Albuterol for congenital myasthenia syndrome

Motivation: Overnight, a patient developed SVT. Cause? Likely secondary to uptitration of albuterol. I was intrigued to see that the indication for albuterol was congenital myasthenia syndrome. What is the evidence for this medication in congenital myasthenia syndromes?

Study: Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myasthenia. Liewluck T, Selcen D, Engel AG. Muscle Nerve. 2011 Nov;44(5):789-94. doi: 10.1002/mus.22176.

Study Design: This was a study in which 3 patients with end plate acetylcholinesterase deficiency and 15 patients with Dok-7 myasthenia were treated with albuterol in an open label study, and pre- and post-intervention questionnaires on disease specific symptoms (9 questions long) were completed. Adverse effects were also queried. These two diseases in particular were chosen because they have been reported to respond to ephedrine (several patients with EP AchE deficiency, reference = Neurology. 2005 Jul 12;65(1):144-6; and Class IV evidence in Dok-7 myasthenia, reference = Neurology. 2010 May 11;74(19):1517-23; Neuromuscul Disord. 2009 Dec;19(12):828-32.), another drug that stimulates the sympathetic system.

Study Result: The study reported a beneficial response to albuterol based on the 9-question survey in terms of patient-reported improved walking distance and stair climbing. In one patient, the trial drug was stopped early because of development of atrial flutter. Other adverse effects included muscle cramps, insomnia, HTN, mild tremor/jittery feeling.

Discussion: This is a small study that offered promising pilot results that - as its authors note - should trigger further testing in larger RCTs, given that the limitations of this study included its small sample size (not surprising given the rarity of diseases studied), and potential bias in patient responses (especially given that it was an open label study). Authors note that the mechanism of symptomatic improvement is unclear. Nevertheless, given the lack of alternative therapies, and in the absence of contraindications to beta-agonists (such as certain tachyarrythmias), albuterol does seem like a reasonable therapy to further pursue in clinical trials for EP AchE deficiency and Dok-7 myasthenia. Currently, however, patients who are prescribed this medication for these diseases need to weigh the risks of a therapy that has not undergone full RCT testing with its potential (and anecdotal) benefits.