Midodrine exacerbates promethazine‐induced akathisia

Astronauts returning from space often experience nausea as well as orthostatic hypotension. Promethazine (PMZ) is the anti‐emetic most frequently prescribed by flight surgeons. Midodrine (Mido) is currently under evaluation as an anti‐orthostatic hypotensive agent. A double blind, randomized, cross over study, to evaluate possible drug interactions, was conducted on 9 subjects at the Johnson Space Center. Subjects visited the laboratory on four separate days and received (in random order); Mido + PMZ, placebo + placebo, Mido + placebo, or PMZ + placebo. Subjects were monitored for behavioral changes on each occasion. Using the Barnes global akathisia score, we compared treatments with a Student's paired t‐test. Significance was determined if p less than 0.05. No subject experienced akathisia with placebo or Mido alone (0/9). Forty‐four percent experienced akathisia with PMZ alone (4/9). The majority, 67%, of the subjects experienced akathisia when they received both Mido and PMZ (6/9). In addition, the severity of akathisia (Barnes global akathisia rating) was significantly greater (p=0.04) with Mido plus PMZ (2.0 +/− 0.6) than with PMZ alone (0.8 +/− 0.4). The fact that the combination of PMZ and Mido produced such profound akathisia in a majority of our subjects was a surprise. While phenothiazines are known to induce akathisia, there is no report that Mido induces akathisia. In clinical settings, patients who are taking midodrine, should not be given promethazine. NASA grant: NAS9‐97005.