Norepinephrine Transport Inhibition for Treatment of Vasovagal Syncope

Abstract

Norepinephrine transporter inhibitors, such as sibutramine, have been shown to prevent vasovagal syncope induced by tilt testing in healthy volunteers. As a test of concept we assessed whether sibutramine prevents fainting in highly symptomatic VVS patients. This was an open label, dose-ranging protocol of sibutramine 10, 15, and 20 mg daily for ≥4 weeks per dose, with progression dictated by response and tolerance. Responders were predefined as having >50% reduction in spell frequency, compared to baseline spell frequency. The cohort included seven subjects (6 women; 32 ± 7 years) who had a median of 593 faints over a median of 180 months. The patients had had 7 ± 4 previous treatment attempts without a satisfactory response. The mean duration of exposure to 10 mg, 15 mg, and 20 mg doses were 45 ± 33 days, 98 ± 89 days, and 137 ± 83 days. Six patients tolerated the maximum dose, and 1 patient dropped out due to adverse effects at 15 mg/day. The median frequency of spells at baseline, 10, 15, and 20 mg/day was 12, 4.4, 2.8, and 1 events/28 days (P = 0.0048). Five patients were responders and 2 were nonresponders. Among responders, the median frequency of spells at baseline, 10, 15, and 20 mg/day was 14, 4.8, 0.8, and 0.4 events per 28 days (P = 0.0089). No patients developed hypertension. In this open label series, sibutramine prevented vasovagal syncope in most highly symptomatic patients.