title: Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept.
abstract: Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid anti-obsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n=15) with near-constant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (p<0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n=8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n=7). One-week post-infusion, 50% of those receiving ketamine (n=8) met criteria for treatment response (≥35% Y-BOCS reduction) vs 0% of those receiving placebo (n=7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.
authors.affiliation: 1] New York State Psychiatric Institute, New York, NY, USA [2] Department of Psychiatry, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Carolyn I
authors.initials: CI
authors.lastname: Rodriguez
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.forename: Amanda
authors.initials: A
authors.lastname: Levinson
authors.forename: Tianshu
authors.initials: T
authors.lastname: Feng
authors.forename: Sue M
authors.initials: SM
authors.lastname: Marcus
authors.forename: Donna
authors.initials: D
authors.lastname: Vermes
authors.forename: Pamela
authors.initials: P
authors.lastname: Flood
authors.forename: Helen B
authors.initials: HB
authors.lastname: Simpson
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine