Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder.
BACKGROUND
After considering the effects of 5-HT receptor agonists with different binding profiles on the symptoms of obsessive-compulsive disorder (OCD), Zohar and Kindler hypothesized that the 5-HT(1D) receptor was implicated in this disorder's pathophysiology.


METHODS
We explored the 5-HT(1D) hypothesis in a 5-day, random, double-blind, placebo-controlled trial of oral sumatriptan 100 mg/day in medication-free adults with OCD. We hypothesized that sumatriptan, a 5-HT(1D) agonist, would diminish 5-HT release, thereby worsening OCD symptoms. We further hypothesized that by beginning to desensitize 5-HT(1D) receptors, sumatriptan pretreatment would promote a faster response or an increased likelihood of response to subsequent treatment with a selective serotonin reuptake inhibitor.


RESULTS
The five sumatriptan subjects' OCD symptom worsening, as measured by the Yale-Brown scale ( upward arrow 17.6% (S.D. 14.6)), was significant when compared to the slight symptom decrease in the five placebo subjects ( downward arrow 5.2% (S.D. 4.9), P<0.015). The sumatriptan group did not exhibit a faster response or greater likelihood of response to a 90-day, open label trial of paroxetine.


CONCLUSIONS
Longer term studies of the effects of 5-HT(1D) agonists on OCD symptoms are indicated. Zolmitriptan, a potent 5-HT(1D) receptor agonist with better penetration of the blood-brain barrier, may be a preferred challenge agent.
Koran
L M
LM
Department of Psychiatry and Behavioral Sciences, Stanford Medical Center, Stanford, CA, USA. lkoran@stanford.edu
Pallanti
S
S
Quercioli
L
L
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000523:psychology; D017374:Paroxetine / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D018170:Sumatriptan / Q000627:therapeutic use*
D017374:Paroxetine; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D018170:Sumatriptan