Neurogenic orthostatic hypotension: A double-blind, placebo-controlled study with midodrine

Severe Hypertension and Bradycardia Secondary to Midodrine Overdose

“…Midodrine is a peripherally acting alpha-1-agonist used to treat conditions such as orthostatic hypotension [1]. We present a case of a young female who overdosed with midodrine and confirmatory corresponding drug concentrations during her clinical course.…”

“…Midodrine is a potent peripherally acting alpha-1-agonist used in the treatment of orthostatic hypotension, recurrent reflex syncope and dialysis-associated hypotension [1][2][3]. Its mechanism of action is to increase peripheral venous resistance and decrease venous capacity, hence increasing the supine and standing blood pressure [4,7].…”

“…Its mechanism of action is to increase peripheral venous resistance and decrease venous capacity, hence increasing the supine and standing blood pressure [4,7]. Notable side effects include compensatory reflex bradycardia [5], urinary urgency or retention, pilomotor reactions [2], pruritus and supine hypertension [1] and risk of bradycardia due to an alpha mediated vagal reflex [3]. Previous studies at therapeutic doses (10 mg) showed minimal or no central nervous system (CNS) side effects as it has poor absorption across the blood-brain barrier [5,6].…”

Midodrine Efficacy in Orthostatic Hypotension

“…In spite of the different trial designs, all four trials reported midodrine to significantly increase standing BP in patients with neurogenic OH (all p < 0.002). [2][3][4][5] Due to "significant heterogeneity" of the effect, the evidence for midodrine improving standing BP was rated as "low." When marked trial design differences exist (trials with 171 versus trials with eight patients; parallel-group versus cross-over studies; differences in dosing; differences in timing of effect assessment-three trials assess the drug-effect one hour after administration, while one trial averages hourly measurements throughout the day without specific timing relative to administration), it would be most adequate to conclude that a meta-analysis is not appropriate, and that the available evidence is better assessed by considering each study independently, since the apparent heterogeneity merely reflects the combination of trials that should not have been combined.…”

“…For example, in the Published online September 9, 2014 (inappropriate) assessment of systolic BP change from supine to standing, three studies show, as expected, no difference or a mildly decreased BP drop comparing placebo/baseline and midodrine, while one study (Jankovic et al) shows an apparent large increase in the BP drop following midodrine compared to placebo (30mmHg). 3 Careful analysis would have revealed that this parallel group study was problematic, due to marked baseline differences between the placebo and the 10 mg midodrine group. Baseline (pre-medication) evaluations revealed an average systolic BP drop of only 33 mmHg in the placebo group versus an average systolic BP drop of 67 mmHg in the 10 mg midodrine group, which accounts for and readily explains the difference after medication, which was 28 mmHg in the placebo group and 58 mmHg in the midodrine group.…”