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Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials.

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

SUBMITTER: Szegedi A

PROVIDER: S-EPMC3152513 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials.

Szegedi Armin A Zhao Jun J van Willigenburg Arjen A Nations Kari R KR Mackle Mary M Panagides John J

BMC psychiatry 20110620

<h4>Background</h4>Asenapine demonstrated superiority over placebo for mania in bipolar I disorder patients experiencing acute current manic or mixed episodes in 2 randomized, placebo-and olanzapine-controlled trials. We report the results of exploratory pooled post hoc analyses from these trials evaluating asenapine's effects on depressive symptoms in patients from these trials with significant baseline depressive symptoms.<h4>Methods</h4>In the original trials (A7501004 [NCT00159744], A7501005 ...[more]

PMID: 21689438

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Project description:BackgroundDepending on the classification system used, 5-40% of manic subjects present with concomitant depressive symptoms. This post-hoc analysis evaluates the hypothesis that (hypo)manic subjects have a higher burden of depression than non-(hypo)manic subjects.MethodsData from 806 Bipolar I or II participants of the Stanley Foundation Bipolar Network (SFBN) were analyzed, comprising 17,937 visits. A split data approach was used to separate evaluation and verification in independent samples. For verification of our hypotheses, we compared mean IDS-C scores ratings of non-manic, hypomanic and manic patients. Data were stored on an SQL-server and extracted using standard SQL functions. Linear correlation coefficients and pivotal tables were used to characterize patient groups.ResultsMean age of participants was 40 ± 12 years (range 18-81). 460 patients (57.1%) were female and 624 were diagnosed as having bipolar I disorder (77.4%) and 182 with bipolar II (22.6%). Data of 17,937 visits were available for analyses, split into odd and even patient numbers and stratified into three groups by YMRS-scores: not manic < 12, hypomanic < 21, manic < 30. Average IDS-C sum scores in manic or hypomanic states were significantly higher (p < .001) than for non-manic states. (Hypo)manic female patients were likely to show more depressive symptoms than males (p < .001). Similar results were obtained when only the core items of the YMRS or only the number of depressive symptoms were considered. Analyzing the frequency of (hypo)manic mixed states applying a proxy of the DSM-5 mixed features specifier extracted from the IDS-C, we found that almost 50% of the (hypo)manic group visits fulfilled DSM-5 mixed features specifier criteria.ConclusionSubjects with a higher manic symptom load are also significantly more likely to experience a higher number of depressive symptoms. Mania and depression are not opposing poles of bipolarity but complement each other.

Project description:Background:Patient characteristics and disease progression may affect response to pharmacologic intervention in bipolar I disorder. Asenapine is approved for acute treatment of manic/mixed episodes of bipolar I disorder in patients 10-17 years old. Post hoc analyses assessed asenapine efficacy in pediatric patients by current manic or mixed episode, number of lifetime episodes, and baseline body mass index (BMI). Patients and methods:Data were obtained from a 3-week, randomized, double-blind, placebo-controlled, parallel-group trial of asenapine 2.5, 5.0, or 10.0 mg twice daily (BID) in male or female patients (10-17 years) with bipolar I disorder (NCT01244815). Patients were stratified by current episode type (Diagnostic and Statistical Manual of Mental Disorders, fourth edition - defined mixed/manic), number of lifetime episodes (<3, 3-5, >5), and baseline BMI tertile. Changes from baseline to day 21 in Young Mania Rating Scale (YMRS) total score and Clinical Global Impressions Scale for use in Bipolar Illness (CGI-BP) were assessed in asenapine subgroups vs placebo. Results:In patients with mixed episodes, differences in YMRS and CGI-BP scores were statistically significant for each asenapine dose vs placebo (P<0.001) at day 21; in patients with manic episodes, significant differences vs placebo were seen in all groups (P<0.05) except 2.5 mg BID on the YMRS. In patients with <3 previous mixed/manic episodes, significant differences in YMRS and CGI-BP scores were observed for all asenapine doses vs placebo (P<0.05). In patients with 3-5 or >5 previous episodes, asenapine 10 mg BID was significantly different than placebo (P<0.05) on both scales; differences vs placebo varied for lower doses. Baseline body weight or BMI did not appear to influence the efficacy of asenapine. Conclusion:Asenapine was effective in the treatment of pediatric patients with bipolar I disorder. Efficacy did not appear to be influenced by the type of current episode, stage of disease progression, or baseline body weight/BMI.

Project description:BackgroundBipolar disorder is a mental illness in which manic and depressive states are repeated, causing psychosocial dysfunction. Manic/hypomanic episodes cause problems with interpersonal, social and financial activities, but there is limited evidence regarding the predictors of manic/hypomanic episodes in real-world clinical practice.MethodsThe multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was administered in an observational study that was conducted to accumulate evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics by conducting a retrospective medical record survey. Our study extracted baseline patient characteristics from September to October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. We investigated the presence or absence of manic/hypomanic episodes over the course of one year from baseline to September-October 2017.ResultsIn total, 2231 participants were included in our study, 29.1% of whom had manic/hypomanic episodes over the course of one year from baseline. Binomial logistic regression analysis revealed that the presence of manic/hypomanic episodes was correlated with lower baseline GAF scores, rapid cycling, personality disorder, bipolar I disorder, and a mood state with manic or mixed features. Substance abuse was also a risk factor for manic episodes. There was no significant association between a baseline antidepressant prescription and manic/hypomanic episodes.ConclusionsIn Japan, 29.1% of outpatients with bipolar disorder had manic/hypomanic episodes over the course of one year. Our study suggested that a low GAF score, rapid cycling, personality disorder, bipolar I disorder, substance abuse, and baseline mood state could be predictors of manic/hypomanic episodes. Based on our findings, an antidepressant prescription is not a predictor of manic/hypomanic episodes.

Project description:BackgroundRating scale items in a 6-week clinical trial of olanzapine versus placebo augmentation in patients with mixed bipolar disorder partially nonresponsive to ≥14 days of divalproex monotherapy were analyzed to characterize symptom patterns that could predict remission. At baseline, the two treatment groups were similar.FindingsFactor analysis with Varimax rotation was performed post hoc on baseline items of the 21-Item Hamilton Depression Rating Scale (HDRS-21) and Young Mania Rating Scale (YMRS). Backwards-elimination logistic regression ascertained factors predictive of protocol-defined endpoint remission (HDRS-21 score ≤ 8 and YMRS score ≤ 12) with subsequent determination of optimally predictive factor score cutoffs.Factors for Psychomotor activity (YMRS items for elevated mood, increased motor activity, and increased speech and HDRS-21 agitation item) and Guilt/Suicidality (HDRS-21 items for guilt and suicidality) significantly predicted endpoint remission in the divalproex+olanzapine group. No factor predicted remission in the divalproex+placebo group. Patients in the divalproex+olanzapine group with high pre-augmentation psychomotor activity (scores ≥10) were more likely to remit compared to those with lower psychomotor activity (odds ratio [OR] = 3.09, 95% confidence interval [CI] = 1.22-7.79), and patients with marginally high Guilt/Suicidality (scores ≥2) were less likely to remit than those with lower scores (OR = 0.37, 95% CI = 0.13-1.03). Remission rates for divalproex+placebo vs. divalproex+olanzapine patients with high psychomotor activity scores were 22% vs. 45% (p = 0.08) and 33% vs. 48% (p = 0.29) for patients with low Guilt/Suicidality scores.ConclusionsPatients who were partially nonresponsive to divalproex treatment with remaining high vs. low psychomotor activity levels or minimal vs. greater guilt/suicidality symptoms were more likely to remit with olanzapine augmentation.Trial registrationClinicalTrials.gov; http://clinicaltrials.gov/ct2/show/NCT00402324?term=NCT00402324&rank=1, Identifier: NCT00402324.

Project description:ObjectivesComposite diagnostic criteria alone are likely to create and introduce biases into diagnoses that subsequently have poor relationships with input symptoms. This study aims to understand the relationships between the diagnoses and the input symptoms, as well as the magnitudes of biases created by diagnostic criteria and introduced into the diagnoses of mental illnesses with large disease burdens (major depressive episodes, dysthymic disorder, and manic episodes).SettingsGeneral psychiatric care.ParticipantsWithout real-world data available to the public, 100 000 subjects were simulated and the input symptoms were assigned based on the assumed prevalence rates (0.05, 0.1, 0.3, 0.5 and 0.7) and correlations between symptoms (0, 0.1, 0.4, 0.7 and 0.9). The input symptoms were extracted from the diagnostic criteria. The diagnostic criteria were transformed into mathematical equations to demonstrate the sources of biases and convert the input symptoms into diagnoses.Primary and secondary outcomesThe relationships between the input symptoms and diagnoses were interpreted using forward stepwise linear regressions. Biases due to data censoring or categorisation introduced into the intermediate variables, and the three diagnoses were measured.ResultsThe prevalence rates of the diagnoses were lower than those of the input symptoms and proportional to the assumed prevalence rates and the correlations between the input symptoms. Certain input or bias variables consistently explained the diagnoses better than the others. Except for 0 correlations and 0.7 prevalence rates of the input symptoms for the diagnosis of dysthymic disorder, the input symptoms could not fully explain the diagnoses.ConclusionsThere are biases created due to composite diagnostic criteria and introduced into the diagnoses. The design of the diagnostic criteria determines the prevalence of the diagnoses and the relationships between the input symptoms, the diagnoses, and the biases. The importance of the input symptoms has been distorted largely by the diagnostic criteria.

Dataset Information

Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials.

Publications

Effects of asenapine on depressive symptoms in patients with bipolar I disorder experiencing acute manic or mixed episodes: a post hoc analysis of two 3-week clinical trials.

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