Comparative efficacy and acceptability of antimanic drugsin acute mania: a multiple-treatments meta-analysis

SummaryBackground Conventional meta-analyses have shown inconsistent results for effi cacy of pharmacological treatmentsfor acute mania. We did a multiple-treatments meta-analysis, which accounted for both direct and indirectcomparisons, to assess the eff ects of all antimanic drugs.Methods We systematically reviewed 68 randomised controlled trials (16 073 participants) from Jan 1, 1980, to Nov 25,2010, which compared any of the following pharmacological drugs at therapeutic dose range for the treatment ofacute mania in adults: aripiprazole, asenapine, carbamazepine, valproate, gabapentin, haloperidol, lamotrigine,lithium, olanzapine, quetiapine, risperidone, topiramate, and ziprasidone. The main outcomes were the meanchange on mania rating scales and the number of patients who dropped out of the allocated treatment at 3 weeks.Analysis was done by intention to treat.Findings Haloperidol (standardised mean diff erence [SMD] –0·56 [95% CI –0·69 to –0·43]), risperidone (–0·50[–0·63 to –0·38), olanzapine (–0·43 [–0·54 to –0·32], lithium (–0·37 [–0·63 to –0·11]), quetiapine (–0·37 [–0·51 to–0·23]), aripiprazole (–0·37 [–0·51 to –0·23]), carbamazepine (–0·36 [–0·60 to –0·11], asenapine (–0·30 [–0·53 to–0·07]), valproate (–0·20 [–0·37 to –0·04]), and ziprasidone (–0·20 [–0·37 to –0·03]) were signifi cantly more eff ectivethan placebo, whereas gabapentin, lamotrigine, and topiramate were not. Haloperidol had the highest number ofsignifi cant diff erences and was signifi cantly more eff ective than lithium (SMD –0·19 [95% CI –0·36 to –0·01]),quetiapine (–0·19 [–0·37 to 0·01]), aripiprazole (–0·19 [–0·36 to –0·02]), carbamazepine (–0·20 [–0·36 to –0·01]),asenapine (–0·26 [–0·52 to 0·01]), valproate (–0·36 [–0·56 to –0·15]), ziprasidone –0·36 [–0·56 to –0·15]), lamotrigine(–0·48 [–0·77 to –0·19]), topiramate (–0·63 [–0·84 to –0·43]), and gabapentin (–0·88 [ –1·40 to –0·36]). Risperidoneand olanzapine had a very similar profi le of comparative effi cacy, being more eff ective than valproate, ziprasidone,lamotrigine, topiramate, and gabapentin. Olanzapine, risperidone, and quetiapine led to signifi cantly fewerdiscontinuations than did lithium, lamotrigine, placebo, topiramate, and gabapentin.Interpretation Overall, antipsychotic drugs were signifi cantly more eff ective than mood stabilisers. Risperidone,olanzapine, and haloperidol should be considered as among the best of the available options for the treatment ofmanic episodes. These results should be considered in the development of clinical practice guidelines