Relapse prevention with cariprazine in patients with early-stage schizophrenia

Abstract

Introduction: Relapse is defined as the return of psychotic symptoms after a period of improvement/stability. Relapse is often associated with the disruptive re‐hospitalization of patients. Importantly, relapse history is a strong predictor of subsequent relapses and poorer outcomes. Therefore, relapse prevention in the beginning of the disorder is especially important. Cariprazine, a novel D3‐D2 partial agonist, has been effective in preventing relapse compared to placebo in stabilized patients with schizophrenia. Objectives: To present the efficacy of cariprazine in preventing relapse in patients with early‐stage schizophrenia. Methods: Post‐hoc analysis of data from a 96 weeks, multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group study in adults with schizophrenia. The study was composed of two parts: a 20‐week open‐label treatment phase and a double‐blind treatment phase up to 72 weeks. During the open‐label phase, patients were stabilized with cariprazine 3.0‐9.0 mg/day. Then, they were randomized to continue cariprazine (fixed dosing: 3.0, 6.0, or 9.0 mg/day) or receive placebo. Relapse was defined as a deterioration of symptom scores as measured by the Positive Negative Syndrome Scale (PANSS), admission to a psychiatric hospital, exhibiting aggressive behaviour, or risk of suicide. In the present analysis, patients with a schizophrenia diagnosis history of 0‐5 years were defined as early‐stage patients. Baseline characteristics, and risk ratios (after the double‐blind phase) with number‐neededto‐ treat (NNT) were calculated. Results: Of 200 patients, 71 (35.5%) met the early‐stage criteria: 32 patients in the cariprazine (CAR) and 39 in the placebo (PBO) arm. The mean age was 31.6 years in both groups with an average illness duration of 2.51+/‐1.03 years in the CAR and 2.75+/‐ 1.24 years in the PBO arm. 47% of patients in the CAR arm and 77% in the PBO arm were men. The average number of previous hospitalisations was comparable in the two groups (CAR: 2.3; PBO: 2.6), as was the severity of illness: mean PANSS Total score: 89.2 (CAR), 90.4 (PBO). Patients in both groups were highly compliant (pill‐count: CAR: 98.2%; PBO: 99.5%). The main reported adverse effects were headache (CAR: 11.3%, PBO: 7.0%), insomnia (CAR: 5.6%, PBO: 4.2%), and increased triglycerides (CAR: 5.6%, PBO: 1.4%), discontinuation due to adverse event was 3.1% in the CAR and 2.6% in the PBO group. Altogether, 9.4% of patients relapsed in the cariprazine group compared to 48.7% on placebo (risk ratio=0.19 (95% confidence interval (CI): 6.3‐59.2%, p=0.0041; NNT: 2.5 (95%CI: 1.7‐5.1). Conclusions: In this post‐hoc analysis of patients within the first five years of schizophrenia, the relative risk of relapse was 81% reduced with cariprazine with prevention of one additional relapse after each third patient exposed to cariprazine vs placebo. Cariprazine seems to be a good treatment option for early‐stage patients for preventing relapse.