Memantine for Treatment-Resistant OCD

Ms. A, a 34-year-old woman, was seen with incapacitating ego-dystonic obsessions, including fear of harm to her daughter and of losing her mind. She developed compulsive checking behavior to decrease the associated anxiety. Obsessive-compulsive symptoms, initially detected at age 16, remitted spontaneously 2 years later. Subsequent postpartum exacerbation of DSM-IV OCD symptoms associated with major depression occurred at age 30. She also met DSM-IV criteria for schizotypal personality disorder.

Subsequent adequate trials with paroxetine and sertraline were ineffective. Add-on risperidone caused marked akathisia and was discontinued. At her presentation, oral clomipramine was initiated and titrated to 300 mg/day; however, 10 weeks later, there was no significant clinical improvement (Yale-Brown Obsessive Compulsive Scale [4] score=35). Addition of a selective dopamine D₂ antagonist, sulpiride (up to 400 mg/day for 4 weeks), was also ineffective (Yale-Brown Obsessive Compulsive Scale score=34). At this point, adding memantine to Ms. A’s regimen of clomipramine (300 mg/day) and sulpiride (400 mg/day) was suggested, and she signed informed consent after explanation of this off-label therapy. Memantine was started at 5 mg/day and titrated to 20 mg/day within 2 weeks. Ms. A reported initial relief on day 7 of combined treatment, and a significant decrease in symptom severity was noted 3 weeks later (Yale-Brown Obsessive Compulsive Scale score=22). There was a substantial reduction in the time occupied by OCD and distress, followed by increased control over obsessions. No clinically significant side effects were noted. Improvement was maintained after 3 months.