Aripiprazole Alone or in Combination for Acute Mania

Summary

A Cochrane review [Abstract] 1 included 10 studies with a total of 3340 patients with acute mania. Eight studies were conducted in adults, and 2 in children/adolescents. In 9 studies DSM-IV criteria were used for the diagnosis. Most of the adults were treated in hospital. The primary efficacy measure in all but one of the studies was mean change in Young Mania Rating Scale (YMRS) total score from baseline. The follow-up time varied from 3 to 12 weeks. The dropout rate was more than 20% for each intervention in 8 trials.

• Aripiprazole monotherapy vs. placebo: 7 studies (n=2239). Two of these included a third comparison arm, either lithium (n=485) or haloperidol (n=480). Aripiprazole was more effective than placebo in reducing manic symptoms in adults and children/adolescents at 3 and 4 weeks but not at 6 weeks (YMRS: MD at 3 weeks -3.66, 95% CI -5.82 to -2.05; 6 studies; n= 1819). Aripiprazole caused more movement disorders, as measured on the Simpson Angus Scale (SAS; MD 0.75, 95% CI 0.20 to 1.30; 4 studies, n=1233), on the Barnes Akathisia Scale (BAS; MD 0.20, 95% CI 0.09 to 0.31; 5 studies, n=1498) and by participant-reported akathisia, with more people requiring treatment with anticholinergic medication (RR 3.28, 95% CI 1.82 to 5.91; 2 studies; n = 730). Aripiprazole also led to more gastrointestinal disturbances (nausea: RR 1.50, 95% CI 1.20 to 1.88; 7 studies, n=2305 and constipation: RR 1.75, 95% CI 1.23 to 2.49; 4 studies, n=1255) and caused more children/adolescents to have a prolactin level that fell below the lower limit of normal.
• Aripiprazole vs. other drug treatments (3 studies): one study used haloperidol (n=347), two others used placebo and active comparator arms: lithium (n=488) and haloperidol (n=485). No significant differences in reducing manic symptoms were noted at 3 weeks (YMRS: MD 0.07, 95% CI -1.24 to 1.37; 3 studies; n=972) or at any other time point up to 12 weeks. At 12 weeks, haloperidol resulted in significantly more movement disorders than aripiprazole, as measured on the SAS (-4.68, 95% CI -5.87 to -3.49; one study, n=333), the BAS (MD -0.48, 95% CI -0.73 to -0.23; one study, n=333) and the Abnormal Involuntary Movement Scale (AIMS: MD -0.67, 95% CI -1.07 to -0.27; one study, n=321) and by participant-reported akathisia. By 12 weeks, investigators reported no difference between aripiprazole and lithium (SAS, BAS, AIMS), except in terms of participant-reported akathisia (RR 2.97, 95% CI 1.37 to 6.43; one study; n=313).

Comment: The quality of the evidence is downgraded by study quality (unclear allocation concealment, high drop-out rate).