Initial symptom severity of bipolar I disorder and the efficacy of olanzapine: a meta-analysis of individual participant data from five placebo-controlled studies

Background The efficacy of antipsychotics across the initial severity range in acute mania remains unclear. Therefore, we decided to examine the influence of baseline severity on the efficacy of olanzapine. Methods We conducted an individual participant data (IPD) meta-analysis of five double-blind, randomized controlled trials comparing olanzapine versus placebo. 939 patients with acute mania associated with bipolar I disorder were included. The relationship between baseline and change scores on the Young Mania Rating Scale (YMRS) up to three weeks for olanzapine versus placebo groups was examined. Findings The interaction between baseline symptom severity and treatment was statistically significant (p =0·013). The greater the baseline severity, the greater the magnitude of the differences between olanzapine and placebo. The mean YMRS score difference was 2·6 points for patients with a baseline score from 20 to 25, 4·7 points for patients with a baseline YMRS score around 30, and 8 points for patients with a baseline score up to 60 Interpretation Benefits of an antipsychotic drug like olanzapine can be expected for the full severity spectrum of patients likely to be treated for acute mania. However, less severely ill patients seem to benefit less in terms of efficacy but still may experience the same side-effects as more severely ill patients. Thus, clinicians and patients should carefully consider the benefit/risk ratio of olanzapine and its additional, prophylactic effect against relapse in the long-term. The generalizability of these results to other antipsychotics, trial designs, and medical conditions remains to be established.