title: Ziprasidone Augmentation of Escitalopram for Major Depressive Disorder: Efficacy Results From a Randomized, Double-Blind, Placebo-Controlled Study.
abstract: OBJECTIVE
  The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.
  
  
  METHODS
  This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures.
  
  
  RESULTS
  Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group.
  
  
  CONCLUSIONS
  Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.
authors.affiliation: From the Massachusetts General Hospital Clinical Trials Network and Institute, the Massachusetts General Hospital Depression Clinical and Research Program, and Harvard Medical School, Boston; the Department of Psychiatry and Psychology, Mayo Medical School, Rochester, Minn.; the Department of Psychiatry and Behavioral Neurobiology, University of Alabama-Birmingham School of Medicine, Birmingham.
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.affiliation: From the Massachusetts General Hospital Clinical Trials Network and Institute, the Massachusetts General Hospital Depression Clinical and Research Program, and Harvard Medical School, Boston; the Department of Psychiatry and Psychology, Mayo Medical School, Rochester, Minn.; the Department of Psychiatry and Behavioral Neurobiology, University of Alabama-Birmingham School of Medicine, Birmingham.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.affiliation: From the Massachusetts General Hospital Clinical Trials Network and Institute, the Massachusetts General Hospital Depression Clinical and Research Program, and Harvard Medical School, Boston; the Department of Psychiatry and Psychology, Mayo Medical School, Rochester, Minn.; the Department of Psychiatry and Behavioral Neurobiology, University of Alabama-Birmingham School of Medicine, Birmingham.
authors.forename: Lee
authors.initials: L
authors.lastname: Baer
authors.affiliation: From the Massachusetts General Hospital Clinical Trials Network and Institute, the Massachusetts General Hospital Depression Clinical and Research Program, and Harvard Medical School, Boston; the Department of Psychiatry and Psychology, Mayo Medical School, Rochester, Minn.; the Department of Psychiatry and Behavioral Neurobiology, University of Alabama-Birmingham School of Medicine, Birmingham.
authors.forename: Michaela B
authors.initials: MB
authors.lastname: Swee
authors.affiliation: From the Massachusetts General Hospital Clinical Trials Network and Institute, the Massachusetts General Hospital Depression Clinical and Research Program, and Harvard Medical School, Boston; the Department of Psychiatry and Psychology, Mayo Medical School, Rochester, Minn.; the Department of Psychiatry and Behavioral Neurobiology, University of Alabama-Birmingham School of Medicine, Birmingham.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Jaeger
authors.affiliation: From the Massachusetts General Hospital Clinical Trials Network and Institute, the Massachusetts General Hospital Depression Clinical and Research Program, and Harvard Medical School, Boston; the Department of Psychiatry and Psychology, Mayo Medical School, Rochester, Minn.; the Department of Psychiatry and Behavioral Neurobiology, University of Alabama-Birmingham School of Medicine, Birmingham.
authors.forename: William V
authors.initials: WV
authors.lastname: Bobo
authors.affiliation: From the Massachusetts General Hospital Clinical Trials Network and Institute, the Massachusetts General Hospital Depression Clinical and Research Program, and Harvard Medical School, Boston; the Department of Psychiatry and Psychology, Mayo Medical School, Rochester, Minn.; the Department of Psychiatry and Behavioral Neurobiology, University of Alabama-Birmingham School of Medicine, Birmingham.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D013844:Thiazoles; D015283:Citalopram; C092292:ziprasidone