Dihydroergotamine in idiopathic orthostatic hypotension: short-term intramuscular and long-term oral therapy

The efficacy of dihydroergotamine (DHE-45) in the treatment of orthostatic hypotension due to deficient circulatory reflexes was investigated in 10 patients. Over the short term, intramuscular DHE-45 induced an increase (P less than 0.005) in supine blood pressure (137 +/- 8.9 to 158 +/- 8.1 mm Hg 15 min after DHE-45 and 142 +/- 9.9 to 183 +/- 7.5 mm Hg 60 min after DHE-45) associated with an increase in total peripheral resistance (TPR) (37 +/- 1.9 to 41 +/- 2.8 U . m2 and 34 +/- 2.2 to 41 +/- 2.3) and no change in cardiac output (CO), plasma renin activity (PRA), or plasma norepinephrine. Eight patients tolerated head-up tilt to a higher angle--the drop of mean arterial pressure at equivalent angles of tilt (pre- and post-DHE-45) was less. The other two patients did not improve. On the other hand, oral DHE-45 (1-mo therapy) did not induce a change in mean arterial pressure, heart rate, CO, or TPR; the only significant hemodynamic change was an increase in the ratio cardiopulmonary volume/total blood volume (12 +/- 1.9% to 16 +/- 0.7%, P less than 0.025). Changes in PRA, plasma aldosterone, and plasma catecholamines were not significant. Response to head-up tilt was variable after the first week of therapy. Blood level 2 hr after an oral dose was one order of magnitude lower (0.1 to 0.2 ng/ml) than after intramuscular injection (1.2 to 3.2 ng/ml). The discrepancy between the effects of intramuscular and oral DHE-45 for treatment of idiopathic orthostatic hypotension in this group of patients might be related to the nature of the disease (autonomic insufficiency) or to low bioavailability, suggesting that either another formulation of the drug or methods to improve absorption are needed for long-term therapy.