Midodrine in Neurogenic Orthostatic Hypotension
Source: Low PA, et al. JAMA 1997;277:1046-1051.
Low and colleagues conducted an interesting study evaluating the use of an alpha-agonist, midodrine, which increases peripheral resistance and reduces orthostatic hypotension. This drug is now approved by the Food and Drug Administration to treat orthostatic hypotension.
Patients were screened in a multicenter, outpatient, double-blind, randomized, parallel-group study if they met the authors' criteria of an orthostatic reduction of at least 15 mmHg, with symptoms of dizziness, lightheadedness, or unsteadiness. These latter symptoms were evaluated with a scoring system, known as a global relief score. This was ascertained by the investigator and the patient.
After randomizing 89 patients to placebo and 82 to midodrine, patients were seen at initiation, one week, two weeks, and after a wash-out period.
The investigators classified the patients into three major categories. The first was orthostatic intolerance, which included postural tachycardia syndrome, orthostatic hypotension with neurocardiogenic syncope, and mitral valve prolapse. The second was autonomic neuropathy, and the third was neurologic disease, including olivopontocerebellar atrophy and spinal cord injury or syringomyelia. Midodrine was very effective in removing the symptoms or the objective finding of orthostatic hypotension. The most common side effects resulting in patients stopping the medicine were the pilomotor reactions, urinary urgency or retention, or supine hypertension. A total of 15 patients stopped the drug.
The authors found that 10 mg of midodrine three times a day elevated the upright blood pressure patients and helped with orthostatic lightheadedness. Both the investigators and the patients recognized this effect within one week.
Comment by Len Scarpinato, DO
We have all seen patients with the "dizzy woozies." As a matter of fact, one was presented on rounds just the other day. Usually I ask my residents immediately whether the patient has diabetes or a heart condition. If it's a new episode, I might think that they have a viral syndrome. If none of these fit, I group them into the "dizzy woozy" category, and oftentimes we are confused.
More interesting are the patients who have these symptoms and have orthostatic hypotension. These patients are usually easy to approach because we can attack this "number." Therapy consists of fludrocortisone, high salt diet, and compression garments. However, this therapy is not without its drawbacks, including electrolyte abnormalities. Hypertension can occur, and then the drug titration becomes a delicate balancing act. (In some cases, you might even have to use a nighttime hypotensive agent.) Most patients can't tolerate this therapy.
When reading Low et al's study, I was struck with the fact that I might now have something to treat my neurogenic orthostatic hypotensive patients. The 10 mg tid dosing seems to be well tolerated, safe, and effective. Additionally, we don't run into the problem of a greatly expanded plasma volume seen in fludrocortisone with the resultant supine hypertension.
As a primary care physician, I am particularly excited about this application. I wonder whether the drug will be found useful in the rest of my patients who have the "dizzy woozies." Only time will tell. For now, midodrine will be one of my options.
Dr. Scarpinato is Associate Professor, Medical College of Wisconsin, Critical Care Curriculum Coordinator, St. Mary's Hospital, Milwaukee.
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