title: Norepinephrine transport inhibition for treatment of vasovagal syncope.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  In this open label series, sibutramine prevented vasovagal syncope in most highly symptomatic patients.
authors: Libin Cardiovascular Institute of Calgary, Calgary, Alberta, Canada. sheldon@ucalgary.ca
authors: Robert S
authors: RS
authors: Sheldon
authors: Debbie
authors: D
authors: Ritchie
authors: Maureen
authors: M
authors: McRae
authors: Satish
authors: S
authors: Raj
mesh_terms: D000328:Adult; D003503:Cyclobutanes / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D019462:Syncope, Vasovagal / Q000188:drug therapy*
chemical_list: D003503:Cyclobutanes; D050484:Norepinephrine Plasma Membrane Transport Proteins; C058254:sibutramine
keywords: hypotension; norepinephrine transporter; sibutramine; syncope; vasovagal