Quetiapine For Bipolar Depression Research Articles

Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for non-systematic adverse events

BackgroundAdverse 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.MethodsWe 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.ResultsWe 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.”ConclusionsSelection 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.

Methods to identify and prioritize patient-centered outcomes for use in comparative effectiveness research

BackgroundWe used various methods for identifying and prioritizing patient-centered outcomes (PCOs) for comparative effectiveness research (CER).MethodsWe considered potential PCOs (“benefits” and “harms”) related to (1) gabapentin for neuropathic pain and (2) quetiapine for bipolar depression. Part 1 (April 2014 to March 2015): we searched for PCO research and core outcome sets (COSs). We conducted electronic searches of bibliographic databases and key websites and examined FDA prescribing information and reports of clinical trials and systematic reviews. We asked patient and clinician co-investigators to identify PCOs. Part 2 (not part of our original study protocol): in 2015, we surveyed members of The TMJ Association, Ltd., a patient group associated with temporomandibular disorders (4130 invitations sent). Participants prioritized (1) the importance of six potential benefits and (2) 21 potential harms selected by the investigators in part 1, using stated preference methods. We calculated descriptive statistics.ResultsIn part 1, we identified a COS for pain, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. The COS identified several important benefits, but it lacked specific recommendations about which potential harms to include in CER. We did not identify a COS for bipolar depression. Research reports, prescribing information, and patient co-investigators helped identify but not prioritize outcomes. We abandoned our electronic search for PCO research because we found it would be resource-intensive and yield few relevant reports. In part 2, surveying patients was useful for prioritizing PCOs. Members of The TMJ Association, Ltd., completed the survey (N = 746) and successfully prioritized both benefits and harms. Participants did not identify many benefits other than those we identified in part 1; several participants identified additional harms.ConclusionsThese exploratory results could inform future research about identifying and prioritizing PCOs. We found that stakeholder co-investigators and research reports contributed to identifying PCOs; surveying a patient group contributed to prioritizing PCOs. Prioritizing potential harms was particularly challenging because there are many more potential harms than potential benefits. Methods for identifying and prioritizing potential benefits for CER might not be appropriate for harms. Further research is needed to determine the generalizability of these results.

Are Hypomanic/Manic Episodes "Induced by" or "Associated with" Quetiapine Initiation?

An increasing number of case reports are concerned with hypomanic/manic symptoms induced by some atypical antipsychotic drugs, especially quetiapine [1]. In the current volume of Drug Safety—Case Reports, the case series published by Rovera et al. [2] demonstrates that quetiapine-related hypomania is an interesting event that is worth being appropriately diagnosed and managed in patients with bipolar disorder. Quetiapine is a second-generation dibenzothiazepine antipsychotic drug approved for the treatment of schizophrenia, major depression, bipolar disorder, bipolar depression, and mania. Several randomized, double-blind, placebo-controlled studies with quetiapine in bipolar depression included treatment-induced hypomania/mania as a secondary outcome, although the incidence of treatment-induced hypomania/mania with quetiapine at a dose of 300 or 600 mg/day seems no higher than that with placebo [3–5].

Cherry-picking by trialists and meta-analysts can drive conclusions about intervention efficacy

ObjectivesThe objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs). Study Design and SettingEligible 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]). ResultsWe 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). ConclusionsDisagreements across data sources affect the effect size, statistical significance, and interpretation of trials and meta-analyses.

Integrating multiple data sources (MUDS) for meta-analysis to improve patient-centered outcomes research: a protocol.

BackgroundSystematic 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.MethodsWe 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.Systematic review registrationCRD42015014037, CRD42015014038

The role of regulators, investigators, and patient participants in the rise of the placebo response in major depressive disorder.

The role of regulators, investigators, and patient participants in the rise of the placebo response in major depressive disorder.

Assuring That Double-Blind Is Blind

Assuring That Double-Blind Is Blind

Safety and Efficacy of Quetiapine in Bipolar Depression

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.

A review of sensitivity and tolerability of antipsychotics in patients with bipolar disorder or schizophrenia: focus on somnolence.

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.

Table of Contents

AbstractTADS results show fluoxetine plus CBT safer and more effective for teen depression.Levetiracetam does not improve behavioral disturbances associated with autism.Somatic symptoms in children with anxiety disorders.Atomoxetine for ADHD with ODD.FDA adds young adults to black box warning on antidepressants.Risperidone vs. quetiapine for disruptive behavior.SSRIs and early adolescent suicide.Study: Prenatal nicotine exposure and ADHD‐I.Epileptiform seizure with sertraline.Approval: Risperidone for irritability with autism.Precaution: Neuropsychiatric events with tamiflu.Label revision: Overdosage risk with venlafaxine.Approval: quetiapine for bipolar depression.

The use of atypical antipsychotics beyond psychoses: efficacy of quetiapine in bipolar disorder

Atypical antpsychotics have been sucessfully used in the treatment of bipolar disorder (BD), either as adjunctive or as monotherapy. Quetiapine is an atypical antipsychotic extensively used in the treatment of psychotic disorders. It has serotonergic and dopaminergic activity and it appears to be selective for the mesolimbic and mesocortical dopamine system. The aim of this paper was to review the recent literature on the use of quetiapine in the treatment of BD. The literature databases currently available online were searched for papers on quetiapine and BD. Papers and reports published between January 1995 and June 2005 were selected and reviewed critically. Augmentative low dose quetiapine was found to be effective in BD partially responsive to conventional mood-stabilizers. Manic and mixed episodes have been the best studied, and quetiapine was found to be effective either as monotherapy or as adjunctive therapy in both randomized clinical trials and open-label studies. Data on the use of quetiapine in bipolar depression showed a significant efficacy and high remission rates. Maintenance data suggested a role of quetiapine as a good alternative to classical mood stabilizers in reducing recurrence rates of BD. A few studies on the efficacy in rapid cycling BD have also been published. Quetiapine is an effective agent for the short- and long-term treatment of BD. The mechanism of action of quetiapine as a mood stabilizer is still unknown. Some preliminary data suggest the involvement of glutamate pathways but further studies are needed to clarify this issue.