Quinine for muscle cramps

Review question

We reviewed the evidence about the effect of quinine on muscle cramps.

Background

Muscle cramps can occur anywhere and in anyone; however, leg cramps are especially common in older people. Quinine is a medicine which has been used to treat cramps for many years. There is conflicting evidence for its ability to reduce cramps. Quinine can cause serious, even fatal adverse events, especially in overdosage.

Study characteristics

This review includes 23 trials, with 1586 participants. The trials compared quinine or quinine-based medicines against inactive treatment (placebo) or other active treatments. We found no new studies when we searched the medical literature again and updated the review in 2014.

Key results and quality of the evidence

The risk of bias in the included trials varied considerably. All 23 trials claimed to be randomised, but many failed to clearly describe how participants were assigned to treatments. There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that there are more minor adverse events with quinine compared to placebo but no increase in major adverse events. However, there are reliable reports from other sources that an overdose of quinine can cause serious harm including death.

Low or moderate quality evidence shows there is no significant difference when comparing quinine to vitamin E or to a quinine-vitamin E mixture. There is evidence from one trial that theophylline combined with quinine improves cramps more than quinine alone. In a single trial there was no significant difference when comparing quinine to xylocaine injections.

More research is needed to clarify the best dose and duration of treatment, as well as alternatives to quinine for cramps.

The evidence is current to October 2014.

Authors' conclusions: 

There is low quality evidence that quinine (200 mg to 500 mg daily) significantly reduces cramp number and cramp days and moderate quality evidence that quinine reduces cramp intensity. There is moderate quality evidence that with use up to 60 days, the incidence of serious adverse events is not significantly greater than for placebo in the identified trials, but because serious adverse events can be rarely fatal, in some countries prescription of quinine is severely restricted.

Evidence from single trials suggests that theophylline combined with quinine improves cramps more than quinine alone, and the effects of xylocaine injections into gastrocnemius are not significantly different to quinine across all outcomes. Low or moderate quality evidence shows no significant difference between quinine and vitamin E or quinine and quinine-vitamin E mixture. Further research into these alternatives, as well other pharmacological and non-pharmacological treatments, is thus warranted.

There is no evidence to judge optimal dosage or duration of quinine treatment. Further studies using different dosages and measurement of serum quinine levels will allow a therapeutic range to be defined for muscle cramp. Because serious adverse events are not common, large population studies are required to more accurately inform incidence. Longer lengths of follow-up in future trials will help determine the duration of action following cessation of quinine as well as long-term adverse events. The search for new therapies, pharmacological and nonpharmacological, should continue and further trials should compare vitamin E, quinine-vitamin E combination, and quinine-theophylline mixture with quinine.

Read the full abstract...
Background: 

Muscle cramps can occur anywhere and for many reasons. Quinine has been used to treat cramps of all causes. However, controversy continues about its efficacy and safety. This review was first published in 2010 and searches were updated in 2014.

Objectives: 

To assess the efficacy and safety of quinine-based agents in treating muscle cramps.

Search strategy: 

On 27 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE. We searched reference lists of articles up to 2014. We also searched for ongoing trials in November 2014.

Selection criteria: 

Randomised controlled trials of people of all ages with muscle cramps in any location and of any cause, treated with quinine or its derivatives.

Data collection and analysis: 

Three review authors independently selected trials for inclusion, assessed risk of bias and extracted data. We contacted study authors for additional information. For comparisons including more than one trial, we assessed the quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Main results: 

We identified 23 trials with a total of 1586 participants. Fifty-eight per cent of these participants were from five unpublished studies. Quinine was compared to placebo (20 trials, n = 1140), vitamin E (four trials, n = 543), a quinine-vitamin E combination (three trials, n = 510), a quinine-theophylline combination (one trial, n = 77), and xylocaine injections into the gastrocnemius muscle (one trial, n = 24). The most commonly used quinine dosage was 300 mg/day (range 200 to 500 mg). We found no new trials for inclusion when searches were updated in 2014.

The risk of bias in the trials varied considerably. All 23 trials claimed to be randomised, but only a minority described randomisation and allocation concealment adequately.

Compared to placebo, quinine significantly reduced cramp number over two weeks by 28%, cramp intensity by 10%, and cramp days by 20%. Cramp duration was not significantly affected.

A significantly greater number of people suffered minor adverse events on quinine than placebo (risk difference (RD) 3%, 95% confidence interval (CI) 0% to 6%), mainly gastrointestinal symptoms. Overdoses of quinine have been reported elsewhere to cause potentially fatal adverse effects, but in the included trials there was no significant difference in major adverse events compared with placebo (RD 0%, 95% CI -1% to 2%). One participant suffered from thrombocytopenia (0.12% risk) on quinine.

A quinine-vitamin E combination, vitamin E alone, and xylocaine injections into gastrocnemius were not significantly different to quinine across all outcomes, including adverse effects. Based on a single trial comparison, quinine alone was significantly less effective than a quinine-theophylline combination but with no significant differences in adverse events.

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