title: Quetiapine monotherapy for mania associated with bipolar disorder: combined analysis of two international, double-blind, randomised, placebo-controlled studies.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of quetiapine monotherapy for mania in bipolar disorder by an a priori defined combined analysis of data from two placebo-controlled studies.
  
  
  METHODS
  The intent-to-treat (ITT) populations from two studies of patients with DSM-IV bipolar I disorder, manic episode, randomised to 12 weeks of double-blind treatment with quetiapine (up to 800 mg/day) or placebo were combined. The primary efficacy endpoint was change in Young Mania Rating Scale (YMRS) score from baseline to Day 21. Secondary endpoints included change from baseline in YMRS to Day 84, YMRS response and remission rates and change from baseline to Days 21 and 84 in the Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI), Clinical Global Impressions-Bipolar (CGI-BP) and the Positive and Negative Syndrome Scale (PANSS). These endpoints were analysed as continuous variables, using an analysis of covariance (ANCOVA), with the baseline as covariate. In order to account for any difference in response between studies, the analyses were stratified by study as a fixed effect, and centre as a random effect. The Cochran-Mantel-Haenszel test was used to analyse binary variables. A chi square test was used to compare the frequency of adverse events between the treatment groups.
  
  
  RESULTS
  The combined analysis included a total of 403 patients from two quetiapine monotherapy studies in patients with bipolar I disorder. A significant improvement in YMRS score was observed from Day 4 (p = 0.021) onward in the quetiapine group compared with placebo. The treatment advantage of quetiapine over placebo continued to increase to Day 21 (p < 0.001) and Day 84 (p < 0.001). Significantly more quetiapine-treated than placebo-treated patients achieved a response (p < 0.001). The average quetiapine dose in responders was approximately 600 mg daily. Of adverse events occurring in > or = 5% of patients, quetiapine-treated patients had a significantly greater incidence versus placebo of somnolence (16.3% vs. 4.0%), dry mouth (15.8% vs. 3%), weight gain (9.1% vs. 1.5%) and dizziness (6.7% vs. 2.5%).
  
  
  CONCLUSIONS
  The data from this combined analysis support the results from the individual studies and indicate that quetiapine monotherapy is effective across a broad range of mood symptoms, fast-acting and well tolerated in the treatment of mania.
authors.affiliation: Hospital Clinic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Spain. evieta@clinic.ub.es
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Jamie
authors.initials: J
authors.lastname: Mullen
authors.forename: Martin
authors.initials: M
authors.lastname: Brecher
authors.forename: Björn
authors.initials: B
authors.lastname: Paulsson
authors.forename: Martin
authors.initials: M
authors.lastname: Jones
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D000069348:Quetiapine Fumarate; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010919:Placebos; D000069348:Quetiapine Fumarate