Memantine augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial.
BACKGROUND
Data from the fields of genetics, neuroimaging, and animal studies, along with case reports and small clinical trials, point to a role for glutamatergic dysfunction in the pathophysiology of obsessive-compulsive disorder (OCD). We report on the first open-label study to test the hypothesis that memantine, a noncompetitive glutamate antagonist, will result in a clinically meaningful reduction in OCD symptoms in adults with treatment-resistant OCD.


METHODS
We recruited 15 adult subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined OCD and a baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18 or higher, who had failed to respond to treatment with a serotonin reuptake inhibitor (SRI), given at an adequate and stable dose for at least 12 weeks. The duration of memantine treatment was 12 weeks, and the dose was gradually increased to a target of 20 mg/d. Response was defined as a 25% or greater reduction in the Y-BOCS score at study end and a Clinical Global Impression-Improvement scale rating of "much" or "very much" improved.


RESULTS
Data from 14 subjects were analyzable. Mean baseline Y-BOCS score was 27.4 (SD, 5.0). Subjects had failed an average of 2.8 (SD, 1.8) SRI trials; 6 subjects had failed augmentation with atypical antipsychotics. At study end, 6 subjects (42.9%) were responders, and response was achieved by EOW4. Responders had significantly lower baseline Y-BOCS scores (2-tailed t tests, P < 0.05, t = 2.2) and had failed fewer SRIs (P <or= 0.05, t = 2.2). Side effects to memantine were mild and transient, and no subject withdrew from the study for an adverse event.


CONCLUSIONS
In this open-label augmentation trial of memantine in treatment-resistant OCD, almost half the subjects had a meaningful improvement in symptoms. Our study was limited by its small size, presence of comorbidities, and lack of control. Large double-blind placebo-controlled trials are needed to further test our findings.
Aboujaoude
Elias
E
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. eaboujaoude@stanford.edu
Barry
John J
JJ
Gamel
Nona
N
D000328:Adult; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use*; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D008559:Memantine; D017367:Selective Serotonin Reuptake Inhibitors