New POTS Treatment?
abstract & commentary
By Michael H. Crawford, MD
Synopsis: Acute acetylcholinesterase inhibition reduced standing heart rate and symptoms in POTS patients.
Source: Raj SR, et al. Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome. Circulation. 2005;111:2734-2740.
The treatment of postural tachycardia syndrome (POTS) is often challenging, and beta-blockers do not always produce the desired effect. Thus, Raj and colleagues hypothesized that acetylcholinesterase inhibition may increase parasympathetic tone both at the ganglionic and post ganglionic receptors, resulting in bradycardia. POTS inclusion criteria were met by 17 patients, and included symptoms of orthostatic intolerance, a heart rate rise of > 30 bpm within 10 minutes of standing in the absence of orthostatic hypotension, and elevated standing norepinephrine levels (> 2.8 nmol/L). Patients were studied in a metabolic research unit where fluid, electrolyte, and drugs were tightly controlled. On separate days, placebo or pyridostigmine 30 mg po was given. Symptoms were logged before drug administration, and 2 and 4 hours afterward. Of the 17 subjects, 15
completed both limbs of the study (12 females). Resting, sitting heart rate was not different between the 2 treatments (87
bpm), but standing heart rate was significantly lower on active treatment (100 vs 111 bpm, P < .001) at 2 hours
but not at 4 hours (104 vs 109 bpm). Also, symptom score decreased on treatment (23 to 15, P < .05) at 4
hours, but not on placebo (19 to 20). Blood pressure was not significantly altered in any position by active drug.
Raj and colleagues concluded that acute acetylcholinesterase inhibition reduced standing heart rate and symptoms in POTS patients.
Commentary
POTS predominantly is a disease of women in their childbearing years and, though rare, causes considerable disability, especially for a young mother. Although usually self-limiting, it often persists for months. Thus, effective treatment would be desirable. Unfortunately, the standard approach of using the same drugs that we use for neurocardiogenic syncope (beta-blockers, clonidine, fludrocortisone) is not always very effective and may cause excessive fatigue and other intolerable side effects. The novel approach in this study is attractive theoretically, and this study provides proof that the concept is sound. Whether pyridostigmine will be effective in longer-term therapy is unknown. There are reports of its successful use in other forms of orthostatic intolerance, but the main potential limitation is gastroenterologic symptoms due to increased intestinal motility. The drug is available as 60 mg tablets and is mainly used for myasthenia gravis. Dosing for that disorder is 60-120 mg po q 3-8 hours, so it is not convenient to take. One advantage over clonidine and beta-blockers is that it does not lower blood pressure. At this point, it may be worth trying in refractory POTS patients, but selecting the correct dose and dosing interval will be an experiment.
By Michael H. Crawford, MD Synopsis: Acute acetylcholinesterase inhibition reduced standing heart rate and symptoms in POTS patients. Source: Raj SR, et al. Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome. Circulation. 2005;111:2734-2740.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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