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Clinical Trial
. 2005 Mar;55(512):181-5.

N-of-1 trials of quinine efficacy in skeletal muscle cramps of the leg

Rachel Woodfield  1 , Felicity Goodyear-Smith, Bruce Arroll
Affiliations
Clinical Trial

N-of-1 trials of quinine efficacy in skeletal muscle cramps of the leg

Rachel Woodfield et al. Br J Gen Pract. 2005 Mar.

Abstract

Background: Skeletal muscle cramps affect over a third of the ambulatory elderly population. Quinine is the established treatment, but there are safety concerns, and evidence for efficacy is conflicting. A recent meta-analysis established a small advantage for quinine, but identified the need for additional studies. N-of-1 trials compare two treatments, in a randomised, double-blind, multiple crossover study on a patient-by-patient basis. They have been used to compare treatments in osteoarthritis and may be suitable for determining the individual efficacy of quinine.

Aim: To establish efficacy and safety of quinine sulphate use for the treatment of leg-muscle cramp.

Design of study: Double-blind, randomised series of n-of-1 controlled trials of quinine versus placebo for muscle cramps.

Setting: New Zealand general practices.

Method: The participants were 13 general practice patients (six males; seven females; median age = 75 years) already prescribed quinine. Following a 2-week washout, each patient received three 4-week treatment blocks of quinine sulphate and matched placebo capsules with an individual, randomised crossover design. The main outcome measures were: patient diaries of cramp occurrence, duration and severity; capsule counts; and blood quinine levels in the final treatment block.

Results: Ten patients completed the trial. Three patients were identified for whom quinine was clearly beneficial (P <0.05), six showed non-significant benefit and one showed no benefit. All patients elected to continue quinine post-study.

Conclusion: Series of n -of-1 studies differentiated patients whom quinine had statistically significant effects; those with trend towards effectiveness; those for whom quinine was probably not effective. Ideally n-of-1 trial should be performed when a patient is commenced on quinine. More cycles in n-of-1 studies of quinine may address issues of statistical power.

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Figures

Figure 1
Figure 1
Changes in numbers of cramps with quinine treatment compared with placebo.
See this image and copyright information in PMC

Comment in

References

    1. Stewart RB, Moore MT, Marks RG, Hale WE. Nocturnal leg cramps in an ambulatory elderly population: An evaluation of risk factors. Journal of Geriatric Drug Therapy. 1993;7:23–46.
    1. Maule B. Nocturnal cramp: quinine versus folklore. Practitioner. 1990;234:420–421. - PubMed
    1. Daniel H. Simple cure for nocturnal leg cramps. N Engl J Med. 1979;301:216. - PubMed
    1. McGee SR. Muscle cramps. Arch Intern Med. 1990;150:511–518. - PubMed
    1. Mandal AK, Abernathy T, Nelluri SN, Stitzel V. Is quinine effective and safe in leg cramps? J Clin Pharmacol. 1995;35:588–593. - PubMed