentially medication nonadherence. Olanzapine/samidorphan is an effective treatment for schizophrenia and bipolar I disorder with less weight gain than olanzapine monotherapy.

Topics: Analgesics, Opioid; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Naltrexone; Olanzapine; Schizophrenia; Weight Gain

Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta-analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD).. A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non-pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within-subject RCBD illness severity before and after treatment. Pre-post random effects meta-analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI).. A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within-subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias.. While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established.

Topics: Aripiprazole; Bipolar Disorder; Citalopram; Fluoxetine; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Venlafaxine Hydrochloride

The 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) guidelines provided clinicians with pragmatic treatment recommendations for bipolar disorder (BD). While these guidelines included commentary on how mixed features may direct treatment selection, specific recommendations were not provided-a critical gap which the current update aims to address.. Overview of research regarding mixed presentations in BD, with treatment recommendations developed using a modified CANMAT/ISBD rating methodology. Limitations are discussed, including the dearth of high-quality data and reliance on expert opinion.. No agents met threshold for first-line treatment of DSM-5 manic or depressive episodes with mixed features. For mania + mixed features second-line treatment options include asenapine, cariprazine, divalproex, and aripiprazole. In depression + mixed features, cariprazine and lurasidone are recommended as second-line options. For DSM-IV defined mixed episodes, with a longer history of research, asenapine and aripiprazole are first-line, and olanzapine (monotherapy or combination), carbamazepine, and divalproex are second-line. Research on maintenance treatments following a DSM-5 mixed presentation is extremely limited, with third-line recommendations based on expert opinion. For maintenance treatment following a DSM-IV mixed episode, quetiapine (monotherapy or combination) is first-line, and lithium and olanzapine identified as second-line options.. The CANMAT and ISBD groups hope these guidelines provide valuable support for clinicians providing care to patients experiencing mixed presentations, as well as further influence investment in research to improve diagnosis and treatment of this common and complex clinical state.

Topics: Antipsychotic Agents; Anxiety; Aripiprazole; Bipolar Disorder; Canada; Humans; Olanzapine; Valproic Acid

The use of ketamine for depression has increased rapidly in the past decades. Ketamine is often prescribed as an add-on to other drugs used in psychiatric patients, but clear information on drug-drug interactions is lacking. With this review, we aim to provide an overview of the pharmacodynamic interactions between ketamine and mood stabilizers, benzodiazepines, monoamine oxidase-inhibitors, antipsychotics, and psychostimulants.. MEDLINE and Web of Science were searched.. Twenty-four studies were included. For lithium, no significant interactions with ketamine were reported. Two out of 5 studies on lamotrigine indicated that the effects of ketamine were attenuated. Benzodiazepines were repeatedly shown to reduce the duration of ketamine's antidepressant effect. For the monoamine oxidase-inhibitor tranylcypromine, case reports showed no relevant changes in vital signs during concurrent S-ketamine use. One paper indicated an interaction between ketamine and haloperidol, 2 other studies did not. Four papers investigated risperidone, including 3 neuroimaging studies showing an attenuating effect of risperidone on ketamine-induced brain perfusion changes. Clozapine significantly blunted ketamine-induced positive symptoms in patients with schizophrenia but not in healthy participants. One paper reported no effect of olanzapine on ketamine's acute psychotomimetic effects.. Current literature shows that benzodiazepines and probably lamotrigine reduce ketamine's treatment outcome, which should be taken into account when considering ketamine treatment. There is evidence for an interaction between ketamine and clozapine, haloperidol, and risperidone. Due to small sample sizes, different subject groups and various outcome parameters, the evidence is of low quality. More studies are needed to provide insight into pharmacodynamic interactions with ketamine.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Depression; Drug Interactions; Female; Haloperidol; Humans; Ketamine; Lithium; Male; Olanzapine; Psychotropic Drugs; Risperidone; Schizophrenia; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Drug Combinations; Humans; Naltrexone; Narcotic Antagonists; Olanzapine; Schizophrenia; Weight Gain

The approvals of psychotropics for bipolar disorder (BD) are mainly based on randomized, double-blind, placebo-controlled trials (RCTs) from North America. It remains unknown whether approved psychotropics have similar efficacy, tolerability, and safety for Asians with BD. The aim of this systematic review was to compare those differences of psychotropics between Asians and North Americans with BD.. MEDLINE, EMBASE, and PsycINFO were searched for RCTs studied in two regions. The effect size, remission/response rate, and risk for discontinuation due to adverse events (AEs), weight gain (WG), nervous systems and gastrointestinal AEs were assessed and compared between two regions with Cohen's d or number needed to treat/harm.. Eleven studies of aripiprazole, olanzapine, risperidone, and quetiapine in BD were included. Similar efficacy and relatively benign tolerability of atypical antipsychotics (AAPs) between Asians and Americans with BD were observed in most studies. The risk for AAP-related WG was similar between two regions. Asians with mania or bipolar depression were more vulnerable to akathisia/tremor or constipation. Japanese and Chinese with bipolar depression were more sensitive to somnolence and dizziness, respectively. Americans were more likely to have dry mouth, nausea, and vomiting.. The number of included psychotropics and papers was small.. Differences in AAP-related efficacy and tolerability were minimal between the two regions, but some AEs appeared to be different. Clinicians should pay attention to these differences to optimize treatment strategies in different races/ethnicities with BD.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Asian People; Bipolar Disorder; Female; Humans; North America; Olanzapine; Quetiapine Fumarate; Risperidone; United States; Weight Gain

Topics: Aggression; Antipsychotic Agents; Bipolar Disorder; Dexmedetomidine; Drug Development; Drugs, Investigational; Humans; Olanzapine; Psychomotor Agitation; Schizophrenia

We investigated the comparative efficacy and tolerability of pharmacological treatment strategies for the treatment of acute bipolar depression.. A systematic review and network meta-analysis was conducted by searching eight registries for published and unpublished, double-blind, randomized controlled trials of pharmacotherapies for the acute treatment of bipolar depression.. PRISMA guidelines were used for abstracting data, while the Cochrane Risk of Bias Tool was used to assess data quality. Data extraction was done independently by two reviewers, with discrepancies resolved by consensus. Data were pooled using a random-effects model.. Primary outcomes were efficacy (response and remission rate) and acceptability (completion of treatment and dropouts due to adverse events). Summary odds ratios (ORs) were estimated using pairwise and network meta-analysis with random effects.. Identified citations (4,404) included 50 trials comprising 11,448 participants. Escitalopram, phenelzine, moclobemide, carbamazepine, sertraline, lithium, paroxetine, aripiprazole, gabapentin and ziprasidone appear to be ineffective as compared to placebo in treatment of bipolar depression. Divalproex, olanzapine/fluoxetine, olanzapine, quetiapine, cariprazine, and lamotrigine, appear to be effective as compared to placebo in treatment of bipolar depression according to the network meta-analysis. Aripiprazole showed higher discontinuation rates versus placebo due to the appearance of any adverse event. Quetiapine was better than placebo at reducing treatment-emergent affective switches. For Bipolar I Disorder, cariprazine, fluoxetine, imipramine, lamotrigine, lurasidone, olanzapine-fluoxetine, and olanzapine were significantly better than placebo at response, while fluoxetine, imipramine, cariprazine, lurasidone, olanzapine-fluoxetine, and olanzapine were significantly better than placebo at remission.. These results could serve evidence-based practice and inform patients, physicians, guideline developers, and policymakers on the relative benefits of the different antidepressants, antipsychotics, and mood-stabilizing agents for the treatment of bipolar depression.. PROSPERO (CRD42019122172).

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Lurasidone Hydrochloride; Network Meta-Analysis; Olanzapine

This review examined the efficacy of mood stabilizers and antipsychotics in patients with bipolar disorder during pregnancy and the postpartum period.. PubMed was searched for reports between 01 January 1996 and 31 December 2019 by using combinations of key words bipolar disorder, pregnancy, postpartum period, puerperium, prophylaxis, mood stabilizers, antipsychotics, lithium, lamotrigine, valproate, carbamazepine, oxcarbazepine, olanzapine, risperidone, quetiapine, aripiprazole, haloperidol, and chlorpromazine.. The present reports included a total of 256 patients using lithium (n = 143), lamotrigine (n = 73), valproate (n = 17), olanzapine (n = 17), quetiapine (n = 4) and haloperidol (n = 1) during pregnancy or the postpartum period. Recurrence rates in pregnant patients using lithium (n = 79) and lamotrigine (n = 17) were 22.7 % and 41.2 %, respectively. According to very limited data, none of the patients using valproate (n = 2), quetiapine (n = 3) or olanzapine (n = 6) experienced a new episode during pregnancy. A recurrence was reported in 12 (70.6 %) of 17 patients using valproate during the postpartum period. The same recurrence rates in patients using lithium (n = 123), lamotrigine (n = 63), olanzapine (n = 17) and quetiapine (n = 3) were 20.3 %, 7.9 %, 11.7 %, and 33.3 %, respectively.. This review suggests that lithium, lamotrigine and olanzapine seem to be effective in preventing new mood episodes in patients with bipolar disorder during the perinatal period.

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Olanzapine; Pregnancy; Quetiapine Fumarate

Atypical or so called second generation antipsychotics (SGA) are playing a role of increasing importance in treatment of bipolar disorder (BD). This study is aimed towards a systematic review of their efficacy when used as monotherapy in order to prevent relapses in the long term treatment. Publications about this subject were identified after a thorough bibliographic research in Medline, The Cochrane Library and Web of Science, employing the PICO method for the creation of a database search strategy and carrying out a critical read and analysis of the found evidence. 14 studies were found which informed about the results of randomized and controlled clinical trials (RCT) about the efficacy of these SGA in monotherapy for BD, when it comes to prevention of relapse, in adult patients diagnosed with either type I or II BD, with a minimum follow-up time of 6 months. Evidence of the use of SGAs for maintenance treatment in BD is limited. Amongst all antipsychotics assessed only aripiprazole, olanzapine, lurasidone, risperidone and quetiapine have been found to be competent for their use in monotherapy, according to RCT.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Quetiapine Fumarate; Risperidone

This systematic review and random-effect model, network meta-analysis of the phase 3 trials in Japan assessed the efficacy and safety profile of lurasidone compared with olanzapine and quetiapine extended-release (QUE-XR) for the treatment of bipolar depression.. The study included double-blind, randomized, placebo-controlled, phase 3 trials in Japan that included patients with bipolar depression. Outcomes included response rate (primary), remission rate (secondary), improvement of Montgomery-Åsberg Depression Rating Scale (MADRS) total score, discontinuation rates, and incidence of individual adverse events.. Three studies were included (n = 1223). Lurasidone and olanzapine but not QUE-XR were superior to placebo in response rate [risk ratio (95% credible interval): lurasidone = 0.78 (0.66, 0.92); olanzapine = 0.84 (0.71, 0.99); QUE-XR = 0.87 (0.73, 1.03)]. Lurasidone, olanzapine and QUE-XR were superior to placebo in remission rate [lurasidone = 0.90 (0.83, 0.98); olanzapine = 0.87 (0.77, 0.99); QUE-XR = 0.84 (0.73, 0.98)] and the improvement of MADRS total score. There were not differences in discontinuation rates between each antipsychotic and placebo. Compared with placebo, lurasidone was higher incidence of akathisia, and increased body weight and blood prolactin level; olanzapine was higher incidence of somnolence and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels; QUE-XR was higher incidence of extrapyramidal symptoms, akathisia, somnolence, dry mouth, constipation and ≥7% weight gain, and increased body weight, blood total cholesterol level, blood LDL cholesterol level, and blood triglyceride levels.. Our results suggested although the efficacy of three SGAs was similar, there were the differences in the safety profile among the SGAs.

Topics: Antipsychotic Agents; Bipolar Disorder; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Humans; Japan; Lurasidone Hydrochloride; Network Meta-Analysis; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic

In this paper, we aimed at reviewing evidence-based treatment options for bipolar mania and proposed tentative evidence-based clinical suggestions regarding the management of a manic episode, especially regarding the choice of the proper mood stabilizer and antipsychotic medication.. A narrative review was undertaken addressing 'treatment of bipolar mania'. Findings have been synthesized and incorporated with clinical experience into a model to support different treatment choices.. To date, there is solid evidence supporting the use of several medications, such as lithium, divalproex, and carbamazepine, and antipsychotics, such as chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, inhaled loxapine, asenapine, and cariprazine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, when making decisions about treatment, personalized treatment is needed, according to the different clinical presentations and more complex clinical situations within the manic episode and considering a long-term view and with the objective of not only a symptomatic but also functional recovery. After remission from acute mania, psychoeducation strategies are useful to ensure adherence.. Despite the evidence forefficacy of many currently available treatments for mania, the majority of RCTs provide little direction for the clinician as to what steps might be optimal in different presentations of mania as well as in the presence of specific patient characteristics. Manic episodes should be managed on a personalized basis considering the clinical course and patient criteria and with the expectation of maintaining that treatment in the long-term.

Topics: Antipsychotic Agents; Bipolar Disorder; Clozapine; Humans; Mania; Olanzapine

In the clinical setting, the nocebo phenomenon is where clinical worsening or adverse events occur as a response to a treatment, in a situation in which conditioning from previous treatment exposure and/or expectations of sickness or symptoms lead to sickness and symptoms in a conditioned or expectant individual. The nocebo response may thus be a confounder in clinical treatment and clinical research. There is a need to know how to predict if an individual is likely to be a nocebo responder, and how significant and commonplace the nocebo effect might be.. An analysis was conducted on nine placebo-controlled, randomized clinical trials of olanzapine for the treatment of bipolar disorder using data from placebo-treated study participants only. Data were analysed to identify participant or study characteristics associated with a nocebo event, defined as any treatment-emergent adverse event (TEAE) or an increase in score from baseline to endpoint for primary measures of clinical symptoms.. A total of 1185 participants were randomized to placebo, of whom 806 (68%) reported a TEAE. Hamilton Depression Rating Scale (HDRS) data were only available for 649 placebo-treated participants, of whom 321 (49.5%) demonstrated worsening. Nocebo events were significantly associated with: not being treatment-naïve, younger age, being located in the USA, being a participant in an earlier study, and being classified as obese compared with normal weight.. A pattern to identify nocebo responders did not emerge, although some prognostic variables were associated with a greater probability of nocebo response. There was some evidence to support the role of expectancy as a cause of nocebo reactions.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Incidence; Male; Middle Aged; Nocebo Effect; Olanzapine; Placebos; Randomized Controlled Trials as Topic

Bipolar disorder places a significant burden on the affected individuals, their family, healthcare systems and the overall economy. More treatment options are needed, especially those with better efficacy and tolerability. Asenapine is a second-generation antipsychotic approved in Europe (brand name Sycrest

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Dizziness; Heterocyclic Compounds, 4 or More Rings; Humans; Olanzapine; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Gain

This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states.. The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.. The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines.. The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Lurasidone Hydrochloride; Olanzapine; Paliperidone Palmitate; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Thiazoles; Valproic Acid

The efficacy of antipsychotics across the initial severity range in patients with acute mania remains unclear. Therefore, we examined the influence of baseline severity on the efficacy of olanzapine.. We did an individual participant data meta-analysis of double-blind, randomised controlled trials that compared olanzapine with placebo, identified through searches of the ClinicalStudyRequest.com database on Feb 2, 2016. We included patients with acute mania associated with bipolar I disorder. We examined the association between baseline and change scores on the Young Mania Rating Scale (YMRS; range 0-60) up to 3 weeks for olanzapine versus placebo groups using eight increasingly complex competing mixed-effects models for repeated measures.. We identified 33 reports, five (15%) of which were eligible and contained data for 939 patients (552 received olanzapine; 387 received placebo). The interaction between baseline severity and treatment was significant (β=0·22, 95% CI 0·05-0·39; p=0·013). The greater the baseline severity, the greater the magnitude of the differences between olanzapine and placebo was expected. The mean estimated YMRS scores were reduced at 3 weeks in both groups, but were greater with olazapine than placebo by 2·56 points for patients with a baseline score of 20-25 (9·26 for olanzapine vs 6·70 for placebo; effect size 0·35, 95% CI 0·11-0·60), by 4·74 points for a baseline score of 25-35 (14·25 vs 9·51; 0·58, 0·34-0·86), and by 8·01 points for a baseline score of 35-60 (21·72 vs 13·71; 0·70, 0·31-1·23).. Benefits of olanzapine can be expected for patients across the full spectrum of symptom severity who are likely to be treated for acute mania. Less severely ill patients seem to benefit less in terms of olanzapine efficacy, but still experience the same side-effects as more severely ill patients. Thus, clinicians and patients should carefully consider the benefit-to-risk ratio of olanzapine and its additional, prophylactic effect against relapse in the long term. The generalisability of these results to other antipsychotics, trial designs, and medical conditions remains to be established.. None.

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Olanzapine; Outcome Assessment, Health Care; Severity of Illness Index

Antipsychotic-induced weight gain (WG) and metabolic abnormalities are major concerns. This review was untaken to answer if there is a weight-neutral second-generation antipsychotic for bipolar disorder (BPD). Areas covered: English-language literature in MEDLINE was searched with the keywords of antipsychotic/second-generation antipsychotic or generic/brand name of second-generation antipsychotic, and BPD/mania/depression or bipolar maintenance, and safety/tolerability or WG/weight increase, and randomized, placebo-controlled trial. Difference between an antipsychotic monotherapy and placebo in absolute weight gain (AWG) and/or ≥ 7% (WG in three phases of BPD was compared based on the data from original publications. The number needed to treat to harm was used for the comparison of ≥ 7% WG. Among antipsychotics with short-term (mania and/or bipolar depression) and long-term (maintenance) studies, olanzapine, asenapine, quetiapine, risperidone had significant WG compared to placebo in both short-term and long-term trials. Aripiprazole did not cause significant WG compared to placebo in short-term studies, but caused significant WG in long-term studies. Paliperidone-ER-induced WG was significant in a mania study as measured with AWG, and ziprasidone caused significant WG in a mania study measured with ≥ 7% WG. Expert commentary: These data suggest that it is unlikely there is a weight-neutral second-generation antipsychotic in BPD.

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

Asenapine (Saphris(®), Sycrest(®)) is an atypical antipsychotic that is administered sublingually twice daily and is approved for schizophrenia in the USA, Japan and other countries, but not in the EU. This article reviews the pharmacology, clinical efficacy and tolerability profile of asenapine in the treatment of adults with schizophrenia. Clinical trials with asenapine have demonstrated efficacy in terms of both positive and negative symptoms of schizophrenia, although findings have not always been consistent. Across three short-term (6-week) studies in acute schizophrenia (including one in Asian patients), asenapine was generally superior to placebo and had broadly similar efficacy to active controls in improving total scores on the Positive and Negative Syndrome Scale. A meta-analysis of four short-term trials with asenapine (that also included a negative study and a failed trial) also showed significant benefit with asenapine over placebo. In longer-term trials and extensions (up to ≈3 years' duration), asenapine was effective relative to placebo in preventing relapse in schizophrenia, but was less effective than olanzapine in patients with schizophrenia or schizoaffective disorder (according to intent-to-treat LOCF analysis). However, in two trials in patients with persistent negative symptoms of schizophrenia, asenapine and olanzapine were similarly effective in reducing negative symptoms at week 26, with asenapine providing better results than olanzapine at week 52 in one of the extensions. The most frequently reported adverse events with asenapine are somnolence, akathisia and oral hypoesthesia. Although potentially associated with more extrapyramidal symptoms, asenapine appears to have less weight gain and metabolic effects than some other antipsychotic agents, such as olanzapine.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Schizophrenia; Treatment Outcome

Bipolar Disorder (BD) long-term treatment is aimed to prevent relapses associated with worsening cognitive impairment and chronicity. Available mood stabilizers, including lithium, fail to prevent relapses in about 40% of bipolar patients. Purpose of the present paper is to review the available data about the efficacy and tolerability of mood stabilizer plus antipsychotic combined treatments.. A research in the main database sources has been conducted to obtain an overview about the efficacy and tolerability of the combination of a mood stabilizer plus an antipsychotic in the long-term treatment of BD. Papers with different methodologies but having relapse prevention as main outcome have been included.. Despite the heterogeneity of studies in terms of methodology, almost all papers reported a major efficacy of combined treatments respect to mood stabilizer mono-therapies but lower tolerability. The antipsychotic that presents more evidence of efficacy in combination with mood stabilizers is quetiapine.. Combined treatments can be a valid option to improve relapse prevention in BD. However, the higher risk for side effects has to be taken into account and specific combinations should be preferred according to patients' medical comorbidity.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Humans; Long-Term Care; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome

The anticonvulsant valproic acid and the atypical antipsychotics olanzapine and quetiapine provide synergistic mood-stabilising, antidepressant and antipsychotic activities in the treatment of bipolar and schizoaffective disorders. Existing literature shows that pharmacokinetic and pharmacodynamics drug-drug interactions (DDIs) possibly occur with the use of such a combination. Clinical reports of a possible interaction between the drugs leading to an increased risk of adverse drug reactions have also emerged. The main objective of this paper is to review the incidence of DDIs between the anticonvulsant and the antipsychotics, to postulate the possible mechanisms of the interaction and to establish whether certain target populations are at an increased susceptibility to such interactions. The usefulness of therapeutic drug monitoring (TDM) of the antipsychotics to monitor for an interaction was also assessed. A systematic database search was carried out using the search engine provided by PubMed using the following key words: olanzapine, quetiapine, valproic acid, pharmacokinetic drug-drug interaction, bipolar disorder, therapeutic drug monitoring.. Evidence of a possible clinically relevant DDI between valproic acid and both antipsychotics has been uncovered. A possible mechanism for the interactions has been postulated, and the importance of TDM has been discussed.. Further research is required to determine whether DDIs occur with the concurrent use of valproic acid and olanzapine or quetiapine, and to investigate the potential of TDM as a clinical tool in improving pharmacotherapy and preventing toxicity.

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Humans; Olanzapine; Quetiapine Fumarate; Valproic Acid

To describe weight changes and metabolic effects of asenapine compared with placebo and olanzapine in adults.. Post hoc analyses were performed using data from 17 asenapine trials (13 schizophrenia and 4 bipolar mania trials) with placebo (5-10 mg twice daily; n = 1,748; 1-6 weeks) and/or olanzapine (5-20 mg, once daily; n = 3,430; 3-100 weeks). Data were pooled based on treatment into placebo-controlled and olanzapine-controlled trials. For trials with placebo and olanzapine treatment groups, the asenapine population was included in both pools. Changes from baseline for weight, body mass index, and fasting lipid and glucose levels were determined. The Medical Dictionary for Regulatory Activities was used to define metabolic adverse events.. Mean (standard error [SE]) weight change was greater with asenapine than with placebo (1.2 [0.2] vs 0.14 [0.2] kg; P < .0001) and similar in schizophrenia and bipolar disorder. Mean changes differed for asenapine versus placebo in triglycerides (1.8 [6.3] vs -12.2 [5.9] mg/dL; P < .01) and fasting glucose (1.9 [1.7] vs -1.6 [1.5] mg/dL; P < .05). In the olanzapine-controlled trials, weight change was significantly lower with asenapine than with olanzapine (0.9 [0.1] vs 3.1 [0.2] kg; P < .0001). Changes associated with asenapine were lower than those with olanzapine in fasting glucose (2.0 vs 3.3 mg/dL), total cholesterol (-0.4 [1.1] vs 6.2 [1.2] mg/dL; P < .0001), low-density lipoprotein cholesterol (-0.3 [1.1] vs 3.1 [1.2] mg/dL; P < .01), and triglycerides (-0.9 [5.4] vs 24.3 [5.8] mg/dL; P < .0001).. Asenapine was associated with greater weight gain and glucose changes than placebo and not associated with a meaningful change in triglycerides or cholesterol levels. Asenapine was not significantly different from olanzapine in change in glucose levels and lower than olanzapine with respect to triglycerides, weight gain, and increased cholesterol.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Cholesterol, LDL; Controlled Clinical Trials as Topic; Dibenzocycloheptenes; Female; Hematologic Tests; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Olanzapine; Schizophrenia; Treatment Outcome; Triglycerides; Weight Gain

Although common and severe, mixed states are rarely the subject of proper clinical trials. The aim of this paper is to systematically review data published in 2013 on the pharmacological treatment of mixed states.. The Medline database was searched for 2013 publications using the following keywords: 'treatment'; 'mixed'; 'bipolar'.. Medline search returned 118 results. Manual inspection of abstracts allowed selecting six papers for further review. The first meta-analysis of the efficacy of second-generation antipsychotics in mixed episodes, published in 2013, showed the efficacy of these agents. Other papers suggested that asenapine and olanzapine were efficacious for mixed episodes, with olanzapine being equally effective in patients with or without substance abuse. Aripiprazole and ziprasidone were reported to be efficacious and safe in treating manic/mixed episodes in children and adolescents. In another trial, Calcitonin was not found to be superior to placebo in treating manic/mixed episodes.. Although data suggest that most agents efficacious for mania may also be efficacious for mixed episodes, further studies are needed to confirm this assumption.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Calcitonin; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Olanzapine; Piperazines; Quinolones; Randomized Controlled Trials as Topic; Thiazoles; Treatment Outcome

Capgras delusion (CD) has multiple etiologies including neurodegenerative disorders and can be associated with violent behavior. CD is a common complication of Alzheimer dementia (AD); however, CD with violent behavior is uncommon in AD. We report escalating violent behavior by a patient with advanced AD and CD who presented to the emergency department (ED) and required admission to an academic medical center.. Case analysis with PubMed literature review.. A 75-year-old male with a 13-year history of progressive AD, asymptomatic bipolar disorder, chronic kidney disease, hypertension, hyperlipidemia, and benign prostatic hypertrophy presented to the ED with recurrent/escalating violence toward his wife, whom he considered an impostor. His psychotropic regimen included potentially inappropriate medications (PIMs) for geriatric/AD patients-topiramate/amitriptyline/chlordiazepoxide/olanzapine-that are associated with delirium, cognitive decline, dementia, and mortality. Renal dosing for topiramate, reduction in PIMs/anticholinergic burden, and substituting haloperidol for olanzapine resolved his violent behavior and CD.. CD in AD is a risk factor for violent behavior. As the geriatric population in the United States grows, CD in patients with AD may present more frequently in the ED, requiring proper treatment. Pharmacovigilance is necessary to minimize PIMs in geriatric/AD patients. Clinicians and other caregivers require further education to appropriately address CD in AD.

Topics: Aged; Aggression; Alzheimer Disease; Amitriptyline; Anticonvulsants; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Capgras Syndrome; Chlordiazepoxide; Fructose; Haloperidol; Humans; Hypnotics and Sedatives; Male; Olanzapine; Potentially Inappropriate Medication List; Renal Insufficiency, Chronic; Topiramate; Violence

Patients with bipolar disorder are symptomatic about half of the time, experiencing depression more often than mania/hypomania. Because patients usually seek treatment during a depressive episode (rather than a manic episode), bipolar depression is commonly misdiagnosed as unipolar depression. Providing an accurate and timely bipolar depression diagnosis is critical for the proper treatment of the patient. Some FDA-approved treatments are helpful during acute and maintenance phases of therapy, but there is a significant unmet need for effective bipolar depression treatments with favorable side-effect profiles. Newer agents offer the promise of improvements in tolerability, but additional research is needed to actualize this promise into better treatments for patients struggling with bipolar depression.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lurasidone Hydrochloride; Olanzapine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Thiazoles

This analysis investigated the correlations between the efficacy of olanzapine monotherapy and the number of concurrent manic symptoms in patients treated for bipolar depression.. Pooled data from 2 placebo-controlled olanzapine studies in patients with bipolar I depression were analyzed (total 1214 patients; 690 olanzapine monotherapy patients and 524 placebo patients). Patients were categorized for mixed features by the number of concurrent manic symptoms at baseline (0, 1 or 2, and ≥3, respectively, as measured by a Young Mania Rating Scale item score ≥1). Efficacy was evaluated by change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to 6 weeks.. Least-squares mean differences between olanzapine and placebo in the change of MADRS total scores were -3.76 (p=0.002), -3.20 (p<0.001), and -3.44 (p=0.002) for mixed features 0, 1 or 2, and ≥3, respectively. The response rates for olanzapine versus (vs.) placebo were 52.6% vs. 39.8%, 50.3% vs. 40.0%, and 42.2% vs. 33.7% for mixed features 0, 1 or 2, and ≥3, respectively. The remission rates for olanzapine vs. placebo group were 46.1% vs. 34.3%, 39.5% vs. 32.0%, and 34.8% vs. 24.1% for mixed features 0, 1 or 2, and ≥3, respectively. No significant interaction between mixed features and treatment was seen in the MADRS changes or response and remission rates.. Post hoc analyses of the data from 2 previous randomized clinical studies.. Olanzapine monotherapy was shown to be effective in the treatment of bipolar depression irrespective of the presence of concurrent manic symptoms.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Humans; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome

Treatment of bipolar depression is complicated by variable response and risk of switch to mania. Guidance is informed by the strength of evidence rather than by comparative data.. We performed a multiple-treatments meta-analysis of randomised, double-blind, controlled comparisons of 4-16 weeks in adults in bipolar depression. The primary efficacy outcome was effect size. The primary acceptability outcome was 'switch to mania'. Secondary outcomes were likelihood of response and withdrawals from trials.. Twenty-nine studies were included (8331 participants). Olanzapine + fluoxetine and olanzapine performed best on primary outcome measure being ranked highest for effect size. Switch to mania was least likely with ziprasidone and then quetiapine. Olanzapine + fluoxetine was also ranked the highest for response with lurasidone second, but olanzapine + fluoxetine and olanzapine had the optimal effect on response and withdrawal from treatment when the two parameters were considered together. Several treatments [monoamine oxidase inhibitors (MAOIs), ziprasidone, aripiprazole and risperidone] have limited or no therapeutic activity in bipolar depression.. Olanzapine + fluoxetine should be first-line treatment. Olanzapine, quetiapine, lurasidone, valproate and selective serotonin re-uptake inhibitors are also recommended. Tricyclic antidepressants and lithium are worthy of consideration but lamotrigine (high risk of switching, less robust efficacy) and MAOIs, ziprasidone, aripiprazole and risperidone (no evidence of efficacy) should not be used.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Depression; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lamotrigine; Lithium Compounds; Lurasidone Hydrochloride; Monoamine Oxidase Inhibitors; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Selective Serotonin Reuptake Inhibitors; Thiazoles; Treatment Outcome; Triazines; Valproic Acid

Olanzapine is one of the SGAs (second-generation antipsychotics) which have been used for the treatment of patients with schizophrenia and bipolar disorder in Japan. Olanzapine has various affinities for multiple receptors, including dopamine D2 receptor, serotonin 5-HT2A, 5-HT2C, 5-HT6 receptors, and adrenaline alpha1, histamine H1, muscarine M1-M5 receptors as well. Therefore, olanzapine is known as MARTA(multi-acting receptor targeted antipsychotics). Numerous studies have been conducted to compare the effectiveness of olanzapine between SGAs and FGAs (first-generation antipsychotics). According to the head-to-head meta-analysis and large-scale studies like CATIE and EUFEST, olanzapine seems to have not only higher efficacy but also less discontinuation comparing to other anti-psychotics.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Humans; Male; Olanzapine; Schizophrenia; Treatment Outcome

Olanzapine was the second first-line atypical antipsychotic medication approved by the Food and Drug Administration (FDA) for the treatment of adult schizophrenia and later approved for adolescent schizophrenia and bipolar disorder. Initial studies performed on adults demonstrated efficacy compared to placebo and a first-generation antipsychotic medication. Initial assessments in adolescents with schizophrenia demonstrated significant symptom reduction without movement disorder, but with weight gain. Later studies reported efficacy for bipolar disorder in teenagers, but with weight gain. The assessment of olanzapine safety in teenagers has shown substantial weight gain and metabolic measures. Because of equivalent efficacy to other atypical antipsychotic medications and the metabolic side-effects, olanzapine is often recommended as a second-use medication.. Studies of olanzapine use in adolescents with schizophrenia or bipolar disorder demonstrate significant reduction in symptoms while causing no movement disorder side-effects. There has been reduction in use of olanzapine with adolescents as newer atypical antipsychotics have emerged associated with less weight gain.. Studies of olanzapine have demonstrated effectiveness in adolescents with a psychotic illness. Metabolic side-effects are a strong concern of the field and have led to the recommendation of using the medication in a secondary fashion.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Schizophrenia

Switching antipsychotic medication in patients undergoing combination therapy for bipolar I disorder is a common clinical practice because of suboptimal drug efficacy or tolerability. Despite the frequency of switching, little is known about the most appropriate switching options. Ziprasidone may be a good alternative for patients with bipolar disorder experiencing a suboptimal response or intolerance to olanzapine in combination with a mood stabilizer because of its mood-stabilizing effect and minimal propensity for clinically significant body weight gain and metabolic disturbances. However, no study has evaluated the efficacy, safety, and tolerability of switching to ziprasidone from olanzapine in combination with a mood stabilizer for treatment of bipolar disorder.. The objective of this study was to evaluate the efficacy and safety of switching to ziprasidone in patients with bipolar I disorder experiencing a suboptimal response or intolerance to olanzapine in combination with lithium or valproate.. An 8-week, prospective, open-label study was conducted among inpatients and outpatients with bipolar I disorder who were taking olanzapine combined with lithium or valproate to treat recent manic or mixed episodes. In subjects experiencing a suboptimal response [≥16 points on the Young Mania Rating Scale (YMRS) at screening and baseline] or intolerance, olanzapine was switched to ziprasidone while maintaining the same dose of their current combined mood stabilizer during the 8-week trial. The primary efficacy measure was the mean change in the YMRS total score. Metabolic parameters were measured to evaluate the improvement in metabolic syndrome.. A total of 56 patients were enrolled, and 46 (82.1 %) completed this study. Switching to ziprasidone was effective and well-tolerated. YMRS total scores were significantly reduced over 8 weeks (mean change, -10.4 ± 10.2). There were significant improvements in metabolic parameters, with mean changes of -0.4 ± 0.8 kg/m(2) in body mass index (BMI), -1.2 ± 2.5 kg in body weight, -21.3 ± 62.7 mg/dL in the fasting triglyceride level, and -13.2 ± 26.6 mg/dL in the total cholesterol level. Greater improvements in BMI, body weight, and dyslipidemia were positively correlated with a higher baseline BMI and abnormal lipid profile.. Ziprasidone appears to be a good switching option for patients with bipolar I disorder experiencing suboptimal response or intolerance with olanzapine in combination with lithium or valproate. In addition, switching to ziprasidone improves metabolic parameters, especially in patients experiencing weight gain or dyslipidemia with olanzapine treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Substitution; Drug Therapy, Combination; Dyslipidemias; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Piperazines; Prospective Studies; Thiazoles; Treatment Outcome; Valproic Acid; Young Adult

Bipolar disorder is a recurrent illness that is amongst the top 30 causes of disability worldwide and is associated with significant healthcare costs. In the past, emphasis was placed solely on the treatment of acute episodes of bipolar disorder; recently, the importance of episode prevention and of minimisation of iatrogenicity has been recognised. For many years, lithium was the only mood stabiliser in common use, and it remains an agent of first choice in the preventative treatment of bipolar disorder. However, an estimated 20% to 40% of patients may not respond adequately to lithium. Valproate is an anticonvulsant drug that has been shown to be effective in acute mania and is frequently used in maintenance treatment of bipolar disorder. When the acceptability of long-term treatment is considered, together with efficacy, the adverse event profile of a medication is also important. This is an update of a Cochrane review first published in 2001 and last updated in 2009.. 1. To determine the efficacy of valproate continuation and maintenance treatment:a) in preventing or attenuating manic, depressive and mixed episodes of bipolar disorder;b) in preventing or attenuating episodes of bipolar disorder in patients with rapid cycling disorder; and; c) in improving patients' general health and social functioning, as measured by global clinical impression, employment and marital stability.2. To review the acceptability to patients of long-term valproate treatment, as measured by numbers of dropouts and reasons for dropping out, by compliance and by reference to patients' expressed views regarding treatment.3. To investigate the adverse effects of valproate treatment (including general prevalence of side effects) and overall mortality rates.. Search of the Cochrane Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register (CCDANCTR) (to January 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years), EMBASE, (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). No language restrictions were applied. Reference lists of relevant papers and previous systematic reviews were handsearched. Pharmaceutical companies marketing valproate and experts in this field were contacted for supplemental data.. Randomised controlled trials allocating participants with bipolar disorder to long-term treatment with valproate or any other mood stabiliser, or antipsychotic drugs, or placebo. Maintenance treatment was defined as treatment instituted specifically or mainly to prevent further episodes of illness.. Three review authors independently extracted data. A double-entry procedure was employed by two review authors. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability. For dichotomous data, risk ratios were calculated with 95% confidence intervals (CIs). For statistically significant results, we calculated the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH). For continuous data, mean differences (MDs) or standardised mean differences (SMDs) were calculated along with 95% CIs. MDs were used when the same scale was used to measure an outcome; SMDs were employed when different scales were used to measure the same outcome. The primary analysis used a fixed-effect model. Binary outcomes were calculated on a strict intention-to-treat (ITT) basis; dropouts were included in this analysis. When data were missing and the method of "last observation carried forward" (LOCF) had been used to do an ITT analysis, then the LOCF data were used.. Six randomised controlled trials (overall 876 participants) lasting 6 to 24 months were included. Two studies (overall 312 participants) compared valproate with placebo, four studies (overall 618 participants) valproate with lithium, one study (overall 23 participants) valproate with olanzapine and one study (overall 220 participants) valproate with the combination of valproate plus lithium. In terms of study quality, most studies reported the methods used to generate random sequence; however, only one study reported enough details on allocation concealment. Four of six included studies described their design as "double blind", but only two trials reported full details about blinding. Valproate was more effective than placebo in preventing study withdrawal due to any mood episode (RR 0.68, 95% CI 0.49 to 0.93; NNTB 8), but no difference in efficacy was found between valproate and lithium (RR 1.02, 95% CI 0.87 to 1.20). Valproate was associated with fewer participants dropping out of treatment for any cause when compared with placebo or lithium (RR 0.82, 95% CI 0.71 to 0.95 and RR 0.87, 95% CI 0.77 to 0.98, respectively). However, combination therapy with lithium plus valproate was more likely to prevent relapse than was monotherapy with valproate (RR 0.78, 95% CI 0.63 to 0.96). Significant differences in adverse event frequencies were found, and lithium was associated with more frequent diarrhoea, polyuria, increased thirst and enuresis, whereas valproate was associated with increased sedation and infection.. Limited evidence supports the efficacy of valproate in the long-term treatment of bipolar disorder. Clinicians and patients should consider acceptability and tolerability profile when choosing between lithium and valproate-their combination or other agents-as long-term treatment for bipolar disorder.

Topics: Antimanic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Humans; Lithium Compounds; Olanzapine; Randomized Controlled Trials as Topic; Secondary Prevention; Valproic Acid

Treatment of acute mania with second-generation antipsychotics has been claimed to involve a lower risk of switch to depression than haloperidol. However, clinical guidelines clearly state that this is not a proven fact.. Meta-analysis of double-blind randomized controlled trials in acute mania, comparing rates of switch to depression with atypical antipsychotics and with haloperidol. Search was conducted in MEDLINE and CENTRAL databases (last search: September 2011).. 8 randomized clinical trials fulfilled inclusion criteria. 2 of them were excluded because of low methodological quality or lack of data. 5 second-generation antipsychotics (aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone) were compared to haloperidol. In the mixed effects model the Risk Ratio for depressive switch was 0.71 (0.52, 0.96) favouring atypical antipsychotics. In the random effects model the difference did not reach statistical significance. In the heterogeneity analysis, exclusion of an outlying aripiprazole trial yielded a Risk Ratio of 0.58 (0.42, 0.82) with a non-significant heterogeneity test. Although no atypical antipsychotic was individually significantly superior to haloperidol, a trend could be seen favouring olanzapine (RR=0.56 [0.29, 1.08]), quetiapine (RR=0.36 [0.10, 1.33]), and ziprasidone (RR=0.51 [0.22, 1.18]).. All trials were industry supported, with some variability in dosage of haloperidol. Switch to depression was not the primary outcome of the trials. Heterogeneity could be explained as a lack of class-effect for atypicals.. Treating acute mania with atypicals is associated to 42% less risk of switch to depression than with haloperidol. Nevertheless, caution should be taken when considering this a class effect, as only olanzapine, quetiapine, and ziprasidone may show a better profile.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Depression; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Industry; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Research Support as Topic; Risperidone; Thiazoles

A proprietary combination of the atypical antipsychotic drug olanzapine and the serotonin reuptake inhibitor fluoxetine (OFC, Symbyax) was approved for the treatment of bipolar depression based on a double-blind, placebo-controlled comparison of olanzapine, OFC, and placebo.. This review considers published controlled and uncontrolled studies of the efficacy, pharmacodynamics, pharmacokinetics, interactions, and adverse effects of OFC. Beyond previously reviewed efficacy studies, an open-label 7-week study of 161 bipolar depressed patients (93% bipolar I), and an 8-week double-blind study of 833 bipolar I depressed patients with an open-label extension were identified. The structure and limitations of clinical trials of OFC are critically addressed.. OFC trades simplicity of administration for loss of flexibility of dosing and lack of a generic preparation, both of which are available for olanzapine and fluoxetine separately. Clinical trials are limited by short-term follow-up, exclusive use of symptom rating scale scores, limitation of subjects to those with depression that is not overly complex or comorbid, lack of consideration of subsyndromal hypomania and mood cycling, and high dropout rates. In the absence of comparisons to mood stabilizers combined with each other and/or antidepressants, the role of OFC in the treatment of bipolar depression remains unclear.

Topics: Animals; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Randomized Controlled Trials as Topic

This review of published studies compares scores on individual items of mania rating scales that systematically recorded symptom severity in persons diagnosed with bipolar disorder to identify age-grouped differences.. An extensive literature search identified item scores from mania rating scales, with a particular emphasis on baseline Young Mania Rating Scale (YMRS) item scores in published double-blind, placebo-controlled studies of bipolar I manic disorder. These baseline YMRS item scores were assessed as a proportion of the total YMRS score and compared by age group. Additional YMRS item/total scores in subjects with bipolar spectrum disorders were added to expand the analysis.. Preadolescents with bipolar disorder had significantly higher YMRS item scores than adolescents on aggression, irritability, and motor activity. Young Mania Rating Scale baseline item scores relative to the YMRS total score revealed that adolescents diagnosed with bipolar I mania scored comparatively higher than did adults on YMRS aggression and irritability items, whereas adults with bipolar I manic disorder scored comparatively higher on the grandiosity and sexual interest items. Age-grouped findings from subjects diagnosed with bipolar I, II, and Not Otherwise Specified (NOS) disorders yielded similar age-grouped results.. In age-grouped YMRS item assessments of bipolar mania, anger dyscontrol was most prominent for youth, whereas disordered thought content was paramount for adults.

Topics: Adolescent; Adult; Age Factors; Aggression; Anger; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Child; Clinical Trials as Topic; Comorbidity; Defense Mechanisms; Female; Humans; Irritable Mood; Male; Middle Aged; Motor Activity; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychometrics; Quinolones; Sexual Behavior; Thinking; Young Adult

Asenapine is a new second-generation antipsychotic (SGA) approved in September 2010 by the European Medicines Agency for the treatment of bipolar disorder. It was significantly more effective than placebo in acute mania or mixed episodes as monotherapy or adjunctive therapy to mood stabilizers (lithium or valproate). Early improvement was seen at day-2 (significant difference with placebo) and was strongly associated with week-3 response and remission. These suggest that the observation of an early improvement in the first week may be clinically an useful tool for individual treatment adjustment during the early course of treatment. Post-hoc analyses of asenapine studies showed significantly better effects on improving depressive symptoms associated with manic symptoms, and physical health related quality of life dimensions as compared to placebo. Asenapine differs from the other SGAs by a good tolerability profile, in particular in terms of metabolic profile. However, it seems to have a significant though moderate link with the occurrence of sedation. This new tolerance profile greatly broadens the scope of SGAs and supports the view of some authors that the term SGA is now outdated. Other therapeutic perspectives of asenapine are being assessed, in particular in specific population (pediatric and elderly patients).

Topics: Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Double-Blind Method; Drug Therapy, Combination; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Randomized Controlled Trials as Topic; Treatment Outcome

All treatment guidelines for acute mania recommend monotherapy with either mood stabilizers (MS) or antipsychotics. The objective of this analysis was to compare the efficacy and acceptability of both drug classes in an expanded set of clinical trials in acute mania.. Randomized double-blind trials comparing MS vs second generation antipsychotics (SGA) in acute mania were identified in a systematic literature search. Change in mania rating scale, responder rates and dropout rates were compared by treatment assignment using Review Manager version 5.0.. Nine studies totaling 1631 patients that compared the MS lithium or valproate against a number of SGAs, and which reported one or more analysis endpoints were identified. Statistically significant advantages were noted in favour of SGA over MS for standardized mean difference (SMD) for change in mania scores (-0.22 [95% CI -0.33 to -0.11]; p < 0.0001), responder rate risk difference (7% [95% CI 1% to 13%]; p = 0.02), and dropout risk difference (-5% [95% CI -10% to -1%]; p = 0.02). This change in SMD for mania scores is equivalent to a 2.5-3 point difference in Young Mania Rating Scale score. Similar trends for SMD were noted when comparing subgroups of lithium and valproate studies against SGAs.. Over half the included studies included olanzapine, and the applicability of these findings, especially to first generation antipsychotic drugs, requires confirmation. This analysis could not assess the relative efficacy of combined MS/SGA vs individual monotherapies.. In acute mania, monotherapy with SGAs demonstrates statistically significant advantages over MS in terms of both efficacy and acceptability, and may be preferable for initial choice of treatment.

Topics: Affect; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Humans; Lithium; Lithium Carbonate; Lithium Compounds; Mood Disorders; Olanzapine; Randomized Controlled Trials as Topic; Valproic Acid

Topics: Adult; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Drug Combinations; Female; Fluoxetine; Humans; Lamotrigine; Olanzapine; Practice Guidelines as Topic; Psychotherapy; Quetiapine Fumarate; Triazines

Olanzapine is an atypical antipsychotic that is useful in schizophrenia and bipolar affective disorder, but its use is associated with troublesome weight gain and metabolic syndrome. A variety of pharmacological agents has been studied in the efforts to reverse weight gain induced by olanzapine, but current evidence is insufficient to support any particular pharmacological approach. We conducted a systematic review and meta-analysis of randomized controlled trials of metformin for the treatment of olanzapine-induced weight gain. Systematic review of the literature revealed 12 studies that had assessed metformin for antipsychotic-induced weight gain. Of these, four studies (n= 105) met the review inclusion criteria and were included in the final analysis. Meta-analysis was performed to see the effect size of the treatment on body weight, waist circumference and body-mass index (BMI). Weighted mean difference (WMD) for body weight was 5.02 (95% CI 3.93, 6.10) kg lower with metformin as compared with placebo at 12 weeks. For waist circumference, the test for heterogeneity was significant (P= 0.00002, I(2) = 85.1%). Therefore, a random effects model was used to calculate WMD, which was 1.42 (95% CI 0.29, 3.13) cm lower with metformin as compared with placebo at 12 weeks. For BMI, WMD was 1.82 (95% CI 1.44, 2.19) kg m(-2) lower with metformin as compared with placebo at 12 weeks. Existing data suggest that short term modest weight loss is possible with metformin in patients with olanzapine-induced weight gain.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Humans; Hypoglycemic Agents; Metformin; Olanzapine; Overweight; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain

Asenapine is an atypical antipsychotic agent available in sublingual formulations (5 or 10 mg) and indicated in the US (Saphris) for the acute treatment, as monotherapy or adjunctive therapy, of manic and mixed episodes and in the EU (Sycrest) for the treatment of moderate to severe manic episodes, in adult patients with bipolar I disorder. In two large (both n = 480), well designed, 3-week trials in adult patients with bipolar I disorder, asenapine monotherapy was significantly more effective than placebo at improving mania symptoms, as assessed using the Young Mania Rating Scale total score (YMRS; primary endpoint), with significant differences between the asenapine and placebo groups occurring after 2 days of treatment. In both trials, Clinical Global Impression for Bipolar Disorder (CGI-BP) scale mania severity scores exceeded those of placebo. In one trial, response and remission rates exceeded those of placebo. In a 9-week extension study that recruited completers from the monotherapy trials, there were no significant differences between asenapine and olanzapine groups in terms in Montgomery-Åsberg Depression Rating Scale (MADRS) scores, CGI-BP mania severity scores, YMRS response rates or YMRS remission rates during the extension phase. In the extension study, the efficacy of asenapine monotherapy appeared to be maintained over 40 weeks (total treatment duration of 52 weeks). In a 12-week trial of asenapine as adjunctive therapy to lithium or valproate, asenapine was more effective than placebo in improving manic symptoms, based on the difference between groups in the YMRS total score at week 3 (primary endpoint). Most adverse events associated with asenapine were of mild to moderate severity, with <7% of asenapine recipients experiencing serious adverse events (vs 7% with placebo). In a pooled analysis of the monotherapy trials, the most common adverse events (occurring in ≥ 5% of patients and at twice the incidence of placebo) reported during acute phase asenapine monotherapy for bipolar mania were somnolence, dizziness, extrapyramidal symptoms (EPS, other than akathisia) and increased bodyweight, which were similar in nature to those occurring during longer-term monotherapy with asenapine. EPS did not worsen in severity during longer-term asenapine monotherapy. Asenapine had minimal effects on plasma glucose, lipid and prolactin levels over both short- and longer-term treatment periods, and had little pro-arrhythmogenic potential. Further active

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Olanzapine; Psychiatric Status Rating Scales

Antipsychotic therapy forms the cornerstone of treatment for people with severe mental illness. Second-generation (atypical) antipsychotics are associated with a significantly lower incidence of extrapyramidal symptoms than the typical, first-generation agents; however, changes in metabolic variables -- including impaired glucose metabolism, diabetes mellitus, weight gain and dyslipidaemia -- have been reported during treatment with second-generation antipsychotics. Understanding any potential link between antipsychotic treatment and the incidence of these events is complicated by the increasing prevalence of obesity and diabetes occurring in the general population and the increased risk of diabetes and changes in metabolic variables in people with schizophrenia. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose level appears to fall on a continuum, with olanzapine appearing to have a greater association than some other atypical antipsychotics. The PubMed database was used to search for publications that included any information on measures of changes in weight, body mass index (BMI) and/or metabolic variables in randomized studies of olanzapine published between 1992 and 2010. In long-term (≥48 weeks) studies of olanzapine, the mean weight gain was 5.6 kg (last observation carried forward; median exposure 573 days). The proportions of patients who gained at least 7%, 15% or 25% of their baseline weight with long-term exposure were 64%, 32% and 12%, respectively. Some studies have suggested that weight gain early during the course of olanzapine treatment may predict clinically significant weight gain following long-term exposure to the drug. Changes in metabolic variables, such as elevated indices of glucose metabolism and triglyceride level, have also been observed during treatment with olanzapine. Consensus guidelines emphasize the importance of appropriate baseline screening and ongoing monitoring of weight gain and metabolic variables for people receiving all antipsychotic treatments. Long-term weight management programmes have been shown to reduce weight gain in some patients.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cardiovascular Diseases; Dyslipidemias; Glucose Metabolism Disorders; Humans; Incidence; Olanzapine; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Factors; Schizophrenia; Weight Gain

In recent years, many papers on the treatment of the depressive phase of bipolar disorder (bipolar depression), especially bipolar I disorder, with high-level evidence, have been reported. The results of meta-analyses have also been reported for some medications. In the pharmacotherapy for bipolar depression, quetiapine (300 mg/day), lithium (more than 0.8 mEq/L), olanzapine (5-20 mg/day) and lamotrigine (200 mg/day) are effective, with high-level evidence. The combination of lithium and lamotrigine is also effective for bipolar depression. There is no evidence for effectiveness of the combination of mood stabilizers and antidepressants for bipolar depression. This paper presents the evidence data of quetiapine, lithium, olanzapine, lamotrigine, carbamazepine, valproate, aripiprazole, antidepressants, a combination of medications, and electroconvulsive therapy for bipolar depression, based on large-size randomized controlled studies and meta-analyses. The first-line medications for bipolar depression in the practice guidelines published for the last three years are also included.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Electroconvulsive Therapy; Episode of Care; Evidence-Based Medicine; Humans; Lamotrigine; Lithium Compounds; Meta-Analysis as Topic; Olanzapine; Practice Guidelines as Topic; Quetiapine Fumarate; Triazines

Bipolar depression, the most common phase of bipolar disorder, causes significant morbidity and mortality. Lithium, anticonvulsants or antidepressants offer some clinical efficacy. However, efficacy can be limited and side effects are sometimes problematic. There is still a major unmet need for effective, well-tolerated agents for the treatment of bipolar depression. The second-generation antipsychotics, with their proven efficacy against manic symptoms, are emerging as candidates for use against the depressive phase of bipolar disorder. Several studies have shown that some second-generation antipsychotics may improve depressive symptoms in mixed episodes in patients with bipolar disorder. More recently, specific studies have been performed in patients with bipolar depressive episodes. Quetiapine or olanzapine, as monotherapy or associated with other compounds, demonstrate an interesting efficacy. The international guidelines for the treatment of bipolar depression have identified quetiapine as a first line treatment in monotherapy. Second generation antipsychotics may prove to be important future treatments for patients with bipolar depression.

Topics: Affect; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Controlled Clinical Trials as Topic; Dibenzothiazepines; Drug Therapy, Combination; Guideline Adherence; Humans; Olanzapine; Quetiapine Fumarate; Treatment Outcome

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression.

Topics: Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Combinations; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Piperazines; Placebos; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Treatment Outcome

Olanzapine was licensed in the USA by the Food and Drug Administration in 2003 for the prevention of relapse in patients with bipolar disorder when the acute manic episode had responded to treatment with olanzapine. However, olanzapine is commonly used in clinical practice for preventing relapse in patients with bipolar disorder even when acute response has not been demonstrated. The aim of this systematic review and meta-analysis is to determine the effectiveness and acceptability of olanzapine in preventing recurrent mood episodes in bipolar disorder. MEDLINE, EMBASE, the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled up to July 2008 were accessed. Only randomised controlled trials comparing olanzapine with placebo or other active drugs for long-term treatment were included. Two reviewers independently extracted data. Authors were contacted to provide additional data. Of the five trials included in this review, four were conducted by Eli Lilly, the manufacturer of olanzapine. Olanzapine was more effective than placebo at preventing manic relapse, but there was no difference between olanzapine (alone or in combination with lithium or valproate) and placebo (alone or in combination with lithium or valproate) in terms of relapse into any mood episode, as defined as primary outcome by authors in each of the primary studies. We conclude that olanzapine may prevent further manic episodes only in patients who have responded to olanzapine in an acute manic or mixed episode and who have not previously had a satisfactory response to lithium or valproate.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Humans; Lithium Compounds; Olanzapine; Randomized Controlled Trials as Topic; Secondary Prevention; Time Factors; Valproic Acid

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

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

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

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

Olanzapine is an atypical antipsychotic that, in addition to its use in adults, is now indicated for the treatment of schizophrenia, and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13-17 years. In a randomized, double-blind, multicentre, 6-week trial in adolescents aged 13-17 years with schizophrenia, the least squares mean reduction from baseline to 6 weeks in the Brief Psychiatric Rating Scale for Children (BPRS-C) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In a randomized, double-blind, multicentre, 3-week trial in adolescents, aged 13-17 years, with manic or mixed episodes associated with bipolar I disorder, the mean reduction from baseline to 3 weeks in the Adolescent Structured Young Mania Rating Scale (YMRS) total score (primary endpoint) was significantly greater with olanzapine than with placebo. In extensions of each of the pivotal placebo-controlled trials in schizophrenia and bipolar mania, open-label treatment with olanzapine for up to 26 weeks produced significant reductions from baseline to endpoint in BPRS-C and YMRS total scores, respectively. Oral olanzapine was generally well tolerated in adolescents with schizophrenia or bipolar mania. Sedation and weight gain were the most common adverse events in placebo-controlled trials. Extrapyramidal symptoms were reported by 10% of olanzapine recipients compared with 6% of placebo recipients. Olanzapine-treated adolescents were likely to experience greater increases in bodyweight, sedation, blood lipids, serum prolactin and liver transaminase levels than olanzapine-treated adults. Therefore, careful consideration of risk-benefit is recommended before using olanzapine in adolescents.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Drug Administration Schedule; Humans; Olanzapine; Schizophrenia; Treatment Outcome

Olanzapine, an atypical antipsychotic was first introduced in 1996 as an oral formulation and is used in the treatment of schizophrenia and bipolar disorder. Recent developments have included parenteral formulations to improve compliance in the treatment of schizophrenia and to treat agitation in patients with schizophrenia and bipolar mania. Olanzapine pamoate long acting injection (depot) is a novel formulation of the atypical antipsychotic olanzapine, which is licensed for the maintenance treatment of schizophrenia. When administered as the pamoate salt, olanzapine has an elimination half-life of approximately 30 days, allowing it to be given at 2- or 4-weekly intervals. An 8-week, randomized, double-blind study in 404 patients acutely ill with schizophrenia demonstrated significant antipsychotic efficacy (versus placebo). A 24-week, randomized, double-blind, active-controlled study in 1,065 schizophrenia patients stabilized with oral olanzapine demonstrated the depot formulation could delay exacerbation of positive symptoms or hospitalization. Apart from local injection reactions and a postinjection delirium/sedation syndrome, no new adverse events additional to those seen with oral olanzapine have been notedto date. The pivotal clinical trials of olanzapine rapid-acting intramuscular injection are reviewed in addition to post-hoc analyses, controlled and naturalistic studies since its launch.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Delayed-Action Preparations; Humans; Injections, Intramuscular; Olanzapine; Schizophrenia

This meta-analysis examined the effectiveness of treatments of bipolar depression. Trials were identified using the MEDLINE, EMBASE, http://www.clinicaltrials.gov, and Cochrane databases (1993 to July 2008). The outcome measures included mean change in Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D) total scores, and rates of response and remission. Overall, 19 publications were included. Medications included quetiapine, lamotrigine, paroxetine, lithium, olanzapine, aripiprazole, phenelzine, and divalproex. The most trials were identified for quetiapine (5) and lamotrigine (6). Not all medications were associated with symptomatic improvement (significant reduction in MADRS/HAM-D total scores vs placebo), with lamotrigine, paroxetine, aripiprazole, and lithium not being different from placebo. Highest reductions in MADRS scores versus placebo were reported for the olanzapine-fluoxetine combination (1 trial: -6.6; 95% confidence interval [CI], -9.59 to -3.61; P = 0.000) and quetiapine monotherapy (5 trials: for 300 mg/d, -4.8; 95% CI, -6.18 to -3.49; P = 0.000; for 600 mg/d, -4.8; 95% CI, -6.22 to -3.28; P = 0.000), with quetiapine monotherapy also showing the highest reduction in HAM-D scores (4 trials: -4.0; 95% CI, -5.0 to -2.9; P = 0.000). All medications except paroxetine, lithium, aripiprazole, and phenelzine significantly improved the ratio of probabilities of response (overall rate, 1.31; 95% CI, 1.22-1.40) and remission (1.32; 95% CI, 1.20-1.45) versus placebo. Variability in efficacy exists between treatments of bipolar depression. Quetiapine and the olanzapine-fluoxetine combination showed the greatest symptomatic improvement. Efficacy considerations will need to be balanced against safety and tolerability of the individual agents.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Triazines

Many patients with bipolar disorder require long-term treatment to prevent recurrence. Antipsychotic drugs are often used to treat acute manic episodes. It is important to clarify whether olanzapine could have a role in long-term prevention of manic and depressive relapses.. To assess the effects of olanzapine, as monotherapy or adjunctive treatment, in preventing manic, depressive and mixed episodes in patients with bipolar affective disorder.. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (September 2006), the Cochrane Central Register of Controlled Trials (September 2006), MEDLINE (1966-December 2007), EMBASE (1980-2006), CINAHL (1982-2006), PsycINFO (1872-2006) and reference lists. We also contacted experts, trialists and pharmaceutical companies in the field.. Randomised controlled trials comparing olanzapine with placebo or other active treatment in long-term treatment of bipolar disorder.. Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information.. Five trials (1165 participants) were included in the review. There was no statistically significant difference between olanzapine and placebo (either alone or in combination with lithium or valproate) in terms of number of participants who experienced relapse into mood episode (random effects RR 0.68, 95% CI 0.43 to 1.07, p = 0.09; 2 studies, n=460), however restricting the analysis to the trial that compared olanzapine monotherapy versus placebo, there was a statistically significant difference in favour of olanzapine (RR 0.58, 95% CI 0.49 to 0.69, p<0.00001). No statistically significant difference was found between olanzapine and other mood stabilisers (lithium or valproate) in preventing symptomatic relapse for any mood episode, however, olanzapine was more effective than lithium in preventing symptomatic manic relapse (RR 0.59, 95% CI 0.39 to 0.89, p = 0.01; 1 study, n=361). Olanzapine either alone or as adjunctive treatment to mood stabilisers was associated with significantly greater weight gain than placebo. By contrast, olanzapine was associated with a lower rate of manic worsening, but with a higher rate of weight increase and depression than lithium.. Though based on a limited amount of information, there is evidence that olanzapine may prevent further mood episodes in patients who have responded to olanzapine during an index manic or mixed episode and who have not previously had a satisfactory response to lithium or valproate. However, notwithstanding these positive results, the current evidence is stronger for lithium as first line maintenance treatment of bipolar disorder.

Topics: Antimanic Agents; Benzodiazepines; Bipolar Disorder; Humans; Lithium Compounds; Olanzapine; Randomized Controlled Trials as Topic; Recurrence; Valproic Acid

To retrospectively examine published cases of neuroleptic malignant syndrome (NMS) in patients aged 18 and below who had been treated with atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole).. Information was collected via MEDLINE searches in February 2006 and May 2007. The term neuroleptic malignant syndrome was used and cross-referenced with individual atypical antipsychotics. The authors also contacted (by telephone and in writing) pharmaceutical companies that produce and market atypical antipsychotics for any data on NMS.. Twenty case reports (written in English only and published from 1991-2007) were identified and reviewed. These publications all described symptoms of NMS in patients aged 18 or younger who had been treated with atypical antipsychotics.. Data were reviewed and compared with 3 diagnostic criteria (DSM-IV-TR, Levenson's, and Caroff and Mann's) for NMS. Interventions and outcomes were also reviewed.. Twenty case reports were identified and presented with a descriptive approach. Sixteen cases met criteria for NMS, with at least 1 of the diagnostic sets utilized. The majority of cases involved male subjects. All patients recovered.. Young patients can develop NMS during treatment with atypical antipsychotics. Symptoms of this disorder are consistent with those described in adults. Although NMS is rare in this population, clinicians should maintain a high index of suspicion. Appropriate caution in treating children and adolescents with any antipsychotic is warranted.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Child; Child, Preschool; Clozapine; Dibenzothiazepines; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Thiazoles

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Humans; Olanzapine; Receptors, Adrenergic; Receptors, Dopamine; Receptors, Serotonin; Schizophrenia; Secondary Prevention; Weight Gain

Medication nonadherence, especially in psychiatric disorders, has been associated with treatment failure and other negative outcomes. Orally disintegrating formulations have been developed as an alternative to improve medication adherence. This report reviews the properties, efficacy, and safety profile of olanzapine as an orally disintegrating tablet, and explores their association with medication compliance compared with standard oral formulation. Medical literature, published on orally disintegrating formulation of olanzapine identified using Pubmed and EMBASE, was used. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug. Studies evaluating the biostability, biodisposability, pharmacokinetics, efficacy, and safety of orally disintegrating olanzapine as treatment of patients with psychiatric disorders were reviewed. Measurement tools included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale, and Nursing Assessment of Medication Acceptance (NAMA). Orally disintegrating olanzapine, an effective atypical antipsychotic with an acceptable safety profile, can facilitate the burden of treatment on patients and caregivers due to its ease of administration. This is especially important in diseases such as schizophrenia and bipolar disorder, which can be chronic and require long-term treatment.

Topics: Administration, Oral; Antipsychotic Agents; Benzodiazepines; Biological Availability; Bipolar Disorder; Chemistry, Pharmaceutical; Drug Delivery Systems; Humans; Olanzapine; Outcome Assessment, Health Care; Patient Compliance; Schizophrenia; Solubility; Tablets

Individuals with bipolar disorder are euthymic approximately half of the time, but recurring mood episodes are common, and time spent ill is predominated by depressive symptoms. Despite the prevalence of depression in bipolar disorder, evidence suggests that antidepressants are not likely to benefit most patients. Lithium, long considered a first-line treatment for bipolar disorder, is not the most effective agent for preventing bipolar depression. This article reviews multiple pharmacologic options that should be considered by clinicians treating bipolar disorder in both acute and maintenance phases.

Topics: Acute Disease; Adverse Drug Reaction Reporting Systems; Affect; Anticonvulsants; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Differential; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluoxetine; Humans; Lithium Carbonate; Long-Term Care; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; United States; United States Food and Drug Administration

This study compared the sensitivity and tolerability of antipsychotics in patients with bipolar disorder or schizophrenia.. English-language literature from January 1966 to December 2006 cited in MEDLINE was searched for the terms antipsychotics, typical antipsychotics, atypical antipsychotic, generic and brand names of antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, and bipolar mania, bipolar depression, bipolar disorder, manic-depressive illness, or schizophrenia, randomized, double blind, and controlled clinical trial.. Randomized, double-blind, placebo-controlled, monotherapy studies of anti-psychotics in both bipolar disorder and schizophrenia were prioritized.. Absolute risk increase (ARI) or reduction (ARR) and the numbers needed to treat to harm (NNTH) or benefit (NNTB) for the discontinuation due to adverse events and somnolence relative to placebo were estimated.. Ten acute trials in mania, 3 in bipolar depression, and 8 in schizophrenia were identified, along with 2 maintenance studies in bipolar disorder and 2 in schizophrenia. In schizophrenia, ziprasidone caused significantly more discontinuations due to adverse events than placebo, with an NNTH of 19, while aripiprazole caused significantly fewer discontinuations due to adverse events than placebo, with an NNTB of 12. In mania, there was no statistically significant difference in discontinuation due to adverse events between antipsychotics and placebo. However, in bipolar depression, both quetiapine and olanzapine caused more discontinuations due to adverse events than placebo, with NNTHs of 7 and 24, respectively. All atypical antipsychotics caused a significantly greater incidence of somnolence than placebo in mania and depression, with NNTHs from 5 to 8 for mania and 2 to 6 for depression. In schizophrenia, only olanzapine, ziprasidone, and aripiprazole (NNTHs from 5 to 14) caused a significantly higher incidence of somnolence. There was no significant difference between schizophrenia and mania in the discontinuation due to adverse events or somnolence of all studied antipsychotics. However, there was a significantly higher incidence of discontinuation due to adverse events and somnolence caused by quetiapine in bipolar depression than that in schizophrenia or mania.. Patients with bipolar disorder appear more sensitive to antipsychotics, and depressed patients are less tolerant to somnolence than those with either mania or schizophrenia.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Sleep Stages; Thiazoles; Treatment Outcome

The second-generation antipsychotic olanzapine has been shown to be efficacious as a treatment for adults with bipolar disorder and is approved by the United States Food and Drug Administration for the treatment of acute manic or mixed episodes as well as for maintenance treatment in bipolar adults.. This review examines the use of olanzapine for the treatment of children and adolescents with bipolar disorder and presents a discussion of the mechanism of action, pharmacokinetic and pharmacodynamic properties of olanzapine in children and adolescents. In addition, efficacy and safety data are reviewed and the risks and benefits of using olanzapine in bipolar youth are summarized.. Articles published in English were identified using a search of the National Library of Medicine from 1990 to 2007 with manual review of references of each article as well as review of the US Clinical Trials database. Articles describing the use of olanzapine in children or adolescents were included.. Olanzapine appears to have a rapid onset of action for mixed and manic episodes, but is associated with metabolic side effects including hyperprolactinemia, diabetes and weight gain. Therefore, olanzapine may best be used in the acute treatment of children and adolescents experiencing a manic or mixed episode as its side-effect profile may limit its use as a maintenance agent in this population.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Diabetes Mellitus; Humans; Hyperprolactinemia; Olanzapine; Weight Gain

This study aimed to compare the treatment responses between smokers and non-smokers in bipolar mania clinical trials.. Post-hoc analysis was conducted on data collected from three double-blind, randomised controlled trials in bipolar mania that had similar inclusion criteria. Patients were randomised to olanzapine (N=70) or placebo (N=69) for 3 weeks in Trial 1, olanzapine (N=234) or haloperidol (N=216) for 12 weeks in Trial 2, and olanzapine (N=125) or divalproex (N=126) for 47 weeks in Trial 3. This study analysed the Young Mania Rating Scale (YMRS) total scores and Clinical Global Impressions scale for bipolar disorder (CGI-BP) mania severity scores between smokers and non-smokers for each trial and for the pooled data from all three trials, using a mixed-effects model repeated measures approach.. For the pooled data, non-smokers showed superior treatment outcomes on both the YMRS (P=0.002) and CGI-BP (P<0.001), as well as longer time to discontinuation for any cause utilising Kaplan-Meier survival curves. For the individual trials, non-smokers showed greater improvement than smokers on both CGI-BP and YMRS in both treatment arms of Trial 2 (CGI-BP: haloperidol P=0.011, olanzapine P=0.042; YMRS: haloperidol P=0.010, olanzapine P=0.019), and in the olanzapine arm of Trial 3 (CGI-BP: P=0.002; YMRS: P=0.006). No significant difference in outcomes was found between smokers and non-smokers in Trial 1.. Post-hoc design, categorical definition of smoking status, unavailable antipsychotic drug levels, confounding effects of trial medications and substance abuse.. Smoking appears to be associated with worse treatment outcomes in mania.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Double-Blind Method; Female; Haloperidol; Humans; Least-Squares Analysis; Male; Meta-Analysis as Topic; Olanzapine; Placebos; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Severity of Illness Index; Smoking; Survival Analysis; Treatment Outcome; Valproic Acid

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

To determine the clinical effectiveness and cost-effectiveness of pharmacological and/or psychosocial interventions for the prevention of relapse in people with bipolar disorder.. Major electronic databases were searched up to September 2005.. Systematic reviews were undertaken on the clinical and economic effectiveness of treatments. An analysis was performed using the methods of mixed treatment comparison (MTC) to enable indirect comparisons to be made between the treatments. An economic model of treatments for the prevention of relapse in bipolar disorder was developed.. Forty-five trials were included in the clinical effectiveness review; all but one studied adults. This review found that for the prevention of all relapses, lithium, valproate, lamotrigine and olanzapine performed better than placebo, with lithium and lamotrigine having the strongest evidence. For depressive relapse prevention, valproate, lamotrigine and imipramine performed better than placebo, with evidence strongest for lamotrigine and weakest for imipramine. For manic relapses, lithium and olanzapine performed significantly better than placebo. The MTC found that the best treatment for bipolar I patients with mainly depressive symptoms was valproate, followed by lithium plus imipramine. For bipolar I patients with mainly manic symptoms, olanzapine was the best treatment. From the studies investigating psychosocial interventions, there were few data for each comparison and outcome. The evidence suggests that cognitive behaviour therapy (CBT), in combination with usual treatment, is effective for the prevention of relapse. Group psychoeducation and possibly family therapy may also have roles as adjunctive therapy for preventing relapse. The results from the decision analytic model developed on the cost-effectiveness of long-term maintenance treatments of bipolar I patients suggest that the choice of treatment is dependent upon a number of factors: the previous episode history of a patient and the mortality benefit assumed for lithium strategies. The results from the base-case analysis for patients with a recent history of depression suggest that valproate, lithium and the combination of lithium and imipramine are potentially cost-effective depending upon the amount that a decision-maker is willing to pay for additional health gain. Using conventional amounts that the NHS is prepared to pay for health gain, then the lithium-based strategies appear to be potentially cost-effective for this group. For patients with a recent history of mania, the choice of pharmacological intervention appears to be between olanzapine and lithium monotherapy. Again using conventional threshold as a reference point, the results suggest that lithium is the most cost-effective therapy. Excluding the additional mortality benefit associated with lithium-based strategies resulted in all treatments for patients with a recent history of a depressive episode being dominated by valproate and, in the case of patients with a recent history of a manic episode, by olanzapine.. Lithium, valproate, lamotrigine and olanzapine are effective as maintenance therapy for the prevention of relapse in bipolar disorder. Olanzapine and lithium are efficacious for the prevention of manic relapses and valproate, lamotrigine and imipramine for the prevention of depressive relapse. There is some evidence that CBT, group psychoeducation and family therapy might be beneficial as adjuncts to pharmacological maintenance treatments. Insufficient information is available regarding the relative tolerability of the treatments or their relative effects on suicide rate and mortality. For patients with a recent depressive episode, valproate, lithium monotherapy and the combination of lithium and imipramine are potentially cost-effective. For patients with a recent manic episode, olanzapine and lithium monotherapy are potentially cost-effective. The cost-effectiveness estimates in both groups of patients were shown to be sensitive to the assumption of a reduced suicidal risk associated with lithium-based strategies. Further research is needed into the adverse effects of all treatments and the differential effects of agents. Good-quality trials of valproate, of combination therapy, e.g. lithium plus a selective serotonin reuptake inhibitor antidepressant, of psychosocial interventions and of the disorder in children are also required.

Topics: Adult; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Cognitive Behavioral Therapy; Cost-Benefit Analysis; Databases, Bibliographic; Female; Humans; Lamotrigine; Lithium; Male; Models, Economic; Olanzapine; Outcome and Process Assessment, Health Care; Randomized Controlled Trials as Topic; Secondary Prevention; Triazines; Valproic Acid

The decision to stay with a treatment or switch to a different one depends on the balance between overall effectiveness, efficacy, and tolerability. One of the challenges with antipsychotic medication treatment of serious mental illness is the risk of weight gain, which can be considerable for some patients. This article reviews the issue of weight gain associated with antipsychotics and places it within the context of metabolic issues in general. The concept of "number needed to treat" is introduced to interpret the results of the Clinical Antipsychotic Trials of Intervention Effectiveness for schizophrenia, particularly to examine the balance between overall effectiveness, efficacy, and tolerability of the different antipsychotic treatments tested. Predictors of weight gain for olanzapine are reviewed for schizophrenia and bipolar disorder, as is a monitoring plan applicable for all patients receiving antipsychotic therapy.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Schizophrenia; Weight Gain

Management of bipolar disorder (BPD) may require multiple medications, including lithium, anticonvulsants, and antipsychotics (both conventional and atypical). Updated treatment guidelines reflect an expanded role for atypical antipsychotics (AAPs) in BPD treatment. Five AAPs--olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole--are approved by the US Food and Drug Administration (FDA) as monotherapy for first-line treatment of acute manic and (except for quetiapine) mixed episodes. Two AAPs--olanzapine (in fixed-dose combination with fluoxetine) and quetiapine--are also FDA approved for bipolar depression. For long-term maintenance therapy, one option is to continue effective, well-tolerated acute phase treatment; however, only olanzapine and aripiprazole are FDA approved for maintenance, based on evidence from randomized, placebo-controlled clinical trials. Although head-to-head comparisons are scarce, meta-analysis data suggest that olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole have similar antimanic efficacy; therefore, AAP selection for this indication should be guided by other considerations such as safety, tolerability, and cost. Safety and tolerability issues to consider when selecting an AAP include metabolic dysfunction (weight gain, type 2 diabetes, and dyslipidemia); hyperprolactinemia; extrapyramidal symptoms; QTc prolongation; and pharmacokinetic drug interactions.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome; Weight Gain

The term "mood stabilizer" has been widely used since the early 1990's but it still does not have a uniform and generally accepted definition. Usually, agents that are effective in ameliorating acute manic or depressive episodes and have some prophylactic efficacy against the recurrence of new phases are considered as mood stabilizers. Lithium is unquestionably the prototype drug of this class; others, like some anticonvulsants, have been subsequently added to the list. Recent clinical research indicates that some of the newer second-generation antipsychotics may have very similar properties. In controlled clinical studies of acute manic and mixed episodes, olanzapine has proved to be at least as effective as lithium, divalproex, or haloperidol - often with additional benefits, such as faster onset of action, or wider spectrum of target symptoms. Added to mood stabilizers, olanzapine significantly enhances their antimanic efficacy. It also has intrinsic antidepressant properties; and in combination with fluoxetine, this has resulted in convincing efficacy in bipolar depressive episodes. Long-term maintenance treatment with olanzapine has extended the periods of remission and shown prophylactic efficacy against the recurrence of both manic and depressive episodes that is comparable or, in the case of preventing manic relapses, even superior to lithium. While none of the current agents meet the most stringent criteria for an "ideal" mood stabilizer, there is strong evidence that olanzapine, just like lithium, is effective across all phases of bipolar disorder without provoking either manic or depressive symptomatology. Regardless of formal definition criteria, this is exactly what clinicians expect of a dependable mood stabilizer.

Topics: Affect; Antidepressive Agents, Second-Generation; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Fluoxetine; Humans; Lithium Compounds; Olanzapine; Selective Serotonin Reuptake Inhibitors

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

Bipolar depression remains one of the most difficult to treat of all mental disorders. Until recently, no treatments, including antidepressants, have consistently shown to be effective in this condition. Olanzapine, an atypical antipsychotic, has been approved by the US Food and Drug Administration for the acute treatment of mania and maintenance prevention of relapse into depression or mania. A clinical trial tested the relative effectiveness of the combination of olanzapine and fluoxetine in bipolar type I depression, against olanzapine alone or placebo. The combination produced a very robust clinical effect acutely and a long-term follow-up study indicated that there was a low rate of induction of mania or mixed states. Therefore, the olanzapine/fluoxetine combination represents a viable alternative for bipolar depression. However, uptake of this combined product in practice has been modest. This is likely to be the result of several factors, including resistance to the use of fixed combination preparations and, more recently, evidence of effectiveness of the atypical quetiapine and the anticonvulsant lamotrigine. Perhaps the greatest resistance to the use of olanzapine alone or in combination has been the problem of weight gain and the attendant risk of type 2 diabetes and the metabolic syndrome. Vigorous management of this problem has been shown to mitigate the potential for weight gain and is required if this combination is to be used. However, many clinicians find management of weight gain in olanzapine treated patients a challenge. In addition, weight, waist circumference, lipids and glucose should be monitored.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Expert Testimony; Fluoxetine; Humans; Olanzapine

Second generation antipsychotic agents are increasingly used in the management of acute mania. A systematic review of the efficacy and safety of these agents, as both monotherapy and in combination with mood stabilisers, was performed to establish the evidence for their use. Randomised controlled trials (RCTs) were critically appraised in more detail than studies that presented lower levels of evidence such as case reports, case series and open label follow up studies. We found 11 RCTs reporting on patients treated with second generation antipsychotics for acute bipolar mania, of which three included randomisation between the second generation antipsychotic and placebo, and eight between a mood stabiliser combined with either the second generation antipsychotic or placebo. Data from non-randomised trials is also presented.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

Olanzapin is an atypical antipsychotic drug, which is approved for use in acute mania and in the prophylaxis of bipolar disorder. There are eight double-blind, placebo-controlled studies, which show its efficacy in the treatment of acute mania, five, which document its efficacy in the long-term treatment of bipolar disorder and one that shows its use in bipolar depression. The following overview presents and critically evaluates these studies. Quality of life aspects on olanzapine treatment and the safety profile of the drug will also be discussed.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Biological Availability; Bipolar Disorder; Brain; Clinical Trials as Topic; Controlled Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Humans; Olanzapine; Quality of Life; Treatment Outcome

Mixed episodes comprise up to 40 % of acute bipolar admissions. They are difficult-to-treat, complex clinical pictures. This review provides an overview of the available literature on the pharmacotherapy of manic-depressive mixed states and suggests treatment options.. Literature was identified by searches in Medline, Embase and the Cochrane Controlled Trials Register. Studies were considered relevant if they contained the keywords mixed mania, mixed state (s), mixed episode (s), treatment, therapy, study or trial.. Overall, there were very few double-blind, placebo-controlled studies specifically designed to treat manic-depressive mixed states. Rather, patients with mixed states comprised a subgroup of the examined patient cohorts. Nevertheless, the data show that acute mixed states do not respond favourably to lithium. Instead, valproate and olanzapine are drugs of first choice. Carbamazepine may play a role in the prevention of mixed states. Antidepressants should be avoided, because they may worsen intraepisodic mood lability. Lamotrigine may be useful in treating mixed states with predominantly depressive symptoms.. More treatment studies specifically designed to treat the complex clinical picture of mixed states are clearly needed. Current treatment recommendations for clinical practice based on the available literature can only target selected aspects of these episodes.

Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Controlled Clinical Trials as Topic; Drug Therapy, Combination; Humans; Lithium Carbonate; Olanzapine; Practice Guidelines as Topic; Treatment Outcome; Valproic Acid

This review describes the pharmacological characteristics of olanzapine (ZYPREXA), outlines the European licensed indications and examines four peer reviewed, randomized, controlled, double blind clinical trials investigating the efficacy of olanzapine as maintenance therapy in patients with bipolar I disorder. These studies range in duration from 47 to 78 weeks and support the view that olanzapine is an effective and well-tolerated pharmacological therapy for relapse prevention in bipolar disorder. Evidence is presented that olanzapine is effective in preventing relapse following an index manic or a mixed episode with or without psychotic features and in patients with a history of rapid cycling. The safety and tolerability of the medicine is also examined, focusing on weight gain and metabolic issues.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Long-Term Care; Olanzapine; Randomized Controlled Trials as Topic; Secondary Prevention

Antipsychotic agents have long had a place in the clinical treatment of bipolar disorder, in both acute and maintenance phases. Recent clinical research conducted with the new generation of antipsychotic agents has contributed enormously to the data available on antipsychotic agents in bipolar disorder. Even now, however, the clinical trial data relates principally to the short-term treatment of acute mania. With the exception of recent data generated during the clinical trial programme for olanzapine, studies of maintenance treatment, conducted with antipsychotic agents, both established and newly-introduced, have generally been small and prone to methodological weakness. As a result, many important clinical questions, concerning the utility of antipsychotic agents in bipolar maintenance, can not be answered by reference to the data. Taken together, the findings of the clinical trials in bipolar maintenance, conducted with antipsychotic agents other than olanzapine, can be regarded only as tentative. As was conducted with olanzapine, larger, more rigorously designed studies are required to provide definitive evidence of efficacy in longer-term treatment. Due to the logistical complexity and expense of these sorts of study, it is likely that, for many antipsychotic agents with a potential role in long-term treatment in bipolar disorder, the definitive studies will never be undertaken.

Topics: Adverse Drug Reaction Reporting Systems; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Evidence-Based Medicine; Humans; Long-Term Care; Olanzapine; Randomized Controlled Trials as Topic; Secondary Prevention

Olanzapine is a novel antipsychotic, approved for the acute and maintenance treatment of schizophrenia and bipolar I disorder. Despite the publicity regarding reported adverse events with the novel antipsychotics, such as weight gain and Type II diabetes mellitus, olanzapine remains a useful and important medicine. It is a selective monoaminergic antagonist with high-affinity binding to a number of receptors thought to be implicated in some psychotic and mood symptoms. The complex pharmacology of olanzapine has lead to studies exploring its use in treating substance abuse, aggression/violence, borderline personality disorder, schizotypal personality disorder, obsessive-compulsive disorder and as a neuroprotective agent in schizophrenia. As the pharmacology of olanzapine and other novel antipsychotics becomes better understood, future effective treatment strategies are likely to match an individual's genetic makeup and receptor profiles to the most compatible agent.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Schizophrenia

The main objectives in treating mania are to control dangerous behaviour, reduce suicide, produce appropriate acute sedation and shorten the episode of mood disturbance. Among different drugs, haloperidol has for many years been used in treating psychotic patients, but it has a troublesome side effect profile.. To assess the effects of haloperidol for the treatment of mania in comparison with placebo or other active drugs, either as monotherapy or add-on treatment.. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (11 October 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (1966-2003), EMBASE (1980-2003), CINAHL (1982-2003), PsycINFO (1872-2003) and reference lists. We also contacted experts, triallists and pharmaceutical companies in the field.. Randomised trials comparing haloperidol with placebo or other active treatment in the treatment of acute manic or mixed episodes in patients with bipolar disorder or schizoaffective disorder.. Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We collected adverse effects information from the trials.. Fifteen trials involving 2022 people were included. Compared to placebo, haloperidol was more effective at reducing manic symptoms, both as monotherapy (Weighted Mean Difference (WMD) -5.85, 95% Confidence Interval (CI) -7.69 to -4.00) and as adjunctive treatment to lithium or valproate (WMD -5.20, 95% CI -9.26 to -1.14). There was a statistically significant difference, with haloperidol being less effective than aripiprazole (Relative Risk (RR) 1.45, 95% CI 1.22 to 1.73). No significant differences between haloperidol and risperidone, olanzapine, carbamazepine or valproate were found. Compared with placebo, a statistically significant difference in favour of haloperidol in failure to complete treatment (RR 0.74, 95% Cl 0.57 to 0.96) was reported. Haloperidol was associated with less weight gain than olanzapine (RR: 0.28, 95% CI 0.12 to 0.67), but with a higher incidence of tremor (RR: 3.01, 95% CI 1.55 to 5.84) and other movement disorders.. There is some evidence that haloperidol is an effective treatment for acute mania. From the limited data available, there was no difference in overall efficacy of treatment between haloperidol and olanzapine or risperidone. Some evidence suggests that haloperidol could be less effective than aripiprazole. Referring to tolerability, when considering the poor evidence comparing drugs, clinicians and patients should consider different side effect profiles as an important issue to inform their choice.

Topics: Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Dibenzothiazepines; Drug Therapy, Combination; Haloperidol; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Sulpiride; Valproic Acid

Bipolar disorder is a chronic disease that may require lifetime treatment. The maintenance therapy of bipolar disorder can be challenging for the treating clinician. Currently, according to the American Psychiatric Association (APA) guidelines, lithium, valproic acid, lamotrigine, carbamazepine, oxcarbazepine, and the antipsychotics are recommended for the maintenance treatment of bipolar disorder. The antipsychotics are recommended to be continued only if the clinician decides that they are necessary for the control of persistent psychosis or for prophylaxis against recurrence. Although the APA guidelines provide sufficient evidence for the use of these mood stabilizers, newer drugs such as the atypical antipsychotics are being investigated for use in the maintenance phase of treatment of bipolar disorder.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Drug Costs; Humans; Olanzapine; Piperazines; Practice Guidelines as Topic; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Thiazoles; United States

The authors review available controlled trials of bipolar maintenance treatment and discuss the strengths and weaknesses of various study designs. Bipolar maintenance trials are organized according to the features of their designs, such as use of responder-enriched samples; inclusion following an index manic versus an index depressive episode; outcome defined as relapse into mania, depression, or either; and use of survival analysis. Pivotal studies of lithium, divalproex, lamotrigine, olanzapine, aripiprazole, and other medications are reviewed. The directional efficacy of the different medications as maintenance treatment is discussed, with treatments differentiated in terms of whether they primarily prolong time to mania or to depression or have bidirectional effects. Also discussed are findings concerning the continuation of acute treatments, including antidepressants, into the maintenance phase; dosage adjustments for maintenance treatment; the rationale for combination treatments; and implications of comorbid substance abuse and strategies for its management. Directions for future research are suggested.

Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Evidence-Based Medicine; Humans; Lamotrigine; Lithium Carbonate; Olanzapine; Piperazines; Quinolones; Triazines; Valproic Acid

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

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

Bipolar disorder is often misdiagnosed as major depressive disorder because of the high frequency of depressive symptomatology in many patients with bipolar disorder. Depressive episodes that are resistant to treatment may also be associated with a worse course of illness in bipolar disorder, but we do not yet understand all the factors in the connection between bipolar disorder and depression. The data on the effectiveness of antidepressants in the treatment of depression in bipolar disorder vary greatly, and there have been few prospective, randomized studies on the subject. From the data so far, the rates of induction of mania for selective serotonin reuptake inhibitors and lamotrigine seem similar to those seen with placebo. The optimal length of time to continue antidepressant treatment in patients with bipolar disorder has not yet been determined; however, research tends to indicate that a longer term of treatment (6 months or more) may aid in the prevention of relapse. Newer U.S. Food and Drug Administration-approved treatments for depression in bipolar disorder include a combination of olanzapine and fluoxetine, which is used for depressive episodes in bipolar disorder, and lamotrigine, which is used for maintenance treatment of bipolar I disorder. Psychoeducation has also been examined as a possible treatment for depression in bipolar disorder, and a study has shown that patients receiving psychoeducation plus medication may have a lower rate of relapse than patients who receive medication alone.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Drug Therapy, Combination; Fluoxetine; Humans; Lamotrigine; Olanzapine; Patient Education as Topic; Psychotherapy; Psychotherapy, Group; Secondary Prevention; Survival Analysis; Triazines

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

Women are not the same as men. While this observation can be considered to subjectively manifest in many different ways, objectively a greater tendency for bipolar II disorder, depressive symptoms, a rapid cycling course, and the consequences of being of child-rearing age can all represent additional challenges for female patients. Despite much recent interest in improving the management of patients with bipolar disorder, relatively little guidance exists relating to female-biased gender-specific issues. This review article will explore how female gender can influence bipolar disorder and its treatment and will focus on epidemiologic differences, the relevance to clinical presentation of events unique to women (particularly contraception, pregnancy, and lactation), and the importance of considering gender when making decisions about the pharmacological management of mood. All female patients should receive counseling regarding family planning and sexually transmitted diseases, as well as the risks of and treatment options during pregnancy and postpartum. Wherever possible, treatment choices should be made in a partnership between patient and clinician.

Topics: Anticonvulsants; Antidepressive Agents; Benzodiazepines; Bipolar Disorder; Counseling; Dibenzothiazepines; Family Planning Services; Female; Humans; Lamotrigine; Lithium Carbonate; Male; Olanzapine; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Risperidone; Teratogens; Triazines; Valproic Acid; Women's Health

As the phenomenology of pediatric bipolar disorder has become better delineated, clinicians are now able to more accurately assess and treat young people suffering from this condition. For pediatric patients with bipolar I disorder and symptoms of mania, medication monotherapy has been shown to lead to symptom amelioration. However, this treatment modality oftentimes does not lead to full symptom remission. In an attempt to address this observation, combination treatment strategies have recently been investigated. Recently, a maintenance study has shown that in youths who achieved remission on a combination of lithium and divalproate therapy, either of these agents alone was equally effective as a treatment strategy. In youths identified as being at genetic high risk for bipolarity who also had problematic affective symptomatology, treatment with divalproate was not found to be superior to placebo; however, those with the greatest degree of genetic risk for familial psychopathology remained in the trial longer than those with more modest amounts of familial psychopathology. These data suggest that intervention in youths with only one affected parent may not be a rational prevention strategy for pharmacological intervention in bipolar disorder, and that cohorts more genetically at risk may be a more appropriate group for preventative pharmacotherapy.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Humans; Lithium Carbonate; Olanzapine; Prospective Studies; Randomized Controlled Trials as Topic; Valproic Acid

There are few controlled studies evaluating the treatment of bipolar mixed states. Evidence suggests that mixed states may be more responsive to some anticonvulsants than to lithium. Olanzapine alone or in combination with divalproate or lithium has been adequately evaluated in randomized clinical trials involving mixed-state patients, whereas risperidone and quetiapine have not. There is also some evidence demonstrating the efficacy of ziprasidone and aripiprazole. The risk of switching to depression is high in mixed states. Conventional antipsychotics, such as haloperidol, may be less efficacious at protecting against a switch to depression than atypical antipsychotics, divalproate or lithium. When choosing drugs for the treatment of mania, and especially for the treatment of mixed states, their efficacy against manic and depressive symptoms, and their safety in terms of the risk of switching to depression should be taken into account.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Electroconvulsive Therapy; Haloperidol; Health Education; Humans; Lithium Carbonate; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Thiazoles

Vieta E, Goikolea JM. Atypical antipsychotics: newer options for mania and maintenance therapy. Bipolar Disord 2005: 7 (Suppl. 4): 21-33. (c) Blackwell Munksgaard, 2005Atypical antipsychotics have been used to treat patients with schizophrenia for many years, but now there is increasing evidence of their utility in the treatment of bipolar disorder. In the past few years several atypical agents have received regulatory approval for use in bipolar mania. Through a review of randomized controlled trials for five commonly used atypical drugs, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole, this article evaluates their efficacy in the acute and maintenance phases of bipolar disorder. The evidence shows that atypical antipsychotics are effective in the treatment of manic symptoms, either alone or in combination with traditional mood stabilizers such as lithium and divalproex. Although emerging data indicate that atypical antipsychotics will be a promising addition to those therapies that are currently available for managing patients during the maintenance phase of bipolar illness, their potential in the long-term management of bipolar disorder remains to be fully explored. Atypical antipsychotics appear to have broadly similar efficacy against manic symptoms of bipolar disorder, but there are important differences in their tolerability profiles, which are likely to be of particular relevance during long-term treatment. A brief assessment of tolerability issues surrounding the use of atypical agents in bipolar disorder and other aspects of treatment that have impact on the clinical effectiveness of the therapy are considered.

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Humans; Lithium Carbonate; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

Since the previous publication of Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in evidence-based treatment options for bipolar disorder. The present guidelines review the new evidence and use criteria to rate strength of evidence and incorporate effectiveness, safety, and tolerability data to determine global clinical recommendations for treatment of various phases of bipolar disorder. The guidelines suggest that although pharmacotherapy forms the cornerstone of management, utilization of adjunctive psychosocial treatments and incorporation of chronic disease management model involving a healthcare team are required in providing optimal management for patients with bipolar disorder. Lithium, valproate and several atypical antipsychotics are first-line treatments for acute mania. Bipolar depression and mixed states are frequently associated with suicidal acts; therefore assessment for suicide should always be an integral part of managing any bipolar patient. Lithium, lamotrigine or various combinations of antidepressant and mood-stabilizing agents are first-line treatments for bipolar depression. First-line options in the maintenance treatment of bipolar disorder are lithium, lamotrigine, valproate and olanzapine. Historical and symptom profiles help with treatment selection. With the growing recognition of bipolar II disorders, it is anticipated that a larger body of evidence will become available to guide treatment of this common and disabling condition. These guidelines also discuss issues related to bipolar disorder in women and those with comorbidity and include a section on safety and monitoring.

Topics: Adolescent; Adult; Age of Onset; Anticonvulsants; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Canada; Chronic Disease; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Drug Monitoring; Female; Humans; Lamotrigine; Lithium Carbonate; Mass Screening; Mood Disorders; Olanzapine; Personality Disorders; Prevalence; Quality of Life; Risk Factors; Substance-Related Disorders; Triazines; Valproic Acid

Despite the considerable burden of bipolar depression, the treatment of this debilitating phase of bipolar disorder is suboptimally addressed by currently available pharmacologic options. Consequently, there is a need for the development of new treatment options with enhanced efficacy and tolerability. Evidence of antidepressant efficacy for some of the atypical antipsychotics in the treatment of bipolar depression has recently emerged. The findings of a large-scale, placebo-controlled, double-blind, randomized clinical study of olanzapine alone and in combination with fluoxetine, and a similar study of quetiapine monotherapy, suggest that some of the atypical antipsychotics may be efficacious in treating depressive symptoms in patients with bipolar I disorder. Subpopulation analyses suggest that quetiapine monotherapy and the olanzapine plus fluoxetine combination appear to be effective in treating depression in patients with a rapid-cycling course. The magnitude of improvement in depressive symptoms in the bipolar I population appears to be larger for quetiapine monotherapy compared with either olanzapine or olanzapine plus fluoxetine; however, the limitations of such a cross-study comparison are acknowledged. Both olanzapine monotherapy and combination therapy, as well as quetiapine monotherapy, were well tolerated. The overall incidence of treatment-emergent mania was low and comparable with placebo in both studies. Somnolence, weight gain, increased appetite and nonfasting glucose and cholesterol levels were more commonly reported in patients treated with olanzapine monotherapy or combination therapy compared with placebo. Dry mouth, sedation/somnolence, dizziness, and constipation were more commonly associated with quetiapine treatment. Large, controlled studies are needed to determine whether other psychotropic agents have antidepressant properties that would make them suitable for use in patients with bipolar depression. In addition, direct comparison of the regimens used in the current study should determine whether the differences evident between them can be confirmed.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

To assess the potential role of atypical antipsychotics as mood stabilizers.. A MedLine, PsychLIT, PubMed, and EMBASE literature search of papers published up to December 2004 was conducted using the names of atypical antipsychotics and a number of key terms relevant to bipolar disorder. Additional articles were retrieved by scrutinizing the bibliographies of review papers and literature known to the authors. Data pertinent to the objective was reviewed according to the various phases of bipolar disorder.. The data is most substantive for the use of atypical antipsychotics in mania, to the extent that an argument for a class effect of significant efficacy can be made. This does not extend to bipolar depression, however, good data is now emerging for some agents and will need to be considered for each individual agent as it accumulates. As regards mixed states and rapid cycling the evidence is thus far sparse and too few maintenance studies have been conducted to make any firm assertions. However, with respect to long-term therapy the atypical antipsychotics do have clinically significant side-effects of which clinicians need to be aware.. Based on the evidence thus far it is perhaps premature to describe the atypical antipsychotics as mood stabilizers. Individual agents may eventually be able to claim this label, however, much further research is needed especially with respect to maintenance and relapse prevention.

Topics: Affect; Amisulpride; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Randomized Controlled Trials as Topic; Risperidone; Secondary Prevention; Sulpiride; Thiazoles

Clinical guidelines for treatment and research of bipolar disorder greatly benefit from the synthesis of data from individual studies. The British Association for Psychopharmacology bases its guidelines on evidence from opinions (level D) to systematic reviews of primary trial data (level A). The report details conclusions of its 1-day consensus meeting to develop guidelines covering diagnosis, clinical management, pharmacotherapy for acute episodes, relapse prevention and treatment discontinuation. Monotherapy for long-term management is preferred, having reduced side-effects and drug interactions and improved compliance. Combination therapy is often preferred for acute episodes, using antipsychotics for mania or antidepressants for depression. Increased efficacy may be attributed to multiple mechanisms of action and potentially lower doses. In clinical practice, maintenance monotherapy has limited success for chronic episodes and polypharmacy is frequently used, though the best combination remains unclear. A new collaborative approach based on simple clinical trials is required to change current medical practice.

Topics: Antimanic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Humans; Olanzapine; Patient Compliance; Secondary Prevention; Treatment Outcome

Topics: Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Cognitive Behavioral Therapy; Humans; Lithium Carbonate; Olanzapine; Piperazines; Thiazoles; Valproic Acid

During recent years there has been a dramatic increase in the use of psychotropic medication for the treatment of bipolar disorder (BPD) in children. There is an emerging set of data to support this use.Mood stabilizers, including lithium and valproic acid (valproate sodium), have generally formed the mainstay of treatment in children and adolescents with BPD. However, the atypical antipsychotics, such as risperidone, aripiprazole, and quetiapine may be more effective as first-line treatment options and in some ways easier to use than the traditional mood stabilizers. As in adults, mood stabilization is often difficult to achieve in pediatric patients with BPD, and combined treatment with mood stabilizers and atypical antipscyhotics is commonly used. Data from controlled trials of psychotropic medications in children and adolescents with BPD are very limited, and hence, in the majority of cases physicians base their treatment decisions on data from case reports, case series, or open trials. More controlled studies of both monotherapy and polypharmacotherapy for BPD in children and adolescents are needed.

Topics: Adolescent; Benzodiazepines; Bipolar Disorder; Carbamazepine; Child; Clozapine; Dibenzothiazepines; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Risperidone; Valproic Acid

Depressive symptoms of bipolar disorder have more negative impact on a patient's life than manic symptoms. This review focused on the emerging efficacy data for treatments in bipolar depression.. English-language literature cited in Medline was searched with terms bipolar depression, clinical trial, and trial. Randomized, placebo-controlled trials of newer studies with older agents and all studies with newer or novel agents were prioritized. Open-label studies of novel agents presented at major scientific meetings were also included.. Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were superior to placebo in the acute treatment of bipolar depression. Lamotrigine only significantly reduced core symptoms of depression compared with placebo. Pramipexole, a dopamine D2/D3 receptor agonist and omega-3 fatty acids, a polyunsaturated fatty acid, augmentation to mood stabilizer (MS) had superiority to placebo in reducing depressive symptoms. Topiramate augmentation of an MS was equally as effective as Bupropion-SR. Patients treated with an MS responded well to the addition of agomelatine, a melatonin receptor agonist with 5-HT2C antagonist properties. However, inositol and repetitive transcranial magnetic stimulation did not separate from placebo. Lamotrigine and olanzapine, and to a lesser extent, divalproex, are superior to placebo in preventing depressive relapses. All agents were relatively well tolerated.. Olanzapine, OFC, and quetiapine are effective in the acute treatment of bipolar depression. Compared with lithium and divalproex, lamotrigine is more effective in preventing bipolar depression. Larger controlled studies of the other agents in the acute and maintenance treatment of bipolar depression are warranted.

Topics: Acetamides; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Dopamine Agonists; Drug Therapy, Combination; Humans; Hypnotics and Sedatives; Lamotrigine; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Secondary Prevention; Transcranial Magnetic Stimulation; Triazines

Symptomatic bipolar patients experience more depressive than manic symptoms, but fewer studies have been designed for bipolar depression than for bipolar mania. Since the antipsychotic agents have been shown to diminish depressive symptoms during the treatment of mania, atypical agents are now being studied for use in bipolar depression.. English-language articles published from 1980 through July 2004 and cited in MEDLINE were searched using the keywords antipsychotics, typical antipsychotics, atypical antipsychotics, bipolar depression, bipolar disorder, manic-depressive illness, placebo, and clinical trial. The generic and brand names of individual antipsychotics were also entered as keywords. Peer-reviewed abstracts of placebo-controlled studies assessing acute or long-term efficacy in bipolar depression presented at major scientific meetings were also reviewed.. Use of a depression rating scale was required for inclusion of studies of the atypical antipsychotic agents in our analysis.. Twenty-one randomized trials and 13 nonrandomized prospective trials were identified. In the only 2 acute, double-blind, placebo-controlled studies of antipsychotics in bipolar depression, the effect size of olanzapine was small (0.32) compared with the effect sizes of quetiapine (0.91-1.09, depending on dose). The effect size in acute mania of olanzapine at week 4 and quetiapine at week 3 was 0.50 and 0.39, respectively. Both olanzapine and quetiapine have been shown to be superior to placebo in the acute treatment of bipolar I depression. In addition, olanzapine has been shown to be more effective than placebo in delaying relapse into bipolar depression. With the exception of a 6-month perphenazine study, there are no other randomized studies of typical antipsychotics that support the conclusion that this class of medication worsens bipolar depression.. Emerging data suggest that the atypical antipsychotic agents have a role in the acute and long-term treatment of bipolar depression. No convincing data support the impression that the typical antipsychotic agents worsen bipolar depression.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Dopamine D2 Receptor Antagonists; Double-Blind Method; Drug Administration Schedule; Humans; Olanzapine; Placebos; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risperidone; Severity of Illness Index; Treatment Outcome

We sought to develop and validate an excitement subscale from the Positive and Negative Syndrome Scale (PANSS) to allow the investigation of mania-like excitement symptoms in clinical trials of patients with schizophrenia using the PANSS and to provide clinicians with a short assessment tool for these states.. Baseline PANSS data from six double-blind, randomized registration trials of olanzapine, three in schizophrenia and three in acute bipolar mania, were used in these post-hoc analyses. Schizophrenia study data were pooled and randomly split in half. Exploratory principal component factor analysis was performed on half of the data. Factors were extracted based on minimum eigenvalue criteria (eigenvalue> or =1); loadings were determined using an equamax rotation. Confirmatory principal component factor analysis was performed on the other half of the data, retaining the original number of factors. Principal component factor analysis was also done for the pooled bipolar studies. Change in the new mania-like factor scores was then correlated with Young Mania Rating Scale (Y-MRS) scores in each bipolar study.. Exploratory principal components analysis on the pooled schizophrenia data extracted five factors: negative, positive, excitement, cognitive, and depressive factors. The mania-like excitement factor was represented by four items (uncooperativeness, poor impulse control, excitement, and hostility), with only moderate loadings by tension and suspiciousness/persecution. Results were similar in the confirmatory analysis and the pooled bipolar studies. Change from baseline to endpoint for the mania-like factor correlated reasonably well (0.64-0.78) with change in Y-MRS scores in the bipolar studies. At baseline, bipolar patients scored higher than patients with schizophrenia on three of four PANSS mania-like factor items: poor impulse control, excitement, and hostility; the converse was true for most other PANSS items.. Factor analyses of the PANSS consistently uncovered an excitement factor including uncooperativeness, poor impulse control, excitement, and hostility items. This factor may be useful in examining manic symptoms in studies where the addition of a scale specific to mania would be burdensome and where symptoms of excitement are part of the clinical presentation.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Olanzapine; Principal Component Analysis; Psychiatric Status Rating Scales; Psychometrics; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology

Atypical antipsychotics offer superior safety and similar efficacy compared with conventional agents in adults with psychotic disorders. Consequently, atypical antipsychotics have been increasingly used in children and adolescents. Because most information now available on pediatric use comes from case reports and small open-label studies rather than large controlled trials, treatment in pediatric patients is often guided by experience with adults or based on limited evidence in youths. Although the literature contains reports on the use of each agent in this class in children, risperidone has been the focus of the greatest number of reports. However, the atypical antipsychotics are not interchangeable; each has a unique pharmacologic profile and may differ considerably in terms of adverse effects. Evidence on the use of atypical antipsychotics in children and adolescents is summarized in this review.

Topics: Adolescent; Age Factors; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Child; Child Development Disorders, Pervasive; Clozapine; Dibenzothiazepines; Humans; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Risperidone; Schizophrenia; Thiazoles; Tic Disorders

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

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

To evaluate the clinical and cost-effectiveness of quetiapine, olanzapine and valproate semisodium in the treatment of mania associated with bipolar disorder.. Electronic databases; industry submissions made to the National Institute for Clinical Excellence.. Randomised trials and economic evaluations that evaluated the effectiveness of quetiapine, olanzapine or valproate semisodium in the treatment of mania associated with bipolar disorder were selected for inclusion. Data were extracted by one reviewer into a Microsoft Access database and checked for quality and accuracy by a second. The quality of the cost-effectiveness studies was assessed using a checklist updated from that developed by Drummond and colleagues. Relative risk and mean difference data were presented as Forest plots but only pooled where this made sense clinically and statistically. Studies were grouped by drug and, within each drug, by comparator used. Chi-squared tests of heterogeneity were performed for the outcomes if pooling was indicated. A probabilistic model was developed to estimate costs from the perspective of the NHS, and health outcomes in terms of response rate, based on an improvement of at least 50% in a patient's baseline manic symptoms derived from an interview-based mania assessment scale. The model evaluated the cost-effectiveness of the alternative drugs when used as part of treatment for the acute manic episode only.. Eighteen randomised trials met the inclusion criteria. Aspects of three of the quetiapine studies were commercial-in-confidence. The quality of the included trials was limited and overall, key methodological criteria were not met in most trials. Quetiapine, olanzapine and valproate semisodium appear superior to placebo in reducing manic symptoms, but may cause side-effects. There appears to be little difference between these treatments and lithium in terms of effectiveness, but quetiapine is associated with somnolence and weight gain, whereas lithium is associated with tremor. Olanzapine as adjunct therapy to mood stabilisers may be more effective than placebo in reducing mania and improving global health, but it is associated with more dry mouth, somnolence, weight gain, increased appetite, tremor and speech disorder. There was little difference between these treatments and haloperidol in reducing mania, but haloperidol was associated with more extrapyramidal side-effects and negative implications for health-related quality of life. Intramuscular olanzapine and lorazepam were equally effective and safe in one very short (24 hour) trial. Valproate semisodium and carbamazepine were equally effective and safe in one small trial in children. Olanzapine may be more effective than valproate semisodium in reducing mania, but was associated with more dry mouth, increased appetite, oedema, somnolence, speech disorder, Parkinson-like symptoms and weight gain. Valproate semisodium was associated with more nausea than olanzapine. The results from the base-case analysis demonstrate that choice of optimal strategy is dependent on the maximum that the health service is prepared to pay per additional responder. For a figure of less than 7179 British pounds per additional responder, haloperidol is the optimal decision; for a spend in excess of this, it would be olanzapine. Under the most favourable scenario in relation to the costs of responders and non-responders beyond the 3-week period considered in the base-case analysis, the incremental cost-effectiveness ratio of olanzapine is reduced to 1236 British pounds.. In comparison with placebo, quetiapine, olanzapine and valproate semisodium appear superior in reducing manic symptoms, but all drugs are associated with adverse events. In comparison with lithium, no significant differences were found between the three drugs in terms of effectiveness, and all were associated with adverse events. Several limitations of the cost-effectiveness analysis exist, which inevitably means that the results should be treated with some caution. There remains a need for well-conducted, randomised, double-blind head-to-head comparisons of drugs used in the treatment of mania associated with bipolar disorder and their cost-effectiveness. Participant demographic, diagnostic characteristics, the treatment of mania in children, the use of adjunctive therapy and long-term safety issues in the elderly population, and acute and long-term treatment are also subjects for further study.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Valproic Acid

Because patients with major psychiatric illnesses increasingly are treated first--and sometimes exclusively--by primary care physicians, improved diagnostic skills and knowledge of treatment options are essential to improved patient outcomes and quality of life. This article reviews the incidence of bipolar disorder and burdens associated with misdiagnosis of the illness. It also emphasizes the evaluation and recognition of bipolar disorders to assist physicians in making accurate diagnoses, as well as reviewing the pharmacologic options used in treatment.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic Errors; Humans; Lamotrigine; Lithium; Olanzapine; Primary Health Care; Triazines; Valproic Acid

In interpreting the maintenance literature for bipolar disorder, attention needs to be paid to important methodological issues. In this article, we initially examine the methodological topics that need to be considered, and we then examine the content of the evidence regarding maintenance treatments. Agents used in the long-term treatment of bipolar disorder possess varying degrees of supportive evidence. By consensus, the number of randomized studies and years of clinical experience with lithium mark it as the evidentially strongest long-term agent for bipolar disorder. Recent studies also demonstrate likely long-term benefit with lamotrigine, and possibly olanzapine. Although we possess fewer randomized data, some such evidence exists and, along with clinical experience, supports the likely long-term utility of valproate in the treatment of bipolar disorder as well. Some psychotherapies also may possess adjunctive maintenance efficacy.

Topics: Anticonvulsants; Antidepressive Agents; Benzodiazepines; Bipolar Disorder; Cognitive Behavioral Therapy; Combined Modality Therapy; Drug Therapy, Combination; Humans; Lamotrigine; Lithium; Olanzapine; Patient Education as Topic; Psychotherapy; Secondary Prevention; Selective Serotonin Reuptake Inhibitors; Triazines; Valproic Acid

There have been major advances in clinical understanding and treatment of bipolar disorder over the past decade. Randomised controlled trials of pharmacological treatments and psychological interventions have shown that there are effective short-term and long-term treatments for the disorder. Despite advances in treatment, diagnosis is often delayed or mistaken, and many people who could benefit are not using the treatments available. Functional and symptomatic recovery from episodes of bipolar disorder is frequently less complete than previously considered, and disability is often profound. Although manic episodes are the distinguishing feature of bipolar disorder, it appears that depression is the predominant mood disturbance and that much of the functional impairment associated with bipolar disorder results from this. Comorbidity with anxiety disorders or substance misuse is common. Advances in genetics, brain imaging and basic pharmacology are starting to provide understanding of the complex causative processes.

Topics: Antimanic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Humans; Lamotrigine; Olanzapine; Selective Serotonin Reuptake Inhibitors; Suicide; Triazines

Depressive episodes are significant in bipolar illness since patients can spend up to one-third of their lives in depression. Although the treatment of bipolar depression remains an understudied area, new data from randomized, controlled trials and naturalistic studies have expanded the range of treatments available. The main aim in the treatment of bipolar depression is the prevention of the patient switching to mania and cycle acceleration, and antidepressant therapy may be contraindicated because of the risk for switching. Guidelines for the acute treatment of bipolar depression emphasize treatment with a mood stabilizer, of which lithium has been the most thoroughly studied in randomized, controlled trials in acute bipolar depression. Lamotrigine has also demonstrated significant efficacy in recent studies and has been approved by the FDA.

Topics: Acute Disease; Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Chemoprevention; Contraindications; Depressive Disorder; Diagnosis, Differential; Drug Therapy, Combination; Humans; Lamotrigine; Lithium; Olanzapine; Triazines; Valproic Acid

Olanzapine is an atypical antipsychotic that is approved in the US and Europe for the oral treatment of acute manic episodes in patients with bipolar I disorder, and for maintenance therapy to prevent recurrence in responders. Oral olanzapine is effective in the treatment of bipolar mania, both as single agent therapy and as adjunctive therapy in combination with lithium or valproate semisodium. In the treatment of acute episodes, olanzapine is superior to placebo and at least as effective as lithium, valproate semisodium, haloperidol and risperidone in reducing the symptoms of mania and inducing remission. Additional comparative studies are required to determine the efficacy of olanzapine relative to newer atypical antipsychotics, such as quetiapine, ziprasidone and aripiprazole. Olanzapine is also effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders, and is currently the only atypical antipsychotic approved for this indication. Current evidence suggests that olanzapine may be more effective than lithium in preventing relapse into mania, but not relapse into depression or relapse overall. Olanzapine is generally well tolerated, and although it is associated with a higher incidence of weight gain than most atypical agents, it has a low incidence of extrapyramidal symptoms (EPS). Therefore, oral olanzapine is a useful first-line or adjunctive agent for both the acute treatment of manic episodes and the long-term prevention of relapse into manic, depressive or mixed episodes associated with bipolar I disorder.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Economics, Pharmaceutical; Half-Life; Humans; Middle Aged; Olanzapine; Quality of Life; Randomized Controlled Trials as Topic; Tissue Distribution

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

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

Mechanisms of action, onset and duration of action, and interactions with other medications--all of these pharmacokinetic properties of pharmacologic agents affect the efficacy and safety of therapeutic regimens for bipolar disorder. For example, antiglutamatergic agents such as lamotrigine may relieve depression but have no impact on mania. Atypical antipsychotics with the dual effect of blocking dopamine and serotonin receptors in the brain decrease psychosis, mania, and, according to some preliminary indications, possibly depression. The impact of these properties has been borne out in clinical studies. Mood stabilizers such as lithium and valproate stabilize mood by significantly decreasing the manic and hypomanic symptoms of bipolar disorder, although they can have effects on depressive symptoms too. Lamotrigine stabilizes mood by reducing depression. The atypical anti-psychotics have been shown to be effective either as monotherapy or in combination with mood stabilizers.

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Lamotrigine; Lithium; Olanzapine; Receptors, GABA; Receptors, Glutamate; Treatment Outcome; Triazines; Valproic Acid

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Anxiety; Benzodiazepines; Bipolar Disorder; Cognition; Dibenzothiazepines; Drug Design; Drug Resistance; Drug Therapy, Combination; Female; Humans; Olanzapine; Quetiapine Fumarate; Risperidone

Olanzapine (Zyprexa, Eli Lilly & Co.) is an atypical antipsychotic medication with once-daily dosing that was originally developed for the treatment of schizophrenia. It has shown broad efficacy in the treatment of bipolar mixed and manic episodes, but is less effective in the treatment of bipolar depression. Double-blind studies have demonstrated a rapid onset of action in acute bipolar mania, significantly greater rates of response compared with placebo, and a remission rate of 88.3% in a 49-week open-label study. Diverse presentations of the illness responded well to olanzapine including patients with rapid-cycling bipolar disorder, mixed episodes, as well as psychotic and nonpsychotic manias. Olanzapine monotherapy improved symptoms of depression related to its sedating and appetite-enhancing profile, but core symptoms such as depressed mood did not improve significantly. However, in combination with fluoxetine, bipolar depressed patients responded without an increased risk of mania. Weight gain and sedation are prominent adverse effects, and it has been associated with atherogenic dyslipidemia and glucose intolerance.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Humans; Olanzapine; Psychiatric Status Rating Scales

A 16-year-old boy developed fever, generalized rigidity, leukocytosis, and increased serum transaminase and creatine kinase levels while receiving treatment with olanzapine and lithium. When both drugs were discontinued, his fever and rigidity subsided and biochemical irregularities spontaneously returned to normal, without any complications. Classic neuroleptic malignant syndrome (NMS) was diagnosed. Concomitant administration of lithium with olanzapine may place patients at risk for NMS. Clinicians need to be aware of this rare but potentially fatal side effect in patients of all ages, and especially in adolescents receiving both drugs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Differential; Drug Therapy, Combination; Humans; Lithium; Male; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine

Depression is common in primary care and more difficult to treat than many clinicians are aware. The goal of treatment is symptomatic remission, and by current estimates 50% or more of patients treated with antidepressant monotherapy may suffer from residual neurovegetative, cognitive, and somatic symptoms. Bipolar disorder, in particular, is more prevalent in primary care than previously recognized, is easily misdiagnosed, and may be a significant source of treatment failure. This article reviews treatment resistance, its causes, and management approaches. Many strategies are straight-forward and within the skill set of primary care clinicians. The use of antidepressants with multiple mechanisms of action may reduce first-order resistance. Antidepressant augmentation strategies (e.g., with lithium or atypical antipsychotics) are often very effective and readily instituted by informed and motivated practitioners.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Depressive Disorder; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Medical Records; Olanzapine; Pirenzepine; Primary Health Care; Psychotherapy

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Lithium Compounds; Olanzapine; Pirenzepine; Valproic Acid

Topics: Acetates; Affect; Amines; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Lithium Compounds; Nipecotic Acids; Olanzapine; Oxcarbazepine; Pirenzepine; Tiagabine; Topiramate; Treatment Outcome; Triazines; Valproic Acid; Zonisamide

Topics: Affect; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Controlled Clinical Trials as Topic; Humans; Lamotrigine; Lithium Compounds; Olanzapine; Pirenzepine; Secondary Prevention; Time Factors; Treatment Outcome; Triazines; Valproic Acid

Topics: Acute Disease; Affect; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chronic Disease; Drug Administration Schedule; Humans; Lithium Compounds; Olanzapine; Pirenzepine; Treatment Outcome; Valproic Acid

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Dyskinesias; Haloperidol; Humans; Hyperglycemia; Hyperprolactinemia; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Thioridazine; Weight Gain

This article explores the roles of monotherapy and drug combinations in finding effective long-term treatment for individual patients with bipolar disorder. While current practice relies heavily on combinations, many bipolar patients can be successfully stabilized if the initial monotherapy is carefully selected according to the patient's clinical characteristics. The data show that (1) unequivocal responders to long-term monotherapies such as lithium, lamotrigine, or atypical neuroleptics each have a very different clinical profile, including clinical presentation and course, comorbidity, and, in particular, family history and (2) bipolar patients who respond very well to a long-term monotherapy have often completely failed on other monotherapies. Combinations appear indicated particularly in bipolar patients who are treatment-resistant to monotherapy, do not tolerate it well, or have not yet exhibited the clinical characteristics needed to choose an effective monotherapy.

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Drug Therapy, Combination; Humans; Lamotrigine; Lithium; Long-Term Care; Olanzapine; Pirenzepine; Treatment Outcome; Triazines

The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well.. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches.. Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed.. Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Donepezil; Fatty Acids, Omega-3; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Indans; Lamotrigine; Lithium Carbonate; Olanzapine; Piperazines; Piperidines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Depression can occur either with or without alternation with periods of mania. Depression that alternates with mania (bipolar depression) is a particularly difficult problem in clinical practice. The evidence base of the treatment for this condition is not strong and the choices at best are limited. Furthermore, although there are a number of effective antidepressants for the non-cycling variety ('unipolar' major depression), > 50% of patients experience incomplete response to any given drug. Given the proportion of the population involved, these represent fairly sizeable markets. Studies over the last several years indicate that the combination of the novel antipsychotic olanzapine and the serotonin-selective re-uptake inhibitor (SSRI), fluoxetine, may be effective for both conditions. One trial in 28 patients showed that this combination was an effective treatment, compared to the individual components with unipolar depressed patients who had not responded to two antidepressants of different chemical classes. Two subsequent large-scale attempts at replication have resulted in failed trials. Patients randomly assigned to antidepressant monotherapies showed a good response, indicating that the populations being studied were not actually treatment-resistant; therefore, more research is needed. Alternatively, a recent study showed that monotherapy with olanzapine produced a greater effect than placebo in bipolar depression and the combination of olanzapine and fluoxetine yielded an even more robust response. However, important questions remain, e.g., the issue of comparative effectiveness, that is to say, whether the same result could occur with combinations of other novel antipsychotics and SSRIs. In addition, there remain significant concerns regarding the safety and tolerability of olanzapine in these populations. Essential questions about the potential for substantial weight gain, Type II diabetes and for the development of tardive dyskinesia (a syndrome of permanent, disfiguring abnormal involuntary movements) remain. These problems will have to be vigorously addressed in order to achieve a substantial market penetration for these conditions.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Fluoxetine; Half-Life; Humans; Mood Disorders; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Electroconvulsive Therapy; Humans; Lithium; Olanzapine; Pirenzepine; Psychotherapy; Reference Standards; Valproic Acid

Olanzapine, an atypical antipsychotic, is used in the treatment of mania both as monotherapy and combined with other medicines.. To review the efficacy and tolerability of olanzapine in the treatment of mania. The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, CINAHL and PsycINFO were searched.. Randomised trials comparing olanzapine with placebo or other drug in acute manic or mixed episodes.. Two reviewers independently extracted data from trial reports. Six trials (1422 participants) were included in the review. There was a high rate of failure to complete treatment on all treatments which may have biased the estimates of relative efficacy. Olanzapine was superior to placebo at reducing manic symptoms as monotherapy (Young Mania Rating Scale (YMRS) - weighted mean difference (WMD): -5.94, 95% CI -9.09 to -2.80) and in combination with lithium/valproate (YMRS) (WMD -4.01, 95% confidence interval -6.06 to -1.96). Olanzapine monotherapy was superior at reducing psychotic symptoms (PANSS positive symptoms subscale WMD: -3.54, 95% CI -5.28 to -1.80). Olanzapine was superior to divalproex at reducing manic symptoms (standardised mean difference (SMD): -0.29, 95% CI -0.50 to -0.08). Olanzapine did not lead to a statistically higher rate of clinical response than haloperidol (RR: 1.03, 95% CI 0.77 to 1.38). Fewer patients discontinued treatment on olanzapine than placebo (RR: 0.62, 95% CI 0.48 to 0.80). Olanzapine caused greater weight gain than placebo (WMD 1.91Kg, 95% CI 1.29 to 2.53) and somnolence (RR: 2.13 95% CI 1.62 to 2.79) but not more depressive symptoms (RR: 0.95, 95% CI 0.65 to 1.40) or movement disorder (WMD: -0.33, 95% CI -0.74 to 0.09). Olanzapine caused more prolactin elevation than placebo (RR: 4.35 95%CI 1.77 to 10.70). Olanzapine caused greater weight gain (WMD: 1.54, 95% CI 1.02 to 2.05); somnolence (RR: 1.80 95% CI 1.32 to 2.46) and movement disorders (SAS - WMD: 0.72 95% CI 0.11 to 1.33) than divalproex but less nausea ( RR: 0.36 95% CI 0.20 to 0.65). Olanzapine caused more weight gain than haloperidol (RR: 3.59, 95% CI 1.49 to 8.64) but less movement disorder (EPS RR: 0.10, 95% CI 0.04 to 0.24).. Olanzapine is an effective treatment for mania and may be more efficacious than divalproex, though leads to more weight gain. Clinicians should consider both the relative efficacy and the different incidence of specific adverse effects of available drugs.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Treatment Failure

Previous studies have examined the safety and tolerability of oral-loaded divalproex sodium in the treatment of acute mania, but not the early efficacy of this dosing strategy. The purpose of this study was to evaluate the early efficacy of oral-loaded divalproex.. In this pooled analysis, 348 subjects from 3 randomized, double-blind, parallel-group, active- or placebo-controlled studies were used to compare the efficacy, safety, and tolerability of oral-loaded divalproex with standard-titration divalproex, lithium, olanzapine, or placebo. Subjects were inpatients diagnosed with acute mania associated with bipolar I disorder (DSM-III-R or -IV and SADS-Change Version). Patients were administered oral-loaded divalproex (20 or 30 mg/kg/day on days 1 and 2 followed by 20 mg/kg/day, and increased at physician's discretion), standard-titration divalproex initiated at 250 mg t.i.d. and titrated to 40-150 microg/mL, lithium (300 mg t.i.d. initial dose) titrated to 0.4 to 1.5 mEq/L, olanzapine (10 mg q.d. initial dose) up to 20 mg/day, or placebo.. The results demonstrate an early efficacy advantage for oral-loaded divalproex compared to standard-titration divalproex at days 5, 7/8, and 10. Efficacy was improved over lithium on day 7/8. There were no efficacy differences between divalproex loading and olanzapine. Divalproex loading showed greater efficacy than placebo at all time points. Divalproex loading was as well tolerated or better tolerated than the other active treatments as measured by adverse events and changes in laboratory parameters.. These results suggest the oral loading of divalproex leads to a more rapid antimanic effect when compared with standard-titration divalproex, lithium, or placebo and is better tolerated than olanzapine and as well tolerated as lithium or standard-titration divalproex.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Tolerance; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Severity of Illness Index; Titrimetry; Treatment Outcome; Valproic Acid

The term bipolar disorder is no longer limited to the classical manic-depressive condition, but now subsumes a wide spectrum of illnesses. As a consequence of this expansion of the classification systems, the therapeutic utility of lithium and other mood stabilizing agents has to be defined anew. The majority treatment recommendations differentiate, symptom-related, between euphoric mania, mixed conditions, mania with psychotic symptoms and rapid cycling manic episodes. Current acute treatment includes, in addition to lithium, in particular carbamazepine and valproate, but also newer antiepileptic drugs such as lamotrigine or atypical neuroleptic agents such as olanzapine and risperidone. Due to the high suicidal risk, patients with bipolar depression often need to be given an antidepressant as well. It must, however, be remembered that in patients with rapid cycling, antidepressants may re-trigger mania.

Topics: Acute Disease; Algorithms; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Humans; Isotopes; Lamotrigine; Lithium; Olanzapine; Pirenzepine; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Triazines; Valproic Acid

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

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

Bipolar disorder is a complex condition including depression, mania, and in many cases associated with comorbid anxiety symptoms and substance abuse. Mood stabilizers including lithium and divalproex have been considered standard therapy for the treatment of patients with bipolar disorder, but remission rates remain inadequate. Conventional antipsychotics have demonstrated efficacy for acute mania, but they appear to have little role in the maintenance treatment of bipolar disorder. Despite substantial evidence of efficacy and recent guideline recommendations, atypical antipsychotics remain underused for the treatment of bipolar disorder. Data from double-blind, controlled trials are available for a number of clinically meaningful efficacy measures, including improvement in manic symptoms, onset of action, response rates, remission rates, improvement in comorbid depressive symptoms, and induction/worsening of mania or depression. Atypical antipsychotics are effective both as alternatives to lithium or divalproex as monotherapy, or in combination with these mood stabilizers, in the acute and likely the maintenance treatment of mania. The atypical antipsychotics represent an effective and relatively safe addition to our armamentarium for the treatment of bipolar disorder.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Humans; Olanzapine; Pirenzepine; Treatment Outcome

Bipolar disorder, despite being a common and debilitating illness, has remarkably few pharmacological therapeutic options, the majority of which, with the exception of lithium, have been borrowed from other medical indications. Furthermore the quantity and quality of controlled clinical data are considerably smaller than in conditions of comparable severity and frequency. Not surprisingly, the clinical outcome of bipolar disorder is frequently suboptimal. Fortunately there are a growing number of novel therapeutic options for its treatment such as atypical antipsychotics, calcium channel blockers and omega-3 fatty acids. This paper summarizes some of the data regarding these "experimental" therapeutic options, focusing principally on atypical antipsychotics as these are now widely prescribed in the management of bipolar disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone

Patients with bipolar disorder frequently receive antipsychotic agents during both the acute and maintenance phases of treatment. Conventional antipsychotics are effective against mania, but they may induce depressive symptoms and expose patients with bipolar disorder to increased risks of tardive dyskinesia. Recent studies have shown risperidone to be effective for acute mania, both as monotherapy and in combination with mood stabilizers; this agent has also shown efficacy as add-on maintenance therapy in open-label studies as it exhibited both antimanic and antidepressant effects. Olanzapine, another novel antipsychotic, is also effective against both manic and depressive symptoms and in the maintenance treatment as indicated by an open-label study. Data on other novel agents are more limited.

Topics: Acute Disease; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Haloperidol; Humans; Lithium; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Risperidone

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

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

Olanzapine, a thienobenzodiazepine derivative, is a psychotropic agent that has shown efficacy in the treatment of patients with bipolar I disorder. Olanzapine has a multireceptorial binding profile including a greater affinity for serotonin 5-HT(2A) than for dopamine D(2) receptors. Olanzapine 5 to 20 mg/day demonstrated significantly greater antimanic efficacy than placebo in two double-blind, randomised 3- or 4-week trials of patients with bipolar I disorder of either manic or mixed episodes, with or without psychotic features. Additionally, in one of these trials, improvements in cognitive function and hostility were superior with olanzapine. In cohorts of severely depressed and rapid cycling patients, improvements in manic and depressive symptoms and in manic symptoms only, were superior with olanzapine compared with placebo. Significant improvements from baseline in symptoms of mania, depression, cognitive functioning and hostility were seen with olanzapine in a 49-week extension phase study. In double-blind trials, olanzapine 10 mg/day appeared to have similar antimanic efficacy to oral lithium 400mg twice daily in the treatment of patients with pure mania (4-week small study). In patients with acute manic or mixed episodes olanzapine 5 to 20 mg/day appeared to be more effective than oral valproate semisodium (divalproex sodium) 500 to 2500 mg/day (3-week study) and at least as effective as oral haloperidol 3 to 15 mg/day (12-week study). Preliminary results from a large 6-week placebo-controlled study suggest that olanzapine 5 to 20 mg/day in combination with mood stabilisers (lithium or valproate semisodium) provides effective augmentation of antimanic treatment of patients with bipolar I disorder, with benefits seen in the first week. Adverse events reported significantly more often with olanzapine than with placebo were somnolence, dry mouth, dizziness and bodyweight gain, and in comparison with valproate semisodium were somnolence, dry mouth, increased appetite and bodyweight gain. Olanzapine was generally well tolerated with no clinically relevant abnormalities in laboratory tests, vital signs or electrocardiogram results.. Olanzapine demonstrated superior efficacy compared with placebo in the short-term treatment of patients with bipolar I disorder with manic or mixed episodes, with or without psychotic features, and was generally well tolerated. According to preliminary data the antimanic efficacy of olanzapine appears similar to that of haloperidol and better than that of valproate semisodium in patients with bipolar I disorder experiencing a manic or mixed episode; among nonpsychotic patients with manic or mixed episodes olanzapine appears to be superior to haloperidol. Available data support the choice of olanzapine as an option in the short-term management of mania in patients with bipolar I disorder with manic or mixed episodes, with or without psychotic features.

Topics: Animals; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors

Cumulative data indicate that atypical antipsychotics can serve as adjunctive as well as alternative agents in the treatment of drug-resistant mood disorders. Olanzapine and risperidone add-on treatment was found to be effective for major depression with psychotic features and good results were achieved with currently available atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine and ziprasidone) in reducing symptoms of acute mania, especially when added to mood stabilizers. The role of atypical antipsychotics in maintenance and prophylactic treatment is not yet clear. Although there are differences in the side effect profiles of the various atypical antipsychotics, their use is limited by adverse effects such as extrapyramidal symptoms, weight gain, somnolence and sexual dysfunction.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Depressive Disorder, Major; Dibenzothiazepines; Humans; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles

Rapid improvement of tardive dyskinesia was identified following initiation of olanzapine in an elderly male patient formally treated with chlorpromazine.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Chronic Disease; Dyskinesia, Drug-Induced; Humans; Male; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors

While the efficacy of antipsychotics as a maintenance treatment for bipolar patients has not been systematically studied, these drugs are commonly used in the long-term treatment of bipolar patients, and it is not unusual for a bipolar patient to be taking 3 to 4 medications, including antipsychotics. Conventional antipsychotics may be comparable to lithium for acute mania, but have limitations when used in the long-term treatment of bipolar disorder. Their adverse effects, which include extrapyramidal side effects, tardive dyskinesia, weight gain, sedation, and sexual dysfunction, often lead to non-compliance; their use may have a negative impact on the overall course of illness; and they may not be as effective as lithium in treating the core manic symptoms over the long term. Atypical antipsychotics may prove useful for bipolar patients who require antipsychotic treatment because of their favorable side effect profile, thymoleptic properties, and positive effect on overall functioning.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Dibenzothiazepines; Humans; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone

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

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

Bipolar disorder is a recurrent and relapsing mood disorder characterized by cycles of depression and mania. This article addresses the treatment of patients with bipolar mania, which remains one of the most difficult challenges facing clinicians. Patients require safe and effective therapeutic approaches for acute episodes of mania and depression, as well as chronic prophylaxis against future episodes. Monotherapeutic approaches are rarely effective, and combination approaches are associated with an increased risk of adverse events. Lithium is the only agent currently approved for the treatment of both acute episodes of mania and maintenance therapy; however, it is associated with a relatively poor response rate, high relapse rate, and less-than-optimal side effect profile. Other recent approaches have included several anticonvulsant agents, as well as conventional and atypical antipsychotic agents.

Topics: Acetates; Amines; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Electroconvulsive Therapy; Electromagnetic Phenomena; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Lithium; Olanzapine; Pirenzepine; Risperidone; Topiramate; Treatment Outcome; Triazines; Valproic Acid

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

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

Bipolar disorder is a lifelong episodic condition characterized by mood swings between mania and depression. In the United States alone, approximately 4 million people are affected by this disorder. Pharmacologic treatment for acute manic episodes or as maintenance therapy includes lithium, valproate, carbamazepine, and typical antipsychotics. However, many patients fail to respond to these treatments due to lack of efficacy or production of side effects leading to patient noncompliance. Non-compliance with pharmacologic treatment is indeed a major risk factor in bipolar disorder patients and needs to be managed with ongoing education, psychotherapy, and a simplified but effective pharmacologic treatment regimen. Recently introduced novel antipsychotics show much promise as mood-stabilizing agents in bipolar patients, with minimal risk of treatment-emergent extrapyramidal symptoms and tardive dyskinesia. Nonetheless, further research is warranted to help clarify the role of novel antipsychotics in the treatment of bipolar disorder.

Topics: Acute Disease; Algorithms; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Clinical Trials as Topic; Humans; Lithium; Olanzapine; Pirenzepine; Research Design; Risk Factors; Treatment Outcome; Treatment Refusal; Valproic Acid

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

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

This clinical trials review is derived from the presentations made at the Third International Conference on Bipolar Disorder, held June 17-19, 1999 in Pittsburgh, PA, published as abstracts in Bipolar Disorders: An International Journal of Psychiatry and Neurosciences, Edited by Jair C. Soares, and Samuel Gershon. In this review, abstracts reporting on the efficacy of "third generation" anti-epileptic agents, including topiramate, lamotrigine, diphenylhydantoin, gabapentin, and the new generation antipsychotic agent, olanzapine in treating bipolar disorders are reviewed.

Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Olanzapine; Phenytoin; Pirenzepine; Topiramate; Treatment Outcome; Triazines

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

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

Traditional neuroleptics are often utilized clinically for the management of bipolar disorder. Although effective as antimanic agents, their mood stabilizing properties are less clear. Additionally, their acute clinical side effect profile and long term risk of tardive dyskinesia, particularly in mood disorder patients, portend significant liability. This review focuses on the use of atypical antipsychotics in the treatment of bipolar disorder focusing on clozapine as the prototypical agent. Although, preclinical research and clinical experience suggest that the atypical antipsychotics are distinctly different from typical antipsychotics, they themselves are heterogeneous in profiles of neuropharmacology, clinical efficacy, and tolerability. The early clinical experience of clozapine as a potential mood stabilizer suggests greater antimanic than antidepressant properties. Conversely, very preliminary clinical experience with risperidone suggests greater antidepressant than antimanic properties and some liability for triggering or exacerbating mania. Olanzapine and sertindole are under investigation in psychotic mood disorders. The foregoing agents and future drugs with atypical neuroleptic properties should come to play an increasingly important role, compared to the older classical neuroleptics, in the acute and long term management of bipolar disorder.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Humans; Imidazoles; Indoles; Olanzapine; Pirenzepine; Risperidone; Trimipramine

Depression in schizophrenia may be partially responsible for the increased suicide rate in schizophrenic patients, which is more than 20 times higher than that found in the general population. Affective disorders in patients with schizophrenia are associated with a poor outcome, an increased risk of relapse, and a high rate of suicide. There is evidence that atypical antipsychotics may contribute to a reduction in suicidality, and although the new drugs are marketed for the treatment of schizophrenia, their novel psychopharmacologic effects suggest the possibility of other therapeutic applications. Recent studies of the efficacy of the novel antipsychotics found that these agents may produce an antidepressant effect in schizophrenia and may be used as either an adjunctive medication or an alternative to mood stabilizers in patients with affective disorders.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Comorbidity; Depressive Disorder; Humans; Mood Disorders; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Schizophrenic Psychology; Suicide; Suicide Prevention

Atypical antipsychotics have become the treatment of choice for patients experiencing a first episode of schizophrenia. In addition, they are often prescribed for conditions such as bipolar disorder and dementia. While clinical trials have not yet established the efficacy of the atypical antipsychotics for these uses, a number of reports offer preliminary evidence that the atypical antipsychotics may be beneficial for affective disorders, substance abuse disorder, senile dementia, and pathologic aggression. Atypical agents may be particularly effective and tolerable in elderly patients who are especially susceptible to the adverse effects of conventional antipsychotic medication. Lower dosages are more necessary for the elderly than for younger adults. Current evidence suggests that clozapine is the most effective atypical antipsychotic for neuroleptic-resistant patients. Risperidone, olanzapine, and quetiapine may also be effective in a subset of these patients.

Topics: Adult; Age Factors; Aged; Algorithms; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Clozapine; Decision Trees; Dementia; Dibenzothiazepines; Female; Humans; Male; Mood Disorders; Olanzapine; Pirenzepine; Quetiapine Fumarate; Risperidone; Schizophrenia

Personality disorder is a common co-occurrence ('comorbidity') among patients with bipolar disorder and appears to affect outcome negatively. However, there is little knowledge about the impact of this comorbidity in the early phases of bipolar disorder. We examined the prevalence and effect of personality disorder co-occurrence on outcome in a cohort of youth with first episode mania with psychotic features.. Seventy-one first episode mania patients, aged 15-29, were assessed at baseline, 6, 12, and 18 months as part of a randomized controlled trial of olanzapine and chlorpromazine as add-on to lithium in first episode mania with psychotic features. The current study involved secondary analysis of trial data.. A co-occurring clinical personality disorder diagnosis was present in 16.9% of patients. Antisocial and narcissistic personality disorders were the most common diagnoses. Patients with co-occurring personality disorder had higher rates of readmission to hospital, lower rates of symptomatic recovery and poorer functional levels at 6 months, but these differences disappeared after 12 and 18 months.. In the early phase of bipolar disorder, patients with personality disorder comorbidity display delayed symptomatic and functional recovery and increased likelihood to need hospital readmissions. These observations suggest that routine assessment for personality disorder and specific interventions are important in order to improve short-term treatment efficacy in this subgroup.

Topics: Adolescent; Adult; Bipolar Disorder; Humans; Mania; Olanzapine; Personality Disorders; Treatment Outcome; Young Adult

It is unknown whether there are differences in efficacy and safety between quetiapine extended-release, 300 mg/d (QUEXR300), and olanzapine, 5-20 mg/d (OLA), for Japanese patients with bipolar depression.. We conducted a Bayesian analysis of data from phase 3 studies in Japan of QUEXR300 and OLA. Outcomes were remission rate (primary), response rate, improvement on the Montgomery-Åsberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale scores, discontinuation rate, and incidence of individual adverse events. We calculated the standardized mean difference (SMD) and the risk ratio (RR) and 95% credible interval (95% CrI) for continuous and dichotomous data, respectively.. There were no significant differences between QUEXR300 and OLA for any of the efficacy outcomes. QUEXR300 was associated with a higher incidence of somnolence than OLA (RR = 5.517; 95% CrI = 1.563, 19.787), while OLA was associated with greater increase body weight (SMD = -0.488; 95% CrI = -0.881, -0.089) and blood prolactin levels (SMD = -0.642; 95% CrI = -1.073, -0.213) than QUEXR300, and a greater decrease in high-density lipoprotein cholesterol levels (SMD = -0.408; 95% CrI = -0.785, -0.030) than QUEXR300.. Although the two drugs' efficacy did not differ, OLA increased the risk of metabolic syndrome and QUEXR300 the risk of somnolence. A large scale, long-term, head-to-head comparison study of QUEXR300 vs OLA for Japanese patients with bipolar depression is needed to confirm the results of the current study.

Topics: Adolescent; Adult; Antipsychotic Agents; Bayes Theorem; Bipolar Disorder; Cholesterol, HDL; Delayed-Action Preparations; Female; Humans; Japan; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prolactin; Quetiapine Fumarate; Weight Gain

We aimed to evaluate melatonin effectiveness in weight gain reduction following olanzapine use for 11-17-year-old bipolar disorder patients.. Seventy-seven adolescent outpatients, subsequent to their initial diagnosis of bipolar I disorder by a psychiatrist, entered this study. After assessing inclusion and exclusion criteria, 48 patients consented to participate. Twenty-four patients were allocated to receive olanzapine, lithium carbonate, and melatonin, and 24 patients were allocated to receive olanzapine, lithium carbonate, and placebo by simple randomization. The Young Mania Rating Scale (YMRS) was performed at baseline. Before treatment and after 6 and 12 weeks of treatment, weight, height, and body mass index (BMI) were measured. Analysis of variance (ANOVA) with repeated measure and t-test were used to analyze data.. Nineteen patients in each group finished the study and their data were entered for analysis. Mean rise in BMI in the melatonin group compared with placebo (2.45 vs. 3.25 respectively) was marginally significant (t = 1.936; df = 36; p = 0.061). ANOVA with repeated measure also showed a marginally significant difference (F = 3.74; df = 1; p = 0.061) between groups and across time in regard to BMI. Mean body weight rise in the melatonin group compared with the placebo group (5.8 kg vs. 8.2 kg respectively) was marginally significant (t = 1.923; df = 28; p = 0.065). ANOVA with repeated measure also showed a marginally significant difference (F = 3.73; df = 1.1; p = 0.056) between groups and across time for body weight.. Coadministration of melatonin with olanzapine and lithium carbonate in adolescents with bipolar disorder could reduce the sharp weight gain side effect of these drugs to near significance.

Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Weight; Child; Double-Blind Method; Humans; Lithium Carbonate; Male; Melatonin; Olanzapine; Psychiatric Status Rating Scales; Time Factors; Weight Gain

Available antipsychotics show different efficacy on manic symptoms of bipolar patients, but few studies have investigated the speed of action of the various compounds. For this reason, purpose of the present paper was to compare antipsychotic mono-therapies in terms of speed of action in a sample of manic bipolar patients. In total, 155 bipolar patients, treated with antipsychotic mono-therapy and followed-up in Inpatient Psychiatry Clinic of University of Milan, were included in this single-blind comparative study. Clinical response was defined as a reduction of Young Mania Rating Scale (YMRS) scores ⩾50%, while remission as a YMRS score <10. After 4 days patients who had been treated with asenapine, were more likely to have achieved a clinical response than those in treatment with haloperidol ( p = 0.001). After 7 days, a more frequent clinical response was achieved by patients treated with asenapine than those who had been treated with haloperidol ( p < 0.001) or olanzapine ( p = 0.047). Asenapine appears to be faster in determining treatment response in manic patients compared with haloperidol and less markedly with olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Female; Haloperidol; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Olanzapine; Single-Blind Method; Time Factors; Treatment Outcome

The aim of this study is to examine the effects of memantine as an adjuvant treatment for obsessive compulsive (OC) symptoms in patients with bipolar disorder (BD) type I, manic phase.. In this 16-week double-blind placebo-controlled randomized clinical trial, 58 patients in the manic phase of BD who had OC symptoms were randomly allocated to receive memantine or placebo plus their routine medications (lithium + olanzapine + clonazepam). The Yale Brown Obsessive Compulsive Behavior Scale was used to assess the outcomes. Adverse effects were also recorded.. Thirty-eight patients (19 in the memantine group and 19 in the placebo group) completed the trial. Throughout the trial, the mean score decreased from 20.26 ± 5.91 to 9.73 ± 5.44 in the memantine group (P < 0.000) and from 22.89 ± 5.70 to 16.63 ± 4.00 in the placebo group (P < 0.000). At the end of the study, 15 (78.94%) patients in the memantine group and 7 (36.84%) patients in the placebo group demonstrated more than 34% decline in the Yale Brown Obsessive Compulsive Behavior Scale score (P < 0.01). No serious adverse effects were reported.. Our double-blind controlled clinical trial showed that memantine is an effective adjuvant agent for reducing OC symptoms in patients with BD. However, it needs to be noted that our study is preliminary, and larger double-blind controlled studies are needed to confirm the results.

Topics: Adjuvants, Pharmaceutic; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clonazepam; Double-Blind Method; Drug Therapy, Combination; Excitatory Amino Acid Antagonists; Female; GABA Modulators; Humans; Lithium Compounds; Male; Memantine; Middle Aged; Obsessive-Compulsive Disorder; Olanzapine; Outcome Assessment, Health Care

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Combined Modality Therapy; Double-Blind Method; Female; Humans; Lithium; Male; Olanzapine; Risperidone; Time Factors; Weight Gain

Survival analysis has superseded most other analytic techniques for maintenance treatment studies over recent decades, despite providing results based solely on a single time-point predefined event. The aim of the present study was to develop the Multi-state Outcome Analysis of Treatments (MOAT), to provide more pragmatic information for clinicians and investigators in guiding maintenance treatment decisions. The present study was one of two published studies on the development of MOAT procedures, involving a one-year comparison of olanzapine versus lithium in recently manic patients.. MOAT partitions total survival time into clinically distinct periods that are operationally defined by cut points on established rating scales. For bipolar disorders, the clinical states are remission, subsyndromal and syndromal mania, mixed states, and subsyndromal and syndromal depression.. MOAT re-analyses of the clinical trial revealed clinically important findings not identified when utilizing Kaplan-Meier survival analyses. Compared to patients treated with lithium, patients taking olanzapine experienced significantly more time in subsyndromal depression. Patients taking lithium spent significantly more time in mixed states than did patients taking olanzapine.. MOAT provided detailed information on treatment outcomes that was not provided by Kaplan-Meier survival analysis. Its capability to identify and aggregate time in different clinical states of bipolar disorder may aid in identifying drug effects that are important in selecting and conducting maintenance treatment.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Lithium Compounds; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Psychiatric Status Rating Scales; Psychometrics; Young Adult

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

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

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

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

Safety and efficacy of long-term olanzapine treatment in Japanese patients with bipolar depression were assessed.. An integrated analysis of data from two studies was performed in olanzapine-treated patients (n = 165) with bipolar depression. Study 1 was a 6-week, double-blind, global study. Patients were randomly assigned to olanzapine or placebo followed by 18 weeks of open-label treatment. Study 2 was an open-label extension of Study 1 involving only Japanese patients. Patients assigned to Pre-olanzapine and Pre-placebo in Study 1 were treated for 24 weeks (total olanzapine exposure 42 or 48 weeks) and newly recruited patients (New-olanzapine) were treated for 48 weeks. Safety outcomes included treatment-emergent adverse events and changes in metabolic parameters. Efficacy outcome was assessed with Montgomery-Åsberg Depression Rating Scale score.. Forty-three percent of patients completed the 42- or 48-week olanzapine treatment period. The most common treatment-emergent adverse event was weight increased (47.9%). Significant increases were seen in weight (3.5 kg), and in fasting glucose (3.5 mg/dL), fasting total cholesterol (8.1 mg/dL), and fasting triglycerides (35.1 mg/dL). Remission rates (Montgomery-Åsberg Depression Rating Scale total score ≤12 at any time) were 79.8% for the Pre-olanzapine group, 90.2% for the Pre-placebo group, and 85.0% for the New-olanzapine group. No patents developed mania during treatment.. Long-term use of olanzapine in a Japanese population with bipolar depression is associated with increases in weight and fasting metabolic measures, and also with improved depressive symptoms with avoidance of mania. Clinicians must carefully consider the benefits and risks of long-term therapy with olanzapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Olanzapine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Young Adult

Depression symptoms are now recognized to be the predominant cause of disability for bipolar disorder (BD) patients. The treatment strategies for the depressed phase of BD remain more anecdotal than data-based. Olanzapine has been investigated as an alternative to antidepressants and a mood stabilizer for acute bipolar depression. The purpose of this study was to assess the efficacy of olanzapine monotherapy for bipolar I depression.. Sixty-eight patients with bipolar I depression were randomly assigned to treatment with olanzapine (mean final dose 14.4 mg/day) (n=34) or placebo (n=34) in a double-blind parallel-group study design. Planned assessments included Montgomery-Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Clinical Global Impressions-Severity of Illness scale (CGI-S), Clinical Global Impressions-Improvement scale (CGI-I), Hamilton Depression scale (HAMD), Hamilton Anxiety scale (HAMA), and Treatment Emergent Symptom Scale (TESS).. Of the 68 patients who were randomly assigned, 57 (83.8 %) completed treatments. Improvements in MADRS total score, CGI-S, CGI-I, and HAMD in the olanzapine group were significantly greater relative to those in the placebo group during the 8-week follow-up period (p<0.001, p=0.0017, p=0.007, and p<0.001, respectively). Rates of categorical treatment response and remission in the olanzapine group (50.0 % and 35.3 %, respectively) were significantly higher than those in the placebo group (20.6 %, p=0.011 and 11.8 %, p=0.022, respectively). At the 8-week treatment, the mean weight and the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels increased significantly in the olanzapine group (p=0.037, p=0.029, p=0.030, and p=0.028, respectively).. Olanzapine is effective in the treatment of bipolar I depression but is associated with significant metabolic side effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome; Young Adult

Bipolar disorder is a highly recurrent disease and has great impact on the function of patients. Depressive symptoms consist of more than 50% of life time during the illness and may lead to self harm or suicidal behaviors. Little is known about the antidepressant effects of olanzapine, an atypical antipsychotic, as monotherapy despite its indication for preventing manic episodes. In contrast, lamotrigine, a mood stabilizer, has been proven to be effective in preventing depression in patients with bipolar disorder. However, no studies have compared the efficacy between lamotrigine and olanzapine in the maintenance treatment of bipolar disorder. This enriched naturalistic study was implemented to assess the effectiveness of olanzapine and lamotrigine as monotherapy in the prevention of recurrence of bipolar disorder.. Patients with bipolar disorder in a euthymic state (Young's Mania Rating Scale (YMRS) score <12, and 21-item Hamilton Depression Rating Scale (HAM-D) score <7) for at least two months, having already received either olanzapine or lamotrigine as the maintenance treatment were recruited. The patients maintained with olanzapine (n = 22) were applied to olanzapine group whereas those maintained with lamotrigine (n = 29) were applied to lamotrigine group. They were followed up for 12 months. Differences in the efficacy between olanzapine and lamotrigine in recurrence prevention were analyzed. The Kaplan-Meier method was used to generate time-to-recurrence curves, and differences between the two groups were compared using the log-rank test.. Olanzapine had a significantly lower recurrence rate of depressive episodes than lamotrigine (20.0% vs. 57.7%, χ2 = 6.62, p = .010). However, olanzapine and lamotrigine had similar mania (15.0% vs. 0%, χ2 = 4.17, p = .075, Fisher's exact test) and any mood episode (35.0% vs. 57.7%, χ2 = 2.33, p = .127) recurrence rates. Olanzapine was significantly superior to lamotrigine in the time to recurrence of depressive episodes (χ2 = 4.55, df = 1, p = .033), but there was no difference in the time to recurrence of any mood episode (χ2 = 1.68, df = 1, p = .195).. This prospective naturalistic study suggests that olanzapine is more effective than lamotrigine in the prevention of depressive episodes in patients with bipolar disorder. Future large-scale randomized studies are warranted to validate our results.. ClinicalTrials.gov ID NCT01864551.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Female; Humans; Lamotrigine; Male; Middle Aged; Olanzapine; Prospective Studies; Treatment Outcome; Triazines

It has not been examined trialed whether obsessive compulsive symptoms in patients with bipolar disorder respond to topiramate as an adjuvant treatment.. This 4-month double-blind placebo-controlled randomized clinical trial examined the efficacy and safety of augmentation with topiramat for treating the patients with bipolar disorder, manic phase type-I, and obsessive compulsive disorder symptoms. Both groups received lithium+olanzapine+clonazepam. However, one group received topiramate and the other group placebo as adjuvant medications. Yale Brown obsessive compulsive behavior scale was used to assess the outcome. Adverse effects were also recorded.. A total of 32 patients completed this trial. The mean score decreased from 24.2(4.8) to 17.6(8.7) in the topiramate group (P<0.003) and from 20.9(2.9) to 9.6(3.5) in the placebo group during this trial (P<0.0001). Additionally, 9(52.9%) out of 17 patients in the topiramate group and 2(12.5%) out of 16 patients in the placebo group showed more than 34% decline in YBOC score (x2=6.0, df=1, P<0.01). No serious adverse effects were detected.. The limitations of the present study were its small sample size and the fact that it was conducted in a single center.. The combination of lithium+olanzapine+clonazepam decreased the symptoms of obsessive compulsive disorder in the patients with bipolar disorder type I. However, topiramate had a more significant effect than placebo on improvement of the patients with bipolar disorder and obsessive compulsive symptoms. This combination seems to be without serious adverse effects.

Topics: Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Clonazepam; Double-Blind Method; Drug Therapy, Combination; Female; Fructose; Humans; Lithium Compounds; Male; Middle Aged; Neuroprotective Agents; Obsessive-Compulsive Disorder; Olanzapine; Selective Serotonin Reuptake Inhibitors; Topiramate; Treatment Outcome

Disturbance in sleep quality is a symptom of Major Depressive Disorder (MDD) and Bipolar Disorder (BD) and thus improving quality of sleep is an important aspect of successful treatment. Here, a prospective, double-blind, randomized, placebo-controlled study examined the effect of olanzapine (an atypical antipsychotic) augmentation therapy on sleep architecture, specifically slow wave sleep (SWS), in the treatment of depression. The effect of olanzapine augmentation therapy on other features of sleep (e.g., sleep continuity) and depression (e.g., illness severity and cognitive function) were also determined.. Patients currently experiencing a major depressive episode and who were on a stable medication were included. Sleep architecture was measured by overnight ambulatory polysomnography. Illness severity was determined using the Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive function was examined using Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Working Memory (SWM), Spatial Span (SSP), and Reaction Time (RTI) tasks. Polysomnographs, clinical measures and cognitive tests were administered at baseline, after 2-4 days of treatment and after 28-31 days of treatment. Twenty-five patients participated in the study (N = 10, N = 15 for placebo and olanzapine treated groups respectively).. The primary objective of the study was to assess the objective (polysomnographic) changes in sleep quality, defined as changes in SWS, following olanzapine treatment for depression. Latency to but not duration of SWS was found to significantly differ between olanzapine- and placebo-treated participants (Hedge's g: 0.97, 0.13 respectively). A significant improvement in olanzapine-treated participants over placebo-treated participants was observed in secondary outcome measures, including sleep efficiency, total sleep time, and sleep latency. Secondary objectives assessed the subjective changes in sleep quality parameters and correlated them with measures of illness severity and changes in cognition. MADRS scores were significantly improved in olanzapine-treated participants over time but not more than placebo treatment. There was no significant difference between olanzapine- and placebo-treated participants in SWM, SSP or RTI tasks.. Olanzapine augmentation treatment generally did not improve SWS but did improve sleep continuity and depression. Olanzapine may be one of few medications that improve sleep continuity, thus directly targeting symptoms of depression.. ClinicalTrials.gov, NCT00520507.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Sleep; Surveys and Questionnaires

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

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

Past traumatic events have been associated with poorer clinical outcomes in people with bipolar disorder. However, the impact of these events in the early stages of the illness remains unclear. The aim of this study was to investigate whether prior traumatic events were related to poorer outcomes 12 months following a first episode of psychotic mania.. Traumatic events were retrospectively evaluated from patient files in a sample of 65 participants who had experienced first episode psychotic mania. Participants were aged between 15 and 28 years and were treated at a specialised early psychosis service. Clinical outcomes were measured by a variety of symptomatic and functioning scales at the 12-month time-point.. Direct-personal traumatic experiences prior to the onset of psychotic mania were reported by 48% of the sample. Participants with past direct-personal trauma had significantly higher symptoms of mania (p=0.02), depression (p=0.03) and psychopathology (p=0.01) 12 months following their first episode compared to participants without past direct-personal trauma, with medium to large effects observed. After adjusting for baseline scores, differences in global functioning (as measured by the Global Assessment of Functioning scale) were non-significant (p=0.05); however, participants with past direct-personal trauma had significantly poorer social and occupational functioning (p=0.04) at the 12-month assessment with medium effect.. Past direct-personal trauma may predict poorer symptomatic and functional outcomes after first episode psychotic mania. Limitations include that the findings represent individuals treated at a specialist early intervention centre for youth and the retrospective assessment of traumatic events may have been underestimated.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Employment; Female; Follow-Up Studies; Humans; Male; Olanzapine; Patient Outcome Assessment; Prospective Studies; Psychiatric Status Rating Scales; Retrospective Studies; Social Behavior; Stress, Psychological; Surveys and Questionnaires; Treatment Outcome; Violence; Young Adult

Olanzapine is the frequently prescribed drug in children and adolescents with bipolar disorder, but unfortunately it has metabolic side-effects. On the other hand, in a number of melatonin studies on sleep cycle, regulation of metabolic abnormalities has been reported. Therefore, we aimed to study effects of melatonin in reducing metabolic side-effects of olanzapine in 11-17 year-old patients with bipolar disorder. Seventy-seven 11-17 year-old outpatients entered into the study after their initial diagnosis of bipolar mood disorder by a psychiatrist. After assessing inclusion and exclusion criteria, 48 patients consented to participate in the study. Of this number, 24 patients were allocated to olanzapine, lithium carbonate, and melatonin and 24 patients were allocated to olanzapine, lithium carbonate, and placebo. Young mania rating scale was performed at baseline. Before treatment initiation and at sixth and twelfth weeks after treatment, Lipid profile, Fasting Blood Sugar (FBS), Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were measured. ANOVA with repeated measure and independent sample t-test were used for data analysis. Nineteen patients in each group completed the study and yielded data for analysis.  ANOVA with repeated measure showed that FBS and Triglyceride (TG) (especially in boys) demonstrated greater increase in the placebo group compared to the melatonin group but the differences were not statistically significant. Melatonin significantly inhibited the rise in Total Cholesterol levels compared to placebo (P=0.032). Mean SBP rose more slowly in the melatonin group (1.05mmHg) compared to placebo (6.36 mmHg) (P=0.023). The trends in DBP did not show any significant pattern. Administration of melatonin along with olanzapine and lithium carbonate could significantly inhibit the rise in cholesterol level and SBP compared to placebo. The effect of melatonin on TG was more obvious in boys. Melatonin was more effective in prevention of SBP rise.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Double-Blind Method; Female; Humans; Lipids; Lithium Carbonate; Male; Melatonin; Olanzapine; Sex Factors

To assess whether early symptom improvement predicts later treatment outcome in acute manic/mixed episodes of bipolar I disorder using Young Mania Rating Scale (YMRS) or Clinical Global Impression scale, bipolar disorders (CGI-BP) assessments.. Data were pooled from two 3-week randomized controlled studies with asenapine (ASE; n=372), olanzapine (OLA; n=391), or placebo (PL; n=197). Early improvement was defined as reduction of YMRS total scores (≥15%, ≥20%, ≥25%) or CGI-BP severity scores (≥1 point change) at days 2, 4, and 7. Treatment outcome at week 3 was defined as response (YMRS: ≥50% score reduction; CGI-BP severity: "minimally ill" or better) or remission (YMRS total score ≤12; CGI-BP severity: "not at all ill"). Odds ratios (ORs) and predictive performance statistics were calculated.. Early improvement occurred in a substantial percentage of patients and was associated with significantly increased ORs for response or remission. For ASE, results were significant as early as day 2 on all measures of YMRS and CGI-severity of mania assessment. For all treatments sensitivity and negative predictive values increased from days 2 to 7 for all YMRS and CGI-BP measures, while specificity values decreased.. In acute manic/mixed episodes, early improvement within 1 week of treatment was associated with significantly increased ORs of endpoint response or remission. While only a subset of early improvers reach the endpoint treatment goals, absence of improvement within week 1 of treatment initiation strongly predicts the unlikely success of subsequent treatment. Further, CGI-based predictors had predictive properties similar to those based on the YMRS scale.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Treatment Outcome; Young Adult

One of the major issues in clinical practice is the accurate differential diagnosis between mixed states and depression, often leading to inappropriate prescriptions of antidepressants in mixed states, and as a consequence, increasing the risk of manic switch and suicide. In order to better define the spectrum of mixed states, it may be useful to develop a dimensional approach. In this context, the MAThyS (Multidimensional Assessment of Thymic States) scale was built to assess activation/inhibition levels in all bipolar mood episodes, and to determine whether a clinical description in terms of activation/inhibition can help better define bipolar states with which both manic and depressive symptoms are associated. The aim of this paper is the validation of the MAThyS scale in 141 bipolar patients in acute states (manic, hypomanic, mixed, or depressive).. The validation of the MAThyS scale was the primary outcome of this 24-week, phase III, open-label, olanzapine single-arm clinical trial. Principal component, factorial analysis, and Cronbach's coefficient calculation (internal consistency) were performed. Concurrent validity (correlations with 17-item Hamilton Depression Rating Scale [HAMD-17], Hamilton Anxiety Rating Scale [HAMA], and Young Mania Rating Scale [YMRS]) and responsiveness to the clinical intervention were assessed (change in MAThyS scale and effect size) at 6 and 24 weeks.. Scree plot of eigenvalues identified a 2-dimension structure ("activation/inhibition level" and "emotional component"). Psychometric properties were good: Cronbach's coefficient was >0.9. Concurrent validity was good with low correlation (-0.19) with the HAMA scale and a higher correlation at baseline with the YMRS (0.72) and HAMD-17(-0.43). As expected, the activation state was predominant in manic, hypomanic, and mixed states while inhibition was predominant in depressive states. MAThyS score improvement was observed (effect size: -0.3 at 6 and 24 weeks).. The MAThyS demonstrated good psychometric properties. The MAThyS scale may help clinicians to better discriminate and follow bipolar episodes, especially the broad spectrum of mixed episodes.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Factor Analysis, Statistical; Humans; Male; Middle Aged; Olanzapine; Principal Component Analysis; Psychiatric Status Rating Scales; Psychometrics; Reproducibility of Results

The efficacy and safety of olanzapine monotherapy are evaluated in Japanese patients from a large, global study of bipolar depression.. This is an analysis of Japanese patients from a 6-week, global (Japan, China, Korea, Taiwan, and the United States), randomized, double-blind, placebo-controlled, Phase 3 study of patients with a depressive episode of bipolar I disorder. The primary outcome was baseline-to-endpoint change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcome measures included the Clinical Global Impressions-Bipolar Version Severity of Illness Scale (CGI-BP), the 17-item Hamilton Depression Rating Scale (HAMD-17) total score, the Young Mania Rating Scale (YMRS) total score, and rates of response (≥50% baseline-to-endpoint reduction in MADRS total score), recovery, and remission.. Of the 156 Japanese patients, 104 had been allocated to olanzapine and 52 to placebo. All results are baseline-to-endpoint change. Compared to placebo, patients in the olanzapine group experienced greater improvement in the primary outcome measure, MADRS total score (-14.9 vs. -10.7; p = .01). They also had greater reductions in the following secondary measures: CGI- BP Depression (-1.41 vs. -0.89; p = .008), CGI-BP Bipolar (-1.31 vs. -0.83; p = .01), HAMD-17 (-11.7 vs. -7.9; p < .01), and YMRS (-0.32 vs. 0.34; p = .03). Differences in rates of response, recovery, and remission were not statistically significant. A greater proportion of olanzapine-treated patients reported treatment- emergent adverse events (87.5% vs. 59.6%; p < .001). Patients treated with olanzapine had greater increases in weight (p < .001) and fasting total cholesterol (p = .008); fasting triglycerides (p = .02), and fasting low-density lipoprotein (p = .01). There was a greater reduction in fasting high-density lipoprotein in olanzapine-treated patients (p = .01). Compared with placebo-group patients, more olanzapine-group patients shifted from borderline to high cholesterol (25.0% vs. 0.0%; p = .007) and had clinically significant weight gain (≥7% body weight) (20.2% vs. 1.9%; p = .001).. Results of this analysis support the efficacy and tolerability of olanzapine for the treatment of bipolar depression in Japanese patients. Results in this population were consistent with those seen in the more ethnically diverse parent study. In making treatment decisions for individual patients, clinicians should carefully consider the risks and benefits of olanzapine treatment.. Clinicatrials.gov ID NCT00510146 Olanzapine Treatment of Patients with Bipolar I Disorder.

Topics: Adolescent; Adult; Antipsychotic Agents; Asian People; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Treatment Outcome

No current data were available regarding the efficacy and safety of olanzapine in Japanese patients with bipolar I disorder with a current manic/mixed episode.. Patients received blindly olanzapine (5-20 mg/day; N=105), haloperidol (2.5-10 mg/day; N=20), or placebo (N=99) for 3 weeks. For the following 3 weeks, the olanzapine and haloperidol groups continued their treatment, while the placebo group switched blindly to olanzapine. The primary efficacy measure was the mean change in Young Mania Rating Scale (YMRS) total score; secondary efficacy measures included bipolar disorder remission rate and switch-to depression. Safety measures included treatment-emergent adverse events (TEAEs), weight and extrapyramidal symptoms (EPSs).. YMRS total score significantly decreased in the olanzapine group compared with the placebo group (-5.62 [95% CI: -8.87, -2.37], p<0.001) after 3 weeks. Compared with haloperidol, olanzapine was not markedly different in improving overall bipolar symptomatology, and fewer olanzapine-treated patients switched to symptomatic depression (2.4% vs 16.7%, p=0.014). Overall incidences of TEAEs were not significantly different among the groups, and EPSs in olanzapine group were less severe than in the haloperidol group.. The small haloperidol sample size limited the conclusions that can be drawn from the statistical comparisons between the active treatments.. This was the first study to evaluate an atypical antipsychotic in Japanese patients with manic bipolar I disorder. Consistent with previous non-Japanese studies, olanzapine was generally well-tolerated and superior to placebo in improving the severity of manic symptoms. Compared to haloperidol, fewer olanzapine-treated patients switched to symptomatic depression, and EPSs were less severe.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Haloperidol; Humans; Japan; Male; Middle Aged; Olanzapine; Young Adult

To assess the safety and efficacy of 18-week olanzapine monotherapy in Japanese patients with bipolar mania, following a 6-week, placebo- and haloperidol-controlled double-blind study (acute study). For those who discontinued the acute study due to lack of efficacy, safety and efficacy was assessed with a combination therapy of olanzapine and a mood stabilizer.. In this open-label, multicenter extension study, patients who completed the acute study received olanzapine (5-20 mg/day) as monotherapy, and patients who discontinued the acute study due to lack of efficacy with greater Young Mania Rating Scale (YMRS) total score than the acute study baseline, received olanzapine in combination with one of three mood stabilizers: lithium, carbamazepine, or valproate. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, weight, and extrapyramidal symptoms (EPSs). Efficacy measures included YMRS total score, and response and remission rates of manic symptoms.. There were no deaths or serious adverse events considered potentially related to olanzapine in the monotherapy group (N = 100) or the combination-therapy group (N = 39). TEAEs occurred in 59.0% and 79.5% of patients in the monotherapy and combination-therapy groups, respectively, and their severities were mostly mild or moderate. Regarding the efficacy measures, in the monotherapy group, mean YMRS change from extension study baseline to endpoint was -3.0, and the response and remission rates at endpoint were 97.0% and 93.0%, respectively. In the combination-therapy group, mean YMRS change from extension-study baseline was -19.8; response and remission rates increased from the extension-study baseline (both 0.0%) to 64.1% and 61.5% respectively by endpoint.. Olanzapine was generally well tolerated during the 18-week extension period in Japanese patients with bipolar mania. Results of both groups were also generally consistent with US and European studies. Monitoring of metabolic parameters is recommended.

Topics: Adult; Affect; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Japan; Lithium; Male; Middle Aged; Olanzapine; Prolactin; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome; Valproic Acid

Weight gain is commonly observed with olanzapine treatment. Zonisamide is an antiepileptic drug associated with weight loss. This study examined the effectiveness of zonisamide in preventing weight gain in 42 patients beginning olanzapine for bipolar disorder or schizophrenia. Each patient had a body mass index of 22 mg/kg or greater and was randomized to taking olanzapine with either zonisamide (n = 20) or placebo (n = 22) for 16 weeks. The primary outcome measure was change in body weight in kilograms from baseline. In the primary analysis using longitudinal regression, patients who received zonisamide had a significantly slower rate of weight gain and increase in body mass index than those who received placebo. The patients treated with zonisamide gained a mean (SD) of 0.9 (3.3) kg, whereas those treated with placebo gained a mean (SD) of 5.0 (5.5) kg; P = 0.01. None of the patients in the zonisamide group, compared with 7 patients (33%) in the placebo group, gained 7% of body weight or greater from baseline (Fisher exact test, P = 0.009). The zonisamide group, however, reported significantly more cognitive impairment as an adverse event than the placebo group (25% vs 0, respectively; P = 0.02). Zonisamide was effective for mitigating weight gain in patients with bipolar disorder or schizophrenia initiating treatment with olanzapine but was associated with cognitive impairment as an adverse event.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Double-Blind Method; Female; Follow-Up Studies; Humans; Isoxazoles; Male; Middle Aged; Olanzapine; Regression Analysis; Schizophrenia; Treatment Outcome; Weight Gain; Young Adult; Zonisamide

Paliperidone ER monotherapy was efficacious in treating acute mania in two 3-week studies in patients with bipolar I disorder. We assessed its efficacy in a study investigating maintenance treatment of clinically stable patients with this disorder.. Patients (n=766), aged 18 to 65 years inclusive, with current manic or mixed episodes were initially randomized (4:1) to flexibly-dosed paliperidone ER (3-12 mg/day) or olanzapine (5-20 mg/day; 3-week acute treatment phase); responders continued the same treatment (12-week continuation phase). Patients on paliperidone ER who achieved remission during this phase were randomized (1:1) to fixed-dose paliperidone ER (n=152) or placebo (n=148); those on olanzapine continued to receive that at fixed dose (n=83) (maintenance phase).. Median time to recurrence of any mood symptoms (primary endpoint) was: 558 days (paliperidone ER), 283 days (placebo) and not observed with olanzapine (<50% of patients experienced recurrence). Time to recurrence of any mood symptoms was significantly longer with paliperidone ER than placebo (p=0.017; based on weighted Z-test at 0.0198 significance level; hazard ratio [placebo: paliperidone ER; unweighted 95% confidence interval]: 1.43 [1.03; 1.98]); the difference was significant for preventing recurrence of manic, but not depressive, symptoms. Treatment-emergent adverse events (maintenance phase) occurred more often in olanzapine group (64%) than placebo (59%) or paliperidone ER groups (55%).. Responder-enriched design prevents extrapolation of data to patients not previously stabilized on paliperidone ER.. Paliperidone ER significantly delayed the time to recurrence of any mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety concerns emerged.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Isoxazoles; Male; Middle Aged; Olanzapine; Paliperidone Palmitate; Pyrimidines; Secondary Prevention; Young Adult

To examine health-related quality of life (HRQoL) in adolescents with bipolar disorder before and after double-blind treatment with olanzapine or placebo.. Parents or legal guardians of 160 adolescents with a manic or mixed episode associated with bipolar I disorder were asked to rate their child's health using the Child Health Questionnaire-Parental Form 50 at baseline, before receiving medication, and then again at the end of participation in a 3-week double-blind placebo-controlled study of olanzapine.. Adolescents in both treatment groups began and ended the study with significantly lower scores than normalized values of healthy peers on several HRQoL subscales (lower ratings indicate more impaired functioning), especially those assessing psychosocial factors. However, participants receiving olanzapine exhibited greater improvement than those in the placebo group across multiple HRQoL subscales, including the Behavior, Family activities, and Mental health subscales. Reduction in manic symptoms was associated with improvement in HRQoL values.. As expected, manic adolescents with bipolar disorder exhibit abnormalities in psychosocial, rather than physical factors associated with HRQoL. Treatment with olanzapine had a greater effect on multiple domains of psychosocial functioning compared with placebo, suggesting that in addition to improving manic symptoms, pharmacologic interventions may lessen some of psychosocial deficits experienced by adolescents with bipolar disorder. However, following 3 weeks of treatment, adolescents with bipolar disorder continued to exhibit deficits in several aspects of psychosocial functioning, indicating that additional pharmacologic and psychosocial interventions may be necessary to further improve functional outcome.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Health Status; Humans; Male; Mental Health; Olanzapine; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Olanzapine has demonstrated efficacy in acute mania and bipolar I disorder (BDI) maintenance, but efficacy in brief therapy in more diverse populations, including patients with bipolar II disorder (BDII)/bipolar disorder not otherwise specified (BDNOS) with syndromal/subsyndromal depressive/mood elevation symptoms and taking/not taking concurrent medications remains to be established.. Fifty adult outpatients (24 BD1, 22 BDII, 4 BDNOS, mean ± SD age 40.8 ± 11.5 years, 28.1% female, already taking 1.1 ± 1.2 [median 1] prescription psychotropics) with 17-item Hamilton Depression Rating Scale (HDRS) ≥10 and/or Young Mania Rating Scale (YMRS) ≥10 and ≤24, were randomized to double-blind olanzapine (2.5-20 mg/day) versus placebo for one week.. Among 45 patients with post-baseline ratings, olanzapine (9.0 ± 5.8 mg/day, n = 23) compared to placebo (n = 22) tended to yield greater Clinical Global Impressions-Bipolar Version-Overall Severity of Illness (-1.4 ± 0.9 versus -0.8 ± 1.1, p = 0.08) and Hamilton Anxiety Scale (-7.9 ± 6.3 versus -3.8 ± 6.1, p = 0.07) improvements, and YMRS/HDRS remission rate (47.8% versus 22.7%, p = 0.08), but significantly increased median weight (+2 versus -1 lbs, p = 0.001), and rates of excessive appetite (54.2% versus 22.7%, p = 0.04) and tremor (50.0% versus 9.1% p = 0.004). Number Needed to Treat and 95% Confidence Interval for YMRS/HDRS remission were 4 (1-∞). Numbers Needed to Harm for excessive appetite and tremor were 4 (1-21) and 3 (1-6), respectively.. Olanzapine tended to yield affective improvement and significantly increased weight, appetite, and tremor. Larger controlled studies appear feasible and warranted to assess brief olanzapine therapy in heterogeneous symptomatic bipolar disorder patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pilot Projects; Psychiatric Status Rating Scales; Treatment Outcome

Post hoc mediator/moderator analyses were designed to identify risk factors and their relationships in predicting relapse in olanzapine- or lithium-treated bipolar patients with an index manic or mixed episode. The aim was to identify moderators that precede and influence other variables to affect relapse and mediators that explain how or why a second variable affects relapse.. We examined DSM-IV-diagnosed bipolar I disorder patients who met symptomatic remission criteria of an index manic or mixed (6.3%) episode after acute (6-12 weeks), open-label, combined therapy with olanzapine (5-20 mg/d; mean dose = 13.5 mg/d) plus lithium (300-1,800 mg/d; mean dose = 1,003.3 mg/d) followed by double-blind randomization to lithium (n = 214) or olanzapine (n = 217) for up to 52 weeks. The study started on August 5, 1999, and finished on June 14, 2002. Mediator/moderator analyses with α cut at .05 were used to understand how variables work together to impact rate of relapse.. For lithium-treated patients, variables identified for relapse were country of residence, smoking status, previous episode history, and previous lithium use. For olanzapine-treated patients, risk factors included smoking status, previous episode history, amount of time patients had a 21-Item Hamilton Depression Rating Scale (HDRS-21) score ≤ 8 at pre-randomization, and HDRS-21 score at randomization. For lithium-treated patients, no mediators/moderators were identified among relapse variables. For olanzapine-treated patients, several baseline variables--such as previous number of mood episodes (manic or depressive)--operate through severity of depressive symptoms prior to remission (mediator) to affect relapse rate. On the other hand, the effect of the patient's pre-remission depressive symptoms on outcome is moderated by the polarity of the first episode, whether manic, depressive, or mixed.. Mediators and moderators may provide valuable information in the treatment planning of patients with bipolar disorder and potentially influence treatment outcomes.

Topics: Adult; Affect; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Recurrence; Risk Factors

Atypical antipsychotics are widely used in bipolar mania. However, the efficacy of atypical antipsychotics in bipolar depression has not been comprehensively explored.. To evaluate olanzapine monotherapy in patients with bipolar depression.. Patients with bipolar depression received olanzapine (5-20 mg/day, n = 343) or placebo (n = 171) for 6 weeks. The primary outcome was change from baseline to end-point in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included: Clinical Global Impression - Bipolar Version (CGI-BP) scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young Mania Rating Scale (YMRS) scores, and the rate of response (≥50% reduction in MADRS at end-point), recovery (MADRS ≤12 for ≥4 weeks plus treatment completion) and remission (MADRS ≤8). The trial was registered with ClinicalTrials.gov (NCT00510146).. Olanzapine demonstrated: significantly greater (P<0.04) improvements on MADRS (least-squares mean change -13.82 v. -11.67), HRSD-17 and YMRS total scores and all CGI-BP subscale scores v. placebo; significantly (P≤0.05) more response and remission, but not recovery; significantly (P<0.01) greater mean increases in weight, fasting cholesterol and triglycerides; and significantly more (P<0.001) patients gained ≥7% body weight.. Olanzapine monotherapy appears to be efficacious in bipolar depression. Additional long-term studies are warranted to confirm these results. Safety findings were consistent with the known safety profile of olanzapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Treatment Outcome; Young Adult

Pharmacogenomic analyses of weight gain during treatment with second-generation antipsychotics have resulted in a number of associations with variants in ankyrin repeat and kinase domain containing 1 (ANKK1)/dopamine D2 receptor (DRD2) and serotonin 2C receptor (HTR2C) genes. These studies primarily assessed subjects with schizophrenia who had prior antipsychotic exposure that may have influenced the amount of weight gained from subsequent therapies. We assessed the relationships between single-nucleotide polymorphisms (SNPs) in these genes with weight gain during treatment with olanzapine in a predominantly antipsychotic-naive population.. The association between 5 ANKK1, 54 DRD2, and 11 HTR2C SNPs and weight change during 8 weeks of olanzapine treatment was assessed in 4 pooled studies of 205 white patients with diagnoses other than schizophrenia who were generally likely to have had limited previous antipsychotic exposure.. The A allele of DRD2 rs2440390(A/G) was associated with greater weight gain in the entire study sample (P = .0473). Three HTR2C SNPs in strong linkage disequilibrium, rs6318, rs2497538, and rs1414334, were associated with greater weight gain in women but not in men (P = .0032, .0012, and .0031, respectively). A significant association with weight gain for 2 HTR2C SNPs previously reported associated with weight gain, -759C/T (rs3813929) and -697G/C (rs518147), was not found.. Associations between weight gain and HTR2C and DRD2 variants in whites newly exposed to olanzapine may present opportunities for the individualization of medication selection and development based on differences in adverse events observed across genotype groups.

Topics: Adult; Alleles; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Borderline Personality Disorder; Depressive Disorder, Treatment-Resistant; Female; Genetic Association Studies; Humans; Linkage Disequilibrium; Male; Mental Disorders; Middle Aged; Olanzapine; Pharmacogenetics; Polymorphism, Single Nucleotide; Risperidone; Schizophrenia; Weight Gain

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

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

Potential predictors of remission in mixed bipolar I disorder were identified using early Clinical Global Impression-Severity (CGI-S) improvement criteria in divalproex-resistant patients randomized to olanzapine augmentation (olanzapine + divalproex; N = 101) in a 6-week, double-blind, placebo-controlled trial. In a post-hoc analysis, receiver operating characteristics of 1-point decreases in the CGI-S total score after 2, 4, 7, and 14 days were examined as predictors of endpoint (Week 6 or last observation) remission of depression and/or mania as defined by 21-item Hamilton Depression Rating Scale (HDRS-21) and Young Mania Rating Scale (YMRS) total score ≤8. Based on a 1-point improvement in CGI-S as a predictor of remission, all odds ratios (ORs) and 95% confidence intervals (CIs) were statistically significant for depression or mania remission criteria. ORs for mixed symptom remission with a decrease ≥1 in CGI-S scores at Day 2 for olanzapine augmentation were (6.727; CI: 2.382, 18.997; p < .001) with negative predictive value = 89.5% and positive predictive value = 44.2%. Changes in HDRS-21 and YMRS individual item scores after 2 days of augmentation as predictors of endpoint remission identified that decreases in HDRS-21 symptom item scores (early, middle, and/or late insomnia; paranoid; agitation; and somatic/gastrointestinal) predicted depressive symptom remission at endpoint, and decreases in YMRS item scores (language-thought disorder and irritability) were associated with manic symptom remission at endpoint. Because remission with augmentation therapy may occur in as few as one in ten individuals who lack very early symptom reduction, lack of early improvement may indicate a need to expediently reassess treatment strategy.

Topics: Adolescent; Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Middle Aged; Olanzapine; Predictive Value of Tests; Retrospective Studies; ROC Curve; Secondary Prevention; Single-Blind Method; Time Factors; Valproic Acid; Young Adult

To evaluate the clinical value of early partial symptomatic improvement in predicting the probability of response during the short-term treatment of bipolar depression.. Blinded data from 10 multicenter, randomized, double-blind, placebo-controlled trials in bipolar I or II depression were used to determine if early improvement (≥20% reduction in depression symptom severity after 14 days of treatment) predicted later short-term response or remission. Sensitivity, specificity, efficiency, and positive and negative predictive values (PPV, NPV) were calculated using an intent to treat analysis of individual and pooled study data.. 1913 patients were randomized to active compounds (aripiprazole, lamotrigine, olanzapine/olanzapine-fluoxetine, and quetiapine), and 1456 to placebo. In the pooled positive studies, early improvement predicted response and remission with high sensitivity (86% and 88%, respectively), but rates of false positives were high (53% and 59%, respectively). Pooled negative predictive values for response/remission (i.e. confidence in knowing the drug will not result in response or remission) were 74% and 82%, respectively, with low rates of false negatives (14% and 12%, respectively).. Early improvement in an individual patient does not appear to be a reliable predictor of eventual response or remission due to an unacceptably high false positive rate. However, the absence of early improvement appears to be a highly reliable predictor of eventual non-response, suggesting that clinicians can have confidence in knowing when a drug is not going to work during short-term treatment. Patients who fail to demonstrate early improvement within the first two weeks of treatment may benefit from a change in therapy.

Topics: Antidepressive Agents, Second-Generation; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Fluoxetine; Humans; Lamotrigine; Olanzapine; Piperazines; Predictive Value of Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Quinolones; Remission Induction; Sensitivity and Specificity; Time Factors; Treatment Outcome; Triazines

This study compared the 2-year outcomes of patients with a manic/mixed episode of bipolar disorder taking olanzapine monotherapy or olanzapine in combination with other agents.. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year, prospective, observational study of clinical and functional outcomes of bipolar patients with an index manic/mixed episode. The study consisted of two phases: acute (12 weeks) and maintenance (follow-up over 2 years). The longitudinal outcome measure was the Clinical Global Impression-Bipolar Disorder scale. Cox regression models compared outcomes of both therapy groups using intention-to-treat and switching medication analysis. Treatment-emergent adverse events were also assessed.. 1076 patients were included in this analysis. 29% took olanzapine as monotherapy (n = 313) and 71% as combination (n = 763) at 12-weeks post-baseline (end of study acute phase). After adjusting for patient characteristics using switching medication analysis, only relapse rates differed (p = 0.01) in favour of monotherapy-treated patients. There was no significant difference in rates of improvement, remission, and recovery. Patients treated with combination therapy reported more tremor (OR 2.37, 95%CI 1.44-3.89) and polyuria (OR 3.08, 95%CI 1.45-6.54) treatment-emergent events than monotherapy, although weight change was greater in the monotherapy group.. Unknown confounding and potential selection bias may differentially impact treatment outcomes.. EMBLEM patients benefitted from the selected therapy to a similar extent. Differences in patient characteristics between those prescribed monotherapy and combination therapy appear to be clinically relevant in the treatment decision. Physicians must balance the benefits and risks when determining appropriate treatment for individual patients.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Male; Olanzapine; Proportional Hazards Models; Psychiatric Status Rating Scales; Secondary Prevention; Time Factors; Treatment Outcome

The staging model suggests that early stages of bipolar disorder respond better to treatments and have a more favourable prognosis. This study aims to provide empirical support for the model, and the allied construct of early intervention.. Pooled data from mania, depression, and maintenance studies of olanzapine were analyzed. Individuals were categorized as having had 0, 1-5, 6-10, or >10 prior episodes of illness, and data were analyzed across these groups.. Response rates for the mania and maintenance studies ranged from 52-69% and 10-50%, respectively, for individuals with 1-5 previous episodes, and from 29-59% and 11-40% for individuals with >5 previous episodes. These rates were significantly higher for the 1-5 group on most measures of response with up to a twofold increase in the chance of responding for those with fewer previous episodes. For the depression studies, response rates were significantly higher for the 1-5 group for two measures only. In the maintenance studies, the chance of relapse to either mania or depression was reduced by 40-60% for those who had experienced 1-5 episodes or 6-10 episodes compared to the >10 episode group, respectively. This trend was statistically significant only for relapse into mania for the 1-5 episode group (p=0.005).. Those individuals at the earliest stages of illness consistently had a more favourable response to treatment. This is consistent with the staging model and underscores the need to support a policy of early intervention.

Topics: Adult; Age of Onset; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Disease Progression; Double-Blind Method; Early Diagnosis; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Models, Psychological; Olanzapine; Prognosis; Psychiatric Status Rating Scales; Recurrence; Treatment Outcome; Young Adult

To evaluate early improvement associated with atypical antipsychotic treatment as a predictor of later response or remission among patients experiencing an acute manic or mixed episode without psychotic features.. A post hoc analysis was performed on data from a 3-week, randomized, double-blind clinical trial of olanzapine (N = 147) or risperidone (N = 127) to treat inpatients aged 18-70 years meeting DSM-IV criteria for bipolar I disorder. Early improvement, measured as percent change (≥ 25% and ≥ 50% cut points) in the Young Mania Rating Scale (YMRS) total score, was assessed after 2 days and 1 week of treatment. Receiver operating characteristic curves, sensitivity and specificity, and positive and negative predictive values were calculated to determine whether early improvement predicted endpoint (week 3) response or remission. The study was conducted from July 2001 through June 2002.. Among 234 patients with ≥ 25% reduction in YMRS total score at week one, 167 (71.4%) responded and 121 (51.7%) remitted at endpoint. Of the 40 patients with < 25% improvement, 25% (n = 10) responded and 5% (n = 2) remitted at endpoint. A total of 157 patients had a ≥ 50% reduction in week 1 YMRS total score, of whom 132 (84.1%) responded and 101 (64.3%) remitted at endpoint. Of the 117 patients with < 50% improvement, 45 (38.5%) responded and 22 (18.8%) remitted at endpoint.. Improvement in manic or mixed symptoms at week 1 appears to be a good predictor of treatment outcome. Patients not having sufficient improvement (< 25% reduction in YMRS score) were less likely to reach response or remission by week 3. Patients who achieved response by week 1 (≥ 50% reduction in YMRS score) were likely to remain responders at endpoint. These data suggest the potential to assess benefit in the treatment of manic or mixed symptoms within 1 week of initiating olanzapine or risperidone.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Remission Induction; Risperidone; ROC Curve; Time Factors; Treatment Outcome; Young Adult

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

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

Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.. In the original trials (A7501004 [NCT00159744], A7501005 [NCT00159796]), 977 patients were randomized to flexible-dose sublingual asenapine (10 mg twice daily on day 1; 5 or 10 mg twice daily thereafter), placebo, or oral olanzapine 5-20 mg once daily for 3 weeks. Three populations were defined using baseline depressive symptoms: (1) Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥20 (n = 132); (2) Clinical Global Impression for Bipolar Disorder-Depression (CGI-BP-D) scale severity score ≥4 (n = 170); (3) diagnosis of mixed episodes (n = 302) by investigative site screening. For each population, asenapine and olanzapine were independently compared with placebo using least squares mean change from baseline on depressive symptom measures.. Decreases in MADRS total score were statistically greater with asenapine versus placebo at days 7 and 21 in all populations; differences between olanzapine and placebo were not significant. Decreases in CGI-BP-D score were significantly greater with asenapine versus placebo at day 7 in all categories and day 21 in population 1; CGI-BP-D score reductions were significantly greater with olanzapine versus placebo at day 21 in population 1 and day 7 in populations 2 and 3.. These post hoc analyses show that asenapine reduced depressive symptoms in bipolar I disorder patients experiencing acute manic or mixed episodes with clinically relevant depressive symptoms at baseline; olanzapine results appeared to be less consistent. Controlled studies of asenapine in patients with acute bipolar depression are necessary to confirm the generalizability of these findings.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Dibenzocycloheptenes; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Severity of Illness Index

This randomized, open-label trial aimed to compare the metabolic effects of olanzapine orally disintegrating tablets (ODT) and solid oral tablets (SOT) in bipolar depressed and mixed outpatients.. Participants were openly randomized to receive olanzapine ODT (n = 13) or SOT (n = 10), 10 to 20 mg, once daily. Weight, body mass index (BMI), Food Craving Inventory (FCI), and Three-Factor Eating Questionnaire (3-FEQ) scores were assessed at baseline and at weeks 1, 2, 4, 6, and 8. Fasting glucose and lipid levels were assessed at baseline and at week 8. Insulin and leptin concentrations were measured just prior to olanzapine baseline dosing, 1 and 2 hours following administration of baseline dose, and at weeks 4 and 8.. Patients showed significant increases in weight, BMI, and leptin area under the concentration-time curve (AUC), but not in FCI or 3-FEQ scores, over 8 weeks of treatment with olanzapine ODT and SOT. However, no significant differences between olanzapine formulations (ODT vs SOT) were observed in any of the measures assessed, except for a significantly lower triglyceride concentration in the ODT group at week 8.. There was no consistent difference in metabolic profile between olanzapine ODT and SOT formulations during short-term treatment of bipolar depressed patients. Potential differences related to effects on triglyceride concentration warrant further confirmation.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Weight; Drug Administration Schedule; Feeding Behavior; Female; Gastrointestinal Hormones; Glycemic Index; Humans; Male; Middle Aged; Olanzapine; Tablets

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

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

Among the available mood stabilizers, it appears that lithium may share an important role for treatment of acute mania. In a study from Sep. 2007 to Apr. 2008 at Razi Psychiatric Hospital we evaluated the efficiency of olanzapine vs. lithium.. Forty (40) female inpatients meeting DSM-IV-TR criteria for acute mania were entered into a 3-week parallel group, double-blind study for random assignment to olanzapine or lithium carbonate in a 1:1 ratio. Primary outcome measurements were the changes in Manic State Rating Scale (MSRS) at baseline and weekly intervals up to the third week. Similarly, overall illness severity was rated using the Clinical Global Impression-Severity of illness scale (CGI-S) at baseline and at the end of the third week. Analysis of the data was accomplished by means of split-plot (mixed) and repeated measures analysis of variance (ANOVA) and t test.. While both olanzapine and lithium were found to be significantly helpful in the improvement of manic symptoms (p<0.05), lithium was considerably more successful by the end of the third week (p<0.0002 and p<0.003, for frequency and intensity of the symptoms). CGI-S also showed important improvements with both olanzapine and lithium (p<0.043 and p<0.015 for olanzapine and lithium).. Though both olanzapine and lithium were effective in the improvement of manic symptoms, lithium was more beneficial.

Topics: Acute Disease; Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Inpatients; Lithium Carbonate; Olanzapine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

To evaluate common genetic variations for association with symptomatic improvement in bipolar I depression following treatment with olanzapine/fluoxetine combination (OFC) or lamotrigine.. Symptom improvement was assessed in 88 OFC-treated and 85 lamotrigine-treated white patients with bipolar I depression in the 7-week acute period of a randomized, double-blind study comparing OFC (6/25, 6/50, 12/25, or 12/50 mg/d [olanzapine/fluoxetine]) with lamotrigine (titrated to 200 mg/d). The original study was conducted from November 2003 to August 2004. Single nucleotide polymorphisms (SNPs) were genotyped in a set of 19 candidate genes corresponding to known sites of activity for olanzapine and fluoxetine or previously associated with antidepressant or antipsychotic response. Primary outcome was the reduction in Montgomery-Asberg Depression Rating Scale (MADRS) total score as assessed by the difference by genotype from baseline to week 7 from a mixed-effects repeated measures analysis with terms for visit, genotype, genotype-by-visit interaction, and baseline MADRS score as a covariate.. SNPs within the dopamine D(3) receptor and histamine H(1) receptor (HRH1) genes were significantly associated with response to OFC. SNPs within the dopamine D(2) receptor, HRH1, dopamine beta-hydroxylase, glucocorticoid receptor, and melanocortin 2 receptor genes were significantly associated with response to lamotrigine.. SNPs in specific candidate genes were associated with symptomatic improvement in a treatment-specific fashion. These results suggest the importance of dopaminergic effects in the treatment of patients with bipolar I depression and the potential utility of genotyping in selection of pharmacologic treatments for bipolar depression.

Topics: Adult; Antidepressive Agents, Second-Generation; Benzodiazepines; Bipolar Disorder; Dopamine beta-Hydroxylase; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Fluoxetine; Genetic Association Studies; Genotype; Humans; Lamotrigine; Male; Olanzapine; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Receptor, Melanocortin, Type 2; Receptors, Dopamine D2; Receptors, Dopamine D3; Receptors, Glucocorticoid; Receptors, Histamine H1; Treatment Outcome; Triazines

We evaluated the efficacy, tolerability, and safety of olanzapine monotherapy in 20 adult patients with bipolar I or II disorder, depressed phase. Patients received open-label olanzapine monotherapy (mean modal dose, 15 mg/day) for 8 weeks. Assessments of psychopathology (Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology [QIDS-SR-16], Young Mania Rating Scale [YMRS]), clinical global state (Clinical Global Impressions [CGI] scale), and safety/tolerability were performed at baseline, and at 1, 2, 4, 6, and 8 weeks. Seventeen patients (85.0%) completed the study. Improvement in MADRS total scores was observed after the first week of treatment, and at all remaining follow-up time points (p < or = 0.005). Parallel improvement in QIDS-SR-16 (p < 0.001) and CGI-Severity (p < 0.001) was observed between baseline and study endpoint. Nine (45%) subjects achieved positive treatment response, eight of whom (40%) also achieved symptom remission. There were significant increases in weight (+3.2 kg, p = 0.001) and body mass index (+1.1 kg/m(2), p = 0.001), but not fasting glucose or lipids, with the exception of reduced triglyceride levels in the overall sample, and reduced HDL cholesterol in females. Olanzapine may be an effective, well-tolerated option for treating acute non-psychotic depression across a variety of bipolar disorder subtypes.

Topics: Adolescent; Adult; Benzodiazepines; Bipolar Disorder; Depression; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome; Young Adult

Asenapine is indicated in adults for acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. This randomized, double-blind, placebo-controlled trial assessed the efficacy, safety, and tolerability of asenapine in bipolar I disorder.. Adults experiencing manic or mixed episodes were randomized to 3 weeks of flexible-dose treatment with sublingual asenapine (day 1: 10mg BID, 5 or 10mg BID thereafter; n=185), placebo (n=98), or oral olanzapine (day 1: 15 mg QD, 5-20mg QD thereafter; n=205). Primary efficacy, YMRS total score change from baseline to day 21, was assessed using ANCOVA with last observation carried forward.. Mean daily doses were 18.4 mg asenapine and 15.9mg olanzapine. Least squares mean changes in YMRS total score on day 21 were significantly greater with asenapine than placebo (-11.5 vs -7.8; P<0.007), with advantage seen as early as day 2 (-3.2 vs -1.7; P=0.022). Changes with olanzapine on days 2 and 21 also exceeded placebo (both P<0.0001). YMRS response and remission rates with olanzapine, but not asenapine, exceeded those of placebo. Incidence of EPS-related adverse events was 10.3%, 3.1%, and 6.8% with asenapine, placebo, and olanzapine, respectively; incidence of clinically significant weight gain (7.2%; 1.2%; 19.0%). Mean weight change (baseline to endpoint) was 0.9, 0.1, and 2.6 kg with asenapine, placebo, and olanzapine, respectively.. As this short-term study was designed for comparisons with placebo, any comparisons between asenapine and olanzapine should be interpreted cautiously.. Asenapine was superior to placebo in reducing YMRS total score and was well tolerated.

Topics: Acute Disease; Administration, Sublingual; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Young Adult

To compare antimanic response to olanzapine therapy in youth with bipolar disorder (BPD) based on the status of comorbidity with obsessive-compulsive disorder (OCD).. Secondary analysis of identically designed 8-week open-label trials of olanzapine therapy in youth with BPD. Severity of mania assessed with the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI) scales.. Of the 52 BPD subjects (mean age 8.4 +/- 3.1 years) enrolled in the olanzapine trials (mean dose 8.5 +/- 4.3 mg/day), 39% (n = 20) met criteria for comorbid OCD. Antimanic response in BPD subjects was significantly worse in the presence of comorbid OCD (YMRS mean reduction: -5.9 +/- 13.1 versus -13.7 +/- 18.8, p = 0.04; > or = 30% reduction: 25% versus 63%, p = 0.008; CGI-Improvement score < or = 2: 25% versus 68%, p = 0.003). There was no difference in the rate of dropouts (50% versus 29%, p = 0.2) or adverse effects in BPD subjects with or without comorbid OCD.. Less than expected antimanic response to olanzapine therapy in the presence of comorbidity with OCD suggests that OCD is an important functionally impairing psychiatric comorbidity that may impact the efficacy of antimanic agents in youth with BPD. This study is limited by its design of secondary analysis of data from trials of an uncontrolled nature. Further prospective controlled trials are warranted.

Topics: Adolescent; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Child; Comorbidity; Female; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

Data from the EMBLEM Study, a 2-year, prospective, observational study of health outcomes associated with acute treatment of patients experiencing a manic/mixed episode of bipolar disorder, was used to compare the effectiveness of olanzapine monotherapy versus risperidone monotherapy, and to investigate whether the treatment effects were similar to those reported in a 3-week, randomized controlled trial assessing the same treatments. Symptom severity measures included the Young Mania Rating Scale (YMRS), the 5-item Hamilton Depression Rating Scale, and the Clinical Global Impression-Bipolar Disorder Scale. A total of 245 EMBLEM inpatients were analyzed with YMRS >or=20: olanzapine (n=209), risperidone (n=36). Both the treatment groups had similar improvements in YMRS from baseline to 6 weeks, but there was a significantly greater improvement in 5-item Hamilton Depression Rating Scale in the olanzapine group. There was a similar improvement in Clinical Global Impression-Bipolar Disorder Scale in both the groups and the occurrence of treatment-emergent adverse events and weight gain did not differ between the treatment groups. The EMBLEM results partly support those of the randomized controlled trial, which suggests olanzapine and risperidone have similar improvements in mania but that olanzapine monotherapy may be more effective than risperidone monotherapy in the treatment of depressive symptoms associated with mania. Limitations include differences in study design, patient population, and length of follow-up.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

Asenapine is approved in the United States for acute treatment of manic or mixed episodes of bipolar I disorder with or without psychotic features. We report the results of long-term treatment with asenapine in patients with bipolar I disorder.. Patients completing either of two 3-week efficacy trials and a subsequent 9-week double-blind extension were eligible for this 40-week double-blind extension. Patients in the 3-week trials were randomized to flexible-dose asenapine (5 or 10mg BID), placebo, or olanzapine (5-20mg QD; included for assay sensitivity only). Patients entering the extension phase maintained their preestablished treatment; those originally randomized to placebo received flexible-dose asenapine (placebo/asenapine). Safety and tolerability endpoints included adverse events (AEs), extrapyramidal symptoms, laboratory values, and anthropometric measures. Efficacy, a secondary assessment, was measured as change in Young Mania Rating Scale (YMRS) total score from 3-week trial baseline to week 52 with asenapine or olanzapine; the placebo/asenapine group was assessed for safety only.. Incidence of treatment-emergent AEs was 71.9%, 86.1%, and 79.4% with placebo/asenapine, asenapine, and olanzapine, respectively. The most frequent treatment-emergent AEs were headache and somnolence with placebo/asenapine; insomnia, sedation, and depression with asenapine; and weight gain, somnolence, and sedation with olanzapine. Among observed cases, mean ± SD changes in YMRS total score at week 52 were -28.6 ± 8.1 and -28.2 ± 6.8 for asenapine and olanzapine, respectively.. The study did not have a long-term placebo group.. In this 52-week extension in patients with bipolar mania, asenapine was well tolerated and long-term maintenance of efficacy was supported.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Double-Blind Method; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Long-Term Care; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Young Adult

To evaluate the efficacy and safety of armodafinil, the longer-lasting isomer of modafinil, when used adjunctively in patients with bipolar depression.. In this 8-week, multicenter, randomized, double-blind, placebo-controlled study conducted between June 2007 and December 2008, patients who were experiencing a major depressive episode associated with bipolar I disorder (according to DSM-IV-TR criteria) despite treatment with lithium, olanzapine, or valproic acid were randomly assigned to adjunctive armodafinil 150 mg/d (n = 128) or placebo (n = 129) administered once daily in the morning. The primary outcome measure was change from baseline in the total 30-item Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C₃₀) score. Secondary outcomes included changes from baseline in scores on the Montgomery-Åsberg Depression Rating Scale, among other psychological symptom scales. Statistical analyses were performed using analysis of covariance (ANCOVA), with study drug and concurrent mood stabilizer treatment for bipolar disorder as factors and the corresponding baseline value as a covariate. A prespecified sensitivity analysis was done using analysis of variance (ANOVA) if a statistically significant treatment-by-baseline interaction was found. Tolerability was also assessed.. A significant baseline-by-treatment interaction in the total IDS-C₃₀ score (P = .08) was found. Patients administered adjunctive armodafinil showed greater improvement in depressive symptoms as seen in the greater mean ± SD change on the total IDS-C₃₀ score (-15.8 ± 11.57) compared with the placebo group (-12.8 ± 12.54) (ANOVA: P = .044; ANCOVA: P = .074). No differences between treatment groups were observed in secondary outcomes. Adverse events reported more frequently in patients receiving adjunctive armodafinil were headache, diarrhea, and insomnia. Armodafinil was not associated with an increased incidence and/or severity of suicidality, depression, or mania or with changes in metabolic profile measurements.. In this proof-of-concept study, adjunctive armodafinil 150 mg/d appeared to improve depressive symptoms according to some, but not all, measures and was generally well tolerated in patients with bipolar depression.. clinicaltrials.gov Identifier: NCT00481195.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antimanic Agents; Benzhydryl Compounds; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Middle Aged; Modafinil; Olanzapine; Valproic Acid

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

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

In a population of patients with manic and mixed mood episodes, olanzapine has proven effective in maintaining response, as compared to placebo. Whether this is true for the subpopulation of patients with a mixed index episode is not known.. Post-hoc analyses were conducted on data from patients presenting with a mixed index episode who were enrolled in a larger double-blind, placebo-controlled trial. Patients who met remission criteria at 2 consecutive weekly visits during 6 to 12 weeks of open-label olanzapine treatment were randomly assigned to olanzapine or placebo treatment for 48 weeks. The incidence of and time to symptomatic relapse were calculated for any mood episode, and for depressive, manic, hypo-manic, and mixed mood episodes.. A total of 121 of 304 patients (39.8%) met criteria for symptomatic remission in the open-label treatment phase and were randomly assigned to olanzapine (n=76) or placebo (n=45). Compared to the placebo group, the olanzapine group had a lower incidence of (59.2% versus 91.1%, p<0.001) and a longer time to (46 versus 15 days, p<0.001) symptomatic relapse of any kind. Olanzapine-treated patients also experienced longer time to depressive symptomatic relapse (85 versus 22 days, p=0.001) and manic symptomatic relapse (too few relapses to calculate versus 42 days, p<0.001) than did placebo-treated patients.. Compared with placebo, olanzapine treatment was associated with longer maintenance of response in patients presenting with a mixed index episode of bipolar I disorder.

Topics: Adult; Affect; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Double-Blind Method; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Secondary Prevention; Time Factors; Treatment Outcome

To determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) compared with lamotrigine (Lam) for long-term treatment of bipolar I depression, this 25-wk, randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/d, n=205) with Lam titrated to 200 mg/d (n=205) in patients with bipolar I disorder, depressed. A protocol-specified analysis of 7-wk outcomes was previously reported. Outcome measures included Clinical Global Impressions-Severity of Illness (CGI-S) (primary), Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS) scores. OFC-treated patients had significantly greater improvement than Lam-treated patients over 25 wk on CGI-S (p=0.008), MADRS (p=0.005), and YMRS (p<0.001) scores, and from baseline across visits from week 5 (titration complete) to the end of the study on CGI-S (p=0.043), MADRS (p=0.017), and YMRS (p=0.001) scores. Of patients in remission after the 7-wk acute phase, there was no significant difference between treatment groups in the incidence of relapse (MADRS >15, p=0.528). Rate of treatment-emergent mania was not significantly different by treatment (p=0.401). OFC-treated patients had more frequent (p<0.05) somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor; Lam-treated patients had more frequent insomnia. There was a significant difference in incidence of treatment-emergent cholesterol > or = 240 (p<0.001) and in weight gain of > or = 7% (p<0.001) in favour of the Lam group. Patients with bipolar I depression had significantly greater symptom improvement over 25 wk on OFC compared with Lam. There was no treatment difference in incidence of relapse. OFC-treated patients had more treatment-emergent adverse events and greater incidence of weight gain and hypercholesterolaemia.

Topics: Adolescent; Adult; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Humans; Lamotrigine; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Time Factors; Treatment Outcome; Triazines; Young Adult

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

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

We hypothesized that predominant episode-polarity would predict response to treatment of depressive episodes in bipolar I disorder (BPD) patients with treatment in a placebo-controlled trial, in the sense that patients with manic predominant polarity (PM) would respond better than patients with depressive predominant polarity (PD).. This post-hoc analysis of a published trial examined outcomes of 788 depressed (MADRS score >or=20) adult BPD patients with baseline and follow-up assessments, according to their predominant polarity based on previous recurrences of mania-hypomania vs. depression in >or=2:1 excess. Patients (total=833) were randomized to an 8-week trial of treatment with placebo (n=377), olanzapine (5-20 mg/day; n=370), or olanzapine/fluoxetine combination (OFC; 6/25, 6/50, or 12/50 mg/day; n=86). Treatment response was based on improvement in Clinical Global Impression of depression severity (CGI-D). We analyzed for associations of this outcome with predominant lifetime illness-polarity, based on retrospective SCID-based assessment of individual clinical history.. Predominant polarity could be demonstrated in 367/788 patients (46.6%), showing a 2.7-fold excess of predominant depressive over manic past-illnesses (34.1%/12.4%), with similar distribution by sex and among treatment-arms. Moreover, based on least-square change in CGI-D severity (based on a mixed model of repeated measures [MMRM]), predominant polarity has different impact in the treatment outcome for each gender. Men with predominantly manic polarity had statistically significant better improvement than men with predominantly depressive polarity. Such difference was not observed in the female population. Other outcome measures yielded similar conclusions.. Predominant previous depressive>manic episodes selectively yielded poorer responses of BPD to treatment for acute BP depression, particularly in men.

Topics: Antidepressive Agents, Second-Generation; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Olanzapine; Predictive Value of Tests; Psychiatric Status Rating Scales; Treatment Outcome; Young Adult

The aim of this 6-month observational study was to examine which clinical, eating- and lifestyle-related factors were associated with weight gain in patients initiating or switching to oral olanzapine for the treatment of schizophrenia or bipolar mania. A total of 622 outpatients in four countries (China, Mexico, Romania, Taiwan) were assessed at monthly intervals for up to 6 months. Mixed model repeated-measures analysis, adjusted for baseline weight, was used to identify which factors were associated with weight gain during olanzapine therapy. After 6 months of therapy, the LS mean weight change was +4.1 kg and 43.9% of the patients had significant (> or = 7%) weight gain. Early significant weight gain after 2 months of therapy occurred in 23.4% of the patients and these patients gained significantly more weight overall. Ten factors were associated with weight gain during 6 months of olanzapine therapy in an exploratory multivariate analysis: country, housing conditions, stronger appetite, excessive amount of food needed to feel full, eating until uncomfortably full, thoughts preoccupied with food, meal location, increased meal frequency, evening snack consumption, and a lower amount of vigorous exercise. These results indicate that the influence of environmental, eating- and lifestyle-related factors should be considered when assessing weight gain during olanzapine therapy.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Demography; Diagnostic and Statistical Manual of Mental Disorders; Feeding Behavior; Female; Health Status; Humans; International Cooperation; Life Style; Male; Obesity; Olanzapine; Prospective Studies; Schizophrenia; Severity of Illness Index; Weight Gain

This 6-week, randomized, double-blind, placebo-controlled trial used simultaneous depression and mania criteria to compare a single mood stabilizer, divalproex, with and without adjunctive olanzapine in patients with bipolar I disorder experiencing acute mixed episodes.. Two hundred two adults, aged 18 to 60 years, who met DSM-IV-TR criteria for bipolar disorder with a current mixed episode and had been taking divalproex for >or=14 days at levels of 75 to 125 microg/mL with inadequate efficacy (21-item Hamilton Depression Rating Scale [HDRS-21] and Young Mania Rating Scale [YMRS] scores >or=16) were randomly assigned to olanzapine 5 to 20 mg/d versus placebo augmentation. HDRS-21, YMRS, Clinical Global Impressions for Bipolar Disorder (CGI-BP), hospitalizations, concomitant medications, and adverse events were assessed. Comparisons included changes in both HDRS-21 and YMRS (primary outcome measure), time to partial response and time to response, CGI-BP improvement, hospitalizations, and safety (secondary outcome measures). The study was conducted from December 2006 to February 2008.. Mean (SD) baseline HDRS-21 and YMRS scores were 22.2 (4.5) and 20.9 (4.4), respectively, with 59% female and 51% white subjects. Mean +/- SE score changes from baseline across the 6-week treatment period for adjunctive olanzapine (n = 100) versus adjunctive placebo (n = 101) arms, respectively, were -9.37 +/- 0.55 versus -7.69 +/- 0.54, P = .022, on the HDRS-21 and -10.15 +/- 0.44 versus -7.68 +/- 0.44 P < .001, on the YMRS. Mean +/- SE score changes from baseline to last observation carried forward for CGI-BP measures were -1.34 +/- 0.11 for adjunctive olanzapine versus -1.06 +/- 0.11 for adjunctive placebo, P = .056. Time to partial response (>or=25% HDRS-21 and YMRS decreases, median 7 versus 14 days) and time to response (>or=50% HDRS-21 and YMRS decreases, median 25 versus 49 days) were significantly shorter with adjunctive olanzapine. Increases in weight (total and >or=7%) and fasting blood glucose were significantly greater with adjunctive olanzapine.. Adjunctive olanzapine yielded greater and earlier reduction of manic and depressive symptoms in mixed-episode patients with inadequate response to at least 2 weeks of divalproex.. clinicaltrials.gov Identifier: NCT00402324.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Olanzapine; Placebos; Psychiatric Status Rating Scales; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome; Valproic Acid

To assess the efficacy and tolerability of asenapine versus olanzapine in the extended treatment of bipolar mania.. Patients with bipolar I disorder experiencing acute manic or mixed episodes who completed either of two 3-week, double-blind trials with asenapine 5 or 10 mg twice daily, olanzapine 5 to 20 mg once daily, or placebo were eligible for this 9-week, double-blind extension study. Patients receiving active medication in the 3-week trials continued the same regimen; those who had received placebo were blindly switched to asenapine but were assessed for safety outcomes only. The primary efficacy measure was the change from baseline to day 84 on the Young Mania Rating Scale (YMRS) total score in the per-protocol population. Results on the primary efficacy outcome were used to determine the noninferiority of asenapine versus olanzapine.. A total of 504 patients (placebo/asenapine, n = 94; asenapine, n = 181; olanzapine, n = 229) were enrolled in the extension study. At day 84, the mean (SD) change from baseline in YMRS total score was -24.4 (8.7) for asenapine and -23.9 (7.9) for olanzapine. Prespecified statistical analysis for noninferiority indicated no significant difference between asenapine and olanzapine. The overall incidence of treatment-emergent adverse events was similar across treatment groups (77% placebo/asenapine, 77% asenapine, 78% olanzapine). Clinically significant weight gain occurred in 10%, 19%, and 31% of the placebo/asenapine, asenapine, and olanzapine groups, respectively.. Asenapine was efficacious, showed noninferiority to olanzapine, and was well tolerated in the extended treatment of patients experiencing manic symptoms associated with bipolar I disorder.

Topics: Acute Disease; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Heterocyclic Compounds, 4 or More Rings; Humans; International Cooperation; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

Asenapine is approved for bipolar disorder and schizophrenia. This was a 3-week, randomized, double-blind, placebo-controlled trial of asenapine for treating acute bipolar mania.. After a single-blind placebo run-in period, adults (n = 488) experiencing manic or mixed episodes were randomized to flexible-dose sublingual asenapine (10 mg BID on day 1; 5 or 10 mg BID thereafter; n = 194), placebo (n = 104), or oral olanzapine (15 mg BID on day 1; 5-20 mg QD thereafter; n = 191). Primary efficacy, change in Young Mania Rating Scale (YMRS) total score from baseline to day 21, was assessed using analysis of covariance with last observation carried forward [(LOCF); primary analysis]. A mixed model for repeated measures [(MMRM); prespecified secondary analysis] was also used to assess efficacy. Tolerability and safety assessments included adverse events, physical examinations, extrapyramidal symptom ratings, and laboratory values.. Mean daily dosages were asenapine 18.2 mg and olanzapine 15.8 mg. Significantly greater least squares (LS) mean +/- SE changes in YMRS scores were observed on day 2 with asenapine (-3.0 +/- 0.4) and olanzapine (-3.4 +/- 0.4) versus placebo (-1.5 +/- 0.5, both p < 0.01) and were maintained until day 21 (-10.8 +/- 0.8 with asenapine, -12.6 +/- 0.8 with olanzapine; both p < or = 0.0001 versus placebo, -5.5 +/- 1.1) with LOCF. The results of MMRM analyses were consistent with those of LOCF. Asenapine had a modest impact on weight and metabolic measures.. These results indicate that asenapine is rapidly acting, efficacious, and well tolerated for patients with bipolar I disorder experiencing an acute manic episode.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Weight; Dibenzocycloheptenes; Dose-Response Relationship, Drug; Double-Blind Method; Electroencephalography; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Models, Statistical; Olanzapine; Patient Compliance; Psychiatric Status Rating Scales; Single-Blind Method; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to test the efficacy and safety of olanzapine + topiramate versus olanzapine monotherapy in the treatment of bipolar disorder (BPD) and treatment-attendant weight gain in children and adolescents.. Subjects (N = 40) were outpatients of both sexes, 6-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BPD (manic, hypomanic, or mixed) and Young Mania Rating Scale (YMRS) total score of >15 treated over 8-week periods in two partially concurrent open-label trials with olanzapine (n = 17) or olanzapine + topiramate (n = 23).. Subjects in both groups experienced a statistically significant reduction in YMRS scores after 8-week, open-label treatment with olanzapine (baseline YMRS = 26.7 +/- 9.5; end-point YMRS = 18.2 +/- 12.5, p = 0.04) and olanzapine +topiramate (baseline YMRS = 31.3 +/- 7.9; end-point YMRS = 20.4 +/- 11.4, p = 0.04). There was no difference in response between the two groups based on YMRS or Clinical Global Impressions-Improvement (CGI-I) scores. Adverse events were few and mild and similar between the two groups, with the exception of weight gain. The weight gain in the olanzapine group was 5.3 +/- 2.1 kg and the weight gain in the olanzapine + topiramate group was statistically significantly lower, 2.6 +/- 3.6 kg.. Augmentation of olanzapine with topiramate resulted in a reduced weight gain over the course of an 8-week, open-label trial when compared with olanzapine treatment alone, but did not lead to greater reduction in symptoms of mania.

Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Drug Therapy, Combination; Female; Fructose; Humans; Male; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Topiramate; Weight Gain

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

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

To evaluate the efficacy and safety of olanzapine, divalproex, and placebo in a randomized, double-blind trial in mild to moderate mania (DSM-IV-TR criteria).. The study was conducted from October 2004 to December 2006. A total of 521 patients from private practices, hospitals, and university clinics were randomly assigned to olanzapine (5-20 mg/day), divalproex (500-2500 mg/day), or placebo for 3 weeks; those completing continued with a 9-week double-blind extension. Efficacy (mean change in Young Mania Rating Scale [YMRS] total score was the primary outcome) and safety were assessed.. After 3 weeks of treatment, olanzapine-treated (N = 215) and placebo-treated (N = 105) patients significantly differed in YMRS baseline-to-endpoint total score change (p = .034; least squares [LS] mean: -9.4 and -7.4, respectively). Such changes were not significantly different between olanzapine vs. divalproex (N = 201) or divalproex vs. placebo. After 12 weeks of treatment, olanzapine- and divalproex-treated patients significantly differed in YMRS baseline-to-endpoint changes (p = .004; LS mean: -13.3 and -10.7, respectively). Of observed cases, 35.4% (35/99; 3 weeks) to 57.1% (28/49; 12 weeks) had valproate plasma concentrations lower than the recommended valproate therapeutic range, but these patients' YMRS scores were lower than those of patients with valproate concentrations above/within range. Compared with divalproex, after 12 weeks, olanzapine-treated patients had significant increases in weight (p < .001) and in glucose (p < .001), triglyceride (p = .003), cholesterol (p = .024), uric acid (p = .027), and prolactin (p < .001) levels. Divalproex-treated patients had significant decreases in leukocytes (p = .044) and platelets (p < .001) compared with olanzapine after 12 weeks of treatment. The incidence of potentially clinically significant weight gain (>/= 7% from baseline) was higher with olanzapine than with divalproex (3-week: p = .064, 6.4% vs. 2.7%; 12-week: p = .002, 18.8% vs. 8.5%; respectively).. Olanzapine was significantly more efficacious than placebo but not divalproex at 3 weeks and significantly more efficacious than divalproex at 12 weeks. Olanzapine-treated patients had significantly greater increases in weight and in glucose, cholesterol, triglyceride, uric acid, and prolactin levels than divalproex-treated patients.. clinicaltrials.gov Identifier: NCT00094549.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Olanzapine; Prolactin; Valproic Acid; Weight Gain

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

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

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

Combinations of olanzapine and carbamazepine are often used in clinical practice in the management of mania.. To assess the efficacy and safety of olanzapine plus carbamazepine in mixed and manic bipolar episodes.. Randomised, double-blind, 6-week trial of olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day; n=58) v. placebo plus carbamazepine (n=60) followed by open-label, 20-week olanzapine (10-30 mg/day) plus carbamazepine (400-1200 mg/day, n=86), with change in manic symptoms as main outcome measure. Safety and pharmacokinetics were also evaluated.. There were no significant differences (baseline to endpoint) in efficacy measures between treatment groups, but at 6 weeks triglyceride levels were significantly higher (P=0.008) and potentially clinically significant weight gain (>or=7%) occurred more frequently (24.6% v. 3.4%, P=0.002) in the combined olanzapine and carbamazepine group. Carbamazepine reduced olanzapine concentrations but olanzapine had no effect on carbamazepine concentrations.. The combination of olanzapine and carbamazepine did not have superior efficacy to carbamazepine alone. The increases in weight and triglycerides observed during combination treatment are a matter of concern.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Treatment Outcome

The aim of the present randomized, single-blind, pilot study was to assess the efficacy of the addition of a second mood stabilizer, either olanzapine or lamotrigine, to lithium in patients with remitted bipolar disorder and comorbid anxiety disorder.. Adult DSM-IV bipolar disorder patients with a current anxiety disorder and a Hamilton Rating Scale for Anxiety (HAM-A) score of 12 or higher, in remission from an affective episode for at least 2 months while on lithium maintenance treatment, were randomly assigned to receive 12 weeks of single-blind olanzapine 5 to 10 mg/day (N = 24) or lamotrigine 50 to 200 mg/day (N = 23) addition to lithium. The primary outcome measure was the HAM-A; secondary outcome measures were the Clinical Global Impressions-Severity of Illness scale and the Global Assessment of Functioning (GAF) scale. Data were collected from July 2005 to February 2007.. Twenty-two patients in the olanzapine and 18 in the lamotrigine group completed the trial. Mean +/- SD final doses of olanzapine and lamotrigine were, respectively, 7.7 +/- 4.2 mg/day and 96.7 +/- 46.7 mg/day in the intent-to-treat sample (N = 47). Both olanzapine and lamotrigine were effective in reducing HAM-A scores from baseline to endpoint (paired t test for completers: t = 11.361, df = 21, p < .001 for olanzapine and t = 6.301, df = 17, p < .001 for lamotrigine). Both drugs were also effective on the secondary outcome measures. Olanzapine was more effective than lamotrigine at weeks 6 and 12 with a last-observation-carried-forward analysis on all 3 outcome measures, while such differences disappeared on the HAM-A and GAF at week 12 with the visit-wise analysis.. The addition of a second mood stabilizer (olanzapine or lamotrigine) to lithium is effective in reducing anxiety symptoms in bipolar disorder patients with a co-occurring anxiety disorder.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lamotrigine; Lithium Carbonate; Male; Middle Aged; Olanzapine; Pilot Projects; Single-Blind Method; Triazines

There is a dearth of available knowledge relating to the efficacy of switching from one psychotropic agent to another in treating patients with acute mania.. This is a post hoc analysis of data from two randomized, placebo-controlled trials of carbamazepine extended-release capsules (CBZ-ERC) in the treatment of mania, to evaluate the efficacy of CBZ-ERC in patients previously nonresponsive to lithium (n 5 40), olanzapine (n 5 38), or valproate (VPA, n 5 77).. In patients previously on lithium, Young Mania Rating Scale (YMRS) scores improved significantly from baseline to end point (27.4 6 SD 3.5 vs. 15.8 6 11.1; P 5 .0002). In patients previously on VPA or olanzapine, YMRS scores significantly improved in both CBZ-ERC- and placebo-treated groups (VPA: CBZ-ERC, P , .0001; placebo, P 5 .0002; olanzapine: CBZ-ERC, P , .0001; placebo, P 5 .0054). Improvement in YMRS was significantly greater in CBZ-ERC-treated patients versus placebo in subjects previously nonresponsive to lithium (CBZ-ERC 11.6 6 10.3 vs. placebo 4.0 6 11.2, P 5 .03), or VPA (CBZ-ERC 10.8 6 11.9 vs. placebo 5.7 6 9.2; P 5 .04), and trending to be greater for those previously nonresponsive to olanzapine (olanzapine 13.2 6 9.3 vs. placebo 7.3 6 9.7, P 5 .06).. CBZ-ERC is an effective therapy for bipolar patients previously nonresponsive to lithium or valproate. Medication switch is frequently associated with symptom improvement.

Topics: Acute Disease; Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Delayed-Action Preparations; Female; Humans; Lithium Compounds; Male; Olanzapine; Valproic Acid

A post hoc analysis of Young Mania Rating Scale (YMRS) item scores was conducted to identify symptoms that may predict impending relapse using prospectively collected data from a double-blind, randomized relapse prevention study of patients treated with olanzapine (N=200, 5-20 mg/d) versus lithium (N=201, 300-1800 mg/d).. Relapses (YMRS > or = 15, or hospitalization) included in this analysis occurred 3-52 weeks after randomization. Repeated measures logistic regression of increases (> or = 1) in YMRS item scores prior to the visit that preceded relapse was used to estimate the odds of relapse.. A total of 31 patients relapsed during the first 3-16 weeks of the study (olanzapine, n=12; lithium, n=19). YMRS items that increased most frequently within a 2-week period preceding relapse were (olanzapine vs. lithium, respectively): increased motor activity/energy (58.3%, 21.1%), irritability (33.3%, 31.6%), decreased need for sleep (25.0%, 10.5%), increased speech (25.0%, 10.5%), and elevated mood (25.0%, 15.8%). YMRS items with significant odds ratios (OR) that predicted relapse in patients treated with olanzapine or lithium, respectively, were: increased motor activity/energy (OR, 35.7; OR, 7.8), irritability (OR, 9.5; OR, 7.8), elevated mood (OR, 8.1; OR, 4.2), and increased sexual interest (OR, 13.7; OR, 7.7).. Early recognition of symptom exacerbation in bipolar mania, particularly increased motor activity-energy may permit clinical interventions to help avert relapse.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Prognosis; Prospective Studies; Psychiatric Status Rating Scales; Secondary Prevention

We explored the relationship between striatal dopamine-2 (D(2)) receptor occupancy and extra-pyramidal symptoms (EPS) in bipolar patients receiving olanzapine. Seventeen patients with a DSM-IV diagnosis of bipolar disorder were treated with 5-45 mg/day olanzapine for at least 14 days. After that period, D(2) receptor occupancy was determined using Iodobenzamide (IBZM) and SPECT. EPS were assessed by the Simpson-Angus Scale (SAS) and Barnes-Akathisia Scale (BAS). We found a dose-dependent increase in occupancy: 5 mg led to 28-50%, 10 mg to 40-68%, 15 mg to 69%, 20 mg to 57-66%, 30 mg to 66% and 45 mg to 80% D(2) receptor occupancy; and a significant correlation between plasma levels and occupancy (R(2)=.55, P=.001). Similar to schizophrenic patients, bipolar patients did not exhibit EPS at D(2) occupancy levels of 28 to 80%. Although we did not find an increased vulnerability for acute EPS in bipolar patients receiving olanzapine at clinical relevant doses, this needs to be replicated with larger sample sizes.

Topics: Adult; Aged; Aged, 80 and over; Benzodiazepines; Bipolar Disorder; Corpus Striatum; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Receptors, Dopamine D2; Selective Serotonin Reuptake Inhibitors; Time Factors; Tomography, Emission-Computed, Single-Photon

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Drug Costs; Hospital Costs; Humans; Lithium Compounds; Markov Chains; Models, Economic; Olanzapine; Reproducibility of Results; Secondary Prevention; Severity of Illness Index; Stochastic Processes; Time Factors; Treatment Outcome; United Kingdom

Breakthrough manic episodes are the rule in bipolar disorders; valproate and olanzapine are considered first-line treatments for manic episodes, nevertheless the two drugs have only been compared in monotherapy studies. In our study we compared the efficacy and safety of valproate and olanzapine added to lithium in the treatment of patients experiencing breakthrough manic episodes while on lithium monotherapy.. Patients with bipolar I or II disorder (SCID-I), in treatment with lithium since at least one year, experiencing a manic or hypomanic relapse were randomly assigned to an open-label add-on therapy with valproate (500-1500 mg/day) or olanzapine (7.5-15.0 mg/day) for 8 weeks. The primary efficacy measure was the Young Mania Rating Scale (YMRS) total.. Twenty-one patients were randomized to receive the add-on therapy with valproate (n=9) or olanzapine (n=12). Both groups showed a significant baseline to endpoint reduction in YMRS total and Clinical Global Impressions-Severity (CGI-S) scores (p<0.001). At endpoint, the mean reduction of YMRS total or CGI-S scores, as well as response or remission rates, was not significantly different between the groups. However, compared with patients in the valproate add-on group, patients treated with olanzapine add-on showed significantly greater reductions in the YMRS total and CGI-S mean scores at weeks 1 through 4 (p<0.05). The rate and profile of adverse events were numerically similar in the two groups.. Open-label design and limited sample size.. Both add-on therapies were efficacious in treating patients with manic or hypomanic relapse, however the olanzapine group showed an earlier response to treatment. These findings can help clinicians in understanding the value of adding other treatments to lithium in patients experiencing a manic or hypomanic relapse.

Topics: Adult; Aged; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Recurrence; Treatment Outcome; Valproic Acid

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

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

The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean +/- SD final dosage: 5.8 +/- 3.8 mg) or olanzapine (mean +/- SD final dosage: 13.6 +/- 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS) and the Clinical Global Impressions - Bipolar version (CGI-BP). There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean +/- SEM pre-treatment value: 6.7 +/- 20.3%; after-treatment: 85.7 +/- 10.9%), total wake time (pre-treatment: 140.0 +/- 92.5 min; after-treatment: 55.2 +/- 44.2 min), and wake time after sleep onset (pre-treatment: 109.7 +/- 70.8 min; after-treatment: 32.2 +/- 20.7 min). Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05). These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brief Psychiatric Rating Scale; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Polysomnography; Sleep; Treatment Outcome

Data from a published double-blind randomized trial comparing olanzapine versus haloperidol in acute mania were used to address the response and tolerability of Latin American patients. Primary efficacy end point was the remission rate (Young Mania Rating Scale score

Topics: Acute Disease; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cholesterol; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Fasting; Female; Haloperidol; Hispanic or Latino; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Remission Induction; Time Factors; Treatment Outcome; Weight Gain; White People

Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables.. Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment.. The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels.. Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Body Weight; Brief Psychiatric Rating Scale; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Energy Metabolism; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Resistance; Leptin; Lipids; Male; Metformin; Middle Aged; Olanzapine; Schizophrenia; Statistics as Topic

This secondary analysis from a randomized double-blind study of acute bipolar depression compared olanzapine monotherapy, olanzapine-fluoxetine combination (OFC) and placebo in patients with or without comorbid anxiety.. Patients with bipolar disorder and a current depressive episode received olanzapine (5-20 mg/day), OFC (6/25, 6/50, or 12/50 mg/day), or placebo in an 8-week trial. Two populations were defined: comorbid (Hamilton Anxiety Rating Scale, HAM-A > or =18) or non-comorbid (HAM-A <18) anxiety. Changes in Montgomery-Asberg Depression Rating Scale (MADRS) and HAM-A total scores, and rates of response (> or =50% decrease from baseline to endpoint) and remission (MADRS < or =12 or HAM-A < or =7) were analyzed.. Baseline MADRS and YMRS scores were significantly higher in patients with comorbid anxiety relative to those without. Patients without comorbid anxiety were more likely to achieve MADRS response and remission than those with comorbid anxiety (relative risk, RR: 1.21 and 1.29, respectively). Patients with comorbid anxiety had greater rates of response and remission with olanzapine and OFC relative to placebo (response RR:1.45 and 2.14; remission RR:1.96 and 2.32, respectively). Response and remission rates on the HAM-A scale were greater for OFC relative to placebo (RR: 2.00 and 3.20). Weight gain was greater for olanzapine (2.59+/-3.24 kg) and OFC (2.79+/-3.23 kg) relative to placebo, as were baseline to endpoint changes in cholesterol levels (6+/-31 and 10+/-67 mg/dL, respectively).. Comorbid anxiety symptoms in patients with bipolar depression have a negative impact on treatment outcome. Olanzapine and, to a greater extent, olanzapine-fluoxetine combination were effective in reducing both depressive and anxiety symptoms in these patients. The significantly greater changes in weight, glucose and cholesterol parameters observed in the olanzapine and olanzapine-fluoxetine combination groups should be entered into the risk-benefit assessment in determining appropriate treatment options for these patients.

Topics: Acute Disease; Adult; Age of Onset; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Comorbidity; Depression; Double-Blind Method; Female; Humans; Male; Olanzapine; Remission Induction; Severity of Illness Index; Surveys and Questionnaires

To determine the safety and effectiveness of long-acting injectable risperidone (LAI-ris) add-on in bipolar patients.. A 6-month, open-label, randomized, pilot trial enrolled 49 bipolar out-patients who were taking a mood stabilizer and an atypical antipsychotic (AAP). Patients were maintained on a mood stabilizer and were randomized to continuation of their current AAP or switched to LAI-ris treatment. Safety outcomes included adverse events and changes in vital signs, laboratory tests and extrapyramidal symptoms (EPS). Effectiveness measures included Clinical Global Impression-Severity, scales assessing mania, depression, anxiety, resource utilization, quality of life, subject satisfaction with treatment, and time to intervention.. Twenty-three subjects were randomized to LAI-ris and 26 to oral AAP. There were no significant differences between the groups in adverse events, EPS change scores, weight or other safety measures. LAI-ris group had significant reductions in symptoms as measured by changes in Clinical Global Impression-Severity scores and Young Mania Rating Scale at endpoint relative to baseline and oral AAP group had reductions in Hamilton Anxiety Rating Scale scores relative to baseline but no significant differences were noted between the groups on any of the efficacy measures.. LAI-ris demonstrated similar effectiveness, safety and tolerability compared to oral AAP in this 6 month pilot trial.

Topics: Administration, Oral; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Lithium Compounds; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Treatment Outcome; Valproic Acid

To determine the effect of intramuscular (IM) olanzapine in severely agitated patients.. This was an open-label multicenter 1-week observational study of IM olanzapine treatment in severely agitated inpatients and psychiatric emergency services with bipolar mania (n = 22) or schizophrenia (n = 52). Mean change from baseline to 2 h post-first injection (LOCF) in agitation was assessed by PANSS-Excited Component (PANSS-EC) (score range: 5-35 points) mean change from baseline to 15, 30, 45, 60, 90, and 120 min post-first injection, and visit-wise mean changes from mixed-model repeated measures analysis of variance. Kaplan-Meier survival curve analyses estimated time to categorical response (rating of

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Injections, Intramuscular; Kaplan-Meier Estimate; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Schizophrenic Psychology

The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents.. A 3-week multicenter, parallel, double-blind, randomized placebo-controlled trial was conducted at 24 sites in the United States and two sites in Puerto Rico. The participants were outpatient and inpatient male and female adolescents 13-17 years of age with an acute manic or mixed episode. Subjects received either olanzapine (2.5-20 mg/day [N=107]) or placebo (N=54). The mean change from baseline to endpoint in the Young Mania Rating Scale total score was the primary outcome measure.. The mean baseline-to-endpoint change in the Young Mania Rating Scale total score was significantly greater for patients receiving olanzapine relative to patients receiving placebo, and a greater proportion of olanzapine-treated patients met response and remission criteria (44.8% versus 18.5% and 35.2% versus 11.1%, respectively). The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain > or =7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%). The mean baseline-to-endpoint changes in prolactin, fasting glucose, fasting total cholesterol, uric acid, and the hepatic enzymes aspartate transaminase and alanine transaminase were significantly greater in patients treated with olanzapine relative to patients receiving placebo.. Olanzapine was effective in the treatment of bipolar mania in adolescent patients. Patients treated with olanzapine, however, had significantly greater weight gain and increases in the levels of hepatic enzymes, prolactin, fasting glucose, fasting total cholesterol, and uric acid.

Topics: Adolescent; Age Factors; Alanine Transaminase; Antipsychotic Agents; Aspartate Aminotransferases; Benzodiazepines; Bipolar Disorder; Blood Glucose; Cholesterol; Double-Blind Method; Fasting; Female; Humans; Male; Obesity; Olanzapine; Placebos; Prolactin; Psychiatric Status Rating Scales; Treatment Outcome; Uric Acid; Weight Gain

An original method based on the use of high-performance liquid chromatography with both coulometric and diode array detection has been developed for the therapeutic drug monitoring of patients with bipolar disorders being treated with olanzapine and lamotrigine. Chromatographic separation was achieved on a reversed-phase C8 column (150 x 4.6 mm internal diameter, 5 microm) using a mobile phase composed of methanol (27%) and a 50.0 mmol/L, pH 3.5 phosphate buffer (73%). For the analysis of olanzapine and its main metabolite, N-desmethylolanzapine, a coulometric detector was used, with electrode 1 set at -200 mV and electrode 2 at +500 mV. Lamotrigine was determined using a diode array detection at 220 nm. The two detectors were connected in series. For the analysis of biological samples, a clean-up procedure was implemented by means of solid-phase extraction using phenyl cartridges and eluting the analytes with methanol; only a small volume of plasma (150 microL) was needed to analyze both olanzapine and lamotrigine. Linear responses were obtained between 0.1 and 50.0 ng mL(-1) for olanzapine, 0.1 and 25.0 ng mL(-1) for N-desmethylolanzapine, and between 0.25 and 10.0 microg mL(-1) for lamotrigine. The extraction yield values were always higher than 90% for all the analytes, with precision (expressed as relative standard deviation values) lower than 3.4%. The method was applied successfully to some human plasma samples drawn from bipolar patients undergoing combined therapy with the two drugs. Satisfactory values for accuracy were obtained, with mean recovery higher than 91%. Thus, the method appears suitable for the investigation of the chemical-clinical correlations in patients receiving therapy with olanzapine and lamotrigine.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chromatography, High Pressure Liquid; Humans; Lamotrigine; Molecular Structure; Olanzapine; Triazines

We used proton magnetic resonance spectroscopy (1H MRS) to compare the in vivo effects of olanzapine on prefrontal N-acetyl-aspartate (NAA) levels in treatment remitters and nonremitters. Secondary aims of this study were to identify neurochemical predictors of successful olanzapine treatment and other neurochemical effects of olanzapine. In all, 20 adolescents admitted for their first hospitalization for bipolar disorder, type I, manic or mixed and 10 demographically matched healthy subjects were recruited. Manic adolescents were treated with olanzapine monotherapy and scanned at three time points (N = 19). Medial and left and right lateral ventral prefrontal NAA, choline, creatine/phosphocreatine, myo-inositol, and glutamate/glutamine were measured at baseline, prior to receiving medication, and on days 7 and 28 of treatment. Healthy subjects did not receive medication but underwent 1H MRS scans at the same time points to assess for normal variability in metabolites over time. Although there was no overall increase in NAA in manic adolescents following 28 days of treatment with olanzapine, olanzapine remitters (N = 11, 58%) exhibited a greater increase in medial ventral prefrontal NAA compared with nonremitters (N = 8, 42%, p = 0.006). Specifically, from baseline to end point, NAA levels decreased in nonremitters (p = 0.03) and increased in remitters (p = 0.05). Manic adolescents treated with olanzapine had an increase from baseline to day 7 in medial (p = 0.002) and right lateral (p = 0.02) ventral prefrontal choline. Baseline medial ventral prefrontal choline was greater in olanzapine remitters than in nonremitters (p = 0.001). Successful treatment of mania with olanzapine may lead to increased ventral prefrontal neuronal viability and/or function as compared to unsuccessful treatment with olanzapine. Additionally, olanzapine-induced increases in choline may lead to alteration of abnormalities in cell membrane metabolism or second messenger pathways that are thought to be involved in the pathophysiology of bipolar disorder.

Topics: Adolescent; Analysis of Variance; Antipsychotic Agents; Aspartic Acid; Benzodiazepines; Bipolar Disorder; Brain Chemistry; Case-Control Studies; Child; Female; Humans; Magnetic Resonance Spectroscopy; Male; Olanzapine; Prefrontal Cortex; Prospective Studies; Protons; Psychiatric Status Rating Scales; Time Factors

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

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

Bipolar disorder outcome worsens as number of manic episodes increases, suggesting that prevention of recurrent episodes early during the disorder could improve patient prognosis. We investigated treatment efficacy in prevention of mood episodes in patients subgrouped by number of prior manic episodes.. This study was a post hoc analysis of data from a multicenter, double-blind, 12-month clinical trial of relapse/recurrence in 431 initially euthymic patients with at least 2 prior manic/ mixed episodes and a DSM-IV diagnosis of bipolar I disorder randomly assigned to olanzapine (5-20 mg/day) or lithium (serum concentration 0.6 to 1.2 mEq/L). Data were collected between August 1999 and June 2002. Patients were subcategorized by illness stage according to number of prior manic/mixed episodes-early stage: 2 prior episodes (N = 53, lithium; N = 48, olanzapine), intermediate stage: 3 to 5 prior episodes (N = 80, lithium; N = 98, olanzapine), and later stage: more than 5 prior episodes (N = 81, lithium; N = 71, olanzapine)-and were evaluated for rates of relapse/recurrence.. There were significant effects for treatment (p < .001) and illness stage (p = .006) but no significant interaction (p = .107) on rate of manic/mixed relapse/recurrence. Rates of manic/ mixed relapse/recurrence for olanzapine versus lithium were 2.1% versus 26.4% (p = .008), 13.3% versus 23.8% (p = .073), and 23.9% versus 33.3% (p = .204) for early-, intermediate-, and later-stage groups, respectively. There was no significant effect for treatment (p = .096) or illness stage (p = .731) for depressive relapse/recurrence.. Early-stage (but not intermediate-or later-stage) patients had a significantly lower rate of relapse/recurrence of manic/mixed episodes with olanzapine compared to lithium. Thus, olanzapine maintenance therapy may be particularly effective early in the course of bipolar illness.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Prognosis; Psychiatric Status Rating Scales; Secondary Prevention; Time Factors; Treatment Outcome

In a placebo-controlled, double-blind study, the authors investigated the efficacy and safety of olanzapine as monotherapy in relapse prevention in bipolar I disorder.. Patients achieving symptomatic remission from a manic or mixed episode of bipolar I disorder (Young Mania Rating Scale [YMRS] total score < or =12 and 21-item Hamilton Depression Rating Scale [HAM-D] score or =15, HAM-D score > or =15, or hospitalization).. Time to symptomatic relapse into any mood episode was significantly longer among patients receiving olanzapine (a median of 174 days, compared with a median of 22 days in patients receiving placebo). Times to symptomatic relapse into manic, depressive, and mixed episodes were all significantly longer among patients receiving olanzapine than among patients receiving placebo. The relapse rate was significantly lower in the olanzapine group (46.7%) than in the placebo group (80.1%). During olanzapine treatment, the most common emergent event was weight gain; during the open-label phase, patients who received olanzapine gained a mean of 3.1 kg (SD=3.4). In double-blind treatment, placebo patients lost a mean of 2.0 kg (SD=4.4) and patients who continued to take olanzapine gained an additional 1.0 kg (SD=5.2).. Compared to placebo, olanzapine delays relapse into subsequent mood episodes in bipolar I disorder patients who responded to open-label acute treatment with olanzapine for a manic or mixed episode.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Obesity; Olanzapine; Placebos; Secondary Prevention; Time Factors; Treatment Outcome; Weight Gain

Gaps remain between rating scale changes obtained in a clinical trial and what those results mean in clinical practice.. To better understand the relevance of results from a clinical trial we examined the relationship between rating scale measures and the clinicians' assessment of illness severity.. Data from a randomized double-blind 8-week study of bipolar I depression were examined post hoc in patients who received placebo (PLA, n = 355), olanzapine (n = 351) (OLZ, 5 to 20 mg/d), or olanzapine-fluoxetine combination (n = 82) (OFC, 6 and 25, 6 and 50, or 12 and 50 mg/d). Principal components analysis identified related symptoms (factors) from Montgomery-Asberg Depression Rating Scale (MADRS) item scores. Regression analysis examined baseline to endpoint changes in factor scores and Clinical Global Impression (CGI) scores. Mixed-effects model repeated measures analysis assessed differences between treatment groups.. MADRS factors identified were: sadness, negative thoughts, detachment, and neurovegetative symptoms. Factor and CGI scores were significantly reduced from baseline to endpoint (LOCF) in the combination therapy group as compared with placebo (p < .01). Changes in factor scores were highly correlated (p < .001) with changes in the CGI. Over 80% of this treatment effect was attributable to indirect effects of improvements in the MADRS factors, the remaining difference could not be explained even when changes in the YMRS and HAMA scores were included in the analytical model.. The changes in MADRS factors were closely aligned with the clinician's assessment of overall depression severity, which may suggest a high degree of clinical relevance for differences observed between treatments.

Topics: Benzodiazepines; Bipolar Disorder; Depression; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

This study evaluated the overall effectiveness and tolerability of atypical antipsychotics (risperidone vs. olanzapine vs. quetiapine) used in the treatment of bipolar inpatients. After screening 463 patients, the medical records of 158 inpatients with bipolar I disorder, who were given olanzapine, risperidone or quetiapine as adjuncts to mood stabilizers for at least 1 month and not administered with any other antipsychotics, were examined. Details of the tolerability and effectiveness were reviewed according to the treatment records during their hospital stay. The results showed equivalent effectiveness based on the Clinical Global Impression (CGI) and Global Assessment Functioning (GAF) score between the three atypical antipsychotics. The frequency of the extrapyramidal symptom-related side effects were higher in the risperidone-treated group than in the olanzapine and quetiapine-treated group. This suggests that risperidone, olanzapine and quetiapine have a comparable effectiveness in inpatients with bipolar I disorder in a naturalistic setting. However, there were some differences in tolerability between these results as reported from previous Western studies.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Evaluation; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Risperidone

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

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

To determine predictors of substantial weight gain (SWG) during treatment of bipolar disorder with olanzapine, data were pooled from 4 long-term randomized, multicenter studies in patients with bipolar mania or mixed mania (N = 948 at initiation of olanzapine). SWG was defined as gaining 5 kg or 7% of initial weight in 30 +/- 2 weeks. Logistic regression estimated odds ratios associated with early weight gain and baseline risk factors for predicting SWG. A classification system to identify patients at risk for SWG was constructed by recursive data partitioning. Baseline characteristics significantly associated with SWG included younger age, nonwhite ethnicity, lower body mass index (BMI), nonrapid cycling, and psychotic features. Weight gain of 2 or more kg in the first 3 weeks of therapy predicted SWG by 30 weeks (sensitivity = 57%; specificity = 71%). A classification system with thresholds for early weight gain, baseline BMI, and ethnicity further improved SWG predictability (sensitivity = 79%; specificity = 70%). In conclusion, patients with bipolar disorder who gained 2 to 3 kg during the first 3 weeks of treatment with olanzapine, SWG was predicted after 30 weeks of treatment. Patients with less pronounced early weight gain might still be at risk for later SWG if they have close to normal BMI (< or =27 kg/m) at treatment initiation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Databases, Factual; Double-Blind Method; Female; Humans; Logistic Models; Male; Odds Ratio; Olanzapine; Predictive Value of Tests; Reproducibility of Results; Weight Gain

The objective of this study was to describe clinical and work functional outcomes associated with 6-month open-label olanzapine treatment for bipolar I disorder.. The study consisted of 249 patients entering a 6-month open label phase after 12 weeks of acute double-blind haloperidol or olanzapine treatment. Baseline for analysis was defined as the beginning of open-label treatment. The clinical outcomes were symptomatic remission defined by a Y-MRS total score < or = 12 and a HAM-D total score < or = 8 at the end of 6 months of treatment. The work functional outcomes included work functional scores, the proportion of patients who reported to 'work' as employee, volunteers, students, or house workers and the proportion of patients who specifically reported to 'work for pay'.. A total of 240 patients reported work functional outcomes post open-label baseline. Among them, 15.4% patients moved into a 'work group' from a 'no-work group' at baseline, while 7.1% did the opposite (p = 0.0065) and 13.3% reported an improvement to 'work for pay' status from a 'not working for pay' status at baseline, while there was 4.2% of worsening in employment status (p = 0.0007). Overall, improvement in the work functional score was found at all post-baseline time points, beginning at month two (p = 0.003).. Results of this study need to be confirmed by double-blind randomized controlled studies. There was a lack of detailed information on work functioning from the questionnaire.. Open-label olanzapine treatment for 6 months was associated with improvements in work functional outcomes in patients with bipolar disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Efficiency; Female; Haloperidol; Health Status; Humans; Male; Middle Aged; Olanzapine; Surveys and Questionnaires; Treatment Outcome; Work

Olanzapine-fluoxetine combination has shown efficacy in the acute treatment of depressive episodes in patients with bipolar I disorder. The present analyses examined the efficacy and safety of longer term treatment with olanzapine-fluoxetine combination or olanzapine monotherapy in a 6-month open-label extension study.. 376 patients with DSM-IV bipolar I disorder, depressed, who completed an acute trial entered the open-label study and received 1 week of olanzapine monotherapy (5-20 mg/day). At all subsequent visits, patients could choose between olanzapine monotherapy or olanzapine-fluoxetine combination (6/25, 6/50, or 12/50 mg/day). Three treatment groups were defined retrospectively according to the medication course taken from week 1: olanzapine, olanzapine-fluoxetine combination, or switched. The efficacy measures were the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions-Bipolar Version, and Young Mania Rating Scale. The study was conducted from July 2000 to May 2002.. Among patients who started in remission, MADRS total scores did not change significantly from baseline to endpoint in the olanzapine-fluoxetine combination (0.8) or olanzapine (0.3) groups, but increased slightly in the switched (2.3, p = .02) group. For patients who started in nonremission, MADRS total scores decreased significantly in all groups (olanzapine-fluoxetine combination: -5.7, p = .001; olanzapine: -11.6, p = .004; switched: -6.4, p = .015). The majority of patients who entered the study in nonremission achieved remission (MADRS total score < or = 12) during the trial (olanzapine-fluoxetine combination: 66.7%, olanzapine: 64.7%, switched: 62.5%). The overall rate of depressive relapse was 27.4%, and the overall incidence of mania emergence was 5.9%.. The present findings suggest that long-term treatment with olanzapine-fluoxetine combination may be a useful option for the management of depressive symptoms and carries a low risk of mania emergence.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cross-Over Studies; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoxetine; Humans; Incidence; Male; Olanzapine; Placebos; Psychiatric Status Rating Scales; Retrospective Studies; Risk Factors; Secondary Prevention; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

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

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

Determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) for treatment of acute bipolar I depression compared with lamotrigine.. The 7-week, acute phase of a randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine ([LMG] titrated to 200 mg/day; N = 205) in patients with DSM-IV-diagnosed bipolar I disorder, depressed. The study was conducted from November 2003 to August 2004.. Completion rates were similar between treatments (OFC, 66.8% vs. LMG, 65.4%; p = .835). OFC-treated patients had significantly greater improvement than lamotrigine-treated patients in change from baseline across the 7-week treatment period on the Clinical Global Impressions-Severity of Illness scale (primary outcome) (p = .002, effect size = 0.26), Montgomery-Asberg Depression Rating Scale (MADRS) (p = .002, effect size = 0.24), and Young Mania Rating Scale total scores (p = .001, effect size = 0.24). Response rates did not significantly differ between groups when defined as > or = 50% reduction in MADRS score (OFC, 68.8% vs. LMG, 59.7%; p = .073). Time to response was significantly shorter for OFC-treated patients (median days [95% CI] = OFC, 17 [14 to 22] vs. LMG, 23 [21 to 34]; p = .010). There was a significant difference in incidence of "suicidal and self-injurious behavior" adverse events (OFC, 0.5% vs. LMG, 3.4%; p = .037). Somnolence, increased appetite, dry mouth, sedation, weight gain, and tremor occurred more frequently (p < .05) in OFC-treated patients than lamotrigine-treated patients. Weight, total cholesterol, and triglyceride levels were significantly elevated in OFC-treated patients compared with lamotrigine-treated patients (all p < or = .001).. Patients with acute bipolar I depression had statistically significantly greater improvement in depressive and manic symptoms, more treatment-emergent adverse events, greater weight gain, and some elevated metabolic factors with OFC than lamotrigine. Treatment differences were of modest size.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoxetine; Humans; Lamotrigine; Male; Olanzapine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Self-Injurious Behavior; Severity of Illness Index; Treatment Outcome; Triazines

To identify symptoms associated with suicidality in bipolar I disorder patients, and to assess suicide risk during treatment with olan-zapine in combination with lithium or divalproex.. We used data from a study (conducted from September 1997 to October 2000) in which DSM-IV bipolar I manic or mixed-episode patients who were partially responsive to at least 2 weeks of lithium or dival-proex monotherapy prior to study entry were randomly assigned to augmentation therapy with olanzapine (5-20 mg/day) or placebo. Among mixed-episode patients with residual suicidality (Hamilton Rating Scale for Depression-item 3 [HAM-D-3] score of 1 or above) at randomization to cotherapy, we identified items in the Young Mania Rating Scale, Positive and Negative Syndrome Scale, and Barnes Akathisia Rating Scale that correlated with HAM-D-3 scores. We used factor analysis of correlated items to identify symptom domains associated with suicidality ratings and assessed changes in symptom factors and HAM-D-3 scores during 6 weeks of combination therapy with olanzapine versus placebo.. In 58 mixed-episode patients, mean +/- SD HAM-D-3 scores averaged 1.36 +/- 0.55 after at least 2 weeks of initial mood stabilizer monotherapy prior to study entry. Factors associated with the HAM-D-3 appeared to represent somatic discomfort, agitated depression, and psychotic features. Combination therapy with olanzapine (N = 36) versus placebo (N = 22) differentially reduced HAM-D-3 scores by 58% versus 29% (p < .05) within 1 week, and all 3 associated symptom factors within 2 weeks by averages of 31% versus 12% (p < .05).. Suicidality in adult, mixed-episode, bipolar I disorder patients was associated with somatic discomfort, agitated depression, and psychosis. Overall, these findings suggest that the addition of an atypical antipsychotic-antimanic agent in some bipolar disorder patients may help to reduce suicidal ideation.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Placebos; Principal Component Analysis; Psychiatric Status Rating Scales; Risk Factors; Suicide; Treatment Outcome; Valproic Acid

The effect of lamotrigine on the steady-state plasma concentrations of the atypical antipsychotics clozapine, olanzapine, and risperidone was investigated in patients with schizophrenia or bipolar disorder stabilized on chronic treatment with clozapine (200-500 mg/day; n = 11), risperidone (3-6 mg/day; n = 10) or olanzapine (10-20 mg/day; n = 14)). Lamotrigine was titrated up to a final dosage of 200 mg/day over 8 weeks, and pharmacokinetic assessments were made at baseline and during treatment weeks 6 and 10, at lamotrigine dosages of 100 and 200 mg/day respectively. The plasma concentrations of clozapine, norclozapine, risperidone, and 9-hydroxy-risperidone did not change significantly during treatment with lamotrigine. The mean plasma concentrations of olanzapine were 31 +/- 7 ng/mL at baseline, 32 +/- 7 ng/mL at week 6, and 36 +/- 9 ng/mL at week 10, the difference between week 10 and baseline being statistically significant (P < 0.05). Adjunctive lamotrigine therapy was well tolerated in all groups. These findings indicate that lamotrigine, at the dosages recommended for use as a mood stabilizer, does not affect the plasma levels of clozapine, risperidone, and their active metabolites. The modest elevation in plasma olanzapine concentration, possibly due to inhibition of UGT1A4-mediated olanzapine glucuronidation, is unlikely to be of clinical significance.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Drug Interactions; Female; Humans; Lamotrigine; Male; Middle Aged; Olanzapine; Risperidone; Schizophrenia; Triazines

Sub-syndromal symptoms in bipolar disorder impair functioning and diminish quality of life.. To examine factors associated with time spent with sub-syndromal symptoms and to characterise how these symptoms influence outcomes.. In a double-blind randomised maintenance trial, patients received either olanzapine or lithium monotherapy for 1 year. Stepwise logistic regression models were used to identify factors that were significant predictors of percentage time spent with sub-syndromal symptoms. The presence of sub-syndromal symptoms during the first 8 weeks was examined as a predictor of subsequent relapse.. Presence of sub-syndromal depressive symptoms during the first 8 weeks significantly increased the likelihood of depressive relapse (relative risk 4.67, P<0.001). Patients with psychotic features and those with a greater number of previous depressive episodes were more likely to experience sub-syndromal depressive symptoms (RR=2.51, P<0.001 and RR=2.35, P=0.03 respectively).. These findings help to identify patients at increased risk of affective relapse and suggest that appropriate therapeutic interventions should be considered even when syndromal-level symptoms are absent.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Female; Humans; Lithium Compounds; Male; Middle Aged; Olanzapine; Prognosis; Remission Induction; Treatment Outcome

To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes.. This 3-week, randomized, controlled, double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N = 165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM-IV criteria for bipolar I disorder, manic or mixed episode, without psychotic features. The study was conducted at 30 sites in the United States between July 2001 and June 2002. The primary outcome measure was the mean change in the Young Mania Rating Scale (YMRS) total score. Secondary measures included the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impressions-Bipolar Version (CGI-BP) severity of illness scale, and the Cognitive Test for Delirium (CTD). Quality of life (Short Form Health Survey [SF-12]), psychological well-being (Psychological General Well-Being [PGWB] inventory), and sexual functioning were also compared.. Mean modal doses for olanzapine and risperidone were 14.7 mg/day and 3.9 mg/day, respectively. Between treatments, there was no difference in mean change in the YMRS, MADRS, CTD, PGWB, or SF-12 measures or in remission or response rates. Significantly more olanzapine-treated patients completed the study compared with risperidone patients (78.7% vs. 67.0%; p = .019). Olanzapine-treated patients had greater HAM-D-21 (p = .040) and CGI-BP (p = .026) score improvement across the study. Olanzapine-treated patients experienced greater elevations in liver function enzymes (p < .05) and increase in weight (2.5 kg vs. 1.6 kg; p = .004), while risperidone-treated patients were more likely to experience prolactin elevation (51.73 ng/mL vs. 8.23 ng/mL; p < .001) and sexual dysfunction (total score increase of 1.75 vs. 0.64; p = .049).. Both olanzapine and risperidone treatment yielded similar improvements in mania. The olanzapine group had significantly greater improvements in secondary measures of severity and depressive symptoms and better study completion rates but experienced more weight gain.

Topics: Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Appetite; Benzodiazepines; Bipolar Disorder; Dizziness; Double-Blind Method; Female; Headache; Humans; Least-Squares Analysis; Male; Middle Aged; Olanzapine; Risperidone; Sleep Stages; Treatment Outcome

Typical experimental categorizations of treatment responses in bipolar disorder (BPD) patients may have limited relationship to clinical recovery or functional status, and there is inadequate research on such clinically important outcomes.. We analyzed data from a study of open continuation of olanzapine treatment following a 3-week placebo-controlled trial involving initially hospitalized adult subjects with DSM-IV BP-I mania to estimate rates and times to symptomatic remission (low scores on standardized symptomatic assessments) and clinical recovery (remission sustained>or=8 weeks), associated clinical factors, and functional outcomes.. During treatment with olanzapine for 27.9+/-20.1 weeks, symptomatic remission was attained by 70% of subjects, half by 8 weeks (95% CI 6-10) weeks, and later lost by 82% of remitted subjects; remitted (versus non-remitted) subjects had slightly lower baseline clinical global impression scores and greater trial-completion. Sustained clinical recovery was attained by only 40 of 113 (35%) of subjects, half by 36 (95% CI 20-40) weeks, and later lost by 45%. Subjects with above-median (>12) initial Hamilton-Depression rating scale depression scores were half as likely to recover (p=0.016) and did so much later (36 versus 12 weeks) than those with lower scores. At final assessment, self-rated well being (SF-36 psychosocial functioning scores) improved substantially more among recovered versus non-recovered subjects (mean changes: 87% versus 23%), and two-thirds of recovered subjects remained unemployed-for-pay while half received disability-compensation.. Clinically meaningful symptomatic remission and recovery in relatively severely ill adult bipolar I manic patients were achieved slowly and sustained by only some patients within an average of 7 months of continuous treatment. These clinically relevant outcomes were worse with relatively high initial dysphoria ratings. Well-being was rated higher by recovered subjects, but their ability to work and live independently were markedly impaired. These findings underscore the emerging view that BPD can often be severe, slow to remit, and disabling, particularly in association with prominent depression-dysphoria symptoms. Improved treatments for BPD are needed, guided by longitudinal assessments of clinically meaningful measures of symptomatic recovery and functional outcome.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Recovery of Function; Treatment Outcome

Treatment-emergent mania is a potential risk when patients with bipolar disorder are treated with antidepressant agents. These subanalyses compare treatment-emergent mania rates in bipolar I depressed patients treated with olanzapine, placebo, or olanzapine/fluoxetine combination.. In this 8-week, double-blind investigation, patients with bipolar I depression (DSM-IV criteria) (N = 833, baseline Montgomery-Asberg Depression Rating Scale total score > or = 20) were randomly assigned to olanzapine (5-20 mg/day, N = 370), placebo (N = 377), or olanzapine/fluoxetine combination (6/25, 6/50, or 12/50 mg/day; N = 86). Treatment-emergent mania was evaluated with the Young Mania Rating Scale (YMRS), the Clinical Global Impressions-Bipolar Edition (CGI-BP) Severity of Mania scale, and adverse events records.. Overall rates of study discontinuation due to mania were low and not significantly different among the therapy groups (p = .358). Incidence of treatment-emergent mania (defined as a YMRS score < 15 at baseline and > or = 15 at any subsequent visit) did not differ significantly among therapy groups (olanzapine 5.7%, placebo 6.7%, olanzapine/fluoxetine combination 6.4%; p = .861). Subjects receiving olanzapine or olanzapine/fluoxetine combination had greater mean decreases in YMRS scores than those receiving placebo (p < .001 for both). Subjects receiving olanzapine or olanzapine/fluoxetine combination also had greater mean decreases in CGI-BP scores than those receiving placebo (p = .040 and p = .003, respectively).. These results suggest that olanzapine/fluoxetine combination does not present a greater risk of treatment-emergent mania compared to olanzapine or placebo over 8 weeks of acute treatment for bipolar I depression. Due to the cyclical nature of bipolar disorder, patients taking olanzapine/fluoxetine combination for bipolar depression should still be monitored for signs or symptoms of emerging mania.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Olanzapine; Placebos; Psychiatric Status Rating Scales; Risk Factors; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

This study examined direct treatment costs based on medication and service use data collected in a 47-week multi-center, double-blind, randomized clinical trial of olanzapine versus divalproex for patients with bipolar disorder and and experiencing acute mania.. Patients who completed the 3-week acute phase and entered into the 44-week maintenance phase (n = 147) of the trial were included. Service use data were collected at weeks 3, 7, 15, 23, 31, 39 and 47 of the maintenance phase. Analyses were conducted to address potential biases from discontinuation patterns and use of this patient sub-sample.. Overall, per patient yearly costs were similar for olanzapine- and divalproex-treated patients ($14 967 vs. $15 801). Psychiatric-related costs accounted for 95.4% and 93.6% of the total costs for olanzapine- and divalproextreated patients, respectively. Study medication costs were significantly higher for olanzapine than for divalproex ($4662 vs. $1755, p < 0.01). However, this was offset by the combined effects of numerically lower costs for several other services with olanzapine treatment. Some of the savings associated with olanzapine treatment compared with divalproex treatment resulted from differences in costs associated with emergency room services ($432 vs. $1346, p < 0.05).. Overall per-patient treatment costs were similar for olanzapine and divalproex. Recognizing challenges in analyzing and generalizing cost outcomes from a clinical trial setting, results provide some much-needed comparative economic information regarding these two medication options for treating mania in bipolar disorder.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost Savings; Double-Blind Method; Female; Health Care Costs; Health Services; Humans; Male; Middle Aged; Olanzapine; Valproic Acid

Current guidelines for the initial treatment of bipolar type I (BP I) and bipolar type II (BP II) major depressive episode (MDE) recommend avoiding the use of antidepressant drugs due to concerns over drug-induced manic switch episodes. However, recent evidence suggests that the manic switch rate during SSRI therapy of BP MDE may be lower than previously thought. This preliminary, placebo-controlled study examines the relative rates of treatment-emergent manic symptoms during fluoxetine monotherapy, olanzapine monotherapy, and combined fluoxetine plus olanzapine therapy of BP I and BP II MDE.. 32 BP I and 2 BP II MDE patients were randomized to receive double-blind therapy with fluoxetine monotherapy 10-30 mg daily, olanzapine monotherapy 5-20 mg daily, combined therapy with fluoxetine 10-40 mg plus olanzapine 5-15 mg daily, or placebo for up to 8 weeks. Outcome measures included the 17-item HAM-D, 17-item HAM-D "atypical" symptom profile (HAM-D 17-R), 28 item HAM-D, Montgomery-Asberg Depression Rating Scale (MADRS), and the Young Mania Rating (YMR) scale.. There were significant reductions over time in mean HAM-D 28 and MADRS ratings for all treatment groups (p<0.006). However, there were no differences among treatment conditions (p=ns). There was no significant increase in YMR scores over time in any treatment group. In contrast, there was a significant reduction in the mean YMR score in the fluoxetine-treated patients over time (p=0.008). No patient met DSM IV criteria for a manic episode.. Cohort sizes were limited and the study was not powered to detect statistical differences in efficacy or mania symptoms among treatment conditions. The dose of fluoxetine was modest and the treatment duration was limited to 8 weeks.. These observations support earlier findings of a low manic switch rate during fluoxetine monotherapy of BP I and BP II MDE, and suggest that fluoxetine may be a safe initial treatment of BP MDE alone or in combination with olanzapine.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Middle Aged; Olanzapine; Placebos; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia. Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement. Trying to minimize this weight gain in a population with an already high prevalence of obesity, mortality and morbidity is of clinical and social importance. This randomized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine.. Fifty-one individuals (29 females, 22 males) who had started on olanzapine in the previous 3 months (mean length of 27 days +/- 20) were recruited through Peninsula Health Psychiatric Services and were randomly assigned to either the intervention (n = 29) or the control group (n = 22). Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period. Weight, waist circumference, body mass index (BMI) and qualitative measures of exercise levels, quality of life, health and body image were collected at baseline at 3 and 6 months.. After 3 months, the control group had gained significantly more weight than the treatment group (6.0 kg vs 2.0 kg, p < or = 0.002). Weight gain of more than 7% of initial weight occurred in 64% of the control group compared to 13% of the treatment group. The control group's BMI increased significantly more than the treatment group's (2 kg/m(2)vs 0.7 kg/m(2), p < or = 0.03). The treatment group reported significantly greater improvements in moderate exercise levels, quality of life, health and body image compared to the controls. At 6 months, the control group continued to show significantly more weight gain since baseline than the treatment group (9.9 kg vs 2.0 kg, p < or = 0.013) and consequently had significantly greater increases in BMI (3.2 kg/m(2)vs 0.8 kg/m(2), p < or = 0.017).. Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Body Image; Body Mass Index; Depressive Disorder, Major; Exercise; Female; Health Status; Humans; Male; Nutritional Physiological Phenomena; Obesity; Olanzapine; Quality of Life; Schizophrenia; Weight Gain

The present study reports the results of an open-label trial on the use of the combination of olanzapine (an atypical antipsychotic) serotonin reuptake inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive-compulsive disorder (OCD). All patients had been suffering from OCD, according to DSM IV criteria, for at least 2 years and had different comorbid disorders; they had been treated with an SRI at adequate dosages for at least 6 months, or had tried different augmentation strategies with no or poor response. As a result, olanzapine was added and continued for 1 year. After 12 weeks of this regimen, most of the patients (17) had shown a reduction in OC symptoms, as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score, which continued throughout subsequent months. Only mild side-effects were recorded and no patient halted the treatment. The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients, especially in those presenting comorbidity with bipolar disorders.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Drug Resistance; Female; Humans; Italy; Long-Term Care; Male; Obsessive-Compulsive Disorder; Olanzapine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors

The authors compared the efficacy of olanzapine and lithium in the prevention of mood episode relapse/recurrence.. Patients with a diagnosis of bipolar disorder (manic/mixed), a history of two or more manic or mixed episodes within 6 years, and a Young Mania Rating Scale total score > or =20 entered the study and received open-label co-treatment with olanzapine and lithium for 6-12 weeks. Those meeting symptomatic remission criteria (Young Mania Rating Scale score < or =12; 21-item Hamilton depression scale score < or =8) were randomly assigned to 52 weeks of double-blind monotherapy with olanzapine, 5-20 mg/day (N=217), or lithium (target blood level: 0.6-1.2 meq/liter) (N=214).. Symptomatic relapse/recurrence (score > or =15 on either the Young Mania Rating Scale or Hamilton depression scale) occurred in 30.0% of olanzapine-treated and 38.8% of lithium-treated patients. The noninferiority of olanzapine relative to lithium (primary objective) in preventing relapse/recurrence was met, since the lower limit of the 95% confidence interval on the 8.8% risk difference (-0.1% to 17.8%) exceeded the predefined noninferiority margin (-7.3%). Secondary results showed that compared with lithium, olanzapine had significantly lower risks of manic episode and mixed episode relapse/recurrence. Depression relapse/recurrence occurred in 15.7% of olanzapine-treated and 10.7% of lithium-treated patients. Mean weight gain during open-label co-treatment was 2.7 kg; during double-blind monotherapy, weight gain was significantly greater with olanzapine (1.8 kg) than with lithium (-1.4 kg).. These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium; Longitudinal Studies; Male; Olanzapine; Psychiatric Status Rating Scales; Secondary Prevention; Treatment Outcome

To evaluate short-term safety and efficacy of atypical antipsychotics in a single-site, prospective, open-label, 8-week study of risperidone and olanzapine monotherapy in preschoolers with bipolar disorder (BPD).. Risperidone was initiated at an open-label dose of .25 mg/day, increased weekly according to response and tolerability to a maximum does of 2.0 mg/day. Olanzapine was initiated at 1.25 mg/day and increased to no more than 10 mg/day.. Thirty-one children aged 4-6 years were treated with olanzapine (n = 15, 6.3 +/- 2.3 mg/day) or risperidone (n = 16, 1.4 +/- .5 mg/day). At study end point (week 8 or last observation carried forward), there was a 18.3 +/- 11.9 point (t = -5.6, p < .001) reduction in risperidone-treated subjects and a 12.1 +/- 10.4 point (t = -4.4, p < .001) reduction in Young Mania Rating Scale (YMRS) scores in olanzapine-treated subjects that did not differ between groups (t = 1.4, p = .2). Response criteria (Clinical Global Impression improvement of "Much" or "Very Much" improved or a YMRS change of >or= 30% or more) indicated no difference in rate of response with risperidone and olanzapine (69% vs. 53%, chi(2)((1)) = .8, p = .4).. This prospective open study suggests that treatment with risperidone or olanzapine may result in a rapid reduction of symptoms of mania in preschool children with BPD. Because of substantial residual symptomatology and adverse effects, however, a pressing need exists to identify additional safe and effective treatments for the management of BPD in this high-risk population.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Child, Preschool; Female; Humans; Male; Olanzapine; Pilot Projects; Prolactin; Prospective Studies; Psychiatric Status Rating Scales; Risperidone; Socioeconomic Factors

Improving patients' health-related quality of life (HRQOL) could be a treatment goal for bipolar depression.. The objectives of these secondary analyses of a previous report were to determine the benefits of olanzapine alone and olanzapine-fluoxetine combination (OFC) for improving HRQOL in patients with bipolar depression using both a generic and a depression-specific HRQOL instrument, and to examine the association between the 2 HRQOL instruments and the construct validity of the depression-specific HRQOL instrument.. This was a double-blind, placebo-controlled, 83-site, international, randomized trial. Adults with bipolar I disorder, most recent episode depressed (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), were randomly assigned to receive olanzapine (6-20 mg/d), OFC (6/25, 12/25, or 12/50 mg/d), or placebo for 8 weeks. HRQOL improvement was calculated as last-observation-carried-forward changes in dimension and component summary scores on Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and total score on the Quality of Life in Depression Scale (QLDS).. Patients were assigned to receive olanzapine (n = 370), [corrected] OFC (n = 86), or placebo (n = 377) [corrected] for 8 weeks. Of 833 enrolled patients, 454 discontinued (olanzapine, 191/370 [51.6%] [corrected]OFC, 31/86 [36.0%]; and placebo, 232/377 [61.6%]) [corrected] Compared with placebo, olanzapine-treated patients exhibited greater improvements on SF-36 mental component summary (MCS) score ( P=0.002) and 3 of 8 SF-36 dimension scores (mental health [P=0.015], role-emotional [P=0.046], and social functioning [P=0.006). OFC-treated patients exhibited greater improvements on MCS score ( P<0.001) vs both placebo and olanzapine), 5 SF-36 dimension scores (general health perception (P<0.001) vs placebo; (P<0.001) vs olanzapinel, mental health [ P=0.001] vs both placebo and olanzapine], role-emotional [ P<0.001] vs placebo; [P=0.007] vs olanzapine], social functioning [ P=0.001] vs placebo; [P=0.032] vs olanzapine], and vitality [P=0.002] vs placebo; [P=0.011] vs olanzapine]), and QLDS total score ( P<0.001] vs both placebo and olanzapine). Changes in SF-36 scores of mental health, social functioning, role-emotional, and vitality were highly correlated to changes in the QLDS total score (all p < -0.5).. Based on these analyses, patients with bipolar depression receiving olanzapine or OFC for 8 weeks had greater improvement in HRQOL than those receiving placebo. OFC treatment was associated with greater improvement in HRQOL than olanzapine alone. The correlation results support the construct validity of the QLDS.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Drug Combinations; Female; Fluoxetine; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Quality of Life; Selective Serotonin Reuptake Inhibitors

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

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

Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder. Aims To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.. Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6-1.2 mmol/l) or valproate (50-125 microg/ml) received lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.. The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy 40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy 42 days; P=0.023).. Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.

Topics: Adult; Aged; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lithium; Male; Middle Aged; Olanzapine; Recurrence; Time Factors; Valproic Acid

Olanzapine is currently marketed not only for the treatment of schizophrenia, but also for the treatment of acute mania and the prevention of relapse in patients successfully treated with this drug for a manic episode. A large body of good clinical trials supports these indications. In the mania trials, olanzapine was more efficacious than placebo, equal or more efficacious than valproate and more efficacious than lithium or valproate monotherapy when used in combination with either drug. A trial that compared olanzapine with haloperidol failed to show superiority of the atypical versus the conventional. Olanzapine showed a modest but statistically significant effect in the treatment of bipolar depression; this modest effect was substantially enhanced in combination with fluoxetine. The long-term trials showed that olanzapine was better than placebo in the prevention of manic and depressive relapse and not inferior to lithium or valproate. The combination of olanzapine with lithium or valproate was also more efficacious than lithium or valproate alone in the prevention of manic relapse in patients partially non-responding to monotherapy with lithium or valproate. All these trials suggest that olanzapine may be a valuable drug in the short- and long-term treatment of bipolar I disorder. However, there are some concerns about the safety and tolerability of olanzapine in this population, as far as weight gain and metabolic syndrome are concerned, which may be addressed in future pharmacovigilance studies.

Topics: Benzodiazepines; Bipolar Disorder; Double-Blind Method; Humans; Multicenter Studies as Topic; Olanzapine; Spain

Topics: Adult; Benzodiazepines; Bipolar Disorder; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine

The objective of this study was to determine the clinical and quality of life outcomes associated with adjunctive treatment of olanzapine added to either lithium or valproic acid/divalproex sodium in patients with bipolar disorder.. Patients with bipolar I disorder, were randomized to receive either olanzapine (5-20 mg) added to mood stabilizer therapy (n=224), or placebo added to mood stabilizer therapy (n=112) for 6 weeks. Changes in clinical outcomes over 6 weeks were measured by the Young Mania Rating Scale (Y-MRS) and the Hamilton Rating Scale for Depression (HAM-D). Quality of life was measured by the Lehman Brief Quality of Life Interview (QLI).. Patients treated with olanzapine added to mood stabilizers, experienced significantly greater mean clinical improvements from baseline on both the Y-MRS and the HAM-D compared to those treated with placebo added to mood stabilizers. Over 6 weeks, patients treated with olanzapine added to mood stabilizers had significantly greater mean improvements from baseline on five of the nine subjective scales on the QLI, compared to patients treated with placebo added to mood stabilizers. Changes in scores on the subjective scales of the QLI were more strongly correlated to changes in depressive symptomatology measured by the HAM-D, than to changes in symptoms of mania measured by the Y-MRS.. The results of this study demonstrate that patients receiving adjunctive treatment have significantly greater improvements in both clinical and quality of life outcomes compared to monotherapy with mood stabilizers.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Lithium Chloride; Male; Olanzapine; Placebos; Quality of Life; Treatment Outcome; Valproic Acid

Rapid-cycling (RC) bipolar disorder patients experience high levels of morbidity, typically respond unsatisfactorily to available treatments, and, so, require additional studies of novel treatments. We report on the first controlled study comparing acute and continuous clinical outcomes in RC and non-RC manic patients treated with olanzapine.. We analyzed data pooled from 2 placebo-controlled, double-blind, 3- to 4-week trials of olanzapine in mania (N = 254), 1 with an open-label extension up to 1 year (N = 113) and controlled supplementation with lithium or fluoxetine as needed, to compare demographic, clinical, and outcome measures between RC and non-RC subgroups of 254 DSM-IV bipolar I manic subjects.. RC (N = 90, 35%) versus non-RC subjects (N = 164, 65%) were younger at intake (p = .02), less often psychotic (p < .0001), and more likely to have familial bipolar disorder (p < .0001), abused substances (p = .01), more previous hospitalizations (p = .004), and many more illness episodes (p < .001). In initial blinded trial outcomes, relative responses (> or = 50% improvement of mania) to olanzapine/placebo were similar in RC and non-RC subjects, though early responses to olanzapine favored RC over non-RC subjects (p = .003), and long-term outcomes favored non-RC subjects (p = .05). Fewer RC subjects achieved strictly defined initial symptomatic remission (p = .014) within a year; RC subjects were more likely to experience recurrences (p = .002), especially of depressive illness (< .001), and had more rehospitalizations (p = .01) and suicide attempts (p = .03).. RC bipolar I patients showed major initial differences and more rapid initial clinical changes, especially toward depression, with less favorable long-term outcomes than non-RC cases during treatment with olanzapine. Inclusion of RC bipolar disorder patients can complicate therapeutic trials, but these patients require further study for differential responsiveness to innovative treatments with methods of assessing clinical response that take their mood instability into account.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Screening Assays, Antitumor; Drug Therapy, Combination; Female; Fluoxetine; Humans; Lithium; Longitudinal Studies; Male; Meta-Analysis as Topic; Olanzapine; Proportional Hazards Models; Psychiatric Status Rating Scales; Survival Analysis; Treatment Outcome

To describe the antidepressant effectiveness of olanzapine and risperidone and compare their tolerability when employed adjunctively in bipolar I/II disorder.. In an observational study, twenty-one ambulatory subjects with DSM-IV defined bipolar I/II disorder, in any phase of the illness, openly received adjunctive risperidone or olanzapine. The primary efficacy parameters were the Hamilton Depression Rating Scale (HDRS-17) and the Maier and Philips Severity Subscale. Secondary efficacy parameters included the Young Mania Rating Scale (YMRS) along with the Clinical Global Impressions Scale (CGI). Response was defined as a significant change from baseline to endpoint in the total mean HDRS-17 score. The primary tolerability parameters were the Abnormal Involuntary Movement Scale (AIMS) along with changes in weight and body mass index (BMI-kg/m2). Patients were evaluated prospectively with repeated monthly assessments for up to 6 months.. Eleven patients openly received risperidone; 10 received olanzapine adjunctive to either lithium or divalproex. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p=0.001), with the mean HDRS-17 total scores falling from 17(SD=3.2) to 5(SD=1.5) by 6 months in the risperidone-treated group and from 18 (SD=1.9) to 7 (SD=2.0) in the olanzapine-treated group. Differences between the risperidone-treated group and the olanzapine-treated group were not significant at 6 months (p=0.754). The mean doses of study medication were 2.88 (SD=1.6) mg/day for the risperidone-treated group and 12.69 (SD=2.3) mg/day for the olanzapine-treated group. Both risperidone and olanzapine were generally well tolerated. No patients developed tardive dyskinesia. Significant weight gain was experienced by patients in both groups [mean weight gain at endpoint was 5.9 kg in risperidone (p=0.023) and 11.3 kg in olanzapine (p=0.001)]. There was a significant difference in weight gain between the risperidone-treated group and the olanzapine-treated group (p=0.001).. These pilot data, from the first prospective comparison study of risperidone and olanzapine in bipolar disorder, suggest that adjunctive administration of either agent may reduce depressive symptom severity. No subjects receiving risperidone or olanzapine developed tardive dyskinesia. Both compounds imparted substantial weight gain with significantly more weight gain accrual with olanzapine. As this was an observational study, the antidepressant effect and tolerability profile of these compounds requires validation via double-blind placebo controlled investigations.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Weight; Chemotherapy, Adjuvant; Depression; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pilot Projects; Prospective Studies; Psychiatric Status Rating Scales; Risperidone; Time Factors; Valproic Acid

Prescription corticosteroids are given for a variety of common medical conditions. Psychiatric symptoms including depression, psychosis, and especially mania are common side effects of corticosteroid therapy. However, minimal data are available on the treatment of corticosteroid-induced psychiatric symptoms.. In this study, 12 outpatients with manic or mixed symptoms secondary to corticosteroids were enrolled in a 5-week prospective, open-label trial of olanzapine. Psychiatric symptom measures included the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Side effects were monitored with the Simpson Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Scale (BAS). Weight and blood glucose were obtained at baseline and exit. Olanzapine dosing was flexible beginning at 2.5 mg/day and titrated upward as necessary to a maximum dose of 20 mg/day. Data were analyzed with Wilcoxon signed rank tests using baseline and exit data on all 12 participants.. Participants showed significant reductions in YMRS (primary outcome measure), HRSD, and BPRS scores with no significant change in the SAS, AIMS, BAS, weight, or blood glucose levels. One participant discontinued early due to lack of efficacy.. These data suggest that olanzapine is well tolerated and appears to be useful for mood disturbances associated with corticosteroid therapy. Controlled trials seem warranted to confirm these observations.

Topics: Adrenal Cortex Hormones; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Prednisone; Prospective Studies; Texas; Treatment Outcome

Few controlled studies examine the treatment of depressive features in mania.. To evaluate the efficacy of olanzapine, in combination with lithium or valproate, for treating depressive symptoms associated with mania.. Secondary analysis of a 6-week, double-blind, randomised study of olanzapine (5-20 mg/day) or placebo combined with ongoing valproate or lithium open treatment for 344 patients in mixed or manic episodes. This analysis focused on a dysphoric subgroup with baseline Hamilton Rating Scale for Depression (HRSD) total scores of 20 or over contrasted with non-dysphoric patients.. In the dysphoric subgroup (n=85) mean HRSD total score improvement was significantly greater in olanzapine co-therapy patients than in those receiving placebo plus lithium or valproate (P<0.001). Substantial contributors to this superiority included the HRSD Maier sub-scale (P=0.013) and the suicide item (P=0.001). Total Young Mania Rating Scale improvement was also superior with olanzapine co-therapy.. In patients with acute dysphoric mania, addition of olanzapine to ongoing lithium or valproate monotherapy significantly improved depressive symptom, mania and suicidality ratings.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Olanzapine; Treatment Outcome; Valproic Acid

Body weight increase during long-term treatment with olanzapine in schizophrenia patients is well documented, but weight gain and its association with other medical measures are less well evaluated in bipolar disorder patients.. We analyzed data from a 3-week, randomized, placebo-controlled trial of olanzapine for acute mania in DSM-IV bipolar I patients, followed by open continuation treatment with olanzapine up to a year. We examined factors associated with increased body mass index (BMI), including ratings of clinical change and selected physiologic measures.. Among 113 subjects treated with olanzapine for a mean +/- SD of 28.6 +/- 19.9 weeks, BMI increased from a baseline mean of 28.8 +/- 6.2 kg/m(2), by 7.9 +/- 10.8% (p < .001), into the obese range (31.0 +/- 6.1 kg/m(2)). Initial BMI change (first 3 weeks of drug exposure) predicted final BMI increases (Spearman rank correlation r(s) = 0.32, p < .001). History of longer illness (p = .006) and lifetime substance abuse (p = .02) were associated with below-median BMI increases. BMI increased much more among 40 subjects achieving symptomatic recovery than in the 73 who did not (by 11.9 +/- 13.2% vs. 5.3 +/- 7.7%; p = .004), with correspondingly longer olanzapine exposure (44.7 +/- 11.8 vs. 19.7 +/- 17.7 weeks; p < .001) at similar doses. On average, serum cholesterol increased 4.8 times more (17.5% vs. 3.6%) and endpoint cholesterol levels were newly 240 mg/dL or greater 3.6 (95% CI = 1.5 to 8.0) times more frequently in subjects with above-median BMI gain, who also experienced significantly larger increases in systolic and diastolic blood pressure, pulse rates, and nonfasting serum glucose than low-BMI-gain subjects.. Weight gain associated with long-term olanzapine treatment for mania was common, substantial, time-dependent, predicted by initial increases, and temporally associated with significant changes in cardiovascular and metabolic measures in bipolar I patients with prolonged illness and already-high basal BMI. An association of weight gain with favorable clinical response probably reflects longer olanzapine treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Longitudinal Studies; Male; Obesity; Olanzapine; Psychiatric Status Rating Scales; Pulse; Treatment Outcome; Weight Gain

Published case reports describe apparent induction or exacerbation of manic-like symptoms during treatment with the atypical antipsychotics olanzapine and risperidone. To date, such reports are from uncontrolled clinical experience and therefore cannot clarify whether the atypical antipsychotics caused such manic-like states or simply failed to prevent them. Presumably, bipolar patients would be at increased risk for this putative adverse event. Therefore, we evaluated the potential of olanzapine to exacerbate symptoms of mania compared to placebo during treatment of bipolar mania.. Two inpatient, double-blind, randomized trials investigating the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of acute mania were combined. Two hundred and fifty-four subjects participated (placebo n=129; olanzapine n=125) in the two studies. Severity of mania was quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc analysis, after double-blind therapy up to 3 weeks, categorical comparison of olanzapine and placebo groups was made for any worsening and worsening by 10 or 20% from baseline Y-MRS scores (LOCF).. The percentage of subjects with exacerbation at endpoint were: any worsening, placebo 37.7%, olanzapine 21.8% (P=0.005); >or=10% worsening, placebo 24.6%, olanzapine 14.5% (P=0.039); >or=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064).. Mania rating scores worsened for some patients during olanzapine therapy. However, this was significantly less common with olanzapine than with placebo. These controlled data suggest that clinical case reports of occurrence of 'mania' during treatment with olanzapine, and possibly those with other atypical antipsychotics, reflect exacerbation in the natural history of bipolar illness, rather than an adverse pharmacological effect.. Post-hoc analysis of pooled data from two different studies.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Disease Progression; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Severity of Illness Index; Treatment Outcome

A substantial proportion of patients with bipolar disorder are characterized by a rapidly cycling course and are particularly resistant to conventional treatment.. This secondary analysis, defined a priori, was conducted on a larger data set from patients with bipolar I disorder to determine the efficacy of a 3-week treatment with the atypical antipsychotic olanzapine (5-20 mg/day, n=19) versus placebo (n=26) in patients with >or=4 episodes in the preceding year.. Significantly fewer placebo patients completed treatment (34.6 vs. 73.7%, P=0.016), and more than half discontinued due to lack of efficacy (53.8 vs. 21.1%, P=0.035). Olanzapine reduced Young Mania Rating Scale (YMRS) total scores significantly more than placebo (-13.9 vs. -4.1, P=0.011). Clinical responses, defined as >or=50% improvement in YMRS, were achieved in 58% of olanzapine patients, compared with 28% of placebo patients (P=0.066). Extrapyramidal symptoms were not significantly changed in either group. Somnolence was the most common adverse event in both groups (olanzapine: 52.6%, placebo: 23.1%; P=0.060). No event occurred significantly more frequently with olanzapine than with placebo. No patients discontinued due to an adverse event.. The duration of this study was limited to 3 weeks, precluding conclusions about long-term efficacy of olanzapine. Moreover, a sizeable placebo effect was obtained, possibly masking optimal therapeutic effect. Despite these limitations, treatment differences in efficacy were highly significant.. These results indicate that olanzapine was effective in reducing symptoms of mania and well tolerated in patients with bipolar I disorder with a rapid-cycling course.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Middle Aged; Olanzapine; Periodicity; Pirenzepine; Placebo Effect; Placebos; Retrospective Studies

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

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

Clinically meaningful recovery from acute mania may not be captured by conventionally reported response categorizations. We defined new and stringent criteria for remission in bipolar mania. Using a cohort of patients with acute mania randomized to treatment with either olanzapine or placebo, we contrasted remission rates to findings using previously reported but more lenient categorical outcome measures of response and euthymia.. We pooled and reanalyzed results through 3 weeks from two published randomized double-blind trials of olanzapine versus placebo for treating acute bipolar mania (1, 2). Response was previously defined as > or = 50% decrease from baseline to endpoint total Young Mania Rating Scale (3) (Y-MRS) scores, and euthymia as an endpoint total Y-MRS score of < or = 12. In this report, remission required an endpoint total Y-MRS score of < or = 7, and an endpoint total Hamilton Depression Rating Scale, (HAM-D21) (4) score of < or = 7 and an endpoint Clinical Global Impression Scale - Bipolar version, CGI-BP (5), overall severity score of < or = 2.. Olanzapine treated subjects achieved statistically significantly greater rates of clinical response, euthymia and remission than those assigned to placebo, 55% versus 29.5%, 50% versus 27%, and 18% versus 7%, respectively.. Olanzapine monotherapy resulted in discernable clinical improvements in mania in over 50% of subjects and just under 20% of subjects achieved a near complete resolution of manic and accompanying depressive symptoms after 3 weeks of treatment. Full remission is an important but potentially elusive goal during short-term management of acute mania.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Female; Humans; Male; Olanzapine; Pirenzepine; Placebos; Remission Induction; Treatment Outcome

Randomized controlled trials have demonstrated the efficacy of olanzapine for treating acute mania or depression symptoms in patients with bipolar disorder. We aimed to evaluate the effectiveness of this medication in more usual care outpatient settings. A consecutive series of 15 patients entered an open, uncontrolled 8-week trial of olanzapine monotherapy. Inclusion criteria included significant hypomanic or manic symptoms greater than or equal to 15 on the Young Mania Rating Scale and no psychotic symptoms. The majority of patients experienced significant decreases in mania ratings and more limited improvement on depression ratings. Most patients reported adverse events consistent with other studies, but few discontinued due to these complaints. This case series highlights the individual variation in response to a proven medication. Furthermore, it highlights that those medications effective at one end of the mood spectrum may not be equally or simultaneously effective with other symptoms, emphasizing the complexity of treating bipolar illness.

Topics: Administration, Oral; Adult; Affect; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Middle Aged; Olanzapine; Outpatients; Pirenzepine; Severity of Illness Index; Treatment Outcome

Divalproex sodium is a mood stabilizer used in the United States for the treatment of acute mania associated with bipolar disorder. Recently, olanzapine, an atypical antipsychotic, was approved for the treatment of acute mania. This study compares the clinical, health-related quality of life (HRQL), and economic outcomes of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder.. This 12-week, double-blind, double-dummy, randomized clinical trial included 120 subjects with DSM-IV bipolar disorder type I hospitalized for an acute manic episode recruited from 21 U.S. clinical centers. Subjects were randomly assigned to treatment with either divalproex or olanzapine and were followed in hospital for up to 21 days. If after 21 days clinical improvements (based on the Mania Rating Scale [MRS]) were not observed, subjects were discontinued. Subjects showing clinical improvement were treated for up to 12 weeks. HRQL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) after hospital discharge (baseline) and at 6 and 12 weeks. Medical resource use and costs were collected over the 12-week study.. A total of 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomized, and 78 (65%) were followed beyond 21 days. No statistically significant differences between the treatment groups for baseline-to-endpoint MRS or Q-LES-Q scores were observed. Total 12-week outpatient medical costs were significantly lower for the divalproex-treated group (541 US dollars) compared with the olanzapine-treated group (1080 US dollars) (p =.004). There was no significant difference in total medical costs between the 2 groups (divalproex = 13,703 US dollars; olanzapine = 15,180 US dollars; p =.88).. Divalproex is associated with lower 12-week outpatient costs compared with olanzapine. Divalproex and olanzapine have similar short-term effects on clinical or HRQL outcomes in bipolar disorder subjects.

Topics: Acute Disease; Adult; Ambulatory Care; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Health Care Costs; Health Services; Health Status; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Quality of Life; Treatment Outcome; Valproic Acid

Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation. In 3 double-blind studies, acutely agitated patients with schizophrenia (N = 311), bipolar mania (N = 201), or dementia (N = 206) were treated with intramuscular (1-3 injections/24 hrs) olanzapine (2.5-10.0 mg), haloperidol (7.5 mg), lorazepam (2.0 mg), or placebo. The Agitation-Calmness Evaluation Scale (ACES; Eli Lilly and Co.) and treatment-emergent adverse events assessed sedation. Across all studies, 1 patient (lorazepam-treated, bipolar) became unarousable. There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across. Excluding asleep patients, agitation remained significantly more reduced with olanzapine than placebo (P <.05). The incidences of adverse events indicative of sedation were not significantly different with olanzapine versus comparators. For the treatment of acute agitation associated with schizophrenia, bipolar mania, or dementia, intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dementia; Double-Blind Method; Drug Administration Schedule; Haloperidol; Humans; Hypnotics and Sedatives; Injections, Intramuscular; Lorazepam; Olanzapine; Pirenzepine; Psychomotor Agitation; Retrospective Studies; Schizophrenia; Treatment Outcome

Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex.. This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest.. Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness.. In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.

Topics: Acute Disease; Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Secondary Prevention; Survival Analysis; Treatment Outcome; Valproic Acid

Prolongation of the QTc interval has been reported during treatment with oral antipsychotic agents and may be more pronounced during parenteral administration. Pooled QTc interval data from acutely agitated patients across four double-blind trials were compared. Databases included: placebo-controlled [two schizophrenia, one bipolar mania trials (n=565)]; haloperidol-controlled [two schizophrenia trials (n=482)]; geriatric placebo-controlled [1 dementia trial (n=204)]. Patients received 1-3 injections of intramuscular (IM) olanzapine (2.5-10 mg/injection), IM haloperidol (7.5 mg/injection), or IM placebo. At 2 and 24 h after IM olanzapine treatment, the mean QTc interval decreased approximately 3 ms from baseline in the placebo- and haloperidol-controlled databases. When there was a statistically significant difference between IM olanzapine and IM placebo, QTc intervals decreased during treatment with IM olanzapine and increased with IM placebo. The incidences of prolonged (endpoint >/=99th percentile of healthy adults or >/=500 ms) or lengthened (increase >/=60 ms) QTc intervals during treatment with IM olanzapine (<3% placebo- and haloperidol-controlled databases, <12% geriatric placebo-controlled database) were never significantly greater than with comparators. These data suggest that IM olanzapine has a favorable QTc interval profile in acutely agitated patients with schizophrenia, bipolar mania, or dementia.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dementia; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Haloperidol; Humans; Injections, Intramuscular; Long QT Syndrome; Olanzapine; Psychomotor Agitation; Schizophrenia

Novel antipsychotics impart substantial weight gain. Persons with bipolar disorder are frequently treated with these and other agents known to impart substantial weight gain. We sought to describe the influence of adjunctive risperidone and olanzapine on body weight, body mass index (BMI, kg/m2) and serum leptin levels over a prospective observation period of 6 months. Throughout the 6-month investigation, significant increases from baseline to end point in weight were noted with both agents; with significantly greater weight gain with olanzapine (t(10) = 2.761, P = 0.023; t(9) = 4.783, P = 0.001). Leptin levels were highly correlated with increases in weight and were significantly elevated from baseline at 4 months (r = 0.658, P < 0.05). Significant increases in weight and body mass index were apparent at 3 months (P < 0.05). The temporal association between weight increase and leptin changes does not support the notion that leptin is a primary promoter of antipsychotic-induced weight gain; however, a secondary perpetuating role cannot be ruled out.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Female; Humans; Leptin; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone; Valproic Acid; Weight Gain

Two double-blind, placebo-controlled trials of olanzapine in acute mania showed significant overall antimanic efficacy, based on reductions in mania ratings. Their subject-level data were pooled to increase statistical power to test for differences in treatment responses among 10 subgroup pairs of interest using generalized estimating equations methods. Similar drug/placebo superiority and responsiveness to olanzapine was found in men versus women, psychotic versus nonpsychotic subjects, and those presenting in mania versus mixed states, and responses were independent of onset age, current age, or prior illness based on episodes, hospitalizations, recent rapid cycling, lifetime substance use, or previous antipsychotic treatment. Olanzapine and placebo responses paralleled closely (r(s) = 0.73). Patients were relatively more responsive to olanzapine who were younger at illness onset, lacked prior substance abuse, and had not previously received antipsychotic treatment (efficacy ratios 1.5-1.7, all P < 0.01). These well-powered comparisons of subgroups of interest indicate broad efficacy of olanzapine in the treatment of acute mania.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Models, Psychological; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Risk

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

Previous studies have examined the safety and tolerability of oral-loaded divalproex sodium in the treatment of acute mania, but not the early efficacy of this dosing strategy. The purpose of this study was to evaluate the early efficacy of oral-loaded divalproex.. In this pooled analysis, 348 subjects from 3 randomized, double-blind, parallel-group, active- or placebo-controlled studies were used to compare the efficacy, safety, and tolerability of oral-loaded divalproex with standard-titration divalproex, lithium, olanzapine, or placebo. Subjects were inpatients diagnosed with acute mania associated with bipolar I disorder (DSM-III-R or -IV and SADS-Change Version). Patients were administered oral-loaded divalproex (20 or 30 mg/kg/day on days 1 and 2 followed by 20 mg/kg/day, and increased at physician's discretion), standard-titration divalproex initiated at 250 mg t.i.d. and titrated to 40-150 microg/mL, lithium (300 mg t.i.d. initial dose) titrated to 0.4 to 1.5 mEq/L, olanzapine (10 mg q.d. initial dose) up to 20 mg/day, or placebo.. The results demonstrate an early efficacy advantage for oral-loaded divalproex compared to standard-titration divalproex at days 5, 7/8, and 10. Efficacy was improved over lithium on day 7/8. There were no efficacy differences between divalproex loading and olanzapine. Divalproex loading showed greater efficacy than placebo at all time points. Divalproex loading was as well tolerated or better tolerated than the other active treatments as measured by adverse events and changes in laboratory parameters.. These results suggest the oral loading of divalproex leads to a more rapid antimanic effect when compared with standard-titration divalproex, lithium, or placebo and is better tolerated than olanzapine and as well tolerated as lithium or standard-titration divalproex.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Tolerance; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Severity of Illness Index; Titrimetry; Treatment Outcome; Valproic Acid

Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression.. To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.. Double-blind, 8-week, randomized controlled trial.. Eighty-four sites (inpatient and outpatient) in 13 countries. Patients A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20. Intervention Patients were randomly assigned to receive placebo (n = 377); olanzapine, 5 to 20 mg/d (n = 370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n = 86).. Changes in MADRS total scores using mixed-effects model repeated-measures analyses.. During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group (P<.001 for all). The olanzapine-fluoxetine group also showed statistically greater improvement than the olanzapine group at weeks 4 through 8. At week 8, MADRS total scores were lower than at baseline by 11.9, 15.0, and 18.5 points in the placebo, olanzapine, and olanzapine-fluoxetine groups, respectively. Remission criteria were met by 24.5% (87/355) of the placebo group, 32.8% (115/351) of the olanzapine group, and 48.8% (40/82) of the olanzapine-fluoxetine group. Treatment-emergent mania (Young Mania Rating Scale score <15 at baseline and > or =15 subsequently) did not differ among groups (placebo, 6.7% [23/345]; olanzapine, 5.7% [19/335]; and olanzapine-fluoxetine, 6.4% [5/78]). Adverse events for olanzapine-fluoxetine therapy were similar to those for olanzapine therapy but also included higher rates of nausea and diarrhea.. Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Double-Blind Method; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome

This randomized controlled trial compares the efficacy and safety of olanzapine vs haloperidol, as well as the quality of life of patients taking these drugs, in patients with bipolar mania.. The design consisted of 2 successive, 6-week, double-blind periods and compared flexible dosing of olanzapine (5-20 mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219).. Rates of remission (Young-Mania Rating Scale score of < or =12 and 21-item Hamilton Rating Scale for Depression score of < or =8 at week 6) were similar for olanzapine- and haloperidol-treated patients (52.1% vs 46.1%, respectively; P =.15). For the subgroup of patients whose index episode did not include psychotic features, rates of remission were significantly greater for the olanzapine group compared with the haloperidol group (56.7% vs 41.6%, P =.04). Relapse into an affective episode (mania and/or depression) occurred in 13.1% and 14.8% of olanzapine- and haloperidol-treated patients, respectively (P =.56). Switch to depression occurred significantly more rapidly with haloperidol than with olanzapine when using survival analysis techniques (P =.04), and significantly more haloperidol-treated patients experienced worsening of extrapyramidal symptoms, as indicated by several measures. Weight gain was significantly greater in the olanzapine group compared with the haloperidol group (2.82 vs 0.02 kg, P<.001). The olanzapine group had significant improvement in quality of life on several dimensions compared with the haloperidol group.. These data suggest that olanzapine does not differ from haloperidol in achieving overall remission of bipolar mania. However, haloperidol carries a higher rate of extrapyramidal symptoms, whereas olanzapine is associated with weight gain.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Personality Inventory; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome

We aimed to compare clinical outcomes, health-related quality of life (HRQOL) and work status associated with olanzapine and haloperidol treatment in patients with bipolar disorder. This double-blind, randomized controlled trial, comparing flexible dosing of olanzapine (5-20 mg/day, n = 234) to haloperidol (3-15 mg/day, n = 219), consisted of a 6-week acute phase, followed by a 6-week continuation phase. Symptomatic remission rates were similar for olanzapine- and haloperidol-treated patients at weeks 6 and 12. At week 6, significant changes in five dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) [general health (P = 0.010), physical functioning (P < 0.001), role limitations due to physical problems (P < 0.001), social functioning (P < 0.05) and vitality (P < 0.01)] and the SF-36 physical components summary score were found in favour of olanzapine compared to haloperidol. At week 12, olanzapine treatment maintained the significantly favourable HRQOL changes. At the end of week 12, patients on olanzapine showed significantly greater improvement than haloperidol in work activities impairment and household activities impairment scores on the Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE/LIFE) activities impairment scores. Subgroup analyses revealed that olanzapine treatment significantly increased a proportion of employed patients and their weekly paid working hours. In conclusion, compared to haloperidol, olanzapine treatment was comparably effective in the remission of bipolar mania and significantly improved HRQOL and work status in patients with bipolar I disorder.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Pirenzepine; Quality of Life; Treatment Outcome; Work

The simultaneous presentation of manic and depressive symptoms in the same patient is fairly common. The terms and have been used as equivalents to mixed states. Pharmacotherapy is less effective in this group of patients. The aim of this study is to determine the effectiveness and safety of olanzapine as an add-on therapy in patients with bipolar disorder with a rapid cycling course during a dysphoric mania episode. Thirteen patients treated with mood stabilizers for at least 1 year and diagnosed with a mixed episode were included in an open trial. All had at least 4 episodes in the last year. Patients with organic diseases, including altered thyroid function, were excluded from the research. Patients were evaluated at inclusion and at day 28. Response was defined as a decrease of 50% in the Young Mania Rating Scale and the Hamilton Rating Scale for Depression concomitant with a Clinical Global Impression improvement of 1 or 2. All patients completed the study. The doses of olanzapine were 16.15 +/- 5.82 mg/day. There was a reduction in the manic and depressive symptoms in all patients. Ten of the 13 patients were considered to have responded to the treatment according to the response definition. Adverse effects included somnolence (23.08%) and weight gain (0.81 +/- 1.96 kg in women, 2.20 +/- 2.28 kg in men). Our results suggest that olanzapine combined with mood stabilizers is safe and effective in the treatment of the manic and the depressive symptoms of dysphoric mania with a rapid cycling course.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Chemotherapy, Adjuvant; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Time Factors; Valproic Acid

To evaluate effects of olanzapine in diverse exacerbations of bipolar disorders.. Twenty-five evaluable bipolar disorder [14 bipolar I (BPI), 10 bipolar II (BPII) and one bipolar disorder not otherwise specified (BP NOS)] outpatients received open olanzapine (15 adjunctive, 10 monotherapy). Thirteen had elevated (11 syndromal, two subsyndromal) and 12 depressed (four syndromal, eight subsyndromal) mood symptoms of at least mild severity, with Clinical Global Impression-Severity (CGI-S) scores of at least 3. Only one had psychotic symptoms.. With open olanzapine (15 adjunctive, 10 monotherapy), overall symptom severity (CGI-S) as well as mood elevation (Young Mania Rating Scale), depression (Hamilton and Montgomery-Asberg Depression Rating Scales), and anxiety (Hamilton Anxiety Rating Scale), rapidly decreased (significantly by days 2-3). Patients with the greatest baseline severity (CGI-S) had the greatest improvement. Fifteen of 25 (60%) patients responded. Time to consistent response was bimodal, with five early (by 0.5 +/- 0.3 weeks) and 10 late (by 7.0 +/- 1.9 weeks) responders. Early compared with late responders had 51% lower final olanzapine doses. Olanzapine was generally well tolerated, with sedation and weight gain the most common adverse effects.. Olanzapine was effective in diverse exacerbations of bipolar disorders. The bimodal distribution of time to response and different final doses are consistent with differential mechanisms mediating early compared with late responses. Controlled studies are warranted to further explore these preliminary observations.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Olanzapine; Pirenzepine; Severity of Illness Index; Surveys and Questionnaires; Time Factors

This study compared the efficacy, safety, and tolerability of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder.. This randomized, 12-week, double-blind, parallel-group, multicenter study included DSM-IV-defined bipolar disorder type I patients hospitalized for acute mania and randomly assigned to treatment with divalproex or olanzapine. After an inpatient period of up to 21 days, subjects were followed as outpatients. Dose adjustment was permitted during the inpatient period. Efficacy was assessed using change from baseline in Mania Rating Scale (MRS) score to day 21; other efficacy measures included the Brief Psychiatric Rating Scale, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Part I, Severity of Illness scale. The primary safety endpoint was change from baseline in weight. Other safety and tolerability endpoints included spontaneous adverse event reporting and changes from baseline in laboratory measures and vital signs.. 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomly assigned to treatment. No significant differences between groups were found for any efficacy variable for change from baseline to day 21. Mean MRS score changes from baseline to day 21 were -14.8 for divalproex and -17.2 for olanzapine (p =.210). A significantly (p <.05) greater proportion of olanzapine-treated subjects experienced somnolence, weight gain, edema, rhinitis, and speech disorder (slurred speech); no adverse events were significantly greater in the divalproex group. A number of laboratory measures also demonstrated significant treatment differences, but the clinical significance of many of these is uncertain. Mean body weight changes were significantly greater in the olanzapine group (+ 8.8 lb [+ 4.0 kg]) than the divalproex group (+ 5.5 lb [+ 2.5 kg], p <.050). One death occurred during the study (olanzapine group, diabetic ketoacidosis).. No significant difference in efficacy was found between treatment groups. Divalproex was associated with a more favorable adverse event profile and significantly less weight gain than olanzapine.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Valproic Acid

A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes.. The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer).. Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech.. Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.

Topics: Acute Disease; Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome; Valproic Acid

The effects of olanzapine and divalproex for the treatment of mania were compared in a large randomized clinical trial.. A 3-week, randomized, double-blind trial compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day in divided doses) for the treatment of patients hospitalized for acute bipolar manic or mixed episodes. The Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to quantify manic and depressive symptoms, respectively. Safety was assessed with several measures.. The protocol defined baseline-to-endpoint improvement in the mean total score on the Young Mania Rating Scale as the primary outcome variable. The mean Young Mania Rating Scale score decreased by 13.4 for patients treated with olanzapine (N=125) and 10.4 for those treated with divalproex (N=123). A priori categorizations defined response and remission rates: 54.4% of olanzapine-treated patients responded (> or = 50% reduction in Young Mania Rating Scale score), compared to 42.3% of divalproex-treated patients; 47.2% of olanzapine-treated patients had remission of mania symptoms (endpoint Young Mania Rating Scale < or = 12), compared to 34.1% of divalproex-treated patients. The decrease in Hamilton depression scale score was similar in the two treatment groups. Completion rates for the 3-week study were similar in both groups. The most common treatment-emergent adverse events (incidence >10%) occurring more frequently during treatment with olanzapine were dry mouth, increased appetite, and somnolence. For divalproex, nausea was more frequently observed. The average weight gain with olanzapine treatment was 2.5 kg, compared to 0.9 kg with divalproex treatment.. The olanzapine treatment group had significantly greater mean improvement of mania ratings and a significantly greater proportion of patients achieving protocol-defined remission, compared with the divalproex treatment group. Significantly more weight gain and cases of dry mouth, increased appetite, and somnolence were reported with olanzapine, while more cases of nausea were reported with divalproex.

Topics: Acute Disease; Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Olanzapine; Pirenzepine; Treatment Outcome; Valproic Acid

A clinically important question for any new treatment for bipolar disorder is whether its efficacy extends to patients who have both responded and failed to respond to other mood stabilizers. In this secondary analysis of a placebo-controlled trial demonstrating olanzapine's efficacy for acute mania, we explore whether its usefulness extends to those patients with a history of poor response to other mood stabilizers.. This 4-week, double-blind, placebo-controlled trial studied olanzapine monotherapy 5-20 mg/day for hospitalized patients in acute manic or mixed bipolar episodes. The primary outcome variable was beginning to endpoint change in the Young-Mania Rating Scale (Y-MRS) total score. We investigated whether prospectively identified history of recent failure to respond to other mood stabilizers predicted response to olanzapine.. As previously reported, olanzapine-treated patients experienced significantly greater improvement in Y-MRS total score and higher remission rates relative to placebo-treated patients. The current analysis compared these outcome parameters in patients with known poor prior response to lithium and/or valproate with all other patients and found no significant group by treatment interactions, i.e., treatment effects were not significantly diminished in non-responders to older mood stabilizing agents.. Olanzapine has been shown to be superior to placebo for the treatment of mania. This secondary analysis suggests that olanzapine monotherapy is similarly effective for patients whether or not they previously have failed to respond to another mood stabilizer for mania. A study limitation is that response to lithium or valproate was determined retrospectively.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index

The objectives of this study were to determine the economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in patients diagnosed with mania.. Patients with a diagnosis of bipolar I disorder with manic or mixed episodes were enrolled in a randomized controlled trial. The study design comprised a 3-week acute phase followed by a 49-week open label extension. In the open label extension, the use of lithium and fluoxetine was permitted for patients who experienced breakthrough symptoms. Clinical, economic, and quality-of-life outcomes of treatment were assessed.. During the acute phase, olanzapine patients experienced a statistically significant greater mean improvement from baseline on the Y-MRS total score compared to the placebo patients. In the open label extension, patients experienced a statistically significant mean change of 11.8 units on the Y-MRS from the end of the acute phase. When compared to costs incurred in the previous 12 months of therapy, patients experienced savings of almost $900 per month during the 49 weeks of olanzapine therapy. These cost savings were largely driven by reductions in in-patient costs during the open label extension. Health-related quality of life improvements measured by the SF-36 were seen on several dimensions both in the 3-week acute phase as well as in the 49-week open label extension.. From a clinical, economic, and quality-of-life outcomes standpoint, olanzapine had a significant impact in the treatment of mania, and could be considered a cost-effective treatment option for use in this population if these findings are extrapolated to non-clinical trial populations.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Costs and Cost Analysis; Female; Humans; Male; Olanzapine; Pirenzepine; Quality of Life

Olanzapine has demonstrated efficacy in the treatment of acute mania in 2 double-blind, placebo-controlled trials. We describe the results of the open-label extension from one of these trials.. In a 3-week, double-blind study of patients with DSM-IV bipolar I disorder, olanzapine was superior to placebo for the treatment of acute manic symptoms. Of the 139 patients who entered the double-blind phase of the 3-week study, 113 patients continued into the 49-week open-label extension. Efficacy measurements including the Young Mania Rating Scale (YMRS), the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Clinical Global Impressions scale-Bipolar Version, and the Positive and Negative Syndrome Scale and safety measurements including the Simpson-Angus scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale were completed throughout. The analysis considered all treatment results, starting with the first olanzapine dose. Adjunctive lithium and fluoxetine were allowed during the open-label extension.. The mean length of olanzapine treatment was 6.6 months, with a mean modal dose of 13.9 mg/day. A significant mean improvement in the YMRS total score, baseline to endpoint (-18.01, p < .001), was observed. During treatment, 88.3% of patients experienced a remission of manic symptoms (YMRS total score < or =12), and only 25.5% subsequently relapsed (YMRS total score > or = 15). Significant improvement in HAM-D-21 scores was observed (p < .001). Forty-one percent of patients were maintained on olanzapine monotherapy. The most common treatment-emergent adverse events reported were somnolence (46.0%), depression (38.9%), and weight gain (36.3%).. During up to 1 year of olanzapine therapy, either as monotherapy or in combination with lithium and/or fluoxetine, patients with bipolar disorder demonstrated significant improvement in mania and depression symptoms with a favorable safety profile. Further double-blind, controlled studies are needed to confirm these results.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluoxetine; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep; Treatment Outcome; Weight Gain

There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.

Topics: Adult; Affect; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cholinergic Antagonists; Double-Blind Method; Female; Heart Rate; Humans; Injections, Intramuscular; Lorazepam; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Psychomotor Agitation; Treatment Outcome

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

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

The aim of this study was to estimate the long-term effectiveness of olanzapine as adjunctive therapy in patients with bipolar disorder who exhibited an inadequate response to mood stabilizers. Twenty-three Research Diagnostic Criteria (RDC) patients with bipolar I and II were assessed by means of the Schedule for Affective Disorders and Schizophrenia and entered if they gave their consent to participate. All of them had experienced frequent relapses, residual subsyndromal symptoms, and inadequate responses to other drugs, such as lithium, valproate, or carbamazepine. While maintaining other drugs, they all received open-label, increasing doses of olanzapine, until achieving clinical response. Other drugs were maintained. The patients were assessed several consecutive times from baseline to the endpoint with the Clinical Global Impressions (CGI) scale for use in bipolar illness. Records of recurrences, hospitalizations, and side effects were also collected. The last-observation-carried-forward analysis showed that there was a significant reduction of CGI scores after the introduction of olanzapine, either in manic symptoms (p = 0.0015), depressive symptoms (p = 0.0063), or global symptoms (p = 0.0003). The most frequent adverse events were somnolence (17%) and weight gain (13%). The mean dose of olanzapine at the end of the 43-week follow-up was 8.1 mg/day. Olanzapine may be a useful medication for the long-term adjunctive treatment of patients with bipolar disorder who exhibit a poor response to mood stabilizers, such as lithium, valproate, or carbamazepine. These results suggest mood-stablizing properties of olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Female; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Recurrence; Time Factors; Treatment Outcome; Weight Gain

The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents.. This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale).. Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001).. Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Topics: Abdominal Pain; Adolescent; Antipsychotic Agents; Appetite; Benzodiazepines; Bipolar Disorder; Brief Psychiatric Rating Scale; Child; Child, Preschool; Disorders of Excessive Somnolence; Female; Humans; Male; Olanzapine; Patient Compliance; Pirenzepine; Prospective Studies; Severity of Illness Index; Time Factors; Weight Gain

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

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

We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania.. Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change.. Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively).. Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep Wake Disorders; 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 first episode of an illness may respond differently to any treatment compared to multiple episodes of the same illness. This study details the treatment response of six first-episode manic patients who participated in a previously reported study of 139 subjects comparing olanzapine to placebo in bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR, Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999; 156: 702-709).. Six first-episode subjects participated in a 3-week double-blind, random assignment, parallel group, placebo-controlled study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y-MRS), Clinical Global Impression, and Hamilton Depression ratings were administered weekly. Lorazepam as rescue medication was permitted for the first 10 days.. Five subjects were randomized to placebo and one to olanzapine. Two subjects (40%) with psychotic mania (who also had their first-illness episode) were assigned to placebo and responded with greater than 50% reduction in the Y-MRS score and also remitted in 3 weeks. Another placebo-assigned subject had a 46% reduction in the Y-MRS scores, and two placebo-assigned subjects worsened. The olanzapine-assigned subject had a 44% reduction in the Y-MRS score. In contrast, 34 of 69 (48.6%) multiple-episode olanzapine subjects responded and 14 of 61 (23.0%) of placebo-treated subjects did.. This preliminary data set suggest there may be differences in treatment response between first-illness episode versus multi-episode bipolar manic subjects. Larger numbers of subjects with these illness characteristics are needed to either confirm or refute this suggestion.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Placebo Effect

The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania.. The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score.. The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group.. The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.

Topics: Acute Disease; Adolescent; Adult; Aged; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Administration Schedule; Female; Headache; Humans; Male; Middle Aged; Olanzapine; Patient Dropouts; Pirenzepine; Placebos; Psychiatric Status Rating Scales; Sleep; Treatment Outcome

Neuroleptics are of established efficacy in mania. Controlled data on the use of olanzapine in mania is however, absent. In this study, 30 patients meeting DSM-IV criteria for mania were randomly allocated to receive either olanzapine or lithium in a 4 week double-blind randomized controlled design. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (lithium 28.2; olanzapine 28.0; P = 0.44); Clinical Global Impression (CGI) improvement scale (lithium 2.75, olanzapine 2.36; P = 0.163) or the Mania Scale (lithium 13.2, olanzapine 10.2; P = 0.315). Olanzapine was however, significantly superior to lithium on the CGI-severity scale at week 4 (lithium 2.83, olanzapine 2.29; P = 0.025). Olanzapine did not differ from lithium in terms of treatment emergent extrapyramidal side-effects as measured by the Simpson-Angus Scale. Olanzapine appears to be at least as effective as lithium in the treatment of mania.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Prospective Studies; Psychiatric Status Rating Scales

We evaluated the response to olanzapine in 14 consecutive patients with bipolar I disorder who were inadequately responsive to standard psychotropic agents.. Fourteen patients with bipolar I disorder by DSM-IV criteria experiencing persistent affective symptoms inadequately responsive to at least one standard mood stabilizer were treated with open-label olanzapine by one of the authors. Response was assessed with the Clinical Global Impression Scale modified for use in bipolar disorder (CGI-BP).. The 14 patients received olanzapine at a mean (SD dosage of 14.1+/-7.2 (range 5-30) mg/day for a mean+/-SD of 101.4+/-56.3 (range 30-217) days of treatment. Of the 14 patients, 8 (57%) displayed much or very much overall improvement in their illness. In general, olanzapine was well tolerated. The most common side effects were sedation, tremor, dry mouth, and appetite stimulation with weight gain.. Data were obtained nonblindly and without a randomized control group, and olanzapine was added to ongoing psychotropic regimens.. Olanzapine may have antimanic and mood-stabilizing effects in some patients with bipolar disorder, and is generally well tolerated. Controlled studies of olanzapine in bipolar disorder appear warranted.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Pirenzepine; Prospective Studies; Retrospective Studies

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delirium; Humans; Mania; Olanzapine; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Medically Unexplained Symptoms; Olanzapine

Transient elevation of liver enzymes is reported in 9 % of patients on olanzapine. However, rare cases of symptomatic hepatotoxicity associated with olanzapine use have been reported in the literature. This case report describes a woman who presented acute hepatitis linked to the use of olanzapine. Similar reports in the literature are also analyzed.. A 43-year-old female patient, treated for bipolar disorder type I by sodium valproate 1500 mg/d, was admitted to hospital for management of a manic episode. Her liver tests at admission were normal. As soon as she was admitted to hospital, the patient was treated by olanzapine 10 mg/day, which was increased to 20 mg/day over 2 weeks, and diazepam, in addition to the sodium valproate 1500 mg/d. Three days after the increase of olanzapine to 20 mg, the patient pre- sented with mucocutaneous jaundice, dark urine with pruritus and vomiting, and a marked alteration of liver enzymes. No etiology was found to explain this hepatotoxicity other than drug origin.. This case report emphasizes the need for a baseline hepatic evaluation before starting olanzapine therapy and regular monitoring of liver enzyme levels, especially among at risk patients.. Une élévation transitoire des enzymes hépatiques est rapportée chez 9 % des patients sous olanzapine, Cependant, de rares cas d’hépatotoxicité symptomatique associée à l’utilisation de l’olanzapine ont été rapportés dans la littérature. Le but de ce rapport de cas est de présenter un cas d’hépatite aiguë induite par l’utilisation de l’olanzapine et de comparer ce cas avec les données de la littérature.. Patiente âgée de 43 ans, suivie pour trouble bipolaire type I sous valproate de sodium 1.500 mg/j, hospitalisée pour prise en charge d’un accès maniaque. Son bilan hépatique à l’admission était sans particularité. Dès son hospitalisation, la patiente a été mise, en plus du valproate de sodium 1.500 mg/j, sous olanzapine 10 mg/j, dose qui a été augmentée à 20 mg/j en 2 semaines et ajout de diazépam. Trois jours après l’augmentation d’olanzapine à 20 mg, la patiente a présenté un ictère cutanéo-muqueux, des urines foncées avec un prurit et des vomissements, avec une perturbation du bilan hépatique. Aucune étiologie n’a été trouvée pour expliquer cette hépatotoxicité, à part l’origine médicamenteuse.. Nous soulignons la nécessité de faire un bilan hépatique de base avant de commencer le traitement par olanzapine et de surveiller régulièrement les taux d’enzymes hépatiques, en particulier chez les patients à risque.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Hepatitis; Humans; Olanzapine

Bipolar (BPD) patients have deficits in cognition, but there are still controversies about the effects of some medications on their cognitive performance. Here, we investigated the relationship between cognition in terms of executive functions, memory, and attention in both first-episode medication-naive BPD patients and BPD patients taking olanzapine. Forty-one healthy controls, 40 unmedicated drug-naive BPD patients, and 34 BPD patients who took only olanzapine were recruited for the study. Cognitive performance was assessed using the Flanker test, Stroop test, and Corsi-block test. Bayesian multivariate regression analysis was run considering maximum robustness to avoid bias and to predict the outcomes. Our results revealed that unmedicated medication-naive BPD patients performed worse than healthy controls and the olanzapine group in some tasks. Additionally, BPD patients who took olanzapine had better cognitive performance than healthy controls and unmedicated BPD patients. The acute cognitive effects were predicted by olanzapine dosage and serum levels (i.e., large effects). The potential pro-cognitive effects of olanzapine in BPD patients should be carefully interpreted by considering various other clinical variables. We expect that our findings will contribute to further research in this area, with the goal of helping other researchers, patients, and the population.

Topics: Bayes Theorem; Bipolar Disorder; Cognition; Executive Function; Humans; Neuropsychological Tests; Olanzapine

Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and its presence adds to the morbidity of BP. While there are no known pharmacological treatments for CD, pediatric BP is responsive to treatment with medications initially indicated for the treatment of psychosis, several of which have Food and Drug Administration (FDA) approval for the treatment of pediatric mania.. The main aim of this secondary analysis was to examine whether pediatric BP comorbid with CD responds similarly to treatment with such selected medications. Considering the well-documented morbidity of CD, this finding could have important clinical and public health significance.. Pediatric BP can be effectively treated with the abovementioned medications in the context of comorbid CD. Based on previous research showing that remission of BP is associated with remission of CD, if confirmed, these findings raise the possibility that antimanic treatment of youth with BP comorbid with CD could have secondary benefits in mitigating the morbidity associated with CD. This is a pilot scale finding, the results of which are promising and should be confirmed by larger and long-term follow-up studies.

Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Child; Clinical Trials as Topic; Conduct Disorder; Humans; Mania; Olanzapine; Piperazines; Prospective Studies; Quetiapine Fumarate; Risperidone; Thiazoles

Topics: Antipsychotic Agents; Bipolar Disorder; Delusions; Humans; Mitochondrial Membranes; Olanzapine; Sleep Initiation and Maintenance Disorders

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

Olanzapine (OLZ) is one of the most effective antipsychotic agents, however, its clinical utility has been limited by weight gain. Samidorphan (SAM) is a μ-opioid receptor antagonist and it can reduce the weight gain associated with OLZ. A combination of OLZ and SAM (OLZ/SAM) has been developed to provide the antipsychotic efficacy of OLZ, while mitigating OLZ-associated weight gain.. A comprehensive literature search was conducted in PubMed. Key search terms included SAM and weight gain associated with OLZ. The pharmacological action, clinical efficacy, and safety of SAM were reviewed.. OLZ can lead to weight gain. SAM is a new drug that acts as an opioid receptor antagonist that can decrease weight gain. SAM mitigates OLZ-associated weight gain while preserving the antipsychotic efficacy of OLZ. Clinical trials have confirmed that OLZ/SAM significantly improved psychotic symptoms, and resulted in significantly less weight gain than OLZ. OLZ/SAM was well tolerated. Therefore, it is a potential new treatment option for schizophrenia.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Naltrexone; Narcotic Antagonists; Olanzapine; Schizophrenia; Weight Gain

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).

Topics: Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Drug-Related Side Effects and Adverse Reactions; Exanthema; Humans; Japan; Lamotrigine; Lithium Carbonate; Olanzapine; Quetiapine Fumarate; Risperidone

Lurasidone is used for treatment of bipolar depression in adults and adolescents. Lurasidone-associated manic switch has been reported in adults but not yet in adolescents. We report a case of lurasidone-induced manic switch in a male adolescent treated for bipolar I depression. Five days after adding lurasidone to his regimen (sodium valproate and olanzapine), our patient became manic with psychotic features. After discontinuation of lurasidone, he was stabilised with electroconvulsive therapy, and the medication was switched to a lithium-quetiapine combination. This case highlights the potential risk of lurasidone-induced manic switch in adolescents with bipolar depression.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Drug Therapy, Combination; Humans; Lithium Compounds; Lurasidone Hydrochloride; Male; Mania; Olanzapine; Quetiapine Fumarate; Valproic Acid

Topics: Antipsychotic Agents; Bipolar Disorder; Depression; Humans; Olanzapine

The aim of this study was to compare the outcomes of monotherapy in individuals with bipolar disorder who are prescribed lithium, valproate, quetiapine, olanzapine, venlafaxine, or citalopram in private psychiatric practices in Germany.. This retrospective study included bipolar disorder patients who had initially started on a monotherapy with lithium, valproate, quetiapine, olanzapine, venlafaxine, or citalopram in 93 private neuropsychiatric practices in Germany between January 2006 and December 2017. Treatment failure was defined as time to discontinuation of medication or addition of another mood stabilizer, antipsychotic, antidepressant, or benzodiazepine.. A total of 4990 bipolar patients was examined for the period between 2006 and 2019. Initially, monotherapy with lithium (n=1.098), valproate (n=502), quetiapine (n=927), olanzapine (n=927), venlafaxine (n=574), or citalopram (n=962) was prescribed. Within 24 months, treatment failure had occurred in 76.3% (lithium), 85.1% (valproate), 84.6% (quetiapine), 85.2% (venlafaxine), 92.1% (olanzapine), and 86.6% (citalopram) of patients, respectively. The hazard ratio for treatment failure compared to lithium as reference was highest for olanzapine at 1.66 (1.46-1.88), followed by citalopram 1.27 (1.15-1.39), quetiapine 1.18 (1.07-1.29), valproate 1.18 (1.06-1.33), and venlafaxine 1.14 (1.02-1.27).. Our results underline the importance of lithium in the maintenance treatment of bipolar disorders.

Topics: Antipsychotic Agents; Bipolar Disorder; Citalopram; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Valproic Acid; Venlafaxine Hydrochloride

The potential of clozapine in severe bipolar disorder is suggested by its efficacy in refractory schizophrenia, but the evidence is limited thus far. This report utilizes data from the standard care pathway of the Systematic Treatment Enhancement Program to examine the clinical impact of clozapine in bipolar disorder, comparing it to two groups, one that received olanzapine and an additional group that received neither drug.. A total of 4,032 outpatients were available for this analysis. Groups for longitudinal analyses are based on the medication used at each visit. Outcomes assessed were clinical status, symptoms subscales, hospitalizations, and death. We utilized mixed models and generalized estimating equations to adjust for baseline differences and investigate longitudinal differences in symptoms, clinical status, and hospitalization rates between groups.. During the study, 1.1% (. Although prescribed to very few patients, the impact of clozapine was notable, with fewer symptoms in patients who had more severe illnesses at baseline. Clozapine could prove to be as successful an intervention for late-stage bipolar disorder as it has been in schizophrenia.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Female; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Outpatients; Program Development; United States

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

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

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Depression; Female; Humans; Intellectual Disability; Lithium; Olanzapine; Pica; Topiramate

Bipolar disorder (BPD) is debilitating disorder, and patients can experience multiple relapses and subsequent hospitalizations. Since pharmacotherapy is the mainstay of treatment for patients with BPD, investigations on the effects of atypical antipsychotics (AAP) on reducing rehospitalization risk are crucial. The objective of study is to explore predictors of 1-year rehospitalization in patients with bipolar I disorder treated with AAP. A retrospective chart review on inpatients with bipolar I disorder was conducted. All participants were followed up for 1 year, and they were subdivided into three AAP treatment groups (olanzapine, risperidone, and quetiapine group). Kaplan-Meier survival analysis was implemented to detect time to rehospitalization due to any mood episodes within 1 year after discharge. Cox proportional regression model was adopted to find predictors of 1-year hospitalization in patients who experienced rehospitalization. One hundred thirty-eight participants were included in the study, and a 1-year rehospitalization rate was 18.1%. Time to rehospitalization did not differ between three AAP treatment groups. Predictors of rehospitalization due to any episode within 1 year were family history of depression and number of previous admission. Our findings can be conducive to understanding prognosis, and predicting rehospitalization risk in patients with BPD on AAP.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Inpatients; Kaplan-Meier Estimate; Male; Olanzapine; Patient Readmission; Quetiapine Fumarate; Retrospective Studies; Risperidone; Time Factors; Young Adult

In December 2019, the novel coronavirus (SARS-CoV-2) infection was first reported in Wuhan city, central China, which has spread rapidly. The common clinical features of patients with SARS-CoV-2 infection included fever, fatigue, and damage to the respiratory or digestive system. However, it is still unclear whether SARS-CoV-2 infection could cause damage to the central nervous system (CNS) inducing psychiatric symptoms.. Herein, we present the first case of SARS-CoV-2 infection with manic-like symptoms and describe the diagnosis, clinical course, and treatment of the case, focusing on the identifications of SARS-CoV-2 in the specimen of cerebrospinal fluid (CSF). The patient developed manic-like symptoms when his vital signs recovered on illness day 17. After manic-like attack, the detection of SARS-CoV-2 specific IgG antibody in CSF was positive, while the reverse transcriptase-polymerase chain reaction (RT-PCR) on CSF for the SARS-CoV-2 was negative. The patient received Olanzapine for treatment and his mood problems concurrently improved as indicated by scores of Young Manic Rating Scale (YMRS).. This is a single case report only, and the RT-PCR test for SARS-CoV-2 in CSF was not performed simultaneously when SARS-CoV-2 was positive in samples of sputum and stool.. This first case of COVID-19 patient with manic-like symptoms highlights the importance of evaluation of mental health status and may contribute to our understanding of potential risk of CNS impairments by SARS-CoV-2 infection.

Topics: Antibodies, Viral; Antipsychotic Agents; Antiviral Agents; Betacoronavirus; Bipolar Disorder; Brain; Chest Pain; China; Clinical Laboratory Techniques; Cobicistat; Coronavirus Infections; COVID-19; COVID-19 Testing; Darunavir; Dyspnea; Fever; Glucocorticoids; Humans; Indoles; Magnetic Resonance Imaging; Male; Methylprednisolone; Middle Aged; Moxifloxacin; Olanzapine; Pandemics; Pharyngitis; Pneumonia, Viral; Reverse Transcriptase Polymerase Chain Reaction; SARS-CoV-2

We report the case of a half-marathon runner who presented with exertional heatstroke (EHS), whose management was confounded by concurrent treatment of his bipolar disorder with olanzapine. Antipsychotics can have a profound effect on thermoregulation and can cause athletes to present with features of neuroleptic malignant syndrome in the setting of EHS. It is vital for medical providers to consider the thermoregulatory effects of all medications, including antipsychotics, when providing care during sporting events.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Body Temperature Regulation; Heat Stroke; Humans; Male; Marathon Running; Olanzapine; Physical Exertion; Running

Manic and hypomanic states associated with antidepressant treatments are relatively common; however, when specifically considering mirtazapine, those side effects are infrequent. The authors report a clinical case regarding a manic episode with dysphoric features in a patient with no personal or family previous psychiatric history. It began two weeks after starting treatment with mirtazapine up to 30 mg/day. This episode was treated discontinuing mirtazapine and initiating olanzapine (10 mg), with symptomatic remission. Mirtazapine has a specific pharmacodynamics, blocking not only post-synaptic serotonergic receptors but also α2-presynaptic adrenergic receptors. Taking this into consideration, it was hypothesized that this case could be attributed to a noradrenergic syndrome, characterized by dysphoria, irritability, insomnia and psychomotor agitation.. O desenvolvimento de estados maníacos e hipomaníacos associado ao uso de antidepressivos é relativamente comum. Contudo, no caso da mirtazapina, este é um efeito secundário raro. Os autores descrevem um caso clínico de um episódio maníaco de características disfóricas, num doente sem antecedentes psiquiátricos pessoais ou familiares, com instalação duas semanas após início de tratamento com mirtazapina até 30 mg/dia. Uma vez suspensa a mirtazapina e iniciada olanzapina (10 mg) verificou-se remissão sintomática. A mirtazapina apresenta uma farmacodinâmica particular, sendo antagonista não só de recetores serotoninérgicos póssinápticos, mas também de recetores adrenérgicos pré-sinápticos α2. Neste sentido, colocou-se a hipótese de se tratar de uma síndrome noradrenérgica, caracterizada por disforia, irritabilidade, insónia e agitação psicomotora.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Male; Middle Aged; Mirtazapine; Olanzapine; Psychoses, Substance-Induced

Olanzapine is a second-generation antipsychotic. Incidence of olanzapine-induced seizures (OIS) is low with monotherapy. Combination therapy with another antipsychotic, drug metabolism and old age are risk factors for OIS. Our patient was a 71-year-old man, admitted to the psychiatry unit. He was managed on the lines of bipolar affective disorder current episode depression and dementia. He was started on olanzapine 1.25 mg two times/day. The patient developed generalised tonic-clonic seizure that lasted for around two and a half minutes within 24 hours of olanzapine treatment. His electroencephalogram showed findings that were suggestive of mild slowing. Our case discusses the incidence of OIS on the subtherapeutic dose. This presentation involves multiple risk factors for OIS: a history of stroke, poststroke seizure, old age and cognitive impairment. Due to scarcity of evidence of OIS; mostly with recommended therapeutic dose range physicians may underestimate seizure risk at subtherapeutic doses.

Topics: Administration, Intravenous; Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Drug Monitoring; Electroencephalography; Humans; Male; Olanzapine; Risk Factors; Seizures; Treatment Outcome; Valproic Acid

Hyponatremia is occasionally unmasked in psychiatric patients during hospitalization after routine blood and urinary tests, and correlates in most cases with an inappropriate secretion of antidiuretic hormone, mainly due to iatrogenic factors. Only a few studies have regarded the combination of psychotropic drugs as triggers of chronic, asymptomatic hyponatremia in bipolar patients, who require to be hospitalized because of the exacerbation of their mental illness. We presented three clinical cases of patients affected by a long-term psychiatric disorder and under polypharmacotherapy for several months. After excluding other potential factors, we hypothesized that pharmacological treatment with a mood stabilizer (oxcarbazepine) associated with a benzodiazepine (delorazepam), a second-generation antipsychotic (olanzapine) or an antidepressant (fluvoxamine), triggered severe hyponatremia ([Na+] ≤125 mEq/L), serum hypo-osmolarity, and elevated inappropriate urine osmolarity added to more diluted sodium concentration. When we discontinued the treatment, clinical conditions of our patients improved, despite the previous administration of hypertonic saline jointly with water restriction. Psychiatrists should consider that bipolar patients on long-term polypharmacotherapy may present a higher risk of severe hyponatremia not clinically detectable. Consequently, routine laboratory tests should be periodically repeated as they represent the only available tool to unmask such electrolyte imbalances.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Hyponatremia; Male; Middle Aged; Nordazepam; Olanzapine; Oxcarbazepine; Psychotropic Drugs

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

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

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Lurasidone Hydrochloride; Olanzapine

Topics: Bipolar Disorder; Humans; Olanzapine; Severity of Illness Index

Topics: Bipolar Disorder; Humans; Olanzapine; Psychiatric Status Rating Scales; Research Design; Severity of Illness Index

The aim of this observational study was to investigate the relationship between metabolic factors and use of selective serotonin reuptake inhibitors (SSRIs) combined with olanzapine, quetiapine or risperidone.. Data from the Norwegian Thematically Organized Psychosis study, a cross-sectional study on 1301 patients with schizophrenia (n=868) or bipolar disorder (n=433), were analyzed. As exposure variables in the linear regression model were included the dose or serum concentration of SSRIs (n=280) and of olanzapine (n=398), quetiapine (n=234) or risperidone (n=128). The main outcome variables were levels of total cholesterol, low and high density lipoprotein (LDL and HDL) cholesterol, triglycerides and glucose.. One defined daily dose (DDD) per day of an SSRI in addition to olanzapine was associated with an increase in total cholesterol of 0.16 (CI 0.01 to 0.32) mmol/L (P=0.042) and an increase in LDL-cholesterol of 0.17 (CI 0.02 to 0.31) mmol/L (P=0.022). An SSRI serum concentration in the middle of the reference interval in addition to quetiapine was associated with an increase in total cholesterol of 0.39 (CI 0.10 to 0.68) mmol/L (P=0.011) and an increase in LDL-cholesterol of 0.29 (0.02 to 0.56) mmol/L (P=0.037). There were no such effects when combined with risperidone.. The findings indicate only minor deteriorations of metabolic variables associated with treatment with an SSRI in addition to olanzapine and quetiapine, and none when combined with risperidone. These results suggest that SSRIs can be used in combination with antipsychotics, and that the possible increase in cardiovascular risk is negligible.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Female; Humans; Male; Metabolic Diseases; Middle Aged; Olanzapine; Quetiapine Fumarate; Risk Factors; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Triglycerides; Young Adult

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third- line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment-emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second- line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence-based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first-line treatments for acute mania. First-line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first-line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidit

Topics: Adolescent; Aged; Algorithms; Antipsychotic Agents; Bipolar Disorder; Bupropion; Child; Evidence-Based Medicine; Female; Humans; Lamotrigine; Lithium Compounds; Olanzapine; Quetiapine Fumarate; Societies, Medical; Suicide; Suicide Prevention; Valproic Acid

Mania-like states occurring due to neurological, metabolic or toxic conditions, without a primary mood disorder have been reported in scientific literature as secondary mania. A major clinical problem in such situations often stems from the difficulty to understand if the mood disturbance is indeed secondary to an organic cause or a coincidental primary mood disorder. Chemotherapy regimens have been associated with multiple psychiatric complications, including psychosis, mania and anxiety. Capecitabine is implicated to be associated with encephalopathy whose clinical presentation often mimics that of psychosis. However, presentations with mania have not been reported until with the capecitabine and oxaliplatin combination chemotherapy regimen. In this report, we describe a case of secondary mania in a patient suffering from carcinoma colon on treatment with chemotherapy regimen of capecitabine and oxaliplatin.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Capecitabine; Colonic Neoplasms; Humans; Male; Middle Aged; Olanzapine; Organoplatinum Compounds; Oxaliplatin

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium Compounds; Male; Olanzapine; Parkinson Disease, Secondary

Olanzapine (OLZ), is used in the treatment of bipolar disorder and schizophrenia, diseases that present oxidative stress in their physiopathology. It has low aqueous solubility, which may lead to low oral bioavailability. The search of new drug delivery systems (DDSs) that may increase dissolution rate of OLZ, associated with the investigation of the antioxidant potential of the loaded-systems become of major importance to understand improvement in bipolar disorder and schizophrenia therapy. Thus, this study aimed to evaluate the in vitro antioxidant potential of two different Layered Double Hydroxides (LDH) loaded with 5% of OLZ (CaAl and NiAl), by radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl and nitric oxid); radical cation scavenging activity (2,2'-azino-bis3-ethylbenzthiazoline-6-sulfonic acid ABTS) and evaluation of inhibition capacity of lipid peroxidation by thiobarbituric acid (TBARS). The results showed that both obtained LDH systems presented in vitro antioxidant capacity when associated with OLZ in all methods performed, and this activity is more pronounced with the systems containing OLZ compared to pure drug. The systems with CaAl was shown to have increased antioxidant potential, compared to NiAl, increasing the antioxidant activity up to 40,83%, 15,84% and 16,73%, as showed by the DPPH, nitric oxide and TBARS tests, respectively. The results revealed that the use of LDHs as a functional excipient may be promising in the pharmaceutical industry for bipolar disorder and schizophrenia therapy.

Topics: Aluminum; Antioxidants; Benzodiazepines; Bipolar Disorder; Calcium; Drug Delivery Systems; Excipients; Free Radical Scavengers; Humans; Hydroxides; Lipid Peroxidation; Nickel; Olanzapine; Oxidative Stress; Schizophrenia; Thiobarbituric Acid Reactive Substances

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

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

Oxcarbazepine is a carbamazepine pre-drug with less drug interactions. Its adverse effects, including hyponatremia, somnolence and ataxia, are dose dependent. Olanzapine is an atypical antipsychotic drug most commonly used to manage psychoses and symptoms of irritability and aggressive behavior. Main side effects include extrapyramidal and anticholinergic symptoms, weight gain, and hyperglycemia.. In this manuscript a case of oxcarbazepine and olanzapine intoxication is discussed. A 45-year-old woman, previously diagnosed with bipolar disorder and chronic alcoholism, was presented two hours after ingestion of 30,000mg of oxcarbazepine and 140 mg of olanzapine, combined with alcohol. She was immediately treated with gastric lavage and administration of activated charcoal. During her hospitalization she was hemodynamically and respiratory stable with no neurological signs and symptoms except for somnolence. Another side effect was hyponatremia. She was discharged from our department in stable clinical condition after being evaluated by a psychiatrist.. Early approach is crucial for the management of drug intoxication. Late symptoms can be avoided through close monitoring of vital signs, mental status and laboratory values. Psychiatric consultation is essential for a better long-term outcome.

Topics: Antipsychotic Agents; Bipolar Disorder; Female; Greece; Humans; Middle Aged; Olanzapine; Oxcarbazepine; Poisoning; Treatment Outcome

Data on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited.. We conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18-75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors.. The study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62-0.93) and 0.83 (95% CI 0.70-0.98), compared to lithium monotherapy).. Register data does not provide information on all clinical parameters affecting treatment choices.. One-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Cohort Studies; Drug Therapy, Combination; Female; Hospitalization; Humans; Lithium Compounds; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Registries; Secondary Prevention; Valproic Acid; Young Adult

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

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

We describe the case of a 62-year-old man with a history of bipolar disorder, previously stable on lithium for over 20 years, who presented with a manic relapse and signs of lithium toxicity in the form of a coarse tremor. Serum lithium levels were in the normal range, and the patient had stage 3 chronic kidney disease. He was admitted for treatment under Section 2 of the Mental Health Act, and after stopping lithium was started on olanzapine. Signs of lithium toxicity improved after withdrawal of lithium. This case highlights the need to treat normal serum lithium levels with caution in patients showing signs of clinical lithium toxicity.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Differential; Humans; Lithium; Male; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Secondary Prevention; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Chlorpheniramine; Diagnosis, Differential; GABA Agents; Histamine H1 Antagonists; Humans; Male; Olanzapine; Substance-Related Disorders; Valproic Acid

Topics: Adult; Benzodiazepines; Bipolar Disorder; Electroconvulsive Therapy; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Young Adult

A case of an adolescent with symptoms of Mania, who developed Drug Reaction with Eosinophilia and Systemic Symptom (DRESS) syndrome on exposure to combination of oral Olanzapine and Sodium Valproate is presented. We have attempted to highlight the atypical presentation of DRESS syndrome in this patient as well as management difficulties in patient who develops DRESS syndrome with the conventional psychotropic medication. Hence, it is necessary for mental health professionals to be vigilant about this life threatening drug reaction associated with high morbidity and mortality, thus ensuring prompt diagnosis and management.

Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Hypersensitivity Syndrome; Drug Therapy, Combination; Humans; Male; Olanzapine; Valproic Acid

Topics: Bipolar Disorder; Humans; Olanzapine

Hypothermia is a rare but serious condition that has been associated with various psychiatric medications. We present a 76-year-old woman with refractory mania who developed multiple episodes of severe hypothermia associated with several psychiatric medications including olanzapine, quetiapine, valproic acid and oxcarbazepine. These episodes resolved following discontinuation of the agents. The patient had never experienced hypothermia before, despite having been on these or similar agents for many years. With traditional treatments for mania not feasible, other medications were used to treat her including lithium, clonazepam, gabapentin and the novel protein kinase c inhibitor tamoxifen. The regimen resulted in some success and importantly, without triggering hypothermia. This case alerts clinicians to the rare side effect of hypothermia in response to various psychiatric medications, the fact that patients can suddenly develop this intolerance and suggests possible medications that may be used safely without triggering hypothermia.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Female; Humans; Hypothermia; Olanzapine; Oxcarbazepine; Quetiapine Fumarate; Recurrence; Valproic Acid

The management of bipolar disorder in pregnant and postpartum women is one of the most difficult issues in clinical practice. Data on the efficacy of mood stabilizers, except lithium and antipsychotics, in the maintenance treatment of bipolar disorders during pregnancy and postpartum period are very limited. This report presents results of prophylaxis with olanzapine and quetiapine with regard to affective episodes in pregnancy to the postpartum period.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Olanzapine; Postpartum Period; Pregnancy; Pregnancy Complications; Quetiapine Fumarate

A recently published analysis of population-based claims data from Ontario, Canada reported higher risks of acute kidney injury (AKI) and related outcomes among older adults who were new users of atypical antipsychotics (AAPs) compared with unexposed patients. In light of these findings, the objective of the current study was to further investigate the risks of AKI and related outcomes among older adults receiving AAPs.. A replication of the previously published analysis was performed using the US Truven MarketScan Medicare Supplemental database (MDCR) among patients aged 65 years and older. Compared with non-users of AAPs, the study compared the risk of AKI and related outcomes with users of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, or paliperidone) using a 1-to-1 propensity score matched analysis. In addition, we performed adapted analyses that: (1) included all covariates used to fit propensity score models in outcome models; and (2) required patients to have a diagnosis of schizophrenia, bipolar disorder, or major depression and a healthcare visit within 90 days prior to the index date.. AKI effect estimates [as odds ratios (ORs) with 95% confidence intervals (CIs)] were significantly elevated in our MDCR replication analyses (OR 1.45, 95% CI 1.32-1.60); however, in adapted analyses, associations were not significant (OR 0.91, 95% CI 0.78-1.07)). In analyses of AKI and related outcomes, results were mostly consistent between the previously published and the MDCR replication analyses. The primary change that attenuated associations in adapted analyses was the requirement for patients to have a mental health condition and a healthcare visit prior to the index date.. The MDCR analysis yielded similar results when the methodology of the previously published analysis was replicated, but, in adapted analyses, we did not find significantly higher risks of AKI and related outcomes. The contrast of results between our replication and adapted analyses may be due to the analytic approach used to compare patients (and potential confounding by indication). Further research is warranted to evaluate these associations, while also examining methods to account for differences in older adults who do and do not use these medications.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Olanzapine; Quetiapine Fumarate; Risperidone; Schizophrenia

It is well recognized that medications have an important role to play in preventing relapse in bipolar disorder. The impact these treatments have on rates of admission to hospital in particular has been less well studied. We combined data on hospitalization from 11 randomized controlled trials in a network meta-analysis. We found that the published evidence demonstrates significant reductions in admission rates compared to placebo from lithium (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.32-0.59), valproate (RR 0.50, 95% CI 0.28-0.90), a combination of lithium and valproate (RR 0.50, 95% CI 0.28-0.90), carbamazepine (RR 0.46, 95% CI 0.29-0.73) and olanzapine (RR 0.27, 95% CI 0.16-0.43). The evidence base contributing to these estimates remains fairly small, leading to broad confidence intervals for estimates of effect. More precise estimates could be obtained if unpublished outcomes data from other trials in this area became available. Several pharmacological treatments appear to be effective at reducing the need for hospital admission in people with bipolar disorder.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Lithium Compounds; Olanzapine; Patient Readmission; Randomized Controlled Trials as Topic; Valproic Acid

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

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

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Citalopram; Comorbidity; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Valproic Acid

Lithium is a first line treatment option in bipolar disorder, but several alternative treatments have been introduced in recent years, such as antiepileptic and atypical antipsychotic drugs. Little is known about how this has changed the prescription patterns. We investigated possible changes in the use of mood stabilizers and antidepressants in Sweden during 2007-2013.. Data was collected from Swedish registers: the National Quality Assurance Register for bipolar disorder (BipoläR), the Prescribed Drug Register, and the Patient Register. Logistic regression models with drug use as outcomes were used to adjust for confounding factors such as sex, age, year of registration, and subtypes of bipolar disorder.. In both bipolar subtypes, lithium use decreased steadily during the study period, while the use of lamotrigine and quetiapine increased. The use of valproate decreased in bipolar II disorder and the use of olanzapine decreased among women. The use of antidepressant remained principally unchanged but increased somewhat in bipolar I disorder.. We only report data from 2007 as the coverage of BipoläR prior to 2007 was too low to allow for reliable analyses.. Significant changes in the prescription of drugs in the treatment of bipolar disorder have occurred in recent years in Sweden. Further studies are needed to clarify whether these changes alter the outcome in bipolar disorder.

Topics: Adult; Aged; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Prescriptions; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Sweden; Valproic Acid

Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved ("off-label") uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.. Retrospective, segmented time-series analysis using new prescription claims during 2003-2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.. During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).. The FDA's sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency's expert judgments to clinical practice.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Decision Making; Drug Approval; Drug Prescriptions; Female; Humans; Male; Middle Aged; Olanzapine; Pediatrics; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles; United States; United States Food and Drug Administration

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

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

Self-harm is a prominent cause of morbidity in patients with bipolar disorder and is strongly associated with suicide. There is evolving evidence that lithium use may reduce suicidal behavior, in addition to concerns that the use of anticonvulsants may increase self-harm. Information is limited about the effects of antipsychotics when used as mood stabilizer treatment. Rates of unintentional injury are poorly defined in bipolar disorder, and understanding drug associations with this outcome may shed light on mechanisms for lithium's potential antisuicidal properties through reduction in impulsive aggression.. To compare rates of self-harm, unintentional injury, and suicide in patients with bipolar disorder who were prescribed lithium, valproate sodium, olanzapine, or quetiapine fumarate.. This investigation was a propensity score (PS)-adjusted and PS-matched longitudinal cohort study in a nationally representative UK sample using electronic health records data collected between January 1, 1995, and December 31, 2013. Participants included all patients diagnosed as having bipolar disorder who were prescribed lithium, valproate, olanzapine, or quetiapine as maintenance mood stabilizer treatment.. The primary outcome was any form of self-harm. Secondary outcomes were unintentional injury and suicide.. Of the 14 396 individuals with a diagnosis of BPD, 6671 were included in the cohort, with 2148 prescribed lithium, 1670 prescribed valproate, 1477 prescribed olanzapine, and 1376 prescribed quetiapine as maintenance mood stabilizer treatment. Self-harm rates were lower in patients prescribed lithium (205; 95% CI, 175-241 per 10 000 person-years at risk [PYAR]) compared with those prescribed valproate (392; 95% CI, 334-460 per 10 000 PYAR), olanzapine (409; 95% CI, 345-483 per 10 000 PYAR), or quetiapine (582; 95% CI, 489-692 per 10 000 PYAR). This association was maintained after PS adjustment (hazard ratio [HR], 1.40; 95% CI, 1.12-1.74 for valproate, olanzapine, or quetiapine vs lithium) and PS matching (HR, 1.51; 95% CI, 1.21-1.88). After PS adjustment, unintentional injury rates were lower for lithium compared with valproate (HR, 1.32; 95% CI, 1.10-1.58) and quetiapine (HR, 1.34; 95% CI, 1.07-1.69) but not olanzapine. The suicide rate in the cohort was 14 (95% CI, 9-21) per 10 000 PYAR. Although this rate was lower in the lithium group than for other treatments, there were too few events to allow accurate estimates.. Patients taking lithium had reduced self-harm and unintentional injury rates. This finding augments limited trial and smaller observational study results. It supports the hypothesis that lithium use reduces impulsive aggression in addition to stabilizing mood.

Topics: Adult; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Cohort Studies; Cross-Sectional Studies; Electronic Health Records; Female; Humans; Lithium Carbonate; Longitudinal Studies; Male; Middle Aged; Olanzapine; Propensity Score; Quetiapine Fumarate; Self-Injurious Behavior; Suicide; Treatment Outcome; United Kingdom; Valproic Acid; Wounds and Injuries

There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine.. We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects.. Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cardiovascular Diseases; Chemical and Drug Induced Liver Injury; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypercalcemia; Hypertension; Lithium Compounds; Longitudinal Studies; Male; Middle Aged; Olanzapine; Propensity Score; Quetiapine Fumarate; Renal Insufficiency; Thyroid Diseases; Valproic Acid

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

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

Depression is the predominant psychosocial and suicide burden in bipolar disorder, yet there is a paucity of evidence-based treatments for bipolar depression.. This post hoc subgroup analysis of data pooled from two 3-week, randomized, placebo- and olanzapine-controlled trials (December 2004-April 2006, N = 489 and November 2004-April 2006, N = 488) examined a subgroup of patients meeting criteria for moderate-to-severe mixed major depressive episodes, defined using DSM-IV-TR criteria for mixed episodes (mania and major depression simultaneously) with a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥ 20.. Decreases in MADRS scores (least squares mean [SE]), the a priori primary outcome, were significantly greater in the asenapine group than in the placebo group from baseline to day 7 (-11.02 [1.82] vs -4.78 [1.89]; P = .0195), day 21 (-14.03 [2.01] vs -7.43 [2.09]; P = .0264), and endpoint (-10.71 [1.76] vs -5.19 [1.98]; P = .039). Decreases in MADRS scores with asenapine were significantly greater than with olanzapine from baseline to day 7 (-6.26 [1.47]; P = .0436). Decreases in Young Mania Rating Scale mean total score were greater with asenapine than with placebo or olanzapine at all time points assessed. A significantly greater reduction from baseline to day 21 in the Short Form-36 mental component summary score was observed with asenapine, but not olanzapine, compared with placebo (16.57 vs 5.97; P = .0093). Asenapine was generally well tolerated.. These data provide support for the potential efficacy of asenapine in mixed major depressive episodes; however, these data cannot be linearly extrapolated to nonmixed major depression.

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzocycloheptenes; Double-Blind Method; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Multicenter Studies as Topic; Olanzapine; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome; Young Adult

Topics: Adult; Antipsychotic Agents; Area Under Curve; Benzodiazepines; Bipolar Disorder; Breast Feeding; Female; Humans; Infant, Newborn; Milk, Human; Olanzapine; Quetiapine Fumarate; Twins

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

Second-generation antipsychotics (SGAP) and mood stabilizers (MS) are prescribed widely for the treatment of bipolar disorder, but they are associated with the risk of relevant side-effects, among which is weight gain. The identification of genes that predispose to weight gain would represent a useful tool to evaluate the risk-benefit ratio of treatment.. This study investigated the genetic factors associated with weight gain in bipolar patients treated with SGAP, MS and their combinations (n=486). Single-nucleotide polymorphisms belonging to 16 candidate genes supported by the literature were investigated in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) genome-wide dataset. Linear regression models were constructed including age, sex, initial weight and prescription of SGAP at high risk for inducing weight gain (olanzapine or clozapine) as covariates. Genes harbouring single-nucleotide polymorphisms associated with phenotypes were investigated by a pathway analysis.. No association was found between phenotypes and individual polymorphisms or pathways after multiple-test correction. HTR2C, LEP, FTO and TBC1D1 represented the top genes for weight gain during treatment with a SGAP and/or MS. A genome-wide signal (FTO rs9930506) associated previously with obesity was associated with psychotropic-induced weight gain. The genes that influenced both SGAP and MS weight gain were FTO, TBC1D1, MTHFR and HRH1. ADCY9, ADCY5 and PRKAG2 were interesting candidate genes that emerged from the pathway analysis.. This study was the first to compare the genes involved in SGAP-induced and MS-induced weight gain. Individual genes probably play a limited role in psychotropic-induced weight gain; further studies should focus on the extension from known candidate genes to wider groups of molecular pathways.

Topics: Adipose Tissue; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Homeostasis; Humans; Male; Olanzapine; Polymorphism, Single Nucleotide; Psychotropic Drugs; Weight Gain

Prior to registration, no clinical trial evaluating safety and tolerability of Zolafren® (Adamed Sp. z o.o., Czosnów, Poland), a generic olanzapine formulation, had been performed. Therefore, the aim of this post-authorization safety study (PASS) was to evaluate the safety and tolerability of Zolafren in patients with bipolar disorder (BD).. Adverse events (AEs) associated with the use of Zolafren were recorded in a PASS, in an open-label, non-randomized, multicenter observational study involving 20,698 outpatients with BD.. Zolafren was used in both monotherapy (82.8%) and polytherapy (17.2%) at a mean dose of 12.1±4.2 mg. The most commonly used formulation was coated tablets (70.9%). Orally dissolving tablets (19.7%) and hard capsules (9.4%) were less commonly used. During a period of 171±47 days of exposure to Zolafren, 5883 AEs were reported in 2138 patients (10.3% of the study population). None of the reported AEs were severe. Zolafren-associated AEs were the reason for discontinuation in 43 patients and the reason for dose reduction in a further 762 patients. The most common AE was weight gain (by 1.6±3.3 kg) which was considered unrelated to the dose of Zolafren. During follow-up, the percentage of patients with very good tolerance with Zolafren increased from 44.4% to 59.8%. The percentage of patients who had confidence in Zolafren also increased.. The results of this PASS support the safety of Zolafren use and indicate a high tolerance in patients treated for BD.. Adamed Sp. z o.o., Czosnów, Poland.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drugs, Generic; Female; Humans; Male; Middle Aged; Olanzapine; Tablets

Many patients with schizophrenia and bipolar disorder have impaired insight and low medication adherence. The aim of this post hoc analysis was to explore the relationship between insight and medication adherence.. We included 903 patients with schizophrenia or bipolar disorder who participated in an observational study conducted in Europe on the outcomes of patients treated with two oral formulations of olanzapine over a 1-year period. Evaluations included Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), insight (Scale to Assess Unawareness of Mental Disorder, SUMD) medication adherence (Medication Adherence Rating Scale, MARS), and therapeutic alliance (Working Alliance Inventory, WAI).. Medication adherence was higher in bipolar patients (mean MARS score (SD) 6.5 (2.8) versus 5.8 (2.7) in schizophrenia; p < 0.001). Patients with schizophrenia had lower insight (i.e., SUMD item 1, unawareness of mental disorder, mean (SD) of 2.5 (1.3) in schizophrenia versus 1.9 (1.2) in bipolar, p < 0.001). Better insight was associated with higher adherence (Spearman Correlation Coefficient, SCC, ranging from 0.39 to 0.49 for the three SUMD general items, p < 0.0001 in all cases). Higher insight was related to a stronger therapeutic alliance (SCC ranging from 0.38 to 0.48, p < 0.0001). A path analysis revealed a positive impact of insight on adherence and alliance and that stronger alliance was related to lower clinical severity (lower CGI score).. Insight and adherence were found to be closely related. Insight impacts on the therapeutic alliance with mental health professionals. These factors are associated to treatment outcomes.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Comprehension; Europe; Female; Humans; Male; Medication Adherence; Middle Aged; Olanzapine; Outpatients; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Based on the recent findings from animal studies, it has been proposed that the therapeutic use of valnoctamide, an anxiolytic drug developed in the early 1960s, be extended to treat other neurological disorders such as epilepsy and bipolar disease. Given the scarcity of adequate data on its prenatal toxicity, a comparative teratogenicity study of valnoctamide and two of the most commonly used drugs to treat bipolar disorder, risperidone and olanzapine, was carried out in a mouse model system.. Pregnant dams were treated with the aforementioned three drugs at the dose levels calculated as an equal proportion of the respective LD50 values of these drugs. The main reproductive indices examined included the numbers of implantations and resorptions, viable and dead fetuses, and fetal gross, visceral and skeletal abnormalities.. The outcomes of the present study indicated that olanzapine was the most teratogenic of the three drugs, inducing maternal-, embryo-, and fetotoxicity. Risperidone also exerted a significant prenatal toxicity, but its adverse effect was less pronounced than that induced by olanzapine. Valnoctamide did not show any teratogenic effect, even when used in relatively higher dosages than olanzapine and risperidone. The observed increased skeletal abnormalities in one of the valnoctamide treatment groups were nonspecific and, as such, signaled a modest developmental delay rather than an indication that the compound could induce structural malformations.. Under our experimental conditions, valnoctamide demonstrated the lowest prenatal toxicity of the three tested drugs.

Topics: Amides; Animals; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Disease Models, Animal; Female; Male; Mice; Olanzapine; Pregnancy; Pregnancy Complications; Risperidone; Teratogenesis

The effects of olanzapine and haloperidol on metabolic parameters in bipolar patients have been evaluated much less comprehensively than in schizophrenic patients. Therefore, in this study, medical records of 343 schizophrenic and bipolar patients treated with haloperidol or olanzapine for 1 year were retrospectively reviewed and metabolic outcomes were evaluated. After 12 months of follow-up, 25.9% of patients showed ≥3 metabolic abnormalities with a point prevalence of 27.2% in the bipolar and 24.9% in the schizophrenic group: 22.0% of the schizophrenic patients treated with haloperidol and 29.8% of those treated with olanzapine achieved ≥3 metabolic alterations; in bipolar patients, these percentages were 15.8% of those treated with haloperidol and 37.8% of those treated with olanzapine (p < 0.0001). Significant changes were reported over time in fasting glucose, triglycerides and cholesterol blood levels, systolic and diastolic blood pressure, body weight, and BMI. Overall, a significant number of schizophrenic and bipolar patients treated with olanzapine showed ≥3 metabolic alterations in the first month of treatment when compared to those treated with haloperidol. Moreover, the number of olanzapine-treated patients developing metabolic changes in the first month was significantly higher in both diagnostic groups when compared to those who reached metabolic abnormal values in the subsequent 11 months. These data suggest that both antipsychotics could increase the metabolic risk in schizophrenic and bipolar patients with a higher prevalence in olanzapine-treated patients. On the other hand, olanzapine-treated patients seem to achieve metabolic abnormalities faster than haloperidol-treated subjects in both diagnostic groups.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Follow-Up Studies; Haloperidol; Humans; Male; Metabolic Diseases; Middle Aged; Olanzapine; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia; Severity of Illness Index

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cyclohexanols; Dibenzothiazepines; Drug Substitution; Drug Therapy, Combination; Female; Humans; Middle Aged; Olanzapine; Quetiapine Fumarate; Restless Legs Syndrome; Treatment Outcome; Venlafaxine Hydrochloride

To assess mood stabilizer (MS) and second-generation antipsychotic (SGA) prescribing trends in bipolar disorder (BD) outpatients referred to a bipolar disorder specialty clinic over the past 12 years.. BD outpatients referred to the Stanford University Bipolar Disorder Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation. Prescription rates for MSs and SGAs were compared during the first (2000-2005) and second (2006-2011) six years.. Among 597 BD patients (mean±SD age 35.4±8.6 years; 58.1% female; 40.7% Type I, 43.6% Type II, and 15.7% Type Not Otherwise Specified; taking 2.6±1.7 prescription psychotropic medications), lamotrigine, quetiapine, and aripiprazole usage more than doubled, from 14.7% to 37.2% (p<0.0001), 7.2% to 19.7% (p<0.0001), and 3.1% to 10.9% (p=0.0003), respectively, while olanzapine and risperidone use decreased by more than half from 15.0% to 6.6% (p=0.0043), and from 8.7% to 3.8% (p=0.039), respectively. SGA use increased from 34.1% to 44.8% (p=0.013), although MS use continued to be more common (in 65.2% for 2006-2011). Use of other individual MSs and SGAs and MSs as a class did not change significantly.. Over 12 years, in patients referred to a BD specialty clinic, lamotrigine, quetiapine, and aripiprazole use more than doubled, and olanzapine and risperidone use decreased by more than half. Tolerability (for lamotrigine, aripiprazole, olanzapine, and risperidone) more than efficacy (for quetiapine) differences may have driven these findings. Additional studies are needed to explore the relative influences of enhanced tolerability versus efficacy upon prescribing practices in BD patients.

Topics: Academic Medical Centers; Adult; Ambulatory Care Facilities; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; California; Dibenzothiazepines; Drug Therapy; Female; Humans; Lamotrigine; Male; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Referral and Consultation; Risperidone; Triazines

Bipolar disorder (BPD) is prevalent and is associated with a significant economic burden. Asenapine, the first tetracyclic antipsychotic approved in Canada for the treatment of BPD, has shown a comparable efficacy profile to other atypical antipsychotics. In addition, it is associated with a favourable metabolic profile and minimal weight gain potential. This study aimed to assess the economic impact of asenapine compared to olanzapine in the treatment of BPD in Canada.. A decision tree combined with a Markov model was constructed to assess the cost-utility of asenapine compared with olanzapine. The decision tree takes into account the occurrence of extrapyramidal symptoms (EPS), the probability of switching to a different antipsychotic, and the probability of gaining weight. The Markov model takes into account long-term metabolic complications including diabetes, hypertension, coronary heart diseases (CHDs), and stroke. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective over a five-year time horizon with yearly cycles.. In the treatment of BPD, asenapine is a dominant strategy over olanzapine from both a MoH and a societal perspective. In fact, asenapine is associated with lower costs and more quality-adjusted life years (QALYs). Results of the probabilistic sensitivity analysis indicated that asenapine remains a dominant strategy in 99.2% of the simulations, in both a MoH and a societal perspective, and this result is robust to the many deterministic sensitivity analyses performed.. This economic evaluation demonstrates that asenapine is a cost-effective strategy compared to olanzapine in the treatment of BPD in Canada.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Canada; Cost-Benefit Analysis; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Olanzapine; Quality-Adjusted Life Years; Weight Gain

The potential involvement of CYP3A43 in systemic olanzapine (OLA) metabolism has been suggested by one reported association between the intronic polymorphism CYP3A43 rs472660G>A and OLA clearance in 235 White and African-American patients. Trough plasma OLA concentrations in AA carriers were predicted on average 48% lower than in GG carriers. In the current study, we evaluated this finding by genotyping 374 White psychiatric patients on long-term OLA treatment. No significant difference in dose-adjusted trough serum OLA concentrations was observed between the seven AA carriers identified and the other two genotypes, without (P=0.6) or with (P=0.23) adjustment for additional covariates previously known to influence systemic OLA exposure. Because of the low prevalence of the rs472660 AA genotype in White populations (2%), larger study cohorts are needed for future association confirmation. Overall, CYP3A43 rs472660 is not likely to be a major contributor towards variability in systemic OLA exposure among White patients.

Topics: Aryl Hydrocarbon Hydroxylases; Benzodiazepines; Bipolar Disorder; Black or African American; Female; Genotype; Humans; Male; Olanzapine; Polymorphism, Genetic; Schizophrenia; White People

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Goiter, Nodular; Hearing Loss, Sensorineural; Humans; Olanzapine; Siblings; Thyroxine; Treatment Outcome; Valproic Acid; Young Adult

Around one-third of patients with bipolar I disorder (BD-I) experience mixed episodes, characterized by both mania and depression, which tend to be more difficult and costly to treat. Atypical antipsychotics are recommended for the treatment of mixed episodes, although evidence of their efficacy, tolerability, and cost in these patients is limited. This study evaluates, from a UK National Health Service perspective, the cost-effectiveness of asenapine vs olanzapine in BD-I patients with mixed episodes.. Cost-effectiveness was assessed using a Markov model. Efficacy was informed by a post-hoc analysis of two short-term clinical trials, with response measured as a composite Young Mania Rating Score and Montgomery-Åsberg Depression Rating Scale end-point. Probabilities of discontinuation and relapse to manic, mixed, and depressive episodes were sourced from published meta-analyses. Direct costs (2012-2013 values) included drug acquisition, monitoring, and resource use related to bipolar disorder as well as selected adverse events. Benefits were measured as quality-adjusted life years (QALYs).. For treating mixed episodes, asenapine generated 0.0187 more QALYs for an additional cost of £24 compared to olanzapine over a 5-year period, corresponding to a £1302 incremental cost-effectiveness ratio. The higher acquisition cost of asenapine was roughly offset by the healthcare savings conferred through its greater efficacy in treating these patients. The model shows that benefits were driven by earlier response to asenapine during acute treatment and were maintained during longer-term follow-up. RESULTS were sensitive to changes in key parameters including short and longer-term efficacy, unit cost, and utilities, but conclusions remained relatively robust.. RESULTS suggest that asenapine is a cost-effective alternative to olanzapine in mixed episode BD-I patients, and may have specific advantages in this population, potentially leading to healthcare sector savings and improved outcomes. Limitations of the analysis stem from gaps in clinical and economic evidence for these patients and should be addressed by future clinical trials.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Cost-Benefit Analysis; Dibenzocycloheptenes; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Markov Chains; Models, Economic; Olanzapine; Quality-Adjusted Life Years; State Medicine; United Kingdom; Weight Gain

Ziprasidone is increasingly used for the treatment of schizophrenia and bipolar disorder. The purpose of this study was to compare healthcare costs and use associated with ziprasidone and olanzapine.. Ziprasidone and olanzapine treatment episodes of schizophrenia and bipolar disorder patients were identified in the 01/2007-12/2010 IMS LifeLink™ Database. The period of analysis for each episode has three components: 6 months prior to the episode initiation date (pre-episode period), 1 month immediately following the episode initiation date (initiation month), and up to 12 months after the end of the initiation month (follow-up period). Ordinary least squares regressions, general linear models, and two-part models were used to compare various types of costs (2007 US$) associated with the use of ziprasidone and olanzapine. Logistic regressions, Poisson regressions, and Hurdle models were used to compare the number of emergency department (ED) visits and hospitalizations associated with each drug.. We identified 7,138 (46.93 %) ziprasidone episodes and 8,072 (53.07 %) olanzapine episodes, and found that patients using ziprasidone were significantly younger (41.50 vs. 45.38 years) and were significantly less likely to be male (29.81 vs. 44.21 %). Regression analysis showed no significant differences in total costs between the two drugs. However, ziprasidone was associated with significantly higher medication costs (US$232, p < 0.01) and outpatient costs (US$501, p < 0.05), yet lower ED costs (-US$73, p < 0.05). Ziprasidone was also associated with fewer ED visits (0.266, p < 0.001) and hospitalizations (1.117, p < 0.001).. Ziprasidone is associated with higher medication costs and outpatient costs than olanzapine; however, it reduces patients' use of ED and inpatient services.

Topics: Adult; Ambulatory Care; Benzodiazepines; Bipolar Disorder; Emergency Service, Hospital; Female; Health Care Costs; Health Services; Humans; Male; Middle Aged; Olanzapine; Piperazines; Schizophrenia; Thiazoles; United States

These analyses compared efficacy of olanzapine in patients with bipolar mania with or without mixed features, as defined in the DSM-5.. Pooled data from 3 placebo-controlled olanzapine studies in patients having bipolar I disorder with manic/mixed episode were analyzed (N=228 olanzapine; N=219 placebo). Patients were categorized for mixed features by number of concurrent depressive symptoms at baseline (0, 1, and 2 [category A; without mixed features], and ≥3 [category B; with mixed features]), as determined by HAM-D17 item score ≥1. Depressive symptoms corresponded to 6 HAM-D17 items in the DSM-5 definition of manic episode with mixed features. Primary efficacy was evaluated by changes in the baseline-to-3-week YMRS total score.. Patients were categorized into A (N=322; 72.0%) or B (N=125; 28.0%). Mean baseline YMRS total scores were 28.1 in category A and 27.8 in category B. Least-squares mean change of YMRS total scores in categories A and B (olanzapine versus placebo) were -11.78 versus -6.86 and -13.21 versus -4.72, respectively. Patients in the olanzapine- compared with placebo-group experienced a greater decrease in YMRS total score for both categories (p<0.001). An interaction between mixed features and treatment was seen in YMRS change at a 0.3 significance level (p=0.175).. The results are from post-hoc analyses.. Olanzapine was efficacious in the treatment of bipolar I mania, in patients both with and without mixed features, defined by DSM-5; however, greater efficacy was observed in patients with mixed features having more severe depressive symptoms.

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

Bipolar disorder is a chronic disease characterized by periods of mania or hypomania, depression, or a combination of both (mixed state). Because bipolar disorder is one of the leading causes of disability, it represents an important economic burden on society. Asenapine (ASE) is a new second-generation antipsychotic developed and approved for the treatment of manic or mixed episodes associated with bipolar disorder. The objective of the present study was to assess the cost-effectiveness of ASE compared to olanzapine (OLA) in the treatment of patients experiencing mixed episodes associated with bipolar I disorder in the context of the Italian National Health Service (NHS).. A pharmacoeconomic model was developed to simulate the management of Italian bipolar I patients with mixed episodes over a 5-year time horizon by combining clinical parameters with resource utilization. An expert panel of Italian psychiatrists and health economists was responsible for adapting a UK model to the Italian context. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio, where effectiveness is measured in terms of quality adjusted life-years gained. Scenario analyses, sensitivity analyses, and a probabilistic sensitivity analysis were performed to test the robustness of the model.. This pharmacoeconomic model showed that ASE resulted to be dominant over OLA; in fact, ASE was associated with lower direct costs (derived largely by the savings from hospitalizations avoided) and also generated a better quality of life. Results were robust to changes in key parameters; both scenario analyses and sensitivity analyses demonstrated model reliability.. Results from this study suggest that the management of bipolar I patients with mixed episodes using ASE as alternative to OLA can lead to cost saving for the Italian NHS and improve patients quality of life.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Dibenzocycloheptenes; Health Services; Heterocyclic Compounds, 4 or More Rings; Humans; Italy; Models, Econometric; Olanzapine; Quality of Life; Quality-Adjusted Life Years; Reproducibility of Results

Based on previous pharmacogenetic findings, we investigated the possible association between SULT4A1-1 haplotype and antipsychotic treatment response.. Using Mixed Model Repeated Measures, we tested the relationship between SULT4A1-1 status (+carrier, -noncarrier) and clinical improvement (in Positive and Negative Syndrome Scale total score) among European ancestry patients treated with paliperidone extended release (n=937), paliperidone palmitate (n=990), risperidone (n=507) and olanzapine (n=381) in 12 schizophrenia, two schizoaffective disorder and three bipolar I disorder trials. SULT4A1-1 haplotype was determined using tagging SNP rs763120.. There was no significant difference between SULT4A1-1(+) and SULT4A1-1(-) patients for treatment response to paliperidone or olanzapine. SULT4A1-1(-) patients had better treatment response to risperidone in one schizophrenia trial, but not in another schizophrenia trial or bipolar mania trial.. Across three psychiatric disorders (n=2815 patients), we observed no consistent association between SULT4A1-1 status and atypical antipsychotic effect.

Topics: Antipsychotic Agents; Benzodiazepines; Biomarkers, Pharmacological; Bipolar Disorder; Genetic Association Studies; Genotype; Haplotypes; Humans; Olanzapine; Risperidone; Schizophrenia; Sulfotransferases; Treatment Outcome

Topics: Adult; Aggression; Antipsychotic Agents; Autopsy; Benzodiazepines; Bipolar Disorder; Catatonia; Death, Sudden; Female; Humans; Hypothyroidism; Incidence; Lorazepam; Obesity; Olanzapine; Ovarian Neoplasms; Patient Admission; Patient Transfer; Pulmonary Embolism; Restraint, Physical; Risk; Valproic Acid; Venous Thrombosis

Like mood stabilizers, most second-generation antipsychotics are widely used to treat patients with bipolar disorder, yet their safety is still a concern. This study explored the association between antipsychotics and mood stabilizers and the risk of pneumonia, and it provides evidence-based information for clinical practice.. In a nationwide cohort of bipolar patients (ICD-9 codes 296.0 to 296.16, 296.4 to 296.81, and 296.89) derived from the National Health Insurance Research Database in Taiwan, who were admitted between July 1, 1998, and December 31, 2006 (N = 9,999), we identified 571 patients who developed pneumonia (ICD-9 codes 480 to 486 and 507) requiring hospitalization defined as cases. On the basis of risk-set sampling in a 1:4 ratio, 2,277 matched controls were selected from the same cohort. We used conditional logistic regression to assess the association between drug exposure and pneumonia and sensitivity analyses to validate the association.. Current use of several antipsychotics separately, including olanzapine (adjusted risk ratio [RR] = 2.97, P < .001), clozapine (RR = 2.59, P < .01), and haloperidol (RR = 3.68, P < .001), is associated with a dose-dependent increase in the risk of pneumonia. Interestingly, lithium has a dose-dependent protective effect from pneumonia. Among certain drug combinations, olanzapine plus carbamazepine had the highest risk (RR = 11.88, P < .01), followed by clozapine plus valproic acid (RR = 4.80, P < .001).. Several antipsychotics, but not mood stabilizers, were associated with the risk of pneumonia, which deserves our concern regarding patient safety. Some of the combinations of therapy resulted in synergy of risk.

Topics: Adolescent; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Case-Control Studies; Clozapine; Cohort Studies; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Evidence-Based Medicine; Female; Hospitalization; Humans; Lithium Carbonate; Male; Middle Aged; Multivariate Analysis; Olanzapine; Pneumonia; Propensity Score; Risk Factors; Taiwan; Valproic Acid; Young Adult

Prognosis of comorbid bipolar disorder (BD) and drug abuse is poor. We assessed the efficacy of olanzapine in manic or mixed BD patients, with (SUD) or without (N-SUD) comorbidity with substance use disorder (SUD) and its effect on drug abuse, days of abuse, and craving.. Eighty patients with BD-I (40 SUD) were hospitalized for a manic or mixed episode and received add-on olanzapine. Assessments were conducted at admission, discharge, and 4 and 8 weeks after discharge. Primary outcome was the proportion of responders and remitters in each group. We used a logistic regression model to adjust for possible confounders. We assessed craving and drug-abuse days with a visual analog scale and the Timeline Follow-Back.. SUD and N-SUD were similar on response and remission, adjusted for sex, age, years ill, age at first episode, first episode depressive, number of hospitalizations, and duration of hospitalization (odds ratio, 1.09; 95% confidence interval, 1.02-2.29). Mood rating scores dropped significantly from baseline to end point in both groups. Timeline follow-back decreased in SUD from 22.5 to 7.3 at 8 weeks postdischarge, whereas craving dropped from 8.3 to 5.1 (P < 0.03).. The effectiveness of short-term olanzapine in BD-I mania or mixed mania did not differ according to SUD comorbidity. Treatment was followed by less substance use/abuse and craving in comorbid bipolar-SUD patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Case-Control Studies; Diagnosis, Dual (Psychiatry); Female; Follow-Up Studies; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Olanzapine; Prospective Studies; Substance-Related Disorders; Time Factors; Treatment Outcome; Young Adult

The efficacy and safety of olanzapine monotherapy in bipolar depression has been evaluated in 2 placebo-controlled studies.. We pooled data from 2 previously published studies examining olanzapine monotherapy in patients with bipolar I depression. Changes from baseline to 6 weeks in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, MADRS-6 (included items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, and pessimistic thoughts) score, and individual MADRS item scores were assessed with an analysis of variance (ANOVA) model. Influence of patient baseline characteristics (age, gender, MADRS total score, age at onset of bipolar disorder, psychotic features, melancholic feature, mixed features [≥2 on ≥3 Young Mania Rating Scale items], and racial origin) on the efficacy of olanzapine monotherapy was examined with an ANOVA model for each factor and stepwise multiple regression analysis.. Included were a total of 690 olanzapine-group and 524 placebo-group patients. MADRS total, MADRS-6, and all individual MADRS item scores (except concentration difficulties and suicidal thoughts) showed significantly (P≤0.05) greater decreases from baseline to 6 weeks in olanzapine-treated patients than those on placebo. The only baseline characteristic associated with response to olanzapine was melancholic feature.. The study was limited by omission of patients with bipolar II disorder, post hoc analysis of data from only two clinical trials, and exclusion of suicidal patients.. Olanzapine monotherapy improved core symptoms of depression in patients with bipolar I depression. Additionally, we identified melancholic feature as a baseline factor associated with improved treatment response to olanzapine.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Randomized Controlled Trials as Topic

In patients with bipolar disorder, olanzapine is commonly used to prevent episodes of acute mania. The drug pramipexole can, in theory, undermine the protective effect of olanzapine. Olanzapine is a dopamine D2 receptor antagonist and pramipexole is a mixed dopamine D2 /D3 receptor agonist. These drugs may therefore theoretically counteract their pharmacological effects. To date, there are no known cases in the literature where this interaction has been described.. We report on a case where a patient with bipolar disorder developed mania after taking pramipexole in combination with olanzapine, and describe the pharmacological background of this interaction.. A patient with bipolar I disorder was hospitalized with a manic episode characterized by agitation and insomnia after taking pramipexole for restless leg syndrome (RLS) in combination with olanzapine. Co-medication, i.e., lithium and mirtazapine, and other circumstances are not likely to have contributed to this effect.. There is a probable interaction between pramipexole and olanzapine, where pramipexole undermines the protective effect of olanzapine, provoking an episode of acute mania and hospitalization. This interaction is of clinical importance since pramipexole is the treatment of choice for RLS, a condition often seen in end-stage renal disease, and has also been investigated as an antidepressant therapy in patients with bipolar disorder.

Topics: Akathisia, Drug-Induced; Benzodiazepines; Benzothiazoles; Bipolar Disorder; Dopamine Agonists; Drug Interactions; Drug Therapy, Combination; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Pramipexole; Restless Legs Syndrome; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzocycloheptenes; Dibenzothiazepines; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Somnambulism

To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome.. This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items.. Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61-43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36-37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64-67%), whereas remission decreased with increasing severity with olanzapine (63-38%) and placebo (49-25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients.. Results are from post-hoc analyses.. These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depression; Diagnostic and Statistical Manual of Mental Disorders; Dibenzocycloheptenes; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Male; Olanzapine; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome

Although a range of pharmacotherapeutical options are available for the treatment of bipolar disorder, patient non-adherence to prescribed treatment regimens and early treatment discontinuation remain among the primary obstacles to effective treatment. Therefore, this observational study assessed time on mood stabilizing medication and retention rates in patients with bipolar disorder (BD).. In an 18-month, prospective, multicenter, non-interventional study conducted in Germany 761 outpatients (≥18 years) with BD and on maintenance therapy were documented. For analysis, patients were stratified by baseline medication: monotherapy olanzapine (OM, N = 186), lithium (LM, N = 152), anticonvulsants (N = 216), other mood stabilizing medication (OMS, N = 44); combination therapy olanzapine/lithium (N = 47), olanzapine/anticonvulsant (N = 68), other combinations (OC, N = 48). Continuation on medication was assessed as retention rates with 95% confidence intervals. Time to discontinuation and relapse-free time were calculated by Kaplan-Meier analysis. A relapse was defined as increase to CGI-BP >3, worsening of CGI-BP by ≥2 points, hospitalization or death related to BD. A Cox regression was calculated for the discontinuation of mood stabilizing therapy (reference: OM). Logistic regression models with stepwise forward selection were used to explore possible predictors of maintenance of treatment and relapse.. After 540 days (18 months), the overall retention rate of baseline medication was 87.7%, without notable differences between the cohorts. The overall mean time on mood stabilizing treatment was 444.7 days, with a range of 377.5 (OMS) to 481 (LM) by cohort. 74.0% of all patients were without relapse, with rates between the cohorts ranging from 58.4% (OC) to 80.2% (LM).. Retention rates exceeded controlled trial results in all treatment cohorts, in addition to other explanations possibly reflecting that the physicians were expertly adapting treatment regimens to the individual patient's disease characteristics and special needs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Germany; Humans; Lithium; Male; Medication Adherence; Middle Aged; Olanzapine; Prospective Studies; Recurrence; Treatment Outcome; Young Adult

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Administration Schedule; Female; Humans; Injections, Intramuscular; Olanzapine

Use of electroconvulsive therapy (ECT) has been infrequently described in patients with systemic lupus erythematosus and is most commonly used in patients with catatonia. In this report, we describe the use of ECT in a young adolescent girl who had bipolar affective disorder associated with systemic lupus erythematosus and was treated with ECT for the depressive episode. The patient achieved remission with a course of 6 ECT treatments.

Topics: Adolescent; Alkylating Agents; Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cyclohexanols; Cyclophosphamide; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Lupus Erythematosus, Systemic; Olanzapine; Prednisolone; Venlafaxine Hydrochloride

The appropriateness of use of generic instead of brand-name medication remains unresolved and controversial in several areas of medicine. Some evidence suggestive of variations in bioavailability and clinical effectiveness between different formulations make policy decisions occasionally difficult. The use of generic olanzapine is a widely acceptable practice on the basis of quality, safety and efficacy data and has been adopted in several countries.. The case of a 14 year old boy with bipolar affective disorder, autism and intellectual disability who had brand-name to generic olanzapine switch associated with rapid deterioration of his mental state is described. This clinical change was not related to any physical illness or other medication adjustment and resolved as rapidly when generic olanzapine was switched back to the brand-name formulation.. Caution should be exercised when policy for switching from brand-name to generic psychotropic medications are made, especially when using medications off label, in extremes of age and in those patients with co-morbid complicating factors such as intellectual disability.

Topics: Adolescent; Antipsychotic Agents; Autistic Disorder; Benzodiazepines; Bipolar Disorder; Drugs, Generic; Humans; Intellectual Disability; Male; Olanzapine; Severity of Illness Index

As much as the ideal treatment goal for severe mental illnesses such as bipolar disorder and schizophrenia is to prevent or delay the recurrence or relapse of acute episodes, when the patient presents with an acute episode, the goal should be to manage behavioural symptoms, and return to prior levels of symptomatic control. In a serious mental illness, the management of the acutely agitated state may require rapid tranquillisation (RT) to control violent and/or disturbed behaviour when all other methods of de-escalation have failed. Current clinical practice guidelines for emergency interventions in the case of acutely disturbed behaviours favour calming the patient by reducing agitation with mild sedation, but not sleep, to allow continued interaction with the patient, to ensure an accurate diagnosis, and to enable patients to be actively engaged in treatment decisions. Pharmacotherapy is an essential element in RT and the available agents used may be unique and separate from the patient's regular course of treatment, primarily because agents used in RT may not be suitable for long-term treatment due to an unfavourable efficacy and safety profile. Therefore, the choice of pharmacotherapy is essential to achieve an effective RT and a smooth transition to standard care and routine daily life for the patient. Of the available agents for RT, aripiprazole demonstrated a favourable efficacy and safety profile both over the short-term - including in its intramuscular form (IM) - and in the long-term treatment of bipolar I disorder and schizophrenia. The objective of this article is to assess the available clinical data on IM aripiprazole as a treatment option for the rapid control of agitation and disturbed behaviours in these conditions and to provide a consensus statement based on the expertise of UK healthcare practitioners in acute treatment units.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Haloperidol; Humans; Hypnotics and Sedatives; Olanzapine; Piperazines; Psychomotor Agitation; Quinolones; Schizophrenia; Tranquilizing Agents

Ischemic colitis is a rare adverse effect of antipsychotic medications and is most commonly associated with the phenothiazine class of antipsychotics and atypical antipsychotics such as clozapine and olanzapine. The risk is further increased when antipsychotics are taken in conjunction with anticholinergics. A 27-year-old man with a history of bipolar disorder and depression presented to the emergency department with 6 days of constipation, abdominal pain, nausea, and nonbloody vomiting. He later developed multiple episodes of hematochezia and fever. Within the preceding 2 weeks, his medication regimen of divalproex sodium, aripiprazole, and trihexyphenidyl, had been changed to olanzapine, benztropine, and bupropion. The patient's physical examination showed diffuse abdominal tenderness, guarding, and distension and laboratory tests revealed a leukocytosis. A computed tomographic scan of the abdomen/pelvis showed colitis extending from the splenic flexure to the sigmoid colon, without evidence of perforation. A colonoscopy revealed severe ischemic colitis involving the descending and sigmoid colon, which was confirmed on biopsy. Given the temporal association between the new medications and onset of symptoms, the patient's ischemic colitis was likely caused by olanzapine or the combination of olanzapine and benztropine, likely secondary to their anticholinergic properties. Thus, providers should take a thorough history and counsel patients regarding the risks of constipation when starting antipsychotic medications, particularly those with anticholinergic activity. Despite the fact that ischemic colitis is such a rare adverse effect of antipsychotic medications, it is important to consider because of its potentially fatal outcomes.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Benztropine; Bipolar Disorder; Colitis, Ischemic; Drug Therapy, Combination; Humans; Male; Muscarinic Antagonists; Olanzapine; Tomography, X-Ray Computed

Bipolar disorder represents a major public health concern and, despite treatment, is characterized by recurring episodes of mania, depression, or mixed states. Prevention of relapse or recurrence is a primary treatment objective in the management of the disorder. The objective of the current study was to identify predictors of relapse/recurrence in patients with bipolar I disorder treated with olanzapine, lithium, divalproex, or olanzapine plus divalproex/lithium.. Data from four clinical trials studying the efficacy of olanzapine compared to placebo and active comparators (lithium, divalproex, olanzapine plus divalproex/lithium) for bipolar I disorder were pooled for this analysis. Patients achieving remission after pharmacological treatment and entering randomized double-blind maintenance phase for 44 to 72 weeks were included. Cox Proportional Hazard models and Kaplan-Meier analyses were used to determine predictors of relapse/recurrence for the pooled data and within each treatment group.. A total of 929 patients meeting the criteria for remission and followed by maintenance treatment were included in this analysis, and 427 patients (46.0%) experienced symptomatic relapse/recurrence during the follow-up period. A 21-item Hamilton Depression Rating Scale (HAMD-21) total score<4, gender, rapid cycling and treatment emerged as significant predictors of relapse/recurrence and may be generalized to treatment with olanzapine and to some extent to treatment with lithium and divalproex. The results on treatment-specific predictors of relapse/recurrence are considered to be exploratory and no adjustments were made for multiple comparisons.. The major findings from this study suggest that a HAMD-21 total score<4 may be a better predictor of maintenance of remission in bipolar I patients than HAMD-21 total score<8. The prophylactic effect of olanzapine, lithium, divalproex, olanzapine plus divalproex or lithium, and placebo was assessed and baseline predictors of relapse/recurrence were identified.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Female; Follow-Up Studies; Humans; Lithium; Male; Middle Aged; Olanzapine; Prognosis; Recurrence; Valproic Acid

Olanzapine is a second-generation antipsychotic, which is also used as a mood stabilizer. We report a case of a 33-year-old psychiatric patient, with bipolar affective disorder, who developed anaphylaxis as a late reaction to olanzapine. This case report shows the possibility, although rare, of a severe late anaphylactic reaction to olanzapine.

Topics: Adult; Anaphylaxis; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dopamine Antagonists; Drug Hypersensitivity; Female; Humans; Olanzapine; Serotonin Antagonists; Treatment Outcome

Topics: Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chemical and Drug Induced Liver Injury; Drug Eruptions; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Liver Function Tests; Neutropenia; Olanzapine; Retreatment; Thrombocytopenia; Valproic Acid

The authors examined trends in the use of second-generation antipsychotics for treatment of bipolar disorder before and after the U.S. Food and Drug Administration's approval in 2000 of olanzapine for use in treating acute manic episodes of bipolar disorder.. The IMS Health National Disease and Therapeutic Index was used to derive monthly patient treatment visits between January 1998 and December 2009 by individuals 18 and older with a diagnosis of bipolar disorder who were treated with one or more pharmacotherapies.. The percentage of treatment visits in which a second-generation antipsychotic was prescribed increased from 18% in 1998 to 49% in 2009. Use of mood stabilizers and first-generation antipsychotics declined substantially. In the 12 months after approval of olanzapine for bipolar disorder, its use increased by 92%, and use of other second-generation antipsychotics increased by 42%.. Second-generation antipsychotics are increasingly used for bipolar disorder, and their effectiveness compared with therapeutic alternatives merits further research.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Approval; Drug Therapy, Combination; Drug Utilization; Humans; Models, Statistical; Olanzapine; Practice Patterns, Physicians'; United States; United States Food and Drug Administration

In recent years, concerns about the use of antipsychotic medications in dementia have grown. There is limited data on mortality risk of atypical antipsychotics for other psychiatric disorders of later life such as bipolar disorder.. Data were derived from the national Department of Veterans Affairs registries for older patients with bipolar disorder (≥65 years) with a new start of an atypical antipsychotic (risperidone, olanzapine, or quetiapine) or valproic acid and derivatives during fiscal years 2001-2008. Six-month mortality rates were compared for individual drug groups.. The sample included 4717 patients. The risperidone cohort had the highest mortality rate (11.8 per 100 person-years) with the quetiapine and valproic acid cohorts having the lowest (5.3 and 4.6 per 100 person-years, respectively). Various methods to adjust for baseline differences including propensity models showed similar patterns.. Among older patients with bipolar disorder, there may be differences in mortality risks among individual antipsychotic agents.

Topics: Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Kaplan-Meier Estimate; Male; Olanzapine; Proportional Hazards Models; Quetiapine Fumarate; Risk Factors; Risperidone; Valproic Acid

This study aims to assess the proportion of patients with schizophrenia or bipolar disorder who discontinued treatment with one of two oral formulations of olanzapine within 12 months in outpatient settings in Germany, Greece, and France.. This 1-year, prospective, observational study included patients who had recently initiated treatment with olanzapine-coated tablets (OC) or the orodispersible (OD) formulation. Primary endpoint was olanzapine discontinuation for any reason. Clinical and functional status were also evaluated.. Out of 927 enrolled patients, 903 were included in the analyses (612 patients with schizophrenia, 291 with bipolar disorder). Within 12 months, 46 of 903 patients discontinued olanzapine. Most (95%) patients remained on olanzapine for 12 months with similar rates for patients with either diagnosis (94.5% for schizophrenia, 94.9% for bipolar disorder) and for both formulations (93.7% with OC, 95.3% with OD). The only factor significantly associated with time to discontinuation was baseline disease severity. Patients with more severe disease at baseline had a lower discontinuation risk. There were significant improvements in functioning and well-being and non-significant improvements in therapeutic alliance and compliance.. No significant difference was seen between discontinuation rates of the two formulations. Higher baseline severity was associated with a lower discontinuation rate.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Weight; Chemistry, Pharmaceutical; Dose-Response Relationship, Drug; Europe; Female; Follow-Up Studies; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Observation; Olanzapine; Outpatients; Patient Compliance; Prospective Studies; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Suicide, Attempted; Treatment Outcome

Bipolar disorder has a significant impact upon a patient's quality of life, imposing a considerable economic burden on the individual, family members and society as a whole. Several medications are indicated for the acute treatment of mania and depression associated with bipolar disorder as well as for maintenance therapy; however, these have varying efficacy, tolerability and costs.. The objective of this study was to develop a new discrete-event simulation model to analyse the long-term consequences of pharmacological therapy for the management of bipolar I and II disorders (acute treatment of episodes of mania and depression as well as maintenance therapy).. Probabilities of remission and relapse were obtained from clinical trial data and meta-analyses. Costs (year 2011 values) were assessed from a UK healthcare payer's perspective, and included pharmacological therapy and resource use associated with the treatment of mood events and selected adverse events. The health effects were measured in terms of QALYs.. For a patient starting with acute depression or in remission at 40 years of age (which was the average age in the clinical trials), quetiapine 300 mg/day was a cost-effective strategy compared with olanzapine 15 mg/day over a 5-year time frame. With acute bipolar depression as a starting episode, the 5-year medical costs were £323 higher and QALYs were 0.038 higher for quetiapine compared with olanzapine, corresponding to a cost-effectiveness ratio of £8600 per QALY gained.. Compared with olanzapine, the results suggest that quetiapine is cost effective as a maintenance treatment for bipolar depression.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Computer Simulation; Cost-Benefit Analysis; Dibenzothiazepines; Humans; Meta-Analysis as Topic; Models, Economic; Olanzapine; Quality-Adjusted Life Years; Quetiapine Fumarate; Remission Induction; Secondary Prevention; United Kingdom

Olanzapine, a world leader in antipsychotic drugs, is used in the treatment of schizophrenia and bipolar disorder. There is considerable interpatient variability in its hepatic clearance. Polymorphic glucuronidation of olanzapine by uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4) was investigated retrospectively in patient samples taken for routine therapeutic drug monitoring (TDM) and in recombinant metabolic systems in vitro. Multivariate analyses revealed that patients who were heterozygous as well as those who were homozygous for the UGT1A4*3 allelic variant had significantly higher concentrations of the major metabolite olanzapine 10-N-glucuronide in serum (+38% (P = 0.011) and +246% (P < 0.001), respectively). This finding was in line with the significant increases in glucuronidation activity of olanzapine observed with recombinant UGT1A4.3 (Val-48) as compared with UGT1A4.1 (Leu-48) (1.3-fold difference, P < 0.001). By contrast, serum concentrations of the parent drug were not significantly influenced by UGT1A4 genotype. Our findings therefore indicate that UGT1A4-mediated metabolism is not a major contributor to interpatient variability in olanzapine levels. However, with respect to other drugs for which UGT1A4 has a dominant role in clearance, increased glucuronidation encoded by UGT1A4*3 might impact the risk for subtherapeutic drug exposure.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Genotype; Glucuronides; Glucuronosyltransferase; Humans; Liver; Male; Metabolic Clearance Rate; Multivariate Analysis; Norway; Olanzapine; Retrospective Studies; Schizophrenia

Antipsychotics are commonly used in bipolar disorder, with newer (SGA) agents increasingly replacing FGA antipsychotics, particularly in bipolar depression. There are few data on differences between FGA and SGA antipsychotics in terms of their relationship to suicidal behavior in bipolar disorder.. This was a retrospective chart review of 161 bipolar veterans treated naturalistically with antipsychotics at a university-affiliated VA hospital and clinics for up to 8 years. Charts were reviewed to determine monthly antipsychotic use and occurrence of suicidal behavior: completed suicide, attempted suicide or hospitalization to prevent suicide. Suicidal behavior events were compared across patients during treatment with individual antipsychotics and FGAs or SGAs as a class.. Non-lethal suicide events were more common during FGA than SGA monotherapy (9 events/110 months of exposure vs. 6 events/381 months of exposure; χ(2)=9.65, p=0.002). Suicide event rates did not differ between FGAs and SGAs when used in conjunction with mood stabilizers. Event rates were lower with lithium than anticonvulsants when used in conjunction with antipsychotics. No differences were found between olanzapine, risperidone and quetiapine.. The retrospective chart review methodology may have led to confounding by indication and diagnostic inaccuracy. No completed suicides occurred. Study participants were primarily male veterans. Results may not be generalizable to SGAs marketed since 2003.. FGA antipsychotic monotherapy may be associated with higher suicidal behavior risk than SGA antipsychotic monotherapy. Antipsychotics used in conjunction with mood stabilizers, particularly lithium, are associated with lower rates, independent of antipsychotic subtype.

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Female; Hospitalization; Humans; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Retrospective Studies; Risperidone; Suicidal Ideation; Suicide; Suicide Prevention; Suicide, Attempted; Veterans

Usher syndrome (or Hallgren syndrome) is an autosomal recessive genetic disorder characterized by sensorineural deafness, retinitis pigmentosa, and variable vestibular deficit; Usher syndrome type II is the most common form. Various neuropsychiatric disorders have been reported to occur in those with Usher syndrome, including schizophrenia-like disorder, atypical psychosis, recurrent depressive illness, neurotic disorder, and mental retardation; however, bipolar disorder is not common in those with Usher syndrome. Herein we describe a 30-year-old male with Usher syndrome type II that developed features indicative of a probable manic episode. The patient had complete remission of symptoms in response to treatment with olanzapine 20 mg d-1. In persons with dual sensory impairment there are inherent problems with assessment and diagnosis is difficult due to their limited communication abilities. The diagnosis of Usher syndrome depends heavily on behavioral observation and disturbances in vegetative functions.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Differential; Humans; Male; Olanzapine; Usher Syndromes

One of the genes suggested to play an important role in the pathophysiology of bipolar disorder (BPD) is PDLIM5, which encodes LIM domain protein. Our main objective was to examine the effect of olanzapine treatment on PDLIM5 mRNA expression in the peripheral blood leukocytes of BPD patients.. We measured the expression of PDLIM5 mRNA from 16 patients with BPD Type I after 0, 4, and 8 weeks of treatment with olanzapine using quantitative real-time PCR. The Young Mania Rating Scale was used to evaluate the severity of manic symptoms in BPD patients. We also compared PDLIM5 mRNA expression in treatment-naïve BPD patients with that in healthy control subjects.. No significant difference was found in PDLIM5 mRNA expression between patients before olanzapine treatment and following 4 and 8 weeks of treatment (p>0.05). Although we observed a significant reduction in the severity of manic symptoms in all BPD patients (p<0.05), the effectiveness of the medication did not significantly correlate with the expression of PDLIM5 mRNA (p>0.05). Interestingly, PDLIM5 mRNA expression differed significantly between treatment-naïve BPD patients and healthy control subjects (p=0.002).. PDLIM5 mRNA expression did not appear to be a reflection of the efficacy of olanzapine in reducing the manic symptoms of BPD. The significant difference in expression of PDLIM5 mRNA in the peripheral blood leukocytes of treatment-naïve BPD patients versus that of healthy control subjects, however, suggests that it may be a good biological marker for BPD.

Topics: Adaptor Proteins, Signal Transducing; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Case-Control Studies; Female; Gene Expression; Genetic Markers; Humans; Leukocytes; LIM Domain Proteins; Male; Middle Aged; Olanzapine; Polymorphism, Single Nucleotide; RNA, Messenger

A 50-year-old, white female patient was diagnosed with schizophrenia in her teens. Her illness did not respond adequately to treatment until she was placed on a combination of fluoxetine and conventional antipsychotics. She discontinued the conventional antipsychotics on a number of occasions, which caused her to become psychotic, but not manic. On two separate occasions she was placed on atypical antipsychotics that were associated with the occurrence of manic symptoms. Once the patient was restarted on conventional antipsychotics, she remained stable.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Substitution; Drug Therapy, Combination; Female; Fluoxetine; Humans; Loxapine; Medication Adherence; Middle Aged; Olanzapine; Recurrence; Risperidone; Schizophrenia

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Olanzapine; Priapism; Young Adult

The Bipolar Comprehensive Outcomes Study (BCOS) is a 2-year, prospective, non-interventional, observational study designed to explore the clinical and functional outcomes associated with 'real-world' treatment of participants with bipolar I or schizoaffective disorder. All participants received treatment as usual. There was no study medication.. Participants prescribed either conventional mood stabilizers (CMS; n = 155) alone, or olanzapine with, or without, CMS (olanzapine ± CMS; n = 84) were assessed every 3 months using several measures, including the Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale, Clinical Global Impressions Scale - Bipolar Version, and the EuroQol Instrument. This paper reports 24-month longitudinal clinical, pharmacological, functional, and socioeconomic data.. On average, participants were 42 (range 18 to 79) years of age, 58%; were female, and 73%; had a diagnosis of bipolar I. Polypharmacy was the usual approach to pharmacological treatment; participants took a median of 5 different psychotropic medications over the course of the study, and spent a median proportion of time of 100%; of the study on mood stabilizers, 90%; on antipsychotics, 9%; on antidepressants, and 5%; on benzodiazepines/hypnotics. By 24 months, the majority of participants had achieved both symptomatic and syndromal remission of both mania and depression. Symptomatic relapse rates were similar for both the CMS alone (65%;) and the olanzapine ± CMS (61%;) cohorts.. Participants with bipolar I or schizoaffective disorder in this study were receiving complex medication treatments that were often discordant with recommendations made in contemporary major treatment guidelines. The majority of study participants demonstrated some clinical and functional improvements, but not all achieved remission of symptoms or syndrome.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Australia; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Middle Aged; Olanzapine; Outcome Assessment, Health Care; Outpatients; Practice Patterns, Physicians'; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quality of Life; Recurrence; Valproic Acid

We report the case of a 69 year-old female patient who was hospitalized for Diogenes syndrome, defined by marked self-neglect, social withdrawal and excessive hoarding, leading to squalor. Somatic causes were eliminated. Her personal history showed an eight-year depressive episode followed by a 20-year hypomanic episode without remission, followed by a persistent manic episode associated with Diogenes syndrome for four years. The Diogenes syndrome was successfully treated with mood stabilizers. Mood disorders - in particular chronic mania (i.e. a manic episode lasting more than two years) - should be considered in cases of Diogenes syndrome and in current classifications.

Topics: Aged; Antimanic Agents; Antipyretics; Benzodiazepines; Bipolar Disorder; Female; Humans; Lithium Compounds; Mood Disorders; Obsessive Behavior; Olanzapine; Social Isolation; Syndrome

Topics: Anxiety; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Selective Serotonin Reuptake Inhibitors

The aim of this study was to explore the role of ethnic origin in the treatment of acute bipolar mania. Treatment outcomes were studied in a post-hoc analysis of African-American (AA, n=41) and Caucasian (CA, n=190) adults treated with olanzapine in three studies conducted in the United States of America. Baseline demographics were similar except that the AA cohort had fewer women compared with the CA cohort (37 vs. 58%; P=0.01). Daily mean modal olanzapine dose and study discontinuation rate for AA and CA were: 16.2 mg vs. 16.6 mg and 41.5 vs. 25.3% (P=0.03), respectively. There were four (23.5% of discontinuers) and 19 (39.6% of discontinuers, P=0.14) discontinuations because of a poor response in the AA and CA groups, respectively. Drug exposure for the AA cohort was 18.7 days and that of the CA cohort was 19.3 days. Both cohorts showed similar symptom improvements, and safety outcomes were not statistically significantly different except for the following treatment-emergent adverse event frequencies for AA and CA cohorts, respectively: agitation (24.4 vs. 10.5%, P=0.04); dysmenorrhoea (20.0 vs. 3.6%, P=0.04); and dizziness postural (7.3 vs. 1.1%, P=0.04). Although study findings [limited by a smaller (18% of total population) AA cohort] need replication, they suggest that while many outcomes were similar in both cohorts, clinicians could benefit from the awareness of factors in the AA population that possibly influence study discontinuation rates, treatment-emergent adverse event reporting, and participation by sex.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Black or African American; Female; Humans; Male; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome; United States; White People

This study compared 1-year risk of psychiatric hospitalization and treatment costs in commercially insured patients with bipolar disorder, treated with aripiprazole, ziprasidone, olanzapine, quetiapine or risperidone.. This was a retrospective propensity score-matched cohort study using the Ingenix Lab/Rx integrated insurance claims dataset. Patients with bipolar disorder and 180 days of pre-index enrollment without antipsychotic exposure who received atypical antipsychotic agents were followed for up to 12 months following the initial antipsychotic prescription. The primary analysis used Cox proportional hazards regression to evaluate time-dependent risk of hospitalization, adjusting for age, sex and pre-index hospitalization. Generalized gamma regression compared post-index costs between treatment groups.. Compared to aripiprazole, ziprasidone, olanzapine and quetiapine had higher risks for hospitalization (hazard ratio 1.96, 1.55 and 1.56, respectively; p < 0.05); risperidone had a numerically higher but not statistically different risk (hazard ratio 1.37; p = 0.10). Mental health treatment costs were significantly lower for aripiprazole compared with ziprasidone (p = 0.004) and quetiapine (p = 0.007), but not compared to olanzapine (p = 0.29) or risperidone (p = 0.80). Total healthcare costs were significantly lower for aripiprazole compared to quetiapine (p = 0.040) but not other comparators.. In commercially insured adults with bipolar disorder followed for 1 year after initiation of atypical antipsychotics, treatment with aripiprazole was associated with a lower risk of psychiatric hospitalization than ziprasidone, quetiapine, olanzapine and risperidone, although this did not reach significance with the latter. Aripiprazole was also associated with significantly lower total healthcare costs than quetiapine, but not the other comparators.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cohort Studies; Databases, Factual; Drug Costs; Female; Health Care Costs; Hospitalization; Humans; Insurance Claim Reporting; Longitudinal Studies; Male; Middle Aged; Olanzapine; Propensity Score; Retrospective Studies; Risk Factors

To assess the short-term impact of Florida Medicaid's policy change on olanzapine discontinuation and health care resource utilization among olanzapine-treated patients with schizophrenia or bipolar diagnoses. The announced policy change, effective on July 11, 2005, but rescinded on September 9, 2005, reclassified olanzapine as nonpreferred and gave physicians 60 days to change antipsychotics for current users.. Prescription patterns, health care resource utilization, and Medicaid payments were compared between patients using olanzapine on July 11, 2005, and matched prior-year controls. For reference, parallel analyses were conducted in New Jersey Medicaid, where access to olanzapine remained constant. The effect of Florida's policy change was also estimated among policy-sensitive olanzapine users by treating year (2004 vs 2005) as an instrumental variable.. Matched Florida cohorts (N = 4,255) showed increases from 2004 to 2005 in 6-month rates of switching from olanzapine (+326%), hospitalization (+19.8%), and emergency room visits (+19.7%) (all P values < .001). Concurrently in the matched New Jersey cohorts (N = 2,680), there were no significant changes in these outcomes from 2004 to 2005. Among matched Florida policy-sensitive olanzapine users, an additional 9.3% experienced hospitalization in 2005 versus 2004 (P < .001), and increased payments for medical services and other antipsychotics largely offset decreased payments for olanzapine.. The announced reclassification of olanzapine to nonpreferred status substantially disrupted the continuity of olanzapine therapy for many Florida Medicaid recipients diagnosed with schizophrenia or bipolar disorder and was associated with increased hospitalization and emergency room visits. During the 6 months following the policy change, increased payments for medical services largely offset reduced payments for olanzapine.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cohort Studies; Female; Florida; Health Care Costs; Humans; Logistic Models; Male; Medicaid; Mental Health Services; Middle Aged; New Jersey; Olanzapine; Policy; Practice Patterns, Physicians'; Schizophrenia; United States

The case of a patient taking high-dosage olanzapine who experienced parkinsonism after smoking cessation is reported.. A 73-year-old Caucasian woman with a recent diagnosis of Parkinson disease and a history of chronic obstructive pulmonary disease, hyperlipidemia, chronic osteoarthritis, and hypothyroidism was hospitalized for altered mental status, weakness, and ambulatory dysfunction. The diagnosis of Parkinson disease was made approximately four months prior. Despite initiation of carbidopa-levodopa, the patient's symptoms did not improve, and her mental and physical status declined. The patient was taking olanzapine 30 mg daily for bipolar disorder and had a 40-pack-year history of smoking, but she quit smoking approximately four months before this hospitalization. The results of a neurologic evaluation suggested that the patient did not have Parkinson disease but was possibly experiencing olanzapine toxicity secondary to smoking cessation. Carbidopa-levodopa was discontinued. Psychiatry was consulted, and a monthlong cross-taper to discontinue olanzapine and initiate aripiprazole with a target dosage of 20 mg daily was recommended. During the course of therapy, the patient's level of alertness and bradykinesia improved. Overall, it was noted that her extrapyramidal symptoms were gradually improving; two days before hospital discharge, she was noted to have no definite remaining evidence of parkinsonism. In this case, use of the Naranjo et al. adverse-drug-reaction probability scale and the drug interaction probability scale indicated that the adverse effects were probably related to the interaction between smoking and olanzapine.. A 73-year-old woman receiving high-dosage olanzapine for bipolar disorder developed parkinsonism after smoking cessation.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Interactions; Female; Humans; Olanzapine; Parkinsonian Disorders; Smoking; Smoking Cessation

Bipolar disorder (BPD) is a devastating long-term disease for which a significant symptom is mania. Rodent models for mania include psychostimulant-induced hyperactivity and single gene alterations, such as in the Clock or DAT genes, but there is still a pressing need for additional models. Recently, our lab isolated a line of mice, termed Madison (MSN), that exhibit behavioral characteristics that may be analogous to symptoms of mania. In this study we quantified possible traits for mania and tested the response to common anti-BPD drugs in altering the behavioral profiles observed in this strain. Relative to other mouse lines, MSN mice showed significant elevations of in-cage hyperactivity levels, significant decreases in daytime sleep, and significant increases in time swimming in the forced swim test. In terms of sexual behavior, the MSN mice showed significantly higher number of mounts and a trend toward higher time mounting. In separate studies, olanzapine and lithium (or respective controls) were administered to MSN mice for at least 2weeks and response to treatments was evaluated. Olanzapine (1mg/kg/day) significantly decreased in-cage hyperactivity and significantly increased time sleeping. Lithium (0.2-0.4% in food) significantly decreased in-cage hyperactivity. Given the behavioral phenotypes and the response to anti-BPD treatments, we propose that MSN mice may provide a possible new model for understanding the neural and genetic basis of phenotypes related to mania and for developing pharmaceutical treatments.

Topics: Animals; Antimanic Agents; Behavior, Animal; Benzodiazepines; Bipolar Disorder; Body Weight; Dark Adaptation; Disease Models, Animal; Exploratory Behavior; Lithium Chloride; Mice; Olanzapine; Sexual Behavior, Animal; Sleep; Swimming

To examine (1) arrest outcomes for adults with schizophrenia and bipolar disorder who were treated with first-generation antipsychotics (FGAs) or second-generation atypical antipsychotics (SGAs) and (2) the interaction between medication class and outpatient services in a Florida Medicaid program.. In a secondary data analysis, Florida Medicaid data covering the period from July 1, 2002, to March 31, 2008, were used to identify persons diagnosed with schizophrenia, schizoaffective disorder, and bipolar disorder and to examine antipsychotic medication episodes lasting at least 60 days. There were 93,999 medication episodes in the population examined (N = 36,519). Medication episodes were coded as (1) SGA-aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting therapy, or ziprasidone; or (2) FGA-any other antipsychotic medication. Outpatient services were defined as the proportion of 30-day periods of each medication episode with at least 1 behavioral health visit. Survival analyses were used to analyze the data, and they were adjusted for the baseline propensity for receiving an SGA.. Second-generation antipsychotic episodes were not associated with reduced arrests compared to FGA episodes; however, the interaction between outpatient services and SGA episodes was significant (hazard ratio [HR] = 0.68; 95% CI, 0.50-0.93; P = .02) such that an SGA episode with an outpatient visit during at least 80% of every 30-day period of the episode was associated with reduced arrests compared to SGA episodes with fewer outpatient services. There was no significant effect for concurrent FGA episodes and outpatient treatment (HR = 0.81; 95% CI, 0.60-1.10; P = .18). Substance use, poor refill compliance, and prior arrest increased risk of subsequent arrest.. The interaction between outpatient visits and treatment with SGAs was significantly associated with reduced arrests. These findings indicate the importance of concurrent antipsychotic medications and outpatient services to affect arrest outcomes for adults with schizophrenia and bipolar disorder.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Clozapine; Crime; Delayed-Action Preparations; Dibenzothiazepines; Female; Florida; Humans; Isoxazoles; Male; Medicaid; Middle Aged; Olanzapine; Outpatients; Paliperidone Palmitate; Piperazines; Propensity Score; Pyrimidines; Quetiapine Fumarate; Quinolones; Risk Factors; Risperidone; Schizophrenia; Treatment Outcome; United States; Young Adult

To assess the cost-effectiveness of aripiprazole versus olanzapine in the treatment of patients with schizophrenia or bipolar disorder in Sweden with focus on the metabolic impact of the treatments.. A Markov health-state transition model was developed. The risks of developing metabolic syndrome after one year of treatment with aripiprazole or olanzapine were derived from a pooled analysis of three randomised clinical trials. The subsequent risks of developing diabetes or coronary heart disease were based on previously published risk models. A societal perspective was applied, adopting a lifetime horizon. Univariate and probabilistic sensitivity analyses were conducted.. Treatment with aripiprazole dominates over olanzapine in both schizophrenia and bipolar disorder. In schizophrenia, quality-adjusted life-years (QALYs) gained were 0.08 and cost savings Swedish kronor (SEK) 30,570 (USD 4000); in bipolar disorder, QALYs gained were 0.09 and cost savings SEK 28,450 (USD 3720). In probabilistic sensitivity analyses, aripiprazole resulted in a dominant outcome in 84% of cases in schizophrenia and in 77% of cases in bipolar syndrome.. The significantly lower risk of developing metabolic syndrome observed with aripiprazole compared with olanzapine is associated with less risk of diabetes and cardiovascular morbidity and mortality that translates into lower overall treatment cost and improved quality of life over time.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Coronary Disease; Costs and Cost Analysis; Female; Humans; Male; Metabolic Diseases; Metabolism; Middle Aged; Olanzapine; Piperazines; Quality-Adjusted Life Years; Quinolones; Risk Assessment; Schizophrenia; Sweden

Topics: Aged, 80 and over; Benzodiazepines; Bipolar Disorder; Delirium; Humans; Male; Olanzapine

Olanzapine is an antipsychotic used in the treatment of schizophrenia, bipolar disorder, and treatment-resistant depression. Glucuronidation by the UDP-glucuronosyltransferase (UGT) family of enzymes is the major mode of olanzapine metabolism, and polymorphisms in these enzymes could contribute to interindividual variability in olanzapine metabolism and therapeutic response.. Cell lines overexpressing individual UGT enzymes were used to determine which UGTs have enzymatic activity against olanzapine, characterize the kinetics of this reaction, and examine the effects of UGT variants on olanzapine metabolism. A bank of 105 human liver microsomes (HLM) were used to perform a phenotype-genotype study comparing glucuronidation activity against UGT genotype.. Cell lines overexpressing the individual UGTs 1A4 and 2B10 exhibited glucuronidation activity against olanzapine. The UGT1A4 variant exhibited a 3.7-fold (P<0.0001) higher Vmax/KM for the formation of the olanzapine-10-N-glucuronide isomer 1, and a 4.3-fold (P<0.0001) higher Vmax/KM for the formation of the olanzapine-10-N-glucuronide isomer 2 than wild-type UGT1A4. The UGT2B10 variant exhibited no glucuronidation activity against olanzapine. In a screening of 105 HLM specimens, there was a 2.1-fold (P=0.04) and 1.6-fold (P=0.0017) increase in the rate of olanzapine-10-N-glucuronide isomer 1 and olanzapine-4'-N-glucuronide formation, and a 2-fold (P=0.02) increase in the overall olanzapine glucuronidation formation, in HLM with the UGT1A4 (*3/*3)/UGT2B10 (*1/*1) genotype compared with HLM with the UGT1A4 (*1/*1)/UGT2B10 (*1/*1) genotype. There was a 1.9-fold (P<0.003) decrease in the formation of both isomers of the olanzapine-10-N-glucuronide, a 2.7-fold (P<0.0001) decrease in olanzapine-4'-N-glucuronide formation, and a 2.1-fold (P=0.0002) decrease in the overall olanzapine glucuronide formation in HLM with at least one UGT2B10*2 allele. In regression analysis, the UGT1A4*3 (P<0.02) and UGT2B10*2 (P<0.002) alleles were significant predictors of the formation of all olanzapine glucuronide isomers.. The UGTs 1A4 and 2B10 glucuronidate olanzapine and functional variants of these UGTs significantly alter olanzapine glucuronidation in vitro. These data suggest that the UGT1A4*3 and UGT2B10*2 alleles contribute significantly to interindividual variability in olanzapine metabolism.

Topics: Antipsychotic Agents; Benzodiazepines; Biomarkers, Pharmacological; Bipolar Disorder; Cell Line; Depressive Disorder, Treatment-Resistant; Genetic Association Studies; Genetic Variation; Genotype; Glucuronosyltransferase; Humans; Microsomes, Liver; Olanzapine; Polymorphism, Single Nucleotide; Regression Analysis; Schizophrenia

Baseline body mass index (BMI), baseline BMI status (normal, overweight, obese) and early (1 month) BMI increases were tested as predictors of 6- and 12-month increases in glucose and lipid measures in 82 olanzapine (OLZ)- and 78 risperidone (RIS)-treated patients with schizophrenia, schizoaffective disorder, or bipolar disorder who participated in a 12-month randomized, prospective metabolic effects study. Baseline BMI predicted greater fasting glucose and HgbA1c levels at 12 months for both treatments. Early BMI change predicted fasting glucose levels at 6 months, but not HgbA1c or BMI, at either time point. For patients who received no concomitant mood stabilizers, early BMI change predicted 12 month HgbA1c values in the OLZ group, and 6- (but not 12-) month fasting glucose and HgbA1c values in the RIS group. Neither baseline BMI nor early BMI change consistently predicted increases in lipids with either drug. OLZ-treated patients with normal baseline BMI had greater increases in total cholesterol, triglycerides, and non-HDL-cholesterol than those who were overweight or obese. In conclusion, higher baseline BMI predicted adverse glycemic changes after 12 months with OLZ and RIS. Individuals with normal baseline BMI may be most susceptible to OLZ-induced hyperlipidosis. Frequency of metabolic screening should be independent of baseline BMI or rapid increases in BMI.

Topics: Adolescent; Adult; Anthropometry; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Fasting; Female; Humans; Lipid Metabolism; Longitudinal Studies; Male; Middle Aged; Olanzapine; Predictive Value of Tests; Retrospective Studies; Risperidone; Schizophrenia; Time Factors; Young Adult

To identify the factors associated with newly prescribed, first-line, second-generation antipsychotics (SgAs) associated with weight gain-olanzapine, risperidone, and quetiapine.. Retrospective medical record review.. Outpatient and inpatient psychiatry services at a tertiary care, academic medical center.. Three hundred forty consecutive adults who had major depressive disorder with psychotic features, bipolar I, bipolar II, bipolar not otherwise specified, or schizoaffective disorder over two time periods (August 30-October 30, 2009, and April 1-May 31, 2010).. Clinical and sociodemographic variables associated with newly prescribed olanzapine, risperidone, and quetiapine were identified by using univariate and multivariate logistic regression. Several clinical factors were individually associated with initiation of these SgAs: mania (odds ratio [OR] 3.6, 95% confidence interval [CI] 1.2-10.8, p=0.02), psychosis (OR 3.3, 95% CI 1.5-6.9, p=0.002), and inpatient treatment (OR 3.8, 95% CI 1.8-7.9, p=0.0005). Prevalent use of lithium (OR 0.3, 95% CI 0.1-0.9, p=0.03) and being married (OR 0.3, 95% CI 0.1-0.8, p=0.02) were inversely associated with new use of an SgA. Mania, psychosis, married status, and lithium use remained independently associated on multivariate analysis. Factors related to metabolic or vascular risk were not associated with SgA initiation.. Psychiatric clinicians were influenced heavily by clinical features related to mental status and acuity when determining whether to prescribe SgAs. However, factors related to vascular risk were not associated. Future observational studies should consider current clinical status as an important factor in determining propensity to receive antipsychotics or other short-term treatments for bipolar and related disorders.

Topics: Academic Medical Centers; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Risperidone; Weight Gain

Topics: Adolescent; Analysis of Variance; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Child; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Spain; Time Factors

Mefloquine (Lariam) is the drug of choice as malaria prophylaxis for travel to chloroquine-resistant areas. Severe neuropsychiatric side effects are rare. We report two clinical cases of mood disorders: mania and a major depressive episode with psychotic characteristics in two patients with mefloquine antimalarial prophylaxis. FIRST CLINICAL CASE: A 31-year-old man had taken mefloquine at a rate of 250mg/week as malaria prophylaxis for his mission in Democratic Republic of Congo. He developed mania with psychotic symptoms after taking five tablets of 250mg of mefloquine. He exhibited an elevated mood and also developed delusions of grandeur, reference and persecution, with auditory hallucinations. The physical examination and the blood laboratory tests were normal. The patient was treated with an atypical neuroleptic (olanzapine 20mg/d) leading to a complete resolution of symptomatology at the end of 3 weeks. SECOND CLINICAL CASE: A 27-year-old man presented a major depressive episode with psychotic symptoms after 1 week on his return from a stay in Democratic Republic of Congo, where he had taken mefloquine during 6 months as malaria prophylaxis (250mg/week). His physical examination and investigations (full blood test, serology and MRN) were normal. The patient was treated with clomipramine (150mg/d) and olanzapine (20mg/d). The outcome was favorable after 4 weeks.. Mefloquine is widely accepted as a safe and effective treatment and a prophylactic agent for chlorquine-resistant malaria. Common neuropsychiatric adverse effects of mefloquine can occur in up to 40% of patients, such as dizziness, sleep disturbances, anorexia, ataxia, and fatigue. Other more serious adverse reactions are rare. They are represented primarily by panic attacks, convulsions, acute psychosis, paranoid delusions, suicidal ideation, disorders of mood: major depressive episode and the manic excitation. The incidence of such neuropsychiatric effects is 1/10,000 to 1/15,000 during the prophylactic treatment. The causal mechanism for the side effects is not known. Several risk factors increasing the neurotoxicity of mefloquine can be identified, the patient with personal or family history of psychiatric disorders are more frequently concerned. Alcohol and the association with other drugs (like quinine) are two other risk factors.. It is relevant for medical practitioners to be aware of the severe neuropsychiatric side effects of mefloquine as malaria prophylaxis. It requires investigation of the risk factors such as personal or family history of psychiatric disorders.

Topics: Adult; Antimalarials; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clomipramine; Depressive Disorder, Major; Drug Therapy, Combination; Humans; Malaria; Male; Mefloquine; Olanzapine; Psychoses, Substance-Induced

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

To determine changes in prescribing patterns in primary care of antipsychotic and mood stabiliser medication in a representative sample of patients with bipolar disorder in the United Kingdom over a fifteen year period and association with socio-demographic factors.. We identified 4700 patients in the Health Improvement Network (THIN) primary care database, who had received treatment for bipolar disorder between 1995 and 2009. The proportion of time for which each individual was prescribed a particular medication was studied, along with variation by sex, age and social depravation status (quintiles of Townsend scores). The number of drugs an individual was taking within a particular year was also examined.. In 1995, 40.6% of patients with bipolar disorder were prescribed a psychotropic medication at least twice. By 2009 this had increased to 78.5% of patients. Valproate registered with the greatest increase in use (22.7%) followed by olanzapine (15.7%) and quetiapine (9.9%). There were differences by age and sex; with young (18-30 year old) women having the biggest increase in proportion of time on medication. There were no differences by social deprivation status. By 2009, 34.2% of women of childbearing age were treated with valproate.. Lithium use overall remained relatively constant, whilst second generation antipsychotic and valproate use increased dramatically. Changes in prescribing practice preceded published trial evidence, especially with the use of second generation antipsychotics, perhaps with inferences being made from treatment of schizophrenia and use of first generation antipsychotics. Women of childbearing age were prescribed valproate frequently, against best advice.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cohort Studies; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Olanzapine; Practice Patterns, Physicians'; Primary Health Care; Quetiapine Fumarate; Retrospective Studies; Social Class; Time Factors; United Kingdom; Valproic Acid

The pharmacological profile of cannabidiol (CBD) has several characteristics in common with drugs known to benefit bipolar affective disorder (BAD), leading to the hypothesis that CBD may have therapeutic properties in BAD. Therefore, the aim of the present report was to directly investigate for the first time the efficacy and safety of CBD in two patients with BAD. Both patients met DSM IV criteria for bipolar I disorder experiencing a manic episode without comorbid conditions. This was an inpatient study, and the efficacy, tolerability and side effects were assessed. Both patients received placebo for the initial 5 days and CBD from the 6th to 30th day (initial oral dose of 600 mg reaching 1200 mg/ day). From the 6th to the 20th day, the first patient (a 34-year-old woman) received adjunctive olanzapine (oral dose of 10-15 mg). On day 31, CBD treatment was discontinued and replaced by placebo for 5 days. The first patient showed symptoms improvement while on olanzapine plus CBD, but showed no additional improvement during CBD monotherapy. The second patient (a 36-year-old woman) had no symptoms improvement with any dose of CBD during the trial. Both patients tolerated CBD very well and no side-effects were reported. These preliminary data suggest that CBD may not be effective for the manic episode of BAD.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cannabidiol; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Olanzapine; Single-Blind Method; Treatment Outcome

Although the relationship between antipsychotic medication, particularly second-generation antipsychotics (SGAs), and metabolic disturbance is increasingly accepted, there is an important, but little recognised, potential interaction between this and the other important serious adverse effect of neuroleptic malignant syndrome (NMS). We report a case of a 35-year old female who developed new onset type II diabetes mellitus with hyperosmolar hyperglycaemic coma and acute renal failure following treatment with a SGA for a first manic episode. The history is strongly suggestive of concurrent NMS. This case raises important questions about non-ketotic, hyperosmolar diabetic coma with antipsychotics, the possible association between hyperglycaemia and hyperthermia, and the direction of causality in this, the recognition of either syndrome when they co-exist and management issues in such patients. These questions are considered in the context of currently available literature.

Topics: Acute Kidney Injury; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Neuroleptic Malignant Syndrome; Olanzapine

We investigated the adequacy of maintenance phase pharmacotherapy received by psychiatric in- and outpatients with bipolar I or II disorder, including patients both with and without a clinical diagnosis of bipolar disorder (BD).. In the Jorvi Bipolar Study (JoBS), a naturalistic prospective 18-month study representing psychiatric in- and outpatients with DSM-IV BD I and II in three Finnish cities, we studied the adequacy of pharmacological treatment received by 154 patients during the first maintenance phase after index episode. Information on treatments prescribed during the follow-up was gathered in interviews and from psychiatric records.. Of the patients with a maintenance phase in follow-up, adequate maintenance treatment was received by 75.3% for some time, but by only 61.0% throughout the maintenance phase and for 69.3% of the time (783/1129 patient months) indicated. Uninterrupted adequate maintenance treatment received was most strongly independently associated with having a clinical diagnosis of BD; other associations included inpatient treatment, rapid cycling and not having a personality disorder.. Adequacy of dosage, duration or serum concentrations were not estimated. Findings represent an upper limit for adequate treatment within the cohort.. Provision or continuity of maintenance treatment was found to be compromised in more than one-third of BD patients during their first follow-up maintenance phase. As expected, clinical diagnosis of BD has a decisive role in determining adequacy of maintenance treatments. However, also rapid cycling may facilitate provision of adequate maintenance treatment, whereas outpatients and those with comorbid personality disorders may be disadvantaged subgroups.

Topics: Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Carbamazepine; Cohort Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lamotrigine; Lithium Carbonate; Long-Term Care; Male; Middle Aged; Olanzapine; Oxcarbazepine; Piperazines; Prospective Studies; Quinolones; Risperidone; Triazines; Valproic Acid

Numerous studies have demonstrated an association between bipolar disorder (BD) and obesity. However, these reports are limited by retrospective or cross-sectional designs, and the assessment of patients with lengthy illnesses. Prospective data, and data on weight gain early in the course of BD, are lacking.. We prospectively measured weight gain and laboratory metabolic indices over 12 months in 47 patients with BD receiving maintenance treatment following their first manic episode, and in 24 age- and gender-matched healthy subjects.. Although approximately two-thirds of patients had experienced previous depressive or hypomanic episodes, there was no difference between patients and healthy subjects in mean body mass index or rates of overweight or obesity at recovery from the first mania. Mean weight gain over 12 months was 4.76kg in patients and 1.50kg in healthy subjects (p=0.047). Combined rates of overweight and obesity at 6 months and 12 months exceeded 50% in patients, and were almost double those of healthy subjects. Logistic regression demonstrated that weight gain in the first 6 months was significantly associated with male gender and prescription of olanzapine or risperidone. Patients who were obese at 6 months and/or 12 months had significantly greater mean serum triglyceride levels and fasting glucose levels than non-obese patients.. This was a naturalistic study.. Even in patients with previous depressions and hypomanias, clinically significant weight gain in BD begins following the first manic episode, suggesting that it is primarily related to treatment with mood stabilizers and second-generation antipsychotics. However, the very small number of patients in our sample who were medication-free precludes a meaningful analysis of the degree to which weight gain might be an inherent feature of post-manic BD.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Body Mass Index; Cholesterol; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Insulin; Lithium Carbonate; Male; Obesity; Olanzapine; Overweight; Prospective Studies; Quetiapine Fumarate; Risperidone; Triglycerides; Valproic Acid; Weight Gain; Young Adult

A case of acute pancreatitis associated with lisinopril and olanzapine is described.. A 69-year-old woman came to the emergency department after four days of experiencing epigastric pressurelike pain that radiated to the left lower quadrant and worsened with ingestion of food. She had started lisinopril three months prior for treatment of hypertension and had been taking olanzapine regularly for bipolar disorder. Upon admission, she was afebrile and hemodynamically stable and exhibited tenderness of the epigastric region. Elevated pancreatic enzymes and abdominal computed tomography (CT) imaging findings confirmed the diagnosis of pancreatitis. Common causes of pancreatitis were ruled out, and it was determined that the recent combination of lisinopril and olanzapine was the likely cause. Food and liquids were withheld, and all oral medications were stopped at hospital admission. Her pain resolved completely after two days. She was discharged on hospital day 4, and all of her medications except lisinopril and olanzapine were resumed. During a follow-up visit with her primary care physician, she reported to be doing well and had no systemic complaints. Olanzapine was reinitiated at that time but was discontinued a month later by her psychiatrist, who was concerned about the development of recurrent symptoms of pancreatitis. Valsartan was prescribed to achieve optimal blood pressure control three weeks after discharge. A follow-up CT scan of the abdomen a month later found no residual pancreatic abnormalities.. The additive effect of two known pancreatitis-causing medications resulted in increased risk and subsequent acute pancreatitis in this patient.

Topics: Acute Disease; Aged; Angiotensin-Converting Enzyme Inhibitors; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Interactions; Drug Therapy, Combination; Female; Humans; Hypertension; Lisinopril; Olanzapine; Pancreatitis

These guidelines are based on a first edition that was published in 2002, and have been edited and updated with the available scientific evidence until September 2009. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute bipolar depression in adults.. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from the clinical trial database clinicaltrials.gov, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into six levels of evidence (A-F). As these guidelines are intended for clinical use, the scientific evidence was finally assigned different grades of recommendation to ensure practicability.. We identified 10 pharmacological monotherapies or combination treatments with at least limited positive evidence for efficacy in bipolar depression, several of them still experimental and backed up only by a single study. Only one medication was considered to be sufficiently studied to merit full positive evidence.. Although major advances have been made since the first edition of this guideline in 2002, there are many areas which still need more intense research to optimize treatment. The majority of treatment recommendations is still based on limited data and leaves considerable areas of uncertainty.

Topics: Adolescent; Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Child; Dibenzothiazepines; Electroconvulsive Therapy; Humans; Lamotrigine; Lithium Compounds; Olanzapine; Psychiatric Status Rating Scales; Psychotherapy; Quetiapine Fumarate; Triazines; Valproic Acid

Agitation is a medical emergency with increased risk for poor outcome. Successful treatment often requires intramuscular (IM) psychotropics. Safety data from the first 21 months of olanzapine IM, approved in the United States for the treatment of agitation associated with schizophrenia and bipolar disorder, are presented.. A Lilly-maintained safety database was searched for all spontaneous adverse events (AEs) reported in temporal association with olanzapine IM treatment.. The estimated worldwide patient exposure to olanzapine IM from January 1, 2004, through September 30, 2005, was 539,000; 160 cases containing AEs were reported from patients with schizophrenia (30%), bipolar disorder (21%), unspecified psychosis (10%), dementia (8%), and depression (5%). Many reported concomitant treatment with benzodiazepines (39%) or other antipsychotics (54%). The most frequently reported events involved the following organ systems: central nervous (21%), cardiac (12%), respiratory (6%), vascular (6%), and psychiatric (5%). Eighty-three cases were considered serious, including 29 fatalities. In these fatalities, concomitant benzodiazepines or other antipsychotics were reported in 66% and 76% of cases, respectively. The most frequently reported events in the fatal cases involved the following organ systems: cardiovascular (41%), respiratory (21%), general (17%), and central nervous (10%). The majority of fatal cases (76%) included comorbid conditions and potentially clinically significant risk factors for AEs.. Clinicians should use care when treating agitated patients, especially when they present with concurrent medical conditions and are treated with multiple medications, which may increase the risk of poor or even fatal outcomes. Clinicians should use caution when using olanzapine IM and parenteral benzodiazepines simultaneously.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Databases as Topic; Fatal Outcome; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Risk Factors; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Olanzapine is an atypical antipsychotic approved for the treatment of adults and adolescents (aged 13 -17 years) with schizophrenia or bipolar I disorder (manic or mixed episodes).. To characterize the pharmacokinetics of olanzapine in adolescents, to estimate the sources of variability, and to identify significant co-variates. In addition, olanzapine pharmacokinetic parameters in adolescents were compared with those in adults to guide appropriate dosing recommendations for adolescent patients.. A population pharmacokinetic modeling study was performed. The majority of pharmacokinetic data for the model came from a multicenter, open-label study in which 4.5 weeks of oral olanzapine 2.5-20 mg once daily was administered to a total of 105 patients aged 13-17 years (41.1-148 kg) who had a diagnosis of schizophrenia or bipolar I disorder. Four blood samples at steady state were obtained from each patient. Olanzapine concentrations in plasma were determined using a validated high-performance liquid chromatography method with electrochemical detection. Similar data from 11 adolescents from three previous studies were also included. A pharmacokinetic model was developed and the potential effects of patient characteristics (sex, bodyweight, age, ethnic origin) were investigated using a nonlinear mixed effects modeling program. The distributions of pharmacokinetic parameters for olanzapine in adolescents were compared with those previously reported in adults (n = 912, diagnosis of schizophrenia, olanzapine 5-20 mg/day) using the Kolmogorov-Smirnov 2-sample test. A visual predictive check was performed using Monte Carlo simulations on an external validation dataset.. The pharmacokinetics of oral olanzapine in adolescent patients were described by a one-compartment pharmacokinetic model. The typical model estimates were 13.6 L/h (70 kg female patient) for oral clearance (CL/F) and 899 L for oral volume of distribution (V/F). Interpatient variability (40.5% for CL/F, 65.4% for V/F) and residual error (27%) were moderate. Bodyweight and sex had a significant influence on CL/F, which was lower in patients with lower weights and approximately 30% higher in males than females. Olanzapine exposure was typically 27% higher in adolescents versus adults. Approximately 77% of adolescents and adults had comparable CL/F values and 69% had comparable V/F values.. The pharmacokinetics of oral olanzapine in adolescent patients are similar to those in adults, and are linear in the dosage range of 2.5-20 mg/day. Given the small magnitude of co-variate effects and the interpatient variability, dose adjustments based on bodyweight or sex are not necessary in adolescents.

Topics: Administration, Oral; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Models, Biological; Multicenter Studies as Topic; Olanzapine; Randomized Controlled Trials as Topic; Schizophrenia; Sex Characteristics

Bipolar illness is associated with significant psychosocial morbidity and health resource utilization. Second generation antipsychotics, used alone or in combination with mood stabilizers are effective in treating acute mania in community settings. This study was designed to compare the change in clinical parameters and resource utilization at one month in a group of patients who required treatment intervention for exacerbation of mania. The clinical response at one year was also evaluated.. 496 patients were enrolled at 75 psychiatric practices across Canada. The Olanzapine cohort (n = 287) included patients who had olanzapine added to their medication regimen or the dose of olanzapine increased. The Other cohort (n = 209) had a medication other than olanzapine added or the dose adjusted. Changes from baseline in the Young Mania Rating Scale (YMRS), Montgomery Asberg Depression Rating Scale, Beck Anxiety Inventory and SF-12 Health Survey were compared at one month using ANCOVA. Categorical variables at one month for health resource utilization, employment status, abuse/dependency, and the number of suicide attempts were compared using Fisher's Exact test. Patients were followed for one year and a subgroup was evaluated.. At one month, patients in the Olanzapine cohort recorded a mean reduction in the YMRS of 11.5, significantly greater than the mean reduction in the Other cohort of 9.7 (ANCOVA P = 0.002). The Olanzapine cohort was significantly improved compared to the Other cohort on the scales for depression and anxiety and did not experience the deterioration in physical functioning seen in the Other cohort. No significant differences were detected in health-related quality-of-life measures, employment status, drug abuse/dependency, number of suicide attempts, mental functioning, emergency room visits or inpatient psychiatric hospitalizations. In a subgroup treated for 12 months with a single second generation antipsychotic, improvements in illness severity measures were maintained with no evidence of significant differences among the antipsychotics.. Patients with bipolar disorder requiring treatment intervention for exacerbation of mania in the community setting responded to olanzapine at one month. In a subset analysis, second generation antipsychotic treatment continued to be beneficial in reducing bipolar symptoms at one year.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Canada; Cohort Studies; Community Mental Health Services; Data Collection; Female; Follow-Up Studies; Health Services; Health Status; Humans; Male; Olanzapine; Personality Inventory; Psychiatric Status Rating Scales; Severity of Illness Index; Suicide, Attempted; Surveys and Questionnaires; Treatment Outcome

Atypical antipsychotic agents constitute one therapeutic approach for bipolar disorder. Since disease course and outcome are variable, further studies are needed to complement limited data supportive of clinical decisions at treatment initiation.. This 12-month, prospective, observational study investigated factors associated with symptomatic remission (total YMRS score < or =12) and full clinical recovery (sustained reduction in CGI-BP-S overall score) in bipolar disorder during treatment with atypical antipsychotics (predominantly olanzapine, risperidone and quetiapine; alone or in combination with a psychotropic such as lithium or valproate) in actual clinical practice.. Amongst 872 enrolled and eligible patients, rates of symptomatic remission and full clinical recovery at 12 months were 93.0 and 78.5%, respectively. Of the baseline factors significantly (P< or =0.05) associated with symptomatic remission, the following categories were positively associated with a higher chance of symptomatic remission: Caucasian ethnicity; higher CGI-BP-S scores; family-dependent living; a previous manic episode; 1, 2 or > or =5 social activities; no work impairment; and being neither satisfied nor dissatisfied with life. Outpatient treatment and historically longer periods of mania were significantly positively associated with full clinical recovery.. While clinical status may also be associated with longer-term remission and recovery, factors relating to social functioning and quality of life are easily assessed and potentially modifiable. Such knowledge may aid physicians' clinical decisions regarding patients with bipolar mania treated with atypical antipsychotics.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Ethnicity; Female; Humans; Lithium Carbonate; Male; Observation; Olanzapine; Personality Disorders; Prospective Studies; Quetiapine Fumarate; Remission Induction; Risperidone; Severity of Illness Index; Substance-Related Disorders; Valproic Acid

Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders.. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups.. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p < 0.001 for all comparisons), total cholesterol increased in the bipolar (p = 0.02) and psychotic (p = 0.01) disorder groups, low-density lipoprotein cholesterol increased in the bipolar group (p = 0.02), and free T4 decreased in the psychotic disorder group (p = 0.05). More patients with bipolar disorder presented overweight plus > or = 1 obesity-related complication at follow-up.. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Biomarkers; Bipolar Disorder; Body Mass Index; Child; Cholesterol, LDL; Chromatography, High Pressure Liquid; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Mental Disorders; Obesity; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Thyroxine; Treatment Outcome; Weight Gain

The aim of this study was to investigate whether lower lithium levels (LoLi) or olanzapine doses (LoOL) are risk factors for future mood episodes in patients with bipolar I disorder.. A post-hoc analysis of the olanzapine-lithium-maintenance study [31] was performed using proportional hazards Cox regression models and marginal structural models (MSMs), adjusting for non-random assignments of dose during treatment.. The LoLi group (<0.6 mmol/L) had a significantly increased risk of manic/mixed (hazard ratio [HR]=1.96, p=0.042), but not depressive (HR=2.11, p=0.272) episodes, compared to the combined medium (0.6-0.79 mmol/L) and high lithium level (≥0.8 mmol/L) groups. There was no significant difference in risk between the two higher lithium level groups (0.6-0.79 mmol/L; ≥0.8 mmol/L) for new manic/mixed (HR=0.96, p=0.893) or depressive (HR=0.95, p=0.922) episodes. The LoOL group (<10mg/day) showed a significantly increased risk of depressive (HR=2.24, p=0.025) episodes compared to the higher olanzapine (HiOL) dose group (HiOL: 10-20 mg/day), while there was no statistically significant difference in risk for manic/mixed episodes between the two groups (HR=0.94, p=0.895).. Lithium levels≥0.6 mmol/L and olanzapine doses≥10mg/day may be necessary for optimal protection against manic/mixed or depressive episodes, respectively in patients with bipolar I disorder.

Topics: Antimanic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Female; Humans; Lithium; Logistic Models; Male; Olanzapine; Proportional Hazards Models; Recurrence; Risk Factors; Severity of Illness Index; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Consciousness Disorders; Dibenzothiazepines; Drug Therapy, Combination; Emergencies; Epilepsy, Tonic-Clonic; Female; Humans; Middle Aged; Olanzapine; Quetiapine Fumarate; Receptors, Adrenergic, alpha; Receptors, Histamine

Bipolar I disorder (BPD I) is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. However, few studies have investigated the cost effectiveness of maintenance treatment options for BPD I.. To determine the cost effectiveness of maintenance treatment with quetiapine fumarate extended-release (XR) tablets in combination with mood stabilizers (lithium or divalproex) in comparison with the following treatments: placebo in combination with lithium or divalproex; no maintenance treatment; lithium monotherapy; lamotrigine monotherapy; olanzapine monotherapy; and aripiprazole monotherapy.. The analysis was conducted from the societal and payer perspectives in the US, using a Markov model. The model simulated a cohort of 1000 stabilized BPD I patients and estimated the quarterly risk in three health states: euthymia, mania and depression. Efficacy data were derived from two randomized, double-blind trials comparing quetiapine + lithium/divalproex with placebo + lithium/divalproex for up to 2 years, as well as other published literature. Resource data were extracted from published literature. Drug costs, hospitalizations and physician visits were among the direct costs. Indirect costs included absenteeism, and mortality rates included suicide. Benefits and costs were discounted at 3% and the price reference year was 2009. Endpoints included number of acute mood episodes, hospitalizations due to an acute mood event and costs per QALY. Probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty in the model inputs.. Treatment with quetiapine XR + lithium/divalproex was associated with reductions in acute mania (46%), acute depression (41%) and related hospitalizations (44%) compared with placebo + lithium/divalproex, and similar reductions in events were observed relative to lithium monotherapy. In the base-case analysis from the payer perspective, the discounted incremental cost per QALY for quetiapine XR + lithium/divalproex compared with placebo + lithium/divalproex was $US22 959, and compared with lithium monotherapy was $US100 235, while all other comparators were dominated. PSA showed these results to be robust to select assumptions.. Quetiapine XR + lithium/divalproex may be a cost-effective maintenance treatment option for patients with BPD I.

Topics: Absenteeism; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Delayed-Action Preparations; Dibenzothiazepines; Drug Therapy, Combination; Fees, Pharmaceutical; Health Care Costs; Hospital Charges; Humans; Lamotrigine; Lithium Compounds; Markov Chains; Models, Economic; Olanzapine; Piperazines; Quality-Adjusted Life Years; Quetiapine Fumarate; Quinolones; Risk; Tablets; Triazines; United States; Valproic Acid

Acute mania requires hospitalization and prompt control of symptoms. The aim of this study was to compare the efficacy of sodium valproate and olanzapine administered alone or in combination in patients suffering from acute mania. Patients (N = 30) suffering from acute mania were divided into two equal groups. Group 1 patients were treated with sodium valproate 250 mg 3 times a day and Group 2 patients received olanzapine 5 mg twice daily. In both groups sodium valproate or olanzapine was given as add-on therapy at 3 weeks. The primary method of assessment was 50% or more improvement on the Young Mania Rating Scale (YMRS). The serum levels of valproic acid were also measured. Sodium valproate and olanzapine were effective in the treatment of acute mania with all patients demonstrating a 50% or more improvement on the YMRS. Sodium valproate-treated patients receiving olanzapine in the third week had a 15.3% decrease in the YMRS score and patients on olanzapine receiving sodium valproate had a 23.7% decrease. Patients who attained serum valproic acid levels of 100 μg/mL showed improvement on the YMRS. The present study supports combination therapy in the management of acute mania and suggests that serum valproic acid levels of 100 microg/mL are necessary for clinical response.

Topics: Acute Disease; Adult; Aged; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Prospective Studies; Valproic Acid

We report a case of severe neuroleptic malignant syndrome developing in a 28-year-old female patient following deliberate self-poisoning with atypical antipsychotic drugs and serotonin reuptake inhibitors. Because of an increasing loss of consciousness she was rapidly transferred to an Intensive Care Unit. Following this, she became progressively febrile associated with rhabdomyolysis and life-threatening organ dysfunctions. Due to fast diagnosis and immediate therapy the patient was treated successfully. This article describes etiology, pathophysiology and symptoms of neuroleptic malignant syndrome. In addition therapeutic options are discussed.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Coma; Creatine Kinase; Critical Care; Dantrolene; Female; Humans; Muscle Relaxants, Central; Myoglobin; Neuroleptic Malignant Syndrome; Olanzapine; Sertraline; Treatment Outcome

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Metabolic Clearance Rate; Olanzapine; Risperidone; Valproic Acid

Bipolar disorder is a debilitating psychiatric illness presenting with recurrent mania and depression. The pathophysiology of bipolar disorder is poorly understood, and molecular targets in the treatment of bipolar disorder remain to be identified. Preclinical studies have suggested that glycogen synthase kinase-3 (GSK3) is a potential therapeutic target in bipolar disorder, but evidence of abnormal GSK3 in human bipolar disorder and its response to treatment is still lacking.. This study was conducted in acutely ill type I bipolar disorder subjects who were hospitalized for a manic episode. The protein level and the inhibitory serine phosphorylation of GSK3 in peripheral blood mononuclear cells of bipolar manic and healthy control subjects were compared, and the response of GSK3 to antimanic treatment was evaluated.. The levels of GSK3α and GSK3β in this group of bipolar manic subjects were higher than healthy controls. Symptom improvement during an eight-week antimanic treatment with lithium, valproate, and atypical antipsychotics was accompanied by a significant increase in the inhibitory serine phosphorylation of GSK3, but not the total level of GSK3, whereas concomitant electroconvulsive therapy treatment during a manic episode appeared to dampen the response of GSK3 to pharmacological treatment.. Results of this study suggest that GSK3 can be modified during the treatment of bipolar mania. This finding in human bipolar disorder is in agreement with preclinical data suggesting that inhibition of GSK3 by increasing serine phosphorylation is a response of GSK3 to psychotropics used in bipolar disorder, supporting the notion that GSK3 is a promising molecular target in the pharmacological treatment of bipolar disorder.

Topics: Adult; Aged; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Electroshock; Female; Gene Expression Regulation, Enzymologic; Glycogen Synthase Kinase 3; Humans; Lithium Chloride; Male; Middle Aged; Olanzapine; Retrospective Studies; Serine; Young Adult

Topics: Aged; Aggression; Antineoplastic Agents; Benzodiazepines; Bipolar Disorder; Humans; Injections, Subcutaneous; Leuprolide; Male; Olanzapine; Paranoid Behavior; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

High prevalence of metabolic syndrome (MS) and related metabolic disturbances in patients with schizophrenia and bipolar affective disorder have been in main focus of interest in recent years since the introduction of second-generation antipsychotics. This study aims to examine these questions: 1) Is there a relation between antipsychotic treatment and MS prevalence? 2) Which antipsychotic users have higher MS prevalence? 3) Do patients on antipsychotic polytherapy have higher rates of MS than patients on antipsychotic monotherapy? 4) Which metabolic parameters are considerably disturbed on which antipsychotic users?. 242 Patients with schizophrenia, schizoaffective disorder and bipolar disorder without any other psychiatric comorbidity according to DSM-IV and using the same antipsychotic(s) and/or mood stabilizers at least for the last 6 months included to the final assessment.. The sample was divided into 7 drug groups. The MS prevalence was highest in the combined antipsychotic (AA) group (48.1%) according to ATP III criteria. According to IDF criteria clozapine (C) group had the highest MS prevalence (74%).. When metabolic parameters evaluated overall, metabolic risk with antipsychotics is found to be highest in clozapine group, followed by combined AP group. Olanzapine and risperidone have intermediate risk while zuclopentixole has lowest.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chi-Square Distribution; Clopenthixol; Clozapine; Cross-Sectional Studies; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prevalence; Risk Assessment; Risk Factors; Risperidone; Schizophrenia; Turkey; Young Adult

Asenapine is a novel psychopharmacologic agent under development for the treatment of schizophrenia and bipolar disorder. We determined and compared the human receptor binding affinities and functional characteristics of asenapine and several antipsychotic drugs. Compounds were tested under comparable assay conditions using cloned human receptors. In comparison with the antipsychotics, asenapine showed high affinity and a different rank order of binding affinities (pKi) for serotonin receptors (5-HT1A [8.6], 5-HT1B [8.4], 5-HT2A [10.2], 5-HT2B [9.8], 5-HT2C [10.5], 5-HT5 [8.8], 5-HT6 [9.6] and 5-HT7 [9.9]), adrenoceptors (alpha1 [8.9], alpha2A [8.9], alpha2B [9.5] and alpha2C [8.9]), dopamine receptors (D1 [8.9], D2 [8.9], D3 [9.4] and D4 [9.0]) and histamine receptors (H1 [9.0] and H2 [8.2]). It had much lower affinity (pKi

Topics: Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Cloning, Molecular; Clozapine; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Histamine Release; Humans; Inhibitory Concentration 50; Molecular Structure; Olanzapine; Psychotropic Drugs; Radioligand Assay; Receptors, Adrenergic; Receptors, Dopamine; Receptors, Dopamine D2; Receptors, Muscarinic; Receptors, Serotonin; Schizophrenia; Substrate Specificity

The rapid progress in treatments for bipolar disorder makes it necessary to revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) published in 2002. This study was performed to timely revise KMAP-BP 2002. A questionnaire comprising 37 questions and 645 treatment options was developed for surveying the opinions of Korean experts. We classified the opinions into three categories: first-, second-, and third-line treatments. Fifty-three (75.7%) of the 70 selected experts answered the questionnaire. For an acute manic episode, the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) was the preferred first-line treatment. Most experts recommended divalproex and lithium as MSs, and olanzapine, quetiapine, and risperidone as AAPs. For moderately to severely depressed bipolar patients, MS monotherapy and a combination of an MS and an antidepressant (AD) were considered to be preferred treatments respectively. A combination of an MS and an AD was the preferred strategy in severe nonpsychotic depression. Most ADs were rated as second-line drugs. Overall, the preference for lamotrigine and AAPs was higher than in KMAP-BP 2002. The algorithm was developed mainly using consensus among experts supplemented with findings of recent clinical trials to ensure that our algorithm was both up to date and balanced. These results suggest that the medication strategies of KMAP-BP are changing rapidly, reflecting recent studies and clinical experiences.

Topics: Algorithms; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Health Personnel; Humans; Korea; Olanzapine; Psychiatry; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Valproic Acid

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

This case report describes the history and hospital course of an otherwise healthy 20-year-old male with bipolar I disorder who developed symptoms of severe lithium toxicity, culminating in a seizure, despite a level of lithium of only 0.8 mEq/L, within the usual therapeutic range. The discussion emphasizes that lithium toxicity is diagnosed by clinical symptoms and can occur even at usual therapeutic blood levels.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Overdose; Humans; Lithium Carbonate; Male; Olanzapine; Seizures; Suicide, Attempted; Young Adult

To describe the safety of olanzapine treatment in adolescents (aged 13-17 years) with schizophrenia or bipolar I disorder, and to compare these data with those of olanzapine-treated adults.. Placebo-controlled database, adolescents: acute phase of 2 double-blind, placebo-controlled trials (3-6 weeks; olanzapine, N = 179, mean age = 15.5 years; placebo, N = 89, mean age = 15.7 years); overall adolescent olanzapine exposure database, adolescents: 4 trials (e.g., the 2 aforementioned studies, each with a 26-week open-label extension phase, and 2 open-label, 4.5- and 24-week trials; N = 454, mean age = 15.9 years); and adult database: 84 clinical trials of up to 32 weeks.. The mean daily dosage of olanzapine was 10.6 mg/day (exposure = 48,946 patient days). In the overall adolescent olanzapine exposure database, the most common adverse events included increased weight (31.7%), somnolence (19.8%), and increased appetite (17.4%). In up to 32 weeks of treatment, when compared with adults, adolescents from the overall adolescent olanzapine exposure database gained statistically significantly more weight (7.4 kg vs. 3.2 kg, p < .001); statistically significantly more adolescents gained > or = 7% of their baseline weight (65.1% vs. 35.6%, p < .001). Adolescents experienced statistically significant within-group baseline-to-endpoint changes in fasting glucose (p < .001), total cholesterol (p = .002), triglycerides (p = .007), and alanine aminotransferase (p < .001). Two patients from the overall adolescent olanzapine exposure database (0.4%) attempted suicide; 13 (2.9%) had suicidal ideation. In the placebo-controlled database, adolescents had statistically significant baseline-to-endpoint increases in prolactin (11.4 micrograms/L, p < .001); 47.4% had high prolactin levels.. The types of adverse events in olanzapine-treated adolescents appear to be similar to those of adults. The magnitude and incidence of weight and prolactin changes were greater in adolescents.. clinicaltrials.gov Identifiers: NCT00051298, NCT00050206, and NCT00113594.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Meta-Analysis as Topic; Olanzapine; Randomized Controlled Trials as Topic; Schizophrenia

We explored the subjective effects associated with olanzapine, risperidone and older antipsychotics.. We conducted a content analysis of an Internet database of comments about prescribed medications.. We analysed 223 comments on risperidone, 170 on olanzapine and 46 relating to three older antipsychotics. The predominant subjective effects produced by all drugs consisted of sedation, cognitive impairment and emotional flattening or indifference. Connections appeared between these effects and Parkinsonian-like symptoms with the older drugs, sexual impairment with risperidone and metabolic effects with olanzapine. The experience of akathisia was frequently linked to suicidal thoughts. Some respondents described how the drugs' subjective effects helped to reduce symptoms of mania, psychosis and anxiety.. The generalisability of Internet data is uncertain. However, the data suggest that adverse subjective effects play a central role in the experience of taking antipsychotic drugs and may be related to the drugs' desired benefits.

Topics: Adult; Affect; Akathisia, Drug-Induced; Antipsychotic Agents; Anxiety Disorders; Attitude to Health; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Female; Health Behavior; Humans; Internet; Male; Middle Aged; Olanzapine; Parkinsonian Disorders; Psychotic Disorders; Risperidone; Sexual Dysfunction, Physiological

We report a case of severe restless legs syndrome (RLS) that occurred as a side effect of olanzapine therapy. It was refractory to treatment with 2 mg of clonazepam and 3 mg ropinirole. There was partial relief with propoxyphene, however, it was stopped because of side effects. The symptoms disappeared once olanzapine was switched to another antipsychotic medication. Only two prior published reports associate olanzapine usage with development of RLS. In one report, low-dose benzodiazepines and ropinirole were associated with resolution of RLS symptoms stating dopamine depletion as the likely etiology. In our patient, however, RLS due to olanzapine was refractory to the trial of both high-dose benzodiazepine and ropinirole. This suggests that RLS occurring as a side effect of olanzapine therapy may have additional causative mechanisms beyond simple dopamine depletion as postulated before. High-dose narcotics, if tolerated, may be an alternative in such refractory cases.

Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Middle Aged; Olanzapine; Piperazines; Quinolones; Restless Legs Syndrome; Valproic Acid

This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions.. Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI) > or = 25 kg/m2 who had received olanzapine treatment in combination with nizatidine (n = 68), sibutramine (n = 42), or amantadine (n = 48). Individual patients were analyzed for categorical weight loss > or= 2 kg and weight gain > or = 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale.. Predictors/correlates of weight loss > or = 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain > or = 1 kg.. The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy.. This analysis was not a clinical trial and did not involve any medical intervention.

Topics: Adult; Amantadine; Appetite; Benzodiazepines; Bipolar Disorder; Cognition Disorders; Cyclobutanes; Drug Therapy, Combination; Feeding Behavior; Female; Humans; Male; Nizatidine; Olanzapine; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain; Weight Loss

There is a dearth of literature on patients erroneously diagnosed and treated for bipolar disorder.. The authors report a case of an adult with attention deficit hyperactivity disorder erroneously diagnosed and treated for bipolar disorder for 6 years. At that point, methylphenidate was initiated. The patient was judged to be a good treatment responder with improvements noted in the clinical global impressions severity scale. It was seen that the improvement was maintained at a 6-month follow-up.. The present case reflects the importance of careful differential diagnosis when evaluating for bipolar disorder.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Benzodiazepines; Bipolar Disorder; Central Nervous System Stimulants; Diagnostic and Statistical Manual of Mental Disorders; Diagnostic Errors; Drug Therapy, Combination; Follow-Up Studies; Humans; Interview, Psychological; Lithium Carbonate; Male; Methylphenidate; Military Personnel; Olanzapine; Treatment Outcome

Clarithromycin is a macrolide antibiotic widely used in children with respiratory infections. Mania is an extremely rare psychiatric side effect. A pediatric case of typical manic symptoms associated with clarithromycin-use and resembling those in adults is presented. It was notable that the patient had no genetic predisposition.

Topics: Anti-Bacterial Agents; Benzodiazepines; Bipolar Disorder; Child; Clarithromycin; Genetic Predisposition to Disease; Humans; Male; Olanzapine

Bipolar disorder has an associated economic burden due to its treatment, including medication and hospitalization costs as well as costs associated with treatment of comorbid conditions. This study compared healthcare costs in patients treated with a mood stabilizer and adjunctive aripiprazole versus adjunctive olanzapine, quetiapine, risperidone or ziprasidone.. A retrospective propensity score-matched cohort study was conducted in the LabRx integrated claims database from January 2003 to December 2006. Patients (18-65 years) with bipolar disorder and 180 days of pre-index enrolment without atypical treatment and 90 days post-index enrolment were eligible. Mood stabilizer therapy was initiated prior to index atypical prescription. Generalized gamma regressions were used to compare the total healthcare costs of adjunctive aripiprazole treatment and treatment with adjunctive olanzapine, quetiapine, risperidone or ziprasidone.. After controlling for differences in baseline characteristics and pre-index cost, psychiatric costs and subtotal psychiatric and general medical costs were higher for all adjunctive atypicals than adjunctive aripiprazole (p<0.001). Based on gamma regressions cost ratios, there was no significant difference in general medical costs between aripiprazole and ziprasidone, olanzapine, or quetiapine; risperidone general medical costs were 18% higher versus aripiprazole (p=0.041). Aripiprazole pharmacy costs were higher than quetiapine and risperidone (p<0.001) but not olanzapine or ziprasidone. Total healthcare costs were higher for ziprasidone, olanzapine, or risperidone (p<0.001) but not quetiapine.. Methodological restriction of patients to those newly initiated on an atypical antipsychotic and incomplete medication history limit the generalizability of the findings.. Adjunctive aripiprazole may have economic benefits over other atypicals in terms of lower psychiatric treatment costs than adjunctive olanzapine, quetiapine, risperidone or ziprasidone, and lower total healthcare costs than adjunctive olanzapine, risperidone or ziprasidone.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Costs and Cost Analysis; Dibenzothiazepines; Drug Therapy, Combination; Female; Health Care Costs; Humans; Male; Middle Aged; Mood Disorders; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risperidone; Thiazoles; Treatment Outcome; Young Adult

To compare the longer-term outcomes of pharmacological treatment of patients with a diagnosis of bipolar affective disorder currently suffering a manic or hypomanic episode prescribed olanzapine or non-olanzapine medication in naturalistic, clinical practice settings in Bosnia-Herzegovina, Slovakia, Slovenia, Turkey, Saudi Arabia and Egypt.. Prospective, observational, non-interventional study conducted over 9 months. Inpatients or outpatients who initiated or changed oral bipolar mania medication were grouped into (1) those prescribed olanzapine at baseline (n = 569) and (2) those not prescribed olanzapine (n = 325).. The change from baseline in the Clinical Global Impression Severity scale for bipolar disorder (CGI-BP-S), the rates of symptomatic response and remission (based on CGI-BP-S) and the frequency and nature of treatment-emergent adverse events. Analyses included (1) linear or logistic regression, with adjustment for confounders, based on the last observation carried forward and (2) weighted repeated measures models that adjusted for treatment switching and patient drop-out.. When results were adjusted for treatment switching and patient drop-out, patients prescribed olanzapine had significantly better CGI-BP-S scores (mean difference = -0.24; 95% confidence interval [CI] -0.33, -0.16; p < 0.001) and significantly greater odds of treatment response (odds ratio [OR] = 1.86; 95% CI 1.31, 2.65; p < 0.001) and symptom remission (OR = 1.65; 95% CI 1.18-2.32; p = 0.003) than those not prescribed olanzapine. The frequency of most adverse events decreased in both groups. Patients prescribed olanzapine had significantly greater weight gain from baseline (mean increase = 2.66 kg; 95% CI 2.35, 2.98) compared with those not prescribed olanzapine (mean increase = 1.85 kg; 95% CI 1.51, 2.19; p < 0.001).. Inclusion of olanzapine is of benefit for pharmacological treatment of patients with bipolar disorder. However, the favourable outcomes observed cannot be directly attributed to olanzapine alone because of the high prevalence of polypharmacy in the patient population.

Topics: Adult; Africa; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Europe; Europe, Eastern; Female; Humans; Long-Term Care; Male; Middle Aged; Middle East; Observation; Olanzapine; Outcome Assessment, Health Care; Prospective Studies; Treatment Outcome; Young Adult

This study compared the safety, tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular (IM) olanzapine or other IM antipsychotics for the treatment of acute agitation.. Patients (N = 2011) from 15 countries participated in this prospective, observational, non-interventional study. Inpatients requiring treatment with at least one IM injection of a short-acting antipsychotic were assessed at baseline and within 7 days after the first IM injection. Treatment groups comprised: (i) patients prescribed IM olanzapine at baseline; and (ii) patients prescribed any other IM antipsychotic medication at baseline. Outcome measures included: treatment-emergent adverse events, concomitant psychotropic medication and the time taken to switch to oral medication.. Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group (34.4% vs. 46.2%, p < 0.001). The most frequently reported adverse events in both groups were: sedation, Parkinsonism, disturbance in attention, akathisia, dystonia and orthostatic hypotension. Fewer patients in the IM olanzapine group used anticholinergics (13.9% vs. 42.5%, p < 0.001) or anxiolytics/hypnotics (47.6% vs. 51.6%, p = 0.023). Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group (median time = 46.5 vs. 48.0 h, p = 0.009).. These findings suggest that IM olanzapine may have a favourable impact on individual patients. However, the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone.

Topics: Acute Disease; Administration, Oral; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Restraint, Physical; Schizophrenia; Treatment Outcome; Young Adult

The aim of this study was to compare the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a randomised controlled trial (RCT) assessing the same treatments.. EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with the treatment of mania. Severity of mania and depression were assessed at baseline and 6 weeks using the YMRS and the 5-item version of the HAMD, respectively.. 621 patients were analysed (n=107 valproate, n=514 olanzapine). Both groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with greater mean improvements in the olanzapine compared with the valproate group. Olanzapine was associated with more weight gain and less gastrointestinal difficulties than valproate.. The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy seems to be more effective than valproate monotherapy in the treatment of acute mania.

Topics: Adult; Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Female; Gastrointestinal Diseases; Humans; Male; Olanzapine; Prospective Studies; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid; Weight Gain

The aim of this study was to estimate the following: (1) the number of acute mood events prevented by adjunctive quetiapine therapy, and the potential cost savings; (2) the number of acute mood event-associated hospitalizations avoided by using adjunctive quetiapine therapy, and the potential cost savings of this intervention; and (3) the economic value of adjunctive quetiapine therapy in the maintenance treatment of bipolar I disorder.. A Markov model was developed to simulate the transitions of newly stabilized adult patients with bipolar I disorder across 4 possible health states: euthymia, acute mania, acute depression, and discontinued/ no active therapy. Clinical data were obtained from 2 randomized, double-blind, Phase III trials of up to 2 years' duration (D1447C00126 and D1447C00127) that evaluated the efficacy and tolerability of quetiapine (versus placebo) when coadministered with lithium or valproate in increasing the time to recurrence of acute mood events in patients with bipolar I disorder. The model evaluated clinical and economic outcomes in 8 quarterly cycles (24 months). Outcome measures included the number of acute mood events, number of hospitalizations related to acute mood events, and their costs. Quality-adjusted life-years (QALYs) were calculated as a secondary outcome. The model was conducted from the perspective of the UK National Health Service, base year 2007.. In the model analysis, adjunctive quetiapine with lithium or valproate was associated with a 54% reduction in the occurrence of acute mood events, a 29% reduction in acute mood event-related hospitalization costs, and a 4% improvement in QALY gains, with 5% lower total direct costs than placebo + lithium/valproate. The incremental cost-effectiveness ratios (in year-2007 pound) were 506 per additional acute mood event avoided, 4261 per additional acute mood event-related hospitalization prevented, and -7453 per additional QALY gained. The sensitivity analyses indicated that these results were robust.. The results of this Markov model with a 2-year time horizon suggest that adjunctive quetiapine and mood-stabilizer therapy with lithium or valproate, compared with mood-stabilizer therapy alone in the maintenance treatment of patients with bipolar I disorder, were associated with fewer acute mood events, fewer acute mood event-related hospitalizations, and lower total costs, thereby improving patient mental health outcomes and minimizing impact on payer budgets, from the perspective of the UK National Health Service.

Topics: Affect; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Dibenzothiazepines; Double-Blind Method; Fluoxetine; Health Status; Humans; Markov Chains; Olanzapine; Quality-Adjusted Life Years; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Valproic Acid

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Dibenzothiazepines; Drug Approval; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Schizophrenia; Thiazoles; United States; United States Food and Drug Administration

To summarize the conceptual and operational definitions of treatment-resistant bipolar depression and to review the evidence-based therapeutic options.. Structured searches of PubMed, Index Medicus, Excerpta Medica and Psyclit conducted in December 2008.. Criteria for treatment resistance in bipolar depression are commonly based on concepts stemming from treatment resistance as defined for unipolar depression, an approach that proved to be inadequate. In fact, the addition of an ad hoc criterion based on lithium and other mood stabilizer unresponsiveness after reaching adequate plasma levels appears to be a patch that attempts to take into account the uniqueness of bipolar depression but fails to become operational. Recent data from randomized clinical trials of new anticonvulsants and second-generation antipsychotics should lead to the development of a modern definition of treatment-resistant bipolar depression, and specific therapeutic algorithms.. We suggest a redefinition of resistant bipolar I and II depression. We propose different degrees of severity within bipolar depression in a stepwise manner.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Resistance; Evidence-Based Practice; Fluoxetine; Humans; Lithium; Olanzapine; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

Topics: Adult; Antimanic Agents; Antineoplastic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Humans; Interferon alpha-2; Interferon-alpha; Male; Melanoma; Olanzapine; Recombinant Proteins; Skin Neoplasms

Diana is a 21-year-old student who lives with her parents. She had been enrolled in college but has taken a temporary leave of absence due to the instability of her bipolar disorder. Since being diagnosed at age 18, Diana's treatment team has been unable to find a medication regimen that would maintain her stability. She has had several breakthrough manic episodes that resulted in significant risky and inappropriate behaviors on campus. The cognitive, motivational, and energy limitations of depression left her unable to keep up with school requirements. Dr. Spiker, her regular psychiatrist, prescribed olanzapine Zyprexa 5 mg. Both Diana and Dr. Spiker are concerned about potential weight gain but consider this intervention necessary, as other medication trials have been unsuccessful.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Combined Modality Therapy; Cooperative Behavior; Empathy; Female; Humans; Interdisciplinary Communication; Menu Planning; Olanzapine; Patient Care Team; Self Efficacy; Social Support; Weight Gain; Young Adult

The effect of valproate on the steady-state plasma concentrations of olanzapine was investigated in 18 patients with bipolar or schizoaffective disorder. Additional valproate, at a dose ranging from 600 to 2000 mg/d, was administered for 4 weeks to patients stabilized on olanzapine (5-20 mg/d). During valproate coadministration, mean plasma olanzapine concentrations decreased significantly from 32.9 +/- 9.7 ng/mL at baseline to 27.4 +/- 9.8 ng/mL at week 2 (P = 0.02), and to 26.9 +/- 9.2 ng/mL at week 4 (P = 0.001). Smoking also decreased plasma olanzapine concentrations. Valproate coadministration with olanzapine was well tolerated and no patient showed a worsening of his or her psychopathological condition. These findings indicate that valproate, at doses of up to 2000 mg/d, is associated with a minimal, presumably not clinically significant, decrease in plasma olanzapine concentrations, possibly as a result of induction of olanzapine metabolism. New studies are needed to confirm that valproate could have mild inductive effects.

Topics: Adult; Aging; Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Psychotic Disorders; Smoking; Time Factors; Valproic Acid; Young Adult

Mixed depression (ie, co-occurrence of syndromal depression and subsyndromal mania/hypomania) is a common variant of bipolar depression. However, its treatment is much understudied. The aim of the study was to assess the efficacy of the antipsychotic and mood-stabilizing agent olanzapine and the efficacy of the combination of an antidepressant (fluoxetine) and olanzapine (olanzapine/fluoxetine combination; OFC) for the treatment of bipolar I mixed depression.. We carried out a post hoc analysis of an 8-week, double-blind trial of adult bipolar I depression treated with placebo (n = 355), olanzapine (5-20 mg/d; n = 351), or OFC (olanzapine/fluoxetine doses: 6/25, 6/50, 12/50 mg/d; n = 82). Studying mixed depression was not a previous goal of the double-blind trial. Subjects in the trial were diagnosed according to DSM-IV and were randomly assigned to treatment during the period June 2000 to December 2001. Mixed depression was defined as the co-occurrence of a major depressive episode and > or = 2 manic/hypomanic symptoms (ie, > or = 2 Young Mania Rating Scale [YMRS] items scoring > or = 2). Response was defined as a > or = 50% reduction in Montgomery-Asberg Depression Rating Scale score and < 2 concurrent manic/hypomanic symptoms. Switching to mania/hypomania was defined as a YMRS score > or = 15.. Frequency of mixed depression was 45.1% in the OFC arm, 49.3% in the olanzapine arm, and 46.8% in the placebo arm (P = .705). The most frequent manic/ hypomanic symptoms of mixed depression were irritability, reduced need for sleep, talkativeness, and racing thoughts. Response rates in patients with nonmixed depression versus patients with mixed depression were the following: in the OFC arm, 48.9% versus 43.2% (OR = 1.24; 95% CI, 0.51-2.98); in the olanzapine arm, 39.9% versus 26.6% (OR = 1.84; 95% CI, 1.17-2.90); in the placebo arm, 27.5% versus 16.3% (OR = 1.94; 95% CI, 1.15-3.28). Response rates in the samples of patients with mixed depression were the following: OFC versus olanzapine, OR = 2.00 (95% CI, 0.96-4.19); OFC versus placebo, OR = 3.91 (95% CI, 1.80-8.49); olanzapine versus placebo, OR = 1.95 (95% CI, 1.14-3.34). It was found that no baseline manic/hypomanic symptom of mixed depression predicted treatment response. A higher number of baseline concurrent manic/hypomanic symptoms predicted a lower response rate in the olanzapine and placebo arms, but not in the OFC arm. The rates of switching were the following: in the OFC arm, 8.5%; in the olanzapine arm, 6.8%; and in the placebo arm, 7.9% (P = .808). The rates of dropouts in patients with mixed depression versus patients with nonmixed depression were not significantly different within any of the treatment arms. The rates of dropouts in the samples of patients with mixed depression were the following: in the OFC arm, 29.7%; in the olanzapine arm, 53.8%; and in the placebo arm, 59.6% (olanzapine vs OFC: OR = 2.66; 95% CI, 1.23-5.75; placebo vs OFC: OR = 3.48; 95% CI, 1.61-7.54; placebo vs olanzapine: OR = 1.30; 95% CI, 0.84-2.01).. Olanzapine/fluoxetine combination may be an effective treatment for bipolar I mixed depression. Statistically, the efficacy of OFC was not significantly different from that of olanzapine, but inspection of the 95% CI showed a trend in favor of a possible superiority of OFC. Supporting the study findings are the similar efficacy of OFC in bipolar mixed depression independent of the number of concurrent manic/hypomanic symptoms, a lower dropout rate, and a similarly low switching rate compared to olanzapine. Contrary to other current limited evidence, an antidepressant (fluoxetine) showed efficacy and did not worsen bipolar mixed depression if combined with a mood-stabilizing agent (olanzapine).

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Comorbidity; Depressive Disorder, Major; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Olanzapine; Placebos; Randomized Controlled Trials as Topic; Risperidone; Treatment Outcome

The number-needed-to-treat (NNT) or the number-needed-to-harm (NNH) analysis was performed on olanzapine and comparators for all known controlled clinical studies of olanzapine for bipolar maintenance treatment or relapse prevention to assess safety and efficacy. Studies compared olanzapine (n = 225) and placebo (n = 136) for 12 months, olanzapine (n = 217) and lithium (n = 214) for 12 months, and olanzapine plus lithium or valproate (n = 72) and placebo plus lithium or valproate (n = 64) for 18 months. For prevention of all-cause treatment discontinuation, the NNT was 7 to 8. For 9 of 11 efficacy and disposition measures examined, beneficial outcomes were more common with olanzapine than placebo. Beneficial outcomes were more common with olanzapine than lithium for 7 measures and more common for olanzapine plus lithium or valproate than placebo plus lithium or valproate for 1 measure. The NNHs of 5 to 8 for a weight gain of 7% or higher and 10 to 11 for the increase in body mass index category to overweight or obese during maintenance treatment indicated that these outcomes were more common for olanzapine or olanzapine plus mood stabilizers than for the comparators. All efficacy and disposition measures showing significant differences between groups for 12 to 18 months have NNTs favoring olanzapine or olanzapine plus lithium or valproate over placebo, lithium, or placebo plus lithium or valproate. However, the NNHs favor these comparators for avoidance of weight gain and of increase in body mass index category to overweight or obese. Clinicians should consider these and other potential benefits and risks in using maintenance treatments for patients with a bipolar disorder.

Topics: Benzodiazepines; Bipolar Disorder; Epidemiologic Measurements; Humans; Olanzapine; Randomized Controlled Trials as Topic; Sample Size; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brazil; Combined Modality Therapy; Electroconvulsive Therapy; Humans; Male; Olanzapine; Treatment Outcome

Topics: Ambulatory Care; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Humans; Olanzapine; Prospective Studies; Randomized Controlled Trials as Topic; Secondary Prevention; Valproic Acid

Topics: Adjuvants, Anesthesia; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine

Promoters of new medications often argue that using newer drug can reduce use of non-drug medical services and therefore reduce total healthcare spending. This cost-offset argument is plausible both in theory and in practice, but rigorous research on specific drugs or drug categories is needed to make targeted and efficient policy and management decisions.. I examined the drug-offset hypothesis for bipolar disorder, an important yet under-studied clinical condition where effective medication treatments can service as substitutes for non-drug medical treatments. I compared two first line long-term treatments, a new atypical antipsychotic medication, olanzapine, and a traditional mood stabilizer, lithium.. I used private sector insurance claims data collected from a nationally representative sample of U.S. health plans between January 1998 and December 2001. I first selected a cohort of patients with bipolar disorder who were continuously enrolled for at least two years. I then used a propensity-score method to match individuals taking each drug on observed variables that are known to affect medication choices. The central challenge for estimation is that drug treatments are not randomly assigned among patients with bipolar disorder. To identify a causal link between choice of drugs and non-drug medical spending, I employed three different advanced econometrics techniques to assess the robustness of findings; namely interrupted time series, differencing strategies, and an instrumental variables approach.. I found that compared to similar lithium users, olanzapine users spent approximately $330 more on monthly average non-drug medical services during the first year after initiation of drug treatment. The higher spending for olanzapine users was accounted for by both higher rates of re-hospitalization and more outpatient visits. In addition, olanzapine cost $153 per month while lithium cost $16 per month. Including the direct cost of the drugs, compared to similar patients taking lithium, patients with bipolar disorder taking olanzapine spent $5,600 more annually on health care services.. These findings do not support the hypothesis that new drugs "pay for themselves" by reducing the need for other health care services in the case of olanzpine for bipolar disorder. This does not mean that the new drug is not "cost-effective" because increased "benefits" associated with the drug in terms of the improved quality of life may be worth the increased costs. However the findings do indicate that "cost-offsets" must be measured and not taken for granted. Incorporating such drug-offset evidence into policy and business decisions can facilitate appropriate clinical practices and improve efficiency of resource allocation. The methods used in this study to test for cost-offsets can be applied to other clinical areas and drug classes.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost Savings; Female; Humans; Insurance Claim Review; Long-Term Care; Male; Olanzapine; Treatment Outcome

Leptin dysregulation has been implicated in the body weight gain and metabolic dysfunction observed with the second generation antipsychotic drugs (SGAD) olanzapine and clozapine.. This study quantified the frequency of subjects with abnormal correlation between leptin and the body mass index controlling for gender (defined as being out of the upper or lower 95% confidence interval in the regression line when combining each group with the drug-free subjects) after prolonged treatment with olanzapine (n=126), clozapine (n=62), first generation antiypsychotics (n=91), other SGAD (n=22), other psychotropic drugs (n=65) and drug-free subjects (n=229).. None of the analysis was significant (p>0.05). In fact, in 17 out of 20 comparisons, the drug-free group had numerically higher frequencies of outliers than the corresponding treatment group. There were 28 outliers (4.7% of the total sample). In agreement with previous studies, cross-sectional analysis did not report gross alterations in serum leptin levels during olanzapine or clozapine administration.. Longitudinal studies should focus on leptin regulation early on treatment, on the frequency of abnormal leptin receptor sensitivity and/or specific polymorphisms in the leptin allele and on several confounding factors in order to design personalized preventive and therapeutic measures.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Clozapine; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Male; Mental Disorders; Middle Aged; Olanzapine; Outliers, DRG; Receptors, Leptin; Schizophrenia; Sex Factors; Weight Gain

Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Hepatolenticular Degeneration; Humans; Lithium Chloride; Male; Olanzapine; Psychiatric Status Rating Scales; Young Adult

Bipolar patients have increased prevalence rates of overweight and obesity compared with the general population. Recent increases in the use of atypical antipsychotics and combination therapies have led to growing concern about obesity and metabolic disturbances. We therefore evaluated weight change and its correlates during the treatment of acute mania in a closed-ward hospital setting.. We evaluated weight change over 4 weeks in 179 consecutive patients with bipolar I disorder presenting with acute manic symptoms.. Overall weight change was +2.7+/-3.0 kg (+4.6+/-5.2%). Whereas 24.6% of patients were obese at baseline, 36.3% were obese after 4 weeks. Duration of illness was correlated with weight change, but its effect was not robust. Baseline weight/BMI, sex, age of onset, and history of previous medication were not significantly correlated with weight changes. Patients prescribed olanzapine plus valproate showed the largest increase in weight (3.8+/-2.9 kg). Overall, patients on any kind of atypical antipsychotics showed greater weight gain than those on typical antipsychotics or without antipsychotics. Combination treatment with antipsychotics and mood stabilizer resulted in greater weight gain than monotherapy with an antipsychotic or mood stabilizer.. The short-term assessment (4 weeks) of weight change and the lack of variables previously reported to be related to weight gain, such as number of depressive episodes, warrant caution in the interpretation of our results.. Even during short period of acute treatment, bipolar patients showed significant weight gain and became obese in a closed-ward setting. Clinicians prescribing combination therapies should pay more attention to weight gain and obesity.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Body Weight; Drug Administration Schedule; Drug Therapy, Combination; Female; Haloperidol; Hospitalization; Humans; Lithium Carbonate; Male; Obesity; Olanzapine; Risperidone; Smoking; Valproic Acid

To evaluate the 12-week outcomes (effectiveness, tolerability, and patterns of medication use) of olanzapine (either in antimanic monotherapy or in combination with other antipsychotics, anticonvulsants, and/or lithium) in patients with bipolar mania or mixed mania.. EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 24-month prospective observational study of in- and outpatients with acute mania/mixed mania conducted in 14 European countries. Primary outcome measures included Clinical Global Impressions-Bipolar Disorder scale (overall, mania, and depression); 5-item Hamilton Depression Rating Scale; and Young Mania Rating Scale. Tolerability measures included a questionnaire to assess patients' symptomatic complaints.. Overall, 2004 patients received olanzapine (olanzapine monotherapy, n=673; olanzapine combination, n=1331). Concomitant therapy with antidepressants and/or anxiolytics was possible in both groups. The countries significantly differed in the use of olanzapine monotherapy versus olanzapine combination (p<.0001). Baseline-to-endpoint changes on the CGI-BP subscales, YMRS, and HAMD-5 were significant within both treatment groups (p<.0001). Olanzapine monotherapy was generally better tolerated than olanzapine combination, particularly with regard to sedation (12% vs 17%; p<.001), tremor (2% vs 5%; p<.001), and akathisia (3% vs 6%; p<.001).. The acute-phase EMBLEM results suggest that in naturalistic settings, olanzapine (both as monotherapy and combination) may be effective in treating patients with bipolar mania. The use of olanzapine monotherapy or combination varies significantly across countries, but combination is generally the rule, rather than the exception.

Topics: Acute Disease; Adult; Ambulatory Care; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cross-Cultural Comparison; Dose-Response Relationship, Drug; Drug Therapy, Combination; Europe; Female; Follow-Up Studies; Humans; Lithium Carbonate; Longitudinal Studies; Male; Middle Aged; Olanzapine; Patient Admission; Prospective Studies; Psychiatric Status Rating Scales; Treatment Outcome

Current definitions of remission for mania and bipolar depression are convention-rather than empirically-based, and their clinical salience is unclear, as few studies have attempted to calibrate them against objective clinical criteria. This study aimed to determine equivalence scores on two widely used clinical rating scales, the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS), that corresponded with an objective global clinical measure of remission in bipolar disorder patients.. Data from four pharmacological randomised controlled trials in bipolar I disorder were analysed. Two trials were conducted for bipolar depression (N=410 and 833), and two for manic or mixed episodes (N=136 and 110). In this study, a Clinical Global Impression-Bipolar Version (CGI-BP) severity score of 1 (normal, not at all ill) was used as the primary comparative measure of remission. The mean total YMRS and MADRS scores in the mania and depression studies, respectively, that corresponded with a CGI-BP severity score of 1 were determined.. The mean YMRS score that corresponded with a CGI-BP severity score of 1 was <4 in both trials (2.6 and 3.0, respectively), and the mean corresponding MADRS score was <5 (4.1 and 4.6, respectively).. Utilising a psychometric definition of remission.. This study suggests that a cut-off score of <5 on the MADRS and <4 on the YMRS approximates a CGI-BP definition of complete remission. Although lower than conventional cut-off scores, these perhaps better represent clinical reality and patient expectations. In the context of clinical trials, study end-points may be more difficult to reach with lower cut-offs, but the outcomes achieved are more likely to be clinically meaningful.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Fluoxetine; Follow-Up Studies; Humans; Lamotrigine; Olanzapine; Personality Assessment; Psychiatric Status Rating Scales; Psychometrics; Randomized Controlled Trials as Topic; Reproducibility of Results; Treatment Outcome; Triazines

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Interactions; Drug Therapy, Combination; Humans; Lithium Compounds; Male; Middle Aged; Olanzapine; Sleep Stages; Somnambulism

The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related.. To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5-20 mg/day), or patients with schizophrenia who received olanzapine (N = 172, 10-20 mg/day), we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW) methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i) stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii) stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses.. While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect.". While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Probability; Psychotic Disorders; Randomized Controlled Trials as Topic; Research Design; Risperidone; Schizophrenia; Selection Bias; Treatment Outcome

The dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1) genes have been related to schizophrenia (SZ) and bipolar disorder (BP) by several whole-genome linkage and associations studies. Few expression studies in post-mortem brains have also reported a lower or a higher expression of DTNBP1 and NRG1, respectively, in SZ. Since the difficulty to access post-mortem brains, we evaluated RNA expression of DTNBP1 and NRG1 in immortalized lymphocytes of SZ patients and unrelated-family controls. An antipsychotic stimulation was also used to challenge the genetic background of the subjects and enhance differential expression. Immortalized lymphocytes of twelve SZ and twelve controls were grown individually in the presence or not of the antipsychotic olanzapine (Zyprexa; EliLilly). RNA was extracted and pooled in four groups of three SZ and four groups of three controls, and used to probe Agilent 18K microchips. Mean gene expression values were contrasted between SZ and control groups using a T-test. For DTNBP1, RNA expression was lower in SZ than in controls before (-28%; p=0.02) and after (-30%; p=0.01) olanzapine stimulation. Similarly, NRG1 GGF2 isoform showed a lower expression in SZ before (-29%; p=0.04) and after (-33%; p=0.02) olanzapine stimulation. In contrast, NRG1 GGF isoform showed no significant difference between SZ and controls (-7%; p=0.61, +3%; p=0.86, respectively), but was slightly repressed by olanzapine in controls (-8%; p=0.008) but not in SZ (+1%; p=0.91). These results are in agreement with those observed in post-mortem brain when the isoforms involved are considered.

Topics: Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carrier Proteins; Cells, Cultured; Control Groups; Dysbindin; Dystrophin-Associated Proteins; Female; Gene Expression; Humans; Lymphocytes; Middle Aged; Nerve Tissue Proteins; Neuregulin-1; Olanzapine; Pharmacogenetics; Protein Isoforms; RNA; Schizophrenia

Topics: Adolescent; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Fever; Fructose; Humans; Olanzapine; Rhabdomyolysis; Topiramate

Photo-onycholysis associated with drugs is an uncommon disorder. We report the case of a woman who developed photo-onycholysis on multiple nails after uptake of olanzapine. Substitution of olanzapine with aripiprazole further exacerbated the problem. The possible mechanisms of photo-onycholysis development by modern atypical antipsychotics, modulating dopamine receptors, are discussed.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Erythema; Female; Humans; Middle Aged; Olanzapine; Onycholysis; Photosensitivity Disorders; Piperazines; Quinolones

There are few independent studies comparing atypical or second-generation antipsychotics (SGAs).. To compare the patterns of use and discontinuation of commonly used SGAs.. Retrospective review of 11,250 case records (2002-2005) of all mental health care contacts in a discrete geographical setting in Scotland. Patterns of use, mean dose, psychotropic co-prescription, duration of treatment, discontinuation rates, and admission rates were examined for amisulpride, clozapine, olanzapine, quetiapine, and risperidone.. Clozapine had a significantly lower discontinuation rate in individuals with schizophrenia, compared to the other 4 SGAs. Off-license prescribing and polypharmacy were common.. SGAs are variously used for schizophrenia and mood disorder and have heterogeneous outcomes, with clozapine being most effective in this study. Independent observational studies such as this complement randomized controlled trials.

Topics: Adult; Aged; Amisulpride; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Medical Records; Middle Aged; Olanzapine; Patient Admission; Polypharmacy; Practice Patterns, Physicians'; Quetiapine Fumarate; Research Design; Retrospective Studies; Risperidone; Schizophrenia; Scotland; Sulpiride

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine

Antipsychotic prescription in pregnancy is a complex topic and raises a great deal of anxiety in professionals. There is limited data about atypical antipsychotic prescription in pregnancy and its possible teratogenicity. There are no randomised controlled studies of atypical antipsychotic use in pregnancy due to obvious reasons of ethical issues. We present two cases where a choice had to be made as to whether to prescribe Olanzapine during pregnancy, with different results.

Topics: Abnormalities, Drug-Induced; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorpromazine; Female; Hand Deformities, Congenital; Humans; Infant, Newborn; Lithium Carbonate; Olanzapine; Pregnancy; Pregnancy Complications; Risk Assessment; Schizophrenia, Disorganized

Topics: Acute Disease; Antipsychotic Agents; Atrial Fibrillation; Benzodiazepines; Bipolar Disorder; Electrocardiography; Humans; Male; Middle Aged; Olanzapine

This is the first study in bipolar patients, aimed to evaluate possible roles of the drugs, [atypical antipsychotics (AA) and mood stabilizers (MS)], inducing metabolic syndrome (MetS).. 125 bipolar patients, diagnosed according to the DSM IV, were assessed cross-sectionally for MetS according to the National Cholesterol Educational Program criteria (NCEP ATP III). Patients included in the study were required to receive medications (AAs: quetiapine, risperidone and olanzapine, and MSs: Lithium, Sodium Valproate, Carbamazepine, Lamotrigine) for at least 3 months. Patients are divided into three groups as only AA users, AA+MS users and only MS users.. Of the patients, 32% were MetS, a proportion higher than normal population and similar as previous studies in bipolar patients. AA taking patients had significantly higher MetS rates than the others (chi(2)=10.47 df=2 p=0.005). Also, AA taking patients had significantly higher MetS rates than MS taking patients (chi(2)=8.86 df=1 p=0.003). There was no significant difference among quetiapine, olanzapine, risperidone usage for MetS prevalences (chi(2)=0.38 df=2 p=0.82).. AA taking bipolar patients had higher MetS rates. Despite already existing data on MetS and antipsychotics, this cross-sectional study is the first research, discusses AAs and MSs for inducing MetS in bipolar disorder. Prospectively designed researches should be conducted for further clarification of the role of these drugs in MetS.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Mass Index; Carbamazepine; Cross-Sectional Studies; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Lamotrigine; Lithium Carbonate; Male; Metabolic Syndrome; Middle Aged; Olanzapine; Prevalence; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Triazines; Valproic Acid

An orally disintegrating tablet formulation of olanzapine (ODT olanzapine) is designed to dissolve rapidly upon contact with saliva. We describe a manic patient who has an esophageal stricture and chronic pharyngitis, two conditions that impede the swallowing of medications. She was successfully treated for her mania with this orally disintegrating formulation. This case report shows that ODT olanzapine may be useful in the psychiatric management of manic and other patients for whom olanzapine is appropriate, and who have an underlying medical condition that impedes swallowing oral medications.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chronic Disease; Esophageal Stenosis; Female; Humans; Olanzapine; Pharyngitis

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Controlled Clinical Trials as Topic; Depression; Fructose; Humans; Lamotrigine; Lithium Compounds; Neuroprotective Agents; Olanzapine; Topiramate; Triazines

The authors describe three patients with foreign accent syndrome during psychotic episodes which resolve with improvement of psychotic symptoms. Psychotic symptoms were worse during the times patients had foreign accents, suggesting a relationship between the presence of the accent and the severity of the psychosis.

Topics: Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Electroencephalography; Female; Humans; Language; Lithium Carbonate; Magnetic Resonance Imaging; Male; Middle Aged; Olanzapine; Positron-Emission Tomography; Psychiatric Status Rating Scales; Psychotic Disorders; Risperidone; Schizophrenic Psychology; Tomography, Emission-Computed, Single-Photon; Valproic Acid; Verbal Behavior

This study compared the relative risk for hospitalization of patients with bipolar and manic disorders receiving atypical and typical antipsychotics.. This retrospective study was based on administrative claims data extracted from the PharMetrics database during 1999 through 2003. Comparisons were made among atypical antipsychotics (risperidone, olanzapine, quetiapine or ziprasidone), as well as between each of these versus a combined group of the leading typical antipsychotics. Relative risk for hospitalization was estimated with Cox proportional regression, which adjusted for differences in patient characteristics.. Risperidone and olanzapine demonstrated higher risks for hospitalization than quetiapine [hazard ratio (HR) 1.19, p < 0.05 for both], translating into higher annual mental health inpatient charges of $260 per patient. Risperidone and olanzapine also showed higher estimated risks than ziprasidone, which approached the p < 0.05 threshold. Differences between each of the atypicals and the combined typicals were not significant. Patients with putative rapid cycling had a threefold greater risk for hospitalization than other patients with bipolar disorder. In these patients, comparisons among atypical antipsychotics showed that risperidone had a significantly higher hospitalization risk than olanzapine (HR 3.31, p < 0.05), resulting in higher annual mental health inpatient charges of $4,930 per patient.. In the treatment of bipolar and manic disorders, risperidone and olanzapine were associated with a higher risk for hospitalization than quetiapine, and possibly ziprasidone. In the treatment of putative rapid cyclers, olanzapine was associated with a lower risk for hospitalization than risperidone.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Therapy; Female; Hospitalization; Humans; Male; Olanzapine; Piperazines; Quetiapine Fumarate; Risk Factors; Risperidone; Thiazoles

The objective of this study was to evaluate effectiveness of commonly used prophylactic treatments for bipolar disorder in a naturalistic setting and to explore factors associated with treatment response.. We reviewed charts of 120 patients with a confirmed diagnosis of bipolar I or bipolar II disorder. The sample consisted of 37 males and 83 females, in the age range of 20 to 81 years (mean age 45+/-14 years), treated at an outpatient psychiatry program in a teaching hospital. In contrast to controlled clinical trials, we did not exclude subjects with co-morbid conditions and/or substance abuse. Treatment outcome was evaluated using a scale for retrospective assessment of prophylactic treatment response. The scale rates the degree of improvement in the course of treatment weighted by the likelihood of response being attributable to the treatment. The inter-reliability of the assessments was good with concordance of ratings of 90% and weighted kappa of 0.8.. Rates of full response to individual mood stabilizers were: lithium 30%, carbamazepine 0%, valproate 13%, lamotrigine 11%, and olanzapine 25%. Lithium responders were more likely to be bipolar II, and had a typically episodic course of illness with earlier onset in comparison with non-responders. Responders to valproate had higher rates of psychosis.. Data were obtained by chart reviews.. Less than one-third of patients treated with lithium achieved remission; the effectiveness of other treatments in this naturalistic sample was even lower.

Topics: Adult; Aged; Aged, 80 and over; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Female; Humans; Lamotrigine; Lithium Carbonate; Male; Middle Aged; Observation; Observer Variation; Olanzapine; Treatment Outcome; Triazines; Valproic Acid

To study the prescribing practices of atypical antipsychotic drugs in French psychiatric hospitals.. A 1-day cross-sectional observational survey was performed in seven psychiatric hospitals to study prescribing practices of the four atypical antipsychotics (AAP) marketed in France. These hospitals are members of the PIC network, a pharmacists' working group based in southwestern France.. Type and dosages of prescribed atypical antipsychotics, indication and concomitant prescriptions.. The study included 1475 adult inpatients' prescriptions with an antipsychotic drug; 647 prescriptions included an AAP with risperidone and olanzapine accounting for about 70% cases. AAP prescriptions concerned psychotic patients in 65% of cases. Patients receiving an AAP in this indication were more likely to be male, were younger, and received higher daily doses than patients treated for other troubles. They were also more likely to receive associated neuroleptic and anticholinergic antiparkinsonian agents. There were 59 prescriptions (9.1%) for bipolar disorders. Clozapine wasn't used in this indication. In 76.3% of cases, mood stabilizers were associated to the AAP prescribed in this indication.. This observational survey underlines the significant place taken by AAP for the treatment of psychiatric diseases in hospital prescribing practices. They show usage patterns of these drugs: dose, indications and concomitant medications, in line or not with current recommendations and reference guidelines. In bipolar disorders, AAPs seem more likely to be associated to an ongoing therapy using mood stabilizer than to replace it.

Topics: Adult; Age Factors; Amisulpride; Antimanic Agents; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; France; Hospitals, Psychiatric; Humans; Male; Mental Disorders; Middle Aged; Olanzapine; Practice Patterns, Physicians'; Psychotic Disorders; Risperidone; Sex Factors; Sulpiride

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Edema; Electrolytes; Female; Foot Diseases; Humans; Olanzapine; Risperidone

The changes in antioxidant-oxidant balance play important roles in the pathophysiology of neuropsychiatric conditions. Bipolar disorder (BD) is a psychiatric condition with recurrent mood disturbances. This study evaluates the effects of treatment with lithium, alone or in combination with antipsychotic olanzapine, on oxidant-antioxidant status and atherogenic character in patients with BD. The blood samples from 15 patients were tested before the treatment (pre-treatment phase) and at the ends of two consecutive treatment periods: period I, treatment with lithium and an antipsychotic drug, olanzapine (first 6 months) and period II, treatment with only lithium (6 months following period I). We measured serum atherogenic lipids (total cholesterol, triglycerides, and LDL-cholesterol), plasma lipid peroxides (thiobarbituric acid-reactive substances), antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) in neutrophils and lymphocytes, and total antioxidant status in plasma. Compared with pre-treatment phase, the lipid parameters were increased with each treatment; especially, LDL-cholesterol was significantly increased only with lithium treatment. These findings alert to be cautious about use of lithium in patients with atherogenic conditions. Moreover, plasma lipid peroxides were decreased significantly after the combination therapy and further decreased with lithium treatment. Antioxidant enzyme activities in lymphocytes were decreased after both types of treatment. Importantly, plasma total antioxidant status was increased only with lithium treatment. Thus, treatment with lithium alone decreases already up-set oxidant status in BD. In conclusion, the combination therapy with olanzapine is better in terms of atherogenic profile, while lithium alone produces better antioxidant status in patients with BD.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Middle Aged; Olanzapine; Oxidative Stress; Thiobarbituric Acid Reactive Substances

The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination.. Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed. The Montgomery-Asberg Depression Rating Scale measured depressive symptoms. Multiple analytic methods were applied, including traditional (mean differences) analysis, pattern analysis, survival analysis of sustained response, mixed-effects regression, and area-under-the-curve analysis.. Traditional analysis showed significantly greater improvement in depression scores at week 1 for olanzapine/fluoxetine combination versus placebo (-9.55 versus -5.08, p < 0.001) and for olanzapine versus placebo (-8.31 versus -5.08, p < 0.001). Pattern analysis revealed olanzapine/fluoxetine combination had a significantly greater percentage of early persistent responders than placebo or olanzapine (32.4% versus 12.7%, p < 0.001; and 18.3%, p < 0.05, respectively). Survival analysis showed a significantly shorter time to sustained response for the combination versus placebo (p < 0.001), for olanzapine versus placebo (p = 0.04), and for the combination versus olanzapine (p = 0.03). Mixed-effects regression analysis revealed a significant therapy-by-time interaction (p < 0.001). Early area-under-the-curve analysis revealed a significantly greater percentage of improvement for the combination versus placebo (26.7% versus 13.9%, p < 0.001) and for olanzapine versus placebo (22.0% versus 13.9%, p < 0.001).. Based on consistent results from related methods of measuring onset, olanzapine/fluoxetine combination demonstrated rapid onset of antidepressant effect (within 7 days) compared to placebo that was sustained over 8 weeks of treatment in a sample of BD patients. Using multiple statistical techniques may help profile a drug's onset of effect.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Olanzapine; Randomized Controlled Trials as Topic; Regression Analysis; Survival Analysis; Treatment Outcome

Topics: Adolescent; Age Factors; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Obesity; Olanzapine; Psychology, Adolescent; Randomized Controlled Trials as Topic; Risk Assessment; Weight Gain

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Humans; Hyperlipidemias; Male; Middle Aged; Olanzapine; Quetiapine Fumarate

Atypical antipsychotics are playing an increasing role in the treatment of bipolar disorder. The objective of this study was to assess the medication treatment patterns and costs associated with different atypical antipsychotics.. PharMetrics Integrated Database for medical and pharmacy claims was used to assess medication patterns and healthcare costs associated with atypical antipsychotics in the treatment of bipolar disorder. Patients who initiated on olanzapine, risperidone, quetiapine or ziprasidone as monotherapy or in combination with other bipolar medications between 01/2003 and 01/2004 were followed for 1 year. Pair-wise group comparisons were made between olanzapine and other atypical antipsychotics using Wilcoxon without adjustment, log linear regression model with adjustment, and propensity score-adjusted bootstrapping methods.. Among 1516 patients with bipolar disorder, olanzapine (n = 507, 51%) was significantly (p < 0.01) more likely to be initiated as the mono-bipolar medication than risperidone (n = 424, 40%), quetiapine (n = 463, 36%) or ziprasidone (n = 122, 25%). Post-initiation, olanzapine was used as the mono-bipolar medication for significantly (p < 0.01) more days (73.4) than risperidone (52.9), quetiapine (56.2) and ziprasidone (36.6). Annual healthcare costs incurred by patients with bipolar disorder varied from $14,216 for risperidone, $15,208 for olanzapine, $18,087 for quetiapine to $18,729 for ziprasidone treatments. No statistically significant differences in the annual healthcare costs were observed between olanzapine and risperidone treatments. Statistically significant differences between olanzapine and quetiapine were observed in two of the three models compared (p < 0.01, Wilcoxon; p = 0.024, log linear; p = 0.390, propensity score-adjusted bootstrapping) and between olanzapine and ziprasidone in one of the three models (p < 0.01, Wilcoxon; p = 0.068, log linear; p = 0.394, propensity score-adjusted bootstrapping).. Those arising from the data source and nature of retrospective assessments. Potential bias may also exist due to the presence of confounding factors and unobserved conditions and characteristics. As such, results of this study need to be considered in the context of its limitations and generalizability should be reserved to similar patient populations.. Antipsychotic medication use patterns were statistically significantly different among atypical antipsychotics in the usual treatment of bipolar disorder. Olanzapine appears to be more likely used as a monobipolar medication compared with risperidone, quetiapine, and ziprasidone. The annual healthcare costs associated with the treatment of bipolar disorder by olanzapine and risperidone were similar, and the costs of these treatments were lower than with quetiapine or ziprasidone.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Costs; Drug Utilization Review; Female; Humans; Male; Middle Aged; Olanzapine

Medication nonadherence is a significant problem among patients with bipolar disorder.. To compare adherence and persistence among patients with bipolar disorder initiated on antipsychotics in a state Medicaid system over a 12 month follow-up period.. Claims data for patients with bipolar disorder from a de-identified Medicaid database were examined. Patients were classified into 4 monotherapy treatment groups (risperidone, olanzapine, quetiapine, or typical antipsychotic) based on the first prescription filled between January 1, 1999, and December 31, 2001. Adherence and persistence were analyzed over a 12 month follow-up period. Adherence was measured using the Medication Possession Ratio (MPR). Persistence was defined as the total number of days from the initiation of treatment to therapy modification (ie, discontinuation, switching, or combination with another antipsychotic). Adjustment for confounding variables was undertaken using ordinary least-squares and Cox proportional hazard regression modeling.. The mean MPRs were 0.68 for risperidone (n = 231), 0.68 for olanzapine (n = 283), 0.71 for quetiapine (n = 106), and 0.46 for typical antipsychotics (n = 205). Patients initiated on typical antipsychotics were 23.6% less adherent than patients initiated on risperidone (p < 0.001). Mean persistence (days) was 194.8 for risperidone, 200.9 for olanzapine, 219.8 for quetiapine, and 179.2 for typical antipsychotics. Extended Cox regression modeling indicated no significant differences between antipsychotics in hazards of therapy modification within 250 days of initiation. However, patients initiated on typical antipsychotics were 5.2 times more likely to modify therapy compared with those initiated on risperidone after 250 days of antipsychotic therapy (p < 0.001).. Adherence and persistence were similar between atypical antipsychotic groups. The typical antipsychotic group, however, demonstrated lower adherence and a greater likelihood of patients modifying therapy compared with the risperidone cohort.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Databases, Factual; Dibenzothiazepines; Female; Follow-Up Studies; Haloperidol; Humans; Male; Medicaid; Middle Aged; Olanzapine; Patient Compliance; Phenothiazines; Proportional Hazards Models; Quetiapine Fumarate; Retrospective Studies; Risperidone

For patients with bipolar disorder in urgent situations, psychiatric and nonpsychiatric clinicians should employ practical approaches to achieve optimum outcomes and ensure safe and rapid reduction of symptoms, such as considering the treatment setting, clinician-patient relationship, and the severity of the patient's symptoms. Because biological, psychological, and social factors affect both the development and the treatment of acute bipolar states, treatment should address each factor to manage the illness.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Emergency Services, Psychiatric; Humans; Impulsive Behavior; Injections, Intramuscular; Olanzapine; Piperazines; Practice Guidelines as Topic; Quinolones; Risperidone; Suicide, Attempted; Thiazoles; Time Factors

Patients with bipolar disorder (BD) on long-term maintenance treatment represent a clinical population with peculiar characteristics, for which available equations to estimate resting energy expenditure (REE) are not suitable. The aim of this study was to measure REE by means of indirect calorimetry in bipolar patients on maintenance treatment and in controls, and to estimate the agreement between measured and predicted REE in both groups.. Patients diagnosed with BD I and healthy controls were assessed for height, weight and body mass index (BMI). Predicted REE was calculated using Harris-Benedict, Schofield, Recommended Nutrients Assumption Levels (LARN), and OUR equations; measurements of REE were performed using a portable indirect calorimeter.. Results for our sample show the most commonly used formulas give a systematic overestimation of REE with respect to measured basal metabolic rate in the patient group. The mean bias was considerably greater for bipolar subjects than for controls.. These results suggest that patients with severe mental illness on long-term psychopharmacologic treatment may have reduced basal energy expenditure that may be a cause of weight gain.

Topics: Adolescent; Adult; Age Factors; Algorithms; Antipsychotic Agents; Basal Metabolism; Benzodiazepines; Bipolar Disorder; Body Height; Body Weight; Calorimetry, Indirect; Energy Metabolism; Female; Humans; Male; Middle Aged; Models, Biological; Nutritional Status; Olanzapine; Rest; Sex Factors

A 25-year-old woman was separated for 6 weeks on account of her suicidal and chaotic behaviour occurring within the framework of a first manic episode. Her response to medication (olanzapine 20 mg, clorazepate 50 mg and lithium (serum level 0.9 mmol/l)) was inadequate. After only one ect treatment her condition had improved to such an extent that she no longer needed to be isolated. After about 4 weeks her mental condition was reasonably good; her medication consisted only of 10 mg of olanzapine and she could be transferred to out-patient care. ect can bring about rapid improvement in patients with therapy-resistant manic symptoms.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clorazepate Dipotassium; Electroconvulsive Therapy; Female; Humans; Olanzapine; Treatment Outcome

This prospective observational study examined the outcomes associated with the treatment of bipolar mania in clinical practice settings in a diverse range of countries: Bosnia, Slovenia, Slovakia, Egypt, Saudi Arabia and Turkey. Particular emphasis was placed on investigating outcomes associated with treatment regimens including and excluding the atypical antipsychotic olanzapine.. In- and outpatients initiating or changing oral medication for the treatment of bipolar mania were grouped into two treatment cohorts: (1) olanzapine (N=569), and (2) non-olanzapine (N=325). Clinical outcome measures included change in Clinical Global Impressions-Bipolar Version Severity of Illness scale (CGI-BP), Young Mania Rating Scale (YMRS) and Hamilton Depression Rating scale- 5 item (HAMD-5) scores, and response and remission rates. Outcomes were analysed by conventional linear or logistic regression, adjusted for potential confounders, using last observation carried forward (LOCF) at endpoint, and a marginal structural model (MSM) approach to account for treatment switching. Results from the 12-week acute phase are presented.. Clinical improvements were observed in both cohorts. While no marked differences were apparent between the groups in adjusted mean baseline to LOCF endpoint change, longitudinal analysis of these variables using MSM averaged over all visits indicated greater improvements in the olanzapine versus non-olanzapine cohort in CGI-BP Overall (-0.26, p<0.001), CGI-BP Mania (-0.19, p<0.001), CGI-BP Depression (-0.10, p=0.003), CGI Psychosis (-0.14, p=0.001), YMRS (-1.70, p<0.001), and HAMD-5 (-0.40, p<0.001) scores.. Inclusion of olanzapine after initiating or switching treatment for bipolar mania appeared to be beneficial during treatment in terms of symptom improvement.

Topics: Acute Disease; Administration, Oral; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cohort Studies; Cross-Cultural Comparison; Drug Therapy, Combination; Drug Utilization; Female; Humans; Long-Term Care; Male; Middle Aged; Olanzapine; Personality Inventory; Prospective Studies; Psychiatric Status Rating Scales; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diabetes, Gestational; Female; Humans; Olanzapine; Pregnancy; Pregnancy Complications; Weight Gain

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Electroconvulsive Therapy; Humans; Lithium; Male; Olanzapine; Psychotic Disorders; Severity of Illness Index; Stevens-Johnson Syndrome; Surveys and Questionnaires; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Olanzapine; Risk Factors

The activity of catechol-O-methyltransferase (COMT) may be related to psychosis susceptibility. The Val108/158Met polymorphism of the COMT gene influences its enzymatic activity and may result in altered concentrations of monoamine metabolites and different clinical responses of patients to pharmacological treatments.. We examined in a sample of 42 bipolar patients if the Val108/158Met polymorphism influences: (a) the presence of psychosis in type I bipolar patients; (b) the blood plasma concentration of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), which are metabolites of dopamine and noradrenaline respectively and (c) the severity of the clinical characteristics of these patients and their response to pharmacological treatment.. No significant associations were found between the studied COMT genotypes and the studied parameters. However, a non-significant aggregation of bipolar patients presenting with psychosis was found in the homozygous Val-Val group. Clinical improvement was found to significantly correlate with the levels of plasma MHPG prior to treatment. Moreover, a significant difference was found between the standard deviations of the concentrations of HVA in the three genotypes, but not in their mean values. Significant associations were not detected between COMT polymorphisms and the initial severity of the disorder, or the clinical response to pharmacological treatment.. The size of the studied sample is somewhat small and comparisons have been made with a previously studied control group.. The Val108/158Met polymorphism does not appear to be a crucial determinant in type I bipolar disorder.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Biogenic Monoamines; Bipolar Disorder; Catechol O-Methyltransferase; Drug Therapy, Combination; Female; Gene Expression; Genetic Predisposition to Disease; Genotype; Homovanillic Acid; Humans; Lithium Carbonate; Male; Methoxyhydroxyphenylglycol; Middle Aged; Olanzapine; Polymorphism, Genetic; Prevalence; Psychotic Disorders; Severity of Illness Index; Treatment Outcome

This retrospective claims-based study evaluated treatment adherence among patients with bipolar or manic disorder treated with atypical and typical antipsychotics.. Claims data for 18,158 antipsychotic treatment episodes in 15,224 commercially insured patients with bipolar or manic disorder (ICD-9-CM criteria), from January 1999 through August 2003, were evaluated. Overall adherence was measured by adherence intensity (medication possession ratio) and treatment duration (length of treatment episodes). Treatment-related factors that may affect medication adherence were also investigated. Pairwise comparisons of the individual atypicals and a combined group of leading typical antipsychotics were undertaken using multiple regression analysis adjusting for differing patient characteristics.. Adherence intensity with quetiapine was 3% greater than with the typicals combined (p=.002) and was greater than with risperidone or olanzapine by 4% (p<.001) and 2% (p=.001), respectively. Olanzapine (2%, p<.001) and ziprasidone (3%, p=.001) showed significantly greater adherence intensity than risperidone. Risperidone (p=.002), olanzapine (p=.055), and the typicals (p=.021) demonstrated negative associations between dose and adherence intensity, while quetiapine showed a nonsignificant trend for a positive association (p=.074). Quetiapine and risperidone had significantly longer treatment durations than the typicals combined (1.05 and 1.00 months, respectively, p<.001) and longer treatment durations than olanzapine (0.75 and 0.79 months, respectively, p<.001) or ziprasidone (0.78 months, p=.002 and 0.69 months, p=.003, respectively). Shorter treatment durations were associated with switching to other antipsychotics or remaining on or switching to other psychotropics (e.g., traditional mood stabilizers) only. All of the atypicals except ziprasidone were associated with a significantly lower likelihood of switching compared with the typicals (p<.05).. The claims-based findings of this study suggest that, for bipolar or manic disorder, quetiapine therapy may be associated with better treatment adherence than typical or some atypical antipsychotics. Estimated differences, however, were relatively small, particularly for adherence intensity.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Costs; Drug Prescriptions; Drug Utilization Review; Episode of Care; Follow-Up Studies; Humans; Insurance Claim Review; International Classification of Diseases; Middle Aged; Olanzapine; Patient Compliance; Piperazines; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone; Thiazoles; Treatment Outcome

The following is a case report analysis intended to draw attention to the need for better care coordination by describing the observed relationship of olanzapine to metabolic changes manifested as uncontrolled diabetes mellitus and weight gain. A 47-year-old male with bipolar I disorder/hallucinations presented to the Veterans Affairs Medical Center (VAMC) with suicidal ideations. He was referred to the psychiatry service where he was treated with olanzapine. He was followed exclusively by the psychiatry service for more than a year. During that time,weight issues and diabetes status were not addressed. Upon presenting to the primary care service a year and a half later, the patient was taking 40 mg per day of olanzapine and had gained 62 pounds, a 30% increase in body weight; glycosylated hemoglobin (A1c) was 11.1%. The patient was enrolled in a weight-loss clinic, and his diabetes medications were adjusted.Subsequently, olanzapine was discontinued because of weight gain and uncontrolled diabetes. Blood sugar and A1c were finally stabilized one month after discontinuation of olanzapine (A1c,6.9%). The patient experienced a relapse in his bipolar disorder,and olanzapine was restarted at 20 to 40 mg per day. His blood sugar became uncontrolled, he gained 13 pounds, and his A1c increased to 9.4%.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Humans; Hyperglycemia; Hypoglycemic Agents; Male; Middle Aged; Olanzapine; Weight Gain

Atypical antipsychotics commonly cause isolated asymptomatic increase in the aminotransferase levels. Among these atypical antipsychotics, mostly transient, asymptomatic increase in hepatic enzymes has been reported with olanzapine, however olanzapine rarely may induce a clinical and/or biological hepatic toxicity. The pathogenesis of olanzapine-associated hepatotoxicity is not well known and is mostly a transient phenomenon. However, substantial and lasting changes may occur and result in symptomatic hepatitis. In the following case report, we report on a 44-year-old female patient diagnosed as Bipolar Disorder Type I, whose liver enzyme levels increased ten fold of normal ranges during the third year of the olanzapine treatment and returned to the normal levels within three weeks after olanzapine discontinuation. Although significant liver enzyme elevations are uncommon during olanzapine treatment, based on reports of serious hepatotoxicity, controlled and longitudinal research are needed to learn side effects of this drug on liver. Clinicians should be aware of possible hepatotoxic effects of atypical antipsychotics and should monitor the liver enzyme levels whenever they feel necessary.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chemical and Drug Induced Liver Injury; Female; Humans; Liver; Olanzapine; Psychiatric Status Rating Scales

The aim of this study was to evaluate internal as well as external validity of the two most frequently used mania scales, the Young Mania Rating Scale (YMRS) and the Bech-Rafaelsen Mania Scale (MAS), in patients with DSM-IV mania. Mokken analysis was used to evaluate internal validity in which a coefficient of homogeneity of 0.40 or higher indicates that the total score is a sufficient statistic. The external validity was evaluated by plasma-level relationship of olanzapine. In total, 20 patients with DSM-IV mania were analysed, and the coefficient of homogeneity was acceptable for the MAS, but not for the YMRS. In a subgroup of females who over 2 weeks had received a fixed dose of 20 mg olanzapine daily, a significant association was found between MAS scores and plasma levels, but this association was not obtained with the YMRS. In conclusion, the MAS was found superior to the YMRS in regard to both internal and external validity.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Olanzapine; Psychiatric Status Rating Scales; Reproducibility of Results; Sensitivity and Specificity

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Catatonia; Humans; Male; Muscle Rigidity; Olanzapine

Agitation is relatively common among Borderline Personality Disorder (BPD) patients in Psychiatric Emergency Services (PES). New injectable atypical antipsychotics are indicated for treatment in agitated psychotic or maniac patients but not for agitated BDP patients. Twenty agitated BPD patients were treated with intramuscular atypical antipsychotics (olanzapine or ziprasidone). Results suggest intramuscular atypical antipsychotics may be effective, fast and safe for treating acute BPD patients.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Borderline Personality Disorder; Comorbidity; Emergency Services, Psychiatric; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Piperazines; Psychiatric Status Rating Scales; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Thiazoles; Treatment Outcome

This report was aimed to evaluate the efficacy of olanzapine treatment as an adjunct therapy to mood stabilizers in the treatment of four adolescents responding insufficiently to mood stabilizers. All patients were diagnosed with bipolar I disorder according to DSM IV criteria. YMRS (Young mania rating scale) and CGI (Clinical global impression, improvement and therapeutic effectiveness scales) were used to evaluate overall response of the episode to the drugs. All patients with no adequate response to mood stabilizers did respond to adjunctive olanzapine treatment (10-30 mg/per day). It has been suggested that antipsychotics may be useful as an adjunct to mood stabilisers in bipolar disorder. However, further research is warranted regarding the use of atypical antipsychotics in children and adolescents.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Female; Humans; Lithium Compounds; Male; Olanzapine

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Edema; Female; Humans; Middle Aged; Olanzapine

Patients with bipolar disorder do not respond to the same therapy in the same way. This potentially necessitates the trial of various treatment modalities in a patient until the illness can be successfully controlled.. Medical histories from 187 patients were reviewed to obtain information on efficacy when patients were switched from their initial drug therapy-immediate-release (IR) or extended-release (ER) carbamazepine (CBZ) tablets, valproic acid, lamotrigine, lithium, olanzapine, and oxcarbazepine-to beaded CBZ extended-release capsules (CBZ-ERC) (Shire, Wayne, PA, USA). Clinical Global Impression-Severity and Clinical Global Impression-Improvement scores were used to assess severity of illness, and response and relapse rates, respectively.. The overall response rate was 79.7%. The greatest percentage of responders to CBZ-ERC treatment was seen in patients originally on lithium (90.5%), followed by those initially treated with oxcarbazepine (84.8%), olanzapine (81.5%), lamotrigine (77.8%), valproic acid (75.4%), and IR or ER CBZ tablets (74.2%). The overall relapse rate was 38.2%. Patients on lithium had the highest relapse rate (52.6%), followed by those on olanzapine (50.0%), valproic acid (34.9%), IR or ER CBZ tablets (34.8%), oxcarbazepine (32.1%), and lamotrigine (28.6%). Adverse events were minimal, with nausea, dizziness, and somnolence being the most frequent.. The encouraging treatment response and adverse event profile observed in this retrospective analysis suggest that CBZ-ERC is an efficacious agent for the treatment of patients with bipolar disorder switched from other psychotropic agents.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Capsules; Carbamazepine; Child; Child, Preschool; Delayed-Action Preparations; Female; Humans; Lamotrigine; Lithium Carbonate; Male; Middle Aged; Olanzapine; Oxcarbazepine; Retrospective Studies; Treatment Outcome; Triazines; Valproic Acid

To present an economic model and cost-effectiveness estimates for lamotrigine in maintenance treatment of bipolar I disorder (BD-I) using outcomes from the pivotal lamotrigine trials. The main comparator treatments in the pivotal trials were lithium and .no maintenance. (acute-only) treatment. A comparison with olanzapine was included as an indirect analysis following publication of data during the course of our research.. A Markov model was built around the 3 health states of euthymia, mania, and depression. The base-case model simulates a cohort of 1,000 patients with BD-I who have recently stabilized after resolution of a bipolar mania episode. The cohort was modeled for a period of 18 months. Resource-use estimates were derived from best available published data, treatment guidelines, a physician survey, and published unit cost data. Outputs were measured in terms of costs per acute mood episode avoided, costs per euthymic day gained, and costs per quality-adjusted life-years (QALYs). Direct health care payer costs are used in the analyses.. The base-case model for patients with a recent manic episode indicated that lamotrigine is the most effective treatment for avoiding both acute depression episodes and all types of acute episodes (depression and mania). It is also the most effective treatment in terms of number of euthymic days achieved (309 days per patient per year). Olanzapine is most effective for avoiding acute mania episodes. Total direct costs of treatment are lowest for the lithium treatment arm (Dollars 8,710 per patient for the 18-month period). All maintenance therapies were cost effective compared with the no-maintenance (acute-only treatment) arm. In the base case, lamotrigine had incremental cost-effectiveness ratios of Dollars 30 per euthymic day and Dollars 2,400 per acute episode avoided compared with lithium. A QALY analysis indicated that lamotrigine is cost effective in patients with a recent manic episode at Dollars 26,000 per QALY. The base-case model indicated that lamotrigine dominates olanzapine, (that is, lamotrigine costs less and is more effective than olanzapine) in patients with a recent manic episode. In a sensitivity analysis using outcomes from the pivotal trial of recently depressed patients, lamotrigine, in comparison with lithium, was not shown to be as cost effective as in the recently manic patients, but it was still cost effective compared with no maintenance treatment.. For a defined cohort of patients with BD-I, the pharmacoeconomic model indicated that prevention of mood episodes with lithium and lamotrigine is cost effective in patients with a recent manic, mixed, or hypomanic episode. The conclusions with respect to the indirect comparison with olanzapine should be validated if and when direct trial data become available. Cost-effectiveness of maintenance treatments for patients with BD-I (recently depressed as well as recently manic) are likely to improve in models with a broader costing perspective and that take a longer time frame. Further research into the outcome implications of health-related quality of life and other BD subgroups are recommended.

Topics: Adult; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cost-Benefit Analysis; Humans; Lamotrigine; Lithium Compounds; Models, Economic; Olanzapine; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Triazines

Intracerebroventricular (ICV) administration of ouabain, a potent sodium pump inhibitor, has been used to model mania. Antipsychotic agents have demonstrated efficacy in the management of acute mania. This study was undertaken to determine the prophylactic efficacy of olanzapine and haloperidol in the ouabain mania model.. Male Sprague-Dawley rats (4-8/group) were treated with two haloperidol decanoate intramuscular shots one week apart (21 mg/kg) or twice daily olanzapine intraperitoneal injections at low dose (1 mg/kg/day) or high dose (6 mg/kg/day) for 7 days prior to ICV administration of ouabain. Open field locomotion was quantified at baseline and after ouabain administration.. Ouabain caused a significant increase in open field locomotion (253.7+/-SEM 55.12 vs control 53.1+/-12.13 squares traversed in 30 min in the olanzapine experiments, P<0.05; and 236.5+/-41.42 vs 129.3+/-38.23, P<0.05 in the haloperidol experiments). Olanzapine alone at low dose (102.2+/-37.7) or high dose (151.2+/-49.2) did not alter open field activity. Low dose olanzapine (176.6+/-73.27) but not high dose (307.5+/-167.32) caused a modest reduction of the ouabain effect. Haloperidol alone significantly reduced motoric activity compared to control (55.6+/-18.0, P<0.05), and prevented ouabain-induced hyperactivity (60.3+/-33.1, P<0.05).. Haloperidol, but not olanzapine, demonstrated efficacy in this mania model, but methodological details may have reduced the effect of olanzapine.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Behavior, Animal; Benzodiazepines; Bipolar Disorder; Disease Models, Animal; Drug Evaluation; Drug Interactions; Enzyme Inhibitors; Exploratory Behavior; Haloperidol; Male; Olanzapine; Ouabain; Rats; Rats, Sprague-Dawley

Topics: Adolescent; Affective Disorders, Psychotic; Anticonvulsants; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Humans; Lamotrigine; Lithium Compounds; Male; Olanzapine; Triazines

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Therapy, Combination; Electroencephalography; Epilepsy, Complex Partial; GABA Agonists; Humans; Male; Nipecotic Acids; Olanzapine; Substance Withdrawal Syndrome; Tiagabine

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Psychiatric Status Rating Scales; Psychometrics; Research Design; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Heparin; Humans; Male; Olanzapine; Pulmonary Embolism; Treatment Outcome

Olanzapine is an atypical antipsychotic drug approved for acute and long-term treatment of bipolar disorder. Although relatively safe as compared to other classical antipsychotic medications, there are a number of uncommon adverse effects of olanzapine such as oral cavity lesions. In addition to the relatively common side effect of dry mouth, several articles have reported an association between olanzapine treatment and the development of oral lesions such as apthous stomatitis, pharyngitis, glossitis and oral ulceration. Although there are several cases in which the tongue was affected in conjunction with stomatitis or pharyngitis, we could not find a case report indicating a direct relationship between olanzapine use and a tongue lesion. We present here the case of a patient with bipolar disorder, who developed recurrent black hairy tongue on two different occasions following the addition of olanzapine to lithium treatment. In the present case, xerostomia (dry mouth), which is an adverse reaction of both olanzapine and lithium, may have played a role in the development of black hairy tongue. All agents with a possible side effect of xerostomia may predispose patients to black hairy tongue, especially when they are administered in combination. To preclude the development of this complication with such drugs, extra time and effort should be given to improving oral hygiene.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Olanzapine; Selective Serotonin Reuptake Inhibitors; Tongue, Hairy

In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Canada; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lamotrigine; Lithium Carbonate; Mood Disorders; Olanzapine; Quetiapine Fumarate; Triazines; Valproic Acid

To assess the perceptions of clinicians in the psychiatric community about pharmacotherapy and its impact on weight gain and adverse metabolic effects in patients with bipolar disorder.. In November 2005, self-administered questionnaires were sent to 7000 psychiatrists who treat bipolar disorder in their clinical practice. An additional mailing of these questionnaires was sent in January 2006 to a different group of 7000 psychiatrists who treat bipolar disorder in their clinical practice. The first 298 completed surveys were analyzed.. Almost half of the respondents (48%) were psychiatrists in individual private practice and 32% were in community mental health centers. About two-thirds of respondents reported that 30-60% of their bipolar patients were overweight. Thirty-eight percent of respondents reported metabolic syndrome present in 20-40% of their patients. Almost all respondents (96%) reported a 20 lb increase in patients' weight as a troublesome potential adverse event associated with the use of some agents. After initiating a new medication, more than 80% of respondents monitored their patients' weight, fasting plasma glucose level, and fasting lipid profile at regular intervals. However, 80% did not monitor waist circumference. Overall, respondents viewed several agents (aripiprazole, ziprasidone, carbamazepine, and lamotrigine) as not (or minimally) problematic in terms of weight gain and adverse metabolic concerns. Clozapine and olanzapine were viewed as highly problematic due to their propensity to induce weight gain and negatively influence lipid and glucose metabolism. Other agents considered to be minimally to moderately problematic in terms of weight gain and metabolic issues were quetiapine, risperidone, lithium, and valproate. Respondents reported that the profile of a bipolar agent in terms of weight gain and adverse metabolic effects was an important consideration in the management of bipolar disorder.. Although the study is limited by a low response rate and self-selection of respondents, clinicians who did respond were concerned about the risks of weight gain and metabolic disturbances in their patients treated with bipolar agents. For most parameters, such concerns were being integrated into clinical care. However, it appears that there is a need to increase clinicians' appreciation of the importance of abdominal obesity and the need to monitor waist circumference. A growing recognition of the differences in weight-gain potential and adverse metabolic effects among agents appears to have had a definite impact on prescribing patterns in the management of bipolar disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Clozapine; Female; Humans; Lipids; Male; Metabolic Syndrome; Olanzapine; Overweight; Perception; Practice Patterns, Physicians'; Weight Gain

The case presented highlights the difficult differential diagnosis of memory-sparing cognitive decline in an elderly patient with previously stable bipolar illness. Many disorders can contribute to cognitive and behavioral deterioration in this population, including reversible causes, particularly delirium and psychiatric illness, and irreversible structural or progressive processes including vascular disease, dementia with Lewy bodies, normal-pressure hydrocephalus, and frontotemporal dementia.

Topics: Age of Onset; Aged; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brain; Cognition Disorders; Dementia; Dementia, Vascular; Disease Progression; Humans; Lithium Compounds; Male; Memory; Mental Disorders; Neuropharmacology; Olanzapine; Psychoses, Substance-Induced; Recovery of Function

The depressive phase of bipolar disorder (bipolar depression) is a difficult-to-treat form of depression. The olanzapine/fluoxetine combination (Symbyax) is the only medication approved to treat this disorder. The precise neural mechanisms responsible for its efficacy are not clearly understood.. In order to further elucidate the neurobiological mechanisms responsible for the beneficial clinical effects of the olanzapine/fluoxetine combination, the current experiment was designed to investigate the effects of chronic coadministration of olanzapine and fluoxetine on electrophysiological activity in the locus coeruleus (LC).. Rats received olanzapine for 3 weeks via subcutaneous osmotic pumps while simultaneously receiving daily intraperitoneal injections of fluoxetine. These chronically treated rats were anesthetized, and single-unit recordings of LC neurons were made.. Chronic administration of olanzapine alone significantly increased firing of LC neurons, while, as reported previously, chronic administration of fluoxetine alone significantly reduced firing of LC neurons. However, in the combination condition, olanzapine was able to block the fluoxetine-induced suppression of the LC, and a significant increase in LC activity was observed.. The observed increase in firing of LC neurons could lead to enhanced levels of norepinephrine release in projection areas and amelioration of the clinical symptoms of bipolar depression.

Topics: Action Potentials; Animals; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brain; Drug Synergism; Fluoxetine; Infusion Pumps; Injections, Intraperitoneal; Injections, Subcutaneous; Locus Coeruleus; Male; Neurons; Olanzapine; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors

The atypical antipsychotics, risperidone, olanzapine, and quetiapine, have been approved by the U.S. Food and Drug Administration for treatment of mania associated with bipolar disorder. Information on the relative mental health resource use of these therapies is helpful to pharmacy managers since differences in efficacy and safety may translate into differences in mental health care utilization. We compared charges for other mental health services associated with risperidone, olanzapine, and quetiapine treatment of patients with bipolar disorder to assess whether there were significant differences between these therapies. A secondary analysis involved dose-equivalent adjustment of the average allowed charge of the 3 atypical antipsychotics.. This was a retrospective study based on administrative data for 46 U.S. commercial health plans represented in a commercial database covering the period January 1998 through April 2002. The 6,625 patients included in the study had at least 2 contiguous pharmacy claims for a study antipsychotic, had received no other antipsychotics concurrently, and had not switched from an alternative antipsychotic in the preceding 90 days. Provider-submitted (billed) charges were selected in preference to paid amounts as being more accurate indicators of relative differences in the use of mental health resources. Mental health care charges were measured per patient per month (PPPM) and included charges for the study antipsychotics and charges for the other mental health care services (inpatient, physician and other ambulatory, and other psychotropic medications). Differences in other mental health care charges PPPM among the 3 therapies were assessed with multivariate regression, adjusting for differing patient characteristics. Differences in antipsychotic drug charges PPPM were assessed after adjustment to reflect an equivalent average daily dose.. Regression estimates adjusted for patient differences did not show statistically significant differences in other mental health care charges PPPM among the 3 antipsychotic drug therapies. Other mental health charges associated with quetiapine were estimated to be 14 US dollars, or 3% lower than those associated with risperidone, but this difference was not statistically significant (P = 0.069). The PPPM charges for quetiapine versus olanzapine and olanzapine versus risperidone were also not different (P = 0.231 and P = 0.39, respectively). After adjusting for differences in average daily dose, risperidone and quetiapine had antipsychotic drug charges that were 84 US dollars and 76 US dollars PPPM lower than those of olanzapine (P < 0.01); the difference between the adjusted drug charges PPPM for risperidone and quetiapine was not significant.. Total charges for mental health services other than the study drug were not different for risperidone, olanzapine, and quetiapine in patients treated for bipolar disorder. However, based on prescription charges, olanzapine appears to be considerably more costly at an equivalent daily dose than either risperidone or quetiapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Utilization; Female; Health Care Costs; Humans; Male; Mental Health Services; Multivariate Analysis; Olanzapine; Quetiapine Fumarate; Regression Analysis; Retrospective Studies; Risperidone

Rabbit syndrome (RS) is a rare extrapyramidal side effect of antipsychotic treatment. It is characterized by involuntary, rhythmic dyskinesias of mouth and lips excluding the tongue, and is most common under typical neuroleptics. There are also several reports of the syndrome in patients with the atypical antipsychotics risperidone and aripiprazole. We report a 74 year-old patient suffering from a bipolar affective disorder, who developed a rabbit syndrome following the intake of 20 mg/d olanzapine. To our knowledge this is the first case report of a RS due to olanzapine.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Humans; Neurologic Examination; Olanzapine; Syndrome

Olanzapine is an atypical antipsychotic that is approved in the US and Europe for the oral treatment of acute manic episodes in patients with bipolar I disorder and for maintenance therapy to prevent recurrence in responders. Oral olanzapine is effective in the treatment of bipolar mania, both as single agent therapy and as adjunctive therapy in combination with lithium or valproate semisodium. In the treatment of acute episodes, olanzapine is superior to placebo and at least as effective as lithium, valproate semisodium, haloperidol and risperidone in reducing the symptoms of mania and inducing remission. Additional comparative studies are required to determine the efficacy of olanzapine relative to newer atypical antipsychotics such as quetiapine, ziprasidone and aripiprazole. Olanzapine is also effective at delaying or preventing relapse during long-term maintenance therapy in treatment responders and is currently the only atypical antipsychotic approved for this indication. Current evidence suggests that olanzapine may be more effective than lithium in preventing relapse into mania, but not relapse into depression or relapse overall. Olanzapine is generally well tolerated and, although it is associated with a higher incidence of weight gain than most atypical agents, it has a low incidence of extrapyramidal symptoms. Therefore, oral olanzapine is a useful first-line or adjunctive agent for both the acute treatment of manic episodes and the long-term prevention of relapse into manic, depressive or mixed episodes associated with bipolar I disorder.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine

Neuroleptic Malignant Syndrome (NMS) is a rare, potentially fatal and idiosyncratic drug reaction. It is characterized by a sudden loss of body temperature control, renal and respiratory failure, muscle rigidity, loss of consciousness and impairment of autonomic nervous system. Although NMS was previously associated with the use of classical high-potency neuroleptics, cases have started to emerge with atypical neuroleptics. This article discusses the first case of NMS in a child, induced by the use of risperidone, olanzapine and quetiapine.

Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Temperature; Child; Dibenzothiazepines; Electroconvulsive Therapy; Female; Humans; Impulsive Behavior; Neuroleptic Malignant Syndrome; Olanzapine; Quetiapine Fumarate; Risperidone; Valproic Acid; Violence

In a new approach to the interpretation of data from flexible-dose studies, we examined the safety and efficacy measurements that preceded and followed dose changes, to identify clinical factors that predict dose change as well as subsequent outcome of clinical status with dose change. This was a post hoc analysis of 3 flexible-dosed olanzapine studies: acutely ill bipolar I patients with an index manic episode (N = 452) who received olanzapine (5-20 mg/d) or haloperidol (3-15 mg/d); acutely ill patients with schizophrenia (N = 339) who received olanzapine (10-20 mg/d) or risperidone (4-12 mg/d) for 28 weeks; and remitted bipolar I patients (N = 361) who received olanzapine (5-20 mg/d) or placebo for 48 weeks. The major findings of this analysis were: an increase in dose was predicted by baseline illness severity in the acute studies, and a decrease in dose was predicted by illness symptom improvement or worsening of adverse events. Dose decrease was followed by significantly decreased efficacy for patients with acute mania treated with olanzapine or haloperidol, and olanzapine dose increases were followed by improved efficacy. Treatment-emergent extrapyramidal symptom adverse events and akathisia typically predicted dose decreases. Techniques used in this analysis may prove to be useful in assessing the relationship between dose change and safety and efficacy measures.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Olanzapine; Predictive Value of Tests; Randomized Controlled Trials as Topic; Retrospective Studies; Schizophrenia; Treatment Outcome

"Conventional" antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs), bupropion, or serotonin-norepinephrine reuptake inhibitors, are not recommended as monotherapy for bipolar depression. Although they are likely to provide effective symptom relief in combination with mood stabilizers, the risk of precipitating a switch to mania often complicates their use even as combination therapy. Recently, 2 psychotropic medications approved for treating acute mania, olanzapine and quetiapine, have also been shown to possess antidepressant activity without destabilizing mood and, as such, are potential mood stabilizers. This article aims to review the mechanism of action of conventional antidepressants and newer agents that are effective in the treatment of bipolar depression. A number of mechanisms have been postulated to play a role in the effective treatment of bipolar depression, including targets as diverse as serotonin (5-HT), norepinephrine, dopamine, gamma-aminobutyric acid (GABA), glutamate, and various second messenger signaling pathways. A review of the data reveals an important point of commonality among the antidepressant treatments, olanzapine, and quetiapine. Antidepressant treatments, such as norepinephrine reuptake inhibitors, SSRIs, and electroconvulsive therapy, induce a reduction of 5-HT(2A) receptors. Both olanzapine and quetiapine not only are antagonists at this receptor but also induce downregulation of 5-HT(2A) receptors. It is possible that the antidepressant efficacy of these agents is mediated by this receptor, while the additional benefit of olanzapine and quetiapine over unimodal antidepressant treatments, in terms of stabilizing mood, may be provided by their concomitant dopamine D(2) antagonism. Further studies should be conducted to examine these hypotheses.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Dopamine; gamma-Aminobutyric Acid; Humans; Neurotransmitter Agents; Norepinephrine; Olanzapine; Quetiapine Fumarate; Second Messenger Systems; Selective Serotonin Reuptake Inhibitors; Serotonin; Synaptic Transmission

Topics: Anticonvulsants; Antipsychotic Agents; Australia; Benzodiazepines; Bipolar Disorder; Carbamazepine; Drug Monitoring; Humans; Lamotrigine; Lithium Carbonate; Olanzapine; Outcome and Process Assessment, Health Care; Surveys and Questionnaires; Treatment Outcome; Triazines; Valproic Acid

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

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Codes of Ethics; Drug Therapy, Combination; Fluoxetine; Humans; Olanzapine; Peer Review, Research; Research Design; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Rapid cycling in bipolar disorder has been associated with greater morbidity. We examine whether rapid cycling affects treatment response to olanzapine or divalproex in acute mania.. A post hoc analysis of a 47-week, randomized, double-blind study compared olanzapine (5-20 mg/day) to divalproex sodium (500-2500 mg/day) for bipolar manic or mixed episodes (N=251). Young Mania Rating Scale (YMRS) scores > or = 20 were required for inclusion. Patients were classified at study entry as "rapid cyclers" if they experienced > or = 4 episodes within the last year. A repeated measures analysis of variance was used to analyze YMRS change from baseline.. A significant three-way interaction (cycling frequency by medication by visit) was found when modeling change in YMRS total scores. For patients with bipolar I disorder identified as rapid cyclers, mania improvement across the trial did not differ significantly between treatment groups (p=0.181). Among non-rapid cyclers, olanzapine-treated patients had significantly greater YMRS improvement than divalproex-treated patients across the trial (p<0.001) and at most time points. Among olanzapine-treated patients, non-rapid cyclers experienced numerically greater YMRS improvement than rapid cyclers throughout the trial; statistically significant differences occurred at weeks 11, 15 and 39. In contrast, among divalproex-treated patients, YMRS scores were significantly better in rapid cyclers than non-rapid cyclers during the first two study weeks but were comparable thereafter. A similar pattern was seen in Clinical Global Impressions-Mania Severity scores. Hamilton Depression scores in rapid versus non-rapid cycling patients differed at some time points but not over the entire trial and differences by cycling status were not treatment-specific.. Apart from the post hoc nature of the analyses, there were high dropout rates in both groups, and cycle frequency was not taken into account.. Rapid cycling patients did less well over long-term treatment than non-rapid cycling patients. Among rapid cycling patients, olanzapine and divalproex appear similarly effective against manic symptoms; however, among non-rapid cycling patients, olanzapine-treated patients experienced superior mania improvement. Olanzapine-treated, non-rapid cyclers experienced greater mania improvement than rapid cyclers. The converse was true of divalproex-treated patients early in treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Personality Assessment; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Drug Therapy, Combination; Humans; Olanzapine; Research Design

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Lithium; Male; Olanzapine; Wit and Humor as Topic

Topics: Adult; Benzodiazepines; Bipolar Disorder; Drug Combinations; Fluoxetine; Humans; Olanzapine; Selective Serotonin Reuptake Inhibitors

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Approval; Drug Combinations; Fluoxetine; Humans; Olanzapine; United States

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Long QT Syndrome; Middle Aged; Olanzapine; Wolff-Parkinson-White Syndrome

Topics: Age Factors; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delirium; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Olanzapine

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Humans; Iatrogenic Disease; Lithium Carbonate; Male; Olanzapine; Priapism

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Olanzapine; Severity of Illness Index

Topics: Adolescent; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Cell Count; Citalopram; Dose-Response Relationship, Drug; Female; Humans; Neutropenia; Olanzapine

The emergence or exacerbation of obsessive-compulsive (OC) symptoms during treatment with atypical antipsychotics, mostly clozapine, has been documented by numerous case reports (reviewed by Lykouras et al., 2003). In six recent reports involving nine cases, (Jonkers and de Haan, 2002; Lykouras et al., 2003) olanzapine was found either to cause de novo emergence or to exacerbate OC symptoms. In six of these cases olanzapine caused exacerbation and in three cases caused de novo emergence of OC symptoms.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Obsessive-Compulsive Disorder; Olanzapine; Schizophrenia

Olanzapine is an effective drug for the long-term treatment of bipolar disorder but is associated with burdensome weight gain. Topiramate is a novel anticonvulsant that may induce weight loss in some patients. This is the first study to address the long-term efficacy and impact on weight of the combination of olanzapine and topiramate in bipolar patients. Twenty-six Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar spectrum patients received olanzapine plus topiramate cotherapy for treatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n = 1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite being euthymic. Efficacy was assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, and the Modified Clinical Global Impressions for Bipolar Disorder. Weight, body mass index, and side effects were collected at every visit. Thirteen (50%) patients completed the 1-year follow-up. By intent-to-treat, patients significantly improved from baseline in Young Mania Rating Scale scores (P < 0.0001), Hamilton Depression Rating Scale (P < 0.05), and Modified Clinical Global Impressions for Bipolar Disorder subscales (mania P < 0.0001, depression P < 0.05, overall P < 0.0001). Most patients gained weight during the first month of combined treatment (mean weight gain 0.7 +/- 0.6 kg), but at the 12-month endpoint, the mean weight change was -0.5 +/- 1.1 kg. The combination of olanzapine and topiramate was efficacious for the long-term treatment of bipolar patients and appeared to carry some benefits for controlling weight gain. Given the limitations of the open, uncontrolled design, further trials are warranted with this combination.

Topics: Adult; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Male; Middle Aged; Olanzapine; Statistics, Nonparametric; Topiramate; Treatment Outcome; Weight Gain

Topics: Administration, Oral; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Humans; Injections, Intramuscular; Long-Term Care; Neuropsychological Tests; Nursing Assessment; Olanzapine; Prognosis; Schizophrenia; Treatment Outcome

Topics: Adult; Benzodiazepines; Bipolar Disorder; Dronabinol; Female; Humans; Libido; Olanzapine; Paroxetine; Psychotropic Drugs; Sexual Behavior; Sexual Dysfunctions, Psychological; Treatment Outcome; Valproic Acid

Topics: Adult; Alcohol Drinking; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cannabinoids; Clitoris; Female; Humans; Olanzapine; Vulvar Diseases

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Piperazines; Quality of Life; Quinolones; Risk Factors; Self-Injurious Behavior; Thiazoles

This study analyzed the effect of olanzapine on a psychopathology-based scale assessing abnormal thought processes and examined the relationship between improvement on this scale and mania and depression improvement in acutely manic patients.. The study sample (N = 254) was pooled from two double-blind, randomized, placebo-controlled clinical trials. Disturbance in thought processes was measured by the Positive and Negative Symptom Scale cognitive component (PANSS-Cognitive) score. Mood severity was measured by the Young-Mania Rating Scale (Y-MRS) and Hamilton Depression Inventory (HAM-D). Last-observation-carried-forward (LOCF) changes from baseline to endpoint (Week 3) were presented for patients who had at least one post-baseline assessment.. Olanzapine-treated patients experienced modest but significant improvement in PANSS-Cognitive score (olanzapine: -4.25 n = 124; placebo: -1.69 n = 120, p < 01), regardless of age, gender, mania subtype (pure, mixed), course (rapid or non-rapid cycling), or the presence or absence of psychotic features. PANSS-Cognitive improvement was more highly correlated with mania than depression improvement.. Olanzapine improved abnormal thought processes measured by the PANSS-Cognitive score in patients with acute mania. This improvement in thought processes was significantly associated with improvement in acute mania. More sensitive and specific neuropsychological testing could help clarify whether improvement in thought processes on olanzapine was independent of mania reduction.

Topics: Acute Disease; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cognition; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Olanzapine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic

Topics: Adult; Benzodiazepines; Bipolar Disorder; Humans; Male; Obsessive-Compulsive Disorder; Olanzapine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Approval; Humans; Olanzapine; United States; United States Food and Drug Administration

Topics: Adolescent; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Benzodiazepines; Bipolar Disorder; Child; Drug Therapy, Combination; Humans; Male; Olanzapine; Piperazines; Thiazoles

The atypical antipsychotics have been recognized to induce diabetes mellitus and ketoacidosis in the adult psychiatric population. This report notes the onset of weight gain, diabetes, and apparent ketosis in a prepubertal boy diagnosed with bipolar disorder and treated with olanzapine. The hyperglycemia rapidly normalized after discontinuation of the olanzapine. Within 2 years, the diabetes recurred. In spite of the normalization of blood-glucose levels, urine ketone tests remained positive and were explained by the fact that patients taking valproic acid may have a false-positive urine test for ketones. Regular monitoring of glucose should be considered in children and adolescents who gain weight while treated with atypical antipsychotics.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Child; Diabetes Mellitus, Type 2; Humans; Male; Olanzapine; Recurrence

Many medical disorders presentwith psychiatric symptoms. Teasing out what is caused by the medical problem and what is underlying psychopathology can be a tremendous challenge. We report the case of a young man with no documented past psychiatric history that developed symptoms consistent with bipolar disorder with mood-congruent psychotic features as well as typhoid fever. In this report, we summarize the biological, psychological, and social underpinnings of this rare and interesting case.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Humans; Lithium Carbonate; Male; Neuropsychological Tests; Olanzapine; Paroxetine; Selective Serotonin Reuptake Inhibitors; Typhoid Fever

Acute manic episodes in bipolar disorder require rapid and effective relief. Bipolar depression is a major component of the bipolar disorder spectrum. Existing treatment options for bipolar depression include lithium, lamotrigine and conventional antidepressants. However, lithium is more effective in treating mania or hypomania than depression, both acutely and prophylactically, lamotrigine has only been demonstrated to be effective in one adequately powered study in acute bipolar I depression, and conventional antidepressants have been associated with emergent mania and cycle acceleration. Symptomatic outpatients can expect to spend, on average, 33% of their time in the depressive phase compared with 11% in the manic phase. Consequently, there is a need for additional agents to effectively treat bipolar depression. The atypical agents olanzapine, risperidone and quetiapine have demonstrated efficacy against the manic phase of bipolar disorder and appear also to have potential in the depressive phase. Olanzapine monotherapy significantly improved depressive symptoms compared with placebo in patients with bipolar disorder in an 8-week randomized, controlled clinical study, but the magnitude of the clinical effect was small. The observed improvement in depressive symptoms became moderately large when olanzapine was combined with the antidepressant fluoxetine. Quetiapine monotherapy also resulted in significant improvements compared with placebo in patients with either bipolar I or bipolar II disorder in another 8-week randomized, controlled clinical study, but the effect size was large. A 6-month open-label study of risperidone added to ongoing therapy demonstrated improvements in depressive symptoms in patients with bipolar and schizoaffective disorders experiencing a manic, hypomanic, mixed or depressive episode. The receptor-binding profile of these agents supports a role in the treatment of depressive symptoms and clinical data are beginning to emerge of their efficacy in both the acute and maintenance setting.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Tolerance; Follow-Up Studies; Humans; Olanzapine; Psychotic Disorders; Risperidone; Time Factors

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dopamine; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales

A substantial number of patients with mania have significant concomitant depressive features, and they may respond differently to mood stabilizers than patients with pure mania. This post-hoc analysis explored the response characteristics of olanzapine versus placebo in bipolar I manic patients with dysphoric and nondysphoric mania (differentiated by baseline Hamilton Depression Rating Scale [HAM-D] score of >20). Two similar, double-blind, randomized trials comparing olanzapine, 5-20 mg, to placebo were pooled for these analyses (N = 246). Mean changes in Young-Mania Rating Scale (Y-MRS) and HAM-D scores during 3 weeks of treatment were examined. Twenty-eight percent of patients had dysphoric mania (olanzapine, n = 33; placebo, n = 35). Among these patients, olanzapine-treated patients had greater improvement within 1 week than did placebo-treated patients on both mania ratings (Y-MRS: -9.7 vs. -3.0 points; = 0.011) and depressive symptom ratings (HAM-D: -9.9 vs. -5.4 points; = 0.025). Among those manic subjects without prominent depressive symptoms (olanzapine, n = 91; placebo, n = 87), mean Y-MRS improvement from baseline to endpoint with olanzapine (-11.5 points) versus placebo (-6.13 points) was comparable to the improvement seen with olanzapine versus placebo in the dysphoric mania subgroup ( = 0.476, test of interaction). In acutely ill manic patients with significant depressive symptoms, olanzapine demonstrated a broad spectrum of efficacy, effectively treating both manic and depressive symptoms. The magnitude of the antimanic response appears similar, regardless of baseline depressive features. Additional experience with putative mood stabilizers and atypical agents in mixed mania should include an exploration of their efficacy in treating both manic and depressive mood symptoms.

Topics: Acute Disease; Affect; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Fluoxetine; Humans; Olanzapine; Pirenzepine

Assessment of therapeutic interventions in bipolar disorder is complicated by rapid, complex clinical changes, high placebo-response rates, and varying times to specific levels of clinical recovery that may not be adequately reflected in averaged rating-scale scores particularly in acute mania, calling for improved methods to evaluate treatment responses. Chengappa et al. (1). propose operational criteria for specific outcomes based on rating-scale data from two placebo-controlled trials of olanzapine in mania.. These trials and other recent research were considered in commenting on the design, conduct, analysis and interpretation of experimental therapeutic trials in mania and to optimize olanzapine versus placebo contrasts by systematically varying end-point criteria for mania (YMRS) and depression (HDRS) ratings.. Olanzapine versus placebo responses were optimally separated at scores of 10 for final paired mania and depression ratings, or 5 for each rating scale considered separately.. Use of empirically determined end-points derived from standard rating scales used in experimental therapeutics research in mood disorders can improve both outcome-assessment and separation of active treatment from placebo responses in acute mania.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Humans; Olanzapine; Pirenzepine; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Liver; Olanzapine; Pirenzepine; Transaminases

Topics: Adult; Ankle; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Edema; Female; Foot Diseases; Humans; Olanzapine; Pirenzepine

Topics: Adult; Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Cyclohexanols; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Drug Interactions; Drug Therapy, Combination; Humans; Male; Obesity; Olanzapine; Pirenzepine; Risk Factors; Valproic Acid; Venlafaxine Hydrochloride

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Dopamine Antagonists; Drug Therapy, Combination; Haloperidol; Humans; Isotopes; Lithium; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors; Time Factors; Valproic Acid

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Hospitalization; Humans; Isotopes; Lithium; Olanzapine; Patient Readmission; Pirenzepine; Placebos; Recurrence; Selective Serotonin Reuptake Inhibitors; Time Factors; Valproic Acid

Topics: Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Bias; Bipolar Disorder; Clinical Trials as Topic; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome; Valproic Acid

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Differential; Humans; Nursing Diagnosis; Olanzapine; Treatment Outcome

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Long-Term Care; Olanzapine; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Feeding and Eating Disorders; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Sleep Wake Disorders; Somnambulism

The present paper describes a case of serotonin syndrome (SS), which developed in a patient with bipolar affective disorder after the addition of olanzapine to her regimen of lithium and citalopram. This appears to be the first report that implicates olanzapine with SS. Clinicians should be aware of the risk of SS when adding atypical antipsychotics, such as olanzapine, to serotonergic agents.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Citalopram; Female; Humans; Lithium Chloride; Middle Aged; Olanzapine; Pirenzepine; Risk Factors; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delusions; Female; Hair Diseases; Humans; Olanzapine; Pirenzepine; Sexual Behavior

The administration of a serotonin reuptake inhibitor may lead to extra pyramidal signs, as reported in the literature. The risk seems to be increased in elderly people. We describe a case of acute dystonic reaction to paroxetine treatment in an elderly patient, who presented with a bipolar affective disorder. The underlying mechanism, possibly generated in the subcortical motor areas, is linked to changes that occur in the pharmacokinetic variables, the decreased neuroplasticity of ageing neurones and to previous exposure to neuroleptic medications.

Topics: Aged; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dystonic Disorders; Electroconvulsive Therapy; Humans; Male; Morpholines; Olanzapine; Paroxetine; Pirenzepine; Reboxetine

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Treatment Outcome

Topics: Acute Disease; Benzodiazepines; Bipolar Disorder; Clinical Trials as Topic; Double-Blind Method; Humans; Olanzapine; Pirenzepine; Placebo Effect; Psychotherapy

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Double-Blind Method; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome

Psychopharmacology research aims to expand the therapeutic ratio between efficacy, on the one hand, and adverse events and safety, on the other. The novel antipsychotics are now the antipsychotics of choice in the treatment of bipolar disorders. They have the advantages of potential antidepressant properties and low risks of extrapyramidal side effects and, especially, of tardive dyskinesia. However, novel antipsychotics may also have varying propensities to cause side effects, such as somnolence, hyperprolactinemia, weight gain (sometimes significant), and possibly diabetes mellitus. The increasing use of these novel agents requires careful assessment and monitoring of emergent side effects and diligent consideration of associated medical complications. Two new anticonvulsants, lamotrigine and topiramate, have recently shown promise in the treatment of bipolar disorders. Most of their adverse effects can be avoided by slow titration toward the recommended doses. In contrast to carbamazepine and valproic acid, topiramate may be associated with weight loss.

Topics: Anticonvulsants; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Female; Fructose; Humans; Lamotrigine; Male; Obesity; Olanzapine; Piperazines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Triazines

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Male; Olanzapine; Pirenzepine

Topics: Adult; Benzodiazepines; Bipolar Disorder; Female; Humans; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine

Topics: Acute Disease; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Administration Schedule; Drug Approval; Humans; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; United States; United States Food and Drug Administration

To report a case of olanzapine-induced hyperglycemia leading to a hyperosmolar, hyperglycemic, nonketonic coma.. A 51-year-old, 85.5-kg (ideal body weight 79.9 kg), white man presented to a Veterans Affairs hospital with a serum glucose concentration of 1596 mg/dL. Soon thereafter, he went into a hyperosmolar, hyperglycemic, nonketonic coma. Olanzapine therapy had been instituted less than six months prior to this event; approximately two months before this event, his blood glucose was 108 mg/dL. Eight days after stopping olanzapine, the glucose concentration returned to normal, and the patient no longer required insulin nor any other glucose-lowering agents.. The insulin resistance caused by olanzapine is normally attributed to the weight gain associated with the drug. In this patient, it appears that olanzapine caused hyperglycemia by a mechanism other than weight gain.. This case report and others from the literature suggest that olanzapine therapy may induce hyperglycemia in some patients.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Blood Glucose; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Male; Middle Aged; Olanzapine; Pirenzepine; Stress Disorders, Post-Traumatic

We present the case of a never medicated patient with a diagnosis of DSM-IV paranoid schizophrenia in which olanzapine therapy induced manic symptoms. The latter remitted after drug discontinuation.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia, Paranoid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Cognitive Behavioral Therapy; Counseling; Exercise; Female; Humans; Male; Obesity; Olanzapine; Pirenzepine; Relaxation Therapy; Schizophrenia; Treatment Outcome; Weight Gain

The simultaneous presentation of both manic and depressive symptoms has long been recognized. Nevertheless, a variable prevalence of dysphoric mania has been reported. The aim of this study was to estimate the prevalence of dysphoric mania among hospitalized patients and to assess the effectiveness of olanzapine in this type of patients.. Eighty-six patients who met DSM-IV criteria for mania were evaluated at admission with a protocol that included McElroy's criteria for dysphoric mania [Am. J. Psychiatry 149 (1992) 1633]. Treatment was administered according to clinical need, using mood stabilizers combined with antipsychotics. Sequential assessments were conducted throughout the study.. Forty-four patients (51.2%) fulfilled McElroy's criteria for dysphoric mania. Fourteen of these dysphoric patients were treated with olanzapine in combination with mood-stabilizers. All patients improved in manic symptoms but patients treated with olanzapine improved significantly more than those treated with other antipsychotics in depressive symptoms.. The lack of randomization is a methodological limitation of this study, so these findings should be considered as preliminary.. Dysphoric symptoms are common in this population of manic patients. Olanzapine in combination with mood-stabilizers may be effective in these patients. Additional controlled studies are needed to replicate these results.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome

We present the case of a 31-year-old woman with recent refractory bipolar disorder who developed a malignant syndrome preceded by catatonic motor features. This resistant case of lethal catatonia responded selectively to high-dose olanzapine treatment. The case illustrates the need to consider lethal catatonia in apparent cases of neuroleptic malignant syndrome that do not respond to conventional treatment with dantrolene and bromocriptine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Catatonia; Electroconvulsive Therapy; Female; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychomotor Agitation

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

Converging evidence indicates that, in controlled drug trials, individuals receiving novel antipsychotic medications have fewer adverse effects than those receiving conventional antipsychotic medications. This in turn may lead to greater patient treatment satisfaction. This study examines patient satisfaction and burden of adverse effects in a county-wide epidemiologic study of first admission psychotic persons with psychosis who were receiving novel antipsychotic drugs (n = 42). Comparisons were made within this group, and between 25 of these persons and 25 others with the same diagnosis and sex, from the same epidemiologic study, who were receiving a comparable regimen of conventional antipsychotic drugs. Patients receiving novel antipsychotics were significantly more satisfied and were significantly less burdened by adverse effects than those receiving conventional antipsychotics. Among the group receiving novel antipsychotics, dosage was not related to satisfaction or burden of adverse effects. For those treated with risperidone (n = 27), there was a difference, approaching statistical significance, for greater satisfaction and less adverse effect burden among those persons with dosages less than 5 mg daily as compared to higher dosages.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Clozapine; Depressive Disorder, Major; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Neurologic Examination; Olanzapine; Patient Satisfaction; Pirenzepine; Risperidone; Schizophrenia; Schizophrenic Psychology

We report on three cases of acutely manic prepubertal children diagnosed with bipolar disorder who were treated with olanzapine in addition to their existing mood stabilizer regimens. All three had marked improvement of their manic symptoms within 3-5 days of beginning olanzapine therapy as measured by clinician-rated instruments. Adverse effects included sedation and weight gain. These results suggest that olanzapine may have an antimanic or mood stabilizing effect in acutely manic children with bipolar disorder.

Topics: Antimanic Agents; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Benzodiazepines; Bipolar Disorder; Child; Drug Therapy, Combination; Humans; Lithium Chloride; Male; Olanzapine; Pirenzepine; Sleep Stages; Valproic Acid; Weight Gain

Whereas the Fiji government provides all aspects of mental health care services free of charge to its citizens, many schizophrenics have failed to respond to classical antipsychotic drugs.. To assess the efficacy and safety of olanzapine among various patients with severe psychiatric disorders.. Naturalistic setting.. Descriptive study.. Outcome was based on reduction of symptoms on the PANSS (> or = 40%) and CGI shift to 1-3.. The were 64 patients (30 males) aged 17-77 years. Thirty six (56.3%) had schizophrenia, eight mania, ten severe depression, four obsessive compulsive disorder (OCD), one each had schizo-affective and delusional disorders, while the remaining had chronic brain diseases.. At weeks 3, 8, 12, the proportion of subjects with 40% improvement was 60.6%, 79.9%, and 76.8%, respectively. Positive and negative symptoms improved. Thirteen (48.1%) of the 27 long-stay treatment--resistant schizophrenics achieved clinical recovery at eight weeks. All with primary diagnosis of severe depression and mania achieved full clinical recovery (mostly within two weeks). Two OCD cases achieved clinical recovery at week eight.. Olanzapine was safe for all categories of patients. There was not a single case of extrapyramidal reaction among subjects who did not have it pre-treatment; and the drug was safe in a suicidal overdose of 205 mg. Most patients experienced weight gain; two adolescent girls had temporary amenorrhoea and one subject had transient rise in liver transaminases which normalised without discontinuing the drug.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Female; Fiji; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Schizophrenia; Severity of Illness Index; Treatment Outcome; Weight Gain

Topics: Adult; Antipsychotic Agents; Behavior; Benzodiazepines; Benztropine; Bipolar Disorder; Drug Interactions; Humans; Male; Muscarinic Antagonists; Olanzapine; Pirenzepine; Risperidone

Bipolar I disorder is estimated to affect 0.6% of adolescents. Lithium, sodium valproate, carbamazapine, and adjunctive treatment with benzodiazapines and antipsychotics have been used to treat bipolar I disorders. We report a case of a 17-year-old adolescent male with bipolar I disorder who responded favorably to the treatment with the atypical antipsychotic olanzapine. We hypothesize that olanzapine's broad affinity for both dopaminergic and serotonergic receptors may be related to the beneficial therapeutic outcome.

Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales

Topics: Benzodiazepines; Bipolar Disorder; Ephedrine; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Urinary Incontinence

Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Diagnosis, Dual (Psychiatry); Drug Therapy, Combination; Female; Hallucinations; Humans; Olanzapine; Pirenzepine; Risperidone; Substance-Related Disorders; Treatment Outcome; Valproic Acid

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Female; Humans; Middle Aged; Neurologic Examination; Olanzapine; Pirenzepine

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

The annual meeting of the American Psychiatric Association focuses on a variety of topics, including those on psychopharmacology. The latest developments are typically those found in the New Research sections, which is where this summary will focus.

Topics: Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Citalopram; Depressive Disorder; Humans; Hypericum; Olanzapine; Phytotherapy; Pirenzepine; Plants, Medicinal; Psychiatry; Psychotropic Drugs; Societies, Scientific; Testosterone; United States

Mood-stabilizing agents are ideally conceptualized as possessing antimanic and antidepressant properties. While research on olanzapine's antimanic effects is growing, data on its possible antidepressant properties are limited. We sought to determine if olanzapine is effective in the add-on treatment of major affective disorders, particularly depressive symptoms, in a naturalistic setting.. All charts of patients meeting DSM-IV criteria for bipolar disorder or unipolar major depressive disorder treated with olanzapine in a private psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impression Scale for Improvement (CGI-I).. Olanzapine was moderately effective in 6/10 (60%) patients. Side-effects were present in 8/10 (80%), most commonly weight gain.. Olanzapine appears to be moderately effective in open add-on treatment in patients with mainly depressive symptoms. Accumulating evidence suggests that olanzapine, and atypical antipsychotics in general, possess mild to moderate adjunctive antidepressant properties.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Treatment Outcome

An open trial was conducted to determine the efficacy of olanzapine in the treatment of bipolar mixed state.. Nine inpatients at a provincial psychiatric hospital who met the DSM-IV criteria for bipolar I disorder, most recent episode mixed.. Olanzapine was added to the existing drug regime in patients who had failed to respond to adequate trials of mood stabilizers used alone or in combination with neuroleptics.. Patients were administered the Clinical Global Impression (CGI) Scale, the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF) Scale before the initiation of olanzapine. These scales were repeated and patients were rated on the improvement subscale of the CGI at the time of discharge.. Pretreatment means (and standard deviations [SD]) for the CGI scale, BPRS and GAF were 5.7 (1.1), 60.7 (13.7) and 17.8 (7.5), respectively. Post-treatment means and SD for the scales were 1.9 (0.6), 6.3 (3.3) and 71.7 (5.6), respectively. Paired t-tests on all measures indicated significant improvement in symptoms with t = 9.43, p < 0.001 for CGI; t = -13.28, p < 0.001 for BPRS; t = -21.83, p < 0.001 for GAF. The mean improvement subscale score of the CGI was 1.3 (SD 0.5) at discharge.. Olanzapine was well-tolerated and was effective in the acute treatment of bipolar mixed state.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Treatment Outcome

Psychotic depression is more common than is generally realized, occurring in an estimated 16% to 54% of depressed patients. In controlled studies of patients with schizophrenia, the atypical antipsychotic olanzapine has been shown to be superior in efficacy to haloperidol at doses of 10 mg/day. Since olanzapine may have antidepressant effects in addition to its antipsychotic properties, the purpose of this study was to assess the safety and efficacy of olanzapine in the treatment of psychotic depression.. Hospitalized patients with the discharge diagnosis of DSM-IV psychotic depression (major depression with psychotic features or bipolar I disorder, depressed phase...with psychotic features) who had been treated with olanzapine during the first 9 months of its availability in the United States were identified. An age- and sex-matched sample of hospitalized patients with psychotic depression treated with other antipsychotics during the same time period was also identified. The medical records were expunged of all references to medication treatment and then reviewed and scored in a blind fashion for indications, doses, response, and side effects.. Fifteen psychotic depression patients (10 women, 5 men), aged 36.9 +/- 10.1 years, who were treated with olanzapine were retrospectively compared with 15 psychotic depression patients (10 women, 5 men), aged 35.0 +/- 8.2 years, treated with other antipsychotics. Ten (67%) of 15 patients taking olanzapine were much or very much improved upon discharge compared with only 4 (27%) of 15 patients taking other antipsychotics (Fisher exact test, p = .037). Olanzapine was well tolerated: no patient discontinued the medication because of side effects. Twelve (80%) of 15 patients in each group were taking antidepressants in addition to the antipsychotic. Of the 3 patients taking olanzapine but not taking an antidepressant, 2 were much or very much improved (1 patient taking olanzapine alone, 1 taking olanzapine plus valproate sodium).. Olanzapine appears to be effective and safe for patients with psychotic depression. Further prospective studies are warranted to ascertain whether olanzapine's unique pharmacologic profile may make it particularly useful for the treatment of psychotic depression either alone or in combination with antidepressants.

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Female; Hospital Records; Hospitalization; Humans; Male; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales; Retrospective Studies; Treatment Outcome

Topics: Adolescent; Adolescent Psychiatry; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dose-Response Relationship, Drug; Humans; Male; Medication Errors; Olanzapine; Pirenzepine

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Olanzapine; Pirenzepine

Clozapine may be effective in adults and adolescents with treatment-resistant bipolar disorder. Olanzapine has a receptor affinity profile similar to that of clozapine.. The responses of seven consecutive adolescents (ages 12-17) with DSM-IV bipolar disorder, manic episode, treated with olanzapine were evaluated. Response to olanzapine was rated as marked, moderate, minimal, none or worse.. Five (71%) adolescents showed a marked or moderate response. The mean+/-SD olanzapine dose was 0.146+/-0.086 mg/kg/day (11+/-6 mg/day).. Olanzapine may have antimanic effects in some adolescents with acute mania. Controlled studies of olanzapine in adolescent bipolar disorder appear to be warranted.

Topics: Acute Disease; Adolescent; Benzodiazepines; Bipolar Disorder; Child; Female; Humans; Male; Olanzapine; Pirenzepine; Psychology, Adolescent; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychiatric Status Rating Scales

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dyskinesia, Drug-Induced; Dystonia; Female; Humans; Olanzapine; Pirenzepine

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chlorprothixene; Clopenthixol; Female; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Recurrence

We report a female patient with a diagnosis of a not otherwise specified psychotic disorder (DSM-IV) who developed hypomania shortly after the introduction of olanzapine treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Olanzapine; Pirenzepine; Psychotic Disorders

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Pirenzepine

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Psychoses, Substance-Induced; Psychotic Disorders

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Olanzapine; Pirenzepine

In controlled studies of patients with schizophrenia, the atypical antipsychotic olanzapine has been shown to be more effective in the treatment of positive and negative symptoms compared with haloperidol at doses of 10 mg/day. However, little is known about the efficacy of olanzapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of olanzapine in the treatment of these psychotic mood disorders in comparison with nonaffective psychotic disorders and to identify clinical factors associated with olanzapine response.. In a naturalistic setting, by reviewing medical records, we assessed response to olanzapine and factors associated with response to olanzapine in 150 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital.. Patients displaying a moderate-to-marked response to olanzapine were more likely to be younger; be female; receive a diagnosis of bipolar disorder; and have a shorter duration of illness, shorter length of stay prior to olanzapine, and longer duration of trial.. Olanzapine may be a useful alternative or adjunctive treatment for patients with bipolar disorder.

Topics: Adolescent; Adult; Affective Disorders, Psychotic; Age Factors; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Controlled Clinical Trials as Topic; Drug Administration Schedule; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Retrospective Studies; Sex Factors; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Lithium; Male; Middle Aged; Olanzapine; Pirenzepine; Thyroxine; Valproic Acid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Administration Schedule; Hospitalization; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia; Substance Withdrawal Syndrome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Psychotic Disorders; Risperidone; Treatment Outcome

Olanzapine is a relatively new antipsychotic agent which appears to be effective in the treatment of both the positive and negative symptoms of schizophrenia. Reported here is the case of a patient who developed symptoms of mania secondary to treatment with olanzapine. Physicians prescribing olanzapine should be aware of this potential complication.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Olanzapine; Pirenzepine; Psychotic Disorders

To report a case of neuroleptic malignant syndrome (NMS) associated with the use of olanzapine.. A 67-year-old white man with bipolar disorder developed nausea and vomiting. After 12 days, he became confused, delirious, and manic. His only medications were olanzapine 10 mg/d and divalproex sodium 500 mg bid. He was admitted to a hospital and treated for dehydration and mania. Olanzapine was given on 6 of the first 7 hospital days. On hospital day 6, typical NMS developed with the body temperature increasing to 39.9 degrees C, obtundation, rigidity, tremor, diaphoresis, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and elevated serum creatine kinase. Olanzapine was stopped after hospital day 7, and the syndrome resolved by hospital day 12.. The patient had all of the major manifestations of NMS. There was no other likely explanation for his illness and he received no other drug likely to be associated with the syndrome. This is the first case reported in which NMS was associated with olanzapine.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Humans; Male; Neuroleptic Malignant Syndrome; Olanzapine; Pirenzepine

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Syndrome

Topics: Adult; Aggression; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia; Schizophrenia, Paranoid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Male; Middle Aged; Olanzapine; Pirenzepine

Olanzapine has emerged as an atypical antipsychotic with few side effects and potentially superior efficacy in the treatment of schizophrenia. To our knowledge there have been few published reports of olanzapine in the treatment of mood disorders. We report on the adjunctive use of this medication in three subjects with mania and two with depression. Response occurred rapidly and patients tolerated the medication. Olanzapine offers promise in the treatment of mood disorders.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Delusions; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Middle Aged; Olanzapine; Pirenzepine; Recurrence