A single-blinded case-control study of memantine in severe obsessive-compulsive disorder.
BACKGROUND
Obsessive-compulsive disorder (OCD) is a common debilitating psychiatric illness that typically improves but does not remit with first-line medication and behavioral treatments. Serotonergic agents including selective serotonin reuptake inhibitors and clomipramine have provided the mainstay of OCD medication management for decades. Combined dopamine/serotonergic agents such as atypical antipsychotics are presently the only OCD-augmenting strategies proven effective via randomized controlled trials. Despite increasing evidence for a pathogenic role of glutamate in OCD, no controlled trials of glutamatergic augmenting agents have been reported.


METHODS
An intent-to-treat sample included 44 subjects receiving standard treatment at the McLean/Massachusetts General Hospital Intensive Residential Treatment (IRT) program, 22 of whom also received memantine augmentation. Admission, monthly and discharge measures of OCD, depression, and psychosocial functioning were collected by raters blinded to augmentation status. Matched controls were selected based on sex, initial OCD severity, psychosocial functioning, and timing of admission. The Clinical Global Improvement Scale captured global clinical change.


RESULTS
Mean (SD) Yale-Brown Obsessive Compulsive Scale score decreases were 7.2 (6.4) among the cases and 4.6 (5.9) among the matched controls, reflecting mean clinical improvement among the cases (27.0% decrease) but not the controls (16.5% decrease). Mean (SD) depression severity score decreases were 5.8 (9.5) among the cases and 4.7 (9.9) among the controls. Initial intrusive obsessions were significantly more severe among marked responders compared with limited response or nonresponse cases (4.4 vs 2.9; t = 2.15; P = 0.048).


CONCLUSIONS
This study provides preliminary supportive evidence for the effectiveness of memantine as a glutamatergic augmenting agent in severe OCD. Future randomized double-blind placebo-controlled trials are warranted.
Stewart
S Evelyn
SE
Obsessive-Compulsive Disorder Institute, McLean Hospital, Belmont, MA 02114, USA. stewart@pngu.mgh.harvard.edu
Jenike
Eric A
EA
Hezel
Dianne M
DM
Stack
Denise Egan
DE
Dodman
Nicholas H
NH
Shuster
Louis
L
Jenike
Michael A
MA
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007297:Inpatients; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000627:therapeutic use*; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D012112:Residential Facilities; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016037:Single-Blind Method; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D018691:Excitatory Amino Acid Antagonists; D008559:Memantine; D017367:Selective Serotonin Reuptake Inhibitors