Memantine Treatment for Obsessive-Compulsive Disorder and Generalized Anxiety Disorder
The objective of this study was to obtain preliminary open-label data on the efficacy and tolerability of memantine, an anti-glutamatergic medication with a unique pharmacodynamic profile, in individuals with OCD and individuals with GAD. Because glutamatergic hyperactivity in frontal and frontal-subcortical circuits may play a role in the symptomatic expression of OCD, and possibly GAD, agents that reduce glutamatergic neurotransmission should provide unique anti-stress and anti-obsessional benefits. Memantine is a specific, uncompetitive antagonist at the NMDA receptor that blocks sustained activation of the NMDA receptor by high concentrations of glutamate under pathological conditions but rapidly leaves the NMDA channel upon transient physiological activation by low concentrations of glutamate.
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Differential Efficacy of Memantine for Obsessive-Compulsive Disorder vs. Generalized Anxiety Disorder: an Open-Label Trial|
- Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) [ Time Frame: baseline, weeks 2,4,6,8,12 ] [ Designated as safety issue: No ]
- Hamilton Anxiety Rating Scale (HARS) [ Time Frame: baseline, weeks 2,4,6,8,12 ] [ Designated as safety issue: No ]
|Study Start Date:||May 2005|
|Study Completion Date:||January 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
This was an open-label study- all subjects received the intervention.
Drug: Namenda (Memantine)
Namenda 10mg BID for 12 weeks
Several case reports and an open-label trial have reported efficacy of anti-glutamatergic medications for the treatment of OCD. In an open-label trial of riluzole, a glutamate release inhibitor, seven of 13 adult patients with OCD improved, and five were categorized as treatment responders. Another open trial found riluzole to be effective for four of six children with treatment-refractory OCD. N-acetylcysteine, an agent that likely attenuates glutamate neurotransmission, was effective as an augmentation in one patient with OCD. Two case reports described memantine treatment of OCD. Poyurovsky et al. reported improvement with memantine augmentation in one patient with treatment resistant OCD, while Pasquini and Biondi noted improvement in one OCD patient with checking compulsions but not in one with contamination obsessions. There have been no controlled or open-label trials of memantine in OCD reported thus far.
Few studies have examined the efficacy of anti-glutamatergic agents in GAD. In an open-label trial of riluzole treatment in 18 patients with GAD, twelve patients responded and eight achieved remission. A double-blind, controlled study found that LY354740, a metabotropic glutamate receptor 2/3 (mGlu2/3) agonist, was significantly more effective than placebo for GAD. No studies of memantine in GAD have been reported thus far. We hypothesized that treatment with memantine would result in significant symptom reduction in both OCD and GAD.
|United States, California|
|Los Angeles, California, United States, 90095|
|Principal Investigator:||Alexander Bystritsky, MD||University of California, Los Angeles|