Evaluating the safety of adjunctive cariprazine in major depressive disorder: Incidence, onset, severity, and time to resolution of common adverse events

Background: Post hoc analyses of phase 3 trials for adjunctive cariprazine in major depressive disorder (MDD) characterized 4 common treatment-emergent adverse events (TEAEs).

Methods: Safety data were pooled from 2 double-blind, randomized controlled trials (NCT03738215, NCT03739203) in adults with MDD who had an inadequate response to 1 to 3 courses of antidepressant therapy (ADT). Participants received 1.5 mg/d or 3.0 mg/d adjunctive cariprazine+ADT or placebo+ADT for 6 weeks. Post hoc analyses assessed the incidence, onset, severity, and time to resolution of nausea, somnolence, insomnia, and akathisia.

Results: The safety population included participants receiving cariprazine+ADT (n=1005) or placebo+ADT (n=503). A higher percentage of participants receiving 3.0 mg/d cariprazine+ADT compared with 1.5 mg/d cariprazine+ADT reported somnolence (5.6% vs 5.0%), insomnia (8.2% vs 6.8%), and akathisia (9.7% vs 6.4%), respectively. For cariprazine-treated participants, most incidences of nausea, somnolence, insomnia, and akathisia were mild or moderate in severity. TEAE-related study discontinuations for participants treated with cariprazine+ADT were generally low: 0.2% for nausea, 0.1% for somnolence, 0.3% for insomnia, and 1.4% for akathisia. Overall, mean time to resolution of these TEAEs in the cariprazine+ADT group ranged from about 1 week for nausea to about 2 weeks for insomnia, somnolence, and akathisia.

Conclusion: Discontinuation rates due to nausea, somnolence, insomnia, and akathisia were low and the majority of TEAEs were mild to moderate in severity, indicating that cariprazine is generally well-tolerated as an adjunctive treatment to ADT for adults with MDD.