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Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials.

ABSTRACT: BACKGROUND:Symptoms of anxiety, irritability, and agitation (AIA) are prevalent among patients with bipolar I disorder (BD-I) mania with depressive symptoms, and could potentially be used to aid physicians in the identification of this more severe form of BD-I. Using data from two clinical trials, the aims of this post hoc analysis were to describe the phenomenology of bipolar mania in terms of AIA and depressive symptoms, and to evaluate the influence of these symptoms on the likelihood of remission during treatment. METHODS:Patients with a BD-I manic or mixed episode (Diagnostic and Statistical Manual of Mental Disorders IV criteria) were randomised to 3 weeks of double-blind treatment with asenapine, placebo, or olanzapine (active comparator). Anxiety was defined as a score of ?3 on the Positive and Negative Syndrome Scale 'anxiety' item, irritability as a score of ?4 on the Young Mania Rating Scale (YMRS) 'irritability' item, and agitation as a score of ?3 on the YMRS 'increased motor activity-energy' item. Depressive symptoms were defined as a score of ?1 on three or more individual Montgomery-Åsberg Depression Rating Scale (MADRS) items, or a MADRS Total score of ?20. RESULTS:A total of 960 patients with BD-I were analysed, 665 with a manic episode and 295 with a mixed episode. At baseline, 61.4% had anxiety, 62.4% had irritability, 76.4% had agitation, and 34.0% had all three AIA symptoms ('severe AIA'); 47.3% had three or more depressive symptoms, and 13.5% had a MADRS total score of ?20. Anxiety, irritability, and severe AIA (but not agitation) were statistically significantly more common in patients with depressive symptoms. Patients with anxiety or severe AIA at baseline were statistically significantly less likely to achieve remission (YMRS total <12). In general, remission rates were higher with asenapine and olanzapine than with placebo, irrespective of baseline AIA or depressive symptoms. CONCLUSIONS:Assessment of AIA symptoms in bipolar mania could enable physicians to identify patients with more severe depressive symptoms, allowing for appropriate intervention. Assessment and monitoring of AIA may help physicians to predict which patients may be harder to treat and at risk for self-harm. Trial registration ClinicalTrials.gov NCT00159744, NCT00159796. Registered 8 September 2005 (retrospectively registered).

SUBMITTER: Suppes T

PROVIDER: S-EPMC5673059 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials.

Suppes Trisha T Eberhard Jonas J Lemming Ole O Young Allan H AH McIntyre Roger S RS

International journal of bipolar disorders 20171106 1

<h4>Background</h4>Symptoms of anxiety, irritability, and agitation (AIA) are prevalent among patients with bipolar I disorder (BD-I) mania with depressive symptoms, and could potentially be used to aid physicians in the identification of this more severe form of BD-I. Using data from two clinical trials, the aims of this post hoc analysis were to describe the phenomenology of bipolar mania in terms of AIA and depressive symptoms, and to evaluate the influence of these symptoms on the likelihood ...[more]

PMID: 29105003

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Project description: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.

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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.

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Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials.

Publications

Anxiety, irritability, and agitation as indicators of bipolar mania with depressive symptoms: a post hoc analysis of two clinical trials.

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