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


METHODS
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.


CONCLUSIONS
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.
Koran
Lorrin M
LM
Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305, USA. lkoran@stanford.edu
Aboujaoude
Elias
E
Bullock
Kim D
KD
Franz
Bettina
B
Gamel
Nona
N
Elliott
Michael
M
D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
D008140:Lorazepam; D009020:Morphine; D009294:Narcotics; D010919:Placebos; D017450:Receptors, Opioid, mu; D017367:Selective Serotonin Reuptake Inhibitors