TABLE 5.
Randomized trials of mono- versus dual pharmacotherapies for bipolar maintenance and relapse prevention
Trial result and intervention | Duration | Outcome | Adverse effects |
---|---|---|---|
Positive trials | |||
Aripiprazole (N=168) or placebo (N=169) plus lithium or divalproex (81) | 12-week acute stabilization followed by 52-week maintenance | Lower 52-week relapse rate (any mood episode) with aripiprazole (mean dose 15.8–16.9 mg/day; 17%) than with placebo (29%); aripiprazole was more effective than placebo for mania but not depressive relapse | Comparable weight changes or metabolic parameters with aripiprazole or placebo |
Lithium plus divalproex combination vs. either monotherapy (BALANCE; 82) | 24 months | Lithium plus divalproex (N=110) was more effective than divalproex monotherapy (N=110) but not lithium monotherapy (N=110); lithium was more effective than divalproex for depressive relapses | No significant differences in serious adverse events among the treatment arms |
Lithium or divalproex plus aripiprazole of placebo (83) | 12-week acute stabilization followed by 52-week maintenance | Adjunctive aripiprazole (mean dose=16.1 mg/day if index episode manic, 16.8 mg/day if mixed) was more effective than placebo for prevention of manic but not mixed episodes | More tremor with aripiprazole than with placebo |
Olanzapine (N=51) or placebo (N=48) plus lithium or divalproex (84) | 18 months | Adjunctive olanzapine (mean dose=8.6 mg/day) was more effective than placebo for symptomatic but not syndromal relapse for mania or depression (but no significant differences for time to mania relapse or time to depressive relapse) | More weight gain and less insomnia with adjunctive olanzapine than with placebo |
Risperidone long-acting injectable (N=65) or placebo (N=59) plus treatment as usual (85) | 16-week open stabilization, then 52 weeks | Adjunctive risperidone long-acting injectable (modal dose 25 mg/day) was more effective than placebo for time to any mood episode | Tremor, insomnia, muscle rigidity, and mania more likely with risperidone long-acting injectable than with placebo |
Ziprasidone (N=127) or placebo (N=113) plus lithium or divalproex (86) | 8-week open stabilization, then 16 weeks | Adjunctive ziprasidone (mean modal doses of 80, 119, and 160 mg/day across three strata) was more effective than placebo in time to any mood episode and, separately, time until a manic or until a depressive relapse | Incidence of tremor greater with ziprasidone than placebo |
Negative trials | |||
Lurasidone (N=246) or placebo (N=250) plus lithium or divalproex (87) | 28 weeks | No advantage for adjunctive lurasidone over placebo in time until recurrence of a depressive, manic, or mixed episode; if index episode polarity was depressed, lurasidone was more effective than placebo for time until recurrence of any mood episode | No clinically meaningful differences with lurasidone versus placebo |
Oxcarbazepine (N=26) or placebo (N=29) plus lithium (88) | 52 weeks | No advantage for adjunctive oxcarbazepine (mean modal dose 1,200 mg/day) over placebo in time until recurrence of any mood episode | Drowsiness, diarrhea, and tremor more common with oxcarbazepine than placebo |