Efficacy and tolerability of treatments for bipolar depression

- Treatments for acute bipolar depression were rated by number-needed-to-treat or harm (NNT, NNH).
- Older antidepressants were more effective than modern agents (NNT=4.5 vs. 7.4).
- Carbamazepine, valproate, lamotrigine were effective (NNT<6).
- Lamotrigine was especially well-tolerated (NNH>20).
- Olanzapine+fluoxetine, lurasidone and quetiapine were most effective antipsychotics (NNT<6).
- Olanzapine, aripiprazole, and ziprasidone were less effective (NNT>10).
- Lurasidone was the best-tolerated antipsychotic (NNH>20).

BackgroundDepression in bipolar disorder is a major therapeutic challenge associated with disability and excess mortality.MethodsWe reviewed findings from randomized placebo-controlled trials concerning efficacy and adverse effects of treatments for acute bipolar depression, including anticonvulsants, antidepressants, lithium, and modern antipsychotics, to compare numbers-needed-to-treat (NNT) versus -to-harm (NNH).ResultsIncluded were data from 22 reports involving 33 drug-placebo pairs. Antidepressants (especially modern drugs) had the most favorable (highest) risk/benefit ratio (pooled NNH/NNT=18.1). Anticonvulsants were effective agents (pooled NNT=5.06), but carbamazepine and valproate were not as well tolerated (NNH<10) as lamotrigine, and they had an unfavorable pooled NNH/NNT (3.75). Some antipsychotics (lurasidone, olanzapine+fluoxetine, and quetiapine (NNT all < 10) were effective though aripiprazole and ziprasidone were not (NNT≥45); olanzapine alone was weakly effective (NNT=11.3), and all but lurasidone (NNH=20.2) were not well tolerated (NNH≤4.18). Lithium appeared to be poorly effective but well tolerated in only one trial.ConclusionsSome anticonvulsants and antipsychotics seemed effective for acute bipolar depression, but most antipsychotics were not well tolerated. Antidepressants were effective and well-tolerated; lithium remains inadequately tested.LimitationsThere are remarkably few short-term treatment trials (2.75/12 treatments), and fewer long-term trials for bipolar depression, possibly arising from exaggerated concerns about inducing mania.