Cariprazine was associated with clinically meaningful improvements across a broad spectrum of mania symptoms in a majority of adult patients with manic or mixed episodes associated with bipolar disorder, according to pooled analyses of phase 2/3 trials of cariprazine presented in 2 posters. The pooled analyses included 3 cariprazine studies [NCT00488618, NCT01058096, NCT01058668] in patients with bipolar mania that all used a design with 3 weeks of double-blind treatment. These studies included 608 patients who received cariprazine and 429 patients who received placebo.

In a poster by Stephen Zukin, MD, Forest Research Institute, Jersey City, New Jersey, USA, at baseline, the majority of patients had at least moderate symptom severity on 8 of 11 individual items on the Young Mania Rating Scale (YMRS). After 3 weeks of cariprazine treatment, the majority of the patients treated with cariprazine had mild or no symptoms on all 4 core YMRS items (irritability, speech, thought content, and disruptive/aggressive behavior; P < .0001). The odds ratios for changes in each of the YMRS single items ranged from 1.6 for increased motor activity to 2.7 for irritability (all P < .001).

Category shift analysis found that patients with moderate or worse symptom severity at baseline had significantly greater shifts to no or mild symptoms with cariprazine treatment vs placebo for each of the 11 items of YMRS. On all 4 YMRS core items, a shift from moderate or worse symptom severity to no or mild symptoms occurred for a significantly greater percentage of patients treated with cariprazine vs placebo (50.5% vs 29.1%; OR, 2.43; P = .0002). Also, at the end of treatment, the percentage of patients with mild or no symptoms on all 11 YMRS domains was significantly higher with cariprazine vs placebo (22.5% vs 13.5%; OR, 1.85; P = .0004).

Another pooled analysis of the same 3 cariprazine studies, from Lakshmi N. Yatham, MBBS, University of British Columbia, Vancouver, British Columbia, Canada, found that the standard definition of treatment response (≥ 50% improvement in YMRS total score) from baseline was met by a significantly higher percentage of patients treated with cariprazine (57%) vs patients who received placebo (36%; P < .0001), and the number needed to treat for response was 5 (95% CI, 4 to 7).

The standard definition of disease remission (YMRS total score ≤ 12) was met by a significantly higher percentage of patients who received cariprazine vs patients who received placebo (46% vs 30%; P < .0001), with a number needed to treat for remission of 7 (95% CI, 5 to 10). Using the stringent remission criteria of complete symptom resolution (YMRS total score ≤ 4), remission rates were 15% with cariprazine vs 9% with placebo (P = .0012), with a number needed to treat of 17 (95% CI, 11 to 49).

Cariprazine was effective and associated with clinically meaningful benefits, as suggested by the low number needed to treat (< 10) using the standard definitions for YMRS response and remission. Cumulative remission rates, based on YMRS score ≤ 12, indicated that a significantly greater percentage of patients treated with cariprazine achieved early remission that was maintained until the end of treatment vs patients who received placebo.

Overall, cariprazine was associated with clinically meaningful improvements on all 11 YMRS symptom domains, suggesting clinically meaningful improvements across a broad spectrum of mania symptoms.