2005 - Memantine for Treatment-Resistant OCD
TO THE EDITOR:
Current options for treatment-resistant obsessive-
compulsive disorder (OCD) include switching to an alternative
selective serotonin reuptake inhibitor or augmentation
with dopamine antagonists or other agents (1).
Evidence from genetic, behavioral, and neuroimaging studies have indicated glutamatergic alteration in OCD (2).
In pediatric OCD patients, the glutamate caudate concentration was abnormally increased, but it decreased after paroxetine treatment (3).
Thus, attenuating glutamatergic hyperactivity might be
beneficial in OCD. We report a therapeutic effect of add-on
memantine, an N-methyl-D-aspartic acid glutamatergic receptor
antagonist, in 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.
Add-on memantine was well tolerated and resulted in clinically
significant reduction of OCD symptom severity.
Prior treatment resistance and the proximity between symptomatic improvement and the initiation of memantine point to its 2192 Am J Psychiatry 162:11, November 2005
LETTERS TO THE EDITOR
ajp.psychiatryonline.org
possible attenuating effect on the symptoms of OCD.
The association of OCD-schizotypal comorbidity with
the beneficial effect of memantine is noteworthy in view
of a pertinence of glutamatergic dysfunction in both OCD
and schizophrenia spectrum disorders (5).
Our case suggests that memantine
may be an option for treatment-resistant OCD, but controlled
studies are needed to substantiate this observation.
References
1. Pallanti S, Hollander E, Goodman WK: A qualitative analysis of nonresponse: management of treatment-refractory obsessivecompulsive disorder. J Clin Psychiatry 2004; 65(suppl 14):6–10
2. Arnold PD, Rosenberg DR, Mundo E, Tharmalingam S, Kennedy
JL, Richter MA: Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive-compulsive disorder: a
preliminary study. Psychopharmacology (Berl) 2004; 174:530–
538
3. Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD,
Stewart CM, Moore GJ: Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine. J Am Acad Child Adolesc Psychiatry 2000;39:1096–1103
4. Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P,
Heninger GR, Charney DS: The Yale-Brown Obsessive Compulsive
Scale, II: validity. Arch Gen Psychiatry 1989; 46:1012–1016
5. Poyurovsky M, Koran LM: Obsessive-compulsive disorder (OCD)
with schizotypy vs schizophrenia with OCD: diagnostic dilemmas
and therapeutic implications. J Psychiatr Res 2005; 39:
399–408
MICHAEL POYUROVSKY, M.D.
RONIT WEIZMAN, M.D.
ABRAHAM WEIZMAN, M.D.
LORRIN KORAN, M.D.
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