title: Adjunctive oral ziprasidone in patients with acute mania treated with lithium or divalproex, part 1: results of a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  To assess the efficacy and safety of adjunctive ziprasidone in subjects with acute mania treated with lithium or divalproex, with an inadequate response to the mood stabilizer.
  
  
  METHODS
  The study enrolled subjects aged 18-65 years who had a primary DSM-IV diagnosis of bipolar I disorder, with the most recent episode manic or mixed, with or without rapid cycling, and a Young Mania Rating Scale (YMRS) score ≥ 18. Subjects were randomized under double-blind conditions to receive ziprasidone, 20 to 40 mg (n = 226) or 60 to 80 mg (n = 232), or placebo (n = 222) twice a day for 3 weeks in addition to their mood stabilizer. The primary efficacy variable was change in YMRS scores from baseline to 3 weeks. Secondary efficacy measures included the Montgomery-Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity of Illness and -Improvement scales, and Global Assessment of Functioning. Computer-administered YMRS was included for quality control and to evaluate study performance. The study was conducted between April 2006 and December 2008.
  
  
  RESULTS
  Least-squares mean ± standard error changes in YMRS scores from baseline to week 3 were -10.2 ± 0.80 in the mood stabilizer + ziprasidone 60- to 80-mg group, -11.0 ± 0.80 in the mood stabilizer + ziprasidone 20- to 40-mg group, and -9.5 ± 0.80 in the mood stabilizer + placebo group. Mean treatment differences between adjunctive ziprasidone groups and placebo were not statistically significant on primary or secondary efficacy measures. Ziprasidone was well tolerated.
  
  
  CONCLUSIONS
  Adjunctive ziprasidone treatment failed to separate from mood stabilizer (lithium or divalproex) treatment on primary and secondary end points.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00312494.
authors.affiliation: Bipolar Clinic and Research Program, Massachusetts General Hospital, 50 Staniford St, 5th Floor, Boston, MA 02114, USA. SachsG@aol.com
authors.forename: Gary S
authors.initials: GS
authors.lastname: Sachs
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Vanderburg
authors.forename: Onur N
authors.initials: ON
authors.lastname: Karayal
authors.forename: Sheela
authors.initials: S
authors.lastname: Kolluri
authors.forename: Mary
authors.initials: M
authors.lastname: Bachinsky
authors.forename: Idil
authors.initials: I
authors.lastname: Cavus
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000175:diagnosis; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D010879:Piperazines; D013844:Thiazoles; D016651:Lithium Carbonate; D014635:Valproic Acid; C092292:ziprasidone