SAN ANTONIO, TX—Cariprazine “may provide benefit for negative symptoms in patients with schizophrenia,” results from a pooled post hoc analysis of 2 randomized, double-blind, placebo- and active-controlled trials presented at the U.S. Psychiatric & Mental Health Congress have shown.

Cariprazine, recently approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder, is a potent dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors.

To investigate the effects of cariprazine in a subset of patients with acute exacerbation of schizophrenia and predominant negative symptoms, Suresh Durgam, MD, of Allergan, Jersey City, NJ, and colleagues analyzed data from the Phase 2/3 studies.

In both trials, the primary outcome was change from baseline in Week 6 in the Positive and Negative Syndrome Scale (PANSS) total score. In the first study, 732 patients received cariprazine 1.5mg, 3mg, and 4.5mg daily, risperidone 4mg daily, or placebo for 6 weeks; in the second, 617 received cariprazine 3mg and 6mg daily, aripiprazole 10mg daily or placebo for 6 weeks.

In the studies, patients had a current diagnosis of schizophrenia with a psychotic episode of less than 2 weeks in duration, a PANSS total score between 80 and 120, a score of ≥4 on the Clinical Global Impressions-Severity, and at least moderate severity, defined as a score of 4 or greater, on 2 or more of the PANSS positive items: delusions, conceptual disorganization, hallucinatory behavior, or suspiciousness/persecution.

Predominant negative symptoms is one of the 3 core symptom domains of schizophrenia, along with positive symptoms and cognitive impairment. For the post hoc analyses, the investigators identified patients based on a model that defined 8 states of schizophrenia; included were those with State 6, as defined by PANSS factor score criteria for each of the 3 domains.

Among the 285 patients in the predominant negative symptoms pooled subset, significant improvements were observed on the PANSS total score for all active treatments vs. placebo, with improvements continuing through Week 6 in all groups.

By Week 2, a significant effect versus placebo was observed for cariprazine 1.5–3mg daily and 4.5–6mg daily and by Week 3 for risperidone on the PNASDS negative factor score, which was maintained through Week 6; however, aripiprazole did not show a significant advantage when compared with placebo after Week 3.

“The largest PANSS total score treatment effects in the predominant negative symptoms subpopulation were observed with cariprazine 4.5mg–6mg daily and risperidone 4mg daily,” Dr. Durgam noted. On the PANSS negative factor score, “the cariprazine 4.5mg–6mg daily treatment group demonstrated the largest treatment effect,” an effect size of 0.79, he added.

“These results provide support for recent findings that demonstrated significantly greater improvement with cariprazine versus risperidone in a prospectively designed study in patients with predominantly negative symptoms,” the study authors concluded.