Midodrine in neurally mediated syncope: a double-blind, randomized, crossover study

Ann Neurol. 2002 Sep;52(3):342-5. doi: 10.1002/ana.10293.


Neurally mediated syncope is the most frequent cause of syncope in patients without structural heart disease. Its most common trigger is a reduction in venous return to the heart due to excessive venous pooling in the legs. We conducted a double-blind, randomized, crossover trial to investigate the efficacy of midodrine, a selective alpha-1 adrenergic agonist that decreases venous capacitance, in preventing neurally mediated syncope triggered by passive head-up tilt. Twelve patients with history of recurrent neurally mediated syncope, which was reproduced during head-up tilt, were randomized to receive a nonpressor dose of midodrine (5mg) or placebo on day 1 and the opposite on day 3. One hour after drug or placebo administration, patients underwent 60-degree head-up tilt lasting 40 minutes (unless hypotension or bradycardia developed first). In the supine position, midodrine produced no significant change in blood pressure or heart rate. The responses to head-up tilt were significantly different on the midodrine and the placebo day: on the placebo day, 67% (8/12) of the subjects suffered neurally mediated syncope, whereas only 17% (2/12) of the subjects developed neurally mediated syncope on the midodrine day (p < 0.02). These results indicate that midodrine significantly improves orthostatic tolerance during head-up tilt in patients with recurrent neurally mediated syncope.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Pressure / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hypotension, Orthostatic / drug therapy
  • Hypotension, Orthostatic / prevention & control
  • Male
  • Middle Aged
  • Midodrine / therapeutic use*
  • Syncope, Vasovagal / drug therapy*
  • Syncope, Vasovagal / prevention & control
  • Tilt-Table Test
  • Vasoconstrictor Agents / therapeutic use*


  • Vasoconstrictor Agents
  • Midodrine