Central serotonergic responsiveness in neurocardiogenic syncope: a clomipramine test challenge.

BACKGROUND Central serotonergic mechanisms appear to participate in the pathogenesis of recurrent neurally mediated syncope. The aim of the study was to investigate the responsiveness of the central serotonergic system by measuring the prolactin and cortisol responses to intravenous administration of the serotonin reuptake inhibitor clomipramine. METHODS AND RESULTS Twenty subjects free of any medical treatment were tested. Twelve had a history of recurrent syncopal attacks and positive tilt test (patient group, mean age 47+/-18 years, 8 men); 8 subjects without syncope and a negative tilt test result served as control subjects (mean age 49+/-10 years, 5 men). Twenty-five milligrams of clomipramine was administered intravenously within 15 minutes, and blood samples were taken at 0, 15, 30, 45, and 60 minutes. Two days later, a tilt test was performed at 60 degrees for 30 minutes and blood samples were taken at 0, 10, 20, and 30 minutes. During the clomipramine challenge, plasma prolactin levels increased in both groups. The levels at 30 minutes were higher in the patient group compared with the control group (17.3+/-7.2 vs 9.3+/-7.6 ng/mL, P=0.05). Similar results were observed for cortisol at 30 minutes (172+/-15 vs 118+/-21 ng/mL P=0. 04) and at 45 minutes (189+/-20 vs 116+/-23 ng/mL, P=0.03). The tilt test was positive in 8 (67%) out of 12 of the patient group and negative in all control subjects. In the samples taken during the tilt test, significant increases in prolactin and cortisol were observed only in the subjects with positive tilt test results. CONCLUSIONS Patients with a history of neurocardiogenic syncope show a higher responsiveness of the central serotonergic system to clomipramine challenge. The results support the view that central serotonergic mechanisms are involved in the pathophysiology of the syndrome.