Memantine Treatment for Obsessive-compulsive Disorder and Generalized Anxiety Disorder
Condition: Obsessive-Compulsive Disorder; Generalized Anxiety Disorder
MeSH terms: Anxiety Disorders; Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Memantine
Intervention type(s): Drug
Intervention description(s): Namenda 10mg BID for 12 weeks
Other intervention name(s): Namenda
Intervention MeSH terms: Memantine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obsessive-compulsive disorder; Generalized anxiety disorder; Memantine; Namenda