title: Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial.
abstract: Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3-9mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9mg/d) or placebo for double-blind treatment (up to 72weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n=99) or cariprazine (n=101). Time to relapse was significantly longer in cariprazine- versus placebo-treated patients (P=.0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI]=0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥10% of patients during open-label treatment; there were no cariprazine adverse events ≥10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060.
authors.affiliation: Allergan, Inc., Jersey City, NJ, USA. Electronic address: suresh.durgam@allergan.com.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
authors.affiliation: Allergan, Inc., Jersey City, NJ, USA.
authors.forename: Willie
authors.initials: W
authors.lastname: Earley
authors.affiliation: Allergan, Inc., Jersey City, NJ, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Allergan, Inc., Jersey City, NJ, USA.
authors.forename: Dayong
authors.initials: D
authors.lastname: Li
authors.affiliation: Allergan, Inc., Jersey City, NJ, USA.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Lu
authors.affiliation: Gedeon Richter Plc, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: W Wolfgang
authors.initials: WW
authors.lastname: Fleischhacker
authors.affiliation: Saint Louis University, St. Louis, MO, USA.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Nasrallah
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D055502:Secondary Prevention; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine
keywords: Cariprazine; Long-term treatment; Oral antipsychotics; Randomized controlled trial; Relapse prevention; Schizophrenia