title: Double-blind, placebo-controlled, pilot trial of paliperidone augmentation in serotonin reuptake inhibitor-resistant obsessive-compulsive disorder.
abstract: OBJECTIVE
  This pilot study explored the efficacy and tolerability of paliperidone augmentation of serotonin reuptake inhibitors (SRIs) in adults with treatment-resistant obsessive-compulsive disorder (OCD).
  
  
  METHODS
  Thirty-four patients aged 24-67 years (mean = 43.7 years, SD = 11.4) who met DSM-IV criteria for OCD and remained symptomatic following 2 or more past adequate SRI trials (including their current medication) were enrolled from May 2008 to March 2012. Participants were treated for 8 weeks in a double-blind study with either paliperidone (up to 9 mg/d) or matching placebo in addition to their SRI. Blinded raters conducted outcome assessments. The primary outcome, obsessive-compulsive symptom severity, was assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS). Secondary outcomes included the Clinical Global Impressions-Severity of Illness and -Improvement scales.
  
  
  RESULTS
  Paliperidone administration resulted in significant baseline-to-posttreatment reductions in obsessive-compulsive symptoms as measured by the YBOCS (P < .01, d = 0.66), although placebo administration also resulted in medium-sized, trend-level significant YBOCS changes (P = .05, d = 0.53). In exploratory analyses examining between-group differences, tests for paliperidone superiority relative to placebo were not significant (P = .14, d = 0.34); however, a numerical trend toward significant between-group differences was found, with a reduction of 7.98 points on the YBOCS for the paliperidone group compared to a reduction of 4.02 points for the placebo group. Paliperidone was generally well tolerated and not associated with significant weight gain (mean [SD] weight: paliperidone, pretreatment 84.70 [27.08] kg, posttreatment 84.84 [18.99] kg; vs placebo, pretreatment 77.50 [25.33] kg, posttreatment 77.43 [19.90] kg; P = .21).
  
  
  CONCLUSIONS
  These results suggest that paliperidone augmentation is well tolerated and has potential efficacy in the short-term treatment of some patients with SRI-resistant OCD. Well-powered, randomized, controlled studies are necessary to more definitively address the efficacy of this treatment strategy.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00632229.
authors.affiliation: Department of Pediatrics, Rothman Center for Neuropsychiatry, University of South Florida, Box 7523, 880 6th St South, St Petersburg, FL 33701, USA. estorch@health.usf.edu
authors.forename: Eric A
authors.initials: EA
authors.lastname: Storch
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Goddard
authors.forename: Jon E
authors.initials: JE
authors.lastname: Grant
authors.forename: Alessandro S
authors.initials: AS
authors.lastname: De Nadai
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Goodman
authors.forename: P Jane
authors.initials: PJ
authors.lastname: Mutch
authors.forename: Carla
authors.initials: C
authors.lastname: Medlock
authors.forename: Brian
authors.initials: B
authors.lastname: Odlaug
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: McDougle
authors.forename: Tanya K
authors.initials: TK
authors.lastname: Murphy
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004351:Drug Resistance / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D000068882:Paliperidone Palmitate; D010865:Pilot Projects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D000068882:Paliperidone Palmitate; D011743:Pyrimidines; D017367:Selective Serotonin Reuptake Inhibitors