title: Effect of cariprazine across the symptoms of mania in bipolar I disorder: Analyses of pooled data from phase II/III trials.
abstract: Bipolar I disorder is a chronic disorder characterized by episodic recurrences of mania, depression, and mixed affective states interspersed with periods of full or partial remission; subsyndromal residual symptoms between episodes are common and disabling. Cariprazine, an atypical antipsychotic, is a potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors. Post-hoc analyses of pooled data from 3 positive trials were conducted to evaluate the effect of cariprazine 3-12 mg/d on the symptoms of mania in inpatients (18-65 years) with bipolar I disorder and a current manic episode. Analyses were based on the pooled intent-to-treat (ITT) population (placebo=429; cariprazine=608). Mean change from baseline to the end of treatment on individual Young Mania Rating Scale (YMRS) items was analysed using a mixed-effects model for repeated measures (MMRM); categorical symptom severity shifts were analysed using logistic regression. Statistically significant improvement in mean change was seen for cariprazine versus placebo on all 11 YMRS items (p<0.0001); significantly more cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment on 11 YMRS items (p<0.0001) and concurrently on the 4 YMRS core symptoms (irritability, speech, content, and disruptive-aggressive behaviour) (p<0.0001). Significantly more cariprazine- versus placebo-treated patients shifted from a Moderate/Worse or Marked/Worse Symptoms categories to Mild/No Symptoms on all 11 (p<0.0001) and 9 of 11 YMRS items (p<0.05), respectively. Results suggest that cariprazine treatment improved mania across YMRS symptoms; a significant percentage of cariprazine- versus placebo-treated patients had mild/no symptoms at the end of treatment.
authors.affiliation: Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. Electronic address: evieta@clinic.ub.es.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Durgam
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Lu
authors.affiliation: Prescott Medical Communications Group, Chicago, IL, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Ruth
authors.affiliation: Gedeon Richter Plc, Budapest, Hungary.
authors.forename: Marc
authors.initials: M
authors.lastname: Debelle
authors.affiliation: Forest Research Institute, Jersey City, NJ, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Zukin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D010879:Piperazines; C533287:cariprazine
keywords: Atypical antipsychotic; Bipolar disorder; Bipolar mania; Cariprazine; Residual symptoms