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 (↑ 17.6% (S.D. 14.6)), was significant when compared to the slight symptom decrease in the five placebo subjects (↓ 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.