Abstract
Background: Schizophrenia is a complex and chronic disorder, and many patients do not achieve complete recovery. Remission, or the alleviation of symptoms to levels that do not significantly interfere with behavior, is therefore an important goal of schizophrenia treatment. The dopamine D3/D2 receptor partial agonist antipsychotic cariprazine is FDA approved in the United States for the treatment of adults with acute schizophrenia and mixed and manic episodes of bipolar disorder. These post hoc analyses investigated the efficacy of cariprazine in maintaining remission in stable patients with schizophrenia.
Methods: Analyses were based on data from a long-term, randomized, double-blind, fixed-dose, placebo-controlled relapse prevention study of cariprazine in patients with schizophrenia (NCT01412060). Patients were first stabilized with cariprazine during a 20-week, open-label phase, and then randomized 1:1 to fixed-dose cariprazine (3, 6, or 9 mg/d) or placebo for up to 72 weeks of double-blind treatment. In these post hoc analyses, the definition of symptomatic remission was based on the Remission in Schizophrenia Working Group criteria: scores ≤3 on the Positive and Negative Syndrome Scale items mannerisms and posturing (G5), unusual thought content (G9), blunted affect (N1), social withdrawal (N4), lack of spontaneity (N6), delusions (P1), conceptual disorganization (P2), and hallucinatory behavior (P3). Sustained remission was defined as meeting remission criteria at the visit in question and all previous double-blind visits. Time to loss of sustained remission was estimated using Kaplan-Meier analysis; P value was based on the log-rank test. The hazard ratio estimate was based on the Cox proportional hazards regression model.
Results: Of the 200 patients randomized to double-blind treatment, approximately 85% met symptomatic remission criteria at randomization. During double-blind treatment, 60.5% of cariprazine-treated patients and 34.9% of placebo-treated patients had sustained remission through their final visit (number needed to treat = 4). Time to loss of sustained remission was significantly longer with cariprazine than with placebo (P = .0020; hazard ratio [95% confidence interval]: 0.51 [0.33–0.79]). For cariprazine- and placebo-treated patients, the mean duration of sustained remission during double-blind treatment was 219.1 ± 194.4 and 157.0 ± 177.5 days, respectively; the median duration of sustained remission was 181.5 days and 85.0 days, respectively.
Conclusion: Cariprazine treatment was associated with significantly higher rates of sustained remission and longer duration of sustained remission compared to placebo, suggesting that cariprazine was effective in maintaining stable, long-term remission in patients with schizophrenia.