title: A 12-week, randomized, double-blind, placebo-controlled, sequential parallel comparison trial of ziprasidone as monotherapy for major depressive disorder.
abstract: OBJECTIVE
  To study ziprasidone monotherapy for major depressive disorder, defined according to the DSM-IV.
  
  
  METHODS
  One hundred twenty outpatients were enrolled between June 2008 and September 2010 in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 fashion to receive ziprasidone for 12 weeks, placebo for 6 weeks followed by ziprasidone for 6 weeks, or placebo for 12 weeks. The main outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS-17), with the Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR), and Clinical Global Impressions-Severity of Illness scale (CGI-S) serving as the study secondary measures.
  
  
  RESULTS
  One hundred twenty patients (53 women [44.1%]) were randomized to treatment. The mean (SD) age of these patients was 43.7 (11.0) years. Mean (SD) baseline HDRS-17, CGI-S, and QIDS-SR scores were 19.9 (5.0), 4.3 (0.6), and 15.6 (3.0), respectively. There was no statistically significant difference in reduction of depressive symptoms, response rates, or remission rates between ziprasidone- or placebo-treated patients. This was true for both the study primary as well as secondary outcome scales.
  
  
  CONCLUSIONS
  In conclusion, treatment with ziprasidone monotherapy was not associated with any statistically significant advantage in efficacy over placebo. Although studies involving larger sample size would be required to have adequate statistical power to detect treatment differences smaller than 2.5 points on the HDRS-17, such differences would be of questionable clinical relevance.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00555997.
authors.affiliation: Center for Treatment-Resistant Depression, Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. gpapakostas@partners.org
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.forename: Ottavio V
authors.initials: OV
authors.lastname: Vitolo
authors.forename: Waguih W
authors.initials: WW
authors.lastname: Ishak
authors.forename: Mark H
authors.initials: MH
authors.lastname: Rapaport
authors.forename: John M
authors.initials: JM
authors.lastname: Zajecka
authors.forename: Gustavo
authors.initials: G
authors.lastname: Kinrys
authors.forename: David
authors.initials: D
authors.lastname: Mischoulon
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Lipkin
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hails
authors.forename: Jonah
authors.initials: J
authors.lastname: Abrams
authors.forename: Sean G
authors.initials: SG
authors.lastname: Ward
authors.forename: Allison
authors.initials: A
authors.lastname: Meisner
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.forename: Andrew
authors.initials: A
authors.lastname: Winokur
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Okasha
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Bari
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory / Q000706:statistics & numerical data; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011594:Psychometrics; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone