Stopping cariprazine may delay incidence of schizophrenia relapse

Cristoph U. Correll

NEW YORK — Discontinuing cariprazine treatment may be linked to delayed incidence of schizophrenia relapse compared with other oral atypical antipsychotics, according to poster data presented here.

“Schizophrenia is a serious, chronic mental health disorder and people with schizophrenia may often forget or resist taking medication, which can increase the risk of relapse episodes,” Christoph U. Correll, MD, professor of psychiatry and molecular medicine, Hofstra Northwell School of Medicine, and medical director of the Recognition and Prevention Program, Zucker Hillside Hospital, told Healio Psychiatry. “This research was conducted to explore whether an oral medication with a long pharmacological half-life, such as cariprazine, may confer continued effects following drug discontinuation based on the timing of relapse and its relationship to estimated plasma drug levels.”

Vraylar (cariprazine, Allergen), an oral atypical antipsychotic approved for the treatment of adults with schizophrenia, forms two active metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). The half-lives are 2 to 4 days for cariprazine, about 1 to 2 days for DCAR and about 1 to 3 weeks for DDCAR.

Because oral atypical antipsychotics with long half-lives can confer continued effects after discontinuing treatment, researchers examined the timing of relapse following the cessation of this drug and its link to predicted plasma levels using data from a long-term, randomized, double-blind, fixed-dose, placebo-controlled relapse prevention study in patients with schizophrenia. Participants were stabilized with cariprazine during a 20-week, open-label phase, then randomized 1:1 to receive cariprazine (3 mg to 9 mg/day) or placebo for up to 72 weeks of treatment.

The results showed treatment with cariprazine was associated with delayed time to relapse compared with placebo (HR = 0.52; P = .0039). Based on Kaplan-Meier curve estimates, cariprazine also showed a time to drug-placebo relapse separation at 6 to 7 weeks post-randomization compared with the curves for the other oral atypical antipsychotics, which demonstrated earlier separation at 1 to 4 weeks. After 4 weeks after the last dose, the investigators also observed the reflection of this pattern in the placebo relapse rates (5% for cariprazine and 8% to 34% for other antipsychotics).

The mean values of plasma concentrations for total cariprazine were 20 nM and 6.1 nM at two and four weeks after last dosage, according to the poster. Based on the estimates for D2 and D3 receptor occupancy by total cariprazine plasma concentrations, which were 13 nM and 3.8 nM, these results suggest that both these receptors remain occupied 2 to 4 weeks after participants receive the last dose, according to the researchers.

“Based on a comparison of published studies, discontinuation of cariprazine treatment appeared to be associated with a delayed incidence of schizophrenia relapse compared to discontinuation of other oral [atypical antipsychotics],” Correll told Healio Psychiatry. “Prospective comparative trials are needed to confirm these results.” – by Savannah Demko

Reference:

Correll CU, et al. Poster P5-123. Presented at: American Psychiatric Association Annual Meeting; May 5-9, 20178; New York.

Disclosures: Correll reports consulting for Alkermes, Allergan, Bristol-Myers Squibb, Forum Pharmaceuticals, Gerson Lerman, Intracellular Therapies, Janssen, Lundbeck, Medavante, Neurocrine Biosciences Inc., Otsuka Pharmaceuticals, Pfizer, Sunovion Pharmaceuticals Inc. and Teva Pharmaceuticals.