Zolmitriptan (a 5-HT_1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder

Abstract.

Rationale: Non-selective serotonin (5-HT) receptor agonists like meta-chlorophenylpiperazine and MK-212 have been used to explore the role of 5-HT in obsessive compulsive disorder (OCD). The results of these studies and the findings of autoradiography and neuroimaging studies, pointed to a possible role of the 5-HT_1B/1D receptor in the pathophysiology of OCD. Recently the selective 5-HT_1B/1D receptor agonist sumatriptan was used to further explore the role of the 5-HT_1B/1D receptor in OCD. Equivocal results with respect to the increase of obsessive compulsive symptoms in patients with OCD were reported. In one study a significant increase in plasma growth hormone (GH) concentration was observed, although sumatriptan does not pass the blood-brain barrier. Objectives: In order to further explore the role of the 5-HT_1B/1D receptor in the pathophysiology of OCD, we performed this study, following the same design as Ho Pian et al. (Psychopharmacology 140:365–370). Methods: In the present study we performed a randomized, double-blind, placebo-controlled, cross-over design with zolmitriptan (5 mg per os), a selective 5-HT_1B/1D receptor agonist with better brain penetrating properties than sumatriptan. Results: We could not detect any changes in obsessive compulsive symptoms, mood, or anxiety levels, although we found a (non-significant) increase in plasma GH levels. Conclusions: Based upon these findings, no evidence was found for a specific role of the 5-HT_1B/1D receptor in OCD. It should be noted, however, that challenge studies in OCD are difficult to perform. Perhaps in the future better challenge paradigms will make it possible to further explore the role of specific receptor types in OCD.