title: High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multicenter double-blind trial.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment.
  
  
  METHODS
  Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995.
  
  
  RESULTS
  The high-dose (250-400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates.
  
  
  CONCLUSIONS
  Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1841 Clifton Road, Atlanta, GA 30329, USA. pninan@emory.edu
authors.forename: Philip T
authors.initials: PT
authors.lastname: Ninan
authors.forename: Lorrin M
authors.initials: LM
authors.lastname: Koran
authors.forename: Ari
authors.initials: A
authors.lastname: Kiev
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Davidson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rasmussen
authors.forename: John M
authors.initials: JM
authors.lastname: Zajecka
authors.forename: Delbert G
authors.initials: DG
authors.lastname: Robinson
authors.forename: Paul
authors.initials: P
authors.lastname: Crits-Christoph
authors.forename: Francine S
authors.initials: FS
authors.lastname: Mandel
authors.forename: Carol
authors.initials: C
authors.lastname: Austin
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000523:psychology; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline