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An exploration of new therapeutic options for nocturnal leg cramps Garrison, Scott Russel

Abstract

THE PROBLEM: Rest cramps (also known as nocturnal leg cramps) are painful muscle contractions, typically in the legs or feet, that occur during prolonged rest - most often while in bed at night. Although common in older adults, safe and effective treatment options are lacking. OPPORTUNITY AND METHOD #1: Magnesium supplements are readily available and widely marketed to consumers for cramp prophylaxis. However the efficacy of magnesium for this indication is unclear and existing clinical trials are limited by the well recognized poor bioavailability of oral magnesium. To better assess the potential efficacy of magnesium in cramp prophylaxis I conducted a (N=46) double-blind, placebo-controlled RCT on community-dwelling rest cramp sufferers to determine whether a more reliable delivery method (5 consecutive days intravenous infusion of 20 mmol magnesium sulfate) could reduce the frequency of rest cramps. I additionally determined whether the response to treatment varied with the extent to which infused magnesium was retained (as measured by 24-hr urinary magnesium excretion) and performed a Cochrane Systematic Literature Review to find and synthesize all relevant randomised trials. OPPORTUNITY AND METHOD #2: Anecdotal evidence suggested several medications might promote muscle cramping. If true, cramp sufferers using these drugs could potentially gain cramp relief through therapeutic substitution or reduction of these agents. To investigate this potential cramp link I searched BC Ministry of Health databases containing diagnostic and prescribing information on the 4.2 million residents of British Columbia to determine, using sequence symmetry methods, whether quinine starts (i.e. new cramp treatment) increased in the year following introduction of the three most commonly prescribed medications with a link to muscle cramps (diuretics, statins and inhaled long-acting beta2-agonists). CONCLUSION: Although its role in pregnancy-associated rest cramps remains unclear, magnesium supplementation does not meaningfully reduce the frequency of rest cramps in older adults. Alternatively, for some cramp sufferers, reduction or discontinuation of select cramp promoting medications (inhaled long-acting beta2-agonists, potassium-sparing diuretics and thiazides) may be a useful therapeutic maneuver. Over a 13 year period 60.3% of quinine users (cramp sufferers) received at least one of these medications. In contrast, statin and loop-diuretic cramp associations were clinically unimportant.

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