Incidence and Characteristics of Akathisia With Adjunctive Cariprazine Treatment in Patients With Major Depressive Disorder

This work was sponsored by AbbVie Background: Post-hoc analysis of phase-3 clinical trials of adjunctive cariprazine aimed to characterize the incidence, severity, and management of akathisia and other extrapyramidal symptoms (EPS) in adult patients with major depressive disorder (MDD). Methods: Patients with MDD and inadequate response to ongoing antidepressant therapy (ADT) were randomized to cariprazine (1.5mg/d+ADT, 3mg/d+ADT) or placebo+ADT for 6-weeks of double-blind treatment. Post-hoc analysis evaluated incidence, severity, time to resolution of akathisia, restlessness, and other EPS; use of rescue medications; rate of discontinuation from treatment-emergent adverse events (TEAEs). Results: 1508 patients (cariprazine+ADT: 1.5mg/d, n=502, 3mg/d, n=503; placebo+ADT, n=503) were included in these 2 studies. Incidence of akathisia was greater with cariprazine 3mg/d+ADT (9.7%) than cariprazine 1.5mg/d+ADT (6.4%) and placebo+ADT (2.0%). Most treated with cariprazine+ADT (94%) experienced mild/moderate akathisia. Incidence of restlessness was 3.8% for patients treated with cariprazine 3mg/d+ADT, 3.6% for cariprazine 1.5mg/d+ADT, and 1.8% for placebo+ADT. For patients treated with cariprazine+ADT and placebo+ADT, EPS-related study discontinuations were 1.4% and 0.4% from akathisia, and 0.2% and 0.0% from restlessness. Rescue medications were used to treat EPS-related TEAEs during the double-blind treatment period in 3% of cariprazine-treated patients and 0.4% of placebo-treated patients. Mean time to resolution of akathisia was shorter in cariprazine versus placebo-treated patients (15.6-days; 19.5-days). Conclusions: Incidence of akathisia was higher for cariprazine than placebo, with lower incidence observed for patients treated with cariprazine 1.5mg/d+ADT versus 3mg/d+ADT, suggesting dose related effect. Most patients experienced mild or moderate akathisia and rates of study discontinuation were low suggesting it was tolerated by most patients.