Abstract
Background The literature on the treatment mixed episodes in Bipolar Disorder [BD] is sparse. Second generation antipsychotics [SGA] have documented efficacy in mania, but not mixed episodes. The objective of this meta-analysis was to ascertain the efficacy of SGA, either as mono- and/or adjunctive therapy, in the treatment of acute mixed episodes of BD, compared to placebo. Methods A MEDLINE search for English language publications of randomized controlled trials [RCTs] comparing SGA with placebo in the treatment of an acute manic/mixed episode of BD, during the period 1990-2012, was performed using the terms 'atypical antipsychotics', 'SGA', 'mixed episodes', 'dysphoric mania' and each SGA independently. 9 RCTs reporting data on 1289 mixed episode patients treated with aripiprazole, asenapine, olanzapine, paliperidone-ER, risperidone, and ziprasidone, either as monotherapy or as adjunctive therapy, versus placebo, for 3-6 weeks, were included in the meta-analysis. We extracted data on the number of patients, SGA, duration of study and mean change in mania and depression scores from baseline to endpoint. Standardized mean difference between SGA and placebo for the mean baseline-to-endpoint change in mania and depression rating scores was calculated, with a 95% confidence limit. Results SGA, either alone or in combination with mood stabilizers, had superior efficacy in treating manic symptoms of mixed episodes compared to placebo (-0.41, 95% CI -0.53, -0.30; overall effect p<0.00001). SGA were equally effective for manic symptoms in mixed episodes and pure mania (p=0.99). SGA had superior efficacy in treating depressive symptoms of mixed episodes (-0.30, 95% CI -0.47, -0.13; p<0.001) compared to placebo in two trials reporting this information. Limitations Thirteen relevant studies could not be included as data for mixed-episodes were not presented separately. Conclusions SGA are effective in treating acute mixed episodes of BD, with predominant manic symptoms. Their efficacy in treating depressed mixed episodes remains unclear.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 408-414 |
| Number of pages | 7 |
| Journal | Journal of Affective Disorders |
| Volume | 150 |
| Issue number | 2 |
| DOIs | |
| State | Published - Sep 5 2013 |
Bibliographical note
Funding Information:Dr. Leonardo Silveira received a scholarship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. Dr. David Bond has received research grants from or is on speaker/advisory boards for the Canadian Institutes of Health Research (CIHR), the UBC Institute of Mental Health/Coast Capital Depression Research Fund, the Canadian Network for Mood and Anxiety Treatments (CANMAT), the Canadian Psychiatric Association, Pfizer, AstraZeneca, Janssen-Ortho, Bristol-Myers Squibb, and Otsuka. Dr. Konstantinos Fountoulakis has received research grants from Pfizer and honoraria from BMS, Pfizer, Lilly, Astra Zeneca and Janssen. Dr Raymond Lam has received research funds from or is on ad-hoc speaker/advisory boards for AstraZeneca, Biovail, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association Foundation, Eli Lilly&Co., Litebook Company, Lundbeck, Lundbeck Institute, Mochida, Pfizer, Servier, St. Jude's Medical, Takeda, and UBC Institute of Mental Health/Coast Capital Savings. Dr Lakshmi Yatham has received research grants from or is on speaker/advisory boards for AstraZeneca, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Eli Lilly&Co., Forest, GlaxoSmithKline, Janssen, Lundbeck, Michael Smith Foundation for Health Research, Novartis, Otsuka, Pfizer, Ranbaxy, Servier, and the Stanley Foundation. Dr. Kesavan Muralidharan and Dr. Mazen Ali have no conflict of interest to declare.
Keywords
- Bipolar disorders
- Mania
- Meta-analysis
- Mixedepisodes
- Randomized controlledtrials
- Second generationantipsychotics