Full-Spectrum Efficacy of Cariprazine on Manic and Depressive Poles of Bipolar I Disorder in Patients Experiencing Manic or Depressive Episodes: Post Hoc Analysis of Randomized Controlled Trial Data

Abstract: Background: Treating patients with bipolar I disorder (BP-I) with an agent that is only effective against one pole may elicit treatment-emergent affective switch (TEAS), or worsening of the opposite pole. The efficacy of cariprazine treatment on mania and depression symptoms and risk of TEAS were evaluated in patients with BP-I mania or depression. Methods: Post hoc analysis evaluated data from patients treated with cariprazine versus placebo in three 21-day, double-blind, placebo-controlled (DBPC) studies in manic/mixed BP-I (Nf1017) and three 6-/8-week DBPC studies in BP-I depression (Nf1363). Changes from baseline (CFB) in Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) total scores were analyzed in patients with ≥1 postbaseline MADRS and YMRS score. Results: In patients with BP-I mania, least squares mean CFB (95% confidence interval) in YMRS total score (mania symptoms) was greater for cariprazine 3–12 mg/d (-18.1 [-19.0, -17.2]) versus placebo (-12.5 [-13.6, -11.5]); greater improvement in MADRS total score (depression symptoms) was also observed (cariprazine=-3.4 [-3.9, -3.0]; placebo=-2.5 [-3.0, -2.0]). In patients with BP-I depression, MADRS results demonstrated greater improvement in depression with cariprazine 1.5–3 mg/d (-14.8 [-15.3, -14.3]) versus placebo (-12.3 [-13.0, -11.6]); YMRS results demonstrated no worsening, but rather numerical improvement, in mania (cariprazine=-1.1 [-1.3, -1.0]; placebo=-1.0 [-1.2, -0.8]). Conclusions: Cariprazine treatment demonstrated full-spectrum efficacy by reducing manic and/or depressive symptoms in patients with BP-I mania or depression. These data demonstrated no significant worsening of opposite pole symptoms with cariprazine, which is consistent with previous results describing low incidence of TEAS.Short Description: Cariprazine is approved to treat patients with bipolar I disorder (BP-I). Pooled data from double-blind, placebo-controlled trials evaluating cariprazine versus placebo were analyzed in patients with BP-I experiencing manic or depressive episodes. Cariprazine treatment was associated with reduced symptoms of mania and depression regardless of whether the presenting episode was manic or depressive, indicating that cariprazine was effective across the full spectrum of BP-I symptom poles and was not associated with treatment-emergent affective switch.Name of Sponsoring Organization(s): AbbVie