A DOUBLE-BLIND, DOSE-RESPONSE STUDY OF MIDODRINE IN NEUROGENIC ORTHOSTATIC HYPOTENSION

Objective: To determine the best therapeutic strategy for the use of m idodrine in patients with neurogenic orthostatic hypotension (NOH). Ba ckground: Midodrine is a peripherally acting a-adrenergic agonist usef ul in the treatment of NOH. However, neither the most effective dosage of midodrine nor the required frequency of administration is establis hed. Design/Methods: Midodrine dose-blood pressure response, pharmacok inetics, and duration of action were examined in a double-blind, place bo-controlled, four-way crossover trial. Twenty-five patients with NOH were randomized to receive on successive days placebo or midodrine 2. 5, 10, or 20 mg. Blood pressures of patients in the supine and standin g positions were measured sequentially. A global assessment of the pat ient's overall symptom improvement after each leg of the study was per formed. Blood levels of midodrine and its active metabolite, desglymid odrine, were assayed. Results: Midodrine significantly increased stand ing systolic blood pressure, with the increase peaking at 1 hour. Ther e was a significant linear relation between midodrine dosage and mean systolic blood pressure. The mean score for global improvement of symp toms was significantly higher for midodrine (10 and 20 mg) compared wi th placebo. The half-life of desglymidodrine was similar to 4 hours. C onclusion: A 10-mg dose of midodrine prescribed two to three times dai ly is effective in increasing orthostatic blood pressure and ameliorat ing symptoms in patients with NOH.