Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder

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BackgroundHostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. MethodsData were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3–12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS–Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. ResultsMost patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [−0.93], disruptive-aggressive behavior [−0.79], combined [−1.75]; P ≤ 0.001 each), YMRS total score (−5.92, P ≤ 0.0001), and all individual YMRS items (−0.25 to −0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LimitationsPost hoc analysis. ConclusionCariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.