Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome

OBJECTIVES We sought to test the hypothesis that activation of the serotonergic system in patients with vasovagal syndrome during the head-up tilt test provokes syncope. BACKGROUND Central serotonergic activation participates in the pathogenesis of neurocardiogenic syncope. Drugs increasing serotonin (5-HT) in the central nervous system have not been tested as drug challenges during the head-up tilt test with clomipramine (Clom-HUT). METHODS The serotonergic re-uptake inhibitor clomipramine was infused (5 mg in 5 min) at the start of Clom-HUT in 55 patients (mean age 40 ± 17 years) with a positive history of recurrent neurocardiogenic syncope and in 22 healthy control subjects (mean age 46 ± 15 years). Blood samples were taken at 0, 5, 10 and 20 min for estimation of plasma prolactin and cortisol as neuroendocrine indicators of central serotonergic responsitivity. All subjects had been previously tested with a basic 60° head-up tilt test (B-HUT) for 30 min, and if negative, isoproterenol infusion was given at the end of the test. RESULTS Twenty-nine (53%) of the 55 patients and none of the 22 control subjects had a positive result in the B-HUT. With Clom-HUT, the proportion of patients who experienced a positive response increased to 80% (n = 44), although this happened to only one control subject. Prolactin and cortisol plasma levels increased significantly in the positive Clom-HUT patient group only. CONCLUSIONS The results indicate an increased responsitivity of the central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion with the tilt test seems to considerably improve its diagnostic value.