Comparison of antipsychotic dose equivalents for acute bipolar mania and schizophrenia

Abstract

Question: Are antipsychotic dose equivalents between acute mania and schizophrenia the same?

Study selection and analysis: Six databases were systematically searched (from inception to 17 September 2022) to identify blinded randomised controlled trials (RCTs) that used a flexible-dose oral antipsychotic drug for patients with acute mania. The mean and SD of the effective dose and the pre-post changes in manic symptoms were extracted. A network meta-analysis (NMA) under a frequentist framework was performed to examine the comparative efficacy between the antipsychotics. A classic mean dose method (sample size weighted) was used to calculate each antipsychotic dose equivalent to 1 mg/day olanzapine for acute mania. The antipsychotic dose equivalents of acute mania were compared with published data for schizophrenia.

Findings: We included 42 RCTs which enrolled 11 396 participants with acute mania. The NMA showed that risperidone was superior to olanzapine (reported standardised mean difference: -022, 95% CI -0.41 to -0.02), while brexpiprazole was inferior to olanzapine (standardised mean difference: 0.36, 95% CI 0.08 to 0.64). The dose equivalents to olanzapine (with SD) were 0.68 (0.23) for haloperidol, 0.32 (0.07) for risperidone, 0.60 (0.11) for paliperidone, 8.00 (1.41) for ziprasidone, 41.46 (5.98) for quetiapine, 1.65 (0.32) for aripiprazole, 1.23 (0.20) for asenapine, 0.53 (0.14) for cariprazine and 0.22 (0.03) for brexpiprazole. Compared with the olanzapine dose equivalents for schizophrenia, those of acute mania were higher for quetiapine (p<0.001, 28.5%) and aripiprazole (p<0.001, 17.0%), but lower for haloperidol (p<0.001, -8.1%) and risperidone (p<0.001, -15.8%).

Conclusions: Antipsychotic drugs have been considered first-line treatment for acute mania, warranting specific dose equivalence for scientific and clinical purposes.

Keywords: Adult psychiatry; Depression & mood disorders.

Figure 1

Comparative efficacy (standardised mean difference) in antimanic outcome of the included antipsychotic drugs. Antipsychotics are shown in grey and reported in order of surface under the curve cumulative ranking (given in parentheses). The results of the pairwise meta-analyses are presented in the upper right half and the results of the network meta-analyses in the left lower half. Comparisons between treatments should be read from left to right and the estimate is in the cell in common between the column-defining treatment and the row-defining treatment. In the left lower half, standard mean differences lower than 0 favour the column-defining treatment, and in the upper right half those lower than 0 favour the row-defining treatment. Cells in blue and bold print indicate significant results. Bold type indicates statistical significance.