title: An 8-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety and Efficacy of Cariprazine in Patients With Bipolar I Depression.
abstract: OBJECTIVE
  The authors evaluated the efficacy, safety, and tolerability of cariprazine, an atypical antipsychotic candidate, in adult patients with acute bipolar I depression.
  
  
  METHODS
  This was an 8-week multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study in adult patients with bipolar I disorder experiencing a current major depressive episode. Patients were randomly assigned (1:1:1:1) to receive placebo or cariprazine at 0.75, 1.5, or 3.0 mg/day. The primary and secondary efficacy parameters were change from baseline to week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions severity subscale (CGI-S), respectively, analyzed using a mixed-effects model for repeated measures on the modified intent-to-treat population.
  
  
  RESULTS
  The intent-to-treat population comprised 571 patients (141 in the placebo group and 140, 145, and 145 in the cariprazine 0.75-, 1.5-, and 3.0-mg/day groups). Cariprazine at 1.5 mg/day showed significantly greater improvement on MADRS total score change from baseline to week 6 compared with placebo; the least squares mean difference was -4.0 (95% CI=-6.3, -1.6; significant after adjustment for multiple comparisons). Cariprazine at 3.0 mg/day showed greater MADRS score reduction than placebo (-2.5, 95% CI=-4.9, -0.1; not significant when adjusted for multiple comparisons). The 0.75 mg/day dosage was similar to placebo. A similar pattern for significance was observed on the CGI-S (1.5 mg/day: least squares mean difference=-0.4, 95% CI=-0.6, -0.1; 3.0 mg/day: -0.3, 95% CI=-0.5, -0.0). The most common adverse events (≥10%) in cariprazine-treated patients were akathisia and insomnia; weight gain was slightly higher with cariprazine than with placebo.
  
  
  CONCLUSIONS
  Cariprazine at 1.5 mg/day demonstrated consistent efficacy compared with placebo across outcomes and was generally well tolerated, suggesting efficacy for the treatment of bipolar I depression.
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: Willie
authors.initials: W
authors.lastname: Earley
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: Alan
authors.initials: A
authors.lastname: Lipschitz
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: István
authors.initials: I
authors.lastname: Laszlovszky
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: György
authors.initials: G
authors.lastname: Németh
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.affiliation: From Forest Research Institute, Jersey City, N.J.; Gedeon Richter, Budapest; Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland; and University of British Columbia, Vancouver.
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; C533287:cariprazine