Clinical Relevance of Treatments for Acute Bipolar Disorder: Balancing Therapeutic and Adverse Effects

Abstract Background The US Food and Drug Administration (FDA) has approved 10 treatments for acute mania, but only 2 for acute bipolar depression. These agents differ from one another with respect to their efficacy and tolerability profiles, such that certain medications may be optimal for some patients but not others. Objective Our aim was to compare the therapeutic and adverse effects of treatments for acute mania and acute bipolar depression to inform clinical decision making. Methods Using data from large, randomized, double-blind, placebo-controlled acute mania and acute bipolar depression trials, we assessed number needed to treat (NNT) for response, number needed to harm (NNH) for sedation/weight gain, and likelihood to help or harm (LHH = NNH ÷ NNT) compared with placebo. Results For acute mania, lithium compared with other FDA-approved agents yielded substantively less sedation (NNH, 27 vs 5−17) yet broadly similar efficacy (NNT, 4 vs 4–8), and thus a more favorable efficacy:sedation likelihood (LHH, 6.8 vs 0.7–3.4). For acute bipolar depression, lamotrigine compared with FDA-approved treatments yielded substantively less sedation (NNH, 42 vs 6–12), weight gain (NNH, −34 vs 6−19), and efficacy (NNT, 12 vs 4–6), but still more favorable efficacy:sedation likelihood (LHH, 3.5) than quetiapine (LHH, 1.0) and efficacy:weight gain likelihood (LHH, −2.8) than the olanzapine plus fluoxetine combination (LHH, 1.5). Conclusions For acute mania, lithium compared with other FDA-approved agents yielded less sedation yet similar efficacy, indicating utility for patients sensitive to sedation. For acute bipolar depression, lamotrigine compared with FDA-approved treatments yielded better tolerability but poorer efficacy, suggesting utility in patients sensitive to sedation/weight gain with milder episodes, whereas the FDA-approved treatments might have utility in patients with more severe episodes.