ArticlesComparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis
Introduction
Mania is a condition of excessively raised mood that affects about 1% of the population, usually occurs in association with episodes of depression, and defines the diagnosis of bipolar disorder. Bipolar disorder is a recurring illness, and one of the leading causes of worldwide disability, especially in those aged 15–44 years.1 Mood stabilisers and antipsychotic drugs have long been the mainstay of treatment of acute mania with and without psychotic features.2 These medicines have been shown to be individually more effective than placebo, but guidelines have not usually attempted to rank the effectiveness of these drugs.3, 4, 5, 6, 7
We report a systematic review of randomised controlled trials that compared efficacy and acceptability of antimanic drugs, either against placebo or against one another, in the treatment of acute mania. We used the method of multiple-treatments meta-analysis, to allow the integration of data from direct and indirect comparisons.8, 9 We had previously compared the effectiveness of antidepressants in unipolar depression in this way.10 This method comprehensively synthesises data to provide a clinically useful summary that can guide treatment decisions.
Section snippets
Study protocol
At the beginning of this project, we drafted a study protocol and subsequently made it freely available to the public on our institutional website before doing the final analyses (webappendix p 1). Furthermore, with the publication of this Article, the overall dataset will be in the public domain for anyone who would be interested to use it.
Search strategy and selection criteria
We searched Medline, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, the Cochrane Central Register of Controlled Trials, and the
Results
In total, we included 68 trials in the multiple-treatments meta-analysis (figure 1, webappendix pp 15–20 for references to included studies and study characteristics). 14 treatments were analysed: aripiprazole, asenapine, carbamazepine, valproate, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, paliperidone, quetiapine, risperidone, topiramate, ziprasidone, and placebo. Most trials (54 [79%] of 68) were two-grouped studies and the rest were three-grouped studies in which one active
Discussion
This study shows both statistically and clinically significant differences between treatments of acute mania. In terms of efficacy, haloperidol, risperidone, and olanzapine outperformed other drugs. In terms of drop-outs, olanzapine, risperidone, and quetiapine were better than haloperidol. These results have potential clinical implications that should be considered in the development of clinical practice guidelines.2, 4, 22, 23, 24 Strikingly, antipsychotic drugs were, overall, significantly
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