Midodrine in neurally mediated syncope: A double‐blind, randomized, crossover study

Abstract 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 α‐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.