Double-blind treatment with oral morphine in treatment-resistant obsessive-compulsive disorder

J Clin Psychiatry. 2005 Mar;66(3):353-9. doi: 10.4088/jcp.v66n0312.

Abstract

Background: Obsessive-compulsive disorder (OCD) often responds inadequately to serotonin reuptake inhibitors (SRIs). A case series reported substantial response to once-weekly oral morphine. We conducted a placebo-controlled, double-blind trial to investigate whether once-weekly oral morphine is effective in SRI-resistant OCD.

Method: Subjects with DSM-IV-defined OCD for > or =3 years who had failed > or =2 adequate SRI trials and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of > or =20 were recruited. Current medications were continued. Subjects were randomly assigned to random-order, 2-week blocks of once-weekly morphine, lorazepam, and placebo. Week 2 dosage was increased, decreased, or maintained depending on response and side effects.

Results: We enrolled 23 subjects, who had failed 2 to 6 SRI trials. The median screening Y-BOCS score was 29. The median Y-BOCS score after morphine (highest dose) was 25 (median decrease = 13%). Seven subjects (30%) were responders (Y-BOCS decreases > or =25%). The median Y-BOCS score after lorazepam (highest dose) was 27 (median decrease = 6%). Four subjects (17%) responded to lorazepam; 1 was a morphine responder. The median Y-BOCS score after placebo (highest dose) was 27 (median decrease = 7%), and no subject responded. Responses differed significantly among the 3 conditions (Friedman 2-way analysis of variance, chir(2) = 13.92, df = 2, p = .01). Wilcoxon matched-pairs signed-rank tests (T = 56.5, p = .05) showed significance for morphine versus placebo but not lorazepam versus placebo.

Conclusion: Our results support the hypothesis that once-weekly oral morphine can reduce symptoms in some treatment-resistant OCD patients. The mechanism of action is unknown. Further studies of mu-agonists and glutamate antagonists are warranted.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Humans
  • Lorazepam / therapeutic use
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology
  • Morphine / therapeutic use*
  • Narcotics / administration & dosage
  • Narcotics / pharmacology
  • Narcotics / therapeutic use*
  • Obsessive-Compulsive Disorder / diagnosis
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / psychology
  • Placebos
  • Psychiatric Status Rating Scales
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / drug effects
  • Serotonin Uptake Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • Narcotics
  • Placebos
  • Receptors, Opioid, mu
  • Serotonin Uptake Inhibitors
  • Morphine
  • Lorazepam