quetiapine-fumarate and Bipolar-Disorder

The prevalence of posttraumatic stress disorder (PTSD) co-occurring in people with bipolar disorder (BD) is high. People with BD and PTSD may experience different outcomes and quality of life after pharmacologic treatment than those with BD alone. This review systematically explores the impact of PTSD on pharmacologic treatment outcomes for adults with BD.. We conducted a systematic search up to November 25, 2021, using MEDLINE Complete, Embase, American Psychological Association PsycInfo, and the Cochrane Central Register of Controlled Trials to identify randomized and nonrandomized studies of pharmacologic interventions for adults with BD that assessed for comorbid PTSD. We used the Newcastle-Ottawa Scale and Cochrane Risk of Bias tool to assess the risk of bias.. The search identified 5093 articles, and we reviewed 62 full-text articles. Two articles met inclusion criteria (N = 438). One article was an observational study, and the other was a randomized comparative effectiveness trial. The observational study examined lithium response rates and found higher response rates in BD alone compared with BD plus PTSD over 4 years. The randomized trial reported more severe symptoms in the BD plus PTSD group than in those with BD alone following 6 months of quetiapine treatment. There was no significant difference in the lithium treatment group at follow-up.. Comorbid PTSD may affect quetiapine and lithium treatment response in those with BD. Because of the high risk of bias and low quality of evidence, however, these results are preliminary. Specific studies exploring comorbid BD and PTSD are required to inform pharmacotherapy selection and guidelines appropriately. (International Prospective Register of Systematic Reviews ID: CRD42020182540).

Topics: Adult; Bipolar Disorder; Cognitive Behavioral Therapy; Humans; Lithium Compounds; Observational Studies as Topic; Quality of Life; Quetiapine Fumarate; Stress Disorders, Post-Traumatic

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

Atypical antipsychotics are newer second-generation antipsychotics with weak dopamine type 2 blocking but potent 5-HT2 antagonistic activity. They are considered first-line treatments for schizophrenia and gradually replace typical antipsychotics. Extrapyramidal side effects are minimal, and they tend to improve impaired cognitive function in psychotics. Quetiapine fumarate is an atypical antipsychotic drug used to treat schizophrenia, mania and depression in people with bipolar disorder combined with other drugs or alone. Quetiapine was developed in 1985 and approved for medical use in the USA in 1997. Thorough computer-aided literature, surveys revealed that numerous analytical methods were reported over the years. The present study reviews analytical methods with their validation parameters published during the last 22 years (1999-2021) either as a single entity or combination in dosage form, and determination from biological samples. Novel strategies for increasing separation quality, such as QbD analysis and green spectroscopy, were discovered during the evaluation, and this review can be utilized for further research reference.

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Quetiapine Fumarate; Schizophrenia

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

The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common psychotropics for BPD. MEDLINE, EMBASE, and PsycINFO were searched for proper studies. The changes in the depressive rating scale, remission/response rates, nervous system adverse events (NSAEs), gastrointestinal adverse events (GIAEs), metabolic parameters, and prolactin were compared between medication and placebo or among medications with the Cohen's d or number needed to treat/harm. The search provided 10 psychotropics for comparison. Atypical antipsychotics (AAPs) were superior to lithium and lamotrigine at alleviating acute depressive symptoms. Lithium was more likely to induce dry mouth and nausea. Cariprazine and aripiprazole seemed to be associated with an increased risk of akathisia and upper GIAEs. Lurasidone was associated with an increased risk of developing akathisia and hyperprolactinemia. Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were associated with an increased risk of NSAEs, metabolic risk, dry mouth, and constipation. Cariprazine, lurasidone, OFC, or quetiapine was optimal monotherapy for BPD. Further studies are needed to assess the efficacy and safety of lamotrigine for treating BPD. Adverse events varied widely across different drug types due to variations in psychopharmacological mechanisms, dosages, titration, and ethnicities.

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lamotrigine; Lithium; Lurasidone Hydrochloride; Psychomotor Agitation; Quetiapine Fumarate

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

In the scientific review, in order to highlight the problem of bipolar affective disorder, a systematic review of the literature in PubMed and Google was conducted, epidemiological data were presented, issues of systematization and pharmacotherapy were considered, including modern meta-analyses and recommendations, including the effectiveness and safety of antipsychotic therapy. Special attention is paid to the place of quetiapine in the treatment of both manic and depressive symptoms of bipolar disorder. Relevant full-text articles, systematic reviews, meta-analyses identified by keywords were analyzed. The review did not include publication of clinical trial results.. С целью освещения проблемы биполярного аффективного расстройства проведен систематический обзор литературы в PubMed и Google, приведены эпидемиологические данные, рассмотрены вопросы систематизации и фармакотерапии, включая современные метаанализы и рекомендации, эффективность и безопасность антипсихотической терапии. Особое внимание уделено месту кветиапина в лечении как маниакальных, так и депрессивных симптомов биполярного расстройства. Анализировались релевантные полнотекстовые статьи, систематические обзоры, метаанализы, выявленные по ключевым словам. В обзор не включались публикации результатов клинических испытаний.

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Mood Disorders; Quetiapine Fumarate

We present the case of a young gentleman with diagnoses of bipolar affective disorder, high body mass index, and obstructive sleep apnoea. He was commenced on zuclopenthixol due to an inadequate response to quetiapine, but this swiftly led to marked physical health deterioration including shortness of breath, back pain, tachycardia, tachypnoea, and hypoxia. He was urgently transferred to hospital where he required intubation and intensive care admission. AFTER excluding other causes, it was felt that commencing zuclopenthixol had induced laryngo-pharyngeal dystonia leading to upper airway compromise and severely impaired respiratory function. He progressively recovered after zuclopenthixol was stopped, and he was transferred back to the psychiatric hospital after eight days. THIS case highlights the potential challenges in diagnosing this rare but potentially fatal reaction to antipsychotics. We review the available literature on other cases including a potential interaction between typical antipsychotics and serotonin-specific reuptake inhibitors. Psychiatrists and emergency physicians should be aware of this condition and be alert in considering the administration of anticholinergics, which could be a simple yet life-saving intervention.

Topics: Antipsychotic Agents; Bipolar Disorder; Clopenthixol; Dystonia; Humans; Male; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors

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

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

Pharmacological treatments recommended for bipolar depression are inconsistent across guidelines. We compared the efficacy and safety of antipsychotics and mood stabilizers for bipolar depression.. A systemic review and meta-analysis of randomized controlled trials comparing antipsychotics and mood stabilizers for bipolar depression was conducted based on a literature search of major electronic databases.. Three studies comparing quetiapine with lithium were identified and analyzed; no other antipsychotic-mood stabilizer combinations were found. The meta-analysis revealed no significant differences between quetiapine and lithium for the following outcomes: (1) remission from depressive episodes (risk ratio [RR]: 1.80, 95% CI: 0.51-6.40, P = 0.36), (2) changes in depressive symptom (standardized mean difference: -0.22, 95% CI: -0.52-0.08, P = 0.15), (3) changes in social function (standardized mean difference: -0.00, 95% CI: -0.19-0.18, P = 0.98), (4) suicide-related events (odds ratio [OR]: 2.35, 95% CI: 0.40-13.65, P = 0.34), (5) severe adverse events (OR: 1.63, 95% CI: 0.51-5.20, P = 0.41), (6) dropouts due to adverse events (RR: 1.19, 95% CI: 0.76-1.87, P = 0.45, 7) dropout for any reasons (RR: 0.95, 95% CI: 0.74-1.22, P = 0.70).. Although this study found no differences in the efficacy and safety of quetiapine and lithium for bipolar depression, a comprehensive comparison of antipsychotics and mood stabilizers was not performed. Further studies are needed to clarify which of these, not just quetiapine and lithium, is more useful for bipolar depression.

Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Bipolar affective disorder (BPAD) is a chronic mental disorder, characterised by mood swings, alternating between depression and manic or hypomanic episodes. Unfortunately, in some patients pharmacological treatment does not bring satisfactory results, and a certain group of patients shows resistance to treatment. Therefore, other treatment methods are sought after, including a change in diet. The most promising nutrition model is the ketogenic diet. In the presented case study of a male patient, thanks to the introduction of the ketogenic diet, full remission of the disease was achieved, doses of lamotrigine were reduced and quetiapine was completely discontinued. Previously, neither lamotrigine monotherapy nor combined treatment with quetiapine achieved euthymia. The effects of the diet may be related to, among others, the influence on ionic channels and increase in blood acidity (similarly to mood stabilisers), increase in gamma-aminobutyric acid (GABA) concentration, modulation of GABAA receptors and blocking of AMPA receptors by medium-chain fatty acids. The ketogenic diet influences glutamate metabolism and nerve cell metabolism, which uses ketone bodies as energy sources. Ketosis can also stimulate the biogenesis of mitochondria, improve brain metabolism, act as a neuroprotective factor, as well as increase glutathione synthesis and reduce oxidative stress. However, there is a need for carefully planned studies, with an appropriate representative group, to verify the potential benefits and risks of introducing the ketogenic diet in patients with BPAD.

Topics: Anticonvulsants; Bipolar Disorder; Diet, Ketogenic; Humans; Lamotrigine; Male; Mood Disorders; Quetiapine Fumarate

To assess the relative efficacy and safety of second-generation antipsychotics for treating major depressive episodes in youths with bipolar disorder.. A systematic literature review using PRISMA guidelines and network meta-analysis (NMA) of randomized controlled trials (RCTs) of second-generation antipsychotics for bipolar depression in youths 10 to 18 years of age was conducted. Efficacy measures included Children's Depression Rating Scale, Revised (CDRS-R) and Clinical Global Impressions-Bipolar Disorder-Severity Depression (CGI-BP-S-depression) and Overall (CGI-BP-S-overall) scores. Available safety outcomes included discontinuations (all-cause, lack of efficacy, adverse events), metabolic parameters (weight change, cholesterol, triglycerides, glucose), changes in prolactin, and somnolence. Results from the NMA were reported as mean changes from baseline or odds ratios (OR) with 95% credible intervals (CrIs).. Four RCTs comparing placebo to lurasidone, quetiapine (1 each for immediate- and extended-release), and the olanzapine-fluoxetine combination (OFC) met all of the inclusion criteria. Lurasidone and OFC demonstrated similar and statistically significant improvements in CDRS-R, but quetiapine did not (lurasidone: -5.70 [-8.66, -2.76]; OFC: -5.01 [-8.63, -1.38]; quetiapine: -1.85 [-5.99, 2.27]). Lurasidone was associated with smaller changes in weight, cholesterol, and triglycerides from baseline compared to OFC and quetiapine. There were no differences in changes in glucose levels among antipsychotics. In addition, lurasidone was associated with smaller change in prolactin levels compared to OFC but not quetiapine.. Evidence from 4 studies in this NMA indicated that lurasidone and OFC, but not quetiapine, were efficacious for the treatment of bipolar depression in youths. Lurasidone was associated with less weight gain and smaller impacts on cholesterol and triglycerides compared with quetiapine and OFC.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Humans; Lurasidone Hydrochloride; Network Meta-Analysis; Quetiapine Fumarate; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Brief Psychiatric Rating Scale; Child; Drug Combinations; Fluoxetine; Humans; Lurasidone Hydrochloride; Pediatrics; Psychopharmacology; Quetiapine Fumarate

This systematic review aimed at providing a critical, comprehensive synthesis of international guidelines' recommendations on the long-term treatment of bipolar disorder type I (BD-I).. MEDLINE/PubMed and EMBASE databases were searched from inception to January 15th, 2019 following PRISMA and PICAR rules. International guidelines providing recommendations for the long-term treatment of BD-I were included. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II.. The final selection yielded five international guidelines, with overall good quality. The evaluation of applicability was the weakest aspect across the guidelines. Differences in their updating strategies and the rating of the evidence, particularly for meta-analyses, randomized clinical trials (RCTs) and observational studies, could be responsible of some level of heterogeneity among recommendations. Nonetheless, the guidelines recommended lithium as the 'gold standard' in the long-term treatment of BD-I. Quetiapine was another possible first-line option as well as aripiprazole (for the prevention of mania). Long-term treatment should contemplate monotherapy, at least initially. Clinicians should check regularly for efficacy and side effects and if necessary, switch to first-line alternatives (i.e. Valproate), combine first-line compounds with different mechanisms of action or switch to second-line options or combinations.. The possibility to monitor improvements in long-term outcomes, namely relapse prevention and inter-episode subthreshold depressive symptoms, based on the application of their recommendations is an unmet need of clinical guidelines. In terms of evidence of clinical guidelines, there is a need for more efficacious treatment strategies for the prevention of bipolar depression.

Topics: Algorithms; Antipsychotic Agents; Bipolar Disorder; Humans; Quetiapine Fumarate; Valproic Acid

A systematic review and meta-analysis of double-blind, randomized placebo-controlled trials were conducted to examine how soon an increase in recurrence risk could be observed among bipolar I disorder (BDI) patients who were clinically stable with the combination therapy of mood stabilizers with second-generation antipsychotics (SGA+MS) treatment following second-generation antipsychotics discontinuation (i.e., MS alone) compared with SGA+MS maintenance.. Embase, PubMed, and CENTRAL databases were used for systematic literature searches until May/22/2020. The primary outcome was the recurrence rate of any mood episode at 6 months. The secondary outcomes were the recurrence rates of manic/hypomanic/mixed and depressive episodes and all-cause discontinuation at 6 months. The recurrence rates at 1, 2, 3, 9, and 12 months were also investigated.. Eight studies (mean study duration = 58.25 ± 33.63 weeks) were identified (SGA+MS group [n = 1,456: 3 aripiprazole+MS studies, 1 lurasidone+MS study, 1 olanzapine+MS study, 2 quetiapine+MS studies, 1 ziprasidone+MS study] and placebo+MS group [n = 1,476]). Pooled SGA+MS exhibited lower recurrence rates of any mood episode, manic/hypomanic/mixed episodes, and depressive episodes as well as reduced all-cause discontinuation at every observational point. The risk ratios (95% confidence interval) of the recurrence rate at 6 months were 0.51 (0.39-0.86) for any mood episode, 0.42 (0.30-0.59) for manic/hypomanic/mixed episodes, and 0.39 (0.28-0.54) for depressive episodes. The RR for all-cause discontinuation was 0.67 (0.50-0.89). Both aripiprazole+MS and quetiapine+MS outperformed placebo+MS in the recurrence of any mood, manic/hypomanic/mixed, and depressive episodes at 6 months.. SGA+MS prevented recurrence for up to 12 months for BDI compared with placebo+MS.

Topics: Antimanic Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Atypical antipsychotics are increasingly used in the treatment of bipolar disorder (BD). This systematic review provides an overview of recently published randomized controlled trials (RCTs) on the efficacy and safety of atypical antipsychotics in BD.. Several studies supported efficacy of quetiapine monotherapy in acute bipolar I (BDI) and bipolar II (BDII) depression. Moreover, quetiapine adjunctive therapy showed superior efficacy to placebo in treatment-resistant bipolar depression. Cariprazine 1.5 mg was effective in treating bipolar I depression. Aripiprazole 400 mg IM once monthly was effective in preventing manic episodes with minimal metabolic effects. In youth with BD, lurasidone was effective and well-tolerated for acute depression while asenapine showed efficacy in treating acute manic and mixed episodes. Recently published RCTs generally support the efficacy of atypical antipsychotics in different phases of BD. Future studies should focus on understudied populations including pediatric BD and geriatric BD and BDII, as well as a focus on cognitive functioning and quality of life measures.

Topics: Adolescent; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Child; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT's) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression.. Efficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement - Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated.. Eighteen RCT's met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (- 4.71 [95% Crl - 6.98, - 2.41]), quetiapine (- 4.80 [- 5.93, - 3.72]), olanzapine (- 4.57 [- 5.92, - 3.20]), and cariprazine (- 2.29 [- 3.47, - 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (- 0.38 [95% Crl - 0.66,-0.10]) and ziprasidone (- 0.58 [- 0.91,-0.26]), but similar to quetiapine (- 0.08 [- 0.36, 0.19])and olanzapine (- 0.04 [- 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl - 0.22, 0.89]) and aripiprazole (0.20 kg [- 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12).. In this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.

Topics: Adult; Antipsychotic Agents; Bayes Theorem; Bipolar Disorder; Depression; Humans; Network Meta-Analysis; Quetiapine Fumarate; Treatment Outcome

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

German S3 guidelines are subject to the highest methodological standards. This includes that they are only valid for a certain time period. Following the first edition in 2012 the first update of the S3 guidelines on bipolar disorder has now been published (2019).. What has changed in the field of pharmacological recommendations comparing the first edition with the update in 2019?. Comparison of the 1st edition from 2012 with the update from 2019 of the S3 guidelines for the diagnostics and treatment of bipolar disorders.. The three principle treatment targets of acute treatment of bipolar depression, acute treatment of mania and phase prophylaxis (maintenance treatment) can be distinguished. For acute treatment of bipolar depression, for the first time a medication has received a level A recommendation: quetiapine. For the acute treatment of mania, several drugs are still recommended with the same level of recommendation (B). Asenapine has been added as the tenth substance. Lithium is still the only drug with a level A recommendation for maintenance and prophylactic treatment and is also the only drug approved for this indication without restrictions. A new recommendation is that in the absence of contraindications, phase prophylaxis with a serum level of at least 0.6 mmol/l should be carried out. With a B recommendation, quetiapine has been added to the drugs for phase prophylactic treatment.. The S3 guidelines make recommendations at the highest scientific level. In view of these findings, lithium is clearly underutilized for maintenance therapy. In the absence of clear contraindications (advanced renal insufficiency), every patient with bipolar disease should be given the chance of lithium prophylaxis for an adequately long period.

Topics: Antipsychotic Agents; Bipolar Disorder; Drug Therapy; Germany; Guidelines as Topic; Humans; Quetiapine Fumarate

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

We examined systematic adverse events (AEs) in Part 1 (of 2) of a study describing the assessment and reporting of AEs in clinical trials.. We examined 52 public and nonpublic data sources about trials of quetiapine for bipolar depression using data from the Multiple Data Sources study. We extracted and compared information about systematic AEs (i.e., AEs assessed for all participants) in six prespecified domains: cardiovascular, cholesterol, endocrine, extrapyramidal symptoms, mania, and weight.. Eligible trials did not assess and report the same systematic AEs, and most results were not available in public sources. Overall, public sources reported 159 results, of which 92 of 159 (58%) included sufficient statistical information to calculate the treatment effect and its precision. Nonpublic sources reported 636 results; 630 of 636 (99%) reported sufficient statistical information.. Systematic AEs were defined and analyzed in many ways, which led to many numerical results. Most systematic AEs were not mentioned in public sources. To minimize bias, methods for defining and analyzing potential AEs should be prespecified in trial registers and protocols. All trial results should be publicly available so that stakeholders can compare benefits and AEs. Trials could report core sets of AEs to facilitate decision-making.

Topics: Bipolar Disorder; Data Accuracy; Drug-Related Side Effects and Adverse Reactions; Gabapentin; Humans; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

We examined nonsystematic adverse events (AEs) in Part 2 (of 2) of a study describing the assessment and reporting AEs in clinical trials.. We examined 21 trials of gabapentin for neuropathic pain (52 sources) and seven trials of quetiapine for bipolar depression (80 sources) using data from the Multiple Data Sources study. We extracted and compared information about nonsystematic AEs (i.e., AEs that were not assessed for every participant), including AEs categorized as "serious." We recorded whether AEs were grouped by anatomic or physiological system.. Trials of the same drug reported information about different AEs. Information in public sources was inadequate for decision-making. No public source reported all AEs, or all serious AEs, identified in nonpublic sources about the same trial. Of trials with only public sources, 2/15 (13%) gabapentin and 0/3 (0%) quetiapine trials grouped AEs by anatomic or physiological system.. Public sources contained little information about nonsystematic AEs, including serious AEs. Grouping might make nonsystematic AEs easier to detect; however, most public sources did not report grouped AEs. Standards are needed to improve the collection and reporting of nonsystematic AEs so that stakeholders can use trials to assess the balance of potential benefits and harms.

Topics: Bipolar Disorder; Data Accuracy; Drug-Related Side Effects and Adverse Reactions; Gabapentin; Humans; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

Substance use disorders (SUDs), including those for alcohol, stimulants, tobacco, opioids and cannabis, in patients with bipolar disorder are a major clinical and public health problem, and are present in the majority of these patients. Nonetheless, the development of effective pharmacological treatments for co-occurring SUDs in bipolar illness have not been well-developed and may be an important practical reason for the reduced effectiveness of these medications in community practice.. We conducted a systematic review of the literature (PubMed, Medline, Google Scholar), and identified N = 29 clinical studies, which evaluated both mental health and SUD outcomes in patients with co-occurring bipolar disorders and SUDs.. Our findings suggest the potential of valproate sodium and lamotrigine as preferred pharmacological agents for the treatment of co-occurring psychiatric and substance use outcomes in these patients. However, many of the reviewed studies are of open-label designs and of modest sample sizes.. Thus, given the gaps in our knowledge, recommendations for treatment of this common and important co-morbidity are preliminary. Accordingly, the conduct of larger, randomized controlled trials for this co-morbidity is clearly needed.

Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Comorbidity; Humans; Lamotrigine; Lithium Compounds; Quetiapine Fumarate; Substance-Related Disorders; Topiramate; Valproic Acid

This study evaluated the efficacy and safety/tolerability of quetiapine extended-release 300 mg/day (QUEXR300), quetiapine immediate-release 600 mg/day (QUEIR600), and quetiapine immediate-release 300 mg/day (QUEIR300) formulations for treating bipolar depression. A random-effect network meta-analysis of 8-week, double-blind, randomized placebo-controlled trials was used to determine the most optimal agent for intervention. Remission rate was set as the primary outcome. Secondary outcomes were response rate, improvement in the Montgomery-Åsberg Depression Rating Scale score, discontinuation rate, and the incidence of individual adverse events. Seven eligible studies including 3267 participants were included in the meta-analysis. The QUEIR600, QUEIR300, and QUEXR300 groups were superior to the placebo group in every efficacy outcome; however, there were no significant differences in the efficacy outcomes among the treatment groups. All treatment groups exhibited higher incidences of extrapyramidal symptoms, dry mouth, somnolence, constipation, and increase in body weight than the placebo group. The QUEIR600 and QUEIR300 groups had higher incidences of dizziness than the placebo group. The QUEIR600 group had a higher discontinuation rate due to adverse events than the placebo group, and the QUEIR300 group had higher blood HbA1c levels than the placebo group. The QUEIR600 and QUEXR300 groups had higher incidences of ≥7% weight gain than the placebo group. The QUEXR300 group had a higher incidence of fatigue than the QURIR300 and placebo groups. In conclusion, there were no significant differences in the efficacies of QUEIR600, QUEIR300, and QUEXR300 in treating bipolar depression; moreover, tolerance to QUEIR600 might be worse than the other treatments.

Topics: Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Humans; Network Meta-Analysis; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic

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

For more than 40 years, lithium has been the gold standard in the long-term treatment of bipolar disorders. In the course of the last 15 years, other drugs have been approved in this indication and are widely used in clinical practice at the expense of lithium. New research from the last few years, however, indicates that lithium is still the first-line treatment in this indication. Against this background and lithium's proven acute antimanic efficacy, we should perhaps be using lithium more regularly (in combination with an atypical antipsychotic, if necessary) right from the start for the acute treatment of a manic episode and, once remission has been achieved and euthymia maintained during continuation treatment, to regularly taper off the atypical antipsychotic, if possible, and continue with lithium as monotherapy for prophylactic treatment. This might lead to lithium being used more consistently with the scientific evidence in the long-term treatment of bipolar disorders. It remains uncertain, however, to predict who will respond to and tolerate lithium prophylactically, and more research is needed to deliver the best possible individualized care to our patients.

Topics: Antimanic Agents; Bipolar Disorder; Databases, Factual; Drug Therapy, Combination; History, 21st Century; Humans; Lithium Compounds; Longitudinal Studies; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

To identify variations in outcomes and results across reports of randomized clinical trials (RCTs).. Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic (e.g., clinical study reports) sources by 2015. We prespecified outcome domains. From each source, we collected "outcomes" (i.e., domain, measure, metric, method of aggregation, and time point); "treatment effect" (i.e., outcome plus the methods of analysis [e.g., how missing data were handled]); and results (i.e., numerical contrasts of treatment and comparison groups). We assessed whether results included sufficient information for meta-analysis.. We found 21 gabapentin (68 public, 6 nonpublic reports) and seven quetiapine RCTs (46 public, 4 nonpublic reports). For four (gabapentin) and seven (quetiapine) prespecified outcome domains, RCTs reported 214 and 81 outcomes by varying four elements. RCTs assessed 605 and 188 treatment effects by varying the analysis of those outcomes. RCTs reported 1,230 and 661 meta-analyzable results, 305 (25%) and 109 (16%) in public reports.. RCTs included hundreds of outcomes and results; a small proportion were in public reports. Trialists and meta-analysts may cherry-pick what they report from multiple sources of RCT information.

Topics: Amines; Analgesics; Antipsychotic Agents; Bipolar Disorder; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Neuralgia; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

The objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs).. Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic sources (clinical study reports [CSRs] and individual participant data [IPD]).. We found 21 gabapentin RCTs (74 reports, 6 IPD) and 7 quetiapine RCTs (50 reports, 1 IPD); most were reported in journal articles (18/21 [86%] and 6/7 [86%], respectively). When available, CSRs contained the most trial design and risk of bias information. CSRs and IPD contained the most results. For the outcome domains "pain intensity" (gabapentin) and "depression" (quetiapine), we found single trials with 68 and 98 different meta-analyzable results, respectively; by purposefully selecting one meta-analyzable result for each RCT, we could change the overall result for pain intensity from effective (standardized mean difference [SMD] = -0.45; 95% confidence interval [CI]: -0.63 to -0.27) to ineffective (SMD = -0.06; 95% CI: -0.24 to 0.12). We could change the effect for depression from a medium effect (SMD = -0.55; 95% CI: -0.85 to -0.25) to a small effect (SMD = -0.26; 95% CI: -0.41 to -0.1).. Disagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.

Topics: Amines; Bias; Bipolar Disorder; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Humans; Meta-Analysis as Topic; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

The aim of this paper is to underline the need for systematic monitoring of patients treated with anticholinergic antipsychotic drugs. We present the clinical history of a 34-year-old adult, treated with quetiapine in combination with other drugs with anticholinergic effects.. A 34-year-old male adult had been suffering from bipolar disorder since 2001. He was treated with risperidone, but he was not compliant due to adverse effects, including decreased libido and erectile dysfunction. On June 5th 2012, it was decided to administrate 600mg per day of quetiapine in combination with tropatepine consequent to an episode of agitation and aggressiveness. On June 14th 2012, while the patient was receiving diazepam and valproic acid, loxapine oral solution was introduced. On June 23th, the patient started mentioning digestive disorders, such as diffuse abdominal pain with constipation but continued to pass gaz. On June 25th, at 6:30 am, he declared abdominal pain, which worsened at 8:15 am despite administration of analgesics, followed by malaise and onset of vomiting. His laboratory tests showed leukocytosis 11.2G/L with neutrophils 7.7G/L. The abdomen's radiograph without preparation showed small bowel and colonic air-fluid levels. The result of the CT scan confirmed an occlusive syndrome affecting the whole small gut and colon. At 1 pm, the patient's condition worsened. He received an intramuscular injection of 100mg of loxapine and an opioid treatment, including tramadol and morphine. At 2:30 pm, the clinical condition further deteriorated with an onset of generalized abdominal contracture, the absence of abdominal breathing, sweating, tachycardia at 104 beats per minute, and hypothermia of 34.5°C. He was transferred to an intensive care unit. Laboratory tests showed metabolic acidosis, elevated liver enzymes and acute renal failure. He received volume expansion and was treated by renal replacement therapy and antibiotics. He was intubated and transferred to the operating room. At laparotomy, both colonic necrosis with perforation and necrosis of the small bowel were seen. The patient underwent total colectomy with small bowel resection, distal ileostomy and closure of the rectal stump. The onset of septic and hemorrhagic state required further surgery on June 26th. The evolution was characterized by multi-organ failure with acute anuric renal failure, multiple cardiac arrests, and systemic bacterial and fungal infection. On July 24th, this unfavorable outcome lead to death. In summary, the patient had an occlusive syndrome due to neuroleptics and complications, including mesenteric ischemia with necrotizing colitis.. Quetiapine, like all antipsychotics, has anticholinergic effects, including cardiac, psychiatric and digestive disorders. The combination of anticholinergic drugs decreases intestinal peristalsis. Without any prompt management, this decrease can result in a colonic ischemia or necrosis. In patients treated with neuroleptics, the onset of constipation must alert medical staff. Systematic monitoring of bowel movements should be performed in any patient receiving anticholinergic drugs.

Topics: Adult; Bipolar Disorder; Cholinergic Antagonists; Colitis, Ischemic; Drug Interactions; Drug Therapy, Combination; Humans; Male; Quetiapine Fumarate

Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.

Topics: Animals; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Evaluation, Preclinical; Humans; Quality of Life; Quetiapine Fumarate

Lithium, the prototypical mood stabilizer, and quetiapine, a second-generation antipsychotic, are widely used acute and maintenance pharmacotherapies for bipolar disorder. The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study was the first comparative effectiveness assessment of lithium versus quetiapine (in combination with adjunctive personalized treatment), and found no overall significant differences in efficacy and safety/tolerability outcomes between lithium and quetiapine. Completion of Bipolar CHOICE offers a timely opportunity to review the evidence regarding lithium and quetiapine for bipolar disorder.. Controlled clinical trials and real-world observational studies that included quetiapine and lithium as monotherapy or as combination therapy were identified by literature search. Selected studies were reviewed in detail.. Review of the available trials suggested comparable efficacy of quetiapine and lithium in acute mania, and possibly greater efficacy for quetiapine compared with lithium in acute bipolar depression and in prevention of recurrent (particularly depressive) episodes. Combination therapy including quetiapine and lithium was generally more effective than either agent alone in acute mania and bipolar maintenance, although adding lithium to quetiapine did not increase efficacy in acute bipolar depression. Safety data for quetiapine and lithium were consistent with the established profiles of the two treatments.. Limitations include those of the available efficacy and effectiveness trial data.. Quetiapine and lithium have overlapping but distinctive roles in different phases of bipolar disorder, and further studies of these agents (particularly in combination with one another) are warranted.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Middle Aged; Observational Studies as Topic; Quetiapine Fumarate; Young Adult

A role for second-generation antipsychotics (SGAs) in the treatment of panic disorders (PD) has been proposed, but the actual usefulness of SGAs in this disorder is unclear. According to the PRISMA guidelines, we undertook an updated systematic review of all of the studies that have examined, in randomized controlled trials, the efficacy and tolerability of SGAs (as either monotherapy or augmentation) in the treatment of PD, with or without other comorbid psychiatric disorders. Studies until 31 December 2015 were identified through PubMed, PsycINFO, Embase, Cochrane Library and Clinical trials.gov. Among 210 studies, five were included (two involving patients with a principal diagnosis of PD and three involving patients with bipolar disorder with comorbid PD or generalized anxiety disorder). All were eight-week trials and involved treatments with quetiapine extended release, risperidone and ziprasidone. Overall, a general lack of efficacy of SGAs on panic symptoms was observed. Some preliminary indications of the antipanic effectiveness of risperidone are insufficient to support its use in PD, primarily due to major limitations of the study. However, several methodological limitations may have negatively affected all of these studies, decreasing the validity of the results and making it difficult to draw reliable conclusions. Except for ziprasidone, SGAs were well tolerated in these short-term trials.

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Panic Disorder; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles

Corticosteroids generally result in short-lasting neuropsychiatric symptoms following cessation, but the following case highlights an unusually long-lasting course of symptoms in a patient following near immediate cessation of medication, despite medication management and electroconvulsive therapy. The case presentation will be followed by a discussion of the presentation, treatment, and management of steroid-induced neuropsychiatric symptoms.. The patient was followed from symptom onset to resolution.. The patient's symptom course was unusually long and required a long course of multimodal therapy.. Corticosteroids are commonly used medications both in a wide variety of medical settings, and despite this, their neuropsychiatric effects are poorly understood. The affective and behavioral symptoms, in particular mania and psychosis, can be unpredictable and challenging to treat as in our patient, who developed a long-lasting psychotic episode on high-dose steroids despite discontinuation and treatment of nearly six months. This was despite having tolerated steroids multiple times in the past.

Topics: Adrenal Cortex Hormones; Bipolar Disorder; Dexamethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroconvulsive Therapy; Hospitalization; Humans; Long-Term Care; Male; Middle Aged; Prednisone; Psychoses, Substance-Induced; Purpura, Thrombocytopenic; Quetiapine Fumarate; Retreatment; Substance Withdrawal Syndrome

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

The safety and efficacy of quetiapine for the treatment of insomnia in adults are reviewed.. Quetiapine was developed for the treatment of psychiatric disorders, but its antagonism of histamine H1- and serotonin type 2A receptors has the added effect of causing sedation. As such, quetiapine is widely used off-label as a treatment for insomnia. Due to quetiapine's potential adverse effects, guidelines for the treatment of insomnia have recommended the drug's use only in patients with specific comorbid psychiatric disorders. The use of quetiapine for the treatment of insomnia in the absence of comorbid conditions has been evaluated in only two clinical trials of 31 patients in total, and very few studies have evaluated quetiapine use in patients with insomnia and other comorbidities. No trials have been conducted comparing quetiapine with an active control (e.g., zolpidem); the data that exist compare quetiapine to a placebo or there is no comparison and all patients are treated with quetiapine. Very few studies have evaluated quetiapine's efficacy in the treatment of insomnia using sleep objective testing, another limitation of the available data on quetiapine.. Robust studies evaluating the safety and efficacy of quetiapine for the treatment of insomnia are lacking. Given its limited efficacy data, its adverse-effect profile, and the availability of agents approved by the Food and Drug Administration for the treatment of insomnia, quetiapine's benefit in the treatment of insomnia has not been proven to outweigh potential risks, even in patients with a comorbid labeled indication for quetiapine.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders

Pancreatitis is a very rare adverse effect of quetiapine treatment, with only 5 cases of quetiapine-associated pancreatitis reported in the English literature to date. Herein, we report one patient who developed severe hypertriglyceridemia (>1000 mg/dL) after quetiapine administration, resulting in acute pancreatitis. An analysis of the underlying pathogenic mechanisms and a review of relevant literature are also presented. Clinicians should be aware of the potentially life-threatening metabolic disturbances and/or pancreatitis associated with quetiapine therapy.

Topics: Acute Disease; Bipolar Disorder; Dibenzothiazepines; Humans; Hypertriglyceridemia; Pancreatitis; Quetiapine Fumarate

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

Precise estimated risks and benefits of quetiapine for acute bipolar depression are needed for clinical practice.. To systematically review the efficacy and the tolerability of quetiapine, either as monotherapy or combination therapy, for acute bipolar depression.. We included all randomized, controlled trials (RCTs) comparing quetiapine with other treatments, including placebo, in patients with acute bipolar depression (bipolar I or II disorder, major depressive episode). Published and unpublished RCTs were identified using the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Knowledge, CINAHL, PsycINFO, the EU Clinical Trials Register database, and ClinicalTrials.gov. The primary outcome was the change scores of depression rating scales.. Eleven RCTs (n=3,488) were included. Two of them were conducted in children and adolescents. The change in depression scores was significantly greater in the quetiapine group compared with the placebo group (mean difference, [MD] =-4.66, 95% confidence interval [CI] -5.59 to -3.73). The significant difference was observed from week 1. Compared with placebo, quetiapine had higher incidence rates of extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain but lower risks of treatment-emergent mania and headache. Quetiapine treatment was associated with significant improvement of clinical global impression, quality of life, sleep quality, anxiety, and functioning.. Quetiapine monotherapy is effective for acute bipolar depression and the prevention of mania/hypomania switching. Its common adverse effects are extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain. The lower risk of headache in quetiapine-treated patients with acute bipolar depression should be further investigated. The evidence for the use of quetiapine combined with mood stabilizers in children and adolescents with acute bipolar depression is too small to support the clinical practice.

Topics: Acute Disease; Bipolar Disorder; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Management of bipolar disorder (BD) requires a complex combination of pharmacological and psychosocial interventions. Over recent decades the therapeutic arsenal for BD has expanded to include lithium, anticonvulsants and second-generation antipsychotics (SGAs). Immediate release (IR) quetiapine fumarate is a SGA approved in several countries for the treatment of patients with schizophrenia and BD or as an add-on treatment for major depressive disorders. Extended release (XR) quetiapine fumarate was developed more recently. There is interest in a once-daily formulation which may improve patient compliance but there may be some differences between quetiapine IR and XR in terms of safety and efficacy. This article provides an update of recent data on the efficacy and safety of quetiapine XR for the treatment of BD.

Topics: Antipsychotic Agents; Bipolar Disorder; Databases, Factual; Dibenzothiazepines; Drug Delivery Systems; Humans; Quetiapine Fumarate

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

A major challenge in the treatment of major depressive episodes associated with bipolar disorder is differentiating this illness from major depressive episodes associated with major depressive disorder. Mistaking the former for the latter will lead to incorrect treatment and poor outcomes. None of the classic antidepressants, serotonin specific reuptake inhibitors, or serotonin-norepinephrine reuptake inhibitors have ever received regulatory approval as monotherapies for the treatment of bipolar depression. At present, there are only 3 approved medication treatments for bipolar depression: olanzapine/fluoxetine combination, quetiapine (immediate or extended release), and lurasidone (monotherapy or adjunctive to lithium or valproate). All 3 have similar efficacy profiles, but they differ in terms of tolerability. Number needed to treat (NNT) and number needed to harm (NNH) can be used to quantify these similarities and differences. The NNTs for response and remission for each of these interventions vs placebo range from 4 to 7, and 5 to 7, respectively, with overlap in terms of their 95% confidence intervals. NNH values less than 10 (vs placebo) were observed for the spontaneously reported adverse events of weight gain and diarrhea for olanzapine/fluoxetine combination (7 and 9, respectively) and somnolence and dry mouth for quetiapine (3 and 4, respectively). There were no NNH values less than 10 (vs placebo) observed with lurasidone treatment. NNH values vs placebo for weight gain of at least 7% from baseline were 6, 16, 58, and 36, for olanzapine/fluoxetine combination, quetiapine, lurasidone monotherapy, and lurasidone combined with lithium or valproate, respectively. Individualizing treatment decisions will require consideration of the different potential adverse events that are more likely to occur with each medication. The metric of the likelihood to be helped or harmed (LHH) is the ratio of NNH to NNT and can illustrate the tradeoffs inherent in selecting medications. A more favorable LHH was noted for treatment with lurasidone. However, OFC and quetiapine monotherapy may still have utility in high urgency situations, particularly in persons who have demonstrated good outcomes with these interventions in the past, and where a pressing clinical need for efficacy mitigates their potential tolerability shortcomings. In terms of maintenance therapy, adjunctive quetiapine is the only agent where the NNT vs lithium or valproate alone is less than 10 for

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Drug Combinations; Drug Therapy, Combination; Fluoxetine; Humans; Isoindoles; Lithium Compounds; Lurasidone Hydrochloride; Quetiapine Fumarate; Thiazoles; Valproic Acid

Depression is the predominant pole of illness disability in bipolar disorder and, compared with acute mania, has less systematic research guiding treatment development. The aim of this review is to present the therapeutic options currently available for managing bipolar depression and to highlight areas of unmet need and future research.. Literature search of PubMed, PsycINFO, and Cochrane databases and bibliographies from 2000 to August 2013 for treatments that have regulatory approval for bipolar depression or early controlled preliminary data on efficacy.. Treatment options for bipolar depression have increased over the last decade, most notably with regulatory approval for olanzapine/fluoxetine combination, quetiapine, and lurasidone. Conventional mood stabilizers lamotrigine and divalproex have meta-analyses suggesting acute antidepressant response. Manual-based psychotherapies also appear to be effective in treating bipolar depression. The therapeutic utility of unimodal antidepressants, as a class, for the treatment of patients with bipolar depression, as a group, remains to be confirmed. There is a substantially unmet need to develop new interventions that are efficacious, effective, and have low side effect burden.. Additional compounds are currently being developed that may ultimately be applicable to the treatment of bipolar depression and early open-trial data encourage further studies, but both of these topics are beyond the scope of this review.. Future registrational trials will need to establish initial efficacy, but increasing interest for personalized or individualized medicine will encourage further studies on individual predictors or biomarkers of response.

Topics: Anticonvulsants; Antidepressive Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Combinations; Fluoxetine; Forecasting; Health Services Needs and Demand; Humans; Isoindoles; Lamotrigine; Lurasidone Hydrochloride; Psychotherapy; Quetiapine Fumarate; Thiazoles; Triazines

Bipolar depression is more pervasive than mania, but has fewer evidence-based treatments.. Using data from multicenter, randomized, double-blind, placebo-controlled trials and meta-analyses, we assessed the number needed to treat (NNT) for response and the number needed to harm (NNH) for selected side effects for older and newer acute bipolar depression treatments.. The 2 older FDA-approved treatments for bipolar depression, olanzapine-fluoxetine combination (OFC) and quetiapine (QTP) monotherapy, were efficacious (response NNT=4 for OFC, NNT=6 for QTP), but similarly likely to yield harms (OFC weight gain NNH=6; QTP sedation/somnolence NNH=5). Commonly used unapproved agents (lamotrigine monotherapy and adjunctive antidepressants) tended to be well-tolerated (with double-digit NNHs), although this advantage was at the cost of inadequate efficacy (response NNT=12 for lamotrigine, NNT=29 for antidepressants). In contrast, the newly approved agent lurasidone was not only efficacious (response NNT=5 for monotherapy, NNT=7 as adjunctive therapy), but also had enhanced tolerability (NNH=15 for akathisia [monotherapy], NNH=16 for nausea [adjunctive]). Although adjunctive armodafinil appeared well tolerated, its efficacy in bipolar depression has not been consistently demonstrated in randomized controlled trials.. NNT and NNH are categorical metrics; only selected NNHs were assessed; limited generalizability of efficacy (versus effectiveness) studies.. For acute bipolar depression, older approved treatments may have utility in high-urgency situations, whereas lamotrigine and antidepressants may have utility in low-urgency situations. Newly approved lurasidone may ultimately prove useful in diverse situations. New drug development needs to focus on not only efficacy but also on tolerability.

Topics: Acute Disease; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Combinations; Fluoxetine; Humans; Isoindoles; Lamotrigine; Lurasidone Hydrochloride; Multicenter Studies as Topic; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Thiazoles; Triazines; Weight Gain

A series of studies were conducted to guide the development and characterise the pharmacokinetics of extended-release quetiapine fumarate (quetiapine XR), a once-daily formulation to control the release of the drug.. Data from these studies are described and discussed herein.. Once-daily quetiapine XR produced a similar area under the plasma concentration-time curve (AUC), minimum plasma concentration (Cmin) and a slightly lower maximum plasma concentration (Cmax) than the equivalent dose of immediate-release quetiapine (quetiapine IR) given twice daily. In a crossover, head-to-head study, total daily exposure, measured by AUC at steady state, was less variable with quetiapine XR versus quetiapine IR (percent coefficient of variation 39.2% versus 51.2%, respectively). Compared with fasting, a high-fat meal increased the AUC and Cmax for quetiapine XR, whereas a light meal had no significant effect on these parameters. Quetiapine XR exhibits a less pronounced D2 receptor occupancy peak and receptor occupancy levels remain higher for longer compared with quetiapine IR. Quetiapine XR was generally well tolerated with a safety profile similar to quetiapine IR, although the intensity of sedation in the first hours of treatment was significantly lower (p < 0.01) with quetiapine XR versus IR.. At steady state, quetiapine XR provided a similar AUC and Cmin and a slightly lower Cmax relative to an equivalent dose of quetiapine IR administered twice daily. Quetiapine XR exhibited linear pharmacokinetics in the dose range tested and no food effect was observed with a light meal. Once-daily dosing and simpler dose titration makes using quetiapine XR convenient for clinicians and patients. Quetiapine XR has predictable pharmacokinetics and was generally well tolerated, with significantly lower intensity of sedation after the first hours of administration compared with quetiapine IR. With once-daily quetiapine XR, the impact of daytime sedation may be mitigated by evening dosing.

Topics: Antipsychotic Agents; Biological Availability; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Eating; Fasting; Humans; Medication Adherence; Quetiapine Fumarate; Schizophrenia

Herein we review the evidence supporting Food and Drug Administration (FDA) approved and emerging treatments for bipolar depression.. A PubMed search of all English-language articles published up to July 2013 was conducted. The search terms were quetiapine, olanzapine-fluoxetine, olanzapine, lurasidone, ketamine, modafinil/armodafinil, and lamotrigine. The search was augmented with a manual review of relevant article reference lists, as well as posters presented at national and international meetings. Articles selected for review were based on the adequacy of sample size, the use of standardized diagnostic instruments, validated assessment measures, and overall manuscript quality.. Olanzapine-fluoxetine combination (OFC), quetiapine, and lurasidone are FDA-approved for the acute treatment of bipolar depression. Lurasidone is the most recently approved agent for bipolar depression. Olanzapine-fluoxetine combination and quetiapine are approved as single modality therapies while lurasidone is approved as a monotherapy and as an adjunct to lithium or divalproex. The overall effect size of the 3 treatments in mitigating depressive symptoms is similar. Clinically significant weight gain and metabolic disruption as well as sedation are significant limitations of OFC and quetiapine. The minimal propensity for weight gain as well as the metabolic neutrality of lurasidone in the bipolar population is a clinically significant advantage. Evidence also supports lamotrigine with compelling evidence as an adjunct to lithium and in recurrence prevention paradigm; suggested evidence also exists for ketamine and modafinil/armodafinil; notwithstanding, these treatments remain investigational.. Relatively few agents are FDA-approved for bipolar depression. The selection and sequencing of agents in bipolar depression should give primacy to those agents that are FDA-approved. Further refinement of the selection process will need to pay careful attention to the relative hazards of weight gain and metabolic disruption in this highly susceptible population. Other agents with differential mechanisms (eg, ketamine) offer a promising alternative in bipolar depression.

Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzhydryl Compounds; Benzodiazepines; Bipolar Disorder; Central Nervous System Stimulants; Depressive Disorder; Dibenzothiazepines; Drug Approval; Drug Combinations; Excitatory Amino Acid Antagonists; Fluoxetine; Humans; Isoindoles; Ketamine; Lamotrigine; Lurasidone Hydrochloride; Modafinil; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Thiazoles; Triazines; United States; United States Food and Drug Administration

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

Quetiapine has been proposed for depression in bipolar patients but a quantitative analysis is lacking. In the present paper, we review and meta-analyze available data about the short-term and long-term efficacy and tolerability of quetiapine for the depressive phase of bipolar disorder or bipolar depression. A literature research was carried out using three electronic databases. Studies providing measures of efficacy and tolerability of quetiapine, either as monotherapy or as augmentation, for bipolar depression were considered. Seven short-term studies and four maintenance studies were included. Short-term studies suggested that patients treated with quetiapine monotherapy were significantly more likely than patients treated with placebo and further active comparators to achieve higher response and remission rates as well as more clinical improvements at the endpoint. Such benefits were significant from the first weeks of treatment onward. Maintenance studies suggested that the combination of quetiapine and mood stabilizers was significantly better than placebo plus mood stabilizers for the prevention of both depressive and manic relapses. Quetiapine was generally well tolerated. Furthermore, several clinical variables moderated outcomes under investigation. In conclusion, quetiapine could have some advantages over traditional treatments for the treatment of bipolar depression.

Topics: Adolescent; Adult; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Dopamine Antagonists; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Norepinephrine; Quetiapine Fumarate; Serotonin Antagonists; Time Factors

Quetiapine (Seroquel®) is an orally administered atypical antipsychotic that is indicated for the treatment of schizophrenia and bipolar disorder, including bipolar depression. An extended-release (XR) formulation of quetiapine is also available. This review summarizes the pharmacological properties, efficacy and tolerability of quetiapine and quetiapine XR in patients with bipolar depression. Quetiapine is an antagonist at both serotonin 5-HT2 and dopamine D2 receptors, and its antipsychotic effects are thought to stem from interactions at these receptors. The antidepressant effects of quetiapine are poorly understood, but may be related to antagonism of 5-HT2A receptors in cortical regions, partial agonism of 5-HT1A in the prefrontal cortex in association with increased extracellular dopamine release in the region, or to reduced synaptic reuptake of noradrenaline resulting from inhibition of the noradrenaline reuptake transporter by the quetiapine metabolite norquetiapine. The efficacy and tolerability of quetiapine was evaluated in five 8-week, randomized, double-blind, placebo-controlled, multicentre or multinational trials in patients with a major depressive episode (MDE) associated with bipolar disorder. Across trials, monotherapy with oral quetiapine 300 or 600 mg/day (or quetiapine XR 300 mg/day) produced significantly greater improvements than placebo in depressive symptoms (primary endpoint), according to the change in the Montgomery-Asberg Depression Rating Scale total score. In general, quetiapine and quetiapine XR were also associated with significantly higher MDE response and remission rates than placebo. Across trials, quetiapine and quetiapine XR produced significantly greater improvements in global severity of illness scores than placebo, according to changes in the Clinical Global Impressions scale score. There were no differences in treatment outcomes between quetiapine 300 mg/day and 600 mg/day dosage groups. Patients with bipolar depression who responded to quetiapine during two 8-week acute treatment trials also benefited from continuing quetiapine therapy for up to 52 weeks. Compared with quetiapine responders randomized to placebo, quetiapine responders who continued quetiapine 300 or 600 mg/day had a significantly reduced risk of recurrence of any mood events and of depression mood events, but not of hypomanic/manic events. In a randomized, double-blind, placebo-controlled trial, quetiapine maintenance therapy for up to 104 weeks

Topics: Administration, Oral; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Humans; Quetiapine Fumarate; Serotonin 5-HT2 Receptor Antagonists

This article briefly summarizes the burden of bipolar disorder and the clinical profile of quetiapine (Seroquel®) in the management of bipolar disorder, followed by a detailed review of pharmacoeconomic analyses. Quetiapine is an atypical antipsychotic that is available in numerous countries as immediate-release and extended-release tablets for the treatment of major psychiatric disorders, including bipolar disorder. Randomized, double-blind, placebo-controlled trials with quetiapine have demonstrated its efficacy in bipolar I and II disorders, and the drug has been generally well tolerated in clinical trials. Three cost-effectiveness analyses of maintenance therapy in bipolar I disorder, which used similar Markov models and incorporated data from key clinical trials and a number of other sources, showed that quetiapine, as adjunctive therapy with mood stabilizers (lithium or divalproex), was a cost-effective treatment option from the healthcare payer perspective in the UK and the US. Quetiapine either dominated comparators (typically mood stabilizers alone) or was associated with incremental cost-effectiveness ratios that were usually well below widely accepted thresholds of cost effectiveness. One of the studies evaluated extended-release quetiapine, although clinical efficacy data used in the Markov model were for the immediate-release formulation. In another analysis, which used a discrete-event simulation model and was conducted from the perspective of the UK healthcare payer, quetiapine monotherapy was cost effective compared with olanzapine monotherapy as maintenance treatment for all phases of bipolar I or II disorder. In this model, favourable results were also shown for quetiapine (with or without mood stabilizers) compared with a wide range of maintenance therapy regimens. Another modelled analysis conducted from the UK healthcare payer perspective showed that quetiapine was dominated by haloperidol in the short-term treatment of a manic episode in patients with bipolar I disorder. Both favourable and unfavourable results have been reported in cost analyses of quetiapine in bipolar disorder (type I or type not specified). Possible explanations for some of the variability in results of the pharmacoeconomic analyses include heterogeneity among the models in terms of input parameters or assumptions in the base-case analyses, country- or region-specific differences in estimates of healthcare resource use and associated costs, variability in treatme

Topics: Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Cost-Benefit Analysis; Dibenzothiazepines; Quetiapine Fumarate; Randomized Controlled Trials as Topic

This article reviews the role of the second generation antipsychotics in the treatment of affective disorders. The treatment of major depressive disorders and the acute and long-term treatment of bipolar affective disorders are also discussed. After the special role of quetiapine is highlighted, a novel psychopharmacological terminology and nomenclature are also introduced.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Drug Therapy, Combination; Humans; Mood Disorders; Psychopharmacology; Quetiapine Fumarate; Randomized Controlled Trials as Topic

The 5-HT2 antagonistic action of quetiapine may disinhibit the dopaminergic system enhancing dopaminergic activity in the forebrain and influencing the mood state. Our objective is to investigate the possible induction of manic symptoms by quetiapine through a case report and a review of the literature.. We report the case of a 54 year old woman suffering from bipolar depression who developed hypomania seven weeks after the initiation of 300 mg/d of quetiapine. A literature review concerning the induction of hypomania or mania by quetiapine have retrieved the presence of seven similar case reports or series.. Available literature points toward an early induction of hypomania or mania with low dosage of quetiapine treatment (between 100 and 400 mg/day never exceeding 600 mg/day). Hypomania or mania are possible short term complications that can be present few days to few weeks of treatment initiation. The discontinuation of the drug or the increase of its dose seems to reverse the hypomanic or manic symptoms. Patients described in the literature suffer mostly from schizophrenia.. The atypical antipsychotic drug quetiapine, which have antidepressant properties at low doses via its indirect dopamine enhancing activity due its serotoninergic antagonism, appears to be involved in the induction of rare hypomanic or manic state in patients suffering from bipolar disorders and to have mood stabilizing properties at higher doses when its dopamine antagonist activity becomes more prominent. Its manic/hypomanic induction properties should not prevent its administration to patients suffering from bipolar disorder.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Middle Aged; Quetiapine Fumarate

Topics: Affective Symptoms; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia

Bipolar II disorder is a common, recurrent, and disabling psychiatric illness, and yet little is known about how best to treat it. The pressing clinical need for evidence-based approaches to the treatment of bipolar II disorder, coupled with recent publication of pertinent studies, calls for an updated review of this literature. This review focuses on a critical examination of the evidence supporting the efficacy of treatments for acute depressive episodes in bipolar II disorder.. A MEDLINE (via Ovid) search of journals, covering the period from January 1950 to January 2009, was performed to identify relevant studies. Keywords used were bipolar II disorder, bipolar disorder, bipolar depression, and pharmacotherapy. Studies were further limited to those that were in adult samples, published in peer-reviewed journals, and written in English.. We examined all randomized trials evaluating the use of pharmacotherapy in the treatment of acute bipolar II depression. Studies with mixed samples of bipolar I and II or bipolar II and unipolar depression were examined as well. Twenty-one randomized trials were identified and reviewed.. Therapeutic agents were rated according to the quality of evidence supporting their efficacy as treatments for bipolar II depression.. Ninety percent of relevant trials were published after 2005. Quetiapine was judged as having compelling evidence supporting its efficacy. Lithium, antidepressants, and pramipexole were judged as having preliminary support for efficacy. Lamotrigine was considered to have mixed support.. Although progress has been made, further research on bipolar II depression is warranted.

Topics: Acute Disease; Antidepressive Agents; Antimanic Agents; Benzhydryl Compounds; Benzothiazoles; Bipolar Disorder; Dibenzothiazepines; Humans; Lamotrigine; Lithium Compounds; Modafinil; Pramipexole; Quetiapine Fumarate; Triazines

Quetiapine extended-release (quetiapine-XR) has been studied in patients with schizophrenia, bipolar mania, bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). The purpose of this study was to compare the tolerability and sensitivity of quetiapine-XR among these psychiatric conditions. The discontinuation due to adverse events (DAEs) and reported somnolence in randomized, double-blind, placebo-controlled studies of quetiapine-XR in these psychiatric conditions were examined. The absolute risk reduction or increase and the number needed to treat to benefit (NNTB) or harm (NNTH) for DAEs and reported somnolence of quetiapine-XR ≥ 300 mg/d relative to placebo were estimated. Data from one study in schizophrenia (n=465), one in mania (n=316), one in bipolar depression (n=280), two in refractory MDD (n=624), two in MDD (n=669) and three in GAD (n=1109) were available. The risk for DAEs of quetiapine-XR relative to placebo was significantly increased in bipolar depression (NNTH=9), refractory MDD (NNTH=8), MDD (NNTH=9), and GAD (NNTH=5), but not in schizophrenia and mania. The risk for reported somnolence of quetiapine-XR relative to placebo was significantly increased in schizophrenia (600 mg/d NNTH=15 and 800 mg/d NNTH=11), mania (NNTH=8), bipolar depression (NNTH=4), refractory MDD (NNTH=5), MDD (NNTH=5) and GAD (NNTH=5). These results suggest that patients with GAD had the poorest tolerability during treatment with quetiapine-XR, but they had a similar sensitivity as those with bipolar depression and MDD. Patients with schizophrenia or mania had a higher tolerability and a lower sensitivity than those with bipolar depression, MDD, or GAD.

Topics: Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Double-Blind Method; Humans; Mental Disorders; Placebos; Quetiapine Fumarate; Risk; Schizophrenia; Treatment Outcome

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

To assess the relationships among quetiapine blood concentration, daily dose, dopamine receptor occupancy, and clinical outcome in order, if possible, to define a target plasma level range in which therapeutic response is enhanced and adverse events are minimized.. A search of the database Embase from 1974 to March 2009 and the databases MEDLINE and PubMed from 1966 to March 2009 was conducted. The drug name quetiapine was searched with each of the terms plasma levels, plasma concentration, therapeutic drug monitoring, and dopamine occupancy.. The search uncovered 42 relevant articles. All published reports of quetiapine plasma or serum concentration were considered for inclusion if reported in relation to a dose, clinical outcome, or dopamine occupancy. After application of exclusion criteria, 20 articles remained.. Trials designed primarily to investigate an interaction between quetiapine and another medication were excluded, as were those designed to compare methods of blood sample analysis.. There was a weak correlation between quetiapine dose and measured plasma concentration (from trough samples). Quetiapine dose was correlated with central dopamine D(2) occupancy, although the relationship between plasma level and D(2) occupancy is less clear.. The dose-response relationship for (immediate-release) quetiapine is established. Data on plasma concentration-response relationships are not sufficiently robust to allow determination of a therapeutic plasma level range for quetiapine. Therapeutic drug monitoring procedures are thus probably not routinely useful in optimizing quetiapine dose. Further examination of the relationship between peak quetiapine plasma concentration and clinical response is necessary.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Biological Availability; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Receptors, Dopamine D2; Schizophrenia; Statistics as Topic; Young Adult

Depression, in the context of bipolar disorder, is more prevalent than hypomania or mania and accounts for most of the disability. Furthermore, the treatment of bipolar depression is more complicated than the treatment of unipolar major depression. Finally, the evidence base for pharmacotherapy of bipolar depression is much smaller than for unipolar depression or hypomania/mania.. The article examines the mechanism of action and pharmacokinetics of quetiapine, its evidence base as a treatment for bipolar depression and related issues of safety and tolerability.. In the context of bipolar disorder, quetiapine is the only monotherapy approved for the treatment of hypomania/mania, depression and as an adjunctive maintenance therapy. In addition to its antipsychotic properties, this broad mood stabilizing potential may uniquely benefit and simplify the management of some bipolar patients who can tolerate this agent.

Topics: Animals; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Quetiapine Fumarate

Olanzapine-fluoxetine combination is one of only two products currently approved by the US FDA for the acute treatment of depressive episodes associated with bipolar disorder.. This treatment evaluation reviews double-blind randomized controlled trials of olanzapine-fluoxetine combination for bipolar depression. A total of three primary study reports are found in the peer-reviewed literature. Additional data regarding the trials are obtained from study synopses disclosed on the internet by the manufacturer and from product labeling.. Number needed to treat for antidepressant response for olanzapine-fluoxetine combination versus placebo in the 8-week trials was 4 (95% CI 3 - 8), and that for remission was 5 (95% CI 3 - 8). Single-digit numbers needed to harm (NNH) values were observed for the treatment-emergent adverse events of weight gain (NNH 7, 95% CI 5 - 16) and diarrhea (NNH 9, 95% CI 5 - 30). NNH versus placebo for weight gain ≥ 7% from baseline was 6 (95% CI 4 - 10). When contrasted with lamotrigine, olanzapine-fluoxetine combination demonstrates statistically significantly greater improvement in depressive and manic symptoms but there is a higher incidence of treatment-emergent adverse events, weight gain and elevation in metabolic factors. Studies that directly compare quetiapine monotherapy with olanzapine-fluoxetine combination, the only two approved products for the treatment of bipolar depression, are not available. Nonetheless, indirect comparisons indicate similar efficacy outcomes but different tolerability profiles, with quetiapine principally being associated with sedation. Additional approved treatment options would be welcome.

Topics: Animals; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Combinations; Fluoxetine; Humans; Quetiapine Fumarate

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

Quetiapine is an atypical antipsychotic approved by the FDA (Food and Drug Administration) for use in the treatment of schizophrenia, acute mania, and bipolar depression. Pharmacologically, it has antagonistic effects on serotonin 5-HT1A and 5-HT2A, dopamine D1 and D2, histamine H1, and adrenergic alpha1 and alpha2 receptors. In addition to reports of its use in schizophrenia and bipolar disorder, many studies have examined the use of quetiapine in the treatment of anxiety disorders and substance use disorders. In the treatment of patients with psychotic or bipolar disorder with a comorbid substance abuse disorder even though quetiapine was prescribed primarily for the treatment of the underlying psychotic symptoms, patients taking this medication reported a significant reduction in substance use. Yet, there are also case reports of quetiapine abuse and dependence; in particular among prisoners and patients diagnosed with substance abuse. Though quetiapine should be used peroral, it is also used intranasally and intravenously in these patient groups. Moreover, in some cases quetiapine is combined with other substances, such as cocaine or marijuana, to increase sedation. This abuse of quetiapine is thought to occur due to the anxiolytic and sedative effects of the drug. There are no controlled studies on quetiapine dependence in the literature and it remains unknown whether or not quetiapine causes dependence. This review aimed to present all published case reports on quetiapine abuse and to discuss the possible mechanisms that underlie its abuse and dependence.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

There has been a recent increase in the number of clinical trials and treatment options for bipolar disorder. This research has resulted in new treatment options. Most second-generation antipsychotics have demonstrated efficacy in the treatment of mania, both in monotherapy and as adjuncts to mood stabilizers. For bipolar depression, nearly all randomized, placebo-controlled studies have demonstrated that antidepressants do not provide any additional benefit to ongoing mood stabilizers. Additionally, antidepressants carry a risk of destabilization of bipolar disorder with an increase in mania, cycling, and chronic irritable dysphoria. Newer non-antidepressant treatments for depression include quetiapine, lamotrigine, modafinil, and pramipexole. These agents are effective for acute treatment and appear to be effective in maintenance. The least-studied phase of bipolar disorder is the maintenance phase. The use of multiple agents appears to be superior to monotherapy in relapse prevention. Despite the many advances in the pharmacotherapy of bipolar disorder, the overall prognosis of this severe illness does not appear to have changed.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzhydryl Compounds; Benzothiazoles; Bipolar Disorder; Diagnosis, Differential; Dibenzothiazepines; Dopamine Agonists; Humans; Lamotrigine; Modafinil; Pramipexole; Prognosis; Psychotherapy; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Triazines

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

During the past decade, there has been a substantial increase in the prescribing of antipsychotics to young patients for a variety of pediatric psychiatric disorders. Quetiapine (Seroquel®) received its initial indication from the U.S. Food and Drug Administration for treatment of schizophrenia in 1997, and it received its second indication for the treatment of mania-associated bipolar disorder in 2004. Currently, in young patients, authorized quetiapine indications are schizophrenia in individuals aged 13 or older and manic episodes associated with bipolar I disorder in children 10 to 17 years old. Quetiapine has different pharmacological actions and acts as an antagonist for following receptors: D(2) receptor, serotonin 5-HT(2A) also known as α(1)-adrenoceptor, histamine 1 receptor and muscarinic acetylcholine receptor. Several studies have shown its favorable profile of effectiveness and tolerability in young bipolar and schizophrenic patients. However, the current data make it very clear that the risks and benefits of this drug need to be weighed individually for each patient.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Humans; Quetiapine Fumarate; Risk Assessment; Risk Factors; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Young Adult

Bipolar disorder is a common, recurrent, and chronic condition associated with significant morbidity and reduced longevity mainly due to the depressive pole of the illness. Despite the great need for effective therapies, relatively few randomized controlled trials have been conducted and, to date, only two agents have been approved by the United States Food and Drug Administration for treatment of bipolar depression (olanzapine/fluoxetine combination and quetiapine). Quetiapine is the first approved monotherapy for treatment of bipolar depression, and an extended-release (XR) form of quetiapine is now available. This once-daily, bioequivalent formulation represents a useful alternative for patients who cannot tolerate twice-daily, immediate-release (IR) quetiapine. Here, we summarize the evidence supporting the efficacy of quetiapine for treatment of bipolar depression, and also review the similarities and differences between the two formulations. Additional research on longer-term use of quetiapine XR is needed to establish the durability of therapeutic effects and tolerability over months or years of therapy, both alone and in combination with other mood stabilizers. Studies on the potential utility of lower doses of quetiapine XR and head-to-head studies to evaluate relative efficacy and cost-effectiveness also are needed.

Topics: Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Drug-Related Side Effects and Adverse Reactions; Humans; Medication Adherence; Quetiapine Fumarate; Therapeutic Equivalency; Treatment Outcome

This 10-day, single-center, open-label, randomized, crossover study compared pharmacokinetic profiles and tolerability of extended release quetiapine fumarate (quetiapine XR) with quetiapine immediate release (quetiapine IR) in patients with schizophrenia, schizoaffective disorder or bipolar disorder. After a 2-day lead-in period during which patients received quetiapine XR 300 mg once daily, patients were randomized to quetiapine IR 150 mg twice daily followed by quetiapine XR 300 mg once daily, or quetiapine XR 300 mg once daily followed by quetiapine IR 150 mg twice daily. Pharmacokinetic parameters were evaluated at the end of each 4-day treatment period at steady state. Vital signs, laboratory values, and adverse events (AEs) were recorded throughout the study. The least squares means (90% confidence interval) of the ratio of the area under the plasma concentration-time curve over a 24 h dosing interval (AUC ([0-24 h])) for quetiapine XR/IR was 1.04 (0.92-1.19) and within the pre-defined range set for equivalence (0.80-1.25). Maximum plasma concentration at steady state (C(max)) was approximately 13% lower for quetiapine XR than for quetiapine IR (495.3 versus 568.1 ng/mL), time to reach C(max) (t(max)) was 5 h versus 2 h and mean concentration at the end of 24 h dosing interval (C(min)) was 95.3 versus 96.5 ng/mL, respectively. No patients withdrew from the study owing to AEs and there were no serious AEs or deaths related to study medication. No unexpected AEs, changes in vital signs or laboratory values were observed. These findings suggest that modifying the formulation does not change the overall absorption or elimination of quetiapine, and support emerging clinical evidence for the use of quetiapine XR as a once daily treatment in patients initiating therapy or those established on quetiapine IR.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Cross-Over Studies; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

Although depression accounts for a large part of the burden associated with bipolar disorder, its drug treatment has been under-studied.. To provide the best available evidence supporting the pharmacotherapy of bipolar depression.. A systematic review was conducted, focusing on randomized, controlled trials (RCTs) and meta-analyses.. Despite FDA approval of both the olanzapine-fluoxetine combination and quetiapine for the treatment of acute bipolar depression, independent RCTs (i.e., not trials conducted 'under the umbrella' of a drug company) have not found any drug to have antidepressant effects similar to those seen in unipolar depression. A practice-based suggestion, valuable for both short- and long-term treatment, might be to have a background of mood stabilizers and to add drugs, following one of several treatment options, trusting to find a drug with a degree of effectiveness by trial and error. The list of drugs that could be used would include all the current antidepressants, the olanzapine-fluoxetine combination and probably quetiapine too. Special features and situations might also influence treatment options.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Drug Combinations; Fluoxetine; Humans; Meta-Analysis as Topic; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Bipolar disorder is a common, debilitating, chronic illness that emerges early in life and has serious consequences such as long-term unemployment and suicide. It confers considerable functional disability to the individual, their family and society as a whole and yet it is often undetected, misdiagnosed and treated poorly. In the past decade, many new treatment strategies have been trialled in the management of bipolar disorder with variable success. The emerging evidence, for pharmacological agents in particular, is promising but when considered alone does not directly translate to real-world clinical populations of bipolar disorder. Data from drug trials are largely based on findings that identify differences between groups determined in a time-limited manner, whereas clinical management concerns the treatment of individuals over the life-long course of the illness. Considering the findings in the context of the individual and their particular needs perhaps best bridges the gap between the evidence from research studies and their application in clinical practice. Specifically, only lithium and valproate have moderate or strong evidence for use across all three phases of bipolar disorder. Anticonvulsants, such as lamotrigine, have strong evidence in maintenance; whereas antipsychotics largely have strong evidence in acute mania, with the exception of quetiapine, which has strong evidence in bipolar depression. Maintenance data for antipsychotics is emerging but at present remains weak. Combinations have strong evidence in acute phases of illness but maintenance data is urgently needed. Conventional antidepressants only have weak evidence in bipolar depression and do not have a role in maintenance therapy. Therefore, this paper summarizes the efficacy data for treating bipolar disorder and also applies clinical considerations to these data when formulating recommendations for the management of bipolar disorder.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Lithium; Practice Patterns, Physicians'; Quetiapine Fumarate

To review the clinical data investigating the efficacy and safety of quetiapine in bipolar depression.. Searches of MEDLINE and PubMed (1977-July 2009) were conducted using the key words quetiapine and bipolar depression. The references of literature found were cross-referenced. The pharmaceutical company that produces quetiapine was contacted to obtain the posters for the EMBOLDEN I and EMBOLDEN II trials.. Only double-blind, placebo-controlled trials were included for review, as well as any subanalyses of the literature that matched this criterion.. There was a total of 5 double-blind, placebo-controlled trials and 5 subanalyses reviewed. The results of these data demonstrated quetiapine's efficacy in the treatment of depressive phases of bipolar disorder, including statistically significant improvement in the Montgomery-Asberg Depression Rating Scale (MADRS). In the trials reviewed in this article, the change in MADRS scores ranged from -15.4 to -16.94 within the quetiapine groups, and from -10.26 to -11.93 in the placebo groups. There were also statistically significant improvements in the Hamilton Anxiety Rating Scale, the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire, the Pittsburgh Sleep Quality Index, and the Sheehan Disability Scale. All of these trials had a duration of 8 weeks and therefore cannot be applied to the long-term use of quetiapine in bipolar depression. The most common adverse events were sedation, somnolence, and dry mouth. The overall dropout rates for the trials reviewed ranged from 24% to 47%.. Based on the literature reviewed here, quetiapine appears to be a safe and efficacious short-term treatment option for bipolar depression. Patients with bipolar type I showed greater improvement on the MADRS than those with bipolar type II. Patients with a rapid-cycling disease course showed an improvement in depressive symptoms, regardless of bipolar type.

Topics: Bipolar Disorder; Clinical Trials as Topic; Dibenzothiazepines; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Sleep Wake Disorders; Treatment Outcome

Topics: Acute Disease; Adult; Affect; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Interview, Psychological; Lithium Carbonate; Long-Term Care; Male; Quetiapine Fumarate

Topics: Acute Disease; Adult; Affect; Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Evidence-Based Medicine; Hospitalization; Humans; Male; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Treatment Outcome; Valproic Acid

Diagnosis of bipolar disorder in children and adolescents is increasing, and the early-onset form of bipolar disorder usually carries more morbidity than later-onset forms. Patient education and psychotherapeutic and psychosocial interventions should be used in conjunction with carefully planned medication regimens. Recent data support the use of atypical antipsychotics for manic or mixed states in children and adolescents. However, more information is needed about long-term treatment of mania, treatment of bipolar depression, and treatment of comorbid psychiatric conditions.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Attention Deficit and Disruptive Behavior Disorders; Bipolar Disorder; Child; Comorbidity; Dibenzothiazepines; Disorders of Excessive Somnolence; Humans; Obesity; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Weight Gain

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

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

Atypical antipsychotics are now widely used in the acute and long-term treatment in bipolar disorder. The role of atypical antipsychotics as acute agents, add-on medications; or as primary mood stabilizers in different phases of bipolar disorder is an important current research tendency. However, in bipolar disorder the mostly used indication of quetiapine is the management of acute manic phases, clinical data and the actual research results suggest that it may have both antidepressant and long-term antimanic effects. Quetiapine enhances the transmission of the central serotonergic networks, by its high antagonistic affinity for 5-HT(2A) and partial agonistic activity for the 5-HT(1A) receptors. The 5HT(1A) partial agonism causes an increase in the dopaminergic neurotransmission of the prefrontal cortex, and also, the affinity for the alpha 2-adrenoceptor brings a relative increase in extracellular noradrenergic release an tone in the prefrontal cortex. Latest research shows that quetiapine's main, active, human plasma metabolite, N-desalkyl quetiapine (norquetiapine), has a high inhibition affinity for the noradrenergic transporter. These data suggest that comparing to other atypical antipsychotics, norquetiapine may have a relatively strong antidepressant potential. Modifying the dopaminergic transmission by quetiapine's D2 receptor blocking activity results indirect mediating the cAMP-PKA and the arrestin-Akt-GSK-3 intracellular signal transduction pathways, which process may explain its long-term antimanic and mood stabilizing capability. Quetiapine's activity on nerve growth factors, histamine H1 receptor, proinflammatory networks may take an important additional part in its efficacy in bipolar depression. Its very fast dissociation from the D2 receptor is an important pharmakokinetic parameter for managing the optimal quetiapine dose in the daily clinical practice. This review tries to organize the actual information on quetiapine's multiplex activity in bipolar disorder.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Dibenzothiazepines; Dopamine; Female; Glutamic Acid; Humans; Male; Middle Aged; Norepinephrine; Quetiapine Fumarate; Receptors, Histamine; Serotonin; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists

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 use of quetiapine as a drug to treat various substance use disorders as well as a drug of abuse is examined.. Quetiapine's effectiveness in treating schizophrenia and bipolar disorder is well-known; however, growing evidence has indicated that it may be useful in the treatment of various substance use disorders. Small-scale studies have been conducted to investigate the potential benefit of quetiapine in patients dependent on alcohol, cocaine, and amphetamines. The results of these two studies provide some evidence that quetiapine may benefit patients diagnosed with a mental illness who are also dependent on cocaine, amphetamines, or both, though more rigorous studies are needed. An unforeseen use of antipsychotics, specifically quetiapine, as drugs of abuse has emerged. Since antipsychotics are not classified as controlled substances, the majority of clinicians may not consider the diversion of antipsychotics for recreational purposes, but evidence of this is increasing, particularly in incarcerated individuals. Intravenous quetiapine abuse was first reported in the literature in 2005. Although most cases of quetiapine abuse have been reported in the correctional setting, inappropriate quetiapine use within the community has been documented. Thus far, all of the documented cases have involved patients with a prior history of substance abuse. Clinicians must be cognizant of the potential for quetiapine as a treatment for substance use disorders and as a drug of abuse.. Quetiapine is a promising treatment for substance use disorders alone or combined with other psychiatric diagnoses, such as bipolar disorder and schizophrenia. Quetiapine abuse has also been documented, particularly in the correctional setting.

Topics: Alcoholism; Amphetamine-Related Disorders; Antipsychotic Agents; Bipolar Disorder; Cocaine-Related Disorders; Dibenzothiazepines; Humans; Illicit Drugs; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

The metric of number needed to treat (NNT), defined as the number of patients who need to be treated to achieve one additional favorable outcome, can help clinicians appraise claims that one intervention is meaningfully superior to the other.. A review of the use of NNT to evaluate the differences between interventions in the treatment of depression, schizophrenia and bipolar disorder. Instead of using disparate measures such as point change on a rating scale, kilograms gained over time or relative differences, results can be converted into a common unit of measure -'patient units'- so that the clinician can anticipate how often actual differences between interventions would be expected to be observed. Calculation of NNT is demonstrated using reports published in the psychiatric literature, together with different graphical techniques to display this.. Clinical trial results expressed as NNT can be easily summarized and communicated effectively to patients, their families and payers. Limitations include ensuring that the NNT metric is calculated from well-designed and well-conducted research that enrolls subjects similar to patients that one treats in actual clinical practice, with doses of medications similar to what is used in the 'real world'. Direct calculation of NNT is limited to binary or dichotomous outcomes.. Using NNT can help predict treatment response in terms of both efficacy and tolerability.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Data Interpretation, Statistical; Depressive Disorder, Major; Dibenzothiazepines; Duloxetine Hydrochloride; Evidence-Based Medicine; Humans; Outcome Assessment, Health Care; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Schizophrenia; Secondary Prevention; Thiophenes; Treatment Outcome

Quetiapine (Seroquel) is the only atypical antipsychotic approved in the US for use as monotherapy in both bipolar mania and depression, offering potential compliance advantages. Monotherapy with oral quetiapine 300 mg/day is effective in the treatment of patients with bipolar I or II depression. Rapid and sustained improvements in depressive and anxiety symptoms are seen with quetiapine, as well as improvements in health-related quality of life (HR-QOL). Quetiapine is generally well tolerated in bipolar depression and is not associated with an increased risk of treatment-emergent mania. Thus, despite the current lack of data from active comparator trials, quetiapine monotherapy should be considered a first-line option for the acute treatment of bipolar depression.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Quetiapine Fumarate

The efficacy and tolerability of quetiapine in the treatment of acute mania were reviewed.. Five randomized, placebo-controlled trials involving quetiapine as monotherapy or adjunct therapy in combination with either divalproex or lithium in the treatment of bipolar mania in either adolescents or adults were identified and reviewed. The primary outcome measure used in the trials was a change in Young Mania Rating Scale total scores. Monotherapy trials evaluated quetiapine, lithium, haloperidol, and placebo. Quetiapine was superior to placebo in both trials. Quetiapine and lithium showed comparable efficacy in one study, though lithium serum concentrations may have been suboptimal. Haloperidol was superior to quetiapine in efficacy at day 21 but similar at day 84. In the two trials evaluating quetiapine or placebo as adjunct therapy to lithium or divalproex, quetiapine was significantly more efficacious than placebo in one trial. In adolescents, quetiapine was more effective than placebo as an adjunct to divalproex. The most common adverse effects clearly attributable to quetiapine in these trials were somnolence and dry mouth. Quetiapine did not induce extrapyramidal effects, but weight gain was notable with the drug.. While quetiapine treatment demonstrated efficacy in the majority of the studies, the robustness of its efficacy is questionable. The use of quetiapine as first-line therapy for acute mania is not recommended based on the available results and cost considerations. However, it may be a useful second-line agent, particularly when sensitivity to extrapyramidal symptoms limits treatment options.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Haloperidol; Humans; Lithium Compounds; Quetiapine Fumarate; Valproic Acid

This article reviews the off-label prescription of quetiapine in the treatment of a broad range of psychiatric disorders including obsessive-compulsive disorder, post-traumatic stress disorder, personality disorder, substance abuse, bipolar disorder (now US FDA approved), anxiety and depression. The article highlights the primary reliance on selective serotonin reuptake inhibitors (SSRIs) in the treatment of these disorders (cf bipolar disorder) and the high percentage of patients (30-60%) that do not respond to SSRIs. The studies suggest that low-dose quetiapine shows good tolerability and efficacy in patients diagnosed with these disorders, particularly in the case of treatment-resistant patients that do not respond to primary treatments including SSRIs and cognitive-behavioral therapy. Quetiapine generally appears to be very effective in trauma-related conditions by improving autonomic stability, and decreasing the stress and anxiety response that arises due to specific fears or triggers. Quetiapine also appears to be particularly useful for normalizing obsessions and compulsions, and improving low mood, irritability and aggressiveness. A greater understanding of the pharmacology of drug alternatives and the neurobiology of psychiatric disorders is required to permit a more personalized medicine approach.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Prescriptions; Humans; Mental Disorders; Obsessive-Compulsive Disorder; Personality Disorders; Quetiapine Fumarate; Stress Disorders, Post-Traumatic; Substance-Related Disorders

Quetiapine (Seroquel) is the only atypical antipsychotic approved in the US for use as monotherapy in both bipolar mania and depression, offering potential compliance advantages. Monotherapy with oral quetiapine 300 mg/day is effective in the treatment of patients with bipolar I or II depression. Rapid and sustained improvements in depressive and anxiety symptoms are seen with quetiapine, as well as improvements in health-related quality of life. Quetiapine is generally well tolerated in bipolar depression and is not associated with an increased risk of treatment-emergent mania. Thus, despite the current lack of data from active comparator trials, quetiapine monotherapy should be considered a first-line option for the acute treatment of bipolar depression.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Quality of Life; Quetiapine Fumarate

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

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

Bipolar disorder is a complex mental illness that is frequently both under-diagnosed and under-treated. The symptoms of bipolar disorder can be confused with other medical illnesses or drug effects or may even be overlooked entirely as extreme character traits. The consequences of delayed diagnosis or misdiagnosis are potentially devastating, including loss of employment, impaired relationships and a severely impaired quality of life. This article will review the historic perspectives of bipolar disorder, the diagnostic criteria for the phases of the illness, and the pharmacologic options available to treat this condition. Quetiapine, an atypical antipsychotic, will be reviewed indepth. Based on extensive trial data, reviewed in this article, quetiapine is approved by the US Food and Drug Administration for use as monotherapy or as adjunctive therapy with other mood stabilizers for the treatment of acute manic episodes of bipolar I disorder. Clinical trials describing the efficacy of quetiapine in other phases of bipolar disorder and in other patient populations are also reviewed. A discussion of the drug profile of quetiapine includes its chemistry, availability, pharmacodynamics, pharmacokinetics and metabolism. Preclinical studies, postmarketing surveillance, safety, tolerability and regulatory issues are also evaluated. Finally, potential future directions for quetiapine are discussed, together with a review of key issues in bipolar disorder management and details of the information resources used in preparing this article.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug and Narcotic Control; Drug Monitoring; Drug Therapy, Combination; Expert Testimony; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Hyperglycemia; Lipids; Quetiapine Fumarate

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

Through a review of randomised, controlled trials, this article evaluates the efficacy and tolerability of quetiapine in the acute and maintenance phases of bipolar disorder. In trials involving mania patients, quetiapine was found to be effective as adjunctive therapy in combination with lithium or valproate, significantly superior to placebo, and equal to lithium or haloperidol as monotherapy. With regard to the prevention of relapses in bipolar disorder, quetiapine seems to differ from other atypical antipsychotics in its characteristics as a mood stabiliser, which are associated with a promising efficacy in the treatment of bipolar depressive episodes. However, further larger controlled long-term prospective studies are needed to confirm the efficacy of quetiapine for the prevention of relapses in bipolar disorder. Quetiapine seems to have a satisfactory safety and tolerability profile, with a low prevalence of extrapyramidal symptom-related adverse events, treatment-emergent depression and weight gain. Sedation is the main side effect of treatment with quetiapine.

Topics: Animals; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Quetiapine Fumarate

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

Topics: Anticonvulsants; Antidepressive Agents; Bipolar Disorder; Controlled Clinical Trials as Topic; Dibenzothiazepines; Drug Resistance; Electric Stimulation Therapy; Electroconvulsive Therapy; Humans; Lithium; Lithium Compounds; Quetiapine Fumarate; Risk Factors; Suicide; Telecommunications; Treatment Outcome; Vagus Nerve

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

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

The use of at least one mood-stabilizing agent is common clinical practice in the treatment of bipolar disorder, regardless of the treatment setting or disease phase. However, a consensus definition of 'mood stabilizer' remains to be established. A mood stabilizer has been operationally described as an agent that is useful in at least one phase of bipolar disorder while not worsening any other phase of the illness. More stringent definitions have been proposed, and it can be argued that a clinically effective mood stabilizer would have efficacy in a broad range of affective, psychotic, behavioral and cognitive domains in all phases of bipolar disorder and would be well tolerated across a range of doses for sustained periods. Clinically effective mood stabilizers should treat mania and depression, while preventing recurrence and improving quality of life. Effective treatment should not precipitate mania, depression, or rapid cycling, and should minimize the burden of treatment-emergent side effects. Data from clinical studies of quetiapine are reviewed in context with the literature discussing traditional and emerging mood stabilizers. Using a liberal definition, the evidence for quetiapine qualifies it as a bimodal mood stabilizer based on its demonstrated effectiveness in the treatment of bipolar mania and depression. Further data suggest that quetiapine has promise across all phases of bipolar disorder with the potential to meet even the most stringent definitions of a mood stabilizer.

Topics: Affect; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Humans; Long-Term Care; Quetiapine Fumarate

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

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

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

Quetiapine (Seroquel), an atypical antipsychotic with established efficacy in the treatment of schizophrenia, shows efficacy in the treatment of acute mania and depression associated with bipolar disorder.Quetiapine, either as monotherapy or in combination with lithium or divalproex sodium (valproate semisodium), is generally well tolerated and effective in reducing manic symptoms in adult and adolescent patients with acute bipolar mania, and is approved for use in adults for this indication. As monotherapy, the drug is also effective in reducing depressive symptoms in patients with bipolar depression. It is associated with a low incidence of extrapyramidal symptom (EPS)-related adverse events and low EPS ratings in bipolar disorder. Quetiapine thus shows potential in the treatment of bipolar depression, and represents a useful agent for the treatment of acute bipolar mania.

Topics: Antipsychotic Agents; Bipolar Disorder; Depression; Dibenzothiazepines; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic

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

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

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

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

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

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

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

Although quetiapine was introduced as an atypical antipsychotic drug with clinical efficacy in schizophrenia patients, it has been used in a variety of disease states over the last 5 years. The most common conditions have included mood and anxiety disorders, obsessive-compulsive disorder, aggression, hostility, posttraumatic stress disorder, borderline personality disorder, delirium, and comorbid substance abuse. Considering its efficacy in a wide variety of neuropsychiatric conditions and its excellent tolerability profile, quetiapine could emerge as a broad-spectrum psychotropic medication that may be helpful in psychiatry across various diagnostic categories. Traditionally, studies on the predictive validity of psychiatric disorders help with nosologic issues and controversies. Assessing quetiapine's tolerability and its overall treatment response might help tease out the predictive validity of various psychiatric syndromes (based currently on an atheoretical descriptive approach) and may shape psychiatric nosology in the future. Quetiapine's low affinity and fast dissociation from postsynaptic dopamine-2 receptors give the least risk of producing acute extrapyramidal side effects, tardive dyskinesia, and neuroleptic malignant syndrome. These factors suggest that the clinical utility of quetiapine in psychiatric conditions other than schizophrenia has not been fully exploited thus far.

Topics: Adult; Aggression; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Borderline Personality Disorder; Clinical Trials as Topic; Comorbidity; Delirium; Depressive Disorder; Dibenzothiazepines; Forecasting; Hostility; Humans; Mental Disorders; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Treatment Outcome

Bipolar disorder is ranked as the sixth most important worldwide cause of disability. Current treatment is based chiefly on lithium and/or anticonvulsants, of which sodium valproate is the most widely used. A significant minority of patients fail to respond fully to current treatments, particularly those with mixed mania and/or rapid cycling. Many patients are unable to tolerate the side-effects of current therapy in the long term, and adverse effects may contribute to the high rate of noncompliance observed in bipolar disorder. The shortcomings of current treatments are reflected in poor outcomes: two-thirds of patients with bipolar disorder require hospitalization on more than one occasion; employment and social functioning are significantly lower than in control groups; 93% of carers suffer at least moderate distress; and 25-50% of patients are believed to attempt suicide at least once. Bipolar disorder shares some features with schizophrenia, and several atypical antipsychotics have demonstrated efficacy in bipolar disorder. Quetiapine has a particularly favourable tolerability profile, with placebo-level extrapyramidal symptoms and prolactin levels across the entire dose range combined with a neutral effect on weight during long-term use, and may be a valuable treatment option in acute mania and bipolar disorder.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Patient Care Planning; Quetiapine Fumarate; Schizophrenia; Severity of Illness Index; Suicide

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

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

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

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

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

Identification of treatment-specific predictors of drug therapies for bipolar disorder (BD) is important because only about half of individuals respond to any specific medication. However, medication response in pediatric BD is variable and not well predicted by clinical characteristics.. A total of 121 youth with early course BD (acute manic/mixed episode) were prospectively recruited and randomized to 6 weeks of double-blind treatment with quetiapine (. Pre-treatment morphometry and morphometric changes occurring during the first week can both independently predict treatment outcome of quetiapine and lithium with balanced accuracy over 75% (all. These findings demonstrate that pre-treatment morphometric measures and acute brain morphometric changes can serve as medication response predictors in pediatric BD. Brain morphometric features may provide promising biomarkers for developing biologically-informed treatment outcome prediction and patient stratification tools for BD treatment development.

Topics: Adolescent; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Brain; Child; Double-Blind Method; Humans; Lithium; Mania; Prospective Studies; Quetiapine Fumarate; Treatment Outcome

Disruptions in the limbic system, and in emotion regulation circuitry that supports affect modulation, have been reported during acute manic episodes of bipolar disorder (BD). The impact of pharmacological treatment on these deficits, especially in youth, remains poorly characterized. 107 youths with acute manic or mixed episodes of bipolar I disorder and 60 group-matched healthy controls were recruited. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. Task-based fMRI studies were performed using an identical pairs continuous performance task (CPT-IP) at pre-treatment baseline and post-treatment weeks one and six. Region of interest analyses focused on the limbic system and ventral PFC - basal ganglia - thalamocortical loop structures known to be involved in emotion regulation. Changes in regional activation were compared between the two treatment groups, and pretreatment regional activation was used to predict treatment outcome. Mania treatment scores improved more rapidly in the quetiapine than lithium treated group, as did significant normalization of neural activation toward that of healthy individuals in left amygdala (p = 0.007), right putamen (p < 0.001), and right globus pallidus (p = 0.003). Activation changes in the right putamen were correlated with reduction of mania symptoms. The limbic and emotion regulation system activation at baseline and week one predicted treatment outcome in youth with bipolar disorder with significant accuracy (up to 87.5%). Our findings document more rapid functional brain changes associated with quetiapine than lithium treatment in youth with bipolar disorder, with most notable changes in the limbic system and emotion regulation circuitry. Pretreatment alterations in these regions predicted treatment response. These findings advance understanding of regional brain alterations in youth with bipolar disorder, and show that fMRI data can predict treatment outcome before it can be determined clinically, highlighting the potential utility of fMRI biomarkers for early prediction of treatment outcomes in bipolar disorder.Clinical Trials Registration: Name: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania. URL: https://clinicaltrials.gov/ . Registration number: NCT00893581.

Topics: Adolescent; Amygdala; Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Emotional Regulation; Humans; Lithium; Lithium Compounds; Magnetic Resonance Imaging; Mania; Quetiapine Fumarate

Unsatisfactory responses to bipolar disorder treatments have necessitated novel therapeutic approaches. Evidence of levetiracetam's effectiveness in mania was reported in previous studies. This study evaluated its efficacy, safety and tolerability as an adjunct to quetiapine in mania. Forty-four patients with Young Mania Rating Scale (YMRS) score ≥20 entered and were randomized to receive levetiracetam plus quetiapine or placebo plus quetiapine for 6 weeks. Patients were assessed using the YMRS and Beck Scale for Suicidal Ideations (BSSI) at baseline and weeks 2, 4 and 6. Changes in the scores, remission rates and response to treatment were compared between the groups. Forty patients completed the trial. The general linear model (GLM) repeated measures demonstrated a significant effect for time × treatment interaction on the YMRS score during the trial (P = 0.04). A greater reduction in YMRS scores was seen in the levetiracetam group compared with the placebo group from baseline to week 4 (P = 0.045). Response to treatment was significantly better in the levetiracetam group (P = 0.046). No significant effect for time × treatment interaction on BSSI score was seen in GLM repeated measures. Finally, there was no significant difference in the frequency of adverse events. Adjunctive levetiracetam is effective, safe and well-tolerated in patients with mania. Further high-quality, large-scale trials are recommended.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Humans; Levetiracetam; Mania; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Patients with bipolar disorder have higher rates of cardiometabolic comorbidities and mortality. Although guidelines emphasize the importance of cardiovascular monitoring, few studies characterized the cardiometabolic risk profile during treatment and their relation to symptomatology and treatment response.. We analyzed data from two similar 24-weeks comparative effectiveness trials, with a combined sample of 770 participants randomized to two different lithium doses, quetiapine (300 mg/day), or standard treatment without lithium. Glucose, lipids and vital signs were measured before and after 24 weeks of treatment. We calculated several cardiovascular risk scores, assessed baseline correlations and compared the four treatment arms via multiple linear regression models.. Higher cholesterol and LDL levels were associated with greater depression severity, showing differential correlations to specific symptoms, particularly agitation, low energy and suicidality. Those randomized to quetiapine showed a significant worsening of cardiometabolic markers during the 24-week trial. Neither baseline nor change in lipid levels correlated with differential treatment response.. Study duration was short from the perspective of cardiometabolic risk markers, and all treatment arms included patients taking adjunct antipsychotics. The trials compared quetiapine to lithium, but not to other medications known to affect similar risk factors.. Treatment with 300 mg/day quetiapine for 24 weeks, representing a short and common dose course, resulted in increased cardiometabolic risk markers, emphasizing the importance of monitoring during mood-stabilizing treatment. The symptom-specific associations are in line with previous studies in unipolar depression, suggesting a cardiometabolic-depression link that needs to be further studied in bipolar depression.

Topics: Antipsychotic Agents; Bipolar Disorder; Cardiovascular Diseases; Depression; Humans; Quetiapine Fumarate

Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established.. A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition.. At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls.. Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD.. Multimodal Neuroimaging of Treatment Effects in Adolescent Mania; https://clinicaltrials.gov/; NCT00893581.

Topics: Adolescent; Bipolar Disorder; Brain; Humans; Magnetic Resonance Imaging; Neural Pathways; Neuroimaging; Quetiapine Fumarate

Childhood trauma affects the course of mood disorders. Researchers are now considering childhood trauma as an influential factor in the treatment of mood disorders. However, the role of childhood trauma in the treatment of bipolar disorder remains understudied.. The effect of childhood trauma on treatment outcomes was evaluated among participants randomised to treatment with lithium or quetiapine in the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study by clinician assessment. Mixed effects linear regression models were used to analyse rates of improvement in symptom severity (assessed with the Bipolar Inventory of Symptoms Scale and the Clinical Global Impression Scale for Bipolar Disorder) and functional impairment (assessed with the Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool).. A history of any childhood trauma was reported by 52.7% of the sample (N = 476). Although participants with a history of any childhood trauma presented with greater symptom severity and functional impairment at most study visits, participants with and without a history of any childhood trauma showed similar rates of improvement in symptom severity and functional impairment over the 24 weeks of treatment.. This is the first study to explore the association between childhood trauma and treatment outcomes during treatment with lithium or quetiapine in the context of a randomised trial. In Bipolar CHOICE, a history of childhood trauma did not inhibit improvement in symptom severity or functional impairment. Nevertheless, these findings need replication across different settings.

Topics: Adverse Childhood Experiences; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Outpatients; Quetiapine Fumarate; Treatment Outcome

Neurocognitive deficits are common in bipolar disorder (BD) across the life span, and functional neuroimaging studies have elucidated anomalous neural circuitry underlying these deficits. Nonetheless, the literature regarding changes in neural circuitry in the context of clinical trials in BD remains sparse. In this issue, Li and Lei et al.

Topics: Adolescent; Bipolar Disorder; Brain; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Mania; Quetiapine Fumarate

The aim of this study is to examine the effects of quetiapine as an adjuvant treatment for obsessive-compulsive (OC) symptoms in patients with bipolar disorder (BD) type I.. In this 8-week double-blind placebo-controlled randomized clinical trial, 47 patients with BD in euthymic phase that had OC symptoms were randomly allocated to receive either quetiapine or placebo plus their routine medications (lithium + clonazepam). Yale-Brown Obsessive-Compulsive Scale (YBOCS) was used to assess the outcomes. Adverse effects were also recorded.. Of 47 BD patients with OC symptoms that were randomly allocated in two groups of quetiapine (n = 24) and placebo group (n = 23), 40 patients (20 in quetiapine group and 20 in placebo group) completed the trial. Throughout the trial, the mean score of YBOCS in the quetiapine group dropped from 24.37 ± 1.51 to 15.26 ± 1.16 (. Our double-blind placebo-controlled clinical trial showed that quetiapine may be an effective adjuvant agent for reducing OC symptoms in BD patients.

Topics: Bipolar Disorder; Clonazepam; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

We aimed to study the probability of bipolar depression response at 24 weeks given initial non-response.. We combined two multi-site, 24-week trials including similar populations following the same evidence-based guidelines randomizing patients to lithium or quetiapine. Additional mood-stabilizing treatment was possible if clinically indicated. We report cumulative proportions of response (>50% improvement in MADRS) and remission (MADRS<10).. We included 592 participants with bipolar depression (mean 39 years, 59% female, mean MADRS 25). Among 393 (66%) participants without response after 2 weeks, 46% responded by 24 weeks; for 291 (49%) without response at 4 weeks, 40% responded and 33% remitted by 24 weeks; for 222 (38%) without a response at 6 weeks, 36% responded and 29% remitted by 24 weeks; for 185 (31%) without a response at 8 weeks, 29% responded and 24% remitted by 24 weeks. Rates were similar for participants who had started an additional mood-stabilizing drug during the first 6 or 8 weeks.. Among patients with bipolar depression and non-response after 6 weeks treatment, representing an adequate bipolar depression trial, only one-third responded by 24 weeks. These results highlight the need for better treatment alternatives for non-responders to evidence-based treatments for bipolar depression.

Topics: Adult; Affect; Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Female; Humans; Lithium; Male; Quetiapine Fumarate; Treatment Outcome

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (C

Topics: Adolescent; Bipolar Disorder; Brain; Child; Connectome; Humans; Lithium; Prospective Studies; Quetiapine Fumarate

To sequentially study the effectiveness of lithium and divalproex monotherapy and adjunctive therapy with quetiapine or lamotrigine in the acute and continuation treatment of bipolar I or II disorder at any phase of illness and at least mild symptom severity.. From June 2011 to December 2016, patients with bipolar I or II disorder (using DSM-IV diagnostic criteria) and CGI-S (Clinical Global Impression-Severity) ⩾ 3 were randomized to receive lithium or divalproex monotherapy for 2 weeks. Patients who had CGI-S-depression ⩾ 3 for 2 weeks at any time after 2-week monotherapy were randomly assigned to receive quetiapine or lamotrigine, or remaining on monotherapy for a total of 26 weeks.. The rates of early termination due to lack of efficacy and side effects and changes in BISS (Bipolar Inventory of Symptoms Scale) and CGI-S total score were not significantly different between lithium and divalproex. The completion rate was significantly higher with adjunctive therapy than with monotherapy. BISS and CGI-S total scores, and their sub-scores were significantly reduced with adjunctive therapy compared to monotherapy. Adjunctive therapy significantly increased survival times compared to monotherapy (hazard ratio = 6.8),. The efficacy of lithium and divalproex as monotherapy was modest. Adjunctive lamotrigine and quetiapine to either one was well-tolerated and equally effective in reducing bipolar symptomatology, but adjunctive therapy should be initiated as early as possible when depression symptoms are present.

Topics: Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Humans; Lamotrigine; Lithium; Quetiapine Fumarate; Treatment Outcome; Valproic Acid

The objectives of this study were to explore covariates of plasma quetiapine concentrations after oral administration of quetiapine extended-release formulation (XR), and to examine the exposure-response relationship in Japanese patients with bipolar depression, using population pharmacokinetics (PopPK) modeling.. In a multicenter, randomized, double-blind, placebo-controlled study of quetiapine XR in patients with bipolar depression, plasma for the measurement of quetiapine concentration was collected at weeks 2, 4, 8, 12, 20, 28, and 52 during oral administration of 150 or 300 mg once daily of quetiapine XR before bedtime. A PopPK model of quetiapine XR was developed using nonlinear mixed-effects modeling with first-order conditional estimation with interactions. The exposure-response relationship was examined using post-hoc exposures. The post-hoc AUC estimate was plotted against the change in the Montgomery-Åsberg Depression Rating Scale (ΔMADRS) total score from baseline to 8 weeks following once-daily doses at 300 mg.. The final PopPK analysis dataset contained 322 patients and 1162 observations (cutoff data at week 28; cutoff date, February 2016). The plasma quetiapine concentration-time profile in patients with bipolar depression after oral administration of quetiapine XR was represented well using a 1-compartment with first-order absorption model. Covariate analysis led to the selection of γ-glutamyl transpeptidase on apparent oral clearance and body weight on apparent volume of distribution as covariates. The final population mean values of apparent oral clearance and apparent volume of distribution were 87.7 L/h and 277 L, respectively, and the interindividual %CVs were 32.6% and 75.0%, respectively.. The effects of covariates on PK parameters were not large compared with the interindividual variability. In addition, there was no clear relationship between the AUC and ΔMADRS. ClinicalTrials.gov identifier: NCT01725308.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Asian People; Bipolar Disorder; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Models, Biological; Quetiapine Fumarate; Young Adult

Quetiapine has been reported to prolong the QT interval, and has been used as a positive control in thorough QT studies. The objective of the present study was to evaluate, in the late stages of clinical development, the QT-prolongation effects of the extended-release (XR) formulation of quetiapine at the approved dose in Japanese patients with bipolar disorder, using concentration-QT modeling and simulation.. Plasma concentrations of quetiapine and 4 of its metabolites (M1, M2, M4, and M5), and the QT interval corrected using the Fridericia formula (QTcF), were used for the concentration-QT analysis. Data from intensive electrocardiogram monitoring at predose and at 4, 6, 10, and 24 h after the administration of the last dose were pooled from a Phase I trial (6949-CL-0006) and from sparse sampling in late-stage clinical trials (6949-CL-0005, -0021, -0022, and -0023) in Japanese patients (N = 505). The upper limit of 1-sided 95% confidence interval (CI) of the changes from baseline in QTcF (ΔQTcF) at the geometric mean Cmax of a therapeutic dose of 300 mg once daily was predicted using a linear mixed-effects model, with the intercept as a random effect specifying a subject effect.. For quetiapine and M2, but not M1, M4, or M5, positive slopes were observed between ΔQTcF and concentration. The predicted upper limits of the 1-sided 95% CIs did not exceed the regulatory threshold of 10 msec. Therefore, QTc prolongation is unlikely to be clinically relevant at the approved dose of quetiapine XR.. In this pooled data analysis of the QT-prolongation effects of the quetiapine XR, positive relationships between ΔQTcF and quetiapine and M2 concentrations were observed. However, the predicted upper limits of the 1-sided 95% CIs did not exceed 10 msec. Therefore, QTc prolongation is unlikely to be clinically relevant at the approved dose. ClinicalTrials.gov identifiers: NCT01725282, NCT01919008, NCT01725308, NCT01737268, and NCT02362412.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Bipolar Disorder; Computer Simulation; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; Models, Biological; Quetiapine Fumarate; Young Adult

Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI.. 482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures.. Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI.. Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk.. Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions.

Topics: Adult; Anxiety; Bipolar Disorder; Comorbidity; Female; Humans; Lithium; Male; Personal Satisfaction; Quetiapine Fumarate; Suicidal Ideation; Suicide, Attempted; Treatment Outcome; Young Adult

Depressive episodes are often prevalent among patients with bipolar disorder, but little is known regarding the differential patterns of development over time. We aimed to determine and characterize trajectories of depressive symptoms among adults with bipolar disorder during 6 months of systematic treatment.. The pragmatic clinical trial, Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE), randomized 482 outpatients with bipolar disorder to lithium or quetiapine. Depressive symptoms were rated at up to 9 visits using the Montgomery-Asberg Depression Rating Scale (MADRS). Growth mixture modeling was utilized to identify trajectories and multinomial regression analysis estimated associations with potential predictors.. Four distinct trajectories of depressive symptoms were identified. The responding class (60.3%) with a rapid reduction and subsequent low level; the partial-responding class (18.4%) with an initial reduction followed by an increase during the remaining weeks; the fluctuating class (11.6%) with a fluctuation in depressive symptoms; and the non-responding class (9.7%) with sustained moderate-severe depressive symptoms. Bipolar type I predicted membership of the non-responding class and randomization to quetiapine predicted membership of either the responding or the non-responding class.. Approximately 30% experienced a partial or fluctuating course, and almost 10% had a chronic course with moderate-severe depression during 6 months. Patients diagnosed with bipolar type 1 had higher risk of being categorized into a class with a worse outcome. While no differences in average overall outcomes occurred between the lithium and quetiapine groups, trajectory analysis revealed that the lithium group had more variable courses.

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Depression; Drug Monitoring; Female; Humans; Lithium Compounds; Male; Prevalence; Prognosis; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial.. Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS.. 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics.. Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders.. Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Comorbidity; Comparative Effectiveness Research; Female; Humans; Lithium; Male; Middle Aged; Prevalence; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome; United States

In an 8-week, randomized, placebo-controlled, double-blind study, an extended-release formulation of quetiapine, quetiapine XR, demonstrated efficacy and safety in Japanese patients with bipolar depression. Bipolar disorder is a chronic disease requiring continuous treatment.. This was a long-term (52-week), open-label, non-controlled extension study to evaluate the long-term safety and efficacy of quetiapine XR in Japanese patients with bipolar depression who had previously completed the initial 8-week double-blind study. Efficacy was determined by the Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Scale 17-item (HAM-D. The mean (SD) MADRS total score decreased from 30.9 (6.9) at baseline to 16.1 (10.6) at week 8, and eventually to 9.1 (8.7) at week 52. The sustained efficacy of quetiapine XR treatment was also shown using HAM-D. The efficacy of quetiapine XR was sustained long-term and no new safety concerns were identified in Japanese patients with bipolar depression.. ClinicalTrials.gov Registration: NCT01725308. Date of registration; 12th November 2012 (retrospectively registered).

Topics: Adult; Affect; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; 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

Activation encompasses energy and activity and is a central feature of bipolar disorder. However, the impact of activation on treatment response of bipolar depression requires further exploration. The aims of this study were to assess the association of decreased activation and sustained remission in bipolar depression and test for factors that could affect this association.. We assessed participants with Diagnostic and Statistical Manual of Mental Disorders (4th ed) bipolar depression ( n = 303) included in a comparative effectiveness study of lithium- and quetiapine-based treatments (the Bipolar CHOICE study). Activation was evaluated using items from the Bipolar Inventory of Symptoms Scale. The selection of these items was based on a dimension of energy and interest symptoms associated with poorer treatment response in major depression.. Decreased activation was associated with lower remission rates in the raw analyses and in a logistic regression model adjusted for baseline severity and subsyndromal manic symptoms (odds ratio = 0.899; p = 0.015). The manic features also predicted lower remission (odds ratio = 0.934; p < 0.001). Remission rates were similar in the two treatment groups.. Decreased activation and subsyndromal manic symptoms predict lower remission rates in bipolar depression. Patients with these features may require specific treatment approaches, but new studies are necessary to identify treatments that could improve outcomes in this population.

Topics: Adult; Bipolar Disorder; Female; Humans; Lithium Compounds; Male; Predictive Value of Tests; Prodromal Symptoms; Quetiapine Fumarate; Remission Induction; Severity of Illness Index; Treatment Outcome; Young Adult

The impact of psychosis on the treatment of bipolar depression is remarkably understudied. The primary aim of this study was to compare treatment outcomes of bipolar depressed individuals with and without psychosis. The secondary aim was to compare the effect of lithium and quetiapine, each with adjunctive personalized treatments (APTs), in the psychotic subgroup.. We assessed participants with DSM-IV bipolar depression included in a comparative effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS) and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP). Mixed models were used to assess the course of symptom change, and Cox regression survival analysis was used to assess the time to remission.. Psychotic features were present in 10.6% (n = 32) of the depressed participants (n = 303). Those with psychotic features had higher scores on the BISS before (75.2 ± 17.6 vs. 54.9 ± 16.3; P < .001) and after (37.2 ± 19.7 vs. 26.3 ± 18.0; P = .003) 6-month treatment. The CGI-S-BP yielded similar results. Participants with and without psychosis had similar course of symptom improvement and similar time to remission. There was no significant difference in the treatment outcomes of lithium (n = 11) and quetiapine (n = 21) among the psychotic subgroup.. Bipolar depressive episodes with psychotic features are more severe, and compared to nonpsychotic depressions, present a similar course of improvement. Given the small number of participants presenting psychosis, the lack of statistically significant difference between lithium- and quetiapine-based treatment of psychotic bipolar depressive episodes needs replication in a larger sample.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Comorbidity; Female; Humans; Lithium Compounds; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Treatment Outcome; Young Adult

Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months. Resting-state fMRI was acquired at baseline, 3 months (patient only) and 12 months. The effects of treatment group, time and their interaction, on striatal functional connectivity were assessed using voxel-wise general linear modelling. At baseline, FEM patients showed reduced connectivity in the dorsal (p = 0.05) and caudal (p = 0.008) cortico-striatal systems when compared to healthy controls at baseline. FEM patients also showed increased connectivity in a circuit linking the ventral striatum with the medial orbitofrontal cortex, cerebellum and thalamus (p = 0.02). Longitudinally, we found a significant interaction between time and treatment group, such that lithium was more rapid, compared to quetiapine, in normalizing abnormally increased functional connectivity, as assessed at 3-month and 12-month follow-ups. The results suggest that FEM is associated with reduced connectivity in dorsal and caudal corticostriatal systems, as well as increased functional connectivity of ventral striatal systems. Lithium appears to act more rapidly than quetiapine in normalizing hyperconnectivity of the ventral striatum with the cerebellum. The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12607000639426). http://www.anzctr.org.au.

Topics: Adolescent; Adult; Antimanic Agents; Bipolar Disorder; Cerebellum; Connectome; Corpus Striatum; Female; Follow-Up Studies; Humans; Lithium Compounds; Magnetic Resonance Imaging; Male; Prefrontal Cortex; Quetiapine Fumarate; Single-Blind Method; Thalamus; Young Adult

Successful medication management for bipolar disorder requires clinicians to monitor and adjust regimens as needed, to achieve maximum effectiveness and patient adherence. This study aims to measure the prevalence of indications for medication adjustment at visits for bipolar disorder treatment; the frequency with which physicians recommend medication adjustments; and how strongly the indications predict the adjustments.. Data included 3,094 visits for 457 patients in Bipolar CHOICE, a comparative effectiveness study that compared treatment with lithium versus quetiapine. A set of indications for adjustment was matched to reports of whether the physician recommended a medication adjustment at that visit, and what type. Associations between indication and adjustment were examined using bivariate tests and hierarchical logistic mixed effects models.. Medication adjustment was recommended at 63% of the visits where one of the indications was present, and at 53% of all visits. In multivariable analyses, adjustment was more likely to be recommended if there was an indication of non-response or side effects, for patients who started on quetiapine rather than lithium, or for patients who were female, married, employed or more educated.. The study's cross-sectional design implies that observed associations could result from confounding variables. Also, the CHOICE trial placed certain restrictions on physicians' medication choices, although this is not likely to have resulted in major alterations of prescribing patterns.. Clinical inertia may help explain the lack of any adjustment recommendation at 37% of the visits where one of the indications was present. Other explanations could also apply, such as watchful waiting.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Comparative Effectiveness Research; Cross-Sectional Studies; Female; Humans; Lithium; Logistic Models; Male; Middle Aged; Practice Patterns, Physicians'; Prevalence; Quetiapine Fumarate

Quetiapine fumarate is an atypical antipsychotic indicated for various mental disorders, but it has not been studied in Japanese patients with bipolar depression.. To evaluate the efficacy and safety of quetiapine XR (extended release) in Japanese patients with bipolar depression.. In this multi-center, randomized, double-blind, placebo-controlled, fixed-dose study of 431 Japanese adults with bipolar I or II disorder, efficacy was determined by analyzing the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary end points included MADRS response and remission rates, Hamilton Depression Scale 17-Item (HAM-D. Once-daily monotherapy with quetiapine XR is an effective and well-tolerated treatment for bipolar depression in Japanese patients.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Japan; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Single-Blind Method

The aim of this study was to compare the effectiveness of lithium versus quetiapine immediate release (IR) monotherapy in patients with bipolar I, II, or subthreshold bipolar disorder at any phase.. Eligible patients were randomized to lithium or quetiapine IR for 16 weeks. The difference in the time to discontinuation from study due to "all causes" between lithium and quetiapine IR groups and changes from baseline to 8 and 16 weeks in depression, mania, anxiety, quality of life (QOL), metabolic profiles, and proinflammatory markers were compared.. Of the 42 patients randomized to lithium (n = 18) and quetiapine IR (n = 24), the median time to discontinuation due to "all causes" was 6 weeks (95% confidence interval, 2-12 weeks) in the lithium group and 8 weeks (95% confidence interval, 6 weeks to not calculable) in the quetiapine IR group. The mean time to discontinuation due to "all causes" was 7.7 ± 1.1 weeks for lithium versus 8.4 ± 0.8 weeks for quetiapine IR (P = 0.54). There was no significant difference between lithium and quetiapine IR in changes in the severity of depression, mania/hypomania, anxiety, and QOL as a whole or only in patients with depressive index episode. The decrease in total cholesterol was significantly larger with lithium than with quetiapine IR (P = 0.05) as a whole, but not only in patients with depression index episode. There was no other significant difference in changes in metabolic panels and inflammatory markers between the 2 groups.. The difference in effectiveness between lithium and quetiapine IR monotherapy in a real-world bipolar population was minimal. Large-sample studies are needed to support or refute this finding.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Female; Humans; Lithium; Male; Middle Aged; Pilot Projects; Quetiapine Fumarate; Treatment Outcome; Young Adult

Although not licensed for acute bipolar depression, lamotrigine has evidence for efficacy in trials and its use is recommended in guidelines. So far there had been no prospective health economic evaluation of its use.. Cost-utility analysis of the CEQUEL trial comparing quetiapine plus lamotrigine vs quetiapine monotherapy (and folic acid vs placebo in an add-on factorial design) for patients with bipolar depression (n = 201) from the health and social care perspective. Differences in costs together with quality-adjusted life years (QALYs) between the groups were assessed over 52 weeks using a regression-based approach.. Health-related quality of life improved substantially for all randomization groups during follow-up with no significant difference in QALYs between any of the comparisons (mean adjusted QALY difference: lamotrigine vs placebo -0.001 (95% CI: -0.05 to 0.05), folic acid vs placebo 0.002 (95% CI: -0.05 to 0.05)). While medication costs in the lamotrigine group were higher than in the placebo group (£647, P < 0.001), mental health community/outpatient costs were significantly lower (-£670, P < 0.001). Mean total costs were similar in the groups (-£180, P = 0.913).. Lamotrigine improved clinical ratings in bipolar depression compared with placebo. This differential effect was not detected using the EQ-5D-3L. The additional cost of lamotrigine was balanced by significant savings in some other medical costs which made its use cost neutral to the health service. Compared to placebo, folic acid produced neither clinical nor significant health economic benefits. The study supports the use of lamotrigine in combination with other drugs to treat bipolar depression.

Topics: Antipsychotic Agents; Bipolar Disorder; Cost-Benefit Analysis; Depression; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Humans; Lamotrigine; Male; Placebos; Quality of Life; Quality-Adjusted Life Years; Quetiapine Fumarate; Treatment Outcome

The aim of this study was to evaluate the effects of quetiapine XR and lithium on actigraphy-measured circadian parameters in patients with bipolar II depression.. This was an 8-week, open-label, prospective, randomized comparative study. The assessments included the 17-item Hamilton Depression Rating Scale score and actigraphic measures concerning the previous 7 days, collected at each visit (weeks 0 [baseline], 1, 2, 4, 6, and 8); the actigraphic data were analyzed with a cosinor analysis.. Medication, time, and the interaction between medication and time were significantly associated with acrophase for the entire group (Ps = 0.003, 0.020, and 0.042, respectively). More specifically, acrophase was significantly delayed at weeks 1 and 6 (Ps = 0.004 and 0.039, respectively) in the quetiapine XR group. The F statistics significantly increased over time for the entire group (P < 0.001), and there was a significant increase in F statistics on weeks 4 and 6 in the quetiapine XR group (Ps = 0.016 and 0.020, respectively) and on weeks 4 and 8 in the lithium group (Ps = 0.001 and 0.016, respectively). In addition, scores on the 17-item Hamilton Depression Rating Scale were significantly associated with the F statistics during 8 weeks for the entire group (P = 0.008).. Both quetiapine XR and lithium affected several circadian parameters, including peak activity time and robustness of circadian rhythm, but exerted different effects on acrophase in patients with bipolar II depression. In particular, clinical depressive symptoms were associated with robustness of circadian rhythm during the course of the 8-week treatment.

Topics: Actigraphy; Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Circadian Rhythm; Female; Humans; Lithium Compounds; Male; Middle Aged; Outcome Assessment, Health Care; Quetiapine Fumarate; Young Adult

This study aims to compare treatment response in bipolar I or II depression and generalized anxiety disorder (GAD) with and without recent alcohol and/or cannabis use disorder (ALC/CAN) to quetiapine-XR (extended release) or placebo.. A randomized, double-blind, 8-week study of quetiapine-XR versus placebo in patients with bipolar I or II depression and GAD with or without a recent ALC/CAN was used to compare changes in Hamilton Depression Rating Scale-17, Hamilton Anxiety Rating Scale, the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16), Clinical Global Impression for Bipolar Disorder-Severity (CGI-BP-S), and Timeline Follow Back within and between groups.. In the quetiapine-XR group, patients with a recent ALC/CAN (n = 22) had significant decreases in QIDS-SR-16 (-9.6 ± 1.6 vs. -3.7 ± 1.7) and CGI-BP-S (-1.6 ± 0.4 vs. -0.8 ± 0.03) than those without a recent ALC/CAN (n = 24). In the placebo group, both patients with a recent ALC/CAN (n = 23) and those without (n = 21) had similar reductions in these measures. The reduction of QIDS-SR-16 scores in patients with a recent ALC/CAN was also significantly different from that of their counterparts in the placebo group. Patients who received quetiapine-XR had larger decreases in the number of drinking days/week (p = 0.17) and number of cannabis joints/week (p = 0.09) compared to those who received placebo.. Quetiapine-XR was superior to placebo in reducing QIDS-SR-16 total score in patients with a recent ALC/CAN. Patients taking quetiapine-XR used less alcohol and cannabis than patients on placebo, suggesting that quetiapine-XR may be of use in patients with bipolar disorder accompanied by GAD and other comorbidities.

Topics: Adult; Alcohol Drinking; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Cannabis; Comorbidity; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Marijuana Smoking; Middle Aged; Quetiapine Fumarate; Self Report; Treatment Outcome

Suicidal ideation occurs frequently among individuals with bipolar disorder; however, its course and persistence over time remains unclear. We aimed to investigate 6-months trajectories of suicidal ideation among adults with bipolar disorder.. The Bipolar CHOICE study randomized 482 outpatients with bipolar disorder to 6 months of lithium- or quetiapine-based treatment including other psychotropic medications as clinically indicated. Participants were asked at 9 visits about suicidal ideation using the Concise Health Risk Tracking scale. We performed latent Growth Mixture Modelling analysis to empirically identify trajectories of suicidal ideation. Multinomial logistic regression analyses were applied to estimate associations between trajectories and potential predictors.. We identified four distinct trajectories. The Moderate-Stable group represented 11.1% and was characterized by constant suicidal ideation. The Moderate-Unstable group included 2.9% with persistent thoughts about suicide with a more fluctuating course. The third (Persistent-low, 20.8%) and fourth group (Persistent-very-low, 65.1%) were characterized by low levels of suicidal ideation. Higher depression scores and previous suicide attempts (non-significant trend) predicted membership of the Moderate-Stable group, whereas randomized treatment did not.. No specific treatments against suicidal ideation were included and suicidal thoughts may persist for several years.. More than one in ten adult outpatients with bipolar disorder had moderately increased suicidal ideation throughout 6 months of pharmacotherapy. The identified predictors may help clinicians to identify those with additional need for treatment against suicidal thoughts and future studies need to investigate whether targeted treatment (pharmacological and non-pharmacological) may improve the course of persistent suicidal ideation.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Lithium; Male; Middle Aged; Outpatients; Psychotropic Drugs; Quetiapine Fumarate; Risk; Suicidal Ideation; Suicide; Suicide, Attempted

CEQUEL (Comparative Evaluation of QUEtiapine plus Lamotrigine combination versus quetiapine monotherapy [and folic acid versus placebo] in bipolar depression) was a double-blind, randomized, placebo-controlled, parallel group, 2×2 factorial trial that examined the effect of adding lamotrigine and/or folic acid (FA) to quetiapine in bipolar depression. Lamotrigine improved depression, but its effectiveness was reduced by FA. We investigated the baseline predictors and correlates of clinical response, and the possible basis of the interaction.. The main outcome was change in depressive symptoms at 12 weeks, measured using the Quick Inventory for Depressive Symptoms-self report version 16 (QIDS-SR16). We examined the relationship between symptoms and lamotrigine levels, and biochemical measures of one-carbon metabolism and functional polymorphisms in catechol-O-methyltransferase (COMT), methylene tetrahydrofolate reductase (MTHFR) and folate hydrolase 1 (FOLH1).. Lamotrigine levels were unaffected by FA and did not differ between those participants who achieved remission and those with persisting symptoms. When participants with subtherapeutic serum levels were excluded, there was a main effect of lamotrigine on the main outcome, although this remained limited to those randomized to FA placebo. None of the biochemical measures correlated with clinical outcome. The negative impact of FA on lamotrigine response was limited to COMT Met carriers. FOLH1 and MTHFR had no effect.. Our results clarify that FA's inhibition of lamotrigine's efficacy is not a pharmacokinetic effect, and that low serum lamotrigine levels contributed to lamotrigine's lack of a main effect at 12 weeks. We were unable to explain the lamotrigine-FA interaction, but our finding that it is modulated by the COMT genotype provides a starting point for follow-on neurobiological investigations. More broadly, our results highlight the value of including biochemical and genetic indices in randomized clinical trials.

Topics: Adult; Bipolar Disorder; Brief Psychiatric Rating Scale; Catechol O-Methyltransferase; Double-Blind Method; Drug Combinations; Female; Folic Acid; Humans; Lamotrigine; Male; Pharmacogenomic Testing; Psychotropic Drugs; Quetiapine Fumarate; Treatment Outcome; Triazines

Patients with bipolar disorder (BD) do not always achieve full remission between episodes. Subthreshold symptoms (depressive, manic or mixed) represent a major cause of relapse and disability in these patients. Immediate release (IR) and extended release (XR) formulations of quetiapine are both indicated for short and long-term treatment of BD. The aim of this study was to evaluate the efficacy of quetiapine XR vs placebo in subthreshold symptomatology when added to previous mood stabilizer treatment. A pilot phase IIIB, multicentre, prospective, placebo controlled, randomized, double blinded study of 12 weeks follow-up was performed (NCT01197846). Patients were randomized to quetiapine XR 300mg or placebo once daily. The primary outcome was the mean change between quetiapine XR and placebo from baseline to study endpoint (week 6) in the Montgomery-Åsberg Depression Rating Scale (MADRS). Quetiapine XR 300mg (n=16) significantly improved depressive subthreshold symptoms compared with placebo (n=16) after 6 weeks (P=0.021). Early response (reduction of at least the 20% of the MADRS total score) and remission rate (reduction in MADRS total score <8 and YMRS<8) did not show differences between groups. Quetiapine XR did not show superiority vs placebo when evaluating subthreshold manic symptoms, instead it was superior when evaluating functioning (GAF score) in BD type I patients (P=0.005). The most common adverse events were somnolence (9.1%), increased appetite, dry mouth and dizziness (6.8%). Quetiapine XR 300mg once daily was significantly more effective than placebo in depressive subthreshold symptoms. Adverse events were consistent with the known side effects of quetiapine.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Antimanic Agents; Bipolar Disorder; Body Weight; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Young Adult

Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (n=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (n=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Female; Gray Matter; Humans; Lithium Compounds; Maintenance Chemotherapy; Male; Neuroprotective Agents; Organ Size; Quetiapine Fumarate; Single-Blind Method; White Matter; Young Adult

Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania.. The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points.. There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition.. Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Cognition; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Intelligence; Lithium Compounds; Male; Memory; Quetiapine Fumarate; Single-Blind Method; Time Factors; Treatment Outcome; Verbal Learning; Young Adult

Depressive symptoms are a major cause of disability in bipolar disorder and there are few safe and effective treatments. The combination of lamotrigine plus quetiapine potentially offers improved outcomes for people with bipolar depression. We aimed to determine if combination therapy with quetiapine plus lamotrigine leads to greater improvement in depressive symptoms over 12 weeks than quetiapine monotherapy plus lamotrigine placebo.. In this double-blind, randomised, placebo-controlled, parallel group, 2 × 2 factorial trial (CEQUEL), patients with DSM-IV bipolar disorder I or II, who were aged 16 years or older, and required new treatment for a depressive episode, were enrolled from 27 sites in the UK. Patients were randomly assigned (1:1) by an adaptive minimisation algorithm to lamotrigine or placebo and to folic acid or placebo. Participants and investigators were masked to the treatment groups. The primary outcome was improvement in depressive symptoms at 12 weeks with the Quick Inventory of Depressive Symptomatology-self report version 16 (QIDS-SR16). Analysis was by modified intention-to-treat. This trial is registered with EUdraCT, number 2007-004513-33.. Between Oct 21, 2008, and April 27, 2012, 202 participants were randomly assigned; 101 to lamotrigine and 101 to placebo. The mean difference in QIDS-SR16 total score between the group receiving lamotrigine versus the placebo group at 12 weeks was -1·73 ([95% CI -3·57 to 0·11]; p=0·066) and at 52 weeks was -2·69 ([-4·89 to -0·49]; p=0·017). Folic acid was not superior to placebo. There was a significant interaction (p=0·028), with folic acid reducing the effectiveness of lamotrigine at 12 weeks. The mean difference on QIDS-SR16 was -4·14 ([95% CI -6·90 to -1·37]; p=0·004) for patients receiving lamotrigine without folic acid compared with 0·12 ([-2·58 to 2·82]; p=0·931) for those receiving lamotrigine and folic acid.. Addition of lamotrigine to quetiapine treatment improved outcomes. Folic acid seems to nullify the effect of lamotrigine. CEQUEL should encourage clinicians and patients to consider lamotrigine for bipolar depression, but also to be aware that concurrent folic acid might reduce its effectiveness.. Medical Research Council.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Folic Acid; Humans; Lamotrigine; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome; Triazines

Quetiapine is an atypical antipsychotic recommended as first-line treatment for acute bipolar depression. The extended-release quetiapine formulation is intended to be administered as an once-daily dosing. The development of an in vitro-in vivo correlation (IVIVC) and the use of in vitro data to predict in vivo bioavailability parameters has been of great interest for the rational development and evaluation process for extended release dosage forms. The aim of this study was to develop an IVIVC for quetiapine extended release formulation. In vitro dissolution rate data were obtained using USP apparatus 2 at 50 rpm, in 3 bio-relevant dissolution media with different pH values (1.2, 4.5 and 6.8). The drug release profiles of the 2 extended release dosage forms were compared using the similarity factor (f 2). The relative bioavailability of quetiapine was evaluated by a single-dose, randomized-sequence, open-label, 2 period cross over study with 16 healthy volunteers. A linear level A IVIVC model was established using percentage of absorbed and dissolved data obtained at pH 1.2. The developed IVIVC model was employed to predict quetiapine concentration-time profiles, as well as the bioequivalence parameters for test formulation. Percent prediction errors were estimated for Cmax and AUC to evaluate the validity of the correlation. The values did not exceed 15%, proving the predictability of the correlation model. In conclusion, the established level A IVIVC model proved to be an excellent tool for predicting the rate and extent of quetiapine absorption as characterized by Cmax and AUC for test formulation.

Topics: Adolescent; Adult; Antipsychotic Agents; Area Under Curve; Biological Availability; Bipolar Disorder; Cross-Over Studies; Delayed-Action Preparations; Drug Liberation; Female; Healthy Volunteers; Humans; Male; Models, Biological; Quetiapine Fumarate; Therapeutic Equivalency; Young Adult

Bipolar disorder is among the 10 most disabling medical conditions worldwide. While lithium has been used extensively for bipolar disorder since the 1970s, second-generation antipsychotics (SGAs) have supplanted lithium since 1998. To date, no randomized comparative-effectiveness study has compared lithium and any SGA.. Within the duration of the study (September 2010-September 2013), participants with bipolar I or II disorder (DSM-IV-TR) were randomized for 6 months to receive lithium (n = 240) or quetiapine (n = 242). Lithium and quetiapine were combined with other medications for bipolar disorder consistent with typical clinical practice (adjunctive personalized treatment [APT], excluding any SGA for the lithium + APT group and excluding lithium or any other SGA for the quetiapine + APT group). Coprimary outcome measures included Clinical Global Impressions-Efficacy Index (CGI-EI) and necessary clinical adjustments, which measured number of changes in adjunctive personalized treatment. Secondary measures included a full range of symptoms, cardiovascular risk, functioning, quality of life, suicidal ideation and behavior, and adverse events.. Participants improved across all measures, and over 20% had a sustained response. Primary (CGI-EI, P = .59; necessary clinical adjustments, P = .15) and secondary outcome changes were not statistically significantly different between the 2 groups. For participants with greater manic/hypomanic symptoms, CGI-EI changes were significantly more favorable with quetiapine + APT (P = .02). Among those with anxiety, the lithium + APT group had fewer necessary clinical adjustments per month (P = .02). Lithium was better tolerated than quetiapine in terms of the burden of side effects frequency (P = .05), intensity (P = .01), and impairment (P = .01).. Despite adequate power to detect clinically meaningful differences, we found outcomes with lithium + APT and quetiapine + APT were not significantly different across 6 months of treatment for bipolar disorder.. ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Lithium; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome

To examine the effects of treatment on functioning impairments and quality of life and assess baseline functioning and employment status as predictors of treatment response in symptomatic individuals from the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (Bipolar CHOICE) study.. Bipolar CHOICE was an 11-site, 6-month randomized effectiveness study comparing lithium to quetiapine, each with adjunctive personalized treatments (APTs). We examined post hoc (1) the effects of treatment on functioning, (2) how changes in functioning differed between treatment responders and nonresponders, and (3) whether functioning and employment status mediated treatment response in 482 participants with DSM-IV-TR bipolar I or II disorder from September 2010 to September 2013.. Treatment was associated with significant improvements in functioning and quality of life, regardless of treatment group (P values < .0001). Responders showed greater improvements in quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire P values < .05) and functioning (Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool P values < .05) than nonresponders. Unemployed or disabled participants at baseline had significantly greater illness severity at baseline than employed participants (P values < .05). Over the study duration, employed participants reported greater improvements in physical health and quality of life in leisure activities than both unemployed and disabled participants (P values < .05). Individuals who saw greater improvement in functioning and quality of life tended to show greater improvements in depressive and anxiety symptoms (P values ≤ .0001), as well as overall illness severity (P values < .001). Early (8 weeks) and very early (4 weeks) clinical changes in mood symptoms predicted changes in functioning and quality of life at 6 months (P values < .001).. Prior disability status was associated with a worse treatment response and prospective illness course. Results implicate functioning and employment status as important markers of illness severity and likelihood of recovery in bipolar disorder, suggesting that interventions that target functional impairment may improve outcomes.. ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Disability Evaluation; Employment; Female; Humans; Lithium; Male; Prospective Studies; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

Quetiapine extended release (XR) has been used to treat various psychiatric disorders, including depressive episodes associated with bipolar I and II disorders. Quetiapine XR is the first approved drug in China for the treatment of bipolar disorder.. The study evaluated the efficacy and safety of short-term quetiapine XR monotherapy in the treatment of depressive episodes of bipolar I and II disorders.. This was an 8-week multi-center, randomized, double-blind, placebo-controlled, fixed-dose phase 3 study. The primary endpoint was the mean change of the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary endpoints included Clinical Global Impressions-Bipolar (CGI-BP) and remission rates.. The study recruited 279 adult bipolar I or II patients currently experiencing depression from 11 Chinese provinces. Of these, 139 received quetiapine XR (300 mg/day) and 140 received placebo for 8 weeks. The mean change in the MADRS total score was significantly greater in the quetiapine XR group than in the placebo group (-19.00 ± 7.88 vs. -16.20 ± 9.32; p = 0.004). Adverse events occurred in 96 patients (65.3 %) in the quetiapine XR group and 72 (49.0 %) in the placebo group. The incidence of serious adverse events did not differ significantly between the groups (p = 0.247).. This study, which is the first to evaluate 300 mg/day quetiapine XR monotherapy for depression in Chinese patients with bipolar disorders, found that this drug was superior to the placebo. Quetiapine XR was generally safe and well tolerated (ClinicalTrials.gov number, NCT01256177).

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Asian People; Bipolar Disorder; China; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Young Adult

The clinical and cognitive responses to repetitive transcranial magnetic stimulation (rTMS) in bipolar II depressed patients remain unclear. In this study, thirty-eight bipolar II depressed patients were randomly assigned into three groups: (i) left high-frequency (n = 12), (ii) right low-frequency (n = 13), (iii) sham stimulation (n = 13), and underwent four-week rTMS with quetiapine concomitantly. Clinical efficacy was evaluated at baseline and weekly intervals using the 17-item Hamilton Depression Rating Scale (HDRS-17) and Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive functioning was assessed before and after the study with the Wisconsin Card Sorting Test (WCST), Stroop Word-Color Interference Test (Stroop), and Trail Making Test (TMT). Thirty-five patients were included in the final analysis. Overall, the mean scores of both the HDRS-17 and the MADRS significantly decreased over the 4-week trial, which did not differ among the three groups. Exploratory analyses revealed no differences in factor scores of HDRS-17s, or in response or remission rates. Scores of WCST, Stroop, or TMT did not differ across the three groups. These findings indicated active rTMS combined with quetiapine was not superior to quetiapine monotherapy in improving depressive symptoms or cognitive performance in patients with bipolar II depression.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Female; Humans; Male; Quetiapine Fumarate; Transcranial Magnetic Stimulation; Treatment Outcome

We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize - i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers.. Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response.. ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors.. These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.

Topics: Adult; Amygdala; Antimanic Agents; Bipolar Disorder; Emotions; Episode of Care; Female; Humans; Lithium; Magnetic Resonance Imaging; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Task Performance and Analysis; Treatment Outcome

Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity.. The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence).. We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides.. There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Asthma; Bipolar Disorder; Cardiovascular Diseases; Comorbidity; Comparative Effectiveness Research; Diabetes Mellitus; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Hyperlipidemias; Lithium Compounds; Male; Metabolic Syndrome; Middle Aged; Neoplasms; Quetiapine Fumarate; Seizures; Smoking; Substance-Related Disorders

A population model describing quetiapine pharmacokinetics (PK) in Western and Chinese patients following oral administration of immediate-release (IR) and extended-release (XR) formulations was developed using plasma concentrations in 127 patients from 5 studies with quetiapine IR and/or XR in Western patients and 1 study with quetiapine XR in Chinese patients. A 1-compartmental model with first-order absorption and first-order elimination adequately described the quetiapine PK. The typical apparent volume of distribution and elimination rate constant of quetiapine were 574 L and 0.12 h(-) (1) , respectively. The estimated population absorption rate constants were 1.46 and 0.10 h(-1) for quetiapine IR and XR, respectively. Covariate analysis revealed that race was not a significant covariate influencing the PK of quetiapine. Simulation conducted with the final quetiapine population PK model predicted that the administration of a 200-mg twice-daily dose of quetiapine IR in Chinese patients would achieve a steady-state AUC (AUCss ) ± standard deviation of 3087 ± 1480 ng · h/mL, which is in close agreement with the reported value (3538 ± 1728 ng · h/mL). The model also predicted that once-daily administration of 300 mg quetiapine IR or XR would achieve similar exposure in terms of AUCss in Chinese patients.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Asian People; Bipolar Disorder; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Models, Biological; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Young Adult

Although a frequent co-occurrence between bipolar disorder (BD) and conduct disorder (CD) in youth has been frequently reported, data about pharmacological management are scarce and focused on BD type I. Second generation antipsychotics are frequently used in clinical practice, but no comparative studies are available. The aim of this exploratory study was to compare efficacy and safety of risperidone and quetiapine in a sample of adolescents presenting a BD type II comorbid with CD. Twenty-two patients diagnosed with a structured interview according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (male/female ratio, 12/10; mean (SD) age 15.0 (1.4) years) were randomized in 2 treatment groups (quetiapine [n = 12] vs risperidone [n = 10]), treated with flexible doses, and followed up for 12 weeks. Efficacy measures assessed manic symptoms, aggression, anxiety, depression, global clinical severity, and impairment. Safety measures included body mass index, serum prolactin, extrapyramidal adverse effects, and electrocardiogram. At the end of the study, all patients improved in all efficacy measures. Both treatments showed similar efficacy in reducing manic symptoms and aggression. Quetiapine was more effective in improving anxiety and depressive symptoms. A change in body mass index was found, and in a post hoc analysis, it was significant only in the risperidone group. Prolactin significantly increased only in the risperidone group. In BD type II, CD comorbidity, quetiapine, or risperidone monotherapy may be effective and relatively safe, although the small sample size, the limited duration of the study, and the design (lack of a blind assessments and of a placebo group) make it difficult to draw definitive conclusions.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Body Mass Index; Conduct Disorder; Female; Humans; Male; Prolactin; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Treatment Outcome

Classic and second-generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the 'real-world' advantages and disadvantages of these medications.. We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This article outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder.. Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments (APTs). The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score, and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT).. The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus APT, across 10 sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. In all, 482 participants were randomized to the study, and 364 completed the study.. The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants' ability to pay for study medications.. We expect that this study will inform our understanding of the benefits and harms of lithium, a classic mood stabilizer, compared to quetiapine, a second-generation antipsychotic with broad-spectrum activity in bipolar disorder, and will provide an example of a well-designed and well-conducted randomized comparative effectiveness clinical trial.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Clinical Protocols; Comparative Effectiveness Research; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Intention to Treat Analysis; Lithium; Male; Middle Aged; Patient Selection; Prospective Studies; Quetiapine Fumarate; Research Design; Single-Blind Method; Treatment Outcome

Bipolar depression is one of the most serious psychiatric conditions. In addition, sleep disturbance in bipolar disorder is common, and therapeutic agents restoring sleep disturbances in bipolar disorder patients will be clinically beneficial. In the current study, we compared the effect of quetiapine XR with lithium on depressive symptoms and sleep in bipolar depression patients during 8 weeks of trial.. An open-label, randomized comparison of sleep-activity and depressive symptoms between 8-week quetiapine XR monotherapy and lithium monotherapy for bipolar depression was conducted. Each assessment consisted of HDRS-17, Clinical Global Impression-severity (CGI-S), and self-reported Pittsburgh Sleep Quality Index (PSQI). Actigraphy-measured sleep parameters were assessed.. A total of 42 patients (35.7±10.9 years; gender: male 15, female 27) with bipolar depression were screened out. Out of 42 patients, six patients were excluded before randomization. After randomization, seven patients were withdrawn. Twenty-nine patients with more than two visits after randomization (lithium group: 17, quetiapine XR group: 12, mean age: 36.1±10.4, gender: male 13, female 16) were included in the final analysis. In both groups, Hamilton Depression Rating Scale (HDRS) scores were significantly decreased at weeks 1, 2, 4, 6, and 8 compared with baseline. Remission rate (HDRS≤7) in the quetiapine XR was significantly higher than that of the lithium group. In the quetiapine XR group, PSQI scores at weeks 1, 2, 4, 6, and 8 was significantly decreased compared with baseline. Sleep efficiency at weeks 6 and 8 was significantly increased. WASO at week 8 was significantly decreased.. First, the present study was conducted with the relatively small number of study subjects. Second, bias could have affected the study results due to its open-label design. Third, study subjects were made up of high proportion of bipolar II disorder patients.. Quetiapine XR monotherapy was more effective in treating bipolar depression than lithium. In particular, quetiapine XR treatment improved both subjective and objective sleep quality in patients with bipolar depression. However, relationship between favorable sleep quality and depressive symptom improvement were limited.

Topics: Adult; Affect; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lithium; Male; Middle Aged; Quetiapine Fumarate; Sleep Wake Disorders

Topics: Antipsychotic Agents; Bipolar Disorder; Cognition; Delayed-Action Preparations; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Quetiapine Fumarate; Treatment Outcome

Quetiapine (QTP) has been shown to be effective as an acute treatment in patients with bipolar depression. Nonetheless, the time at onset of QTP antidepressant action has not been clarified. We aimed to evaluate the onset of the antidepressant effect of QTP extended release (XR) in bipolar depression. We also compared the different efficacy and adverse effect profile of 300- and 600-mg/d dosages.. Twenty-one acutely bipolar depressed patients were recruited; 13 were treated with QTP XR 300 and 8 with 600 mg/d. Assessment was performed with Hamilton Depression Rating Scale (also considering clusters "core," "somatic anxiety," "psychic anxiety," "activity," and "delusion"), Hamilton Anxiety Rating Scale, Dosage Record and Treatment Emergent Symptom Scale.. Quetiapine XR was effective since the first 3 days of treatment in reducing all the efficacy measures except for somatic anxiety. The comparison of 300- and 600-mg dosages was limited by the small sample size. However, the analysis did not show any significant difference in terms of efficacy, although with a trend in favor of 600 mg. The incidence of hypotension was significantly higher in patients taking QTP 600 mg (P = 0.004).. Quetiapine seems to be effective in bipolar depression within the first days of treatment. There may be not a significant advantage for the 600-mg dose in comparison with the 300-mg one. The clinical effect seems to be not associated with sedation, suggesting that it may be due to the molecular drug effect. Further studies focusing on the first days of treatment are needed to confirm our findings.

Topics: Acute Disease; Adult; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Time Factors; Treatment Outcome

Little is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders.. The study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-based treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up. Selected outcomes were also compared between patients who did and did not initiate benzodiazepines during follow-up using stabilized inverse probability weighted analyses.. Significant improvement in all outcome measures occurred within each benzodiazepine exposure group. Benzodiazepine users (at baseline or during follow-up) experienced significantly less improvement in BISS total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users. There were no significant differences in these measures between patients who did and did not initiate benzodiazepines during follow-up in the weighted analyses. There was no significant effect of benzodiazepine use on any outcome measure in patients with comorbid anxiety or substance use disorders.. This is a secondary analysis of data from a randomized effectiveness trial that was not designed to address differential treatment response according to benzodiazepine use.. Adjunctive benzodiazepines may not significantly affect clinical outcome in lithium- or quetiapine-treated patients with bipolar I or II disorder over 6 months, after controlling for potential confounding factors.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Lithium Compounds; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome

Quetiapine is an atypical antipsychotic with demonstrated efficacy in the treatment of adolescent schizophrenia and pediatric bipolar mania. Large, placebo-controlled studies of interventions in pediatric bipolar depression are lacking. The current study investigated the efficacy and safety of quetiapine extended-release (XR) in patients 10-17 years of age, with acute bipolar depression.. This multicenter, double-blind, randomized, placebo-controlled study investigated quetiapine XR (dose range, 150-300 mg/day) in pediatric outpatients with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar I or bipolar II disorder (current or most recent episode depressed) treated for up to 8 weeks (ClinicalTrials.gov identifier: NCT00811473). The primary study outcome was mean change in Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary efficacy outcomes included CDRS-R-based response and remission rates.. Of 193 patients randomized to treatment, 144 patients completed the study (75.3% of quetiapine XR group [n=70]; 74.0% of placebo group [n=74]). Least squares mean changes in CDRS-R total score at week 8 were: -29.6 (SE, 1.65) with quetiapine XR and -27.3 (SE, 1.60) with placebo, a between-treatment group difference of -2.29 (SE, 1.99; 95% CI, -6.22, 1.65; p=0.25; mixed-model for repeated measures analysis). Rates of response and remission did not differ significantly between treatment groups. The safety profile of quetiapine XR was broadly consistent with the profile reported previously in adult studies of quetiapine XR and pediatric studies of quetiapine immediate-release (IR). Potentially clinically significant elevations in clinical chemistry values included triglycerides (9.3%, quetiapine XR; 1.4%, placebo group) and thyroid stimulating hormone (4.7%, quetiapine XR; 0%, placebo group). An adverse event potentially related to diabetes mellitus occurred in 3.3% of the quetiapine XR versus no adverse events in the placebo group.. Quetiapine XR did not demonstrate efficacy relative to placebo in this 8 week study of pediatric bipolar depression. Quetiapine XR was generally safe and well tolerated.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Outpatients; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Alcohol dependence is common in bipolar disorder (BPD) and associated with treatment nonadherence, violence, and hospitalization. Quetiapine is a standard treatment for BPD. We previously reported improvement in depressive symptoms, but not alcohol use, with quetiapine in BPD and alcohol dependence. However, mean alcohol use was low and a larger effect size on alcohol-related measures was observed in those with higher levels of alcohol consumption. In this study, efficacy of quetiapine in patients with BPD and alcohol dependence was examined in patients with higher mean baseline alcohol use than in the prior study.. Ninety outpatients with bipolar I or II disorders, depressed or mixed mood state, and current alcohol dependence were randomized to 12 weeks of sustained release quetiapine (to 600 mg/d) add-on therapy or placebo. Drinking was quantified using the Timeline Follow Back method. Additional assessment tools included the Hamilton Rating Scale for Depression, Inventory of Depressive Symptomatology-Self-Report, Young Mania Rating Scale, Penn Alcohol Craving Scale, liver enzymes, and side effects. Alcohol use and mood were analyzed using a declining-effects random-regression model.. Baseline and demographic characteristics in the 2 groups were similar. No significant between-group differences were observed on the primary outcome measure of drinks per day or other alcohol-related or mood measures (p > 0.05). Overall side effect burden, glucose, and cholesterol were similar in the 2 groups. However, a significant weight increase was observed with quetiapine at week 6 (+2.9 lbs [SE 1.4] quetiapine vs. -2.0 lbs [SE 1.4], p = 0.03), but not at week 12. Scores on the Barnes Akathisia Scale increased significantly more (p = 0.04) with quetiapine (+0.40 [SE 0.3]) than placebo (-0.52 [SE 0.3]) at week 6 but not week 12. Retention (survival) in the study was similar in the groups.. Findings suggest that quetiapine does not reduce alcohol consumption in patients with BPD and alcohol dependence.

Topics: Adult; Alcohol Drinking; Alcoholism; Antipsychotic Agents; Bipolar Disorder; Craving; Delayed-Action Preparations; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Young Adult

To study the efficacy and safety of quetiapine-XR as monotherapy or adjunctive therapy to a mood stabilizer in acute bipolar I or II depression with comorbid generalized anxiety disorder (GAD) and other comorbidities.. The study was conducted from January 2007 to November 2011. The Mini-International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV bipolar disorder, GAD, and other Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. The Hamilton Depression Rating Scale-17 items (HDRS-17) was used as a primary outcome to evaluate the difference between the 2 groups using the change from baseline to end of study. Last observation carried forward and mixed-effects modeling for repeated measures were used to analyze the primary and secondary outcome measures.. Of the 120 patients screened, 100 patients were randomized to receive quetiapine-XR (n = 50) or placebo (n = 50). Twenty-six patients in the quetiapine-XR and 18 in the placebo group completed the study. The mean quetiapine-XR dose was 276 ± 50 mg/d (50-300 mg/d). There was no significant difference between the 2 groups in the change from baseline to end of study in HDRS-17 total score with an effect size of 0.19 favoring quetiapine-XR. There were also no significant differences between the 2 groups in secondary efficacy and safety outcome measures.. Quetiapine-XR was not significantly superior to placebo in bipolar I or II depression with GAD and other comorbidities, suggesting that data from relatively "pure" bipolar patients may not be generalizable to a highly comorbid population.. ClinicalTrials.gov identifier: NCT00671853.

Topics: Acute Disease; Adult; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Comorbidity; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Drug Synergism; Female; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Treatment Outcome

To examine the longer-term efficacy of quetiapine monotherapy in bipolar depression in a preplanned pooling of data from the EMBOLDEN I and II studies.. Patients (N = 584) with bipolar I or II disorder (most recent episode: depressed) who achieved remission after 8 weeks of treatment with quetiapine (300 or 600 mg/day) were randomised to the same quetiapine dose or placebo for 26-52 weeks or until mood event recurrence.. The risk for recurrence of a mood event was significantly lower with quetiapine than placebo (HR 0.51 (95% CI: 0.38-0.69); < 0.001). Quetiapine was associated with a lower risk for recurrence of depressive events (HR 0.43 (95% CI: 0.30-0.62); P < 0.001) but recurrence of manic/hypomanic events was not significantly reduced (HR 0.75 (95% CI: 0.45-1.24; P = 0.263). There was a lower risk of recurrence of mood events in bipolar I (HR 0.58 (95% CI: 0.41-0.82), P = 0.002) and bipolar II patients (HR 0.33 (95% CI: 0.18-0.60), P < 0.001). Discontinuation rates due to adverse events were 4.3, 4.0 and 1.7% for quetiapine 300 mg/day, 600 mg/day and placebo, respectively. Safety data, including changes in lipid and glucose parameters, were consistent with the recognized profile of quetiapine.. The efficacy of quetiapine monotherapy in bipolar depression is maintained during continued treatment for 26-52 weeks. Quetiapine was generally well tolerated.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Placebos; Quetiapine Fumarate; Recurrence; Time Factors; Treatment Outcome

To evaluate the efficacy and safety of quetiapine monotherapy in children and adolescents with mania associated with bipolar I disorder.. Patients aged 10 to 17 years, with a DSM-IV-TR diagnosis of a manic episode associated with bipolar I disorder and Young Mania Rating Scale (YMRS) total score ≥ 20 were randomized to 3 weeks of quetiapine (400 or 600 mg/d) or placebo. The primary efficacy measure was change in YMRS total score. The study was conducted at 34 centers in the United States between August 2004 and July 2006.. The intent-to-treat population included 277 patients. Least squares mean change in YMRS score from baseline to end point by mixed-model, repeated-measures analysis was -14.25, -15.60, and -9.04 for quetiapine 400 mg/d, quetiapine 600 mg/d, and placebo, respectively (P < .001, each quetiapine dose vs placebo). Significant improvement in YMRS score versus placebo was first observed at day 4 (P = .015) with quetiapine 400 mg/d and day 7 (P < .001) with quetiapine 600 mg/d. Mean changes in body weight at day 21 (observed cases) were 1.7 kg for both quetiapine doses and 0.4 kg for placebo. Numerically larger mean increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides were observed with quetiapine than placebo. Adverse events associated with quetiapine were mostly mild to moderate in intensity.. In this 3-week study, quetiapine was significantly more effective than placebo in improving manic symptoms in youth with mania associated with bipolar disorder. Treatment was generally well tolerated and adverse events were broadly consistent with the known profile of quetiapine in adults with bipolar disorder.. ClinicalTrials.gov identifier: NCT00090311.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Approval; Female; Humans; Intention to Treat Analysis; Least-Squares Analysis; Male; Psychiatric Status Rating Scales; Psychometrics; Quetiapine Fumarate; United States; United States Food and Drug Administration

To compare the efficacy and safety of adjunctive quetiapine (QTP) versus placebo (PBO) for patients with bipolar II disorder (BDII) currently experiencing mixed hypomanic symptoms in a 2-site, randomized, placebo-controlled, double-blind, 8-week investigation.. Participants included 55 adults (age 18-65 years) who met criteria for BDII on the Structured Clinical Interview for DSM-IV-TR (SCID). Entrance criteria included a stable medication regimen for ≥2 weeks and hypomania with mixed symptoms (>12 on the Young Mania Rating Scale [YMRS] and >15 on the Montgomery Asberg Depression Rating Scale [MADRS] at two consecutive visits 1-3 days apart). Participants were randomly assigned to receive adjunctive quetiapine (n=30) or placebo (n=25).. Adjunctive quetiapine demonstrated significantly greater improvement than placebo in Clinical Global Impression for Bipolar Disorder Overall Severity scores (F(1)=10.12, p=.002) and MADRS scores (F(1)=6.93, p=.0138), but no significant differences were observed for YMRS scores (F(1)=3.68, p=.069). Side effects of quetiapine were consistent with those observed in previous clinical trials, with sedation/somnolence being the most common, occurring in 53.3% with QTP and 20.0% with PBO.. While QTP was significantly more effective than PBO for overall and depressive symptoms of BDII, there was no significant difference between groups in reducing symptoms of hypomania. Hypomania improved across both groups throughout the study.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Treatment Outcome; Young Adult

To determine the efficacy and safety of quetiapine combined with lithium or divalproex for preventing mood events in patients with bipolar I disorder. In this pooled analysis of two similar long-term studies (D1447C00126 [NCT00107731] and D1447C00127 [NCT00081380]), lithium and divalproex treatment groups were analyzed separately.. Patients received open-label quetiapine (400-800 mg/d) plus lithium or divalproex to achieve ≥12 weeks of clinical stability before being randomized to double-blind combination treatment with quetiapine (400-800 mg/d) or placebo plus lithium or divalproex for up to 104 weeks. The primary endpoint was time to first mood event postrandomization following open stabilization.. Of 3,414 patients in the stabilization phase, 1,326 were randomized. There were no differences in the risk of recurrence of mood, mania, or depression between quetiapine plus lithium or quetiapine plus divalproex. Among patients co-treated with placebo and lithium, the risk of recurrence of a mania event was significantly higher than among patients co-treated with placebo and divalproex. In patients with an index episode of mania, placebo plus lithium was associated with a significantly higher risk of recurrence of a mania event than placebo plus divalproex. Safety data were generally consistent with recognized safety profiles.. In patients with bipolar I disorder previously stabilized on quetiapine and lithium or divalproex, maintenance therapy with quetiapine significantly increased the time to recurrence of a mood event (mania or depression) versus placebo, regardless of whether it was combined with lithium or divalproex.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium; Male; Middle Aged; Quetiapine Fumarate; Secondary Prevention; Treatment Outcome; Valproic Acid

The treatment of bipolar disorder (BD) remains a challenge due to the complexity of the disease. Current guidelines represent an effort to assist clinicians in routine practice but have several limitations, particularly concerning long-term treatment. The ARIQUELI (efficacy and tolerability of the combination of lithium or aripiprazole in young bipolar non or partial responders to quetiapine monotherapy) study aims to evaluate two different augmentation strategies for quetiapine nonresponders or partial responders in acute and maintenance phases of BD treatment.. The ARIQUELI study is a single-site, parallel-group, randomized, outcome assessor-blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic/hypomanic or mixed episode, aged 18 to 40 years, are eligible. After diagnostic assessments, patients initiated treatment in phase I with quetiapine. Nonresponders or partial responders after 8 weeks are allocated into one of two groups, potentiated with either lithium (0.5 to 0.8 mEq/l) or aripiprazole (10 or 15 mg). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blinded to the treatment. The primary outcome is the evaluation of changes in mean scores on the CGI-BP-M between baseline and the endpoint at the end of each study phase.. The ARIQUELI study is currently in progress, with patients undergoing acute treatment (phase I), potentiation (phase II) and maintenance (phase III). The study will be extended until January 2015. Trials comparing lithium and aripiprazole with potentiate treatment in young BD I nonresponders to quetiapine in monotherapy can provide relevant information on the safety of these drugs in clinical practice. Long-term treatment is an issue of great importance and should be evaluated further through more in-depth studies given that BD is a chronic disease.. ClinicalTrials.gov identifier: NCT01710163.

Topics: Adolescent; Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Brazil; Clinical Protocols; Dibenzothiazepines; Drug Synergism; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Piperazines; Psychiatric Status Rating Scales; Quetiapine Fumarate; Quinolones; Research Design; Time Factors; Treatment Outcome; Young Adult

Individuals with bipolar disorder lead a sedentary lifestyle associated with worse course of illness and recurrence of symptoms. Identifying potentially modifiable predictors of exercise frequency could lead to interventions with powerful consequences on the course of illness and overall health.. The present study examines baseline reports of exercise frequency of bipolar patients in a multi-site comparative effectiveness study of a second generation antipsychotic (quetiapine) versus a classic mood stabilizer (lithium). Demographics, quality of life, functioning, and mood symptoms were assessed.. Approximately 40% of participants reported not exercising regularly (at least once per week). Less frequent weekly exercise was associated with higher BMI, more time depressed, more depressive symptoms, and lower quality of life and functioning. In contrast, more frequent exercise was associated with experiencing more mania in the past year and more current manic symptoms.. Exercise frequency was measured by self-report and details of the exercise were not collected. Analyses rely on baseline data, allowing only for association analyses. Directionality and predictive validity cannot be determined. Data were collected in the context of a clinical trial and thus, it is possible that the generalizability of the findings could be limited.. There appears to be a mood-specific relationship between exercise frequency and polarity such that depression is associated with less exercise and mania with more exercise in individuals with bipolar disorder. This suggests that increasing or decreasing exercise could be a targeted intervention for patients with depressive or mood elevation symptoms, respectively.

Topics: Adult; Affect; Antipsychotic Agents; Bipolar Disorder; Comparative Effectiveness Research; Dibenzothiazepines; Exercise; Female; Humans; Lithium Compounds; Male; Middle Aged; Quality of Life; Quetiapine Fumarate

The purpose of this study was to describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder.. Medically healthy boys and girls with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) diagnosis of schizophrenia (ages 13-17 years) or a manic episode of bipolar I disorder (ages 10-17 years) who participated in one of two acute, double-blind, placebo-controlled studies of immediate-release quetiapine were potentially eligible to enroll in a 26-week, open-label study. During the open-label study, quetiapine was flexibly dosed at 400-800 mg/day, with options to reduce dosing to 200 mg/day based on tolerability. Safety and tolerability outcomes assessed from open-label baseline to week 26 included adverse events (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and vital signs.. Of 381 patients enrolled in the open-label study (n=176, schizophrenia; n=205, bipolar disorder diagnosis), 237 patients (62.2%) completed the 26-week study period (71.0%, schizophrenia; 54.6%, bipolar disorder). The most common AEs reported during the study included somnolence, headache, sedation, weight increase, and vomiting. A total of 14.9% of patients experienced a shift to potentially clinically significant low levels of high-density lipoprotein cholesterol and 10.2% of patients experienced a shift to potentially clinically significant high triglyceride levels. Weight gain ≥ 7% was reported in 35.6% of patients between open-label baseline and final visit. After adjustment for normal growth, 18.3% of study participants experienced clinically significant weight gain (i.e., increase in body mass index ≥ 0.5 standard deviations from baseline).. In this 26-week study, quetiapine flexibly dosed at 400-800 mg/day, with options to reduce dosing based on tolerability, was generally safe and well tolerated in youth. Clinicians should monitor lipid profiles and weight gain in youth with schizophrenia or bipolar disorder during treatment with quetiapine.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Schizophrenia

Anxiety disorders complicate the treatment of bipolar disorder but are seldom the focus of bipolar treatment studies.. The anxiolytic effect of quetiapine XR 50-300 mg/day compared to divalproex ER (500-3000 mg/day) was tested in an 8-week, double-blind, placebo-controlled, randomized clinical trial in 149 patients with bipolar disorder and a co-occurring panic disorder or GAD. The primary efficacy measure was the Clinician Global Improvement-21 Anxiety Scale (CGI-21). Secondary measures included the Hamilton Anxiety Scale (HAM-A) and Sheehan Panic Disorder Scale (SPS).. Repeated measures last-observation-carried-forward (LOCF) analyses of variance demonstrated significant treatment-by-time interaction effects on 3 of the 4 anxiety measures. Quetiapine XR at a mean endpoint dose of 186 mg/day produced rapid sustained improvements relative to baseline, divalproex ER and placebo on anxiety. Mean baseline-to-endpoint improvement was significantly greater for quetiapine XR compared to divalproex ER and placebo on the HAM-A and SPS. Both active medications were well tolerated, but weight gain was higher on quetiapine XR.. The study was limited to 8 weeks and to patients with bipolar disorder and comorbid panic disorder or GAD. The results may not be applicable to quetiapine XR as an add-on treatment to mood stabilizers or to bipolar disorder comorbid with other anxiety disorders.. Quetiapine XR in a dose range of 50-300 mg/day appears to reduce anxiety in bipolar patients with comorbid panic disorder or GAD treated for 8 weeks. The efficacy of other second-generation antipsychotics and mood stabilizers in patients with bipolar disorder and a co-occurring anxiety disorder should be investigated in double-blind, placebo-controlled studies.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Panic Disorder; Quetiapine Fumarate; Treatment Outcome; Valproic Acid; Weight Gain

There is no robust proof that the efficacy of lithium in the prevention of manic and depressive episodes in bipolar disorder depends on its plasma level. This analysis aimed to compare the effect of lithium within the presumed therapeutic range of 0.6-1.2 mEq/L and below 0.6 mEq/L with that of placebo.. We carried out a post hoc analysis of a double-blind trial in which patients aged ≥18 years with bipolar I disorder (DSM-IV) who had achieved stabilization from a manic, depressive, or mixed episode during open-label treatment with quetiapine were randomized to continue quetiapine or to switch to lithium or placebo for up to 104 weeks. Of patients randomized to lithium, 201 obtained median lithium levels between 0.6 and 1.2 mEq/L, and 137 obtained median lithium levels <0.6 mEq/L. Their outcomes were compared with those of patients receiving placebo (n = 404). The primary outcome was time to recurrence of any mood event; additional outcomes included time to recurrence of a manic or depressive event.. Times to recurrence of any mood event as well as a manic or depressive event were significantly longer for the lithium 0.6-1.2 mEq/L group versus placebo and versus lithium <0.6 mEq/L, with no differences between lithium <0.6 mEq/L and placebo..   The results support and expand previous findings that lithium should be dosed high enough to achieve plasma levels ≥0.6 mEq/L in order to achieve an effect in the prevention of both manic and depressive recurrences of bipolar I disorder. A major limitation is that the composition of the two lithium groups was not based on randomization.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Substitution; Female; Humans; International Cooperation; Lithium Chloride; Male; Middle Aged; Outcome Assessment, Health Care; Psychiatric Status Rating Scales; Quetiapine Fumarate; Statistics, Nonparametric; Time Factors

Although bipolar disorder frequently onsets in the preschool years, treatment studies to guide management of these highly dysfunctional children are limited. This study evaluates the response to quetiapine monotherapy in preschool and school age children with bipolar spectrum disorder (BSD).. Two eight-week, prospective, open-label trials utilizing identical methodology to assess the effectiveness and tolerability of quetiapine monotherapy in the treatment of BSD in preschool (age 4-6 years) and school age children (age 6-15 years).. Forty-nine children (30 preschool and 19 school age) with BSD (Young Mania Rating Scale [YMRS] at entry: 34.5±5.5 and 30±6.5 respectively) were enrolled and 34 (20 preschool and 14 school age) completed the trial. Quetiapine was titrated to a mean endpoint dose of 175.8±63.8 mg/day in preschool and 248.7±153.1 mg/day in school age children. At endpoint, treatment with quetiapine was associated with similar and statistically significant improvement in mean YMRS scores in preschool (-14.5±11.5, p<0.001) and school age (-13±9.8, p<0.001) children. Quetiapine was generally well tolerated with treatment limiting adverse-events observed in 3/30 preschool and 1/19 school age children. Quetiapine monotherapy in preschool and school age children was associated with significant weight gain (+3.1±1.8 and +7.4±7.7 lb respectively, p<0.001) and with clinically insignificant changes in vital signs.. As an uncontrolled study, the assessments were not blind to treatment and the effects of treatment cannot be separated from time.. Open-label quetiapine treatment was beneficial for the treatment of BSD in preschool and school age children. Further controlled trials are warranted.

Topics: Adolescent; Antimanic Agents; Bipolar Disorder; Child; Child, Preschool; Dibenzothiazepines; Female; Humans; Male; Prospective Studies; Quetiapine Fumarate

The differential roles of psychotherapy and pharmacotherapy in the management of bipolar (BP) II depression are unknown. As a first step toward exploring this issue, we conducted a pilot study to evaluate the feasibility and acceptability of comparing a BP-specific psychotherapy [Interpersonal and Social Rhythm Therapy (IPSRT)] to quetiapine as treatments for BP-II depression.. Unmedicated individuals (n = 25) meeting DSM-IV criteria for BP-II disorder, currently depressed, were randomly assigned to weekly sessions of IPSRT (n = 14) or quetiapine (n = 11), flexibly dosed from 25-300 mg. Participants were assessed with weekly measures of mood and followed for 12 weeks. Treatment preference was queried prior to randomization.. Using mixed effects models, both groups showed significant declines in the 25-item Hamilton Rating Scale for Depression [F(1,21) = 44, p < 0.0001] and Young Mania Rating Scale [F(1,21) = 20, p = 0.0002] scores over time but no group-by-time interactions. Dropout rates were 21% (n = 3) and 27% (n = 3) in the IPSRT and quetiapine groups, respectively. Overall response rates (defined as ≥ 50% reduction in depression scores without an increase in mania scores) were 29% (n = 4) in the IPSRT group and 27% (n = 3) in the quetiapine group. Measures of treatment satisfaction were high in both groups. Treatment preference was not associated with outcomes.. Outcomes in participants with BP-II depression assigned to IPSRT monotherapy or quetiapine did not differ over 12 weeks in this small study. Follow-up trials should examine characteristics that predict differential response to psychotherapy and pharmacotherapy.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Psychotherapy; Quetiapine Fumarate; Retrospective Studies

Mood stabilizers have been reported to affect brain concentrations of myo-inositol (mI) and N-acetylaspartate (NAA). We examined the effects of quetiapine (QUET), an atypical antipsychotic, on these neurochemicals, and potential predictors of response to QUET in adolescents with bipolar depression.. Twenty-six adolescents with bipolar depression participated in an 8-week placebo-controlled trial of QUET monotherapy. Subjects were scanned at baseline and after 8 weeks with proton magnetic resonance spectroscopy (1H-MRS) at 3T and 4T at two sites, with 8 cm(3) voxels placed in the right and left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). LCModel was used to calculate absolute concentrations of NAA and mI.. Twenty-six subjects had pre- and posttreatment scans (mean age=15.6 years, 9 boys). Of these subjects, 5 out of 16 subjects receiving QUET and 5 out of 10 receiving placebo (PBO) were responders (50% decrease in Children's Depression Rating Scale [CDRS] score). Although baseline ACC mI did not predict responder status, responders had significantly lower posttreatment ACC mI values than did nonresponders (3.27±.71 vs. 4.23±.70; p=0.004). There were no significant differences in the changes in ACC and DLPFC NAA levels in the QUET group compared with the PBO group (ACC: -0.55±1.3 vs.+0.25±1.5, p=0.23; right-DLPFC: -0.55±1.3 vs. 0.33±0.89, p=0.13; left-DLPFC: -0.04±0.91 vs.+0.29±0.61, p=0.41).. We found that posttreatment, not baseline, ACC mI levels were associated with response to QUET in adolescents with bipolar depression. There were no differences in NAA concentration changes between the QUET and PBO groups. Larger studies including different brain regions would help to clarify the effects of QUET on neurochemistry in patients with bipolar disorder.

Topics: Adolescent; Antipsychotic Agents; Aspartic Acid; Bipolar Disorder; Child; Dibenzothiazepines; Female; Gyrus Cinguli; Humans; Inositol; Magnetic Resonance Imaging; Male; Prefrontal Cortex; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Molecules that are involved in neuronal intercommunication and adaptability of neural networks, such as brain-derived neurotrophic factor (BDNF), are targets of pathophysiological investigation in bipolar disorder (BD). Quetiapine is an attested treatment in this disorder, used in acute mood episodes. The aim of this study was to report prospective changes in serum BDNF levels in drug-free patients in acute mood episodes of BD who received treatment with extended-release quetiapine along a 16 week follow-up. Assessments were performed at baseline and weeks 2, 4, 8 and 16 with the Young Mania Rating Scale, the Hamilton Depression Rating Scale and the Clinical Global Impression severity scale. In these visits, serum BDNF levels were measured. Mixed effect models were used to investigate longitudinal changes. Twenty-five patients were included for this analysis, seventeen in a current depressive episode and eight in a manic/mixed episode. A significant improvement from baseline to endpoint was displayed. In the mixed model, significant main effects for episode and time appeared, and a time versus episode interaction showing increasing BDNF levels with time in those with a depressive episode, but a decrease in BDNF levels with time in those with a manic/mixed episode. BDNF may be a biomarker with differential response according to the polarity of mood episodes.

Topics: Acute Disease; Adult; Antipsychotic Agents; Biomarkers; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Delayed-Action Preparations; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Treatment Outcome

A human-volunteer study reported lower sedation intensity during escalation of the extended-release formulation of quetiapine fumarate (quetiapine XR) than the immediate-release (IR) formulation.. To test the hypothesis that the profile of initial tolerability, including sedation, differs between the extended-release (XR) and immediate-release (IR) formulations of quetiapine in patients with bipolar depression.. In a randomized, double-blind, double-dummy, parallel-group, Phase IV study, male and female inpatients aged 18 to 50 years with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnosis of bipolar I or II depression were randomized after washout to receive placebo on day 1 and quetiapine XR or IR at escalating doses of 50, 100, 200, 300, and 300 mg once daily on the evenings of days 2 to 6, with hospital discharge on day 7. Sedation intensity was assessed by a self-reported modified Bond-Lader visual analog scale (VAS) score.. Of 139 randomized patients, 134 completed the study. Mean patient age was 39.0 years; mean weight, 91.3 kg; and mean body mass index (calculated as weight in kilograms divided by height in meters squared), 31.0. Sedation intensity 1 hour after administration of the 50-mg dose (the primary study measure) was statistically significantly lower with quetiapine XR versus IR (mean [SD] VAS score: 33.4 [26.92] vs 44.0 [31.76]; least squares mean difference: 12.55, P = 0.009; modified intention-to-treat population). Sedation intensity was found in secondary analyses to be significantly lower with quetiapine XR than with quetiapine IR 1, 2, and 3 hours after each dose on days 2 to 6 (P ≤ 0.05), with similar sedation intensity between the treatment groups 4 to 14 hours postdose. Rates of treatment-related adverse events were 47.1% with quetiapine XR versus 59.4% with quetiapine IR. Three serious adverse events (4.3%) occurred in the quetiapine XR group. Adverse events led to study discontinuation in 1 patient (1.4%) in the quetiapine XR group and in 2 patients (2.9%) in the IR group.. During the initial dose-escalation period studied, patients with bipolar depression reported statistically significantly lower sedation intensity in the 1 to 3 hours after taking quetiapine XR compared with the IR formulation. Overall tolerability for both formulations was consistent with the known profile of quetiapine. ClinicalTrials.gov identifier: NCT00926393.

Topics: Adolescent; Adult; Analysis of Variance; Antipsychotic Agents; Bipolar Disorder; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Least-Squares Analysis; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Self Report; Sleep; Time Factors; Treatment Outcome; United States; Wakefulness; Young Adult

To evaluate quetiapine in patients with bipolar I disorder with mixed symptoms.. Data from 2 studies (D1447C00126, D1447C00127) were pooled and mixed events analyzed separately. Patients received quetiapine (400-800mg/day) plus lithium/divalproex to achieve ≥12 weeks of clinical stability, followed by double-blind quetiapine (400-800mg/day) or placebo, plus lithium/divalproex, for up to 104 weeks. Primary endpoint was time to first mood event post-randomization.. The ITT population included 1326 patients, of whom 445 had a mixed episode at study entry, 219 received quetiapine plus lithium/divalproex, and 226 received placebo plus lithium/divalproex. Mood events were reported by fewer quetiapine-plus-lithium/divalproex than placebo-plus-lithium/divalproex-treated patients (21.0% vs 54.0%), and included mixed (6.4% vs 22.1%), pure manic (5.0% vs 13.3%), and pure depressed events (9.6% vs 18.6%). Hazard ratios (HR) for time to recurrence were longer for quetiapine plus lithium/divalproex than placebo plus lithium/divalproex for mixed (HR=0.23; 95% CI: 0.13-0.42; p<0.0001), pure manic (HR=0.30; 95% CI: 0.15-0.60; p=0.0007), and pure depressed events (HR=0.38; 95% CI: 0.22-0.64; p=0.0003). No new safety concerns were noted.. The post hoc nature of the analyses as patients were not randomized according to index symptom status.. In stable patients with bipolar I disorder, quetiapine plus lithium/divalproex significantly increased time to recurrence of mood events versus placebo in patients with mixed symptoms at study entry and time to occurrence of mixed-mood events in patients with any mood episode at study entry.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Male; Quality of Life; Quetiapine Fumarate; Recurrence; Treatment Outcome; Valproic Acid; 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

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

Quetiapine, combined with lithium or divalproex, demonstrates efficacy in the maintenance treatment of bipolar I disorder. This study investigated the efficacy and safety of quetiapine monotherapy as maintenance treatment in bipolar I disorder compared with switching to placebo or lithium.. Patients aged ≥ 18 years with DSM-IV-diagnosed bipolar I disorder and a current or recent manic, depressive, or mixed episode received open-label quetiapine (300-800 mg/d) for 4-24 weeks. Patients achieving stabilization were randomized to continue quetiapine or to switch to placebo or lithium (0.6-1.2 mEq/L) for up to 104 weeks in a double-blind trial. Outcome measures included times to recurrence of any mood event (primary outcome measure), manic event, or depressive event. Safety assessments included adverse events and laboratory values. The study was terminated early after planned interim analysis provided positive results. The study was conducted between March 2005 and July 2007.. Of 2,438 patients starting open-label quetiapine, 1,226 (50.3%) were randomized to double-blind treatment, including 1,172 (95.6%) in the intent-to-treat population. Time to recurrence of any mood event was significantly longer for quetiapine versus placebo (hazard ratio [HR] = 0.29; 95% CI, 0.23-0.38; P < .0001) and for lithium versus placebo (HR = 0.46; 95% CI, 0.36-0.59; P < .0001). Quetiapine and lithium significantly increased time to recurrence of both manic events (quetiapine: HR = 0.29; 95% CI, 0.21-0.40; P < .0001; lithium: HR = 0.37; 95% CI, 0.27-0.53; P < .0001) and depressive events (quetiapine: HR = 0.30; 95% CI, 0.20-0.44; P < .0001; lithium: HR = 0.59; 95% CI, 0.42-0.84; P < .004) compared with placebo. Overall rates of adverse events were generally similar between treatment groups, and safety findings for quetiapine were consistent with its known profile.. In patients stabilized during acute quetiapine treatment, continuation of quetiapine significantly increased time to recurrence of any mood, manic, or depressive event compared with switching to placebo. Switching to lithium was also more effective than placebo for the prevention of manic and depressive events.. clinicaltrials.gov Identifier: NCT00314184.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lithium; Male; Middle Aged; Placebos; Proportional Hazards Models; Quetiapine Fumarate; Secondary Prevention; Treatment Outcome

Bipolar disorder, a highly recurrent and chronic condition, often necessitates periods of hospitalization and requires lifelong treatment with medication. It is characterized by alternating episodes of mania and depression. Given the severity of mania, physicians must be able to control symptoms rapidly.. The purpose of this pivotal, Phase III trial was to evaluate the efficacy and tolerability of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy in improving manic symptoms in patients with bipolar I disorder.. This was a 3-week, randomized, parallel-group, double-blind, placebo-controlled study. Patients aged 18 to 65 years with bipolar I disorder (most recent episode manic or mixed; with or without rapid cycling) were randomized to receive placebo or quetiapine XR monotherapy once daily (300 mg on day 1; 600 mg on day 2; flexible dosing, 400-800 mg, from day 3 through day 22 [study end point, week 3]). The primary outcome measure was the change from baseline to study end in the Young Mania Rating Scale (YMRS) total score. Secondary outcome measures included the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, YMRS response (≥50% reduction in YMRS) and remission (YMRS score ≤12 at final visit) rates, and change from baseline to week 3 in Clinical Global Impression-Bipolar-Severity of Illness (CGI-BP-S) and CGI-BP-Change (CGI-BP-C) scores. Safety profile and tolerability evaluations included monitoring of adverse events, clinical laboratory values, vital signs, extrapyramidal symptoms (including akathisia), and electrocardiogram results.. Compared with placebo (n = 159), quetiapine XR monotherapy (n = 149; mean daily dose, 604 mg) significantly improved manic symptoms starting at day 4 (first assessment; P < 0.001), with sustained improvement to study end (week 3; P < 0.001). MADRS scores showed greater improvement from baseline to study end with quetiapine XR than with placebo (P = 0.004). Response and remission rates were significantly greater (P < 0.01) with quetiapine XR than with placebo at study end. Quetiapine XR also resulted in significant improvements over placebo in CGI-BP-S and CGI-BP-C scores (P < 0.001 and P < 0.001, respectively). Adverse events were mild to moderate in intensity; the most common ones associated with quetiapine XR were sedation, dry mouth, and somnolence.. This 3-week trial suggests that quetiapine XR (400-800 mg) once-daily monotherapy is efficacious (from day 4) and generally well tolerated in patients with manic or mixed episodes of bipolar I disorder.

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Quetiapine Fumarate

To evaluate the effectiveness of quetiapine extended release once daily in bipolar depression.. Double-blind, placebo-controlled study in acutely depressed adults with bipolar I or II disorder, with or without rapid cycling. Patients were randomized to 8 weeks of quetiapine extended release (XR) 300 mg daily monotherapy or placebo. The primary outcome measure was change from baseline to Week 8 in MADRS total score.. Quetiapine XR 300 mg once daily (N=133) showed significantly greater improvement in depressive symptoms compared with placebo (N=137) from Week 1 (p<0.001) through to Week 8 (p<0.001). Mean change in MADRS total score at Week 8 was -17.4 in the quetiapine XR group and -11.9 in the placebo group (p<0.001). Response (>or=50 reduction in MADRS total score) and remission (MADRS total score

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate

There are no randomized, placebo-controlled data for quetiapine in outpatients with bipolar spectrum disorder (ambulatory BSD) and moderate-to-severe hypomanic or mild manic symptoms (hypomania/mild mania).. An 8-week, randomized, double-blind, placebo-controlled trial of quetiapine in ambulatory BSD with hypomanic/mild manic symptoms, defined operationally as a score of >or=3 but <5 on the mania subscale of the Clinical Global Impressions Scale Modified for Bipolar Illness (CGI-BP) at baseline and one prior study visit, at least 3 days but no more than 2 weeks apart. The primary outcome measure was the rate of change in the Young Mania Rating Scale score (YMRS).. During the 8-week study period, patients receiving quetiapine (average daily dose=232mg) had a marginally greater rate of reduction in mean total YMRS score than patients receiving placebo (p=0.06). Additionally, CGI-BP mania (p=0.01) and the CGI-BP overall (p<0.001) scores were significantly reduced and the CGI-depression score (p=0.08) was marginally reduced in the quetiapine group. Six (32%) quetiapine patients and 8 (40%) placebo patients did not complete the trial.. Small sample size and high attrition (36%).. Quetiapine was marginally more effective than placebo in reducing hypomanic/mild manic symptoms in ambulatory BSD as assessed by the YMRS. It was more effective than placebo in reducing manic symptoms and global bipolar symptoms as assessed by the CGI-BP. The drug's discontinuation rate was similar to placebo's. Controlled trials of quetiapine and other compounds with mood stabilizing properties in larger groups of ambulatory BSD patients with hypomanic/mild manic symptoms appear warranted.

Topics: Adult; Affect; Ambulatory Care; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Psychometrics; Quetiapine Fumarate; Treatment Outcome

The aim of this study was to evaluate the efficacy and tolerability of quetiapine and paroxetine monotherapy for major depression in bipolar disorder.. 740 patients (478 bipolar I, 262 bipolar II) with major depressive episodes (DSM-IV) were randomly assigned to quetiapine 300 mg/d (n = 245), quetiapine 600 mg/d (n = 247), paroxetine 20 mg/d (n = 122), or placebo (n = 126) for 8 weeks. The primary end point was the change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from May 2005 to May 2007.. Mean MADRS score change from baseline at 8 weeks was -16.19 for quetiapine 300 mg, -16.31 for quetiapine 600 mg, -13.76 for paroxetine, and -12.60 for placebo (P < .001 for both quetiapine doses, P = .313 for paroxetine, vs placebo). Quetiapine-treated (both doses), but not paroxetine-treated, patients showed significantly greater improvements (P < or = .05) in most secondary outcomes measures at week 8 versus the placebo group. Paroxetine significantly improved Hamilton Anxiety Rating Scale scores versus placebo (P < .05) but not MADRS or Hamilton Depression Rating Scale (HDRS) scores. Both quetiapine doses were associated with greater improvements than paroxetine for MADRS and HDRS scores. The most common adverse events were dry mouth, somnolence, sedation, and dizziness with quetiapine (both doses) and dry mouth, sedation, headache, insomnia, and nausea with paroxetine. The incidence of treatment-emergent mania/hypomania was lower with quetiapine compared with paroxetine and placebo.. Quetiapine (300 or 600 mg/d), but not paroxetine, was more effective than placebo for treating acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated.. clinicaltrials.gov Identifier: NCT00119652.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antimanic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Paroxetine; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

The aim of this study was to compare the efficacy and tolerability of quetiapine and lithium monotherapy with that of placebo for a major depressive episode in bipolar disorder.. 802 patients with DSM-IV-defined bipolar disorder (499 bipolar I, 303 bipolar II) were randomly allocated to quetiapine 300 mg/d (n = 265), quetiapine 600 mg/d (n = 268), lithium 600 to 1800 mg/d (n = 136), or placebo (n = 133) for 8 weeks. Primary endpoint was the change in Montgomery-Asberg Depression Rating Scale (MADRS) total score. The study was conducted from August 2005 to May 2007.. Mean MADRS total score change from baseline at week 8 was -15.4 for quetiapine 300 mg/d, -16.1 for quetiapine 600 mg/d, -13.6 for lithium, and -11.8 for placebo (P < .001 for both quetiapine doses, P = .123 for lithium, vs placebo). Quetiapine 600 mg/d was significantly more effective than lithium in improving MADRS total score at week 8 (P = .013). Quetiapine-treated (both doses), but not lithium-treated, patients showed significant improvements (P < .05) in MADRS response and remission rates, Hamilton Depression Rating Scale (HDRS), Clinical Global Impressions-Bipolar-Severity of Illness and -Change, and Hamilton Anxiety Rating Scale (HARS) scores at week 8 versus placebo. Both quetiapine doses were more effective than lithium at week 8 on the HDRS and HARS. The most common adverse events were somnolence, dry mouth, and dizziness with quetiapine (both doses) and nausea with lithium.. Quetiapine (300 or 600 mg/d) was more effective than placebo for the treatment of episodes of acute depression in bipolar disorder. Lithium did not significantly differ from placebo on the main measures of efficacy. Both treatments were generally well tolerated.. clinicaltrials.gov Identifier: NCT00206141.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antimanic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Humans; Lithium Compounds; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

To assess quetiapine effectiveness in bipolar disorder (BD) patients in a clinical setting.. We naturalistically administered open quetiapine to outpatients assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation, and monitored longitudinally with the STEP-BD Clinical Monitoring Form.. 96 patients (36 BD I, 50 BD II, 9 BD NOS, 1 Schizoaffective Bipolar Type, mean ± SD age 42.3 ± 13.8 years, 66.7% female) received quetiapine, combined with an average of 2.5 (in 66.7% of patients at least 2) other psychotropic medications and 0.9 non-psychotropic medications, started most often during depressive symptoms (53.1%) or euthymia (37.5%). Mean quetiapine duration and final dose were 385 days and 196 mg/day (50.0% of patients took ≤75 mg/day). Quetiapine was discontinued in 38.5% of trials, after on average 307 days, most often (in 19.8%) due to CNS adverse effects (primarily sedation). In 38.5% of trials quetiapine was continued on average 328 days with no subsequent psychotropic added. In 22.9% quetiapine was continued on average 613 days, but had subsequent psychotropic added after on average 113 days, most often for depressive symptoms. In 67 trials started at Stanford, quetiapine tended to primarily maintain euthymia and relieve depressive symptoms. In 29 trials started prior to Stanford, continuing quetiapine tended to primarily maintain euthymia and relieve mood elevation symptoms. Aside from sedation, quetiapine was generally well tolerated.. In bipolar disorder outpatients quetiapine had a moderate (38.5%, with 385-day mean duration) discontinuation rate, and commonly did not require subsequent additional pharmacotherapy, suggesting effectiveness in a clinical setting.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depression; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Longitudinal Studies; Male; Middle Aged; Outpatients; Psychiatric Status Rating Scales; Psychotropic Drugs; Quetiapine Fumarate; Time Factors; Treatment Outcome

To evaluate the antimanic efficacy and safety of paliperidone extended-release (ER) tablets in patients with bipolar I disorder.. This study included a 3-week, double-blind, acute treatment phase (paliperidone ER versus placebo, with quetiapine as control), and a 9-week, double-blind, maintenance phase (paliperidone ER versus quetiapine). Patients [n = 493; Young Mania Rating Scale (YMRS) score >or= 20] were randomized (2:2:1) to flexibly dosed paliperidone ER (3-12 mg/day), quetiapine (400-800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy.. Paliperidone ER was superior to placebo at the 3-week endpoint {primary outcome; least-squares mean difference in change from baseline in YMRS scores [95% confidence interval (CI)]: -5.5 (-7.57; -3.35); p < 0.001} and noninferior to quetiapine at the 12-week endpoint [least-squares mean difference (95% CI): 1.7 (-0.47; 3.96)]. The median mode dose during the 12-week treatment period was 9 mg for paliperidone ER and 600 mg for quetiapine. The most common (>or= 10%) treatment-emergent adverse events during the 12-week period were: headache (16%), somnolence (10%), and akathisia (10%) for paliperidone ER; somnolence (21%), sedation and dry mouth (17% each), headache (14%), and dizziness (13%) for quetiapine. Body weight increase >or= 7% from baseline to 12-week endpoint was 8% with paliperidone ER and 17% with quetiapine. A higher percentage of paliperidone ER (13.9%) versus quetiapine patients (7.5%) 'switched to depression' at the12-week endpoint.. Paliperidone ER (3-12 mg/day) was efficacious and tolerable in the treatment of acute mania.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Delivery Systems; Female; Follow-Up Studies; Humans; Isoxazoles; Male; Middle Aged; Paliperidone Palmitate; Psychiatric Status Rating Scales; Pyrimidines; Quetiapine Fumarate; Treatment Outcome

This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence.. Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12-week, placebo-controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions-Severity of Illness score.. Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was -0.36 with quetiapine and -0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine.. The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence.

Topics: Adult; Alcohol Drinking; Alcoholism; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Middle Aged; Quetiapine Fumarate; Valproic Acid

The purpose of the study was to determine the effectiveness and tolerability of quetiapine as a maintenance treatment preventing against relapse or recurrence of acute mood episodes in adolescent patients diagnosed with bipolar disorder.. Consenting patients meeting DSM-IV lifetime criteria for a bipolar disorder and clinically appropriate for maintenance treatment were enrolled in a 48-week open prospective study. After being acutely stabilized (CGI-S < or = 3 for 4 consecutive weeks), patients were started or continued on quetiapine and other medications were weaned off over an 8-week period. Quetiapine monotherapy was continued for 40-weeks and other mood stabilizers or antidepressants were added if clinically indicated. A neurocognitive test battery assessing the most reliable findings in adult patients was administered at fixed time points throughout the study to patients and matched controls.. Of the 21 enrolled patients, 18 completed the 48-week study. Thirteen patients were able to be maintained without relapse or recurrence in good quality remission on quetiapine monotherapy, while 5 patients required additional medication to treat impairing residual depressive and/or anxiety symptoms. According to symptom ratings and global functioning scores, the quality of remission for all patients was very good.Neurocognitive test performance over treatment was equivalent to that of a matched control group of never ill adolescents. Quetiapine was generally well tolerated with no serious adverse effects.. This study suggests that a proportion of adolescent patients diagnosed with bipolar disorder can be successfully maintained on quetiapine monotherapy. The good quality of clinical remission and preserved neurocognitive functioning underscores the importance of early diagnosis and effective stabilization.. D1441L00024.

Topics: Adolescent; Age of Onset; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Secondary Prevention; Severity of Illness Index; Young Adult

The authors evaluated the efficacy and safety of quetiapine plus lithium or divalproex in the prevention of recurrent mood events in patients with stabilized bipolar I disorder.. A total of 1,953 patients received open-label quetiapine (400-800 mg/day in flexible, divided doses) with either lithium or divalproex (target serum concentrations 0.5-1.2 meq/liter and 50-125 microg/ml, respectively) for up to 36 weeks. After at least 12 weeks of clinical stability, 628 patients were randomly assigned to double-blind treatment with quetiapine or placebo, in combination with lithium or divalproex, for up to 104 weeks. The primary efficacy measure was time to recurrence of any mood event (mania, depression, or a mixed episode).. Fewer patients in the quetiapine group experienced a mood event compared with the placebo group (20.3% versus 52.1%). The hazard ratio for time to recurrence of a mood event was 0.32. Hazard ratios were similar for mania and depression events (0.30 and 0.33, respectively). Sedation, weight increase, and hypothyroidism occurred more frequently in the quetiapine group, as did discontinuations due to adverse events. The incidence and incidence density of a single emergent blood glucose value > or =126 mg/dl were higher in the quetiapine group (12.6% versus 5.4%; 18.44 versus 9.56 patients per 100 patient-years). Adverse events were generally consistent with the known tolerability profile of quetiapine.. In patients stabilized on quetiapine plus lithium or divalproex, continued treatment was associated with a significant risk reduction in the time to recurrence of any mood event compared with placebo and lithium or divalproex.

Topics: Adult; Affect; Antimanic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Long-Term Care; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Valproic Acid; Young Adult

To conduct a pilot study comparing the effects of quetiapine and placebo for the treatment of depressive episodes in adolescents with bipolar I disorder.. Thirty-two adolescents (ages 12-18 years) with a depressive episode associated with bipolar I disorder were randomized to eight weeks of double-blind treatment with quetiapine, 300-600 mg/day, or placebo. This two-site study was conducted from March 2006 through August 2007. The primary efficacy measure was change in Children's Depression Rating Scale-Revised Version (CDRS-R) scores from baseline to endpoint. Secondary efficacy measures included change in CDRS-R scores over the eight-week study period (PROC MIXED), changes from baseline to endpoint in Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS), and Clinical Global Impression-Bipolar Version Severity (CGI-BP-S) scores, as well as response and remission rates. Safety and tolerability were assessed weekly.. There was no statistically significant treatment group difference in change in CDRS-R scores from baseline to endpoint (p = 0.89, effect size =-0.05, 95% confidence interval: -0.77-0.68), nor in the average rate of change over the eight weeks of the study (p = 0.95). Additionally, there were no statistically significant differences in response (placebo =67% versus quetiapine = 71%) or remission (placebo = 40% versus quetiapine = 35%) rates, or change in HAM-A, YMRS, or CGI-BP-S scores (all p > 0.7) between treatment groups. Dizziness was more commonly reported in the quetiapine (41%) than in the placebo (7%) group (Fisher's exact test, p = 0.04).. The results suggest that quetiapine monotherapy is no more effective than placebo for the treatment of depression in adolescents with bipolar disorder. However, limitations of the study, including the high placebo response rate, may have contributed to our findings and should be considered in the design of future investigations of pharmacological interventions for this population.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Body Weight; Child; Depression; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Metabolome; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Bipolar I disorder is a recurrent illness that affects 1% of the US population and constitutes a large economic burden. Few studies have investigated the cost-effectiveness of maintenance treatment options. The objective of this analysis was to assess the cost-effectiveness of quetiapine (QTP) in combination with lithium (Li) or divalproex (DVP) compared with that of Li or DVP alone for maintenance treatment of bipolar disorder.. The cost-effectiveness of maintenance treatment with QTP in combination with Li or DVP was compared with placebo (PBO) in combination with Li or DVP from a US direct costs perspective using a Markov model. The model simulated a cohort of 1,000 stabilized patients with bipolar I disorder and estimated the quarterly risk in three health states: euthymia, mania, and depression. Efficacy data were derived from two randomized, double-blind, placebo-controlled trials comparing QTP + Li/DVP with PBO + Li/DVP for up to 2 years. Resource data were obtained from published literature. Direct costs included drug costs, hospitalizations, and physician visits. Outcomes and costs were discounted at 3% and the price reference year was 2007. Endpoints included the number of acute mood episodes, hospitalizations due to an acute mood event, and costs per quality-adjusted life-years. A probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty.. In the base-case analysis, QTP + Li/DVP dominated PBO + Li/DVP. The PSA showed these results to be robust. In addition, treatment with QTP + Li/DVP was associated with reductions in acute manic episodes (46%), acute depressive episodes (41%), and related hospitalizations (44%) compared with PBO + Li/DVP.. These analyses, based on two randomized clinical trials, suggest that QTP + Li/DVP is a cost-effective maintenance treatment option for patients with bipolar I disorder compared with Li or DVP alone.

Topics: Adolescent; Adult; Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Cost-Benefit Analysis; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Markov Chains; Middle Aged; Quetiapine Fumarate; Severity of Illness Index; Valproic Acid; Young Adult

This study examined the efficacy and safety of quetiapine in combination with lithium or divalproex compared with placebo with lithium or divalproex in the prevention of recurrent mood events in bipolar I patients, most recent episode mania, depression, or mixed.. Patients received open-label quetiapine (400-800 mg/day; flexible, divided doses) with lithium or divalproex (target serum concentrations 0.5-1.2 mEq/L and 50-125 microg/mL, respectively) for up to 36 weeks to achieve at least 12 weeks of clinical stability. Patients were subsequently randomized to double-blind treatment with quetiapine (400-800 mg/day) plus lithium/divalproex or placebo plus lithium/divalproex for up to 104 weeks. The primary endpoint was time to recurrence of any mood event.. Treatment with quetiapine in combination with lithium/divalproex significantly increased the time to recurrence of any mood event compared with placebo plus lithium/divalproex. The proportion of patients having a mood event was markedly lower in the quetiapine than in the placebo group (18.5% versus 49.0%). The hazard ratio for time to recurrence of a mood event was 0.28 (P<0.001), a mania event 0.30 (P<0.001), and a depression event 0.26 (P<0.001) corresponding to risk reductions of 72%, 70%, and 74%, respectively. During the randomization phase, the most common adverse events occurring in > or =5% in the quetiapine group were somnolence, nasopharyngitis, and headache. Insomnia was more common in the placebo group. During the randomization phase, there was an increase in weight of 0.5 kg in the quetiapine group and a reduction of 1.9 kg in the placebo group. The incidence and incidence density of a single emergent fasting blood glucose value> or =126 mg/dL was higher with quetiapine than with placebo (9.3% versus 4.1%; 17.6 versus 9.5 patients per 100 patient-years).. This was an enriched sample of patients with bipolar I disorder responding to treatment with quetiapine plus lithium/divalproex.. Maintenance treatment with quetiapine in combination with lithium/divalproex significantly increased time to recurrence of any event (mania, depression, or mixed) irrespective of the polarity of the index episode compared with placebo with lithium/divalproex. Long-term treatment with quetiapine was generally well-tolerated. Quetiapine with lithium/divalproex can provide an effective long-term treatment option for bipolar I disorder to prevent recurrences not only of mania but also depression.

Topics: Antipsychotic Agents; Bipolar Disorder; Demography; Dibenzothiazepines; Disorders of Excessive Somnolence; Female; Headache; Humans; International Cooperation; Lithium Carbonate; Male; Nasopharyngitis; Quetiapine Fumarate; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Valproic Acid; Young Adult

The primary objective was to compare the efficacy and tolerability of quetiapine and risperidone in the treatment of mood symptoms, drug cravings, and drug use in outpatients with concurrent DSM-IV-defined bipolar I or II disorder and cocaine or methamphetamine dependence.. Men and women of all ethnic origins, 20 to 50 years of age, were eligible to participate. Persons were excluded if they were inpatients, met DSM-IV criteria for substance-induced mood disorder, had any other substance dependence, were euthymic or suicidal, had any life-threatening illnesses, or were currently receiving antipsychotic medications. Duration of the trial was 20 weeks. Study participants attended weekly visits and were evaluated for mood symptoms, drug cravings, drug use, and medication side effects. Treatment outcomes were analyzed using linear mixed models. Fixed-effects terms for medication group, study week, and group-by-study-week were included in the models. The study was conducted between October 2002 and November 2006.. Of 124 consenting outpatients, an evaluable sample of 80 patients who attended baseline and at least 1 follow-up study visit was formed. The mean +/- SD exit dose for quetiapine was 303.6 +/- 151.9 mg/day and 3.1 +/- 1.2 mg/day for risperidone. Both quetiapine (N = 42) and risperidone (N = 38) significantly improved manic and depressive symptoms and reduced drug cravings (p < .0005) compared to baseline. Decreased drug cravings were related to less frequent drug use (p = .03). The 2 medications did not significantly differ in their effects on mood symptoms, drug craving, or drug use.. Relative to baseline mood and drug-craving status, both quetiapine and risperidone were associated with manic, mixed, and depressive symptom improvement and reduced drug cravings. Both medications were well tolerated. The interpretation of these results is limited by the absence of a placebo control.. clinicaltrials.gov Identifier: NCT00227123.

Topics: Adult; Amphetamine-Related Disorders; Antipsychotic Agents; Bipolar Disorder; Cocaine-Related Disorders; Comorbidity; Demography; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Electrocardiography; Female; Humans; Male; Methamphetamine; Middle Aged; Quetiapine Fumarate; Risperidone

The depressive symptoms of bipolar disorder impact health-related quality of life, quality of sleep and functioning. The BOLDER I and II trials demonstrated that quetiapine significantly improves depressive symptoms in patients with acute bipolar depression. Post-hoc analysis of the BOLDER I and II data permits a detailed investigation of the effects of quetiapine on these other measures in this patient population.. Secondary analysis was performed on data from BOLDER I and II, which were two 8-week, double-blind, randomized, placebo-controlled studies of quetiapine at fixed doses (300 or 600 mg/day) in a total of 1051 patients with acute depressive episodes of bipolar I or II disorder. Measures included the Short-Form Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q SF) in BOLDER I and II, the Pittsburgh Sleep Quality Index (PSQI) in BOLDER I, and the Sheehan Disability Scale (SDS) in BOLDER II. Analyses of Q-LES-Q SF score changes were based on data from the combined BOLDER I and II populations, and analyses of PSQI and SDS score changes were based on BOLDER I and BOLDER II populations, respectively.. Assessments at day 57 by mixed-model repeated measures analysis demonstrated that quetiapine relative to placebo provided significant or numerical improvements in rating scale score on the Q-LES-Q SF (10.89 with 300 mg/day and 12.14 with 600 mg/day vs. 7.79 with placebo; p<0.001 for each quetiapine dose), PSQI (-5.34 and -6.00 vs. -3.35; p<0.001, each dose), and SDS (-7.78 and -8.25 vs. -6.49; p=0.156 and 0.054, respectively). Effect sizes at day 57 with quetiapine 300 and 600 mg/day, respectively, were 0.34 and 0.46 for Q-LES-Q SF, 0.59 and 0.79 for PSQI, and 0.17 and 0.23 for SDS. Improvements were evident at first post-baseline assessment on day 29 and were consistent over the majority of rating scale domains. Quetiapine was generally well tolerated and most adverse events were of mild to moderate intensity.. Quetiapine monotherapy is effective in improving impairment in important aspects of life that accompany improvements in depressive symptoms in patients with acute bipolar depression.

Topics: Acute Disease; Adolescent; Adult; Aged; Ambulatory Care; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Health Status; Humans; Male; Middle Aged; Personal Satisfaction; Placebos; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Sleep; Surveys and Questionnaires; Treatment Outcome

Rapid-cycling bipolar disorder is often characterized by a lack of response to psychopharmacological treatment, and a standard therapy has not been developed yet. The aim of this study was to examine the long-term efficacy and safety of a monotherapy with quetiapine or sodium valproate (VPA) in patients with rapid-cycling bipolar disorder.. This open-label, randomized, parallel group monotherapy pilot study was conducted at 3 German centers. A sample of 38 remitted or partly remitted patients with bipolar disorder and rapid cycling (quetiapine n = 22; VPA n = 16) were treated with quetiapine or VPA (flexible dose design) for 12 months.. Forty-one percent of the patients with quetiapine and 50% with VPA completed the trial. On the basis of ITT-LOCF, Life Chart Method data showed that patients being treated with quetiapine had significantly less moderate to severe depressive days than patients on VPA (mean +/- SD, 11.7 +/- 16.9 days vs 27.7 +/- 24.9 days; P = 0.04) while they did not differ in the number of days with manic or hypomanic symptoms. Furthermore, according to the Clinical Global Impression Scale, bipolar version, the responder rates tended to be higher for quetiapine than for VPA. There were no differences found evaluating the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Scale, and the Young Mania Rating Scale. The incidence of adverse events, especially of orthostatic dysregulation, sedation, and weight gain, was significantly higher in the quetiapine group.. In this study, quetiapine was more effective than VPA on the number of depressive days and similar to VPA in the treatment of manic symptoms. Quetiapine was associated with a greater incidence of side effects, particularly orthostatic dysregulation, sedation, and weight gain.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Hypotension, Orthostatic; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Psychometrics; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Valproic Acid; Weight Gain

A post hoc analysis of pooled data from two quetiapine monotherapy clinical trials was conducted to evaluate the efficacy and tolerability of quetiapine therapy (twice daily, 400-800 mg/day) among bipolar manic adults aged 55 years and older. The primary efficacy endpoint was the change from baseline in Young Mania Rating Scale (YMRS) total score at Day 21. A secondary endpoint was change from baseline in YMRS score at Day 84.. A total of 407 patients made up the safety population, consisting of 59 older adults (aged >or=55 years) and 348 younger adults. A total of 403 patients made up the efficacy population, consisting of 59 older adults and 344 younger adults. Efficacy outcomes were analyzed using covariance models (ANCOVA); descriptive statistics are presented for safety outcomes.. Both older and younger individuals treated with quetiapine had significant improvement from baseline on YMRS scores compared with placebo-treated patients. The older adult group demonstrated a sustained reduction in YMRS score compared with placebo that was apparent by Day 4 of treatment. For the quetiapine treatment groups, the most common adverse effects (at a frequency >or=10%) were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness in older adults, and dry mouth, somnolence, and insomnia in younger adults. For the placebo treatment groups, insomnia was the most common adverse event in both older and younger adults.. This secondary analysis suggests that quetiapine represents a potentially useful treatment option among older adults with bipolar I mania. Studies with a primary focus of geriatric bipolar mania, and including larger patient numbers, are needed to confirm these findings.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Evaluation; Female; Geriatrics; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Time Factors; Young Adult

The authors examined long-term effectiveness and study retention during open-label quetiapine treatment for rapid cycling bipolar disorder.. An open-label, nonrandomized trial was conducted in 41 patients with rapid-cycling bipolar disorder (type I=33, type II=7, NOS=1) who received flexibly dosed quetiapine monotherapy (n=19) or add-on therapy (n=22) for up to one year. Linear growth curves were calculated to assess longitudinal changes in depression and mania.. Linear growth curves demonstrated highly significant reductions in manic (p<.0001) and depressive (p<.0001) symptoms. Effect sizes were large against manic symptoms (add-on therapy: Cohen's d=0.66; monotherapy: Cohen's d=0.75) but small-to-moderate against depression (monotherapy: d=0.29; add-on therapy: d=0.40). Most patients (68%) prematurely terminated the protocol (mean duration: 18.0+/-16.9 weeks, mean dose: 195.6+/-196.1 mg/day), most often because of the need for additional psychotropic treatments.. The study protocol involved an open label design with no placebo or active comparator group. The sample size provided adequate statistical power to detect large but not medium or small within-group effects. Premature dropout during the first six months precluded inferences about longer-term treatment outcome.. These observational findings provisionally suggest some benefit with quetiapine for both manic and depressive symptoms in rapid cycling bipolar disorder, at dosages somewhat lower than previously described either for mania or bipolar depression. The relatively high dropout rate underscores the complexity of rapid cycling bipolar disorder and likely necessity for pharmacotherapy adjustments over time.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Depression; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Surveys and Questionnaires; Treatment Outcome

To investigate the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar II disorder.. A post-hoc evaluation was conducted in 351 patients with bipolar II depression combined from two similarly designed double-blind, randomized, placebo-controlled, 8-week studies of quetiapine (300 or 600 mg/day) that included patients with bipolar I or II disorder (DSM-IV) exhibiting moderate to severe depression. The primary endpoint was change from baseline to week 8 in MADRS total score. Secondary endpoints included HAM-D, HAM-A, and CGI.. In patients with bipolar II disorder, improvement in mean MADRS total score from baseline was significantly greater with quetiapine 300 (n = 107) and 600 mg/day (n = 106) from the first assessment (week 1) through week 8 compared with placebo (n = 108). The mean change from baseline at week 8 for quetiapine 300 and 600 mg/day versus placebo was -17.1 and -17.9 versus -13.3 (P = 0.005 and P = 0.001 versus placebo), respectively. Change in HAM-D, HAM-A, and CGI were also significantly greater for quetiapine groups versus placebo. Common adverse events in the quetiapine groups included dry mouth, sedation, and somnolence.. Quetiapine demonstrated significant efficacy as monotherapy, compared with placebo, for the treatment of acute depressive episodes in bipolar II disorder.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

To assess the efficacy and tolerability of quetiapine in Chinese patients hospitalized with acute bipolar mania.. This was a 4-week, multicenter, randomized, double-blind, lithium-controlled, parallel-group study. Secondary endpoints in the primary analysis were: response rate (> or = 50% decrease from baseline in YMRS total score) and remission rate as defined using 3 criteria: YMRS total score < or = 12, YMRS total score < or = 12 + MADRS total score < or = 8, and YMRS total score < or = 8. Other measures included: change from baseline at Day 28 in YMRS, PANSS, and MADRS total score. Adverse event (AE) data were collected throughout the study.. 73 (94.8%) quetiapine and 62 (80.5%) lithium patients completed the study. Mean (SD) quetiapine doses for the ITT population and responders were 648.2 (111.84)mg/day and 637.5 (118.78)mg/day, respectively, while mean lithium concentrations for the ITT population and responders were 0.80 (0.28)mmol/L and 0.80 (0.22)mmol/L, respectively. Of patients who responded to quetiapine at Day 28, 88.3% were receiving 600-800mg/day. At Day 28 YMRS response rate was significantly greater with quetiapine than lithium (77.9% vs. 59.7%, p = 0.0132), and remission rates using the 3 criteria were significantly greater with quetiapine than lithium: YMRS total score < or = 12 (70.1% vs. 48.1%, p = 0.0071), YMRS < or = 12 + MADRS < or = 8 (70.1% vs. 48.1%; p = 0.0071), and YMRS < or = 8 (51.9% vs. 32.5%; p = 0.0147). Significant decreases were observed in PANSS, YMRS, and MADRS total scores for both groups. The most common AEs experienced by patients receiving quetiapine were constipation, dizziness, diarrhea, alanine aminotransferase increase, palpitations, aspartate aminotransferase increase, pharyngolaryngeal pain, upper respiratory tract infection and dry mouth. In patients receiving lithium, the most common AEs were nausea (16.9%), constipation (13.0%), vomiting (13.0%), nasopharyngitis (11.7%), dizziness (6.5%), diarrhea (6.5%), and upper respiratory tract infection (6.5%).. Quetiapine was shown to be clinically effective in patients with acute bipolar mania. There were side effects with quetiapine similar to those reported in other studies that included other ethnic populations of patients.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; China; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lithium Compounds; Male; Middle Aged; Placebos; Polypharmacy; Quetiapine Fumarate; Remission Induction; Time Factors; Treatment Outcome

Alcohol dependence is extremely common in patients with bipolar disorder, and it is associated with unfavorable outcomes, including treatment nonadherence, violence, and cognitive impairment. However, few treatment trials have been conducted in this population. Quetiapine is an atypical antipsychotic medication that is used to treat the mood symptoms of bipolar disorder. In this study, the efficacy of quetiapine in reducing alcohol use and improving mood symptoms was assessed in patients with bipolar disorder and alcohol abuse or dependence.. One hundred fifteen outpatients with bipolar disorder and alcohol abuse or dependence were randomly assigned to 12 weeks of quetiapine (titrated to 600 mg/day) add-on therapy or placebo. Alcohol use and mood were assessed. The study was conducted from November 2002 to September 2005.. One hundred two participants (49% with bipolar I disorder, 82% depressed, and 97% with alcohol dependence) returned for at least 1 postbaseline assessment and were used in the random regression analysis. No statistically significant between-group differences were found on alcohol use measures or the Young Mania Rating Scale. However, based on a random regression analysis, scores on the Hamilton Rating Scale for Depression (HAM-D) decreased statistically significantly more in the quetiapine than in the placebo group during the trial (p < .05). The between-group difference was largely due to differences in HAM-D scores during the first 6 weeks of the trial, with the placebo group showing greater improvement during the second half of the trial.. Quetiapine therapy was associated with a statistically significant decrease in depressive symptoms, but not alcohol use, in patients with bipolar disorder and alcohol dependence (p < .05).

Topics: Adult; Alcoholism; Ambulatory Care; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Patient Compliance; Quetiapine Fumarate

To investigate the efficacy and tolerability of quetiapine monotherapy for the treatment of major depressive episodes in patients with bipolar I disorder, as a post hoc analysis of data from 2 large studies, the BipOLar DEpRession (BOLDER) I and II studies, which investigated the overall efficacy of quetiapine in both bipolar I and II disorder.. A combined cohort of patients with depressive episodes in bipolar I disorder (DSM-IV criteria) (N = 694) from 2 nearly identical double-blind, randomized, placebo-controlled studies that each randomly assigned patients with bipolar I and II disorder to 8 weeks of treatment with quetiapine 300 or 600 mg/day or placebo was analyzed. The primary efficacy measure was change from baseline to end of treatment (week 8) in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores.. In the combined cohort of patients with depressive episodes in bipolar I disorder from 2 studies, there were significantly greater clinical improvements in mean MADRS total scores among patients who received quetiapine compared with placebo from baseline to week 1 and through week 8 (at week 8: quetiapine 300 mg/day = -19.4; 600 mg/day = -19.6; placebo = -12.6; p < .001 for each dose), providing effect sizes of 0.78 and 0.80, respectively. Changes in MADRS were unrelated to reports of sedation and somnolence. The most common adverse events (AEs) with quetiapine were dry mouth, somnolence, sedation, dizziness, and constipation. Rates of withdrawal because of these AEs were relatively low.. Quetiapine monotherapy (300 and 600 mg/day) is more effective than placebo and generally well tolerated for the treatment of depressive episodes in patients with bipolar I disorder.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Mass Screening; Quetiapine Fumarate; Treatment Outcome

Bipolar depression is associated with significant morbidity, high risk of suicide and substantial impairment of health-related quality of life (QOL), which adversely affects family/social relationships and occupational functioning. Depressive symptomatology is the primary determinant of quality of life, and there is a paucity of clinical trial data on how treatments affect quality of life. This 8-week, randomized, double-blind, parallel-group, placebo-controlled study in 542 patients with bipolar I or II depression used the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire to assess the effect of quetiapine monotherapy, 300 or 600 mg/day, on quality of life. Quality of sleep was also measured using the Pittsburgh Sleep Quality Index. Both doses of quetiapine significantly improved quality of life over baseline values in comparison with placebo, which was evident at first assessment (week 4) and continued up to week 8. The improvement in quality of life was consistent over the majority of the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire domains, and was evident in patients classified as responders on the basis of clinical efficacy measures. Quetiapine therapy also effected a significant improvement in quality of sleep compared with placebo. Improved quality of life may enhance patient compliance, and assessment of quality of life should be incorporated into future clinical trials in bipolar depression.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Least-Squares Analysis; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Sleep; Time Factors; Treatment Outcome

To investigate the effects of antidepressant therapy plus quetiapine on major depression, motor activity, daytime sleepiness and quality of sleep.. Patients (N = 27) with major depressive disorder received a standard antidepressant treatment (Venlafaxine, Escitalopram) plus flexible dose of quetiapine. Patients' depression was monitored with HAM-D-21, motor activity was continuously measured with actigraphy and sleep parameters with the Pittsburgh Sleep Quality Index (PSQI) over 4 weeks.. Whereas depression, quality of sleep and daytime sleepiness showed a significant improvement over 4 weeks, change of daytime motor activity was significant only between the wash out period and the last 2 days of the study. Repeated measures of variance indicate an independent influence of quetiapine on improved depression, motor activity and sleep. While we found only a mild decrease of daytime sleepiness during the first week of treatment, the further decline of daytime sleepiness got significant after 2 weeks of treatment with quetiapine, even at high mean daily doses and despite the sedative effects of quetiapine.. Antidepressant treatment plus quetiapine is possibly a suitable treatment strategy to improve clinical depression, quality of sleep and motor activity. Future research is needed to understand the pharmacological interactions between antidepressants and quetiapine in major depression.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Arousal; Bipolar Disorder; Circadian Rhythm; Citalopram; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Motor Activity; Quetiapine Fumarate; Sleep; Treatment Outcome; Venlafaxine Hydrochloride

The objectives of this analysis are to elucidate the clinical significance of antidepressant effects with quetiapine by evaluating number needed to treat as well as time to response and remission with quetiapine monotherapy in patients with acute bipolar depression. A post-hoc analysis was conducted of 542 patients with bipolar I or II disorder, (moderate to severe depression), randomized to 8 weeks of double-blind treatment with quetiapine 600 mg/day (n=180), quetiapine 300 mg/day (n=181), or placebo (n=181). Number needed to treat, time to response (> or =50% reduction from baseline in Montgomery-Asberg Depression Rating Scale total score) and time to remission (Montgomery-Asberg Depression Rating Scale total score < or =12) were evaluated. Response rates at week 8 were 58.2 and 57.6% for quetiapine 600 and 300 mg/day, respectively, and 36.1% for placebo (P<0.001). Remission rates were 52.9% for both quetiapine groups and 28.4% for placebo (P<0.001). The number needed to treat was five for both response and remission for quetiapine (600 and 300 mg/day) compared with placebo. Median time to response and remission were significantly shorter with quetiapine 600 and 300 mg/day than placebo. No between-group difference was found in the incidence of treatment-emergent mania or hypomania (quetiapine 600 mg/day: 2.2%, quetiapine 300 mg/day: 3.9, and placebo: 3.9%). In conclusion, quetiapine compared with placebo significantly reduces time to response and remission compared with placebo, and has a favorable number needed to treat.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Humans; Kaplan-Meier Estimate; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Remission Induction; Treatment Outcome

To investigate the effectiveness and tolerability of quetiapine for the treatment of adolescents at high risk for developing bipolar I disorder.. Twenty adolescents (aged 12-18 years) with mood symptoms that did not meet DSM-IV-TR criteria for bipolar I disorder and who had at least one first-degree relative with bipolar I disorder were recruited from August 2003 to June 2005 to participate in a single-blind, 12-week prospective study of quetiapine. Subjects were diagnosed using the Washington University in St. Louis Kiddie Schedule of Affective Disorders and Schizophrenia and were symptomatic, defined by a Young Mania Rating Scale (YMRS) score > or = 12 or a Childhood Depression Rating Scale-Revised Version (CDRS-R) score > or = 28 at baseline. The primary effectiveness measure was an endpoint Clinical Global Impressions-Improvement scale (CGI-I) score < or = 2 ("much" or "very much" improved). Secondary efficacy measures included change from baseline to endpoint in YMRS and CDRS-R scores.. Mood disorder diagnoses in the adolescents consisted of bipolar disorder not otherwise specified (N = 11), dysthymia (N = 3), bipolar II disorder (N = 3), cyclothymia (N = 2), and major depressive disorder (N = 1). The majority of patients (N = 12, 60%) were non-responders to previous trials of psychotropic agents. Fifteen subjects (75%) completed all study visits. Eighty-seven percent of patients were responders (CGI-I < or = 2) to quetiapine at week 12 (mean +/- SD endpoint dose = 460 +/- 88 mg/day). YMRS scores decreased from 18.1 +/- 5.5 at baseline to 8.7 +/- 7.9 at endpoint (p < .0001), and CDRS-R scores decreased from 38.2 +/- 9.8 to 27.7 +/- 9.3, (p = .0003). The most frequently reported adverse events were somnolence, headache, musculoskeletal pain, and dyspepsia. No subjects discontinued study participation due to adverse events.. Although these findings are limited by the small sample size and open-label treatment, the results suggest that quetiapine may be an effective treatment for mood symptoms in adolescents with a familial risk for developing bipolar I disorder.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Female; Genetic Predisposition to Disease; Humans; Male; Mood Disorders; Quetiapine Fumarate; Single-Blind Method

The aim of this study was to evaluate the efficacy and tolerability of quetiapine combined with lithium or divalproex in the treatment of bipolar mania. Patients were randomized to 6 weeks of quetiapine (up to 800 mg/day) and lithium/divalproex (Li/DVP) (target trough serum concentrations of 0.7-1.0 mEq/L and 50-100 microg/mL, respectively) or placebo and lithium/divalproex. Quetiapine+lithium/divalproex treatment (n=104) showed a 2.0-point greater improvement on the primary outcome (change from baseline in Young Mania Rating Scale total score at day 21) compared with placebo+lithium/divalproex (n=96), and a 2.8-point greater difference by day 42, but the differences between groups were not statistically significant. Other efficacy measures, however, did show a statistically significant advantage in favor of quetiapine+lithium/divalproex over lithium/divalproex monotherapy at day 42. Improvement of mean Young Mania Rating Scale scores with quetiapine+lithium/divalproex was numerically but not statistically significantly greater than lithium/divalproex monotherapy in the treatment of bipolar mania. Potential reasons for the failure of quetiapine+lithium/divalproex to differentiate from placebo+lithium/divalproex treatment on the primary outcome measure and the implications of this for the treatment of mania and future studies are discussed. Overall, the combination of quetiapine with lithium or divalproex was well tolerated.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Valproic Acid

To investigate the efficacy and tolerability of quetiapine monotherapy in patients with bipolar I or II disorder with a rapid-cycling disease course.. Adult patients with a DSM-IV diagnosis of bipolar disorder, most recent episode depressed, with a rapid-cycling disease course from a previously completed multicenter trial randomized to 8 weeks of treatment with quetiapine 600 mg/day (n = 31), quetiapine 300 mg/day (n = 42), or placebo (n = 35) were included in this sub-analysis. The primary efficacy variable was change from baseline to week 8 in Montgomery-Asberg Depression Rating Scale (MADRS) total score.. Quetiapine (600 and 300 mg/day) provided significantly greater mean reductions from baseline to week 8 in the MADRS total score than placebo (-21.1, -20.7 versus -11.6, both p < 0.001) in this patient population. Effect sizes in patients with a rapid-cycling disease course were 1.2 (600 mg/day) and 1.1 (300 mg/day) and were similar for bipolar I (0.98 and 1.22) and bipolar II (1.45 and 0.97) sub-groups. Significant improvements were also noted on the Clinical Global Impression, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire scales. Quetiapine was generally well tolerated with moderate increases in weight and extrapyramidal side effects compared to placebo. The incidence of treatment-emergent mania was similar to placebo.. Quetiapine monotherapy (600 or 300 mg/day) is clinically effective and well tolerated in the short-term treatment of depressive episodes in patients with bipolar I or II disorder who have a rapid-cycling disease course.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Secondary Prevention; Treatment Outcome

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 whether there is a pharmacokinetic drug interaction between quetiapine fumarate and divalproex sodium.. The pharmacokinetics and short-term tolerability and safety of coadministered quetiapine and divalproex were examined in adults with schizophrenia/schizoaffective disorder (Cohort A) or bipolar disorder (Cohort B) in an open-label, parallel, 2-cohort drug-interaction study conducted at three centers in the United States. Cohort A was administered quetiapine (150 mg bid) prospectively for 13 days, with divalproex (500 mg bid) added on days 6-13. Cohort B was administered divalproex (500 mg bid) for 16 days, with quetiapine (150 mg bid) added on days 9-16. Quetiapine and valproic acid plasma concentration-time data over a 12-h steady-state dosing interval were used to determine C(max), T(max), C(min), area under the plasma concentration-time curve (AUC(tau)), and oral clearance (CL/F).. In Cohort A (n = 18), addition of divalproex did increase the C(max) of quetiapine by 17% but did not change AUC(tau). In Cohort B (n = 15), addition of quetiapine decreased both total valproic acid C(max) and AUC(tau) by 11%. No differences were observed in adverse events (AEs) with either quetiapine or divalproex monotherapy or their combination.. Combination therapy with quetiapine (150 mg bid) and divalproex (500 mg bid) resulted in small and statistically non-significant pharmacokinetic changes.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Area Under Curve; Bipolar Disorder; Cohort Studies; Dibenzothiazepines; Drug Interactions; Female; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; United States; Valproic Acid

Antipsychotic medications differ in their sedative potential, which can affect cognitive performance. The primary objective of this double-blind study was to compare the effects of treatment initiation with risperidone and quetiapine on cognitive function in subjects with stable bipolar disorder.. Subjects had a DSM-IV diagnosis of bipolar I disorder in partial or full remission and a Young Mania Rating Scale score

Topics: Adult; Antipsychotic Agents; Attention; Bipolar Disorder; Cognition; Cognition Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Memory; Middle Aged; Quetiapine Fumarate; Reaction Time; Risperidone; Sleep Stages; Sleep Wake Disorders

To determine the comparative efficacy of quetiapine and divalproex for the treatment of adolescent mania.. Fifty adolescents (ages 12-18 years) with bipolar I disorder, manic or mixed episode, were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days for this double-blind study, which was conducted from July 2002 through January 2004. The primary efficacy measure was change in Young Mania Rating Scale (YMRS) score across the study period.. Repeated measures analysis of variance using the last-observation carried forward data indicated no statistically significant group difference in YMRS scores across the 28 days of the study (p = 0.3). Mixed regression analyses (comparison of slopes) revealed that improvement in YMRS scores occurred more rapidly in the quetiapine than in the divalproex group for both the last-observation carried forward (p = 0.01) and observed data (p = 0.03). Response and remission rates were significantly greater in the quetiapine than in the divalproex group (p < .03). Rates of adverse events did not differ significantly between groups.. The results suggest that quetiapine is at least as effective as divalproex in the treatment of acute manic symptoms associated with adolescent bipolar disorder; however, a quicker reduction of manic symptoms may occur with quetiapine as compared with divalproex. Quetiapine may be useful as monotherapy for the treatment of adolescents with manic or mixed episodes, although placebo-controlled studies are necessary.

Topics: Adolescent; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Double-Blind Method; Drug Tolerance; Female; Humans; Male; Pilot Projects; Quetiapine Fumarate; Valproic Acid

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

Quetiapine monotherapy shows efficacy in bipolar depression. The analyses in this multicenter, double-blind, randomized, fixed-dose, placebo-controlled study evaluated effects of quetiapine monotherapy on anxiety symptoms in bipolar depression.. Of 542 outpatients randomly assigned to treatment, 539 with bipolar I (N = 358) or bipolar II (N = 181) disorder experiencing a major depressive episode (DSM-IV) received 8 weeks of quetiapine monotherapy (600 or 300 mg/day) or placebo between September 2002 and October 2003. Anxiety assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and relevant items from the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Rating Scale for Depression (HAM-D). Analyses evaluated the pooled dose groups versus placebo.. At week 8, quetiapine 600 and 300 mg/day each demonstrated significant improvements in HAM-A total score versus placebo (-10.8 and -9.9 vs. -6.7, p < .001). Quetiapine (pooled doses) significantly improved HAM-A total score from week 1. In bipolar I depression, quetiapine showed significant improvement in HAM-A total score versus placebo (-10.4 vs. -5.1, p < .001). In bipolar I depression, quetiapine also showed significant improvements versus placebo on the HAM-A anxious mood and tension items, HAM-A psychic and somatic subscales, MADRS inner tension item, and HAM-D psychic anxiety item (all p < .001), but not the HAM-D somatic anxiety item. In bipolar II depression, quetiapine reduced the HAM-A total score more than placebo, but the difference was not statistically significant (-9.8 vs. -9.0, p = .473). In bipolar II depression, quetiapine showed significant improvement versus placebo on the HAM-A anxious mood, MADRS inner tension, and HAM-D psychic anxiety items (all p < .01).. Quetiapine monotherapy shows efficacy in treating anxiety symptoms in bipolar I depression; however, the anxiolytic effects in bipolar II disorder require further investigation.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Comorbidity; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Female; Humans; Longitudinal Studies; Male; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

In this open-label pilot study, 20 adult patients hospitalized for acute bipolar mania received oral quetiapine as a single evening dose of 200 mg on day 1, increased by 200 mg/day on days 2, 3, and 4 until 800 mg/day taken in 2 divided doses on day 4. From day 5 onward, patients received a flexible total dose of 400-800 mg/day until completion of 3 weeks of treatment. Safety and tolerability were assessed by adverse-event (AE)-related dropouts in week 1, incidence of AEs including EPS, changes in electrocardiogram, and vital signs. Efficacy was assessed using the YMRS, PANSS, and CGI scales. Nineteen of 20 patients (95%) completed the quetiapine rapid titration during week 1. Significant improvement was observed in YMRS, PANSS, and CGI Severity of Illness scores by day 5, and was maintained throughout the study. A reduction of > or = 50% in YMRS score was achieved by 75% of patients by day 7, and maintained to day 21. Overall, 20% of patients discontinued due to AEs. Agitation was the most common cause of AE-related study discontinuation. Thirty-five per cent of patients required dose adjustment due to AEs after rapid dose administration was completed. Most patients tolerated rapid titration of quetiapine to 800 mg/day by day 4 of therapy, with a significant improvement in manic symptoms by day 7 of treatment.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Female; Humans; Male; Middle Aged; Pilot Projects; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Treatment Outcome

Bipolar disorder (BD) is a disabling and often chronic condition. Patients with BD suffer from depression at least one-third of the time, but they do not always respond well to conventional mood stabilizers. Attempts to treat them with antidepressants can provoke a switch to mania or increased cycling. Our open-label trial aimed to assess the long-term response of patients with bipolar depression to the addition of quetiapine to their usual treatment. Our study also sought to assess the safety and tolerability of quetiapine in patients with BD.. To meet inclusion criteria for the study, patients had a DSM-IV diagnosis of type I or II BD, were aged 18 years and older, currently suffered from depression with a score of > 18 on the Hamilton Depression Rating Scale (HDRS), and had no change in antidepressant use for at least 3 weeks prior to the study. We added quetiapine to patients' medication and attempted to increase the dosage to at least 400 mg daily. Outcome was measured at baseline and once monthly for 12 months on the HDRS, the Young Mania Rating Scale, the Clinical Global Impression Scale (CGI), and the Abnormal Involuntary Movement Scale.. There were 19 patients enrolled in the study (6 men and 13 women), 2 of whom dropped out because they could not tolerate the drug. Seventeen completed at least 2 assessments, and 7 patients completed the full 12-month trial. Data for the 17 patients (that is, last observation carried forward) at 12 months shows HDRS scores reduced from 27.2 to 12.1 and CGI scores reduced from 4.7 to 2.6.. Quetiapine seems to be helpful to and relatively well tolerated by patients with bipolar depression when it is added to their usual treatment. There is, however, a need for controlled trials.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Depressive Disorder; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Periodicity; Prospective Studies; Quetiapine Fumarate; Surveys and Questionnaires; Treatment Outcome

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P

Topics: Adolescent; Adult; Aged; Analysis of Variance; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Double-Blind Method; Female; Humans; Least-Squares Analysis; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Time Factors; Treatment Outcome; United States

The aim of this study was to compare the efficacy and tolerability of quetiapine and divalproex for the treatment of impulsivity and reactive aggression in adolescents with co-occurring bipolar disorder and disruptive behavior disorders.. Patients were included in this post hoc analysis if they scored > or = 14 on the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC) and > or = 4 on at least one of the PANSS EC items, had a current diagnosis of bipolar I disorder, manic or mixed episode, and had a lifetime and/or current diagnosis of a disruptive behavioral disorder (DBD) [conduct disorder (CD) or oppositional defiant disorder (ODD)]. Thirty-three (92%) of the 36 subjects with bipolar disorder and DBD met the PANSS EC inclusion criteria. These thirty-three adolescents were randomized to quetiapine (400-600 mg/day) or divalproex (serum level 80-120 microg/mL) for 28 days in this double-blinded study. The primary efficacy measure was change in PANSS Excited Component (EC) score over the study period and at each time point.. Repeated measures analysis of variance (ANOVA) demonstrated statistically significant within-treatment-group effects for divalproex (baseline = 20.6, end point = 13.3, p < 0.0001) and quetiapine (baseline = 18.8, end point = 10.8, p < 0.0001) for the PANSS EC. There were no statistically significant treatment group differences in PANSS EC changes from baseline to end point scores (p = 0.7, d = 0.14). Mixed regression analyses (comparison of slopes, DAY*TREATMENT) revealed that there was no significant difference in the rate of improvement in the PANSS EC scores between the two treatment groups [F(1,31) = 0.78, p = 0.39, d = 0.28].. Quetiapine and divalproex showed similar efficacy for the treatment of impulsivity and reactive aggression related to co-occurring bipolar and disruptive behavior disorders in adolescents. Quetiapine and divalproex are both useful as monotherapy for the treatment of impulsivity and reactive aggression in adolescents with bipolar and disruptive behavior disorders. Placebo-controlled studies are necessary.

Topics: Adolescent; Aggression; Antimanic Agents; Antipsychotic Agents; Attention Deficit and Disruptive Behavior Disorders; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Child; Dibenzothiazepines; Double-Blind Method; Humans; Impulsive Behavior; Quetiapine Fumarate; Valproic Acid

To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder.. In an international, multicenter, double-blind, parallel-group, 12-week study, patients with a DSM-IV diagnosis of bipolar I disorder (manic episode) were randomly assigned to treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or lithium. The primary efficacy measure was change from baseline in Young Mania Rating Scale (YMRS) score at day 21. Data were gathered from April 2001 to May 2002.. More patients in the quetiapine (72/107) and lithium (67/98) groups completed the study compared with the placebo group (35/97). Improvement (reduction) in YMRS score was significantly greater for quetiapine than placebo at day 7 (-8.03 vs. -4.89; p < .01), and the difference between groups continued to increase over time to day 21 (-14.6 vs. -6.7; p < .001) and to endpoint at day 84 (-20.3 vs. -9.0; p < .001). Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 (53.3% vs. 27.4%; p < .001) and at day 84 (72.0% vs. 41.1%; p < .001). Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures. Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure. The most common adverse events for quetiapine were dry mouth, somnolence, and weight gain, while lithium was associated with tremor and insomnia. The quetiapine and placebo groups had similar, low levels of extrapyramidal symptom-related adverse events.. Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Hyperprolactinemia; Lithium; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome

This study evaluated the overall effectiveness and tolerability of adjunctive quetiapine as a continuation therapy for the long-term treatment of bipolar mania. Twenty-three patients were enrolled in this study and received quetiapine add-on treatment in combination with their existing or new mood stabilizers. The clinical assessment was carried out using the Young Mania Rating Scale (YMRS), Clinical Global Impression-severity(CGI-s), Hamilton Depression Rating Scale scores-17 item, Simpson-Angus Rating Scale and Barnes Akathisia Rating Scale at the baseline, 1, 4, 12 and 24 weeks. The YMRS and CGI-s decreased significantly from the baseline to the endpoint by 89.7% and 78.3%, respectively (p < 0.0001; p < 0.0001). By the end of the study, 22 patients showed at least 50% improvement in the YMRS score. This study suggests that quetiapine can be used as an adjunct in the long-term treatment of bipolar mania.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Korea; Long-Term Care; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

To evaluate the efficacy and safety of quetiapine monotherapy for mania in bipolar disorder by an a priori defined combined analysis of data from two placebo-controlled studies.. The intent-to-treat (ITT) populations from two studies of patients with DSM-IV bipolar I disorder, manic episode, randomised to 12 weeks of double-blind treatment with quetiapine (up to 800 mg/day) or placebo were combined. The primary efficacy endpoint was change in Young Mania Rating Scale (YMRS) score from baseline to Day 21. Secondary endpoints included change from baseline in YMRS to Day 84, YMRS response and remission rates and change from baseline to Days 21 and 84 in the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI), Clinical Global Impressions-Bipolar (CGI-BP) and the Positive and Negative Syndrome Scale (PANSS). These endpoints were analysed as continuous variables, using an analysis of covariance (ANCOVA), with the baseline as covariate. In order to account for any difference in response between studies, the analyses were stratified by study as a fixed effect, and centre as a random effect. The Cochran-Mantel-Haenszel test was used to analyse binary variables. A chi square test was used to compare the frequency of adverse events between the treatment groups.. The combined analysis included a total of 403 patients from two quetiapine monotherapy studies in patients with bipolar I disorder. A significant improvement in YMRS score was observed from Day 4 (p = 0.021) onward in the quetiapine group compared with placebo. The treatment advantage of quetiapine over placebo continued to increase to Day 21 (p < 0.001) and Day 84 (p < 0.001). Significantly more quetiapine-treated than placebo-treated patients achieved a response (p < 0.001). The average quetiapine dose in responders was approximately 600 mg daily. Of adverse events occurring in > or = 5% of patients, quetiapine-treated patients had a significantly greater incidence versus placebo of somnolence (16.3% vs. 4.0%), dry mouth (15.8% vs. 3%), weight gain (9.1% vs. 1.5%) and dizziness (6.7% vs. 2.5%).. The data from this combined analysis support the results from the individual studies and indicate that quetiapine monotherapy is effective across a broad range of mood symptoms, fast-acting and well tolerated in the treatment of mania.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Placebos; Quetiapine Fumarate; Treatment Outcome

There is a major unmet need for effective options in the treatment of bipolar depression.. Five hundred forty-two outpatients with bipolar I (N=360) or II (N=182) disorder experiencing a major depressive episode (DSM-IV) were randomly assigned to 8 weeks of quetiapine (600 or 300 mg/day) or placebo. The primary efficacy measure was mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale total score. Additional efficacy assessments included the Hamilton Depression Rating Scale, Clinical Global Impression of severity and improvement, Hamilton Anxiety Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Enjoyment and Satisfaction Questionnaire.. Quetiapine at either dose demonstrated statistically significant improvement in Montgomery-Asberg Depression Rating Scale total scores compared with placebo from week 1 onward. The proportions of patients meeting response criteria (> or =50% Montgomery-Asberg Depression Rating Scale score improvement) at the final assessment in the groups taking 600 and 300 mg/day of quetiapine were 58.2% and 57.6%, respectively, versus 36.1% for placebo. The proportions of patients meeting remission criteria (Montgomery-Asberg Depression Rating Scale < or =12) were 52.9% in the groups taking 600 and 300 mg/day of quetiapine versus 28.4% for placebo. Quetiapine at 600 and 300 mg/day significantly improved 9 of 10 and 8 of 10 Montgomery-Asberg Depression Rating Scale items, respectively, compared to placebo, including the core symptoms of depression. Treatment-emergent mania rates were low and similar for the quetiapine and placebo groups (3.2% and 3.9%, respectively).. Quetiapine monotherapy is efficacious and well tolerated for the treatment of bipolar depression.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Patients (n=302) with bipolar I disorder (manic episode) were randomised to 12 weeks' double-blind treatment with quetiapine (flexibly dosed up to 800 mg/day), placebo, or haloperidol (up to 8 mg/day). The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale (YMRS) score.. YMRS score improved with quetiapine at Day 21 (-12.29 versus -8.32 for placebo; P<0.01). The difference in favor of quetiapine increased by Day 84 (-17.52 versus -9.48; P<0.001). Haloperidol also showed an advantage over placebo at Days 21 and 84 (P<0.001). There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21. The only common adverse event with quetiapine was somnolence (12.7%). Extrapyramidal symptoms (EPS), including akathisia, occurred at 59.6% with haloperidol, 12.7% with quetiapine, 15.8% with placebo. Most quetiapine responders (84%) received a dose of 400-800 mg/day.. Quetiapine was effective and well tolerated. The efficacy and tolerability profile of haloperidol (including its propensity for EPS) supported study validity.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Haloperidol; Humans; Male; Middle Aged; Patient Selection; Placebos; Quetiapine Fumarate; Safety

The present trial was designed as a pilot study to re-examine how fast the dose of quetiapine in combination with mood stabilizers can be titrated upward in acutely ill patients with bipolar mania. Patients were assigned to either a rapid titration group (RTG) or a conventional titration group (CTG). Quetiapine was administered twice daily in a 3-day period in the RTG (200 mg/day on day 1; 400 mg/day on day 2; and 600 mg/day on day 3) and in a 5-day period in the CTG (50 mg/day on day 1; 100 mg/day on day 2; 200 mg/day on day 3; 300 mg/day on day 4; and 400 mg/day on day 5). The Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity (CGI-S) scores were assessed at days 1 (baseline), 3, 5, 7, 14 and 21. The Barnes Akathisia Rating Scale and Simpson-Angus Rating Scale (SARS) were assessed at days 1, 2, 3, 4, 5, 6, 7, 14 and 21. RTG and CTG showed significant improvement on the scores of YMRS and CGI-S during the study without group differences. Both treatments were well tolerated without clinically significant differences in tolerability measures. Treatment was not limited by adverse events in the two groups. This study demonstrates the potential benefit and tolerability of rapid titration of quetiapine in the treatment of acutely ill bipolar disorder. This preliminary study proposes that rapid titration of quetipaine in combination with a mood stabilizer for the treatment of bipolar mania is effective and tolerable in comparison with conventional titration. A controlled study with a larger cohort should be performed.

Topics: Adolescent; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate

Topics: Adult; Alcohol Drinking; Alcoholism; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Disruptive, Impulse Control, and Conduct Disorders; Female; Humans; Male; Middle Aged; Mood Disorders; Quetiapine Fumarate; Treatment Outcome

The atypical antipsychotics are being increasingly used to control acute manic episodes, and data are emerging to support their mood-stabilizing and antidepressant properties. This study investigated the short-term efficacy of quetiapine as an add-on therapy in the treatment of acute mania.. This study was a 4-week, open-label, add-on, prospective investigation using quetiapine in addition to mood stabilizers. Data on 18 patients fulfilling DSM-IV diagnostic criteria for bipolar I disorder were analysed. The Young mania rating scale (YMRS), the Hamilton scale for depression (HDRS), the brief psychiatric rating scale (BPRS) and extrapyramidal symptom rating scale (ESRS) were applied at baseline and at weeks 1, 2 and 4. The clinical global impression scale (CGI) was evaluated at baseline and week 4.. The addition of quetiapine produced a statistically significant improvement on the YMRS, HDRS, BPRS and CGI score at week 4 from baseline (p<0.005). Quetiapine was well tolerated, with no subjects discontinuing because of side effects.. The combination of quetiapine was associated with a substantial symptomatic improvement in patients with acute mania. Randomized placebo-controlled prospective studies are needed.

Topics: Adult; Affect; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate

Evaluate the efficacy and tolerability of quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) in the treatment of acute mania.. Patients were randomized to 21 days of double-blind treatment with QTP plus Li/DVP, or placebo (PBO) plus Li/DVP. QTP was rapidly dosed up to a maximum of 800 mg/day; Li was dosed to 0.7-1.0 mEq/L; or DVP to 50-100 microg/mL.. Fifty-six of 91 (61.5%) individuals in the QTP + Li/DVP group compared with 49 of 100 (49%) taking PBO + Li/DVP completed the study. A significantly greater mean reduction in total Young Mania Rating Scale (YMRS) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group (-13.76 versus -9.93; p = 0.021). The response rate (> or =50% YMRS improvement) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients (54.3% versus 32.6%; p = 0.005), as was the proportion of patients achieving clinical remission (YMRS < 12) (45.7% versus 25.8%; p = 0.007). Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar (CGI-BP) Severity of Illness scores (-1.38 versus -0.78; p = 0.001). The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria. Common adverse events (at least 10% and twice the rate of Li/DVP) in the QTP + Li/DVP group included somnolence, dry mouth, asthenia, and postural hypotension.. Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania. Combination therapy was well-tolerated and most adverse events were mild, withdrawal because of adverse events being only 5% compared with 6% on Li or DVP monotherapy.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Electrocardiography; Female; Humans; Lithium Carbonate; Male; Quetiapine Fumarate; Valproic Acid

Quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) for the treatment of mania was evaluated in 2 double-blind, placebo-controlled studies. Patients were randomized to 3 or 6 weeks of treatment with QTP plus Li/DVP or placebo (PBO) plus Li/DVP. Quetiapine was dosed up to 800 mg/d; Li was dosed to achieve serum concentrations of 0.7-1.0 mEq/L and DVP to 50-100 microg/mL. A total of 402 patients were randomized: 197 to QTP + Li/DVP and 205 to PBO + Li/DVP. The mean quetiapine dose in responders was 492 (+/-204) mg/d. Improvement in the Young Mania Rating Scale (YMRS) at day 21 in the QTP + Li/DVP group (-15.29) was statistically superior to the PBO + Li/DVP group (-12.19) (P < 0.05). A statistically significant difference in favor of quetiapine was observed within the first week (P < 0.05). Significantly more QTP + Li/DVP patients achieved a response (> or =50% decrease in the YMRS) at day 21 (QTP + Li/DVP, 55.7%; PBO + Li/DVP, 41.6%;P < 0.01). Improvements in Clinical Global Impression-Bipolar Severity of Illness scores by day 21 were also significantly greater in QTP + Li/DVP-treated patients (-1.59) versus PBO + Li/DVP (-1.19) (P < 0.01). Common adverse events (> or =5% and twice that in the PBO + Li/DVP group) in the QTP + Li/DVP group were somnolence, dry mouth, and asthenia. Quetiapine combined with Li/DVP was not associated with extrapyramidal symptoms (including akathisia) or emergent depression. More QTP + Li/DVP-treated patients completed the trial, and there was no difference in discontinuation rates due to adverse events between the two groups. Quetiapine, in combination with lithium or divalproex, is well tolerated and has superior efficacy to lithium or divalproex alone in the treatment of bipolar mania.

Topics: Adolescent; Adult; Analysis of Variance; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Valproic Acid

Quetiapine is an atypical antipsychotic agent that has been approved for the treatment of schizophrenia in over 75 countries; it has been used to treat more than 4 million individuals since its launch in 1997. After quetiapine was found to improve mood and reduce aggression in patients with schizophrenia, researchers began investigating the drug in other indications. Quetiapine, as monotherapy or combined with mood stabilizers, significantly reduces measures of disease severity and acute mania in a variety of bipolar disorder patients, and displays excellent tolerability for a drug in its class. Of particular note is the incidence of extrapyramidal symptoms at levels similar to those seen with placebo. A phase III trial program in bipolar disorder is presently ongoing and includes five randomized, double-blind, controlled trials already reported and several other studies which are ongoing or planned.

Topics: Adolescent; Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Molecular Structure; Multicenter Studies as Topic; Quetiapine Fumarate; Structure-Activity Relationship

Quetiapine is a novel, atypical antipsychotic agent that has been shown to provide long-term efficacy without serious adverse effects in adults. This is the first study of the extended use of quetiapine in adolescents. Five boys and 5 girls, ages 12.3 to 15.9 years, with diagnoses of schizoaffective disorder (n = 7) or bipolar disorder with psychotic features (n = 3) were eligible for entry into this single-site, 88-week, open-label trial. Subjects had completed a pharmacokinetic study over 23 days, during which the dosage of quetiapine was increased sequentially from 25 mg bid to a maximum of 400 mg bid (800 mg/day) (McConville et al. 2000). In the open-label extension of this trial, which followed directly after this trial, a physician's choice design allowed for flexible dose titration of quetiapine by the study physician to an optimal dose for each patient, with ending doses ranging from 300 mg/day to 800 mg/day. Concomitant medications, especially for anxiety and/or manic symptoms, were allowed as deemed necessary. Tolerability and safety were assessed using clinical laboratory tests, physical examinations, measurements of vital signs, interviews for selective symptomatology, and electrocardiograms. Psychiatric measurements included the 18-item Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and the modified Scale for the Assessment of Negative Symptoms (SANS). Neurologic symptom ratings included the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Mean BPRS, CGI, and SANS scores improved significantly during the trial (p < 0.05). No extrapyramidal symptoms or evidence of tardive dyskinesia was seen. Clinically, there was a nonsignificant increase in mean weight and body mass index at week 64. This long-term study suggests that quetiapine is a well-tolerated antipsychotic agent that is efficacious for the treatment of symptoms of selected psychotic disorders in adolescents.

Topics: Adolescent; Adolescent Psychiatry; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Time Factors; Treatment Outcome

The literature on the use of quetiapine for the treatment of bipolar disorder (BD) is limited to case reports, and there are no systematic studies on the efficacy of quetiapine in the prophylactic treatment of BD. The aim of the present study was to compare the efficacy of flexible doses of quetiapine and well established mood stabilizers in the maintenance treatment of BD.. Twenty-eight DSM-IV BD outpatients were consecutively recruited into the study and were randomized to receive one of two open-label treatments, with quetiapine or classical mood stabilizers at flexible doses for 12 months. Clinical assessment was carried out using BPRS, CGI, YMRS and the 21-item HAM-D at baseline (T0) and every 2 months until the end of the study. ANOVAs with repeated measures were applied to the rating scale scores considering the time and the treatment group as main factors.. All patients experienced a significant improvement on the BPRS, CGI and HAM-D scores, with no significant side-effects and a good compliance.. This study should be considered preliminary given the small sample size investigated and the open-label design.. If these results will be replicated on larger samples and in controlled studies, there could be relevant implications for the use of quetiapine as an alternative maintenance treatment for BD.

Topics: Administration, Oral; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome

This randomized, double-blind, placebo-controlled study examined the efficacy and tolerability of quetiapine in combination with divalproex (DVP) for acute mania in adolescents with bipolar disorder. It was hypothesized that DVP in combination with quetiapine would be more effective than DVP alone for treating mania associated with adolescent bipolar disorder. Furthermore, it was hypothesized that quetiapine would be well tolerated.. Thirty manic or mixed bipolar I adolescents (12-18 years) received an initial DVP dose of 20 mg/kg and were randomly assigned to 6 weeks of combination therapy with quetiapine, which was titrated to 450 mg/day (n = 15) or placebo (n = 15). Primary efficacy measures were change from baseline to endpoint in Young Mania Rating Scale (YMRS) score and YMRS response rate. Safety and tolerability were assessed weekly.. The DVP + quetiapine group demonstrated a statistically significantly greater reduction in YMRS scores from baseline to endpoint than the DVP + placebo group (F(1,27) = 5.04, p =.03). Moreover, YMRS response rate was significantly greater in the DVP + quetiapine group than in the DVP + placebo group (87% versus 53%; Fisher exact test, p =.05). No significant group differences from baseline to endpoint in safety measures were noted. Sedation, rated as mild or moderate, was significantly more common in the DVP + quetiapine group than in the DVP + placebo group.. The findings of this study indicate that quetiapine in combination with DVP is more effective for the treatment of adolescent bipolar mania than DVP alone. In addition, the results suggest that quetiapine is well tolerated when used in combination with DVP for the treatment of mania.

Topics: Acute Disease; Adolescent; Analysis of Variance; Antimanic Agents; Bipolar Disorder; Child; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Quetiapine Fumarate; Valproic Acid

This prospective open-label study assessed the impact of add-on quetiapine in the treatment of rapid cycling bipolar patients.. Fourteen rapid cycling bipolar patients were treated with quetiapine, which was added to their ongoing medication regimen for 112 +/- 33 days. At the beginning of the study, five were manic, three were in a mixed state, three were depressed, two hypomanic and one was euthymic. Patients were assessed prospectively with a modified version of the Clinical Global Impression Scale for Bipolars (CGI-BP), the Young Scale for mania (YMRS) and the Hamilton Scale for Depression (HDRS).. A significant reduction of the following scale scores was observed: a 1.8 point reduction for the general CGI-BP (p = 0.013), a -1.3 point for the mania subscale (p = 0.016), a -1.01 point for the YMRS (p = 0.025). Improvement in depressive symptoms was not significant, neither in the CGI-BP (-1 point, p = 0.074) nor in the HDRS (-5.2 points, p = NS). The most common side-effect was sedation (n = 6, 43%). Doses of quetiapine were significantly reduced by the end of the study (443 +/- 235 mg/day versus 268 +/- 190 mg/day, p = 0.008) and they also differed according to the initial episode to be treated (720 +/- 84 mg/day for mania, and 183 +/- 29 mg/day for depression, p = 0.023).. Quetiapine could possibly be an effective treatment for rapid cycling bipolar patients. Adequate doses for acute episodes could significantly differ according to the episode polarity and the length of treatment.

Topics: Activity Cycles; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Tolerance; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Surveys and Questionnaires

The aim of this study was to assess the effect of oral quetiapine on the steady-state pharmacokinetics of lithium.. This was an open-label trial in patients with schizophrenia, schizoaffective disorder, or bipolar disorder who had demonstrated tolerability to combination lithium/ antipsychotic therapy. Patients received lithium for at least 1 week before screening and throughout the 18-day trial. Quetiapine was coadministered in fixed, stepwise, increasing doses of 25 to 250 mg TID on days 4 through 11, and maintained at 250 mg TID on days 12 through 14. Blood samples were drawn to monitor plasma concentrations of lithium and quetiapine. Psychiatric assessments included the Brief Psychiatric Rating Scale, the Clinical Global Impression severity of illness item, and the modified Scale for the Assessment of Negative Symptoms. Neurologic function was assessed using the Simpson-Angus Scale and the Abnormal Involuntary Movement Scale. Other assessments included clinical laboratory testing, electrocardiography, physical examinations, and monitoring for spontaneously reported adverse events.. Nine men and 1 woman (mean [SE] age, 32.8 [1.9] years; mean [SE] body weight, 87.6 [3.3] kg) entered and completed the 18-day trial. Eight patients had bipolar disorder, 1 had paranoid schizophrenia, and 1 had schizoaffective disorder. Morning trough concentrations of lithium in serum (days 2, 6, 8, 10, 12, 14, and 17), as well as quetiapine and 2 of its metabolites in plasma (days 12, 13, and 14), did not appear to vary noticeably. Small increases were observed in the mean values of the area under the 12-hour serum lithium concentration-time curve and the maximum and minimum observed serum lithium concentrations when quetiapine was added to the lithium regimen. However, the increases were not considered clinically relevant by the investigators and were not statistically significant. A total of 91 adverse events were reported, 67 (73.6%) of which were not attributed to trial treatment. The most commonly reported adverse events during coadministration of lithium and quetiapine were somnolence (90.0% [9/10]), asthenia (70.0% [7/10]), dry mouth (30.0% [3/10]), nausea (30.0% [3/10]), vomiting (30.0% [3/10]), dizziness (30.0% [3/10]), tremor (30.0% [3/10]), and insomnia (20.0% [2/10]). There were no serious adverse events.. Measures of lithium and quetiapine concentrations did not vary significantly during combination therapy. Coadministered lithium and quetiapine were well tolerated in the patients studied.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Female; Humans; Lithium; Male; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric illness. Therefore, treatments that stabilize mood and decrease drug use or cravings are of great interest. Atypical antipsychotics are in widespread use in patients with bipolar disorder. However, minimal data are available on their use in bipolar patients with comorbid substance abuse.. Open-label, add-on, quetiapine therapy was examined for 12 weeks in 17 outpatients with bipolar disorder and cocaine dependence. Subjects were evaluated with a structured clinical interview; Hamilton Depression Rating (HDRS), Young Mania Rating (YMRS), Brief Psychiatric Rating (BPRS) scales; and Cocaine Craving Questionnaire (CCQ). Urine samples and self-reported drug use were also obtained. Data were analyzed using a last observation carried forward method on all subjects given medication at baseline.. Significant improvement from baseline to exit was observed in HDRS, YMRS, BPRS and CCQ scores (p < or = 0.05). Dollars spent on cocaine and days/week of cocaine use decreased non-significantly, and urine drug screens did not change significantly from baseline to exit. Quetiapine was well tolerated, with no subjects to our knowledge discontinuing because of side-effects.. The use of quetiapine was associated with substantial improvement in psychiatric symptoms and cocaine cravings. The findings are promising and suggest larger controlled trials of quetiapine are needed in this population.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cocaine-Related Disorders; Comorbidity; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Female; Humans; Male; Personality Inventory; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

The effects of haloperidol, risperidone, and thioridazine on the pharmacokinetics and side-effect profile of quetiapine were investigated in 36 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a single-center, two-period, multiple-dose, open-label, randomized trial. Over a one-to two-week period, quetiapine doses were escalated to 300 mg twice daily (bid). Patients were then treated for at least 7 days at the target quetiapine dose and subsequently entered into the combination therapy period, receiving haloperidol (7.5 mg, bid), risperidone (3 mg, bid), or thioridazine (200 mg, bid) for 8.5 days (after 3 days of dose escalation). Key assessments included the pharmacokinetics of quetiapine at steady state (area under the curve within a dosing interval [AUCtSS], maximum [CmaxSS], and minimum [CminSS] observed plasma concentrations, and oral clearance [Cl/f]), as well as the UKU Side Effect Rating Scale scores and safety evaluations. Neither risperidone nor haloperidol had significant effects on quetiapine pharmacokinetics. However, thioridazine produced statistically significant changes, decreasing the least squares means values of the AUCtSS, CmaxSS, and CminSS by 40%, 47%, and 31%, respectively, and increasing Cl/f by 68%. Increases in the following adverse events were noted during coadministration: somnolence (risperidone), insomnia and dry mouth (all three coadministered therapies), and dizziness (thioridazine). UKU side effect items that became worse in >or= 25% of patients during each coadministration period included sedation and increased sleep duration. Results of laboratory tests, electrocardiograms, and vital sign measurements revealed few clinically important changes. Clinical stability can be maintained with good tolerability during the transition from quetiapine monotherapy to periods of coadministration with haloperidol, risperidone, or thioridazine. Coadministration of either haloperidol or risperidone did not have any important effects on the steady-state pharmacokinetics of quetiapine. Thioridazine significantly increased the oral clearance of quetiapine. Increased doses of quetiapine may be necessary to control psychotic symptoms when thioridazine is coadministered with quetiapine.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Haloperidol; Humans; Male; Metabolic Clearance Rate; Middle Aged; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Schizophrenia; Schizophrenic Psychology; Thioridazine

The effects of fluoxetine and imipramine on the pharmacokinetics and nonpsychiatric side effect profile of quetiapine fumarate were investigated in 26 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a multicenter, two-period, multiple-dose, open-label, randomized trial. Over a 1- to 2-week period, patients were titrated to a 300-mg twice-daily dose of quetiapine. Patients treated for at least 7 days at the target dose entered a combination therapy period, receiving fluoxetine (60 mg daily) or imipramine (75 mg twice daily) for 8 days. Key assessments included pharmacokinetic analysis of quetiapine, the Udvalg for kliniske undersøgelser (UKU) Side Effect Rating Scale, and safety evaluations (e.g., adverse events, electrocardiograms, laboratory tests, and vital signs). Fluoxetine increased the quetiapine area under the plasma concentration time curve during a 12-hour interval (+12%), maximum plasma concentration during the dosing interval (C(ss)(max); +26%), and minimum plasma concentration at the end of the dosing interval (+8%), although it decreased oral clearance (-11%). The change in C(ss)(max) was statistically although not clinically significant. Imipramine did not affect the pharmacokinetics of quetiapine. Overall, scores on the UKU Side Effect Rating Scale improved during combination therapy with either agent, and no statistically significant deterioration was observed for any item. For safety assessments, the only clinically remarkable event was an imipramine-associated complete left bundle branch block in one patient. No unexpected side effects were reported. In conclusion, combination therapy with quetiapine and fluoxetine or imipramine had a minimal effect on quetiapine pharmacokinetics and was well tolerated.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Imipramine; Male; Metabolic Clearance Rate; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.

Topics: Adolescent; Adult; Analysis of Variance; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Humans; Male; Middle Aged; Phenytoin; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Use of antipsychotic medication intermittently or over the long term may be necessary in treating patients with bipolar disorder whose symptoms have responded suboptimally to standard mood-stabilizing agents. Quetiapine fumarate is an effective novel antipsychotic with mixed serotonergic (5-HT2) and dopaminergic (D2) activity. This is an open-label, 12-week prospective study to assess the efficacy and tolerability of quetiapine in the treatment of patients with bipolar and schizoaffective disorder who were suboptimally responsive to mood stabilizers alone.. Participants in the study were inpatients or outpatients with a DSM-IV diagnosis of bipolar or schizoaffective disorder. Baseline psychopathology was evaluated with the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), and the Hamilton Rating Scale for Depression (HAM-D). Involuntary movements were rated with the Simpson-Angus Neurologic Rating Scale. Quetiapine was added on an open-label basis and increased to optimum clinical dosage. Psychopathology and Abnormal Involuntary Movement Scale ratings were repeated weekly for the first 4 weeks and then again at weeks 8 and 12.. Ten individuals with bipolar disorder and 10 with schizoaffective disorder received quetiapine therapy. Overall, patients improved, with significant improvement in BPRS (p < .001), YMRS (p = .043), and HAM-D scores (p = .002). Simpson-Angus score also significantly decreased (p = .02). Overall. quetiapine was well tolerated by patients in this group with serious mood disorders. The mean +/- SD quetiapine dose was 202.9 +/- 124.3 mg/day (range, 50-400 mg/day). Mean weight gain was 10.9 lb (4.9 kg).. Although limited by its small size, open-label design, and relative gender homogeneity, this study suggests that quetiapine therapy may be useful in the treatment of individuals with serious mood disorders who are suboptimally responsive to mood stabilizers alone. These preliminary findings should be explored in larger, controlled trials.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Humans; Lithium; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Valproic Acid; Weight Gain

The "microbiota-gut-brain axis" which bridges the brain and gut microbiota is involved in the pathological mechanisms of bipolar disorder (BD), but rare is known about the exact association patterns and the potential for clinical diagnosis and treatment outcome prediction.. At baseline, fecal samples and resting-state MRI data were collected from 103 BD depression patients and 39 healthy controls (HCs) for metagenomic sequencing and network-based functional connectivity (FC), grey matter volume (GMV) analyses. All patients then received 4-weeks quetiapine treatment and were further classified as responders and non-responders. Based on pre-treatment datasets, the correlation networks were established between gut microbiota and neuroimaging measures and the multimodal kernal combination support vector machine (SVM) classifiers were constructed to distinguish BD patients from HCs, and quetiapine responders from non-responders.. The multi-modal pre-treatment characteristics of quetiapine responders, were closer to the HCs compared to non-responders. And the correlation network analyses found the substantial correlations existed in HC between the Anaerotruncus_ unclassified，Porphyromonas_asaccharolytica，Actinomyces_graevenitzii et al. and the functional connectomes involved default mode network (DMN),somatomotor (SM), visual, limbic and basal ganglia networks were disrupted in BD. Moreover, in terms of the multimodal classifier, it reached optimized area under curve (AUC-ROC) at 0.9517 when classified BD from HC, and also acquired 0.8292 discriminating quetiapine responders from non-responders, which consistently better than even using the best unique modality.. Lack post-treatment and external validation datasets; size of HCs is modest.. Multi-modalities of combining pre-treatment gut microbiota with neuroimaging endophenotypes might be a superior approach for accurate diagnosis and quetiapine efficacy prediction in BD.

Topics: Bipolar Disorder; Brain; Gastrointestinal Microbiome; Gray Matter; Humans; Magnetic Resonance Imaging; Quetiapine Fumarate

It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage.. The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively.. We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Female; Humans; Male; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Quetiapine, an atypical second-generation antipsychotic drug, is approved for treatment of schizophrenia, bipolar disorder, and depression. Due to the limitations of clinical trials, the association between quetiapine and rare cardiac adverse events (AEs) is still unclear. This study is to evaluate quetiapine-associated cardiac AEs through data mining of FDA Adverse Event Reporting System (FAERS).. Reporting odds ratio (ROR) was used to quantify the signals of quetiapine-related cardiac AEs from the first quarter (Q1) of 2018-2022 Q1. Serious and nonserious cases were compared, and signals were prioritized using a rating scale.. A total of 1004 cases of quetiapine-associated cardiac AEs were identified, with 31 signals being detected, among which 13 AEs were identified as new and unexpected signals. Besides, nine and 22 cardiac AEs were identified as moderate and weak clinical priority. The median TTO for moderate and weak clinical priority signals were 0 and 4 days, respectively. All of the cardiac AEs had early failure type characteristics, suggesting that most of the patients developed cardiac AEs in a few days after quetiapine treatment, and that the risk of cardiac AEs occurrence would be gradually decreased over time.. Our study provided valuable evidence for health-care professionals to mitigate the risk of quetiapine-associated cardiac AEs based on an extensive analysis of a real-world, large-sample FAERS database, and prioritize cardiac AE signals.

Topics: Adverse Drug Reaction Reporting Systems; Antipsychotic Agents; Bipolar Disorder; Humans; Quetiapine Fumarate; United States; United States Food and Drug Administration

Quetiapine is a drug used to treat schizophrenia, bipolar disorder, and major depressive disorder. However, it can cause mild or severe hepatic adverse events and rarely fatal liver damage. This study was aimed at investigating hepatic toxicity caused by quetiapine use by analyzing the information captured from hospital electronic health records by using the Observational Medical Outcomes Partnership common data model (CDM).. This was a retrospective observational study involving a nested case-control method. A CDM based on an electronic health record database from five hospitals between January 2009 and May 2020 was used. We analyzed the status of quetiapine use, adverse events, and hepatic impairment.. The numbers of patients with non-serious and severe hepatic adverse reactions were 2566 (5.05%) and 835 (1.64%) out of 50 766 patients, respectively. After adjusting for covariates, the odds ratio of hepatic adverse events was 2.35 (95% CI: 2.03-2.72), and the odds ratio of severe hepatic adverse events was 1.76 (95% CI: 1.16-2.66).. Our findings suggest that quetiapine should be cautiously used, and hepatic function should be monitored in patients using quetiapine because it can cause mild or severe hepatic adverse events, complications, and in rare cases, fatal liver damage.

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Humans; Liver; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Edema; Humans; Quetiapine Fumarate; Valproic Acid

The molecular mechanism(s) underpinning the clinical efficacy of the current drugs for bipolar disorder (BD) are largely unknown. This study evaluated the transcriptional perturbations potentially playing roles in the therapeutic efficacy of four commonly prescribed psychotropic drugs used to treat BD. NT2-N cells were treated with lamotrigine, lithium, quetiapine, valproate or vehicle control for 24 h. Genome-wide mRNA expression was quantified by RNA-sequencing. Incorporating drug-induced gene expression profiles with BD-associated transcriptional changes from post-mortem brains, we identified potential therapeutic-relevant genes associated with both drug treatments and BD pathophysiology and focused on expression quantitative trait loci (eQTL) genes with genome-wide association with BD. Each eQTL gene was ranked based on its potential role in the therapeutic effect across multiple drugs. The expression of highest-ranked eQTL genes were measured by RT-qPCR to confirm their transcriptional changes observed in RNA-seq. We found 775 genes for which at least 2 drugs reversed expression levels relative to the differential expression in post-mortem brains. Pathway analysis identified enriched biological processes highlighting mitochondrial and endoplasmic reticulum function. Differential expression of SRPK2 and CHDH was confirmed by RT-qPCR following multiple-dose treatments. We pinpointed potential genes involved in the beneficial effects of drugs used for BD and their main associated biological pathways. CHDH, which encodes a mitochondrial protein, had a significant dose-responsive downregulation following treatment with increasing doses of quetiapine and lamotrigine, which in combination with the enriched mitochondrial pathways suggests potential therapeutic roles and demand more studies on mitochondrial involvement in BD to identify novel treatment targets.

Topics: Bipolar Disorder; Genome-Wide Association Study; Humans; Lamotrigine; Protein Serine-Threonine Kinases; Quantitative Trait Loci; Quetiapine Fumarate

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

To evaluate the effectiveness of low doses (25-75 mg/day) of quetiapine (Seroquel) in patients with bipolar affective disorders in a euthymic state with signs of impaired impulse control.. The main criteria for patients' selection were as follows: both sex, diagnoses of bipolar affective disorders, remission (euthymic state), adult age (from 18 to 60 years old), stable basic therapy. The duration of the study was 6 weeks, a dose of quetiapine (Seroquel) varied from 25 to 75 mg. The examinations were carried out with the Barratt scale, computerized Go-No-Go and Balloon tests.. The study group included 32 patients (11 men and 21 women), mean age 31.2±9.7 years (minimum 18, maximum 60 years). The changes in Barratt total score (. The results of the study showed that add-on of the low doses of quetiapine (Seroquel) significantly decreases impaired impulse control in remitted patients with bipolar affective disorders both in self-evaluation and in risk-taking experimental test. The drop of high level of impulsivity can improve the quality and stability of remission and reduce behavioral risks due to impaired impulse control.. Оценить эффективность применения малых доз (25—75 мг/сут) кветиапина (Сероквеля) в отношении коррекции симптомов импульсивности у пациентов с диагнозом биполярного аффективного расстройства (БАР) в эутимическом состоянии с признаками нарушения контроля импульсов.. В исследование включены 32 пациента (11 мужчин и 21 женщина), средний возраст 31,2±9,7 года (от 18 до 60 лет) с диагнозом БАР в эутимическом состоянии, находящихся на стабильной терапии. Продолжительность исследования составляла 6 нед, в рамках которых пациенты принимали дозу кветиапина (Сероквеля) от 25 до 75 мг. Обследования проводили по шкале Барратта, компьютеризированным тестам Go-No-Go и «Воздушный шар».. Статистически значимое улучшение отмечено по общему баллу шкалы Барратта (. Полученные данные свидетельствуют в пользу того, что введение низких доз кветиапина (Сероквеля) в терапию пациентов с БАР и повышенной импульсивностью в межприступный период может существенно повысить качество и стабильность ремиссии, а также снизить поведенческие риски вследствие нарушения контроля импульсов.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Cyclothymic Disorder; Dibenzothiazepines; Female; Humans; Impulsive Behavior; Male; Middle Aged; Psychometrics; Quetiapine Fumarate; Young Adult

Recent studies proposed the existence of a correlation between patients' inflammatory status and therapy response in bipolar disorder (BD). Here we investigated the correlation between levels of inflammatory markers and quetiapine (QUE) effects in BD patients.. In 15 hospitalised BD patients, we investigated changes in inflammatory markers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and cytokines after a 6-week treatment with QUE monotherapy.. We found QUE treatment to significantly reduce CRP and IL-6 plasma levels. Moreover, we found higher CRP and IL-6 plasma levels at baseline correlated with better improvement of patients' clinical symptoms.. The reported results, although preliminary, could be useful in clinical practice, providing not only markers for QUE response, but also allowing for identification of new targets and new therapies for the treatment of this condition.

Topics: Biomarkers; Bipolar Disorder; Blood Sedimentation; C-Reactive Protein; Humans; Interleukin-6; Quetiapine Fumarate

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

The efficacy of vortioxetine in major depressive disorder has been evaluated in many studies. However, there is a lack of studies assessing vortioxetine in bipolar depression.. In 60 patients with bipolar depression, vortioxetine 10-20 mg daily was added to current mood stabilizing medication during 24-week, naturalistic, openlabel study. The most frequent mood stabilizers were lamotrigine, quetiapine, olanzapine, and valproates. The therapeutic efficacy was evaluated by the Clinical Global Impression - Improvement (CGI-I) and Clinical Global Impression - Severity (CGI-S) scales. Patients were classified as responding to vortioxetine when they achieved 1 or 2 points on the CGI-I scale at any stage of observation. The criterion of remission was defined as score 1 at the CGI-S.. 73% of all patients (44/60) responded to vortioxetine and 52% (31/60) achieved clinical remission of depressive symptoms (in mean 8.97 ± 4.05 weeks). There were no significant associations between vortioxetine response/remission rates and: (1) the dose, (2) BD type, (3) clinical stage, (4) presence of rapid cycling, (5) history of psychotic symptoms, analyzed depressive symptoms, and (6) concomitantly used mood stabilizer. 4 patients (6.7%) stopped treatment due to adverse effects (nausea), and 7 patients (11.7%) discontinued treatment due to the phase switch. 14 patients (23%) experienced a loss of vortioxetine effectiveness after the initial response or remission.. The results indicate relatively high rates of response and remission during 24-week treatment in depressed bipolar patients receiving vortioxetine concomitantly with a mood stabilizer. This may indicate that vortioxetine added to a mood stabilizer may constitute an efficient and well tolerated therapeutic option in bipolar depression.

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Double-Blind Method; Humans; Quetiapine Fumarate; Treatment Outcome; Vortioxetine

Editor's note: This is the next installment in a series on electrocardiogram (ECG) interpretation. Nurses in all settings should know the basics, as medications and physiological changes can cause cardiac arrhythmias. Each article will start with a brief case scenario and an ECG strip and then take you step by step through analyzing the heart rhythm.

Topics: Bipolar Disorder; Death, Sudden, Cardiac; Electrocardiography; Electrolytes; Emergency Service, Hospital; Female; Humans; Intensive Care Units; Middle Aged; Nurse's Role; Out-of-Hospital Cardiac Arrest; Quetiapine Fumarate; Return of Spontaneous Circulation; Torsades de Pointes; Unconsciousness

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

The aim was to describe the pre-diagnostic and post-diagnostic psychopharmacological treatment of bipolar disorder over the past two decades.. We identified all 16 288 individuals aged ≥ 18 years, who received their first diagnosis of bipolar disorder at a psychiatric hospital in Denmark between 1997 and 2014. For each calendar year, we calculated the proportion of patients (with index date in the respective calendar years) who were prescribed psychopharmacological treatment in the 2 years preceding and the 2 years following the date of the first diagnosis of bipolar disorder. For patients diagnosed with bipolar disorder from 2007 to 2010 (n = 3949), we described the psychopharmacological treatment from 1995 to 2016, that is, from up to 16 years prior to and up to 10 years after the diagnosis.. Concomitant use of ≥ 2 antidepressants in the 2 years preceding the bipolar disorder diagnosis increased over the study period. In the 2 years following the diagnosis, the use of lithium decreased, while use of atypical antipsychotics (particularly quetiapine), valproate, and lamotrigine increased over the study period. During the 10 years following the diagnosis, 53%-90% of the patients received any psychotropic drug while 12%-26% received treatment with an antidepressant without overlapping treatment with a mood-stabilizing drug.. The increased use of two or more antidepressants suggests more focus on bipolar disorder as a differential diagnosis to treatment-resistant unipolar depression. The decreased use of lithium (consistent with international trends) and the prevalent use of antidepressants without overlapping treatment with a drug with mood-stabilizing properties are concerning.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Psychotropic Drugs; Quetiapine Fumarate

Obsessive-compulsive disorder (OCD) is a prevalent and clinically significant comorbid condition in patients with bipolar disorder. Treatment of bipolar disorder/OCD patients is challenging. We report the results of an open-label, short-term, prospective investigation of quetiapine monotherapy in 16 patients (three men and 13 women, aged 18-56 years) hospitalized for acute bipolar depression who in addition met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for OCD. The participants were treated with quetiapine in a dose range of 150-600 mg (mean 347 mg) for a mean duration of 4.3 ± 1.4 weeks (range 3-7 weeks). Eleven (68.8%) of the 16 study participants fulfilled the predefined criteria for response, namely a score of 'very much improved' (four patients) and 'much improved' (seven patients) on the Clinical Global Impression - Improvement scale. Treatment with quetiapine was associated with a statistically significant decrease from baseline in the relevant rating scales for the assessment of depressive, manic and OCD symptoms. Quetiapine was well tolerated. The most frequently reported side effects were sedation, orthostatic hypotension and constipation. Durability of the positive therapeutic effect of quetiapine monotherapy in patients with bipolar disorder/OCD comorbidity and the necessity for subsequent augmentation with anti-OCD agents need to be addressed in future controlled studies.

Topics: Adolescent; Adult; Bipolar Disorder; Comorbidity; Female; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Prospective Studies; Quetiapine Fumarate; Treatment Outcome; Young Adult

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

Serotonergic medications are used for the prevention and treatment of depression during pregnancy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause poor neonatal adaptation, which has been attributed to withdrawal versus toxicity. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is often used as an adjunctive agent to selective serotonin reuptake inhibitors or SNRIs for refractory depression. Quetiapine, an atypical antipsychotic, may also be used in more complex cases. When combined with serotonergic drugs, bupropion and quetiapine are associated with increased risk of serotonin syndrome in adults. We describe a neonate exposed to venlafaxine (an SNRI), bupropion, and quetiapine in utero who presented nearly immediately after birth with encephalopathy and abnormal movements. The severity and rapidity of symptoms may be attributable to potentiation of venlafaxine's serotonergic effects by bupropion and quetiapine. Neonatal providers should be aware of maternal medications and prepare for possible adverse effects, particularly from common psychotropic exposures.

Topics: Antidepressive Agents; Bipolar Disorder; Brain Diseases; Bupropion; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Humans; Infant, Newborn; Male; Neurotransmitter Uptake Inhibitors; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Stress Disorders, Post-Traumatic; Venlafaxine Hydrochloride

To compare the risk of hospitalization for adult Medicaid beneficiaries with bipolar I disorder treated with lurasidone vs. other oral atypical antipsychotics (AAPs) as monotherapy.. A retrospective cohort study of the IBM MarketScan Multi-State Medicaid Claims database identified adults with bipolar I disorder who initiated an AAP (index date) between 1 January 2014 and 30 June 2019. Patients were continuously enrolled 12 months pre- and 24 months post-index date. Each month during the post-index period was categorized as monotherapy with lurasidone, aripiprazole, olanzapine, quetiapine or risperidone, no/minimal treatment, or other. Marginal structural models were performed to estimate hospitalization risk and length of stay (LOS) (all-cause and bipolar I disorder-related) compared to lurasidone.. The analysis included 8262 adults. Compared to lurasidone, the adjusted odds ratios (aORs) of all-cause hospitalization were significantly higher for olanzapine (aOR = 1.60, 95% CI = 1.09-2.10) and quetiapine (aOR = 1.54, 95% CI = 1.18-1.89). The risk was significantly higher for bipolar I disorder-related hospitalization for quetiapine (aOR = 1.57, 95% CI = 1.10-2.04) and risperidone (aOR = 1.80, 95% CI = 1.04-2.56) compared to lurasidone. The bipolar I disorder-related LOS per 100 patient-months was more than twice as long for quetiapine (8.42 days) compared to lurasidone (3.97 days,. Lurasidone-treated adult Medicaid patients with bipolar I disorder had significantly lower risk of all-cause hospitalization than those treated with olanzapine and quetiapine and lower risk of bipolar I disorder-related hospitalization than quetiapine and risperidone. Bipolar I disorder-related hospital LOS was significantly shorter for patients treated with lurasidone compared to quetiapine.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Hospitalization; Humans; Lurasidone Hydrochloride; Medicaid; Quetiapine Fumarate; Retrospective Studies; United States

The Psychopharmacology Algorithm Project at the Harvard South Shore Program (PAPHSS) published algorithms for bipolar depression in 1999 and 2010. Developments over the past 9 years suggest that another update is needed.. The 2010 algorithm and associated references were reevaluated. A literature search was conducted on PubMed for recent studies and review articles to see what changes in the recommendations were justified. Exceptions to the main algorithm for special patient populations, including those with attention-deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), substance use disorders, anxiety disorders, and women of childbearing potential, and those with common medical comorbidities were considered.. Electroconvulsive therapy (ECT) is still the first-line option for patients in need of urgent treatment. Five medications are recommended for early usage in acute bipolar depression, singly or in combinations when monotherapy fails, the order to be determined by considerations such as side effect vulnerability and patient preference. The five are lamotrigine, lurasidone, lithium, quetiapine, and cariprazine. After trials of these, possible options include antidepressants (bupropion and selective serotonin reuptake inhibitors are preferred) or valproate (very small evidence-base). In bipolar II depression, the support for antidepressants is a little stronger but depression with mixed features and rapid cycling would usually lead to further postponement of antidepressants. Olanzapine+fluoxetine, though Food and Drug Administration (FDA) approved for bipolar depression, is not considered until beyond this point, due to metabolic side effects. The algorithm concludes with a table of other possible treatments that have some evidence.. This revision incorporates the latest FDA-approved treatments (lurasidone and cariprazine) and important new studies and organizes the evidence systematically.

Topics: Algorithms; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Psychopharmacology; Quetiapine Fumarate

Topics: Adult; Agoraphobia; Antibodies, Monoclonal, Humanized; Antidepressive Agents; Antimanic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder; Depressive Disorder, Major; Female; Humans; Lithium Carbonate; Male; Mental Disorders; Middle Aged; Nordazepam; Panic Disorder; Paroxetine; Psoriasis; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Valproic Acid

The aim of this study was to describe the treatment of bipolar disorder patients in psychiatric private practices in Germany in 2009 and 2018.. This retrospective study included patients with bipolar disorder who had received at least one prescription for antidepressants, antipsychotics, antiepileptic drugs or benzodiazepines in 93 neuropsychiatric private practices in Germany between January 2009 and December 2018. Outcomes of this study were the prevalence of prescriptions for defined mood stabilizers, antipsychotics, antidepressants, and benzodiazepines, and the prevalence of mono and combination therapy in 2009 and 2018.. 1,815 and 2,322 patients with bipolar disorder were examined in 2009 and 2018, respectively. Compared to 2009, there was a decrease in the proportion of prescriptions for mood stabilizers by 2018 (58.6% to 49.5%) especially for lithium (from 31.4% to 26.2%) and an increase in the prescription of antipsychotics (38.4% in 2009 and 53.1% in 2018) and antidepressants (32.6% in 2009 and 45.1% in 2018). The share of combination therapy increased moderately from 39.3% to 41%.. Quetiapine has displaced lithium from the number one medication of the most commonly prescribed drugs in patients with bipolar disorders. The rate of patients in this study receiving monotherapy was surprisingly high.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Prescriptions; Female; Germany; Humans; Lithium; Male; Middle Aged; Prevalence; Quetiapine Fumarate; Retrospective Studies; Young Adult

Bipolar disorder is a heritable disorder, and we aimed to assess the impact of family history of mental disorders in first-degree relatives on the severity and course of bipolar disorder.. The Bipolar CHOICE (lithium versus quetiapine) and LiTMUS (optimized treatment with versus without lithium) comparative effectiveness studies were similar trials among bipolar disorder outpatients studying four different randomized treatment arms for 24 weeks. Patients self-reported on six severe mental disorders among first-degree relatives. We performed ANOVA and linear regression regarding disease severity measures, sociodemographic and cardiometabolic markers and mixed effects linear regression to evaluate treatment response.. Among 757 patients, 644 (85.1%) reported at least one first-degree relative with a severe mental disorder (mean=2.8; standard deviation=2.2; range=0-13). Depression (67.1%), alcohol abuse (51.0%) and bipolar disorder (47.0%) were the most frequently reported disorders. Familial psychiatric history correlated with several disease severity measures (hospitalizations, suicide attempts, and earlier onset) and sociodemographic markers (lower education and household income) but not with cardiometabolic markers (e.g. cholesterol or waist circumference) or cardiovascular risk scores, e.g. the Framingham risk score. Patients with familial psychiatric history tended to require more psychopharmacological treatment (p=0.054) but responded similarly (all p>0.1) to all four treatment arms.. Our findings indicate that familial psychiatric history is common among outpatients with bipolar disorder and correlates with disease severity and sociodemographic measures. Patients with a greater familial psychiatric load required more intense treatment but achieved similar treatment responses compared to patients without familial psychiatric history.

Topics: Bipolar Disorder; Humans; Lithium; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Suicide, Attempted

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

Topics: Adolescent; Antipsychotic Agents; Attention; Bipolar Disorder; Double-Blind Method; Female; Humans; Lithium; Male; Ohio; Quetiapine Fumarate

Topics: Adolescent; Antiparkinson Agents; Antipsychotic Agents; Aripiprazole; Benztropine; Bipolar Disorder; Dystonia; Humans; Lithium; Male; Marijuana Abuse; Quetiapine Fumarate; Risk-Taking

We describe a case of concomitant use of carbamazepine and quetiapine, with a highly relevant interaction that requires attention. The combination of these drugs can be prescribed in psychiatry, for example in bipolar disorder, but also in other disciplines. Pharmacotherapy is one of the cornerstones in the treatment of bipolar disorders, and a combination of drugs is frequently used. Carbamazepine, an anti-epileptic drug that is effective as a mood stabilizer, and quetiapine, a second-generation antipsychotic, are both recommended in the Dutch guideline. Besides monotherapy is a combination of both drugs possible. It is striking that carbamazepine and quetiapine have a strong pharmacokinetic interaction via the metabolizing liver enzyme, CYP3A4. This interaction results in a factor 10 reduction of quetiapine blood levels. This may result in a possible loss of clinical efficacy of quetiapine.

Topics: Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Humans; Psychotropic Drugs; Quetiapine Fumarate

To create a gene expression signature (GES) to represent the biological effects of a combination of known drugs for bipolar disorder (BD) on cultured human neuronal cells (NT2-N) and rat brains, which also has evidence of differential expression in individuals with BD. To use the GES to identify new drugs for BD using Connectivity Map (CMap).

Topics: Animals; Bipolar Disorder; Drug Repositioning; Lamotrigine; Pharmaceutical Preparations; Quetiapine Fumarate; Rats; Transcriptome

Adverse events (AEs) in clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials or across sources for a single trial may produce inconsistent information about the adverse events associated with interventions.. We compared the methods authors use to decide which AEs to include in a particular source (i.e., "selection criteria"), including the number of different types of AEs reported (i.e., rather than the number of events). We compared sources (e.g., journal articles, clinical study reports (CSRs)) of trials for two drug-indications-gabapentin for neuropathic pain and quetiapine for bipolar depression. Electronic searches were completed in 2015. We identified selection criteria and assessed how criteria affected AE reporting.. We identified 21 gabapentin and 7 quetiapine trials. We found 6 gabapentin CSRs and 2 quetiapine CSRs, all written by drug manufacturers. All CSRs reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion "occurring in ≥2% of participants in any treatment group," while only 5/316 (2%) AEs met the criterion "occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.". Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might "cherry-pick" AEs based on results. Even if investigators pre-specify selection criteria, selective reporting will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems identified in this study.

Topics: Adverse Drug Reaction Reporting Systems; Bipolar Disorder; Gabapentin; Humans; Information Dissemination; Neuralgia; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Report

Randomized trials with patient-reported outcomes are commonly plagued by missing data. The analysis of such trials relies on untestable assumptions about the missing data mechanism. To address this issue, it has been recommended that the sensitivity of the trial results to assumptions should be a mandatory reporting requirement. In this paper, we discuss a recently developed methodology (Scharfstein et al., Biometrics, 2018) for conducting sensitivity analysis of randomized trials in which outcomes are scheduled to be measured at fixed points in time after randomization and some subjects prematurely withdraw from study participation. The methodology is explicated in the context of a placebo-controlled randomized trial designed to evaluate a treatment for bipolar disorder. We present a comprehensive data analysis and a simulation study to evaluate the performance of the method. A software package entitled SAMON (R and SAS versions) that implements our methods is available at www.missingdatamatters.org .

Topics: Antidepressive Agents; Bipolar Disorder; Data Interpretation, Statistical; Humans; Patient Reported Outcome Measures; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Software

Topics: Antipsychotic Agents; Bipolar Disorder; Cost-Benefit Analysis; Folic Acid; Humans; Lamotrigine; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Cost-Benefit Analysis; Folic Acid; Humans; Lamotrigine; Quetiapine Fumarate

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Drug Therapy, Combination; Humans; Male; Middle Aged; Olfaction Disorders; Quetiapine Fumarate; Taste Disorders; Valproic Acid

Lithium and quetiapine are known to be effective treatments for bipolar disorder. However, little information is available to inform prediction of response to these medications. Machine-learning methods can identify predictors of response by examining variables simultaneously. Further evaluation of models on a test sample can estimate how well these models would generalize to other samples.. Data (N = 482) were drawn from a randomized clinical trial of outpatients with bipolar I or II disorder who received adjunctive personalized treatment plus either lithium or quetiapine. Elastic net regularization (ENR) was used to generate models for lithium and quetiapine; these models were evaluated on a test set.. Predictions from the lithium model explained 17.4% of the variance in actual observed scores of patients who received lithium in the test set, while predictions from the quetiapine model explained 32.1% of the variance of patients that received quetiapine. Of the baseline variables selected, those with the largest parameter estimates were: severity of mania; attention-deficit/hyperactivity disorder (ADHD) comorbidity; nonsuicidal self-injurious behavior; employment; and comorbidity with each of two anxiety disorders (social phobia/society anxiety and agoraphobia). Predictive accuracy of the ENR model outperformed the simple and basic theoretical models.. ENR is an effective approach for building optimal and generalizable models. Variables identified through this methodology can inform future research on predictors of response to lithium and quetiapine, as well as future modeling efforts of treatment choice in bipolar disorder.

Topics: Adult; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Comorbidity; Female; Humans; Lithium Compounds; Machine Learning; Male; Models, Biological; Precision Medicine; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.. Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.. Compared to participants with WBC counts of 4.5-10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.. An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.

Topics: Adult; Affect; Antimanic Agents; Bipolar Disorder; Female; Humans; Leukocyte Count; Lithium; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome; Young Adult

Bipolar patients experience sleep disturbances during and between mood episodes. Yet the impact of sleep on treatment with different medications has not been fully explored. The purpose of this paper is to explore the potential impact of poor sleep at baseline on outcomes in a randomized effectiveness trial of quetiapine and lithium.. The Bipolar CHOICE study was a 6-month, parallel group, multisite randomized controlled trial. Participants with bipolar disorder (N = 482; 59% female and age 18-70 years) received quetiapine or lithium. Patients were allowed to also receive adjunctive personalized treatments, which were guideline-informed, empirically-based medications added to treatment as needed. Medication changes were recorded as necessary clinical adjustments (NCA). Fisher's exact tests, mixed-regression models, and Mann-Whitney U tests were used to assess demographic and clinical characteristics as well as whether sleep disturbance would predict outcomes.. 63% of patients had baseline sleep disturbance. Individuals with sleep disturbance had worse bipolar illness severity, greater severity of depression, mania, anxiety, irritability, and psychosis, were less likely to have sustained response (17% vs. 29%; adjusted RR: 0.55, 95% CI: 0.38-0.78, p = 0.0006) and had more NCAs (median 0.71 vs. 0.59, p = 0.03).. Our findings were limited by how we defined sleep disturbance, and by how severity of sleep disturbance was assessed with one item with a non-sleep specific measure.. Baseline sleep disturbance was associated with more severe bipolar symptoms and worse 6-month outcomes. Further research is warranted on improving sleep in bipolar disorder, especially the role of psychosocial interventions.

Topics: Adolescent; Adult; Affect; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Choice Behavior; Female; Humans; Irritable Mood; Lithium Compounds; Male; Middle Aged; Psychotic Disorders; Quetiapine Fumarate; Sleep Wake Disorders; Treatment Outcome

Quetiapine is effective in treating depressive symptoms in major depressive disorder and bipolar disorder, but the mechanisms underlying its antidepressants effects are unknown. Norquetiapine, a metabolite of quetiapine, has high affinity for norepinephrine transporter, which might account for its therapeutic efficacy.. In this study, we used positron emission tomography with (S,S)-[11C]O-methyl reboxetine to estimate norepinephrine transporter density and assess the relationship between norepinephrine transporter occupancy by quetiapine XR and improvement in depression in patients with major depressive disorder (n=5) and bipolar disorder (n=5). After the baseline positron emission tomography scan, patients were treated with quetiapine XR with a target dose of 150 mg in major depressive disorder and 300 mg in bipolar disorder. Patients had a second positron emission tomography scan at the end of week 2 and a final scan at week 7.. Norepinephrine transporter density was significantly lower in locus ceruleus in patients compared with healthy subjects. Further, there was a significant positive correlation between quetiapine XR dose and norepinephrine transporter occupancy in locus ceruleus at week 2. The norepinephrine transporter occupancy at week 2 in hypothalamus but not in other regions predicted improvement in depression as reflected by reduction in MADRS scores from baseline to week 7. The estimated dose of quetiapine XR associated with 50% norepinephrine transporter occupancy in hypothalamus at week 2 was 256 mg and the estimated plasma levels of norquetiapine to achieve 50% norepinephrine transporter occupancy was 36.8 µg/L.. These data provide preliminary support for the hypothesis that norepinephrine transporter occupancy by norquetiapine may be a contributor to the antidepressant effects of quetiapine.

Topics: Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Dibenzothiazepines; Female; Humans; Hypothalamus; Locus Coeruleus; Male; Middle Aged; Norepinephrine Plasma Membrane Transport Proteins; Positron-Emission Tomography; Quetiapine Fumarate; Reboxetine; Young Adult

Data for individual trials included in systematic reviews may be available in multiple sources. For example, a single trial might be reported in 2 journal articles and 3 conference abstracts. Because of differences across sources, source selection can influence the results of systematic reviews. We used our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study, and evidence from previous studies, to develop practical guidance for using multiple data sources in systematic reviews. We recommend the following: (1) Specify which sources you will use. Before beginning a systematic review, consider which sources are likely to contain the most useful data. Try to identify all relevant reports and to extract information from the most reliable sources. (2) Link individual trials with multiple sources. Write to authors to determine which sources are likely related to the same trials. Use a modified Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flowchart to document both the selection of trials and the selection of sources. (3) Follow a prespecified protocol for extracting trial characteristics from multiple sources. Identify differences among sources, and contact study authors to resolve differences if possible. (4) Prespecify outcomes and results to examine in the review and meta-analysis. In your protocol, describe how you will handle multiple outcomes within each domain of interest. Look for outcomes using all eligible sources. (5) Identify which data sources were included in the review. Consider whether the results might have been influenced by data sources used. (6) To reduce bias, and to reduce research waste, share the data used in your review.

Topics: Amines; Bipolar Disorder; Clinical Trials as Topic; Cyclohexanecarboxylic Acids; Data Collection; Gabapentin; gamma-Aminobutyric Acid; Humans; Information Storage and Retrieval; Meta-Analysis as Topic; Neuralgia; Quetiapine Fumarate; Research Report; Review Literature as Topic; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Pregnancy; Pregnancy Complications; Puerperal Disorders; Quetiapine Fumarate; Young Adult

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

Complaints of hypoglycemia resemble the sedative effect of antipsychotics. As such, clinicians may overlook hypoglycemia in patients with psychiatric disorders. Here, a case of hypoglycemia associated with hyperinsulinemia induced by quetiapine in a female patient with bipolar disorder is reported. The case suggests that clinicians should be aware of the potential for hypoglycemia induced by second-generation antipsychotics.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Diagnostic Errors; Female; Humans; Hypoglycemia; Middle Aged; Quetiapine Fumarate

Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations.. To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder.. This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N = 18 018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was used as his or her own control to eliminate selection bias. The study adjusted for the effect of concomitant psychotropic medications, duration of illness, and the temporal orders of exposure and nonexposure periods. Statistical analysis was conducted from January 1, 1996, to December 31, 2012.. Adjusted hazard ratios (HRs) for rehospitalization were calculated.. Among the cohort (9558 women and 8460 men; mean [SD] age, 46.6 [17.0] years), 9721 patients (54.0%) had at least 1 psychiatric rehospitalization. In comparison between use and no use among specific agents reaching nominal statistical significance, risperidone long-acting injection (HR, 0.58 [95% CI, 0.34-1.00]), gabapentin (HR, 0.58 [95% CI, 0.44-0.77]), perphenazine long-acting injection (HR, 0.60 [95% CI, 0.41-0.88]), and lithium carbonate (HR, 0.67 [95% CI, 0.60-0.73]) were associated with the lowest risk of psychiatric rehospitalization. Concerning all-cause hospitalization, lithium (HR, 0.71 [95% CI, 0.66-0.76]) was associated with the lowest risk. The most frequently used antipsychotic treatment, quetiapine fumarate, showed only modest effectiveness (risk of psychiatric rehospitalization: HR, 0.92 [95% CI, 0.85-0.98]; risk of all-cause hospitalization: HR, 0.93 [95% CI, 0.88-0.98]). Long-acting injections were associated with substantially better outcomes compared with identical oral antipsychotics (risk of psychiatric rehospitalization: HR, 0.70 [95% CI, 0.55-0.90]; risk of all-cause hospitalization: HR, 0.70 [95% CI, 0.57-0.86]). Results from sensitivity analyses showed consistent beneficial effects only for lithium and for long-acting injections compared with their oral counterparts.. Lithium was the most effective mood stabilizer, and long-acting injections the most effective antipsychotics, in preventing hospitalization due to mental or physical illness.

Topics: Administration, Oral; Adult; Bipolar Disorder; Cohort Studies; Delayed-Action Preparations; Drug Therapy, Combination; Female; Follow-Up Studies; Gabapentin; Humans; Injections, Intramuscular; Lithium Carbonate; Male; Middle Aged; Patient Readmission; Perphenazine; Prospective Studies; Psychotropic Drugs; Quetiapine Fumarate; Risk; Risperidone; Treatment Outcome

To evaluate the impact of 2 policy changes on quetiapine dispensing in Australia: removal of prior authorisation for prescribing (policy 1: July 2007) and removal of repeat prescriptions for 25-mg quetiapine (policy 2: January 2014).. We performed an interrupted time series analysis using Pharmaceutical Benefits Scheme claims data (July 2005 to December 2015). We assessed the impact of both policies on monthly quetiapine dispensing (25 mg and >25 mg) and the impact of policy change 2 on monthly rates of 25-mg discontinuation and switching from 25 mg to other quetiapine strengths. We also estimated the impact of both policies on the proportion of people with potentially inappropriate therapy (no evidence of dose escalation) following 25-mg initiation.. Following removal of prior authorisation, 25-mg and >25-mg quetiapine dispensing in the Pharmaceutical Benefits Scheme 10% sample increased by 11/month (95% CI: 2-21) and 14/month (95% CI: 8-20), respectively. After removing 25-mg repeats, there was a permanent decrease of 1072 (95% CI 773-1371) dispensings and an increase in discontinuation of this strength; 48% of people dispensed the 25-mg strength that discontinued, discontinued quetiapine completely; the remainder continued to use higher quetiapine strengths. We observed minimal switching to other quetiapine strengths. There was no change in inappropriate 25-mg therapy following policy change 1 and a small decrease (79% to 76%, P = 0.05) following policy change 2.. More nuanced policies are needed to ensure the appropriate access to 25-mg quetiapine for dose escalation while discouraging use for indications where the evidence of risk and benefit is unclear.

Topics: Antipsychotic Agents; Anxiety; Australia; Bipolar Disorder; Dose-Response Relationship, Drug; Drug and Narcotic Control; Drug Prescriptions; Drug Utilization; Drug Utilization Review; Humans; Interrupted Time Series Analysis; Off-Label Use; Policy Making; Practice Patterns, Physicians'; Quetiapine Fumarate; Schizophrenia; Sleep Initiation and Maintenance Disorders

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium Compounds; Quetiapine Fumarate; Time-to-Treatment

Topics: Antipsychotic Agents; Bipolar Disorder; Child; Female; Humans; Pancreatitis; Quetiapine Fumarate

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

The development of mania during weaning is an underreported phenomenon that has received little attention in the recent past. Lack of timely diagnosis and effective management can negatively affect not only the mother but also her family. Main issue: I describe the case of a woman who experienced onset of mixed mania during weaning. At that time, she was diagnosed with bipolar I disorder, current episode manic, and a mixed-features specifier. The woman had a history of bipolar II disorder and a family history of postpartum depression and bipolar disorder.. I prescribed quetiapine 200 mg at bedtime, and symptoms resolved within a couple of days. The woman is still taking the prescribed dose and has not had any recurrences since.. Weaning may act as a trigger for mixed mania, especially for women who have a history of bipolar disorder. Careful monitoring should occur during weaning for mothers with risk factors for bipolar disorder. Early recognition of symptoms and aggressive management is necessary to prevent hospitalization.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Breast Feeding; Female; Humans; Quetiapine Fumarate; Weaning

The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls. Patients were randomly assigned to treatment with quetiapine or lithium after pretreatment data collection. A hierarchical cluster analysis was performed using pretreatment cortical thickness data that identified two discrete patient subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed widespread greater cortical thickness mainly across heteromodal cortex but also involving some regions of unimodal cortex, while those in subgroup 2 (n = 36) showed regional cortical thinning mainly in superior temporal and superior parietal regions. Patients within subgroup 1 showed a significantly higher response rate to quetiapine than those in subgroup 2 (100% vs 53%). No statistically significant difference was found in lithium response rate between the patient subgroups (63% vs 53%). Pretreatment clinical ratings and neuropsychological data did not differ across subgroups. Our findings suggest the existence of distinct and clinically relevant subgroups of pediatric bipolar patients, as defined by pattern of cortical thickness. These groups appear to differentially respond to antipsychotic treatment-notably with greater cortical thickness relative to controls predicting better treatment response.

Topics: Adolescent; Antidepressive Agents; Bipolar Disorder; Cerebral Cortex; Child; Female; Humans; Lithium Carbonate; Magnetic Resonance Imaging; Male; Organ Size; Predictive Value of Tests; Quetiapine Fumarate; Treatment Outcome

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

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Colitis, Ischemic; Female; Humans; Quetiapine Fumarate

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

The aim of this study was to analyze the relationships between quetiapine and N-desalkylquetiapine plasma levels and clinical improvement, particularly, in regard to depressive and anxious symptoms and to hostility.. This was a prospective observational study that involved 37 outpatients diagnosed as having bipolar disorder I or II. All the patients were observed during a clinical acute and postacute phase. Patients were prescribed 50-800 mg of quetiapine. Patients were evaluated at baseline, after 15 days and after 3 months using the Brief Psychiatry Rating Scale with particular reference to the dimensions of depression, anxiety, and hostility. The plasma concentrations of quetiapine and N-desalkylquetiapine were determined after 3 months using blood samples taken at steady state.. There was a significant relationship between the N-desalkylquetiapine/quetiapine ratio and the improvement in the depression dimension, and there was not a significant relationship between the N-desalkylquetiapine/quetiapine ratio and anxiety and hostility improvement. Quetiapine treatment was well tolerated, and there were no extrapyramidal, anticholinergic, or other side effects to note. There was no relationship between plasma quetiapine or N-desalkylquetiapine concentrations and side effects.. Our findings confirm the efficacy of quetiapine on depressive symptoms, and the available data support that quetiapine's antidepressant activity is mediated by the active metabolite norquetiapine, and it exemplifies the case of an active metabolite that can make a drug like quetiapine originally introduced as an antipsychotic a useful antidepressant agent.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Anxiety; Bipolar Disorder; Depression; Female; Humans; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Treatment Outcome

Bipolar disorder (BD) spectrum and alcohol use disorders (AUDs) commonly occur together. Comorbidity between the two conditions predisposes patients to elevated risks of adverse outcomes, including hospitalization and suicide, compared with either condition alone. Despite the consistent relationship observed between BD and AUD, the underlying cause remains incompletely characterized. Few trials conducted have been able to identify promising interventions for patients with these disease states. The antipsychotic quetiapine has been evaluated most commonly as a therapeutic agent for patients with BD and AUD followed by naltrexone and acamprosate. Randomized controlled trials of quetiapine have consistently reported a lack of efficacy for the treatment of patients with BD and AUD. Trials of acamprosate have also been negative but small in size. Results of the sole randomized controlled trial of naltrexone have found large treatment effect sizes, but no statistically significant difference between treatment groups. Other agents including the antipsychotic aripiprazole, mood stabilizing agents including lamotrigine, lithium, and divalproex, and the antiepileptic agent topiramate have also been evaluated for the treatment of BD and AUD with mixed findings. The lone statistically significant treatment effect was observed in a randomized, placebo-controlled trial of divalproex added on to lithium which demonstrated a reduction in alcohol use. This review summarizes the available clinical evidence and current guideline recommendations for the treatment of comorbid BD and AUD, and provides discussion and recommendations based on the current literature.

Topics: Alcoholism; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Comorbidity; Humans; Quetiapine Fumarate; Valproic Acid

Topics: Accidental Falls; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Middle Aged; Quetiapine Fumarate; Skull Fractures; Vertigo

Topics: Antipsychotic Agents; Bipolar Disorder; Female; Hepatitis; Humans; Jaundice; Middle Aged; Quetiapine Fumarate

Topics: Antidepressive Agents; Antimanic Agents; Bipolar Disorder; Carbamazepine; Delirium; Depression; Dose-Response Relationship, Drug; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Electroconvulsive Therapy; Female; Humans; Lithium Compounds; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

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

Carbamazepine and quetiapine are drugs that are used as mood stabilizers in the treatment of bipolar disorders. A series of studies has shown that concurrent use of carbamazepine decreases quetiapine serum level due to induction of CYP3A enzymes by carbamazepine.. In a 30-year-old bipolar patient with mania treated with quetiapine 1200 mg and carbamazepine 900 mg per day, we measured quetiapine serum level before and after carbamazepine withdrawal.. No serum quetiapine was detected during concurrent use of carbamazepine and was lower than the therapeutic range almost 2 weeks after carbamazepine withdrawal. The patient suffered from sedation when her serum level of quetiapine was 181 ng/ml and because she was quiet we started slowly to decrease to a quetiapine dose of 600 mg. Her serum level (45 ng/ml) was again below therapeutic levels after 3 weeks of carbamazepine withdrawal.. We hypothesize that induction of CYP3A lasts even after carbamazepine withdrawal. Our hypothesis was confirmed during the next treatment of mania. The patient had been off carbamazepine for 1 year and her serum level was four times higher (210 ng/ml) on 600 mg of quetiapine than 3 weeks after carbamazepine withdrawal. The influence of carbamazepine on CYP3A enzymes lasted at least 3 weeks after carbamazepine withdrawal which is in accordance with CYP3A de-induction lasting 3 weeks. This could be important information for psychiatrists to know that in some patients it is better to use a minimum washout period of 3 weeks for carbamazepine before new treatment with quetiapine.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Drug Interactions; Female; Humans; Quetiapine Fumarate

The aim of the present paper is to open the discourse regarding the unmet needs of specific patients, especially those with substance use disorder and/or personality disorder where 'multimorbidities', and/or 'overdiagnosis' and/or 'diagnosis overlap' are frequent. An additional aim is to review the main therapeutic purpose and concepts of Gestalt therapy which might be appropriate in the treatment of these patients often characterized by their difficulties in being aware and in contact in the 'here and now'.. I first start with an overview of Gestalt therapy concepts. Then, I illustrate Gestalt's 'here and now' and awareness concepts applied during 18 sessions with an inpatient diagnosed with substance use and bipolar disorders. In addition, the patient had to face an open criminal charge, was regarded as having an antisocial personality disorder and argued suffering from post-traumatic stress disorder.. After this two-month therapy period, the patient entered for the first time a daily rehabilitation program in the community, where he was doing well (this after a few prior hospitalizations). The awareness development in the 'here and now' through which different contact styles and cycles of experiences are experienced is a process that allowed the patient to start experiencing contact with himself, his true needs and his environment. This contributed to his well-being improvement, led and supported his rehabilitation and reinsertion within the society and decrease his relapses, either with drugs or criminal activities. Copyright © 2016 John Wiley & Sons, Ltd.. People with substance use disorder (where 'multimorbidities', 'overdiagnosis' or 'diagnosis overlap' are frequent), people with personality disorder(s) or people who have difficulties in defining what really disturbs them are the same people who could benefit of GT encouraging awareness and contact development in the 'here and now'. Gestalt therapy should not be regarded as a practitioner's toolbox but as a therapeutic process allowing awareness and I-boundaries development in the 'here and now' through authentic and genuine relationships. The therapist's awareness and contact with themselves and their environment are reflected in the therapist's relaxed but awake and aware state of mind as well as their wise, spontaneous and mindful approach.

Topics: Adult; Antisocial Personality Disorder; Awareness; Bipolar Disorder; Child; Child Abuse; Combined Modality Therapy; Comorbidity; Diagnosis, Dual (Psychiatry); Follow-Up Studies; Gestalt Therapy; Hospitalization; Humans; Illicit Drugs; Israel; Life Change Events; Male; Quetiapine Fumarate; Substance-Related Disorders

We present the case of two healthy infants born to a bipolar female maintained on low-dose lamotrigine and quetiapine.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Infant, Newborn; Lamotrigine; Pregnancy; Pregnancy Outcome; Quetiapine Fumarate; Treatment Outcome; Triazines

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

Brugada pattern can be found on the electrocardiogram (ECG) of patients with altered mental status, usually with fever or drug intoxication. Diagnosis remains challenging, because the ECG changes are dynamic and variable. In addition, triggers are not always clearly identified. In patients with atrial fibrillation (AF), the use of class IC antidysrhythmic drugs can unmask a Brugada pattern on the ECG, especially if combined with other medications acting on sodium channels.. A 62-year-old man with a medical history of AF was admitted to our emergency department for altered mental status. The ECG at the time of admission showed a Brugada pattern, triggered by a flecainide overdose (about 1 g), in association with an unknown dose of lamotrigine and quetiapine. After discontinuation of all medications, the Brugada pattern disappeared and his ECG showed no abnormalities. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients with AF, the use of class IC antidysrhythmic drugs, if overdosed, can trigger a Brugada ECG pattern, and therefore it can increase the risk for malignant dysrhythmias. It is important to provide, to all patients with a Brugada ECG pattern, a list of drugs to avoid, and to underline the synergistic interplay between drugs, taking into consideration all patients' comorbidities.

Topics: Atrial Fibrillation; Bipolar Disorder; Brugada Syndrome; Consciousness Disorders; Drug Overdose; Electrocardiography; Emergency Service, Hospital; Flecainide; Humans; Lamotrigine; Male; Middle Aged; Quetiapine Fumarate; Sodium Channel Blockers; Stroke; Suicide, Attempted; Triazines

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

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

We report a 78-year-old man without past psychiatric history who experienced his first manic episode successfully treated with quetiapine and lorazepam, but was ultimately found to have AIDS and Cryptococcus neoformans meningitis. Our presented case highlights the importance of comprehensive differential diagnoses to rule out secondary causes of psychiatric symptoms presenting for the first time in elderly patients.

Topics: Aged; AIDS-Related Opportunistic Infections; Antipsychotic Agents; Bipolar Disorder; Cryptococcus neoformans; Diagnosis, Differential; Humans; Lorazepam; Male; Meningitis, Cryptococcal; Quetiapine Fumarate; Treatment Outcome

Topics: Bipolar Disorder; Female; Humans; Lithium; Male; Quetiapine Fumarate

Quetiapine is an atypical antipsychotic that can stabilise mood from any index episode of bipolar disorder. This study investigated the effects of seven-day quetiapine administration on sleep, circadian rhythms and emotional processing in healthy volunteers.. Twenty healthy volunteers received 150 mg quetiapine XL for seven nights and 20 matched controls received placebo. Sleep-wake actigraphy was completed for one week both pre-dose and during drug treatment. On Day 8, participants completed emotional processing tasks.. Actigraphy revealed that quetiapine treatment increased sleep duration and efficiency, delayed final wake time and had a tendency to reduce within-day variability. There were no effects of quetiapine on subjective ratings of mood or energy. Quetiapine-treated participants showed diminished bias towards positive words and away from negative words during recognition memory. Quetiapine did not significantly affect facial expression recognition, emotional word categorisation, emotion-potentiated startle or emotional word/faces dot-probe vigilance reaction times.. These changes in sleep timing and circadian rhythmicity in healthy volunteers may be relevant to quetiapine's therapeutic actions. Effects on emotional processing did not emulate the effects of antidepressants. The effects of quetiapine on sleep and circadian rhythms in patients with bipolar disorder merit further investigation to elucidate its mechanisms of action.

Topics: Adolescent; Adult; Affect; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Circadian Rhythm; Emotions; Facial Expression; Female; Healthy Volunteers; Humans; Male; Memory; Quetiapine Fumarate; Reaction Time; Sleep; Sleep Wake Disorders; Young Adult

A post-authorisation safety study was carried out as part of the EU Risk Management Plan to examine the long-term (up to 12 months) use of quetiapine XL as prescribed in general practice in England.. To present a description of the drug utilisation characteristics of quetiapine XL.. An observational, population-based cohort design using the technique of Modified Prescription-Event Monitoring (M-PEM). Patients were identified from dispensed prescriptions issued by general practitioners (GPs) for quetiapine XL between September 2008 and February 2013. Questionnaires were sent to GPs 12 months following the 1st prescription for each individual patient, requesting drug utilisation information. Cohort accrual was extended to recruit additional elderly patients (special population of interest). Summary descriptive statistics were calculated.. The final M-PEM cohort consisted of 13,276 patients; median age 43 years (IQR: 33, 55) and 59.0% females. Indications for prescribing included bipolar disorder (n=3820), MDD (n=2844), schizophrenia (n=2373) and other (non-licensed) indications (n=3750). Where specified, 59.3% (7869/13,276) were reported to have used quetiapine IR (immediate release formulation) previously at any time. The median start dose was highest for patients with schizophrenia (300 mg/day [IQR 150, 450]). The final elderly cohort consisted of 3127 patients and 28.5% had indications associated with dementia. The median start dose for elderly patients was highest for patients with schizophrenia or BD (both 100mg/day [IQR 50, 300]).. The prevalence of off-label prescribing in terms of indication and high doses was common, as was use in special populations such as the very elderly. Whilst off-label use may be unavoidable in certain situations, GPs may need to re-evaluate prescribing in circumstances where there may be safety concerns. This study demonstrates the ongoing importance of observational studies such as M-PEM to gather real-world clinical data to support the post-marketing benefit:risk management of new medications, or existing medications for which license extensions have been approved.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Cohort Studies; Drug Utilization; England; Female; General Practice; Humans; Long Term Adverse Effects; Male; Middle Aged; Needs Assessment; Practice Patterns, Physicians'; Product Surveillance, Postmarketing; Quetiapine Fumarate; Schizophrenia; Surveys and Questionnaires

The first weeks of treatment with antipsychotics are important for the development of their long-term efficacy. The objective of this study was to identify factors related to early clinical effects and quality of life (QoL) improvements with quetiapine extended-release (XR).. Six hundred and sixty-five patients starting with quetiapine XR were followed up for 8 weeks (schizophrenia = 153, major depression = 200, bipolar depression = 252, other psychiatric conditions = 60). Clinical effects were assessed by the Clinical Global Impression of Change scale (CGI-C), QoL by the visual analog scale (VAS) of the EQ-5D (QoL-VAS), and adherence by the Moriksy scale. Adverse events were explored: movement disorders by the UKU and Simpson-Angus scales, weight gain by calibrated balances, and diurnal somnolence by the Epworth Somnolence Scale (ESS).. The mean dose of quetiapine XR during follow-up was 195.6 ± 154.8 mg/day. CGI and QoL-VAS scores improved significantly at week 8 by 2.7 ± 0.1 points and 25.1 ± 0.9 points. Adverse events were observed in 34 and 26 % of patients at weeks 4 and 8, respectively. A significant reduction in ESS score was also observed at week 8. Factors independently associated with change in QoL-VAS ≥20 points (n = 292, 43 %) were female gender, more severe disease at baseline, higher antipsychotic dose during follow-up, and improvements in somnolence. Factors independently associated with clinically significant improvement (CGI-C ≥5, n = 610, 93 %) were greater change in QoL-VAS, less frequent movement disorders at baseline, and lack of adverse events during follow-up, especially somnolence.. Results from this real-setting, large observational study in Central America suggest that disease severity at baseline, gender, antipsychotic dose, and occurrence of adverse reactions has a significant impact on the early clinical effects of quetiapine XR. Clinicaltrials.gov registration number NCT02409823.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Patient Compliance; Prospective Studies; Psychotic Disorders; Quality of Life; Quetiapine Fumarate; Schizophrenia; Sleep Stages; Treatment Outcome; Weight Gain

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

Topics: Anti-Bacterial Agents; Bipolar Disorder; Diuretics; Female; Heart Failure; Humans; Inappropriate Prescribing; Pneumonia; Quetiapine Fumarate; Torsades de Pointes

Topics: Anti-Bacterial Agents; Bipolar Disorder; Diuretics; Female; Heart Failure; Humans; Inappropriate Prescribing; Pneumonia; Quetiapine Fumarate; Torsades de Pointes

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

To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania.. Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA.. The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P > 0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P < 0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P < 0.05).. Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.

Topics: Aggression; Antipsychotic Agents; Biomarkers; Bipolar Disorder; Case-Control Studies; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Humans; Interleukin-17; Lithium Compounds; Quetiapine Fumarate; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Folic Acid; Humans; Lamotrigine; Quetiapine Fumarate; Triazines

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

Topics: Adult; Antimanic Agents; Bipolar Disorder; Depression, Postpartum; Female; Humans; Lamotrigine; Postpartum Period; Quetiapine Fumarate; Triazines; Young Adult

Evaluate the impact of quetiapine extended release (XR) versus quetiapine immediate release (IR) on hospitalization length in acute bipolar mania using Truven Health Analytics MarketScan Hospital Drug Database.. Generalized linear model analyses were used, adjusting for patient and hospital characteristics.. Using data from 3088 discharges, quetiapine XR reduced hospitalization length by 6.7% versus quetiapine IR (p = 0.11; no statistically significant differences between groups), corresponding to 0.6 fewer days in hospital. Excluding the outlier, quetiapine XR significantly reduced hospitalization length by 9.6% versus quetiapine IR (p = 0.02), corresponding to 0.9 days.. Inpatient use of quetiapine XR in acute bipolar mania may be associated with reduced hospitalization length (7-10%), possibly owing to the faster titration schedule versus quetiapine IR.

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Comparative Effectiveness Research; Delayed-Action Preparations; Dibenzothiazepines; Female; Hospitalization; Humans; Length of Stay; Male; Quetiapine Fumarate; Retrospective Studies

Oxidative stress is defined as exposure to excessive oxidants and/or decrease in antioxidant capacity. Several studies have shown the effects of free radicals and antioxidant defense systems in bipolar disorder. We aimed to investigate the role of thioredoxin (TRX), which is a novel oxidative stress marker in patients with bipolar disorder.. Sixty-eight hospitalized bipolar patients who were in manic episode were included in the study. As a control group, 30 healthy people were elected. Two groups were formed. The first group consisted of patients who were undergoing electroconvulsive treatment + antipsychotic treatment (haloperidol+quetiapine) and members of the other group were taking only antipsychotic treatment. Plasma thioredoxin levels were measured before and after treatment.. Pretreatment plasma TRX levels of patients were significantly lower than the controls (P < 0.05). Comparing pre- and post-treatment plasma TRX levels of all patients, post-treatment plasma TRX levels were significantly lower than the pre-treatment plasma TRX levels (P < 0.05). When we compared TRX levels between the electroconvulsive treatment + antipsychotic treatment group and the antipsychotic treatment group (P > 0.05) and within groups (P > 0.05) we did not find any statistically significant difference.. Oxidative balance is impaired in bipolar disorder manic episode in favor of the oxidants. Decreased plasma TRX levels in the manic episode probably mean that antioxidant capacity is decreased in the bipolar disorder patients in the manic episode. Further studies in euthymic and depressive states are also needed to gain more insight into the role of TRX in bipolar disorder.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Case-Control Studies; Combined Modality Therapy; Electroconvulsive Therapy; Haloperidol; Humans; Male; Middle Aged; Oxidative Stress; Quetiapine Fumarate; Thioredoxins

Several lines of evidence suggest that abnormalities within portions of the extended limbic network involved in affective regulation and expression contribute to the neuropathophysiology of bipolar disorder. In particular, portions of the prefrontal cortex have been implicated in the appearance of manic symptomatology. The effect of atypical antipsychotics on activation of these regions, however, remains poorly understood.. Twenty-two patients diagnosed with bipolar mania and 26 healthy subjects participated in a baseline functional magnetic resonance imaging scan during which they performed a continuous performance task with neutral and emotional distractors. Nineteen patients with bipolar disorder were treated for eight weeks with quetiapine monotherapy and then rescanned. Regional activity in response to emotional stimuli was compared between healthy and manic subjects at baseline; and in the subjects with bipolar disorder between baseline and eight-week scans.. At baseline, functional activity did not differ between subjects with bipolar disorder and healthy subjects in any region examined. After eight weeks of treatment, subjects with bipolar disorder showed a significant decrease in ratings on the Young Mania Rating Scale (YMRS) (p < 0.001), and increased activation in the right orbitofrontal cortex (OFC) (p = 0.002); there was a significant association between increased right OFC activity and YMRS improvement (p = 0.003).. These findings are consistent with suggestions that mania involves a loss of emotional modulatory activity in the prefrontal cortex--restoration of the relatively greater elevation in prefrontal activity widely observed in euthymic patients is associated with clinical improvement. It is not clear, however, whether changes are related to quetiapine treatment or represent a non-specific marker of affective change.

Topics: Adolescent; Adult; Affect; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prefrontal Cortex; Quetiapine Fumarate; Young Adult

Growing evidence suggests that immune dysfunction may be involved in the physiopathology of bipolar disorders, with typical first-line treatment using lithium and quetiapine serving to restore pro-inflammation status. This study aimed to explore the relationship between inflammatory cytokines-especially regulatory factors and the effect of combination treatment-with quetiapine and lithium in manic patients.. 41 patients of bipolar I disorder with manic episode were enrolled and received combination treatment with quetiapine and lithium. Blood sampling and assessments were performed at baseline and after 8-week treatment. YMRS was used to evaluate the severity of manic symptoms at the same time of detecting plasma levels. A control group comprised of 36 age and gender matched healthy volunteers were enrolled, and their blood samples were assessed at the time of enrollment.. TGF-β1 and IL-23 plasma levels in patients were significantly higher than healthy controls at baseline (P<0.05). When comparing remitted patients with non-remitted patients, initial plasma level TGF-β1 was higher (P=0.029) while IL-23 was lower (P=0.035). The plasma levels of TNF-α, TGF-β1, IL-23 and IL-17 significantly decreased after treatment among the patients who achieved response (P<0.05).. The relatively small sample size in patients and control groups should be considered as a limitation of the study.. The high initial plasma level of TGF-β1 and low initial plasma level of IL-23 indicated better prognosis during combination treatment with quetiapine and lithium in manic patients. The trend of decreasing plasma levels of TNF-α, TGF-β1, IL-23 and IL-17 indicated therapeutic effect.

Topics: Adult; Antipsychotic Agents; Biomarkers; Bipolar Disorder; Case-Control Studies; Dibenzothiazepines; Female; Humans; Interleukin-17; Interleukin-23; Lithium Compounds; Male; Middle Aged; Predictive Value of Tests; Prognosis; Quetiapine Fumarate; Severity of Illness Index; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

An 18-year-old man diagnosed with attention-deficit hyperactivity disorder was recently started on quetiapine in addition to regular methylphenidate, which he had been taking for a number of years. He presented with chest pain and inferolateral ST elevation, and underwent urgent coronary angiography, which showed normal coronary arteries. The initial troponin level was raised and an inpatient echocardiogram showed mild left ventricular systolic dysfunction with no evidence of regional wall motion abnormality. Cardiac MRI showed subepicardial late gadolinium enhancement, which was suggestive of myocarditis. Quetiapine and methylphenidate were discontinued and the patient was discharged home after 1 week. He was followed up within 8 weeks with complete recovery and no symptoms.

Topics: Adolescent; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Chest Pain; Diagnosis, Differential; Dibenzothiazepines; Dopamine Uptake Inhibitors; Humans; Male; Methylphenidate; Myocardial Infarction; Myocarditis; Quetiapine Fumarate; Treatment Outcome

Topics: Analgesics, Opioid; Antidepressive Agents, Second-Generation; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Citalopram; Depressive Disorder; Drug Interactions; Humans; Lithium Compounds; Low Back Pain; Male; Middle Aged; Quetiapine Fumarate; Sulfates; Tramadol

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Hypothyroidism; Infant, Newborn; Infant, Newborn, Diseases; Lamotrigine; Maternal-Fetal Exchange; Phenobarbital; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Substance Withdrawal Syndrome; Triazines

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

This study examines characteristics of individuals with bipolar disorder who sought psychotherapy versus those who did not.. Bipolar CHOICE was an 11-site comparative effectiveness study of lithium versus quetiapine in symptomatic outpatients (N = 482) with bipolar disorder. At baseline, participants' psychotherapy use within the past 3 months, mood, functioning, and overall health were assessed. Logistic regressions were used to test whether psychotherapy users and non-users differed on various demographic and clinical variables at baseline. Mixed-effects regression was used to determine whether psychotherapy groups differed on response to treatment over the 6-month study. Kaplan-Meier plots and log-rank tests were employed to test whether there were any differences in time to recovery (CGI-BP ≤ 2 for at least 8 weeks) between the groups.. Thirty one percent of participants reported using psychotherapy services. Psychotherapy users reported greater medication side effect burden than non-users and were more likely to have moderate to high suicide risk and at least one anxiety disorder. Participants not utilizing medications or psychotherapy had greater mania symptom severity, were younger, and less educated than medication only users. Medication only users were more likely to be married than the other participants.. These data suggest that a minority of individuals with bipolar disorder attend psychotherapy services, and those that do have greater illness burden.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Lithium; Logistic Models; Male; Middle Aged; Psychotherapy; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Lithium; Male; Penile Erection; Priapism; Quetiapine Fumarate

A 39-year-old man with bipolar disorder was hospitalised for depression. He was started on quetiapine (titrated up to 300 mg), lactulose (a laxative) and tropatepine (an anticholinergic). Valpromide (a mood stabiliser) and prazepam were later added and rapidly withdrawn. Seven days after quetiapine initiation, the patient reported abdominal pain and constipation; 2 days later, CT revealed an important distention of the colon including the caecum and a pre-perforation. A subtotal colectomy was performed and histology confirmed necrotising ischaemic colitis. The patient survived. This is the first case reported so far of ischaemic colitis related to quetiapine, in the absence of other antipsychotics simultaneously prescribed. Tropatepine likely acted as a cofactor to determine colitis. Clinicians need to be aware of the potential danger of the co-prescription of quetiapine with tropatepine (and possibly other anticholinergics).

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Colectomy; Colitis, Ischemic; Humans; Male; Quetiapine Fumarate; Treatment Outcome

Inconsistent findings concerning brain-derived neurotrophic factor (BDNF) levels across different episodes in bipolar disorder have been reported, which is also in line with the treatment effects on BDNF levels in acute mania. We aimed to compare plasma BDNF level alterations after pure antipsychotic drug or ECT plus antipsychotic drug treatment in acute mania.. Sixty-eight patients with mania were divided into two treatment arms: the antipsychotic treatment arm (AP) and electroconvulsive therapy (ECT)+AP arm. In addition, 30 healthy controls were included in the study.. There was no significant statistical difference according to mean age, education level, marital and working status between patients and healthy controls. The initial serum BDNF level in patients with acute mania was significantly lower than healthy controls. The initial BDNF level between the ECT arm and AP arm was not significant. The BDNF level decreased significantly after reaching remission in patients with acute mania. The change in BDNF level in the AP arm was not significant while in the ECT arm it was significant after treatment.. In this study, for the first time we revealed a significant decrease in BDNF levels after ECT sessions in acute manic patients. Besides clinical remission after treatment in acute mania, the decrement in BDNF levels does not seem to be related to clinical response. Thus cumulative effects of mood episodes for the ongoing decrease in BDNF levels might be borne in mind despite the achievement of remission and/or more time being required for an increase in BDNF levels after treatment.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Electroconvulsive Therapy; Female; Haloperidol; Humans; Male; Outcome Assessment, Health Care; Quetiapine Fumarate

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Colitis, Ischemic; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Radiography, Abdominal

It has been suggested that amphetamine abuse and withdrawal mimics the diverse nature of bipolar disorder symptomatology in humans. Here, we determined if a single paradigm of amphetamine sensitization would be sufficient to produce both manic- and depressive-related behaviors in mice. CD-1 mice were subcutaneously dosed for 5 days with 1.8 mg/kg d-amphetamine or vehicle. On days 6-31 of withdrawal, amphetamine-sensitized (AS) mice were compared to vehicle-treated (VT) mice on a range of behavioral and biochemical endpoints. AS mice demonstrated reliable mania- and depression-related behaviors from day 7 to day 28 of withdrawal. Relative to VT mice, AS mice exhibited long-lasting mania-like hyperactivity following either an acute 30-min restraint stress or a low-dose 1 mg/kg d-amphetamine challenge, which was attenuated by the mood-stabilizers lithium and quetiapine. In absence of any challenge, AS mice showed anhedonia-like decreases in sucrose preference and depression-like impairments in the off-line consolidation of motor memory, as reflected by the lack of spontaneous improvement across days of training on the rotarod. AS mice also demonstrated a functional impairment in nest building, an ethologically-relevant activity of daily living. Western blot analyses revealed a significant increase in methylation of histone 3 at lysine 9 (H3K9), but not lysine 4 (H3K4), in hippocampus of AS mice relative to VT mice. In situ hybridization for the immediate-early gene activity-regulated cytoskeleton-associated protein (Arc) further revealed heightened activation of corticolimbic structures, decreased functional connectivity between frontal cortex and striatum, and increased functional connectivity between the amygdala and hippocampus of AS mice. The effects of amphetamine sensitization were blunted in C57BL/6J mice relative to CD-1 mice. These results show that a single amphetamine sensitization protocol is sufficient to produce behavioral, functional, and biochemical phenotypes in mice that are relevant to bipolar disorder.

Topics: Anhedonia; Animals; Bipolar Disorder; Cerebral Cortex; Dextroamphetamine; Disease Models, Animal; Limbic System; Lithium Compounds; Male; Memory Consolidation; Mice; Mice, Inbred C57BL; Motor Activity; Nesting Behavior; Neural Pathways; Psychotropic Drugs; Quetiapine Fumarate; Restraint, Physical; Species Specificity; Stress, Psychological; Substance Withdrawal Syndrome

Second-generation antipsychotics have well-known metabolic side effects such as hyperlipidaemia and hyperglycaemia. A middle-aged man presented with epigastric and flank pain associated with nausea, and was noted to have elevated triglycerides (3590 mg/dL or 40.53 mmol/L), lipase and glucose. Haematological parameters revealed neutropenia with pancytopaenia. The patient was started on conservative management for acute pancreatitis, and on intravenous insulin and oral gemfibrozil for lowering of his triglycerides. He gradually improved and was transitioned to oral atorvastatin and fenofibrate. His triglycerides, glucose and leucocyte counts normalised at discharge and he was transitioned to ziprasidone. The combination of hypertriglyceridaemia, worsening hyperglycaemia and neutropenia made us suspect quetiapine as the causative agent. Medications cause only 0.1-7% of acute pancreatitis cases, with quetiapine implicated in only five-reported cases. Hypertriglyceridaemia (>600 mg/dL or 6.77 mmol/L) is frequently reported with quetiapine use, but severe hypertriglyceridaemia (>1000 mg/dL or 11.29 mmol/L) has been reported in <10 patients.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Humans; Hypertriglyceridemia; Male; Middle Aged; Pancreatitis; Quetiapine Fumarate; Treatment Outcome

Bipolar disorder imposes a high economic burden on patients and society. Lurasidone and quetiapine extended-release (XR) are atypical antipsychotic agents indicated for monotherapy treatment of bipolar depression. Lurasidone is also indicated as adjunctive therapy with lithium or valproate for depressive episodes associated with bipolar disorder. The objective of this analysis was to estimate the cost-effectiveness of lurasidone and quetiapine XR in patients with bipolar depression.. A cost-effectiveness model was developed to compare lurasidone to quetiapine XR. The model was based on a US third-party payer perspective over a 3-month time horizon. The effectiveness measure in the model was the percentage of patients achieving remission (Montgomery-Åsberg Depression Rating Scale [MADRS] total score ≤12 by weeks 6-8). The comparison of remission rates was made through an adjusted indirect treatment comparison of lurasidone and quetiapine XR pivotal trials using placebo as the common comparator. Resource utilization for remission vs no remission was estimated from published expert panel data, and resource costs were obtained from a retrospective database study of bipolar I depression patients. Drug costs were estimated using the mean dose from clinical trials and wholesale acquisition costs.. Over the 3-month model time period, lurasidone and quetiapine XR patients, respectively, had similar mean numbers of emergency department visits (0.48 vs 0.50), inpatient days (2.1 vs 2.2), and office visits (9.3 vs 9.6). More lurasidone than quetiapine XR patients achieved remission (52.0% vs 43.2%) with slightly higher total costs ($4982 vs $4676), resulting in an incremental cost-effectiveness ratio of $3474 per remission. The probabilistic sensitivity analysis showed lurasidone had an 86% probability of being cost-effective compared to quetiapine XR at a willingness-to-pay threshold of $10,000 per remission.. Lurasidone may be a cost-effective option when compared to quetiapine XR for the treatment of adults with bipolar depression.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Insurance Claim Review; Lurasidone Hydrochloride; Models, Economic; Quetiapine Fumarate; Remission Induction; Retrospective Studies; United States

Depression in bipolar disorder is a major therapeutic challenge associated with disability and excess mortality.. We reviewed findings from randomized placebo-controlled trials concerning efficacy and adverse effects of treatments for acute bipolar depression, including anticonvulsants, antidepressants, lithium, and modern antipsychotics, to compare numbers-needed-to-treat (NNT) versus -to-harm (NNH).. Included were data from 22 reports involving 33 drug-placebo pairs. Antidepressants (especially modern drugs) had the most favorable (highest) risk/benefit ratio (pooled NNH/NNT=18.1). Anticonvulsants were effective agents (pooled NNT=5.06), but carbamazepine and valproate were not as well tolerated (NNH<10) as lamotrigine, and they had an unfavorable pooled NNH/NNT (3.75). Some antipsychotics (lurasidone, olanzapine+fluoxetine, and quetiapine (NNT all < 10) were effective though aripiprazole and ziprasidone were not (NNT≥45); olanzapine alone was weakly effective (NNT=11.3), and all but lurasidone (NNH=20.2) were not well tolerated (NNH≤4.18). Lithium appeared to be poorly effective but well tolerated in only one trial.. Some anticonvulsants and antipsychotics seemed effective for acute bipolar depression, but most antipsychotics were not well tolerated. Antidepressants were effective and well-tolerated; lithium remains inadequately tested.. There are remarkably few short-term treatment trials (2.75/12 treatments), and fewer long-term trials for bipolar depression, possibly arising from exaggerated concerns about inducing mania.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Combinations; Drug Therapy, Combination; Fluoxetine; Humans; Lurasidone Hydrochloride; Quetiapine Fumarate; Randomized Controlled Trials as Topic

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Depressive Disorder, Treatment-Resistant; Drug Interactions; Drug Therapy, Combination; Fluoxetine; Humans; Ketamine; Lithium Compounds; Lorazepam; Middle Aged; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Restless Legs Syndrome

Topics: Adolescent; Adrenal Cortex Hormones; Antipsychotic Agents; Bipolar Disorder; Fluorometholone; Humans; Male; Ophthalmic Solutions; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Female; Humans; Middle Aged; Parkinson Disease; Quetiapine Fumarate

Topics: Anti-Bacterial Agents; Antipsychotic Agents; Bipolar Disorder; Diuretics; Electrocardiography; Female; Heart Failure; Humans; Hypokalemia; Inappropriate Prescribing; Middle Aged; Pneumonia; Quetiapine Fumarate; Torsades de Pointes; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Depression, Postpartum; Female; Humans; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome; Young Adult

Deficits in long-chain omega-3 (LCn-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with the pathophysiology of bipolar disorder. However, LCn-3 fatty acid status at the initial onset of mania and its association with treatment response are not known. Erythrocyte membrane fatty acid composition was determined in first-episode bipolar manic or mixed (n=40) and healthy (n=40) subjects. Mood symptom ratings were obtained with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS). Erythrocyte fatty acid composition and clinical ratings were also determined within a sub-group of bipolar subjects following 8-week (n=19) or 52-week (n=11) open-label treatment with lithium or quetiapine. At baseline bipolar subjects exhibited significantly lower erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition compared with healthy subjects (-23%, p<0.0001). EPA (20:5n-3) and docosapentanoic acid (22:5n-3), and LCn-6 fatty acids including arachidonic acid were not different. Following 8- or 52-week treatment with lithium or quetiapine, YMRS and HDRS total scores decreased significantly whereas erythrocyte fatty acids including DHA did not change. These data indicate that selective erythrocyte DHA deficits coincide with the initial onset of manic symptoms, and reductions in mood symptoms following treatment are not mediated by changes in fatty acid status.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Docosahexaenoic Acids; Eicosapentaenoic Acid; Erythrocyte Membrane; Fatty Acids, Unsaturated; Female; Healthy Volunteers; Humans; Lithium; Male; Psychological Tests; Quetiapine Fumarate; Young Adult

Systematic reviews should provide trustworthy guidance to decision-makers, but their credibility is challenged by the selective reporting of trial results and outcomes. Some trials are not published, and even among clinical trials that are published partially (e.g., as conference abstracts), many are never published in full. Although there are many potential sources of published and unpublished data for systematic reviews, there are no established methods for choosing among multiple reports or data sources about the same trial.. We will conduct systematic reviews of the effectiveness and safety of two interventions following the Institute of Medicine (IOM) guidelines: (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. For the review of gabapentin, we will include adult participants with neuropathic pain who do not require ventilator support. For the review of quetiapine, we will include adult participants with acute bipolar depression (excluding mixed or rapid cycling episodes). We will compare these drugs (used alone or in combination with other interventions) with placebo or with the same intervention alone; direct comparisons with other medications will be excluded. For each review, we will conduct highly sensitive electronic searches, and the results of the searches will be assessed by two independent reviewers. Outcomes, study characteristics, and risk of bias ratings will be extracted from multiple reports by two individuals working independently, stored in a publicly available database (Systematic Review Data Repository) and analyzed using commonly available statistical software. In each review, we will conduct a series of meta-analyses using data from different sources to determine how the results are affected by the inclusion of data from multiple published sources (e.g., journal articles and conference abstracts) as well as unpublished aggregate data (e.g., "clinical study reports") and individual participant data (IPD). We will identify patient-centered outcomes in each report and identify differences in the reporting of these outcomes across sources.. CRD42015014037 , CRD42015014038.

Topics: Amines; Analgesics; Antipsychotic Agents; Bipolar Disorder; Cyclohexanecarboxylic Acids; Data Interpretation, Statistical; Gabapentin; gamma-Aminobutyric Acid; Humans; Meta-Analysis as Topic; Neuralgia; Outcome Assessment, Health Care; Patient-Centered Care; Quetiapine Fumarate; Research Design; Selection Bias; Systematic Reviews as Topic

Topics: Bipolar Disorder; Depression; Gynecomastia; Humans; Mental Processes; Quetiapine Fumarate; Reward; Risperidone

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

Pregnancy in women with severe mental illness (SMI) often bring added dimensions of complexity; considering that this group of women are choosing to have children at increasing rates, more highly complex cases will require management. A 31-year-old primigravida with a diagnosis of bipolar affective disorder was treated with an antidepressant, mood stabiliser and antipsychotic. This case discusses preconception counselling, pregnancy and labour management that resulted in the delivery of a 4,200 g baby at 39 weeks by emergency caesarian section. This case highlights the collaborative approach to care that is needed in this group of women and the need for increasing awareness and knowledge in health professionals. It follows the management from preconception through to the postpartum period.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Cesarean Section; Dibenzothiazepines; Female; Humans; Infant, Newborn; Lithium; Phenelzine; Preconception Care; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Quetiapine Fumarate; Treatment Outcome

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 (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder.. We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine.. In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state.

Topics: Adolescent; Autistic Disorder; Basal Ganglia; Bipolar Disorder; Brain Diseases; Calcinosis; Catatonia; Diagnosis, Differential; Dibenzothiazepines; Humans; Magnetic Resonance Imaging; Male; Quetiapine Fumarate; Tomography, X-Ray Computed

Presently, the use of atypical antipsychotics is getting increasingly widespread. There are several mania/hypomania cases that have been associated with atypical antipsychotic treatment that also display antimanic, antidepressive and anxiolytic effects in addition to their antipsychotic effects. In this study, a case of schizophrenia in which manic symptoms developed after increasing the dosage of quetiapine to 300 mg/day, and subsequently disappeared after cessation of treatment is presented. Although the blockage of 5HT2 receptors and the disinhibition of frontal dopamine secretion seemed to be the reasons for the development of the mania/hypomania related to atypical antipsychotics, the mechanism is not clear. During the use of atypical antipsychotics, clinicians should be cautious to patients' mood fluctuations.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Diagnosis, Differential; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Pregnancy; Pregnancy Complications; Quetiapine Fumarate

Topics: Adolescent; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Tics

Topics: Adolescent; Autistic Disorder; Bipolar Disorder; Contraceptives, Oral, Combined; Dibenzothiazepines; Female; Humans; Menstrual Cycle; Mood Disorders; Quetiapine Fumarate

We investigated serum total oxidative and anti-oxidative status in manic patients. Group1 was formed as ECT+antipsychotic, group2 was antipsychotic and healthy volunteers as group3. The anti-oxidative status was significantly lower in group1 than group3. No significant change was found between pre and post-treatment oxidative and anti-oxidative status, whereas significantly increased oxidative stress index has been found in group2. Total anti-oxidative status in manic states seems to be inadequate which remains to be maintained after the treatment.

Topics: Antioxidants; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Electroconvulsive Therapy; Haloperidol; Humans; Male; Oxidants; Oxidative Stress; Quetiapine Fumarate

Quetiapine is a dibenzothiazepine derivative, similar to clozapine, which has the highest risk of causing blood dyscrasias, especially neutropenia. There are some case reports about this side effect of quetiapine, but possible risk factors are seldom discussed and identified. A case of a patient with hepatocellular carcinoma that developed neutropenia after treatment with quetiapine is described here.. A 62-year-old Taiwanese widow with bipolar disorder was diagnosed with hepatocellular carcinoma at age 60. She developed leucopenia after being treated with quetiapine. After quetiapine was discontinued, her white blood cell count returned to normal.. Although neutropenia is not a common side effect of quetiapine, physicians should be cautious about its presentation and associated risk factors. Hepatic dysfunction may be one of the possible risk factors, and concomitant fever may be a diagnostic marker for adverse reaction to quetiapine.

Topics: Antipsychotic Agents; Bipolar Disorder; Carcinoma, Hepatocellular; Dibenzothiazepines; Female; Humans; Liver Function Tests; Liver Neoplasms; Middle Aged; Neutropenia; Quetiapine Fumarate; Risk Factors; Taiwan

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Pedophilia; Quetiapine Fumarate; Valproic Acid

Bipolar manic episodes often require hospital admission to ensure patient safety. The antipsychotic quetiapine is a common treatment for bipolar mania and is available in immediate release (IR) and extended release (XR) formulations; however, outcomes in patients receiving these different formulations have not been directly compared in an acute hospital setting.. We conducted a multinational, observational, retrospective cohort study to describe and compare hospital stay in patients admitted for an acute bipolar manic episode treated with quetiapine IR or XR from 1 October 2009-1 October 2010. The primary outcome measure was comparison of length of stay (LOS) using zero-truncated negative binomial regression.. In total, 1230 patients were included (659 in the IR cohort; 571 in the XR cohort). The median LOS (interquartile range) was 18.0 days (12.0, 28.0) in the IR cohort and 20.0 days (12.0, 34.0) in the XR cohort, respectively. LOS was not significantly associated with quetiapine formulation irrespective of whether or not clinical characteristics were taken into account (p = 0.820 and p = 0.386, respectively). Overall, 84.2% and 84.4% of patients in the IR and XR cohorts, respectively, had not previously used quetiapine; of these patients, 78.7% and 68.9% received one total daily dose, and 14.4% and 23.9% received dose titration. Over half of patients received antipsychotic monotherapy (53.1% and 58.3% in the IR and XR cohorts, respectively) and most received a daily quetiapine dose ≥ 400 mg (64.9% and 71.8%, respectively, for quetiapine monotherapy and 59.9% and 80.3%, respectively, for combination treatment). As a secondary outcome, multivariate analysis was used to identify other factors that affect LOS. Factors associated with a longer hospital stay included public funding versus private, maximum number of new medications administered, did not receive lithium and did not receive anxiolytics, sedatives/hypnotics (all p < 0.0001). Factors associated with a shorter hospital stay included presence of drug/alcohol abuse, living accompanied and having a psychiatric medical history (all p < 0.05).. LOS was not found to be associated with quetiapine formulation. However, most patients received only one total daily dose of quetiapine without dose titration, which was unexpected and contrary to current recommendations.. NCT01239589.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Female; Hospitalization; Humans; Length of Stay; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome

The aim was to evaluate the impact of quetiapine extended release (XR) on hospitalization length and cost in schizophrenia or bipolar disorder, versus quetiapine immediate release (IR), using Premier Perspective™ inpatient hospital database data.. Inpatient discharges classified within diagnosis-related group 430 (psychoses), prescribed quetiapine XR or IR, were identified. Patients had International Classification of Disease-9 diagnosis of schizophrenia or bipolar disorder. The impact of the XR formulation on hospitalization length and costs was assessed using generalized linear model analyses.. A total of 30,429 discharges between 1 January 2008 and 30 June 2009 were analyzed. Patients who received quetiapine XR had significantly reduced hospitalization length (10.73% estimated reduction; p = 0.001) and cost (9.52% estimated reduction; p < 0.001), versus IR. This corresponds to a 1.0-day reduction in hospitalization (10.73% of 9.2 days) and US$532 reduction in hospitalization cost (9.52% of US$5588) per patient, based on least squares mean estimations. Evaluation of patient subpopulations suggested the reduction in length of hospitalization for quetiapine XR versus IR was driven mainly by patients with bipolar disorder, whereas cost reduction was driven mainly by patients with schizophrenia.. Inpatient use of quetiapine XR in schizophrenia or bipolar disorder is associated with reduced hospitalization length and cost, possibly due to the faster titration schedule versus quetiapine IR.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Costs and Cost Analysis; Delayed-Action Preparations; Dibenzothiazepines; Female; Humans; Length of Stay; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; United States; Young Adult

Patients with bipolar disorder spend more time depressed than manic, but fewer clinical trials have been conducted investigating treatments for bipolar depression than for bipolar mania. Olanzapine-fluoxetine combination, quetiapine, and lurasidone are the only FDA-approved treatments for bipolar depression. Clinical trials of these drugs show similar efficacy but different side effect profiles. Clinicians, therefore, should consider possible adverse events and individual patient characteristics when selecting treatments.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Drug Combinations; Fluoxetine; Humans; Isoindoles; Lurasidone Hydrochloride; Quetiapine Fumarate; Thiazoles

In recent years, intense controversies have evolved about the existence and exact diagnostic criteria of pediatric bipolar affective disorder. The present study aims to discuss pediatric bipolar affective disorder based on the current literature focussing on the diagnostic prospects. Based on a case study, a process of bipolar disorder developed in childhood is depicted exemplarily. Because of the high comorbidity and overlapping symptoms of paediatric bipolar affective disorder and other psychiatric disorders, the major impact of the differential diagnosis has to be stressed. An early diagnosis and the treatment possibilities are discussed.

Topics: Adolescent; Age of Onset; Antipsychotic Agents; Bipolar Disorder; Child; Diagnosis, Differential; Dibenzothiazepines; Humans; Hypnotics and Sedatives; Male; Mianserin; Mirtazapine; Neuropsychological Tests; Psychiatric Status Rating Scales; Quetiapine Fumarate; Social Behavior; Treatment Outcome

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Child; China; Cohort Studies; Dibenzothiazepines; Double-Blind Method; Earthquakes; Humans; Irritable Mood; Longitudinal Studies; Psychotic Disorders; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk Factors; Sleep Wake Disorders; Suicide; Suicide Prevention; Suicide, Attempted; Survivors; Treatment Outcome

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders; Somnambulism

Topics: Antipsychotic Agents; Bipolar Disorder; Citalopram; Dibenzothiazepines; Dietary Carbohydrates; Eating; Female; Humans; Middle Aged; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Weight Gain

We report upon a case of a 55 year old patient with a bipolar affective disorder, presenting herself with a depressive symptomatology in addition to a severe motor perturbation. The main emphasis upon admittance was perfecting and improving her latest medication. Four weeks prior to her stay at our clinic a thorough neurological examination had taken place in terms of an invalidity pension trial which did not result in any diagnostic findings. Therefore a neurological disease seemed at first highly unlikely. Even though the prior testing was negative, the ensuing neurological examination at our clinic resulted in movement disorders very much indicative of Huntington's Disease. A detailed investigation in regards to the particular family history of the patient was positive for Huntington's Disease. However, whether the patient's mother had also been a genetic carrier of Huntington's Disease was still unknown at the time the patient was admitted to our clinic. It was nevertheless discovered that her mother had also suffered from a bipolar affective disorder. A genetic testing that followed the neurological examination of the patient proved positive for Huntington's Disease. Neuro-imaging resulted in a bicaudate-index of 2.4 (the critical value is 1.8). In a clinical psychological test battery the ensuing results were highly uncommon for patients with solely a bipolar affective disorder people. Under the medical regimen of Quetiapine, Citalopram and Tiaprid the patient's mood could be stabilized and there was some improvement of her motor pertubation.

Topics: Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Citalopram; Dibenzothiazepines; Female; Genetic Testing; Heterozygote; Humans; Huntington Disease; Magnetic Resonance Imaging; Middle Aged; Movement Disorders; Neurologic Examination; Neuropsychological Tests; Pedigree; Positron-Emission Tomography; Quetiapine Fumarate; Tiapride Hydrochloride

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

Although the neurophysiology underlying pharmacotherapy for bipolar disorder remains poorly understood, recent studies suggest that therapeutic mechanisms may be reflected in changes in concentrations of N-acetylaspartate (NAA), a putative measure of neuronal integrity and metabolism. In this study, we used magnetic resonance spectroscopy (MRS) to examine prefrontal NAA in patients receiving quetiapine for bipolar mania. On the basis of previous findings, we hypothesized that remission would be associated with increased NAA concentrations in the prefrontal cortex. Thirty-one manic bipolar patients and 13 healthy subjects were recruited to participate in this prospective study. All subjects participated in MRS at baseline and after 8 weeks of treatment. Bipolar subjects received open-label quetiapine monotherapy (mean dose [SD], 584 [191] mg). Fourteen patients remitted (Young Mania Rating Scale ≤ 12) ("remitters"), 11 patients did not ("nonremitters"), and 6 patients were lost to follow-up. Bipolar and healthy subjects did not significantly differ in baseline NAA or degree of change during the 8 weeks. Remitters showed greater mean baseline NAA concentrations in the right ventrolateral prefrontal cortex compared with nonremitters (P < 0.05). In the anterior cingulate, remitters showed near significantly decreased baseline NAA concentrations at baseline (P < 0.06), and significant differences in NAA change during the 8 weeks of treatment (P < 0.03). Manic patients who remitted with quetiapine treatment in the course of this study exhibited distinct patterns of baseline prefrontal NAA concentration, coupled with decreased NAA in the anterior cingulate with treatment; the latter possibly reflecting disparate effects of quetiapine on neuronal metabolism. These data support suggestions that therapeutic effects of quetiapine involve metabolic effects on specific prefrontal regions.

Topics: Adolescent; Adult; Antipsychotic Agents; Aspartic Acid; Biomarkers; Bipolar Disorder; Case-Control Studies; Dibenzothiazepines; Female; Gyrus Cinguli; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Prefrontal Cortex; Prospective Studies; Quetiapine Fumarate; Remission Induction; Time Factors; Treatment Outcome; Young Adult

The primary objective of this study was to assess patient and treatment variables that have an impact on inpatient antipsychotic treatment continuation and 30-day hospital readmission rates in patients with bipolar disorder treated with aripiprazole or quetiapine.. This was a retrospective cohort study of adult patients with bipolar disorder admitted to a psychiatric hospital. Patients who were initiated on aripiprazole or quetiapine during hospitalization were included in the analysis. The two groups were compared with regards to antipsychotic treatment continuation to discharge and 30-day hospital readmission rates using logistic regression analysis.. A total of 336 patients were included in the study. No difference in inpatient antipsychotic treatment continuation rates to discharge were observed, with 85.3% and 84.9% of patients in the aripiprazole and quetiapine cohorts, respectively, continuing treatment with the index antipsychotic to discharge (p = 0.92). Logistic regression analysis revealed that patients were more likely to be prescribed their index antipsychotic at discharge if they were younger than 40 years of age (OR = 2.05, 95% CI =1.08-3.89) and/or diagnosed with a bipolar depressed (OR = 3.05, 95% CI = 1.05-8.85) or mixed episode (OR = 4.14, 95% CI = 1.24-13.87) compared with a manic episode. Patients treated with divalproex (OR = 0.49, 95% CI = 0.25-0.94) or a benzodiazepine (OR = 0.37, 95% CI = 0.18-0.75) at discharge were less likely to be prescribed the index antipsychotic at discharge. Continuation of the index antipsychotic to discharge did not have an impact on readmission rates; admissions during the year before the index hospitalization were the only predictor of 30-day readmission rates (OR = 2.44, 95% CI = 1.08-5.48).. No difference was observed in inpatient antipsychotic treatment continuation and 30-day hospital readmission rates in patients treated with either aripiprazole or quetiapine.

Topics: Adolescent; Adult; Age Factors; Aged; Antimanic Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Bipolar Disorder; Cohort Studies; Dibenzothiazepines; Drug Administration Schedule; Drug Therapy, Combination; Female; Hospitalization; Hospitals, Psychiatric; Humans; Inpatients; Male; Middle Aged; Odds Ratio; Patient Readmission; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Valproic Acid; Young Adult

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Resistance; Drug Substitution; Drug Therapy, Combination; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Recurrence; Sertraline

Hyperammonemia is one of the rare nevertheless serious side effects associated with valproic acid treatment. Two cases of valproic acid induced hyperammonemia are detailed in this article.. Case one describes an adult male who developed hyperammonemia after acute exposure to valproic acid as a treatment for his bipolar disorder-manic episode. Case two developed a similar pattern of toxicity but after chronic exposure to valproic acid. Both patients were receiving a combination of valproic acid and quetiapine.. Measurement of the ammonium level should be considered where there is a decreased level of consciousness in patients receiving valproic acid irrespective of the diagnosis and even after a long term exposure. A possible risk of hyperammonemia can result from a combination of valproic acid and quetiapine, however further studies are yet needed to confirm this hypothesis.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Interactions; Humans; Hyperammonemia; Male; Quetiapine Fumarate; Valproic Acid; Young Adult

Topics: Adult; Antimanic Agents; Bipolar Disorder; China; Cognition Disorders; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Quetiapine Fumarate; Valproic Acid; Young Adult

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Circadian Rhythm; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Self-Injurious Behavior

Nesfatin 1 is a newly identified peptide structured satiety hormone that is claimed to be responsible for the provision of appetite and metabolic regulation in hypothalamus. The change in appetite and energy is a well-known clinical feature of affective disorders and within treatment. We aimed to investigate serum nesfatin 1 level in patients with bipolar disorder who were in manic episode and the influences of treatment modalities on nesfatin 1 level.. Sixty eight patients were elected and were divided into two groups as: antipsychotic treatment (haloperidol 10-30 mg/daily+quetiapine 100-900 mg/daily) arm and ECT+antipsychotic treatment arm. And 30 healthy controls were included in the study.. There was no significant difference according to mean age between patients and controls. Initial nesfatin 1 levels in patients and in both subgroups of patients were statistically lower than in healthy control group. The initial level of nesfatin 1 between ECT+antipsychotic and pure antipsychotic patient groups was not statistically significant. We found a trend of increment in nesfatin 1 level after treatment in both patient groups.. This study is the first that revealed significantly lower nesfatin 1 level in manic episode than healthy controls. ECT+antipsychotic and antipsychotic treatments have no significant effects on nesfatin 1 level after manic episode treatment. These findings should be interpreted cautiously because of small sample size and being drug free only for one week.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Calcium-Binding Proteins; Case-Control Studies; Dibenzothiazepines; DNA-Binding Proteins; Drug Therapy, Combination; Electroconvulsive Therapy; Haloperidol; Humans; Male; Middle Aged; Nerve Tissue Proteins; Nucleobindins; Quetiapine Fumarate; Young Adult

Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders (DBDs) (oppositional-defiant disorder or conduct disorder), with negative implications on treatment strategy and outcome. The aim of this study was to assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9 ± 2.0 years), diagnosed with a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the patients were treated with quetiapine monotherapy (mean final dose 258 ± 124 mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%) were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2 and CGI-Severity [CGI-S] ≤ 3 and improvement of at least 30% Children's Global Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS significantly improved (p<0.0001). Nine out of the 16 patients with suicidality (56.3%) had a reduction in this severe symptom during the follow-up. Nonresponders were more frequently males, and more frequently had an attention-deficit/hyperactivity disorder (ADHD) comorbidity. Eight patients (20.0%) experienced moderate to severe sedation and eight (20.0%) experienced increased appetite and weight gain. In these severely impaired adolescents, quetiapine monotherapy was well tolerated and effective in>50% of the patients.

Topics: Adolescent; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Child; Conduct Disorder; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Suicidal Ideation; Treatment Outcome

Differences in treatment patterns, health care resource use, and costs are expected among patients newly treated with quetiapine extended release (XR) or quetiapine immediate release (IR).. To compare treatment patterns, health care resource use, and costs in patients with bipolar disorder newly treated with quetiapine XR or quetiapine IR.. This was an observational, retrospective cohort study that used HealthCore Integrated Research Database-identified patients (age range, 18-64 years) with an International Classification of Disease, Ninth Revision diagnosis of bipolar disorder and ≥1 pharmacy claim for quetiapine XR or quetiapine IR between October 2, 2008, and July 31, 2010. Outcomes were as follows: patient characteristics at the index date (first claim for quetiapine XR or quetiapine IR); 12-month preindex clinical characteristics, health care resource use, and costs; and 12-month postindex treatment patterns, health care resource use, and costs, assessed using generalized linear models (adjusted for index date and preindex patient demographic characteristics, clinical characteristics, health care resource use, and costs).. In total, 3049 patients with bipolar disorder were analyzed (651 in the quetiapine XR group and 2398 in the quetiapine IR group). Of patients initiating treatment with quetiapine XR, 8.8% had no change in or discontinuation of their index therapy compared with 5.7% of patients treated with quetiapine IR (adjusted odds ratio, 1.44; 95% confidence interval, 1.03-2.00; P = 0.0317). The average daily dose (adjusted mean) of quetiapine XR was higher than quetiapine IR (225 vs 175 mg/d, P < 0.0001). An average daily dose of 300 to 800 mg was reached sooner (15.6 vs 30.8 days, P = 0.0049) and in more patients (44.2% vs 27.2%, P < 0.0001) who were taking quetiapine XR compared with patients taking quetiapine IR. No differences in total health care costs were found between the cohorts; however, patients taking quetiapine XR were less likely to be hospitalized for mental health-related reasons (12.1% vs 18.3%, P = 0.0022) and incurred lower mental health-related costs (US $6686 vs US $7577, P = 0.0063) compared with patients taking quetiapine IR.. Treatment patterns and dosing differ in patients with bipolar disorder treated with quetiapine XR compared with those treated with quetiapine IR. Mental health-related hospitalizations and costs may be reduced in the 12 months after patients initiating treatment with quetiapine XR compared with initiating treatment with quetiapine IR.

Topics: Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Delayed-Action Preparations; Dibenzothiazepines; Female; Health Care Costs; Humans; Insurance Claim Review; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; United States; Young Adult

Exacerbation of symptoms in mood disorders such as bipolar disorders, major depressive disorders and premenstrual dysphoric disorders could be influenced by the hormonal changes of the menstrual cycles in female patients. Menarche has been related to onset of mood symptoms, which at times have been described as menstrual psychoses and could represent an early presentation of Pediatric bipolar disorders. Pediatric bipolar disorders appear to be characterized by less clearly defined mood episodes, shorter duration of these episodes, and different hallmark symptoms than in adults. This report describes a pediatric patient who had no previous psychiatric symptoms and for whom menstrual psychosis was the presenting symptom of bipolar disorder not otherwise specified.

Topics: Adolescent; Age of Onset; Anorexia; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Estrogens; Female; Hallucinations; Humans; Menarche; Paranoid Disorders; Periodicity; Premenstrual Syndrome; Psychomotor Agitation; Quetiapine Fumarate; Sleep Initiation and Maintenance Disorders

A 24-year-old man with bipolar disorder who was started on quetiapine as an adjunct to valproate (mood stabiliser) after a depressive episode switched to a manic episode while on the drug. The manic episode resolved following the withdrawal of quetiapine. This case illustrates the rare possibility of quetiapine emergent manic episode which a clinician needs to be aware of in the context of the management of bipolar disorders.

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Diagnosis, Differential; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Treatment Outcome; Young Adult

There are few studies of female stalkers in literature addressing different study populations. There appears to be a high incidence of mental disease among female stalkers, having an important role in inducing the harassment. We present a woman affected by a bipolar disorder who had a long affair with her victim, broken off in 2007. Stalking began in January 2009 and continued for 6 months, during which time she was not taking drugs and was in a decompensated clinical phase. In July 2009, she was denounced for harassment; the authorities demanded a psychiatric examination. The woman then resumed taking the medication regularly. In December 2009, although she was in complete remission, she began stalking once more. This case shows that even when there seems to be an evident relation between psychopathology and crime, it is always necessary to evaluate to what extent the mental disorder is responsible for the criminal behavior.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Commitment of Mentally Ill; Dibenzothiazepines; Female; Forensic Psychiatry; Haloperidol; Humans; Quetiapine Fumarate; Stalking; Valproic Acid

A 40-year-old female patient with bipolar disorder and premenstrual dysphoric disorder did not present any physical evidence of virilization, treated with quetiapine and lithium carbonate. Laboratory testing showed evidence of hyperandrogenism (Testosterone levels 88.5ng/dL). After control, testosterone levels were normal (free testosterone 0.20 pg/ml, total testosterone 27.90ng/dl), as free thyroxine levels decreased (T4 0.83ng/dl) and increased progesterone levels (progesterone 3.80ng/ml). We consider an association between increased androgenic hormone levels in women, quetiapine and lithium carbonate treatment as well as the presence of an affective disorder and premenstrual dysphoric disorder. Some relevant patents are also outlined in this review.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Hyperandrogenism; Lithium Carbonate; Patents as Topic; Premenstrual Syndrome; Quetiapine Fumarate; Testosterone

The use of quetiapine for treatment of bipolar disorders at a higher dosage than the licensed range is not unusual in clinical practice. Quetiapine is predominantly metabolised by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2D6. The large interindividual variability of those isozyme activities could contribute to the variability observed in quetiapine dosage. The aim of the present study is to evaluate if the use of high dosages of quetiapine in some patients, as compared to patients treated with a dosage in the licensed range (up to 800 mg/day), could be explained by a high activity of CYP3A4 and/or of CYP2D6. CYP3A4 activities were determined using the midazolam metabolic ratio in 21 bipolar and schizoaffective bipolar patients genotyped for CYP2D6. 9 patients were treated with a high quetiapine dosage (mean ± SD, median; range: 1467 ± 625, 1200; 1000-3000 mg/day) and 11 with a normal quetiapine dosage (433 ± 274, 350; 100-800 mg/day). One patient in the high dose and one patient in the normal dose groups were genotyped as CYP2D6 ultrarapid metabolizers. CYP3A4 activities were not significantly different between the two groups (midazolam metabolic ratio: 9.4 ± 8.2; 6.2; 1.7-26.8 vs 3.9 ± 2.3; 3.8; 1.5-7.6, in the normal dose group as compared to the high dose group, respectively, NS). The use of high quetiapine dosage for the patients included in the present study cannot be explained by variations in pharmacokinetics parameters such as a high activity of CYP3A4 and/or of CYP2D6.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Quetiapine Fumarate

Depressive mood in adolescents with bipolar disorder (BDd) is associated with significant morbidity and mortality, but we have limited information about neural correlates of depression and treatment response in BDd. Ten adolescents with BDd (8 females, mean age = 15.6 ± 0.9) completed two (fearful and happy) face gender labeling fMRI experiments at baseline and after 6-weeks of open treatment. Whole-brain analysis was used at baseline to compare their neural activity with those of 10 age and sex-matched healthy controls (HC). For comparisons of the neural activity at baseline and after treatment of youth with BDd, region of interest analysis for dorsal/ventral prefrontal, anterior cingulate, and amygdala activity, and significant regions identified by wholebrain analysis between BDd and HC were analyzed. There was significant improvement in depression scores (mean percentage change on the Child Depression Rating Scale-Revised 57 % ± 28). Neural activity after treatment was decreased in left occipital cortex in the intense fearful experiment, but increased in left insula, left cerebellum, and right ventrolateral prefrontal cortex in the intense happy experiment. Greater improvement in depression was associated with baseline higher activity in ventral ACC to mild happy faces. Study sample size was relatively small for subgroup analysis and consisted of mainly female adolescents that were predominantly on psychotropic medications during scanning. Our results of reduced negative emotion processing versus increased positive emotion processing after treatment of depression (improvement of cognitive bias to negative and away from positive) are consistent with the improvement of depression according to Beck's cognitive theory.

Topics: Adolescent; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Brain; Citalopram; Depressive Disorder; Dibenzothiazepines; Drug Therapy, Combination; Emotions; Facial Expression; Female; Humans; Lamotrigine; Magnetic Resonance Imaging; Male; Piperazines; Psychotropic Drugs; Quetiapine Fumarate; Quinolones; Sertraline; Triazines; Valproic Acid

Although associations between antipsychotic use and neuropsychological impairment in bipolar I disorder have been observed, there is a lack of studies comparing the effects of specific agents used in this population. We compared performance between patients receiving maintenance treatment with mood stabilizer monotherapy (n=15), adjunctive risperidone (n=15) or quetiapine (n=17), and a group of demographically matched healthy controls (n=28) on tests of executive function (working memory, set shifting, and inhibition) and verbal learning. Despite having a similar clinical profile, patients being treated with risperidone showed significantly impaired working memory, set-shifting, and verbal learning (P<0.05) compared with those either on mood stabilizer monotherapy or adjunctive quetiapine. Although randomized controlled trials are required to confirm the cognitive side effects of medications prescribed for maintenance treatment of bipolar I disorder, preliminary results indicate that addition of risperidone to a mood stabilizer has a negative impact on executive function and verbal learning, an effect not shared with quetiapine.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Attention; Bipolar Disorder; British Columbia; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Drug Therapy, Combination; Executive Function; Female; Humans; Longitudinal Studies; Male; Memory, Short-Term; Neurotoxicity Syndromes; Quetiapine Fumarate; Risperidone; Severity of Illness Index; Verbal Learning; Young Adult

Assess quetiapine plus lamotrigine (QTP+LTG) combination maintenance therapy effectiveness in challenging bipolar disorder (BD).. Outpatients assessed with the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Affective Disorders Evaluation and followed with the STEP-BD Clinical Monitoring Form were naturalistically prescribed QTP+LTG.. Fifty-four outpatients with challenging BD, taking in addition to QTP+LTG, a mean±SD of 2.1±1.6 (in 63.0% at least 2) other psychotropic and 2.3±1.9 non-psychotropic prescription medications, had QTP+LTG maintenance trials. Median(mean±SD) QTP+LTG duration was 401(730±756) days. Final QTP and LTG doses were 87.5(188±211) and 300(287±108) mg/day, respectively. Half (27/54) of patients discontinued QTP (in 19), LTG (in 6), or QTP+LTG (in 2), after 294(415±414) days - due to side-effects in 10, inefficacy in seven, non-adherence in five, and other reasons in five. 42.6%(23/54) had additional pharmacotherapy intervention for emergent mood symptoms, after 175(261±237) days, with at least one psychotropic added (in 16/54) or substantively (by ≥50%) increased (in 7/54). 55.6%(30/54) had recurrent mood episodes, after 126(187±158) days, most often depressive (in 35.2%), although 64.8%(35/54) were euthymic at final visit taking QTP+LTG. Sedation increased significantly during treatment among those with side-effect discontinuations, and 19.2%(10/52, all having QTP added to LTG) had clinically significant (≥7%) weight gain.. No placebo comparison group. Small sample of predominantly female Caucasian insured outpatients taking complex concurrent medication regimens.. Additional studies are warranted to confirm our preliminary observation that QTP+LTG maintenance may be effective in patients with challenging BD.

Topics: Adult; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lamotrigine; Male; Middle Aged; Psychotropic Drugs; Quetiapine Fumarate; Triazines

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

Bipolar disorder is characterized by mood instability, which can be challenging to manage. First-line pharmacological approaches usually involve lithium, anticonvulsants and antipsychotics. Over the past fifteen years, several second-generation antipsychotics have demonstrated benefits for various phases of this disorder.. This article examines the pharmacodynamics and pharmacokinetics of quetiapine ; its evidence base as an acute and maintenance monotherapy or adjunctive therapy for bipolar manic or mixed episodes is also discussed, along with the related issues of its safety and tolerability.. In the context of bipolar disorder, quetiapine is the only agent approved as a monotherapy or adjunct therapy for acute manic/mixed episodes in adults and adolescents; as a monotherapy for acute depressive episodes in adults; and as an adjunctive maintenance therapy for bipolar I and II disorder in adults. In addition to its antipsychotic properties, this broad mood-stabilizing potential may simplify the management of select patients.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Quetiapine Fumarate

Topics: Aged, 80 and over; Antimanic Agents; Antipsychotic Agents; Asian People; Bipolar Disorder; Dementia, Vascular; Dibenzothiazepines; Drug Monitoring; Drug Therapy, Combination; Female; Hallucinations; Humans; Male; Middle Aged; Neutropenia; Psychomotor Agitation; Quetiapine Fumarate; Treatment Outcome; Valproic Acid

Topics: Adult; Anti-Anxiety Agents; Antimanic Agents; Antipsychotic Agents; Anxiety Disorders; Bipolar Disorder; Clonazepam; Delayed-Action Preparations; Delusions; Dibenzothiazepines; Drug Monitoring; Drug Therapy, Combination; Humans; Male; Mianserin; Mirtazapine; Neutropenia; Polypharmacy; Quetiapine Fumarate; Suicidal Ideation; Treatment Outcome; Valproic Acid

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

Despite the dissemination of second generation antipsychotics for schizophrenia and bipolar disorder, outcomes remain suboptimal, largely due to poor treatment and drug adherence. The primary aim of the current study was to assess the tolerability, validity and feasibility of the pocket-sized electronic diary Medicus®.. Our case observations attempted to evaluate eighteen patients suffering from schizophrenia and bipolar disorder. All of the patients were treated with the second generation antipsychotic quetiapine. We followed them up in two German medical centers over two years.. The present results display an improvement of mood-stability in all patients treated with quetiapine. All patients were in regular contact to their psychiatrist over a period of 24 months. A complete description of the coherences between the symptoms was essential for estimation, which was conducted by Medicus®. Moreover, Medicus® seem to be useful for improving compliance within a medication regimen.. Although uncontrolled case observations can only be interpreted with caution, Medicus® seems to deserve further investigation and may hold the potential to optimize treatment and drug adherence in patients suffering from schizophrenia and bipolar disorders.

Topics: Adolescent; Adult; Affect; Aged; Antipsychotic Agents; Anxiety; Bipolar Disorder; Data Collection; Dibenzothiazepines; Feasibility Studies; Female; Humans; Longitudinal Studies; Male; Medication Adherence; Middle Aged; Quetiapine Fumarate; Reminder Systems; 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

Schizophrenia and bipolar disorder are chronic debilitating disorders that are often treated with second-generation antipsychotic agents, such as aripiprazole, quetiapine, and ziprasidone. While patients who are hospitalized for schizophrenia and bipolar disorder often receive these agents at discharge, comparatively little information exists on subsequent patterns of pharmacotherapy.. Using a database linking hospital admission records to health insurance claims, we identified all patients hospitalized for schizophrenia (ICD-9-CM diagnosis code 295.XX) or bipolar disorder (296.0, 296.1, 296.4-296.89) between January 1, 2001 and September 30, 2008 who received aripiprazole, quetiapine, or ziprasidone at discharge. Patients not continuously enrolled for 6 months before and after hospitalization ("pre-admission" and "follow-up", respectively) were excluded. We examined patterns of use of these agents during follow-up, including adherence with treatment (using medication possession ratios [MPRs] and cumulative medication gaps [CMGs]) and therapy switching. Analyses were undertaken separately for patients with schizophrenia and bipolar disorder, respectively.. We identified a total of 43 patients with schizophrenia, and 84 patients with bipolar disorder. During the 6-month period following hospitalization, patients with schizophrenia received an average of 101 therapy-days with the second-generation antipsychotic agent prescribed at discharge; for patients with bipolar disorder, the corresponding value was 68 therapy-days. Mean MPR at 6 months was 55.1% for schizophrenia patients, and 37.3% for those with bipolar disorder; approximately one-quarter of patients switched to another agent over this period.. Medication compliance is poor in patients with schizophrenia or bipolar disorder who initiate treatment with aripiprazole, quetiapine, or ziprasidone at hospital discharge.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Databases, Factual; Dibenzothiazepines; Female; Humans; Male; Medication Adherence; Patient Discharge; Piperazines; Quetiapine Fumarate; Quinolones; Retrospective Studies; Schizophrenia; Thiazoles

Quetiapine is an atypical antipsychotic licensed for the treatment of schizophrenia and bipolar disorder and as an adjunctive for patients with unipolar depression. Case reports suggest a potential for drug abuse, especially among individuals with prior or current abuse of other substances.

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Humans; Quetiapine Fumarate; Schizophrenia; Substance-Related Disorders

Bipolar disorder; migraines and epilepsy are three prevalent conditions, of which little is understood about their pathophysiological processes. Co-morbidities often present between two of these conditions, but it is uncommon for all three to co-exist in a patient. Here, we present a middle-aged gentleman, seen in the outpatient department of a district general hospital in England, who suffers from severe effects of all three disorders, with no other medical history. Clinical difficulties have arisen in the diagnosis and treatment of his bipolar disorder. Management of his depressive episodes with simple selective serotonin reuptake inhibitors and mood stabilisers were either ineffective, or precipitated complicating adverse effects. Persistent use of citalopram is likely to have triggered bipolar disorder, whilst quetiapine induced seizures. The clinical problems presented question the possibility that bipolar disorder; migraines and epilepsy may fall on the same spectrum of disorders. This could contribute towards the complexities in treating his conditions. Further insight into their link and interactions would facilitate diagnoses of these conditions, as well as improve treatment strategies when they are presented co-morbidly.

Topics: Adult; Affect; Anger; Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Bipolar Disorder; Citalopram; Comorbidity; Dibenzothiazepines; Drug Therapy, Combination; Epilepsy, Generalized; Humans; Male; Migraine Disorders; Quetiapine Fumarate; Violence

There exists a growing argument in favour of a more dimensional approach to the diagnosis and treatment of psychiatric patients. This encompasses first the idea of a spectrum of symptoms correlating to severity within a single disorder, and secondly, the idea of spectra of different disorders sharing overlapping collections of symptoms. Here we consider the issue in light of specific clinical examples we have observed, which support the idea of a 'mental illness spectrum', both with symptoms within a single disorder, and between different mental disorders.

Topics: Antipsychotic Agents; Bipolar Disorder; Borderline Personality Disorder; Combined Modality Therapy; Comorbidity; Depressive Disorder, Major; Diagnosis, Differential; Dibenzothiazepines; Humans; International Classification of Diseases; Mental Disorders; Prodromal Symptoms; Psychotherapy; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Heart Transplantation; Humans; Male; Quetiapine Fumarate

Topics: Aged; Bipolar Disorder; Dibenzothiazepines; Disease Progression; Dose-Response Relationship, Drug; Humans; Male; Quetiapine Fumarate; Time Factors

Lamotrigine and quetiapine are commonly used in bipolar disorder, but there are no published systematic studies of their use in combination for treatment-resistant bipolar depression.. We studied 39 trials in outpatients (15 with bipolar I disorder, 22 with bipolar II disorder, and 1 with bipolar disorder not otherwise specified; 1 patient had 2 trials) with depression resistant to quetiapine or lamotrigine who were taking a mean of 1.7 other prescription psychotropic medications. Patients were given either open-label lamotrigine or quetiapine naturalistically, for up to 12 weeks of combination therapy.. Lamotrigine (mean dose, 204.2 mg/d) plus quetiapine (mean dose, 188.5 mg/d) increased the euthymia rate (0.0% to 46.2%), decreased syndromal (79.5% to 30.8%) and subsyndromal (20.5% to 15.4%) depression rates, and improved Clinical Global Impression-Severity (mean change, -1.0) and Global Assessment of Functioning (mean change, +5.9) scores. Approximately one-fifth of patients discontinued therapy (20.5%) or required subsequent additional pharmacotherapy (20.5%). Only 10.3% discontinued due to adverse effects, and there was no significant change in mean body weight.. The findings of this uncontrolled open pilot study must be viewed with caution. However, randomized, double-blind, placebo-controlled studies are warranted to confirm the possibility that combination therapy with lamotrigine and quetiapine is effective and well tolerated in patients with treatment-resistant bipolar depression.

Topics: Adult; Affect; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Resistance; Drug Therapy, Combination; Female; Humans; Interview, Psychological; Lamotrigine; Male; Middle Aged; Monitoring, Physiologic; Pilot Projects; Psychiatric Status Rating Scales; Quetiapine Fumarate; Severity of Illness Index; Treatment Outcome; Triazines; Xerostomia

Quetiapine is an atypical antipsychotic drug that was recently also approved for the treatment of uni- and bipolar depression. The antidepressive response is considered to be mediated by the metabolite N-desalkylquetiapine, and the aim of this study was to assess the interindividual pharmacokinetic variability of quetiapine and N-desalkylquetiapine in psychiatric patients based on therapeutic drug monitoring samples.. Serum measurements of quetiapine and N-desalkylquetiapine performed between October 2007 and July 2008 were retrospectively included from a routine therapeutic drug monitoring database. Pharmacokinetic variability was expressed as the 5-95 percentile range in dose-adjusted serum concentrations (C/D ratios). The impact of age (65 years or older), gender, and sampling time on the C/D ratios was studied by linear mixed model analysis. Samples from patients comedicated with CYP3A4 inducers or inhibitors were examined separately.. In total, 927 serum samples from 601 patients were included (all using quetiapine immediate-release tablets). The 5-95 percentiles of the C/D ratio ranged 15-fold (0.14-2.1 nmol/L/mg) for quetiapine and fivefold (0.44-2.1 nmol/L/mg) for N-desalkylquetiapine. Elderly (65 years or older) obtained 1.5- and 1.2-fold higher C/D ratios of quetiapine (P = 0.002) and N-desalkylquetiapine (P = 0.03) compared with younger patients, respectively. Sampling time was also found to significantly affect the C/D ratios of quetiapine (P = 0.001), whereas gender was not a significant variable (P > 0.13). In three patients treated with potent CYP3A4 inducers, the observed C/D ratios of quetiapine and N-desalkylquetiapine were 77% and 11% lower than the mean C/D ratio in the study population, respectively.. The pharmacokinetic variability was greater for quetiapine compared with N-desalkylquetiapine. Age 65 years or older and comedication with CYP3A4 inducers affected the serum levels of both agents, but the relative impact was greater on quetiapine.

Topics: Age Factors; Antipsychotic Agents; Bipolar Disorder; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Reproducibility of Results; Retrospective Studies; Sex Characteristics; Time Factors

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Practice Guidelines as Topic; Quetiapine Fumarate

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

Combination therapy with valproic acid plus quetiapine is recommended as one of the first-line approaches to treatment of manic or mixed episodes in patients with bipolar disorder.. A 66-year-old patient with this psychiatric disease developed parkinsonism and cognitive decline during concomitant treatment with both drugs. The rapid onset of symptoms soon after use of the combination suggested an interaction/using the Karch-Lasagna criteria, the interaction was judged to be definite.. Their evidence on a pharmacokinetic drug interaction between the two drugs is conflicting but possible underlying mechanisms proposed include CYP3A4 inhibition. As concomitant use of valproate and quetiapine is now quite frequent in bipolar disorder, this potential interaction should be closely monitored, especially in the elderly.

Topics: Aged; Antimanic Agents; Bipolar Disorder; Cognition Disorders; Cytochrome P-450 CYP3A; Dibenzothiazepines; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Parkinson Disease, Secondary; Quetiapine Fumarate; Treatment Outcome; Valproic Acid

Only three cases of ultradian or ultra-ultra-rapid cycling are to be found in the literature till now. The case of a 19-year-old patient is added and her successful treatment described. Discontinuation of the antidepressive medication and the introduction of lamotrigine and quetiapine resulted in the very stabilization of mood which was necessary for successful antidepressive treatment with reboxetine.

Topics: Affect; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Lamotrigine; Morpholines; Quetiapine Fumarate; Reboxetine; Treatment Outcome; Triazines; Young Adult

To report a case of branch retinal vein occlusion in a young adult with bipolar mood disorder treated with quetiapine fumarate.. A 29 years old gentleman who was taking quetiapine fumarate for 3 years for bipolar mood disorder, presented with sudden vision loss. He was found to have a superior temporal branch retinal vein occlusion associated with hypercholesterolemia.. Atypical antipsychotic drugs have metabolic side effects which require regular monitoring and prompt treatment.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Follow-Up Studies; Humans; Male; Quetiapine Fumarate; Retina; Retinal Vein Occlusion; Tomography, Optical Coherence; Visual Acuity

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

The treatment of bipolar disorders is based on the concomitant use of the mood stabilizers and antipsychotics. In the first case carbamazepine is frequently used, in the second case second-generation (atypical) neuroleptics like quetiapine. This drug combination in a significant number of cases prevent recurrence of mania and depression, normalizes mood and emotion and improves lifestyle. However, this treatment is related to increased interactions and risk of the side effects. Even greater risks involve mixed drug intoxications with these groups of drugs. In this paper we present acute poisoning with carbamazepine and quetiapine complicated cardiotoxic effects in the form of arrhythmias and conduction disorders of the heart. This symptoms disappeared spontaneously after resolution of the poisoning.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Arrhythmias, Cardiac; Bipolar Disorder; Carbamazepine; Dibenzothiazepines; Drug Interactions; Female; Heart Conduction System; Humans; Middle Aged; Mood Disorders; Quetiapine Fumarate

There is increasing concern about the development of diabetes mellitus and associated complications in patients administrating second-generation antipsychotics. Previous reports indicate that the risk of quetiapine, although relatively lower, is not negligible. We report a patient with bipolar disorder who, after treating with low-dose quetiapine, develops newly-onset diabetes and hyperglycemic hyperosmolar state. Clinical manifestations and managements of quetiapine-associated diabetes are addressed, and we recommend routine monitoring of serum glucose after initiating quetiapine treatment at any given dose.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Blood Glucose; Diabetes Mellitus; Dibenzothiazepines; Drug Monitoring; Humans; Hyperglycemia; Male; Osmolar Concentration; Quetiapine Fumarate

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

Patients with hyperthymic and cyclothymic temperaments often develop symptoms that fail to meet diagnostic criteria for bipolar disorders. These patients can be conceived as having bipolar disorder NOS (not otherwise specified), a bipolar spectrum disorder, cyclothymic disorder or cluster B personality traits. Here, we describe four of these patients with mild to moderate symptoms affecting mood, behaviour, emotional reactivity and sleep. Treatment with low-dose quetiapine (25-75 mg/day at night) lead to sustained symptom remission. Two of them were on quetiapine monotherapy. Such low doses occupy a minority of D2 and 5-HT2 receptors, which may nevertheless be of therapeutic value in mild cases. Alternatively, other mechanisms more likely to occur at low doses, such as antagonism of H1, alpha(1B)-adrenergic and other serotonin receptors, as well as reduction cortisol secretion, may be involved in the therapeutic efficacy of quetiapine.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cyclothymic Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Middle Aged; Quetiapine Fumarate; Temperament

We conducted an electronic chart review of a sample of all people attending secondary mental health care, in the county of Lanarkshire, Scotland, who were commenced on quetiapine for the following mood disorders: non-psychotic depression (n = 171), psychotic depression (n = 39), bipolar mania (n = 24), bipolar depression (n = 38) and bipolar mixed states (n = 31), between 2002 and 2007. We retrospectively assigned severity and improvement Clinical Global Impression (CGI) scores to measure effectiveness. Quetiapine was co-prescribed with antidepressants in 75-97% of depressive disorders. Commencing quetiapine was associated with clinical improvement in >64% of all patients, median doses (200-400 mg/day). For all depressive subtypes (non-psychotic, psychotic and bipolar) quetiapine was associated with improvement in 69% of patients. Across CGI measures, bipolar mania patients had the best outcome (89% improved). In bipolar mania, higher maximum doses were associated with greater improvement and 45% were continued on antidepressants. The results should be interpreted with caution due to the observational nature of the study and findings may not be attributed to the effects of quetiapine alone. Quetiapine was used mainly as an adjunct to other antidepressant and mood stabilising agents. The pharmacological profile of quetiapine suggests its properties extend beyond antipsychotic action, to antidepressant, anxiolytic and mood stabilising effects.

Topics: Adult; Affect; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Male; Mental Health Services; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Scotland; Severity of Illness Index; Time Factors; Treatment Outcome

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

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

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Hydrocortisone; Male; Middle Aged; Polysomnography; Quetiapine Fumarate; Sleep Wake Disorders; Young Adult

Queatiapine has been used in bipolar mania and most recently in bipolar depression with good results; however, its use in maintenance treatment has not been established yet. A case of a woman suffering from bipolar I disorder who underwent bone marrow transplantation twice because of leukaemia is presented. The use of quetiapine as a monotherapy was efficient and safe and proved to be a good treatment in mood stabilization for 1 year.

Topics: Antipsychotic Agents; Bipolar Disorder; Bone Marrow Transplantation; Dibenzothiazepines; Female; Humans; Leukemia, Myeloid, Acute; Middle Aged; Quetiapine Fumarate; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Compulsive Behavior; Dibenzothiazepines; Drug Therapy, Combination; Exercise; Humans; Impulsive Behavior; Male; Middle Aged; Quetiapine Fumarate; Treatment Outcome; Valproic Acid

Malignant neuroleptic syndrome (MNS) is a serious and potentially fatal side-effect of neuroleptic treatment. Beside antipsychotic drugs, other psychotropic drugs such as antidepressants and lithium carbonate can cause this life threatening side-effect. Underlying mechanism of this side-effect is still unknown and debated. So far some risk factors have been identified, with clinical observations and recent pharmacogenetic research suggesting (with inconsistent findings) correlation between genetic mechanisms and predisposition to MNS. Polymorphisms of CYP2D6 enzyme through which most psychotropic drugs are metabolized and TaqIA DRD2 which is target for antipsychotic drugs could be the link between pharmacogenetic factors and potential for development of MNS. In this paper we present two case reports with clinical presentation of three consecutive MNS. One patient developed MNS while he was taking combination of drugs: first time haloperidol, promazine and fluphenazine, second time fluphenazine and perazine and third time clozapine, promazine and valproic acid consecutively. The other patient developed MNS while taking following combination of drugs: first time haloperidol and lithium carbonate, second time risperidone and third time clozapine consecutively. Pharmacogenetic analysis for CYP2D6 and TaqI A DRD2 polymorphisms for both patients was done. Genotypisation of CYP2D6*1*3*4*5*6 in both patients showed no evidence of poor metabolizer phenotype. On the other hand, first patient was heterozygous for CYP2D6*4 (genotype *1/*4). CYP2D6 polymorphisms could have clinical significance because may lead to toxicity and unwanted side-effects in standard usual antipsychotic dose ranges. Analysis Taql A DRD2 polymorphism for first patient showed that he is heterozygous for A1 allele (genotype A1A2) which is commonly associated with predisposition to MNS. According to our literature three consecutive MNS are rarely described, and incidence of MNS generally is too low to perform clinical research. Many patophysiological mechanisms may probably underlie this complex and potentially fatal syndrome, still unknown etiology. But, genetic mechanisms could be significant. Further pharmacogenetic research, findings and analysis in patients who develop single or repeated MNS are strongly recommended. In long term, pharmacogenetic analysis, implemented in daily clinical practice, could help in prevention of this extremely serious side-effect.

Topics: Adult; Alleles; Antipsychotic Agents; Bipolar Disorder; Clozapine; Cytochrome P-450 CYP2D6; Dibenzothiazepines; Drug Therapy, Combination; Fluphenazine; Genetic Carrier Screening; Genotype; Haloperidol; Humans; Lithium Carbonate; Male; Neuroleptic Malignant Syndrome; Perazine; Polymorphism, Genetic; Psychotic Disorders; Quetiapine Fumarate; Receptors, Dopamine D2; Recurrence; Risperidone

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

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Middle Aged; Paroxetine; Quetiapine Fumarate; Restless Legs Syndrome

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

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Electrocardiography; Humans; Male; Middle Aged; Quetiapine Fumarate; Sick Sinus Syndrome

Quetiapine is an atypical antipsychotic with favorable properties in the treatment of bipolar disorder, but it has recently been associated with respiratory dysfunction.. In this case report, we describe a patient who developed quetiapine-induced hyperventilation and dyspnea after being treated with quetiapine.. To our knowledge, this is the first case presented with quetiapine-induced hyperventilation in a patient with bipolar disorder.. We recommend a quick reduction of the quetiapine dosage and a change to an alternative antipsychotic for patients treated with quetiapine, who report such respiratory symptoms without a somatic cause for the symptoms.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dyspnea; Humans; Hyperventilation; Male; Quetiapine Fumarate; Respiratory Rate

The aim of this study was to evaluate the tolerability and efficacy of rapid quetiapine loading in youth diagnosed with pediatric bipolar disorder (PBD).. Quetiapine was started at 100 mg/day, and increased to 400 mg/day by day 5 in 75 bipolar children (6-16 years), presenting in an acute manic or hypomanic episode. Subsequent dose adjustments were predicated on the clinical picture. Response was defined as a ≥ 50% reduction in baseline scores on the Young Mania Rating Scale (YMRS). Clinical Global Impression-Improvement Scale (CGI-I) scores of "2 much improved" or "1 very much improved" were used as secondary measures of response. Remission was defined as a YMRS score of ≤ 12. Adverse events, blood pressure, weight change, somnolence, extrapyramidal syndrome (EPS), and akathisia were monitored to determine tolerability.. At 8 weeks, 94% of the sample had a CGI-I score ≤ 2, and 70% were in remission at 6 months. Sedation was reported by 50% of subjects during the first week; this rate dropped to 5.6% at 6 months.. The findings indicate that rapid dose administration of quetiapine in children and adolescents with PBD is generally well tolerated and efficacious.

Topics: Adolescent; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Child; Dibenzothiazepines; Female; Humans; Male; Psychiatric Status Rating Scales; Quetiapine Fumarate; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Diabetes Mellitus; Dibenzothiazepines; Drug Industry; Humans; Legislation, Drug; Marketing; Quetiapine Fumarate; Schizophrenia

This study analyzed and defined specific factors that account for attrition in clinical research for patients with bipolar and substance-related disorders.. Data were analyzed from two completed studies: an open-label trial of lamotrigine in patients with bipolar disorder (BPD) and cocaine-related disorder, and a placebo-controlled trial of quetiapine in patients with BPD and alcohol-related disorders. Correlations and Independent sample t-tests were performed to assess the impact of baseline characteristics including on length of study participation. Significance was set at the p=0.05 level.. In the lamotrigine-treated patients, the presence of an amphetamine-related disorder, in addition to cocaine-related disorders, was associated with a shorter time in the study. In the quetiapine-treated patients higher scores on the Addiction Severity Index Legal subscale were associated with shorter length in the study. The presence of panic disorder was associated with shorter time in both studies.. Although the data were taken from the two largest clinical trials, to date, in patients with BPD and substance-related disorders, the sample sizes were relatively modest. In addition, the baseline assessments were somewhat different in the two studies limiting our ability to make conclusions on differences between patients with BPD and cocaine use versus alcohol use.. This study adds to an emerging literature on the significance of panic disorder in patients with BPD.

Topics: Adult; Alcohol-Related Disorders; Amphetamine-Related Disorders; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Cocaine-Related Disorders; Comorbidity; Diagnosis, Dual (Psychiatry); Dibenzothiazepines; Female; Humans; Lamotrigine; Male; Panic Disorder; Patient Dropouts; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Severity of Illness Index; Substance-Related Disorders; Time Factors; Triazines

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

We report a case of quetiapine-induced dysphagia in a geriatric patient which improved with discontinuation of the antipsychotic. The patient had developed dysphagia while being treated with antipsychotics for bipolar disorder. The patient's dysphagia showed significant improvement when she was taken off quetiapine. We review the available literature on antipsychotic-related dysphagia and suggest that clinicians need to be aware of the potential for this syndrome even with lower potency antipsychotics.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Deglutition Disorders; Diagnosis, Differential; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Quetiapine Fumarate

The aim of the current study was to evaluate quetiapine doses used across diagnosis categories in a sample of psychiatric inpatients.. Discharge letters of all adult inpatients who had received quetiapine between 1999 and 2005 were retrospectively reviewed. Logistic regressions were carried-out to assess links between quetiapine discharge dosage (> or =800 mg/day vs. <800 mg/day), diagnostic categories, substance abuse or dependence, benzodiazepine discharge doses, age and sex.. The data of 231 patients were included. Five hundred and for discharge documents were analyzed: 113 for psychotic disorders, 190 for personality disorders, 134 for bipolar and schizoaffective bipolar disorders, 29 for unipolar depression or anxiety disorders, and 35 for mental retardation. Considering psychotic disorders as a reference group, patients with personality disorders were statistically significantly less likely to be in the high quetiapine dosage group at discharge (P = 0.007, OR = 0.1 and CI [0.03; 0.6]).. Quetiapine seems to be used in a variety of clinical situations, with a wide range of doses and a lower dosage in patients treated for personality disorders.

Topics: Adult; Antipsychotic Agents; Anxiety Disorders; Benzodiazepines; Bipolar Disorder; Cross-Sectional Studies; Depressive Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Intellectual Disability; Male; Mental Disorders; Middle Aged; Patient Discharge; Patient Readmission; Personality Disorders; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies

Topics: Antipsychotic Agents; Bipolar Disorder; Congresses as Topic; Delayed-Action Preparations; Dibenzothiazepines; Drug Approval; Humans; Quetiapine Fumarate; Risperidone; Schizophrenia; United States; United States Food and Drug Administration

A 55-year-old man with congenital hemiparesis of the right side, three episodes of generalised tonic-clonic seizure at 16 years of age, and two episodes of severe depression and two episodes of hypomania in the past, presented with severe depression with psychotic symptoms. Computed tomography of the brain showed a grey matter-lined cerebrospinal fluid-filled cleft in the left cerebral hemisphere, involving the temporoparietal region. He was diagnosed to have bipolar II disorder, and was currently severely depressed with psychotic symptoms and schizencephaly. He improved with sodium valproate 1,000 mg/day, quetiapine 450 mg/day and escitalopram 20 mg/day after three weeks without any emergent side effects, and was maintaining well at three months follow-up. Although uncommon, schizencephaly may be considered as one of the differentials in cases of bipolar disorder along with congenital hemiparesis, mental retardation and/or seizures; and neuroimaging should be done to confirm the diagnosis.

Topics: Bipolar Disorder; Brain; Citalopram; Depression; Diagnosis, Differential; Dibenzothiazepines; Humans; Male; Malformations of Cortical Development; Middle Aged; Quetiapine Fumarate; Seizures; Tomography, X-Ray Computed; Treatment Outcome; Valproic Acid

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

Topics: Antipsychotic Agents; Bipolar Disorder; Clonazepam; Dibenzothiazepines; Female; Humans; Hypnotics and Sedatives; Middle Aged; Pyridines; Quetiapine Fumarate; Self Medication; Substance-Related Disorders; Zolpidem

Topics: Affect; Antipsychotic Agents; Bipolar Disorder; Central Nervous System Stimulants; Comorbidity; Dibenzothiazepines; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Self Medication; Substance-Related Disorders

The purpose of this article is to review the utilization and dosing of ziprasidone in a state hospital system and to compare the dosing to dosing recommendations contained in product labeling that suggest a starting dose of 40 mg/day and a target dose range of 40 to 160 mg/day for schizophrenia.. Dosing of ziprasidone was examined from the time when it was first marketed in 2001 up to and including calendar year 2006 using a database that contains patient information and drug prescription information for every inpatient within the adult civil facilities of the New York State psychiatric hospital system operated by the New York State Office of Mental Health. Supporting evidence for a therapeutic dose response for ziprasidone was examined by conducting a PubMed search for the period January 1, 1990, to June 1, 2008, identifying English-language articles related to ziprasidone dose in schizophrenia using the search terms ziprasidone, dose, and schizophrenia.. Although the highest efficacious dose of ziprasidone recommended in the manufacturer's product label is 160 mg/day, the mean dose of ziprasidone prescribed among patients hospitalized in New York State in calendar year 2006 and receiving antipsychotic medication (N = 7154) was 179 mg/day (N = 709), with 51.6% receiving doses in excess of 160 mg/day (N = 366). Patients discharged on treatment with ziprasidone (N = 189) received a mean dose of 206 mg/day. Patients with schizophrenia with a history of prior state hospital admission were more likely to receive doses greater than 160 mg/day. Clinicians in hospitals with the highest prescribing rates for ziprasidone were more likely to prescribe ziprasidone in excess of 160 mg/day. The initial dose on the first day for new starts on treatment with ziprasidone was 91 mg/day (N = 112). Published anecdotal reports describe the use of ziprasidone in excess of 160 mg/day and up to 640 mg/day among patients not responding to lower doses, but, currently, there are no published reports from double-blind randomized clinical trials establishing the utility of this high-dose treatment strategy.. Dosing of ziprasidone in a large state hospital system is higher than what has been established in the registration program for schizophrenia. Although there is anecdotal evidence describing the use of ziprasidone in excess of 160 mg/day, controlled clinical trials are needed to determine if these higher doses are more effective.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Utilization; Female; Hospitalization; Hospitals, Psychiatric; Hospitals, State; Humans; Male; Piperazines; Prescription Drugs; Product Labeling; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Aged; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Edema; Female; Foot Diseases; Humans; Quetiapine Fumarate; Valproic Acid

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Failure; Withholding Treatment

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

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Middle Aged; Psychotic Disorders; Quetiapine Fumarate

Topics: Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Humans; Lithium Compounds; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Valproic Acid

Research on postpartum mood disorders has focused primarily on major depressive disorder, bipolar I disorder, and puerperal psychosis and has largely ignored or neglected bipolar II disorder. Hypomanic symptoms are common after delivery but frequently unrecognized. DSM-IV does not consider early postpartum hypomania as a significant diagnostic feature. Although postpartum hypomania may not cause marked impairment in social or occupational functioning, it is often associated with subsequent, often disabling depression. Preliminary evidence suggests that bipolar II depression arising in the postpartum period is often misdiagnosed as unipolar major depressive disorder. The consequences of the misdiagnosis can be particularly serious because of delayed initiation of appropriate treatment and the inappropriate prescription of antidepressants. Moreover, no pharmacological or psychotherapeutic studies of bipolar postpartum depression are available to guide clinical decision making. Also lacking are screening instruments designed specifically for use before or after delivery in women with suspected bipolar depression. It is recommended that the treatment of postpartum bipolar depression follow the same guidelines as the treatment of nonpuerperal bipolar II depression, using medications that are compatible with lactation.

Topics: Adult; Anticonvulsants; Antidepressive Agents; Bipolar Disorder; Breast Feeding; Depression, Postpartum; Depressive Disorder, Major; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Female; Humans; Lactation; Lithium Compounds; Mass Screening; Milk, Human; Pregnancy; Pregnancy Complications; Psychiatric Status Rating Scales; Quetiapine Fumarate; Surveys and Questionnaires

Psychomotor retardation (PR) is among the most important features of depression. This study investigates the development of day- and night-time as well as intensity and quantity of circadian motor activity during a 4-week course of treatment among 27 patients with depression compared to 27 healthy controls. A diagnosis of major depression was made using SCID. Motor activity was continuously measured with an actigraph during the study and clinical course of depression with HAM-D-21. Motor activity was described as the quantity and intensity of movements during day- and night- time. Clinically improved patients had significantly intensified movements after 4 weeks, compared to subjects with <50% improvement on HAM-D. While the measures of day-time level of movements captured the clinical improvement of depression, clinical improvement was not reflected by the night-time measurements. This study demonstrates that the separated analysis of level and quantity of movements supports a better understanding of the nature of psychomotor retardation during depression. The subdivision in day- and night-time activity objectively measured with actigraphy captures distinct patterns of motor activity and represents prognostic factors in the treatment outcome of depression. The study also highlights the importance of studying the intensity of movements separately from the quantity of movements in relation to treatment outcome.

Topics: Actigraphy; Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Circadian Rhythm; Citalopram; Cyclohexanols; Depressive Disorder, Major; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Longitudinal Studies; Male; Middle Aged; Motor Activity; Personality Inventory; Prognosis; Prospective Studies; Quetiapine Fumarate; Signal Processing, Computer-Assisted; Sleep Initiation and Maintenance Disorders; Treatment Outcome; Venlafaxine Hydrochloride

The goal of this study was to examine provider prescribing habits following carbamazepine discontinuation and to assess for the presence of antipsychotic-related adverse drug reactions due to the loss of car-bamazepine-related induction of the cytochrome P450 enzyme (CYP) 3A4 and p-glycoprotein.. A retrospective chart review of patient records from January 2006 through December 2007 at the Veterans Affairs (VA) San Diego Healthcare System was done, which focused on the co-prescription of carbamazepine and a second-generation (atypical) antipsychotic (aripiprazole, quetiapine, risperidone) that is significantly affected by CYP3A4/p-glycoprotein induction. The cases in which carbamazepine was discontinued while the antipsychotic was continued during the 2-year time frame were then analyzed further. Data were collected concerning documentation of antipsychotic-related adverse drug reactions that occurred after carbamazepine was discontinued and prescribers' responses to carbamazepine discontinuation.. Nine patients were identified who had concomitant prescriptions for carbamazepine and a second-generation antipsychotic and who then discontinued carbamazepine. In only one case did the provider initially decrease the dose of the antipsychotic when carbamazepine was discontinued. Two patients experienced akathisia 3 weeks after carbamazepine was discontinued.. Many providers are not adjusting the dose of second-generation antipsychotics after discontinuation of a CYP3A4/p-glycoprotein inducer, placing patients at risk for adverse drug reactions. In addition to provider education, mechanisms need to be integrated into the current prescription processing software to alert providers of kinetic changes related to medication discontinuation. In addition, when discontinuing carbamazepine in patients who are being concomitantly treated with a second-generation antipsychotic that is a CYP3A4/p-glycoprotein substrate, providers should arrange for patient follow-up 2-4 weeks after carbamazepine discontinuation to evaluate patients for antipsychotic-related adverse drug reactions.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Carbamazepine; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Enzyme Induction; Female; Humans; Male; Medical Audit; Middle Aged; Piperazines; Psychotic Disorders; Quetiapine Fumarate; Quinolones; Retrospective Studies; Risk Factors; Risperidone

Topics: Adolescent; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Fructose; Humans; Immunoassay; Marijuana Abuse; Patient Compliance; Quetiapine Fumarate; Topiramate

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Masticatory Muscles; Middle Aged; Muscle Hypertonia; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dopamine Agonists; Female; Humans; Indoles; Middle Aged; Quetiapine Fumarate; Restless Legs Syndrome; Treatment Outcome

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Central Nervous System Agents; Dibenzothiazepines; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Evidence-Based Medicine; Humans; Lamotrigine; Lithium Compounds; Quetiapine Fumarate; Treatment Outcome; Triazines

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Approval; Humans; Quetiapine Fumarate; United States; United States Food and Drug Administration

Nowadays, there is a widespread use of atypical (second-generation) antipsychotics as an adjunct pharmacotherapy in psychiatry clinics, especially at lower doses in several diagnoses. Here, 2 cases are reported where patients with diagnosed schizophrenia displayed manic symptoms on quetiapine 100 mg/d. The cases presented here had no history of mood disorders. It is discussed that the mania/hypomania may be associated with quetiapine treatment and defined as an adverse effect. Manic symptoms may be a 'probable adverse effect' according to the Naranjo adverse drug reactions probability scale, with a score of 6 points in both our cases. Several studies have suggested that quetiapine-induced mania/hypomania may be associated with frontal dopamine release via serotonin 5HT2A receptor blockade. Hence, clinicians should monitor the mood alterations of patients carefully during the atypical antipsychotic treatment. This is also the conclusion of our study as the patients may be slow metabolisers of CYP450-3A4, as suggested by their previous side effects on different antipsychotics.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia

The aim of this naturalistic study was to compare the effectiveness of quetiapine and classical mood stabilizers, as mono- or combination therapy, in the long-term treatment of Bipolar Disorder (BD).. 232 DSM-IV BD I (n=91) or BD II (n=141) patients, treated and followed up for four years, were studied. Mood stabilizers were chosen by the treating psychiatrists on the basis of their clinical judgement. The sample was subdivided into 6 treatment groups: quetiapine (n=41), lithium (n=39), sodium valproate (n=73), lamotrigine (n=31), quetiapine plus lithium (n=25), and quetiapine plus sodium valproate (n=23). Throughout the 4-year follow-up period patients were assessed monthly, or whenever a recurrence occurred, by the administration of HAMD-21 and of the YMRS. Primary outcome measures were the duration of euthymia and the cumulative proportion of subjects who maintained euthymia. Kaplan-Meier survival analyses were done to tabulate and compare the differences in survival distributions across the different treatment groups (Log-Rank Mantel-Cox test).. The combined treatments with quetiapine plus lithium or sodium valproate were more effective overall in maintaining euthymia, (percentages of patients who maintained euthymia: 29.3% for quetiapine, 46.2% for lithium, 32.9% for sodium valproate, 41.9% lamotrigine, 80% for quetiapine plus lithium, and 78.3% for quetiapine plus sodium valproate). In addition, quetiapine monotherapy was as effective as lithium monotherapy or combination treatment with lithium or sodium valproate in preventing the recurrence of major depressive episodes.. The main limitations of the study are the lack of randomized, controlled conditions and the low doses of quetiapine used.. If the results from this study will be replicated, there will be important implications for the use of quetiapine in the long-term treatment of BD.

Topics: Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Lamotrigine; Lithium Carbonate; Longitudinal Studies; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Triazines; Valproic Acid

Topics: Antipsychotic Agents; Bipolar Disorder; Cystic Fibrosis; Dibenzothiazepines; Humans; Male; Middle Aged; Quetiapine Fumarate; Transplants

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: Adult; Antipsychotic Agents; Bipolar Disorder; Brain Injuries; Citalopram; Dibenzothiazepines; Drug Administration Schedule; Humans; Male; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bias; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Antipsychotic Agents; Bias; Bipolar Disorder; Data Interpretation, Statistical; Dibenzothiazepines; Double-Blind Method; Humans; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

In patients with bipolar disorder, recent brain imaging studies have reported cingulate cortex volume change. We performed a volumetric magnetic resonance imaging (MRI) study to assess the subregions of the cingulate gyrus; left anterior cingulate (LAC), left posterior cingulate (LPC), right anterior cingulate (RAC), and right posterior cingulate (RPC). Our sample consisted of bipolar patients that are either unmedicated (n=10), on valproate monotherapy (n=10) or on valproate plus quetiapine (n=10) versus healthy comparisons (n=10). Thirty right-handed bipolar disordered patients were recruited. Of them, 10 were first-applying patients who never had taken any drug for this condition (medication-naive group), 10 were on valproate treatment (valproate group) and 10 were on valproate plus quetiapine treatment (valproate plus quetiapine group). Cingulate gyrus volumes included both cortex and white matter. Drug-free patients had significantly smaller LAC and LPC volumes compared with valproate and valproate plus quetiapine groups and healthy controls. In addition, in post hoc comparisons, a trend toward significant difference was found between valproate plus quetiapine group and valproate group in regard to only LAC. Our findings suggest that valproate and quetiapine may have neuroprotective effects.

Topics: Adolescent; Adult; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dominance, Cerebral; Drug Therapy, Combination; Female; Gyrus Cinguli; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Quetiapine Fumarate; Statistics as Topic; Treatment Outcome; Valproic Acid

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

To determine whether the coprescribing of two or more antipsychotics, a relatively frequent practice with little data to support its safety and efficacy, is associated with an increased prevalence of metabolic syndrome.. 364 newly admitted adults treated with second-generation antipsychotics underwent assessments evaluating antipsychotic polytherapy, and of the presence of metabolic syndrome and triglycerides/high-density lipoprotein cholesterol ratio>3.5 (TG/HDL), a sensitive marker of insulin resistance. The correlates of antipsychotic polytherapy and associations with metabolic syndrome and TG/HDL were determined by univariate comparisons and multiple logistic regression analyses.. Antipsychotic polytherapy was present in 70 patients (19.2%) and was significantly more likely in patients with schizophrenia and those treated with clozapine, quetiapine or ziprasidone (p<0.0001). Compared with antipsychotic monotherapy, polytherapy was associated with elevated rates of metabolic syndrome (50.0% vs. 34.3%, p=0.015) and TG/HDL (50.7% vs. 35.0%, p=0.016). However, in logistic regression analyses, metabolic syndrome was significantly associated with higher body mass index (BMI), older age, a diagnosis of bipolar disorder or schizophrenia, and cotreatment with a first-generation antipsychotic (r(2): 0.25, p<0.0001). The TG/HDL marker of insulin resistance was associated with higher BMI, male sex, Caucasian race and absence of aripiprazole treatment (r(2): 0.14, p<0.0001). Antipsychotic polypharmacy dropped out of both multivariate models.. Compared with patients receiving antipsychotic monotherapy, patients on antipsychotic polytherapy have higher rates of metabolic syndrome and lipid markers of insulin resistance. However, antipsychotic polytherapy is not independently associated with the prevalence of these abnormalities, which are related to known demographic, clinical and anthropometric risk factors.

Topics: Adult; Age Factors; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Body Mass Index; Cholesterol, HDL; Clozapine; Cross-Sectional Studies; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Piperazines; Quetiapine Fumarate; Quinolones; Risk Factors; Schizophrenia; Thiazoles; Triglycerides

No study to date has examined the effects of mood stabilizer alone and the combination of mood stabilizer and atypical antipsychotic, quetiapine, on hippocampal neurochemical markers of bipolar disordered patients concurrently. We therefore undertook a proton magnetic resonance spectroscopy (1H MRS) study of drug-free patients with bipolar disorder (drug-free group), patients undergoing valproate treatment (valproate group), patients administered valproate+quetiapine (valprote+quetiapine group) and healthy controls, focusing on the in vivo neuroanatomy of the hippocampus.. Thirty patients from the Firat University School of Medicine Department of Psychiatry and 10 healthy controls gave written informed consent to participate in the study. The patients and controls underwent proton magnetic resonance spectroscopic imaging (1H MRSI), and measures of N-acetylaspartate (NAA), choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in hippocampal regions were obtained.. The drug-free patients had significantly lower NAA/CRE and NAA/CHO ratios compared with the valproate and valproate+quetiapine groups and the healthy controls. The lower NAA/CRE and NAA/CHO ratios remained statistically significant even after covarying for age or whole brain volume compared with the valproate and valproate+quetiapine groups and healthy controls. In post hoc comparisons, a significant difference was found between the valproate+quetiapine group and the valproate group only with regard to NAA/CHO.. Our findings suggest that valproate has a neuroprotective effect. In post hoc comparisons, a significant difference was found between the valproate+quetiapine and the valproate group with regard to NAA/CHO, indicating that the addition of quetiapine further increases the level of NAA and provides an additional neuroprotective effect.

Topics: Adult; Analysis of Variance; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Male; Quetiapine Fumarate; Valproic Acid

Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum.. Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed.. Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly.. Since the decision of the German Federal Court in 2002 'off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its 'off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect.. In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Bipolar Disorder; Dementia; Dibenzothiazepines; Drug Utilization; Female; Germany; Humans; Male; Middle Aged; Mood Disorders; Psychomotor Agitation; Quetiapine Fumarate; Schizophrenia

Although the maximal quetiapine doses in the published studies were restricted to 800 mg/day, higher quetiapine doses are not unusual in clinical practice. The aim of the present study was to evaluate the effectiveness, tolerability and clinical reasons associated to the use of high dosage of quetiapine (>800 mg), when used under routine clinical conditions, in a sample of bipolar disorder and schizoaffective bipolar inpatients.. Charts of all bipolar and schizoaffective adult inpatients, who had received quetiapine for a mood episode between 1999 and 2005 were retrospectively reviewed. These charts also included the assessment of manic and depressive symptoms on admission and at discharge using the Beck-Rafaelsen Mania Scale (MAS) and the Montgomery Asberg depression rating scale (MADRS), respectively.. Data of 50 patients were analyzed. The overall F in repeated measures ANOVA revealed a significant MAS scores reduction between admission and discharge. MAS scores reduction did not differ between the high and low quetiapine groups. Similarly, a significant MADRS reduction was found. Again, no differences between the high and the low dose group were found. Logistic regression analysis of the 50 patients revealed only mixed episodes predicted high quetiapine dosage.. The present study confirms quetiapine efficiency and tolerability in the treatment of bipolar episodes, even in doses > to 800 mg and found a link between quetiapine doses and mixed episodes.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies

Alopecia has previously been reported with the atypical antipsychotic medicines olanzapine and risperidone, but has not been described with quetiapine. Case reports of alopecia associated with quetiapine reported to the New Zealand Intensive Medicines Monitoring Programme were reviewed. The World Health Organization international spontaneous reporting database was also searched for additional case reports. Literature searches were conducted for previous reports of alopecia associated with quetiapine. The Intensive Medicines Monitoring Programme database included two case reports of alopecia associated with quetiapine. Assessment of these cases suggested a causal relationship with the medicine. The World Health Organization international database included a further 15 case reports, providing evidence supporting this association. No previously published reports of alopecia associated with quetiapine were identified. In conclusion, these are the first published case reports of alopecia associated with quetiapine.

Topics: Adult; Affective Disorders, Psychotic; Alopecia; Antipsychotic Agents; Azabicyclo Compounds; Bipolar Disorder; Citalopram; Clonazepam; Dibenzothiazepines; Female; Humans; Hypnotics and Sedatives; Piperazines; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Mood Disorders; Piperazines; Quetiapine Fumarate; Quinolones; Schizophrenia, Paranoid

To examine abnormalities in health-related quality of life (HRQOL) and to determine whether pharmacological intervention with divalproex or quetiapine alters HRQOL abnormalities in bipolar adolescents.. Parents of 23 adolescents diagnosed 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 (CHQ-PF 50) at baseline, prior to receiving medication and then at 28 days later.. Manic adolescents exhibited significantly worse HRQOL than national norms at baseline on all subscales of the CHQ-P50 except for those assessing physical well-being. Twenty eight days later, similar results were obtained for the divalproex group. Significant improvements in HRQOL, particularly on the psychosocial subscales, occurred for both groups.. HRQOL for bipolar youth improves following pharmacological treatments. However, distinct effects of specific treatments may exist, and impairment in several domains persists.

Topics: Activities of Daily Living; Adolescent; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Personality Assessment; Quality of Life; Quetiapine Fumarate; Sick Role; Social Adjustment; Valproic Acid

Agitation and aggression are potentially disruptive and dangerous features of bipolar mania. This analysis evaluated the effects of quetiapine on agitation and aggression in patients with bipolar I mania.. Four double-blind, randomized, controlled trials were conducted using similar protocols; 407 patients with bipolar I mania were randomized to quetiapine monotherapy (200-800 mg/day) or placebo for 12 weeks, and 402 patients were randomized to quetiapine (200-800 mg/day) or placebo in combination with lithium (Li) or divalproex (DVP) for 3 or 6 weeks. Measurements of agitation included the Positive and Negative Syndrome Scale (PANSS) Activation subscale, PANSS Supplemental Aggression Risk subscale scores, and Young Mania Rating Scale (YMRS) items relevant to agitation.. Initial reductions in both the PANSS Activation and PANSS Supplemental Aggression Risk subscale scores were noted by Day 4 with quetiapine and placebo. The reduction in PANSS Activation subscale scores was significantly greater with quetiapine monotherapy than placebo first at Day 21 (-3.5 versus -1.4, P<0.001) and also at Day 84 (-4.8 versus -1.2, P<0.001). The improvement in PANSS Supplemental Aggression Risk subscale score was significantly greater with quetiapine monotherapy than placebo by Day 14 (P<0.01) and all time points thereafter including Day 21 (-4.0 versus -1.8, P<0.001) and Day 84 (-5.6 versus -1.7, P<0.001). In combination therapy, the mean improvement in PANSS Activation subscale score at Day 21 was numerically but not significantly different with QTP+Li/DVP than PBO+Li/DVP (-4.2 versus -3.2, P=0.087). The mean PANSS Supplemental Aggression Risk subscale scores were significantly improved at Day 21 with QTP+Li/DVP versus PBO+Li/DVP (-5.05 versus -3.69, P<0.05).. Quetiapine is an effective and appropriate treatment choice in managing agitation and aggression associated with bipolar mania.

Topics: Adult; Aggression; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clinical Trials, Phase III as Topic; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Hostility; Humans; Lithium Compounds; Male; Multicenter Studies as Topic; Prospective Studies; Psychiatric Status Rating Scales; Psychomotor Agitation; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

To analyze the available evidence from randomized clinical trials regarding the effective dose range and optimal dose of quetiapine when treating bipolar I disorder patients with acute mania.. Patients with acute mania were treated with quetiapine as monotherapy (for 12 weeks) or in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 69.5 microg/mL) (Li/DVP) (for 3-6 weeks) in four double-blind, placebo-controlled studies according to a predetermined dosing schedule. Guidance for the dosing of quetiapine involved increasing the first day's dose (100 mg/day) by 100 mg on a daily basis until Day 4 (400 mg/day), then adjusting the dose up to 600 mg/day at Day 5, and up to 800 mg/day thereafter. Pooled data from the two monotherapy studies and the two combination therapy studies have been used to evaluate the effective quetiapine dose range. As the dose was flexible, effective dose was estimated by the mean last-week dose among responders. The mean last-week dose was defined as the median dose during the 7 days before the last available Young Mania Rating Scale (YMRS) assessment. Patients who achieved a > or = 50% decrease in the YMRS total score from baseline to end of treatment with quetiapine were considered responders. Tolerability was assessed from direct patient reports.. According to randomized clinical trials, administration of quetiapine compared with placebo achieved a statistically significant improvement in change from baseline YMRS score within the first week and onward, as monotherapy or in combination with Li/DVP. The average quetiapine dose (+/-SD) in responders during the last week of treatment was 575 (+/-175) at Day 21 and 598 (+/-198) mg/day at Day 84 for monotherapy, and 584+/-208 mg/day at Day 21 for combination therapy, with most responders receiving doses within the range of 400-800 mg/day. Dose escalation was rapid, with 92% of patients treated with monotherapy and 80% of patients treated with combination therapy reaching doses of 400 mg/day by Day 4, in accordance with protocol-defined dosing guidance. This dose administration schedule was generally well tolerated.. The mean last-week median dose among responders suggests that 600 mg/day of quetiapine is an effective target dose in acute mania.

Topics: Acute Disease; Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium Compounds; Male; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Dibenzothiazepines; Humans; Quetiapine Fumarate; Treatment Outcome

To evaluate the effects of quetiapine monotherapy compared with placebo on acute (3-week) and more sustained (12-week) rates of response and remission/euthymia in bipolar disorder patients with acute mania.. Two similar 12-week multicenter, double-blind, placebo-controlled, parallel-group studies were conducted, with an a priori decision to combine the data and analyze response and remission rates. Response was measured as a decrease of at least 50% in Young Mania Rating Scale (YMRS) scores from baseline to Day 21 and Day 84. Five remission/euthymia criteria were employed to determine efficacy at Day 21 and Day 84: (i) YMRS score < or = 12; (ii) YMRS score < or = 12 and Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 10; (iii) YMRS score < or = 12 and MADRS score < or = 8; (iv) YMRS score < or = 8; and (v) YMRS score < or = 8 plus a score < or = 2 for the YMRS core items of Irritability, Speech, Content, and Disruptive/Aggressive Behavior.. Patients treated with quetiapine (n=208) and placebo (n=195) had mean YMRS scores at entry of 33.3+/-6.3 and 33.5+/-6.7, respectively. Significantly higher response rates were observed with quetiapine compared with placebo, at Days 21 (48.1% versus 31.3%; p<0.001) and 84 (66.8% versus 40.0%; p<0.001). At Day 21, remission/euthymia rates with quetiapine monotherapy versus placebo were: 37.5% versus 23.1% (YMRS < or = 12), 35.6% versus 21.5% (YMRS < or = 12+MADRS < or = 10), 35.1% versus 20.0% (YMRS < or = 12+MADRS < or = 8), 25.0% versus 14.4% (YMRS < or = 8), and 21.6% versus 14.4% (YMRS < or = 8 plus core items < or = 2) (p<0.01 for all comparisons except YMRS < or = 8 plus core items < or = 2: p=0.06). By Day 84, these had increased to: 65.4% versus 35.9% (YMRS < or = 12), 60.1% versus 30.8% (YMRS < or = 12+MADRS < or = 10), 58.7% versus 29.7% (YMRS < or = 12+MADRS < or = 8), 60.1% versus 30.3% (YMRS < or = 8), and 56.7% versus 29.7% (YMRS < or = 8 plus core items < or = 2) (p<0.001 for all comparisons). The average daily dose of quetiapine in responders was 575 mg/day at Day 21 and 598 mg/day at Day 84. Quetiapine was generally well tolerated.. Quetiapine was associated with significantly higher response and remission/euthymia rates compared with placebo with most criteria used, in patients with acute mania at the end of both 3 and 12 weeks.

Topics: Acute Disease; Adolescent; Adult; Affect; Aged; Antimanic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multicenter Studies as Topic; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome

To review the safety/tolerability of quetiapine in four placebo-controlled studies in patients with bipolar I disorder experiencing acute mania.. Four double-blind, placebo-controlled studies evaluated quetiapine monotherapy (12 weeks) or quetiapine in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 68.6 microg/mL) (Li/DVP) (3 and 6 weeks) in patients with acute mania. Pooled data from the two monotherapy studies and the two combination therapy studies have been evaluated in the analysis presented here. Adverse event reporting, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) scores were recorded.. Most adverse events were mild to moderate. Common adverse events (> or = 5% and at least twice the placebo rate) with quetiapine monotherapy and combination therapy were somnolence, dry mouth, weight gain, dizziness, asthenia, pharyngitis, and postural hypotension. Treatment-related discontinuations due to adverse events were not significantly different between quetiapine and placebo, nor was the incidence of extrapyramidal symptoms (including akathisia) (quetiapine monotherapy 12.9% vs placebo 13.1%; combination therapy 21.4% vs placebo 19.2%). Mean change from baseline to endpoint in SAS and BARS scores was not significantly different between groups. Mean weight change at treatment end with quetiapine compared with placebo was +1.8 vs -0.15 kg in monotherapy; and +1.97 vs +0.27 kg with combination therapy. No patients discontinued due to weight gain. The effect of quetiapine monotherapy on serum prolactin levels was no different from placebo.. Quetiapine monotherapy and combination therapy were well tolerated in the treatment of acute mania.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium Compounds; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

The aim of this analysis was to compare the rates of remission/euthymia in patients with bipolar mania receiving quetiapine in combination with lithium/divalproex (QTP+Li/DVP) versus placebo (PBO) in combination with Li/DVP (PBO+Li/DVP).. A pooled analysis of two (one 3-week and one 6-week) double-blind studies of a total of 370 patients hospitalized with bipolar I mania who received quetiapine (up to 800 mg/day) in combination with Li (mean serum concentration 0.76 mEq/L) or DVP (mean serum concentration 69.5 microg/mL) was performed. For both studies, data were analyzed at Day 21. In addition, for the 6-week study, data were analyzed at Day 42. Five different criteria for remission/euthymia were used: (i) Young Mania Rating Scale (YMRS) score < or = 12; (ii) YMRS score < or = 12 plus a Montgomery-Asberg Depression Rating Scale (MADRS) score < or = 10; (iii) YMRS score < or = 12+MADRS score < or = 8; (iv) YMRS score < or = 8; and (v) YMRS score < or = 8 plus a score < or = 2 for the YMRS core items of Irritability, Speech, Content, and Disruptive/Aggressive Behavior.. In the pooled analysis, Day 21 remission rates (YMRS < or = 12) were significantly higher in patients treated with QTP+Li/DVP compared with those who received PBO+Li/DVP (48.7% versus 33.0%, p=0.003). Rates of remission/euthymia (YMRS < or = 12+MADRS < or = 10) were similarly improved with QTP+Li/DVP compared with Li/DVP alone (43.2% versus 26.5%, p=0.001). Using the most stringent criteria (YMRS < or = 12+MADRS < or = 8), rates of remission/euthymia were again significantly higher with QTP+Li/DVP than with Li/DVP alone (38.4% versus 25.9%, p=0.014). More patients treated with quetiapine met the stringent criterion of YMRS < or = 8 (31.9% versus 24.3%; p=NS). A trend in favor of quetiapine was also observed for the more stringent criterion of YMRS < or = 8 plus core items < or = 2 (28.1% versus 23.2%; p=NS). For the 6-week study, at Day 42, YMRS was < or = 12 in 68.3% of patients treated with QTP+Li/DVP compared with 57.3% of those who received PBO+Li/DVP (p=NS). Respective rates based on the remission criterion of YMRS < or = 8 were 36.5% and 32.3% (p=NS), and with YMRS < or = 8 and core items < or = 2 were 53.8% and 45.8% (p=NS). However, a significant difference was observed between patients treated with QTP+Li/DVP versus those treated with PBO+Li/DVP using criteria of YMRS < or = 12+MADRS < or = 10 (63.5% versus 49.0%, p<0.05) or YMRS < or = 12+MADRS < or = 8 (61.5% versus 46.9%, p<0.05).. At Days 21 and 42, quetiapine combined with Li/DVP compared to Li/DVP monotherapy yielded significant, sustained improvements in the rate of clinical remission/euthymia in patients with bipolar mania. Longer-term studies are warranted to assess whether quetiapine combined with other mood stabilizing medications can yield even longer-term resolution of symptoms of acute mania while concurrently preventing emergence of depressive symptoms.

Topics: Acute Disease; Affect; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium Compounds; Multicenter Studies as Topic; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

Late-onset bipolar disorder is rare and can be precipitated by organic brain disorders. While the association between hyperthyroidism and mania is well described, mania or hypomania precipitated by hypothyroidism is rare. The authors present late-onset bipolar disorder in a 72-year-old woman presenting with mania and psychosis, which appear to have been precipitated by autoimmune hypothyroidism. This case shows the importance of ascertaining the thyroid status in patients with mood and psychotic disorders, especially in elderly patients and in patients lacking prominent signs of thyroid disease.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Hypothyroidism; Psychotic Disorders; Quetiapine Fumarate; Thyroxine

An ideal antimanic therapy is well tolerated and offers full multidimensional symptom relief. The efficacy of quetiapine in the treatment of acute bipolar mania has previously been established. This post-hoc analysis aims to extend our understanding of quetiapine's antimanic efficacy by evaluating its therapeutic effect across the full spectrum of manic symptoms.. Patient-level data from four similar, randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of quetiapine in bipolar disorder patients with DSM-IV acute mania were combined. Two trials investigated quetiapine as monotherapy (twice daily) and two trials assessed the combination of quetiapine with either lithium (Li) or divalproex (DVP). Changes in scores on the total Young Mania Rating Scale (YMRS), and on each of the 11 items comprising the YMRS, were the primary measures of interest in this analysis. Changes in the Supplemental Aggression and Agitation subscales of the Positive and Negative Syndrome Scale (PANSS) were secondary measures analyzed.. Quetiapine as monotherapy, or in combination with Li or DVP, was a highly effective treatment for acute mania, as shown by overall change scores in the total YMRS. Patients treated with quetiapine monotherapy exhibited a significantly greater reduction (versus placebo) in YMRS total scores at Day 4 (-3.5 versus -2.2; p=0.021), with an increasing between-group difference reported throughout the duration of the trials at Day 21 (-13.6 versus -7.8; p<0.001) and at study endpoint on Day 84 (-19.0 versus -9.6; p<0.001). Quetiapine was also superior in efficacy to placebo on all categorical (i.e., response and remission rates) and secondary outcome parameters. On each of the 11 YMRS items, including the double-weighted core manic items, quetiapine was significantly superior to placebo (p<0.05). Effect sizes at Day 84 ranged from 0.37 to 0.61. Quetiapine in combination with Li/DVP offered a significant benefit over Li/DVP monotherapy, starting at Day 7 (p<0.05) and continuing to the primary study endpoint on Day 21 (p=0.01). Four of 11 YMRS items improved significantly more on quetiapine combination therapy than on Li/DVP monotherapy. The efficacy of quetiapine in these trials appeared independent of baseline disease severity, the presence of psychosis, and treatment-emergent sedation/somnolence. Quetiapine monotherapy produced significantly greater improvement than placebo on the PANSS Activation and the PANSS Supplemental Aggression Risk subscale scores. Similar findings were obtained with quetiapine combined with Li or DVP.. Patients with bipolar disorder may report severe and complex manic symptoms. The results herein indicate that quetiapine is efficacious across the multiple dimensions of mania, including medically serious symptoms commonly encountered in practice.

Topics: Acute Disease; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Lithium Compounds; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Treatment Outcome; Valproic Acid

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 purpose of this study was to determine optimal criteria for defining response and remission in adolescents with acute mania.. Data were analyzed from three treatment studies of adolescents with acute mania (N = 99). Trained raters completed the Young Mania Rating Scale (YMRS), and clinicians completed the Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) independent of YMRS ratings. For response, the percentages of reduction in YMRS scores from baseline to endpoint were compared with CGI-BP Mania Improvement scores. For remission, endpoint YMRS scores were compared with CGI-BP Mania Severity scores. Signal detection analyses were conducted to evaluate the efficiency of selected cutoffs associated with response and remission.. A > or =55% reduction in YMRS scores from baseline to endpoint was the optimal cutoff defining response. An absolute endpoint YMRS score < or =12 was the optimal cutoff defining remission.. The results of this signal detection analysis in adolescent mania suggest that current commonly used cutoffs to define response (> or =50% reduction) and remission (< or =12) may be appropriate with regard to efficiency. Studies with methods specifically tailored to evaluate and compare these rating scales and larger patient samples from multiple sites are needed to confirm these preliminary findings.

Topics: Acute Disease; Adolescent; Antimanic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Remission Induction; Sensitivity and Specificity; Signal Detection, Psychological; Surveys and Questionnaires; Treatment Outcome; Valproic Acid

Topics: Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Dibenzothiazepines; Drug Approval; Drug Monitoring; Humans; Nursing Assessment; Patient Selection; Psychopharmacology; Quetiapine Fumarate; Risk Factors; Time Factors; Treatment Outcome; United States; United States Food and Drug Administration

The aim of the current study was to evaluate the relationship between quetiapine's effect on the improvement of mood symptoms in bipolar patients and brain metabolite level changes as measured by proton magnetic resonance spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were recruited and treated with quetiapine for 12 weeks. Clinical assessment was performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale (CGI-S) at baseline and weekly intervals during the 12-week period. In order to evaluate metabolite level changes over time, (1)H-MRS scans were acquired at baseline and week 12. There were significant reductions in YMRS scores (by 43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week-period. Lactate levels significantly decreased over the 12-week study period (22.4%). This change in lactate levels was more prominent in quetiapine responders than in non-responders. Additionally, there was a positive correlation between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our findings suggest that quetiapine's antimanic and antidepressant efficacy in patients with rapid cycling bipolar disorder may potentially be related to decreased lactate levels in frontal regions of the brain.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Lactic Acid; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Protons; Quetiapine Fumarate; Severity of Illness Index

The foregoing is a case report about a 30-year-old woman, who was referred to our psychiatry clinic with a clinical picture of manic episode, at the 21st week of her first pregnancy. She had a history of bipolar affective disorder for 12 years, had two previous manic episodes and had stopped taking lithium 6 months ago because of her plans to become pregnant. Quetiapine was begun and the dose was slowly increased to 1200 mg/day after 2 weeks. She continued to receive quetiapine throughout her pregnancy. Her obstetrical and perinatal examinations were done by a consultant obstetrician. At the follow-up, she had given birth to a boy, at 39th week of her pregnancy, with an Apgar score of 10. Follow-up of the infant up to 3 months reveals normal physical and psychomotor development. The pros and cons of quetiapine use during pregnancy are discussed.

Topics: Adult; Antipsychotic Agents; Apgar Score; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Quetiapine Fumarate

Quetiapine is an atypical antipsychotic agent approved by the FDA for the treatment of schizophrenia, acute mania, and bipolar depression. Recently, reports of medication abuse, particularly intranasal and i.v. abuse, have been described. Three cases of oral misuse of quetiapine are presented and clinical implications are discussed. Clinicians should exercise caution when prescribing quetiapine to patients at risk for substance abuse.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Middle Aged; Quetiapine Fumarate; Substance-Related Disorders

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder, Major; Dibenzothiazepines; Estrogen Replacement Therapy; Female; Humans; Hysterectomy; Menopause; Middle Aged; Postmenopause; Quetiapine Fumarate; Valproic Acid

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dibenzothiazepines; Humans; Hyperlipidemias; Male; Middle Aged; Olanzapine; Quetiapine Fumarate

Continuation treatment for bipolar disorder often consists of a mood stabilizer and a second-generation antipsychotic. Quetiapine has been shown to be an effective treatment for acute mania and acute bipolar depression, but there are limited data for its use in continuation treatment. This study examined the effectiveness of open-label adjunctive quetiapine therapy for continuation treatment in patients with bipolar disorder. Prospectively collected life chart data from 63 outpatients with bipolar disorders, most recent episodes depressed, manic, or cycling, who received adjunctive quetiapine therapy as part of standard acute treatment were analyzed. Patients had 4 or more weeks of prequetiapine baseline data and at least 2 weeks of quetiapine treatment with no other medication changes. Patients were grouped by baseline symptoms; depression only, mania only, or both mania and depression (cycling group). Owing to small mania and well groups (n=4), differences between depression and cycling groups were examined and mania and well groups excluded. Fifty-five patients were included in the analyses. The primary outcome measure was change in mood severity from baseline to change in treatment regimen, as measured by the NIMH Life Charting Method. Patients received adjunctive quetiapine for a mean of 122 (SD=149) days. Both groups showed significant improvement in depression ratings and time spent depressed by week 10. Both groups showed significant improvement in overall mood. No between-group differences in improvement were found. Adjunctive quetiapine may be useful as continuation treatment in bipolar populations with both pure depressive and cycling symptoms. Further controlled studies are warranted.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Databases, Factual; Depression; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Fructose; Humans; Lamotrigine; Lithium Compounds; Male; Middle Aged; Mood Disorders; Prospective Studies; Quetiapine Fumarate; Time Factors; Topiramate; Treatment Outcome; Triazines

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

Secondary mania develops in as many as 9% of persons with traumatic brain injuries. The treatment of posttraumatic mania is not well defined, and agents traditionally used for the treatment of idiopathic manic episodes may not be well suited for use among individuals with traumatic brain injuries. Atypical antipsychotics are indicated for the treatment of idiopathic bipolar disorder, and have been used for other purposes among individuals with posttraumatic neuropsychiatric disturbances. This article offers the first description of the treatment of posttraumatic mania using the atypical antipsychotic quetiapine. Beneficial effects of this agent on posttraumatic mania, cognitive impairments, and functional disability in the subacute post-injury period are described. Possible mechanisms of action are discussed and the need for additional investigation of quetiapine for posttraumatic mania is highlighted.

Topics: Accidents, Traffic; Adult; Antipsychotic Agents; Bipolar Disorder; Brain; Brain Injuries; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Tomography, X-Ray Computed

Topics: Antipsychotic Agents; Behavioral Symptoms; Bipolar Disorder; Dementia; Dibenzothiazepines; Female; Humans; Mental Status Schedule; Middle Aged; Quetiapine Fumarate; Syndrome; Treatment Outcome; Valproic Acid

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Cyclohexanols; Dibenzothiazepines; Female; Humans; Postpartum Period; Pregnancy; Pregnancy Outcome; Pregnancy Trimesters; Quetiapine Fumarate; Sleep Wake Disorders; Trazodone; Venlafaxine Hydrochloride

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dexfenfluramine; Dibenzothiazepines; Drug Resistance; Female; Follow-Up Studies; Humans; Quetiapine Fumarate; Serotonin Receptor Agonists; Severity of Illness Index; Suicide, Attempted; Time Factors

To quickly reduce symptoms and to optimize long-term outcome, patients with an acute episode of schizophrenia or mania require prompt treatment intervention. The atypical antipsychotic quetiapine ('Seroquel') has been approved for the treatment of schizophrenia and manic episodes associated with bipolar disorder. For patients with acute symptoms such as aggression or agitation, higher doses of quetiapine than the recommended initiation schedule are often required. This report presents the tolerability findings from rapid initiation with high-dose quetiapine for eight patients who were consecutively admitted with acute symptoms of schizophrenia (n 5) or mania (n 3). The results from this case series show that quetiapine treatment could be safely titrated at a more rapid rate and to doses greater than that described in the current prescribing information. For most patients, rapid dose escalation was well tolerated; no serious side effects were observed and vital clinical parameters were unchanged; one patient experienced transient somnolence. In conclusion, these results suggest that rapid dose escalation of quetiapine could be a useful treatment approach for acutely ill patients with schizophrenia and bipolar mania in order to improve acute symptoms and support the need for randomized controlled trials. However, dose adjustments should be considered with respect to each patient's individual level of tolerability.

Topics: Acute Disease; Adolescent; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Creatine Kinase; Dibenzothiazepines; Drug Therapy, Combination; Humans; Male; Mianserin; Mirtazapine; Quetiapine Fumarate

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lamotrigine; Lithium; Male; Quetiapine Fumarate; Triazines; Valproic Acid

Quetiapine is an atypical antipsychotic that has shown efficacy in the treatment of positive and negative symptoms in schizophrenia without causing extrapyramidal symptoms (EPS). To date, there are two monotherapy and two combination therapy studies with a double blind, placebo-controlled design on the use of quetiapine in mania. Several open studies and case reports support the results of the controlled trials suggesting that quetiapine is effective in treating the broad spectrum of manic symptoms and is tolerated well.

Topics: Acute Disease; Antipsychotic Agents; Bipolar Disorder; Controlled Clinical Trials as Topic; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Humans; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Topics: Aged; Antimanic Agents; Bipolar Disorder; Brain; Cerebellum; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Lithium Carbonate; Lorazepam; Male; Neuropsychological Tests; Quetiapine Fumarate; Tomography, Emission-Computed, Single-Photon

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

Topics: Adult; Anticonvulsants; Bipolar Disorder; Darkness; Dibenzothiazepines; Dose-Response Relationship, Drug; Female; Humans; Phobic Disorders; Quetiapine Fumarate

Quetiapine (Seroquel), an atypical antipsychotic with established efficacy in the treatment of schizophrenia, shows efficacy in the treatment of acute mania and depression associated with bipolar disorder.Quetiapine, either as monotherapy or in combination with lithium or divalproex sodium (valproate semisodium), is generally well tolerated and effective in reducing manic symptoms in adult and adolescent patients with acute bipolar mania, and is approved for use in adults for this indication. As monotherapy, the drug is also effective in reducing depressive symptoms in patients with bipolar depression. It is associated with a low incidence of extrapyramidal symptom (EPS)-related adverse events and low EPS ratings in bipolar disorder. Quetiapine thus shows potential in the treatment of bipolar depression, and represents a useful agent for the treatment of acute bipolar mania.

Topics: Antipsychotic Agents; Bipolar Disorder; Depression; Dibenzothiazepines; Humans; Quetiapine Fumarate

The aim of this study was to explore relationships between the Children's Depression Rating Scale-Revised (CDRS-R) and Hamilton Rating Scale for Depression (HAM-D) in adolescent bipolar disorder. We hypothesized that CDRS-R and HAM-D scores would be significantly correlated and both scales would be sensitive to change resulting from treatment.. Data from a randomized, double-blind, placebo-controlled study of quetiapine with divalproex versus divalproex alone (n = 30) and an open-label study of lithium (n = 27) were used. Assessments using the CDRS-R and HAM-D were completed separately without any dependence on ratings from the alternate rating scale or specific order. All raters for symptom rating scales were blinded to the study for which they were completing a patient assessment and the intent to conduct these post hoc analyses and were different from those who performed diagnostic interviews. Relationships between these measures were assessed using the Pearson correlation coefficient, and receiver operator characteristic curves evaluated the ability of CDRS-R and HAM-D scores to predict the level of global improvement.. The mean (+/- standard deviation) age of subjects was 15.0 +/- 1.6 years. Baseline CDRS-R and HAM-D scores were moderately correlated (r = 0.63; p < 0.001), while week 6 scores showed stronger correlation (r = 0.88; p < 0.001). Both measures showed significant main effects for time on treatment (CDRS-R: F(3.4,191.2) = 39.4, p < 0.001; HAM-D: F(3.9,217.9) = 38.5, p < 0.001). A CDRS-R score of 30.5 and HAM-D score of 7.5 represent the highest sensitivity and specificity in classifying responders and nonresponders. A 42.2% and 60.6% reduction in baseline CDRS-R and HAM-D scores, respectively, provided the highest sensitivity and specificity.. Our preliminary results demonstrated that CDRS-R and HAM-D scores were significantly correlated, suggesting that either measure may be used to assess depressive symptoms in studies of adolescent bipolar disorder. Limitations to this study included a relatively small pooled sample, variation in clinician judgment, and study design not specific for the comparison of rating scales. Studies with methods specific to evaluate and compare these rating scales and larger patient samples from multiple treatment sites are needed to confirm these findings.

Topics: Adolescent; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Clinical Trials as Topic; Depression; Dibenzothiazepines; Humans; Lithium Carbonate; Psychiatric Status Rating Scales; Quetiapine Fumarate; Valproic Acid

Quetiapine fumarate (Seroquel) is a dibenzothiazepine psychotropic agent that was introduced in 1997 for treating psychoses. Quetiapine is being found with increasing frequency in postmortem cases in Virginia. We report the postmortem results and histories of 20 quetiapine cases from the Office of the Chief Medical Examiner in Virginia covering the period 1999 through 2004. Quetiapine was extracted from blood using a basic drug solid-phase extraction (SPE) and identified by full scan electron impact gas chromatography-mass spectrometry (GC-MS). Quetiapine quantification was accomplished by forming the trimethylsilyl derivative with bis(trimethylsilyl)trifluoracetamide/trimethylchlorosilane and using selected ion monitoring GC-MS. The quetiapine trimethylsilyl derivative ions acquired were m/z 210, 239, and 322. Methapyrilene was the internal standard, and ions m/z 97 and 58 were monitored. The method was linear from 0.1 to 5.0 mg/L with a limit of quantitation of 0.1 mg/L. The quetiapine mean and range of concentrations found in each tissue are as follows: peripheral blood, 7.7 mg/L (0.14-37 mg/L, n = 17); heart blood, 23.63 mg/L (0.53-76 mg/L, n = 4); liver, 91 mg/Kg (1.1-510 mg/Kg, n = 19); bile, 44 mg/L (6.0-96 mg/L, n = 4); urine, 15 mg/L (1.9-37 mg/L, n = 8); gastric, 897 mg total (3.5-3960 mg, n = 7); and vitreous, 1.4 mg/L (0.2-3.2 mg/L, n = 5). The average of all blood concentrations in 18 cases in which quetiapine contributed to the cause of death was 7.95 mg/L (0.4-76 mg/L). The manner of death in 13 of those cases was suicide, two were undetermined, and three were accidents. In two cases in which quetiapine was an incidental finding, the blood concentrations were 0.14 and 1.0 mg/L. Quetiapine and other toxicological findings are presented with the cause and manner of death to assist in interpreting future quetiapine findings in postmortem samples.

Topics: Adolescent; Adult; Antipsychotic Agents; Autopsy; Bile; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Drug Overdose; Female; Gas Chromatography-Mass Spectrometry; Gastric Juice; Humans; Liver; Male; Middle Aged; Quetiapine Fumarate; Suicide; Tissue Distribution; Virginia

Quetiapine is a novel and atypical antipsychotic agent with serotonin 5-HT2A antagonism higher than D2 blockade. However, it has the lowest affinity for serotonin receptors among atypical antipsychotics. Besides its D2 blockade, it is not as great as seen with risperidone and olanzapine and is even less than that of clozapine. Open-label and controlled trials suggest efficacy of quetiapine as an adjunct therapy in patients with obsessive-compulsive disorder, refractory to treatment with selective serotonin reuptake inhibitors. There is one report of quetiapine exacerbating obsessive-compulsive symptoms (OCS). We report 5 cases with bipolar I disorder (n = 3), psychotic depression (n = 1), and schizophrenia (n = 1) in which quetiapine produced de novo OCS. The underlying pathogenetic mechanisms and the risk factors for this action of quetiapine and of atypical antipsychotics, in general, are not yet known. The description of 5 patients with different diagnoses supports the issue of OCS exacerbation or induction with atypical antipsychotics. Clinicians' awareness and close monitoring of the patients is warranted.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Schizophrenia

The use of atypical antipsychotic medication is increasing, with an increase in reported side-effects. The first reported case of quetiapine and citalopram-associated serotonin syndrome is discussed with reference to a Medline, Embase, and PsycINFO literature search. The putative aetiological mechanism is supersensitivity of 5-HT(1A) receptors (quetiapine) within an environment of increased synaptic available serotonin (citalopram). The symptom profile of serotonin syndrome overlaps with neuroleptic malignant syndrome, but can be reliably differentiated using a time and toxicity scale.

Topics: Adult; Alprazolam; Anti-Anxiety Agents; Antipsychotic Agents; Bipolar Disorder; Citalopram; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Quetiapine Fumarate; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Serotonin Syndrome; Treatment Outcome

To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania.. Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage.. The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo.. In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo.

Topics: Adult; Akathisia, Drug-Induced; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Drug Therapy, Combination; Female; Haloperidol; Humans; Lithium Compounds; Male; Middle Aged; Multicenter Studies as Topic; Neurologic Examination; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Risk; Treatment Outcome; Valproic Acid

To present a tool that allows estimation of the budget impact of treatments for acute mania in bipolar I disorder from a US healthcare payer perspective.. Using discrete event simulation, the course of individuals is simulated beginning with hospitalization. Discharge depends on symptom level measured by the Young Mania Rating Scale (YMRS). The treatment effect is determined using time-dependent regression equations derived from trial data, and decision rules obtained from clinical experts. Outcomes include: time to response and symptom resolution; proportion of subjects reaching each outcome; number of adverse events. Costs were obtained from hospital discharge databases, the National Medicare Physician Fee Schedule and RedBook. Different scenarios are examined, each describing the proportion of subjects on the various treatments (lithium, divalproex sodium, olanzapine, risperidone, and quetiapine--monotherapy and in combination with lithium). Analyses are intention-to-treat over 100 days, corresponding to follow-up in mania trials. Despite its flexibility and structural adaptability, the model has some important limitations related to the characteristics of the clinical trials. These include focus on inpatient management of acute mania, use of the YMRS as the model driver, polypharmacy restricted to two-drug regimens, no explicit consideration of titration and dose changes, and relatively short time horizon.. Scenarios with a greater proportion of quetiapine users (5% vs. 40% and 100%) result in a smaller impact on the healthcare budget (6912, 6277, and 5525 dollars per patient, respectively) and improvements in patient outcomes (e.g., 43%, 47%, and 54% responding at day 21; 74%, 77%, and 80% remitting by day 84). Sensitivity analyses showed that the budget impact is influenced by drug prices, discharge criteria and side-effect management.. Results suggest that increased use of quetiapine for bipolar mania in the US is economically justified and improves health outcomes. In addition, this model illustrates that discrete event simulation is a useful and versatile tool for budget impact analyses.

Topics: Antipsychotic Agents; Bipolar Disorder; Budgets; Clinical Trials as Topic; Dibenzothiazepines; Drug Costs; Economics, Pharmaceutical; Health Care Costs; Hospitalization; Humans; Length of Stay; Models, Economic; Quetiapine Fumarate; Treatment Outcome; United States

This research assesses the development of the night-activity rhythm and quality of sleep during course of treatment among patients with unipolar or bipolar depression and receiving antidepressant treatment plus quetiapine. Twenty-seven patients with major depressive episode were included into a 4-week follow-up study and compared with 27 healthy controls. Motor activity was continuously measured with an electronic wrist device (actigraphy), sleep was assessed with the Pittsburgh Sleep Quality Index, and patients were clinically assessed with the Hamilton depression score. All patients received a standard antidepressant treatment plus quetiapine. Whereas we found a rapid and maintaining improvement of subjective sleep parameters during the 4-week study, we observed a rapid improvement of some objective sleep parameters (actigraph) within the first week, but no further significant change of objective sleep parameters during the rest of the study. Another main finding of this study is that changes of subjectively and objectively assessed sleep parameters do not necessarily reflect clinical improvement of depression during the same timeline. Despite partial clinical remission, objective sleep parameters still showed significantly different patterns compared with controls. This study is the first to examine the effect of quetiapine on locomotor activity alongside with sleep in depression. As the studied patients with depression showed improvement in subjective and objective sleep parameters, quetiapine may be a promising drug for patients with depression and insomnia. Further studies need to investigate in detail the timeline of clinical remission and alterations of objective and subjective sleep parameters.

Topics: Adult; Aged; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Case-Control Studies; Circadian Rhythm; Depressive Disorder; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Motor Activity; Polysomnography; Psychiatric Status Rating Scales; Quetiapine Fumarate; Research Design; Sleep; Sleep Initiation and Maintenance Disorders; Time Factors

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

Topics: Acne Vulgaris; Adolescent; Anti-Bacterial Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lithium Carbonate; Minocycline; Quetiapine Fumarate

Topics: Anti-Inflammatory Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Graft Rejection; Humans; Injections, Intravenous; Liver Transplantation; Male; Methylprednisolone; Middle Aged; Quetiapine Fumarate

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

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Nausea; Prochlorperazine; Quetiapine Fumarate; Substance Withdrawal Syndrome; Treatment Outcome

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

"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: Adult; Antipsychotic Agents; Anxiety; Bipolar Disorder; Comorbidity; Dibenzothiazepines; Female; Humans; Phobic Disorders; Quetiapine Fumarate; Treatment Outcome

Topics: Agranulocytosis; Antipsychotic Agents; Bipolar Disorder; Clozapine; Dibenzothiazepines; Female; Humans; Leukopenia; Middle Aged; Quetiapine Fumarate

Topics: Activities of Daily Living; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Humans; Patient Compliance; Psychiatric Status Rating Scales; Quality of Life; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

This study evaluated the overall efficacy and tolerability of quetiapine in the treatment of inpatients with acute mania who are intolerant to risperidone in combination with a mood stabilizer. Eighteen patients completed this 3-week trial. The efficacy and tolerability was assessed upon admission, at baseline, and 1 and 3 weeks later. The Young mania rating scale (YMRS) and clinical global impression-severity (CGI-s) scores from the baseline to the endpoint, decreased by 39.8% and 40.0%, respectively. Fifteen (78.9%) and 18 (94.7%) patients exhibited at least a 50% improvement in the YMRS and CGI-s scores by the end of the trial. Measurements taken through the Barnes akathisia rating scale (BARS), the Simpson-Angus rating scale (SARS) and the drug attitude inventory shortened version-10 (DAI-10) also showed significant improvement. This study suggests that quetiapine may hold promise as an alternative regimen that does not worsen the psychopathology, particularly for those vulnerable to the side effects of drugs, including atypical agents such as risperidone, in naturalistic treatment settings.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Risperidone; Treatment Outcome

Observations made with quetiapine (QUET) in this case give clues for some aspects of its use for patients with bipolar disorder. Weight gain (11 kg; 16.6% increase in 21 weeks) and improvement in manic symptoms occurred after QUET add-on to lithium (Li). Patient's mood improved after QUET add-on without causing extrapyramidal symptoms (EPS), while QUET was discontinued due to weight gain. Short-term QUET add-on to Li may help mood stabilization in bipolar I disorder. Weight changes must be observed carefully.

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Weight Gain

Quetiapine, a new atypical antipsychotic, was added to ongoing treatment of bipolar I outpatients (n=15) for symptoms of illness (mood lability, irritability, psychosis and/or difficulty sleeping). All evaluations were prospectively obtained, with the majority of patients (n=9) showing much or very much improvement on the Clinical Global Impression for Bipolar Disorder (CGI-BP). Somatic complaints were limited. Mean (SD) duration before changes in medication regimens was 134 (100) days. Studies of the use of quetiapine in maintenance treatment of bipolar disorder are warranted.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Humans; Prospective Studies; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Comorbidity; Depression, Postpartum; Dibenzothiazepines; Female; Humans; Hyperprolactinemia; Piperazines; Quetiapine Fumarate; Risperidone; Thiazoles; Treatment Outcome

Quetiapine (Seroquel) is an atypical antipsychotic drug belonging to a new chemical class, the benzothiazepine derivatives. We present three cases from the Provincial Toxicology Center of British Columbia, Canada in which suicidal overdose deaths were associated with quetiapine. The blood specimens were initially subjected to a thorough qualitative analysis. Basic drugs were screened for by liquid-liquid extraction followed by gas chromatography-nitrogen-phosphorus (GC-NPD) and gas chromatography-mass spectrometry-electron impact detection utilizing both in-house and commercial search libraries. Acidic and neutral drugs were screened for by liquid-liquid extraction followed by high-performance liquid chromatography-diode-array detection. Volatiles were assayed by gas chromatography-flame-ionization detection. Quetiapine was assayed in biological specimens by basic extraction with n-butyl chloride and derivatized with 50 microL of MTBSTFA and separation by GC-NPD. Linearity was observed up to 2.0 mg/L. Samples with concentrations exceeding the linearity were diluted. These cases were chosen for study because they were all deaths as a result of suicidal ingestion of drugs in which quetiapine was considered a significant factor. The concentrations of quetiapine in these cases are 6-16 times greater than the upper reported therapeutic range (0.1-1.0 mg/L). In case #1, the concentrations of quetiapine found were 7.20 mg/L (19 micromol/L) in blood and 0.93 mg/L (2.4 micromol/L) in vitreous fluid. In case #2, the concentrations of quetiapine found were 16 mg/L in blood (42 micromol/L), 120 mg/kg (310 micromol/kg) in liver, and 1.8 mg/L (4.6 micromol/L) in vitreous fluid. In case #3, the concentrations of quetiapine found in femoral blood was 5.90 mg/L (15 micromol/L). In all cases, drugs in addition to quetiapine were detected, but in cases #1 and #2, the cause of death was considered to be a quetiapine overdose and the other drugs were not considered to be contributory. Case #3 was considered a mixed drug overdose.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Overdose; Fatal Outcome; Female; Gas Chromatography-Mass Spectrometry; Humans; Middle Aged; Quetiapine Fumarate; Schizophrenia; Suicide

We report the clinical history of a patient with drug induced liver injury due to quetiapine who ultimately developed subfulminant hepatic failure and died. The clinical presentation, laboratory data, as well as liver histopathology were supportive of the putative diagnosis of drug induced liver injury. To our knowledge, this is the first report of the important association between quetiapine and drug induced liver injury.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Fatal Outcome; Female; Humans; Liver Failure; Middle Aged; Quetiapine Fumarate

The aim of this study was to assess the safety and effectiveness of quetiapine for children and adolescents with bipolar disorder when used as monotherapy or in combination with other agents.. The outpatient medical charts of youths with a Diagnostic and Statistical Manual of Mental Disorders-fourth edition (text revision) (DSM-IV-TR) diagnosis of bipolar disorder who were treated with quetiapine were retrospectively reviewed using the Clinical Global Impression (CGI) Scale.. Thirty-two patients (mean age, 10.8 +/- 3.9 years) with bipolar disorder, type I (n = 16), type II (n = 10), cyclothymia (n = 2), and bipolar not otherwise specified (NOS) (n = 4) who had been treated (mean duration, 6.1 +/- 5.9 months) openly with quetiapine (mean dose, 397.4 +/- 221.4 mg/day) were identified. Fourteen patients (43.8%) received only quetiapine. No serious adverse events occurred. Response rate (defined by a CGI-Improvement (CGI-I) score of < or =2 at end point) was 80.0% for the entire group and 78.6% for the subgroup who received quetiapine monotherapy. CGI-Severity (CGI-S) scores significantly improved from baseline to end point for both groups.. Preliminary results suggest that quetiapine is a safe and effective treatment for both children and adolescents with bipolar disorder when used as monotherapy or in combination with other agents.

Topics: Adolescent; Bipolar Disorder; Child; Child, Preschool; Dibenzothiazepines; Female; Humans; Male; Quetiapine Fumarate; Retrospective Studies; Statistics, Nonparametric

A young woman presented with multiple central hypersensitivity disorders, including fibromyalgia, headache, pelvic pain and several smooth muscle spasm disorders, including irritable bowel syndrome, irritable bladder and Raynaud's phenomenon. She also had significant fatigue and sleep problems. Her case illustrates the importance and surprising frequency of atypical bipolar mood disorders in people with multiple central hypersensitivity pain disorders, especially with depression and anxiety resistant to antidepressant treatment. Considering neurological mechanisms common to her overlapping disorders was very helpful in guiding treatment choices. This experience illustrates the value of serotonin receptor type 2 (5HT2) inhibition with atypical neuroleptics, of neural cation channel and glutamate inhibition with anticonvulsants, and the potential usefulness of antidepressants after establishing 5HT2 control to enhance downward inhibitory tracts. Medications with combined usefulness for both bipolar mood and pain disorders were highly effective for her multiple hypersensitivity problems.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Fibromyalgia; Humans; Hypersensitivity; Irritable Bowel Syndrome; Migraine Disorders; Pain; Quetiapine Fumarate; Serotonin; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Muscular Diseases; Pain; Quetiapine Fumarate

This case illustrates the induction of manic-like symptoms in a 26-year-old male patient with DSM-IV paranoid schizophrenia following treatment with quetiapine. The only drug he had received prior to quetiapine was risperidone which was occasionally taken in the previous 3 years. The manic symptoms remitted after quetiapine withdrawal.

Topics: Adult; Bipolar Disorder; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Psychotic Disorders; Quetiapine Fumarate; Severity of Illness Index

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Mood Disorders; Quetiapine Fumarate; Schizophrenia

Despite therapeutic treatment with lithium or valproate, patients with bipolar I disorder often require adjunctive therapy to treat persistent symptoms. In order to evaluate the effects of quetiapine for bipolar symptoms inadequately responsive to mood stabilizers, a retrospective chart review was undertaken at the Veterans Affairs (VA) Long Beach Mood Disorders Clinic for all bipolar I outpatients who had been prescribed adjunctive quetiapine during an 18-month study period. Among 75 lithium- or valproate-treated patients receiving quetiapine, 16 were identified in whom therapeutic treatment with lithium (> or =0.8 meq/l) or valproate (> or =75 microg/ml) could be verified during the 2-month period prior to quetiapine initiation. Chart notes were utilized by the principal investigator to assign Clinical Global Impression Bipolar ratings (CGI-BP) before and after 30-120 days of quetiapine treatment (mean=173+/-157 mg). Nine of 16 lithium- or valproate-stabilized bipolar patients (56%) were judged much or very much improved in CGI-BP overall ratings following adjunctive quetiapine. In addition, for the entire sample, quetiapine augmentation resulted in significant improvements in clinician-rated bipolar severity scores (CGI-BP) for mania, depression, and overall bipolar illness. The majority of quetiapine-related symptomatic improvement was due to diminished insomnia, agitation, irritability, and mood disturbance. Side effects were mild and transitory including sedation and dizziness. Low-dose quetiapine may be a useful and well-tolerated adjunct for some bipolar patients with incomplete response to lithium or valproate.

Topics: Adult; Aged; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Lithium; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Valproic Acid

A young man with a 13 year history of Tourette disorder and obsessive-compulsive disorder developed mania on clomipramine. Quetiapine 600 mg, daily was followed by resolution of the mania and improvement of the symptoms of Tourette disorder and obsessive compulsive disorder. It seems that quetiapine may be useful in treatment of Tourette disorder with or without comorbid disorders.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Clomipramine; Dibenzothiazepines; Humans; Male; Obsessive-Compulsive Disorder; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Tourette Syndrome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Dibenzothiazepines; Humans; Male; Quetiapine Fumarate; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Middle Aged; Obsessive-Compulsive Disorder; Quetiapine Fumarate

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroconvulsive Therapy; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Neurologic Examination; Parkinsonian Disorders; Quetiapine Fumarate; Risk Factors

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Diazepam; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Haloperidol; Humans; Quetiapine Fumarate; Schizophrenia, Paranoid; Severity of Illness Index

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

Quetiapine fumarate (Seroquel) is an atypical antipsychotic agent approved for the treatment of psychosis. It is extensively metabolized by the CYP450 3A4 isozyme. The principal aim of the study was to investigate the effect of multiple doses of cimetidine, a nonspecific P450 inhibitor, on the steady-state pharmacokinetics of quetiapine. Thirteen patients (seven completers) with selected psychotic disorders received escalating doses of quetiapine from 25 to 150 mg three times daily on days 3 to 8 and were then maintained at 150 mg three times daily until day 19. Cimetidine (400 mg) was initiated on the afternoon of day 15 and administered three times daily with every dose of quetiapine thereafter. Quetiapine plasma concentrations were measured before and after cimetidine coadministration, and quetiapine pharmacokinetic parameters were calculated. Of the 13 men who entered the study, seven completed it. A slight increase in quetiapine plasma levels and reduction in oral clearance were observed after cimetidine coadministration. No serious adverse events were observed during quetiapine treatment. No clinically relevant alterations in quetiapine pharmacokinetics were observed after cimetidine coadministration in patients with psychotic disorders.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Cimetidine; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Humans; Male; Metabolic Clearance Rate; Middle Aged; Mixed Function Oxygenases; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypertriglyceridemia; Quetiapine Fumarate; Risk Factors

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Psychotic Disorders; Quetiapine Fumarate

Topics: Adolescent; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Humans; Male; Psychotic Disorders; Quetiapine Fumarate

Topics: Acetates; Adult; Amines; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lithium; Quetiapine Fumarate; Topiramate

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Lithium Carbonate; Psychotherapy; Quetiapine Fumarate

Quetiapine fumarate is a recently marketed atypical antipsychotic medication proved to be effective in the treatment of schizophrenia and schizoaffective disorder in the younger population. There is a paucity of studies of this drug in the elderly and more data are needed on the effects of quetiapine in this population, especially those with comorbid medical illnesses. Quetiapine was used to treat seven elderly hospitalized patients between 61 and 72 years of age who manifested signs of psychosis related to schizophrenia, schizoaffective disorder, or bipolar disorder. All patients had been treated previously with conventional antipsychotics or other atypical antipsychotics. Response was assessed by observation of patient's behavior. Four patients responded to treatment; three did not respond. Positive symptoms decreased markedly in all four responders. Negative symptoms showed marked decrease in two patients and moderate decrease in one patient. Preexisting extrapyramidal symptoms (EPS) diminished in three patients. Transient hypotension, dizziness, and somnolence occurred in two patients. No other side effects were noted. No adverse consequences occurred when lithium, carbamazepine, valproic acid, or venlafaxine was given concurrently. The reduction of positive and negative symptoms of schizophrenia and lack of significant EPS and minimal sedative, hypotensive, and anticholinergic side effects indicate that quetiapine may be a safe and effective medication for the elderly.

Topics: Aged; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology

In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response.. In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria.. Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding.. Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Depressive Disorder; Dibenzothiazepines; Female; Hospital Records; Humans; Male; Prognosis; Psychotic Disorders; Quetiapine Fumarate; Retrospective Studies; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Child; Child Psychiatry; Dibenzothiazepines; Female; Humans; Quetiapine Fumarate; Recurrence; Treatment Outcome

To determine if quetiapine, an atypical antipsychotic agent approved for the treatment of schizophrenia, is effective in the treatment of bipolar disorder.. A retrospective chart review identified six patients with DSM-IV bipolar disorder, type I, who received open uncontrolled treatment with quetiapine in the setting of nonresponse or intolerance to traditional mood-stabilizing treatments. Treatment response was based on moderate to marked improvement on the Clinical Global Impression-Bipolar Disorder (CGI-BP) scale.. Two of six patients showed evidence of response. The main side effect noted was sedation.. Quetiapine may be a useful treatment for some patients with treatment-resistant bipolar disorder. Further studies are needed to assess quetiapine's effect more rigorously.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Retrospective Studies; Treatment Outcome