Efficacy and safety of adjunctive cariprazine based on background antidepressant class in major depressive disorder
Background: To characterize safety outcomes of adjunctive cariprazine by background antidepressant therapy (ADT), post hoc analyses were conducted on data from 2 randomized controlled trials.
Methods: Data were pooled from 2 double-blind, 6-week, phase 3 trials (NCT03738215, NCT03739203) of adults with major depressive disorder (MDD) who had an inadequate response to 1 to 3 ADTs. Participants received 1.5 or 3.0mg/d cariprazine+ADT or placebo+ADT. Post hoc analyses evaluated cariprazine efficacy and incidence of 6 treatment-emergent adverse events: akathisia, weight gain, sexual adverse events, insomnia, nausea, and somnolence, stratified by background ADT class.
Results: The pooled safety population for all treatment groups included 1508 adults. The most common background ADT classes were selective serotonin reuptake inhibitors (SSRIs, 63.0% of participants) and serotonin-norepinephrine reuptake inhibitors (SNRIs, 24.6%). Efficacy measured by the mean Montgomery–Åsberg Depression Rating Scale total score changes by ADT class were greater for cariprazine+ADT vs placebo+ADT, with trends generally similar across ADT class. Focusing on the 2 most utilized ADTs (SSRIs and SNRIs), akathisia incidence was 7.1% for 1.5mg/d cariprazine+SSRIs vs 6.3% for 1.5mg/d cariprazine+SNRIs, 9.0% vs 13.1% for 3.0mg/d cariprazine+ADT, and 0.9% vs 1.7% for placebo+ADT, respectively. Similarly, weight gain incidence was 1.9% for 1.5mg/d cariprazine+SSRIs vs 3.2% for 1.5mg/d cariprazine+SNRIs, 2.2 % vs 3.1% for 3.0mg/d cariprazine+ADT, and 0.6% vs 0% for placebo+ADT, respectively. Overall incidence of any sexual adverse event was low for both ADT classes with either cariprazine dose.
Conclusion: Although some variation was observed across ADT classes, the overall safety profile of cariprazine remains consistent.
