Sumatriptan (5-HT 1D receptor agonist) does not exacerbate symptoms in obsessive compulsive disorder

Abstract

The non-selective serotonin (5-HT) receptor agonist meta-chlorophenylpiperazine (mCPP) has been reported to elicit symptoms in patients with obsessive compulsive disorder (OCD). MK-212, another non-selective 5-HT receptor agonist, does not seem to induce obsessive compulsive symptoms in OCD patients. The major pharmacological difference between mCPP and MK-212 is their affinity for the 5-HT(ID) receptor. The aim of this study was to explore the role of the 5-HT(ID) receptor in the pathophysiology of OCD, by using a challenge paradigm with the selective 5-HT(ID) receptor agonist sumatriptan (Imigran). A randomized, double-blind, placebo-controlled crossover challenge with sumatriptan (100 mg PO) was performed in 15 OCD patients. Neither the obsessive compulsive symptoms nor mood or anxiety symptoms changed significantly following sumatriptan administration as compared to placebo. Sumatriptan did induce a significant increase in plasma growth hormone (GH) levels. In the present study, no indication were found for the role of the 5-HT(ID) receptor in the pathophysiology of OCD. It should be noted, however, that sumatriptan does not readily pass the blood-brain barrier. Selective 5-HT(ID) receptors with better brain penetrating properties may shed more light on the role of this 5-HT receptor subtype in OCD.

Serotonergic Dissection of Obsessive Compulsive Symptoms: A Challenge Study with m-Chlorophenylpiperazine and Sumatriptan

“…This is in line with the relative affinities of the two drugs to the 5-HT 1D receptor. These results are in line with previous challenge studies with sumatriptan [15][16][17] but contradict others [16,18], possibly because there are two types of OCD patients -responders and non-responders to sumatriptan -depending on genetic factors such as polymorphisms at the 5-HT 1D receptor locus [19].…”

“…In cases in which no exacerbation on sumatriptan challenge was found, it has been claimed that sumatriptan does not cross the blood-brain barrier [18]. Two noteworthy arguments arise -the first is that possibly anxiety disorders, among other affective disorders, differ from the normal population by the high permeability of the bloodbrain barrier.…”

Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder

“…These results are in accordance with those of the study by Ho Pian et al (1998) where the 5-HT 1B/1D receptor agonist sumatriptan was used in a similar design. The data of the present study do not support a role of 5-HT 1B/1D receptors in the pathophysiology of OCD.…”

“…Other studies with sumatriptan compared healthy subjects with patients and found blunted GH responses in patients with seasonal affective disorder and depression (Yatham et al 1997a,b;Cleare et al 1998). In manic patients (Yatham et al 1997b) and in OCD patients (Ho Pian et al 1998) an increase in GH levels comparable with controls was seen after the use of sumatriptan.…”

“…In a recent study, Ho Pian et al (1998) used sumatriptan to provoke symptoms in OCD patients. No behavioral effects were found of sumatriptan.…”