Comparative efficacy and acceptability of mood stabilizer and second generation antipsychotic monotherapy for acute mania - A systematic review and meta-analysis

BackgroundAll treatment guidelines for acute mania recommend monotherapy with either mood stabilizers (MS) or antipsychotics. The objective of this analysis was to compare the efficacy and acceptability of both drug classes in an expanded set of clinical trials in acute mania.MethodRandomized double-blind trials comparing MS vs second generation antipsychotics (SGA) in acute mania were identified in a systematic literature search. Change in mania rating scale, responder rates and dropout rates were compared by treatment assignment using Review Manager version 5.0.ResultsNine studies totaling 1631 patients that compared the MS lithium or valproate against a number of SGAs, and which reported one or more analysis endpoints were identified. Statistically significant advantages were noted in favour of SGA over MS for standardized mean difference (SMD) for change in mania scores (− 0.22 [95% CI − 0.33 to − 0.11]; p < 0.0001), responder rate risk difference (7% [95% CI 1% to 13%]; p = 0.02), and dropout risk difference (− 5% [95% CI − 10% to − 1%]; p = 0.02). This change in SMD for mania scores is equivalent to a 2.5-3 point difference in Young Mania Rating Scale score. Similar trends for SMD were noted when comparing subgroups of lithium and valproate studies against SGAs.LimitationsOver half the included studies included olanzapine, and the applicability of these findings, especially to first generation antipsychotic drugs, requires confirmation. This analysis could not assess the relative efficacy of combined MS/SGA vs individual monotherapies.ConclusionIn acute mania, monotherapy with SGAs demonstrates statistically significant advantages over MS in terms of both efficacy and acceptability, and may be preferable for initial choice of treatment.