title: Riluzole augmentation in treatment-refractory obsessive-compulsive disorder: a pilot randomized placebo-controlled trial.
abstract: OBJECTIVE
  Obsessive-compulsive disorder (OCD) affects approximately 2.5% of the population and is associated with significant morbidity. Many patients receive little benefit from the best available treatments, and even those who do respond often suffer from significant residual symptoms. Convergent evidence suggests that abnormalities in glutamate homeostasis and neurotransmission may contribute to OCD and that glutamate-modulating medications may be of benefit in patients whose symptoms are refractory to standard interventions. Small open-label trials of augmentation of serotonin reuptake inhibitor (SRI) pharmacotherapy with the glutamate modulator riluzole have suggested benefit in adults with refractory symptoms. We report a pilot randomized placebo-controlled trial of riluzole augmentation of ongoing SRI treatment in SRI-refractory patients.
  
  
  METHODS
  Outpatients (n = 27) and inpatients (n = 11) with DSM-IV OCD on stable SRI pharmacotherapy were randomized between November 2006 and December 2012 to receive riluzole 50 mg or placebo twice a day and followed for 12 weeks after a 2-week placebo lead-in phase.
  
  
  RESULTS
  Riluzole was well tolerated; 1 patient experienced moderate nausea, but none discontinued treatment due to side effects. While there was nominally greater Y-BOCS improvement in the riluzole group (our primary outcome) compared to placebo, it did not reach statistical significance. In the outpatient subsample, a trend suggesting benefit from riluzole augmentation for obsessions (P = .056, 2-tailed, uncorrected) was found in a secondary analysis. Among outpatients, more achieved at least a partial response (> 25% improvement) with riluzole than with placebo (P = .02 in a secondary analysis).
  
  
  CONCLUSIONS
  Riluzole may be of benefit to a subset of patients. Larger samples would be required to detect effects of the order suggested by the nominal improvement in our outpatient subsample.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00523718.
authors.affiliation: 34 Park St, W315, New Haven, CT 06519 Christopher.pittenger@yale.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pittenger
authors.forename: Michael H
authors.initials: MH
authors.lastname: Bloch
authors.forename: Suzanne
authors.initials: S
authors.lastname: Wasylink
authors.forename: Eileen
authors.initials: E
authors.lastname: Billingslea
authors.forename: Ryan
authors.initials: R
authors.lastname: Simpson
authors.forename: Ewgeni
authors.initials: E
authors.lastname: Jakubovski
authors.forename: Ben
authors.initials: B
authors.lastname: Kelmendi
authors.forename: Gerard
authors.initials: G
authors.lastname: Sanacora
authors.forename: Vladimir
authors.initials: V
authors.lastname: Coric
mesh_terms: D000328:Adult; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D010865:Pilot Projects; D019782:Riluzole / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole; D017367:Selective Serotonin Reuptake Inhibitors