Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials.
OBJECTIVE
We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials in acute bipolar mania to summarize available data on drug treatment of mania.


METHODS
We included trials of medications licensed in the USA or UK for the treatment of any phase of bipolar disorder. Outcomes investigated were changes in mania scores, attrition, extrapyramidal effects and weight change. Data were combined through meta-analyses.


RESULTS
We included 13 studies (involving 3,089 subjects) and identified 2 studies for each of the following medications: carbamazepine, haloperidol, lithium, olanzapine, quetiapine, risperidone, valproate semisodium and aripiprazole. All drugs showed significant benefit compared with placebo for reduction in mania scores. Compared with placebo, for all antipsychotics pooled, response to treatment (> or =50% reduction in Young Mania Rating Scale scores) was increased more than 1.7 times [relative risk (RR) = 1.74, 95% confidence interval (CI) = 1.54, 1.96]; for all mood stabilizers pooled, response to treatment was doubled (RR 2.01, 95% CI = 1.66, 2.43). Overall withdrawals were 34% fewer (24-43%) with antipsychotics, and 26% fewer (10-39%) with mood stabilizers. However, for carbamazepine, aripiprazole and lithium an increase in risk of withdrawal could not be excluded. Small but significant increases in extrapyramidal side effects occurred with risperidone and aripiprazole.


CONCLUSIONS
Antipsychotics and mood stabilizers are significantly more effective than placebo for the treatment of acute mania. Their effect sizes are similar. Small differences between effect sizes may be due to differences in the patients included in the studies or to chance. Carbamazepine and lithium may be more poorly tolerated, and antipsychotics cause more extrapyramidal side effects.
Smith
Lesley A
LA
Medical Research Matters, Eynsham, UK.
Cornelius
Victoria
V
Warnock
Adrian
A
Tacchi
Mary Jane
MJ
Taylor
David
D
D000339:Affect / Q000187:drug effects; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D010054:Brief Psychiatric Rating Scale; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013375:Substance Withdrawal Syndrome; D016896:Treatment Outcome
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D002220:Carbamazepine