Cariprazine as an Adjunctive Treatment for Major Depressive Disorder: Assessment of Benefit and Risk Using Number Needed to Treat and Number Needed to Harm

This work was sponsored by AbbVie Background:Post-hoc analysis investigated efficacy and tolerability of adjunctive cariprazine (CAR) in patients with major depressive disorder (MDD) using number needed to treat (NNT), number needed to harm (NNH), likelihood to be helped/harmed (LHH). Methods:Data from five Phase-II/III studies. Efficacy outcomes included acute response (≥50% decrease from MADRS baseline ). Tolerability outcomes: adverse events (AEs); rates of discontinuation from AE. Results:Week-8 MADRS response rates for CAR 2-4.5 mg/day vs. placebo were 134/271(49.4%) vs. 101/264(38.3%); NNT=9 (95%CI 6-36). Week-6 MADRS response rates for CAR 1.5 mg/day vs. placebo were 110/250(44.0%) vs. 87/249(34.9%); NNT=11 (95%CI 6-193). Pooled CAR ≥1 mg/day group: Week-6 MADRS response rates were 765/1887(40.5%) CAR vs. 354/1101(32.2%) placebo; NNT=12 (95%CI 9-21); rates of akathisia vs. placebo were 209/1893(11.0%) vs. 25/1108(2.3%); NNH=12 (95% CI 10-14); rates of discontinuation from AE vs. placebo were 122/1893(6.4%) vs. 26/1108(2.3%) [NNH=25 (95%CI 19-38)]; rates of weight gain ≥7% from baseline vs. placebo were 35/1893(1.8%) vs. 12/1108(1.1%) [NNH of 131 (ns)]. NNH for akathisia vs. placebo was 24(95%CI 17-43) for 1-2 mg/day plus 1.5 mg/day dose groups, and 9(95% CI 7-11) for 2-4.5 mg/day plus 3 mg/day dose groups. NNH for discontinuation from AE vs. placebo was 94 (ns) for 1-2 mg/day plus 1.5 mg/day dose groups, and 17(95%CI 13-28) for 2-4.5 mg/day plus 3 mg/day dose groups. LHH comparing MADRS response vs. discontinuation from AE is >1, and >>1 for lower-dose range. Lower CAR dose range demonstrated better NNH regarding discontinuation from AE. Conclusion:Benefit-risk profile of CAR is favorable for MDD adjunctive treatment.