601 Sibutramine, A Norepinephrine Transport Inhibitor, Prevents Vasovagal Syncope

Abstract

Norepinephrine transport inhibitors such as Reboxetine and Sibutramine block vasovagal syncope (VVS) induced by tilt testing. We aimed to determine whether Sibutramine prevents fainting in highly symptomatic VVS patients. Seven of the most severely affected and treatment-resistant patients with VVS underwent open label, compassionate treatment with incremental doses of Sibutramine. The dose-ranging protocol was 10, 15, and 20 mg daily for at least 4 weeks per dose, with progression through the stages dictated by response and tolerance. A positive response was predefined as >50% reduction in symptom frequency, compared to symptom frequency in the preceding month. There were 7 subjects, (6 women), 32±7 years old, who had had a median of 529 faints over a median of 172 months. In the preceding year they had a median 200 faints, and in the preceding month a median 8 faints (mean 6.4±5 faints). One of the patients had severe presyncope as a target outcome event. They had had 7±5 previous treatment attempts and responded satisfactorily to none. Three patient groups are reported. The TOTAL population is comprised of all 7 patients. The RESPONDER population is comprised of the 5 patients who had a >50% response. The PERSISTENTLY RESPONDING population is comprised of the 3 patients who did not have a late recurrence of frequent syncope. The TOTAL population received a mean top dose of 17.9 mg/day. At 10, 15, and 20 mg/day the symptom frequency compared to baseline was 53%, 36%, and 18% on a patient-specific basis. The RESPONDER population received a mean top dose of 17 mg/day. At 10, 15, and 20 mg/day the symptom frequency compared to baseline was 25%, 26%, and 6% on a patient-specific basis. The PERSISTENTLY RESPONDING population received a mean top dose of 15 mg/day. At 10, 15, and 20 mg/day the symptom frequency compared to baseline was 23%, 3%, and 0% on a patient-specific basis. Side effects were predictable and dose-related. Of the 7 patients, none had related side effects on 10 mg/day; 2 had side effects on 15 mg/day; and 4 had side effects on 20 mg day. They were mild and patients usually rated them as less severe than the syncope they were preventing, or attempting to prevent. None had hypertension. Sibutramine prevents VVS in most highly symptomatic patients. NET inhibitors show promise in preventing VVS and require further assessment.