Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysis

Abstract

In recent years, combinations of pharmacological treatments have become common for the treatment of bipolar disorder type I (BP I); however, this practice is usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as an option in the treatment of acute phases of BP I. Therefore, we evaluated comparative data of commonly prescribed MDRs for both manic and depressive phases of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the ClinicalStudyResults.org and other data sources were searched from 1949 to March 2009 for placebo and active controlled randomized clinical trials (RCTs). Risk ratios (RRs) for response, remission, and discontinuation rates due to adverse events (AEs), lack of efficacy, or discontinuation due to any cause, and the number needed to treat or harm (NNT or NNH) were calculated for each medication individually and for all evaluable trials combined. The authors included 31 RCTs in the analyses comparing a MDR with placebo or with active treatment for acute mania, and 9 RCTs comparing a MDR with placebo or with active treatment for bipolar depression. According to the collected evidence, most of the MDRs when compared to placebo showed significant response and remission rates in acute mania. In the case of bipolar depression only quetiapine and, to a lesser extent, olanzapine showed efficacy as MDR. Overall, MDRs were well tolerated with low discontinuation rates due to any cause or AE, although AE profiles differed among treatments. We concluded that most MDRs were efficacious and safe in the treatment of manic episodes, but very few MDRs have demonstrated being efficacious for bipolar depressive episodes.

Fig. 1

Flow of information diagram through the different phases of the systematic review.

Fig. 2

Random risk ratios and 95% confidence intervals (CIs) for response rates with a monotherapy drug regimen (MDR) vs. placebo in the treatment of acute manic episodes. Response is defined as a reduction ≥50% in the baseline total score in the primary efficacy measure after 3–6 wk of treatment. ER-CBZ, Extended-release carbamazepine capsules; M-H, Mantel–Haenszel.

Fig. 3

Random risk ratios and 95% confidence intervals (CIs) for response rates with a monotherapy drug regimen (MDR) vs. placebo in the treatment of depressive episodes Response is defined as a reduction ≥50% in the baseline total score in the primary efficacy measure after 7–10 wk of treatment. M-H, Mantel–Haenszel.