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Various medications and behavioral treatments for sleep-related leg cramps have been tried, but the quality of the evidence is low. Quinine seems to be effective, but dangerous. β-Agonists may be one of the more common causes of secondary leg cramps. Statins may not be implicated in leg cramps as much as has been believed. Potassium-sparing diuretics may have a higher incidence of sleep-related leg cramps than potassium-depleting diuretics. Plantar flexion of the feet may elicit most sleep-related leg cramps. More research into behavioral treatments is needed. A standardized sleep-related leg cramp questionnaire would be useful to expand research., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Leg cramps are common in pregnant women. Currently, there is no standard treatment for pregnancy-induced leg cramps. The objective of this study was to evaluate the therapeutic efficacy of oral magnesium in pregnant women with leg cramps. This double-blinded, randomised, placebo-controlled trial included 86 healthy pregnant women, 14-34 weeks of gestation who had leg cramps at least twice per week. The study period was 4 weeks. Eighty women completed the study. Forty-one women were assigned to magnesium bisglycinate chelate (300 mg per day) and 39 women to placebo. Details of leg cramps were recorded before beginning the treatment and the fourth week of study. Outcome measure was the reduction of cramp frequency after treatment and cramp intensity measured by 100-mm visual analogue scale. Fifty per cent reduction of cramp frequency was significantly higher in the magnesium group than the placebo group (86.0% vs. 60.5%, P=0.007). The 50% reduction of cramp intensity was also significantly higher in the treatment group than in the placebo group (69.8% vs. 48.8%, P=0.048). There were no significant differences between the two groups in terms of side effects such as nausea and diarrhoea. These results demonstrated that oral magnesium supplement can improve the frequency and intensity of pregnancy-induced leg cramps. Therefore, oral magnesium may be a treatment option for women suffering from pregnancy-induced leg cramps., (© 2012 Blackwell Publishing Ltd.)

Introduction: Involuntary, localised leg cramps are common and typically affect the calf muscles at night., Methods and Outcomes: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for idiopathic leg cramps? What are the effects of treatments for leg cramps in pregnancy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA)., Results: We found 12 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics, anti-epileptic drugs, calcium salts, compression hosiery, magnesium salts, multivitamin and mineral supplements, quinine alone or with theophylline, sodium chloride, and stretching exercises.

Objective: To review the efficacy and tolerability profiles of quinine in nocturnal and dialysis-associated leg cramps and to examine potential alternative agents., Data Sources: Selection and extraction: a MEDLINE/PubMed, English-language literature search from 1966 to the present using quinine, leg cramps, vitamin E, verapamil, muscle relaxants, gabapentin as search terms., Data Synthesis: Quinine, an alkaloid originally isolated from the cinchona tree, has been used for many years to treat/prevent leg cramps. In the mid-1990s, the Food and Drug Administration (FDA) banned over-the-counter availability of quinine and marketing of prescription quinine products for leg cramps. In early 2007, FDA banned all prescription quinine products other than Qualaquin. FDA acted in this manner because of a perception that quinine is not effective for this condition and that its risk potential far exceeds its efficacy potential. Efficacy trials for quinine in leg cramps have numerous design flaws that have resulted in poor quality data, producing both positive and negative findings. Two meta-analyses have reached different conclusions. Superimposed on the questionable efficacy of quinine is the well-known toxicity profile of the drug, involving the hematologic, renal, neurologic, cardiac, and endocrine systems., Conclusion: Are there any alternatives to quinine for leg cramps? Data are available supporting the potential efficacy of verapamil, gabapentin, carisoprodol, and orphenadrine in the general population, and vitamin E in the dialysis population. One or more of these agents should be tried before resorting to a time-limited (four- to six-week) trial of quinine for the treatment/prevention of leg cramps.

A 68-year-old woman presented with generalized weakness and a rash on her lower extremities. The weakness began one week earlier, shortly after treatment for leg cramps and two days before the rash appeared. She had also had blood-streaked sputum a few days before admission. There was no history of bleeding diathesis, nose bleeding, hematuria, vasculitis, muscle or joint aches, cinchonism, or exposure to tuberculosis. She denied fever, chills, night sweats, leg pain or swelling, chest pain, or abdominal pain.

Benign nocturnal leg cramps are a relatively common and bothersome complaint, particularly among the elderly. Careful history taking and physical examination can exclude the majority of disorders in the differential diagnosis. Mechanical treatment of an acute muscle cramp involves stretching of the affected muscle. Prophylaxis includes both mechanical and pharmacologic measures. The efficacy of quinine sulfate has been supported in the majority of well-designed studies, but its use is controversial, and the FDA has banned over-the-counter quinine-based products used for leg cramps. Potentially fatal hypersensitivity reactions and thrombocytopenia can occur with use of quinine.

Leg cramps are a common problem, especially in the elderly. The differential diagnosis is extensive and includes the following conditions: true cramps, such as those related to heat, hemodialysis and electrolyte disturbances, as well as idiopathic cramps (the most common type); contractures occurring in conditions such as metabolic myopathies and thyroid disease; tetany, which is usually related to electrolyte disturbances, and dystonias, such as occupational cramps and those related to antipsychotic medications. Other leg problems that are not cramps, such as restless legs syndrome and periodic leg movements, also must be distinguished. The etiology of idiopathic leg cramps is not clear. Treatments for leg cramps include stretching exercises, quinine sulfate and vitamin E, but no treatment is conclusively effective. Nonetheless, in many patients relief of symptoms is achieved with one or more of these treatments.

Objective: Our purpose was to determine whether women with pregnancy-related leg cramps would benefit from oral magnesium supplementation., Study Design: Seventy-three women with pregnancy-related leg cramps were interviewed about their symptoms in a prospective, double-blind, randomized trial. Initial serum magnesium levels and diurnal magnesium excretion was determined in 50% of the patients. Oral magnesium or placebo was given for 3 weeks, after which new interviews and laboratory analyses were performed., Results: Serum magnesium levels in these patients were at or below the lower reference limit, as is also often the case in healthy pregnant patients. Oral magnesium substitution decreased leg cramp distress (p < 0.05 compared with the placebo group, p < 0.001 compared with initial complaints), but did not significantly increase serum magnesium levels, excess magnesium being excreted as measured by an increase in urinary magnesium levels (p < 0.002)., Conclusion: Oral magnesium supplementation seems to be a valuable therapeutic tool in the treatment of pregnancy-related leg cramps.

Objective: To assess quantitatively the efficacy of quinine (as quinine sulphate) compared with placebo in the treatment of nocturnal leg cramps., Design: A meta-analysis of six randomised, double blind, crossover trials., Setting: Randomised trials that were available as of April 1994., Subjects: A total of 107 general ambulatory patients who suffered from regular nocturnal leg cramps from six clinical trials., Results: Data from individual patients were used to calculate point estimates and 95% confidence intervals for each of the outcome measures reported by these studies. Treatment with quinine resulted in a significant reduction in the number of cramps for a four week period compared with placebo (8.83 fewer cramps; 95% confidence interval 4.16 to 13.49). Treatment with quinine reduced the number of nights with cramps by 27.4% (24.0% to 30.8%) compared with placebo. Treatment did not produce a significant change in the severity or duration of individual nocturnal leg cramps. Side effects were uncommon., Conclusions: The results indicate that quinine can prevent nocturnal leg cramps in general ambulatory populations. Given the possible serious side effects of treatment with quinine, the benefits and risks in patients taking this drug should be closely monitored.

Objective: To study the efficacy of quinine in the prevention of nocturnal leg muscle cramps., Design: Double-blind, randomized, crossover trial with four periods of observation, each lasting 2 weeks., Setting: General internal medicine outpatient clinic., Participants: Ambulatory outpatients who experienced an estimated two or more typical nocturnal leg cramps per week., Intervention: 200 mg of quinine taken at bedtime., Main Outcome Measures: Self-reported ratings of leg cramp frequency, duration, and intensity., Results: Sixteen patients completed the trial. During the 2 weeks patients used quinine, there was no statistically significant reduction in mean leg cramp number (quinine 3.5 vs placebo 4.2, P = 0.48), mean leg cramp duration (quinine 152 seconds vs placebo 163 seconds, P = 0.89), or patient ratings of severity using a 1 (low) to 10 (high) scale (quinine = 4.2 vs placebo = 4.0, P = 0.83)., Conclusion: No significant reduction in nocturnal leg cramp frequency, intensity, or duration could be found using nightly quinine in this study. Since quinine is not without the potential for side effects and drug interactions, clinicians need to carefully consider the likelihood of modest benefit associated with quinine against the potential for side effects and drug-drug interactions.

164 patients (m = 45, w = 119; age 55.7 +/- 14.7 years) took part in a multicentric controlled parallel-double blind study in which efficacy and tolerability of the combination quinine sulfate (CAS 6119-70-6) plus theophylline ethylene diamine (CTED, CAS 317-34-0) (Limptar) in the treatment of the recurrent nocturnal leg cramps were investigated. Only patients who suffered before the begin of the study in at least three nights per week from leg cramps were included. The duration of the study was three weeks. In the first week all patients were treated in a single blind design with placebo. The subsequent 2 weeks were carried out double-blind. The global efficacy judged by the physicians and investigated for the 126 patients who took the compounds at least four days within the random phase was remarkably better for the combination than for quinine or placebo (very good and good in 87.1 vs. 63.7 vs. 39.5% of the cases; p less than 0.001; x-test). In 117 patients an analysis of the time course of the efficacy could be done from the notes in the diary (minimum duration of treatment 11 d). Already within the first week there was a highly significant decrease of nights with leg cramps within the CTED group (n = 34) from 4.68 (95% confidential interval 2.26-7.0) to 2.25 (0-6.78) in comparison to placebo (n = 40; from 4.32 [1.9-7.0] to 3.69 [1.22-6.91]) and quinine (n = 43; from 4.78 [2.22-7.0] to 3.27 [0-7.0]; F-test; p = 0.0001 resp. 0.0012).(ABSTRACT TRUNCATED AT 250 WORDS)

Up to 30 per cent of pregnant women suffer from leg cramps. The cause of these cramps is not known, but changes in calcium concentration have been suggested. Therefore 42 pregnant women with leg cramps were studied. No differences in total serum or ionized serum calcium concentrations were found as compared with a control group of pregnant women without leg cramps. Twenty-one patients were treated with 1 g calcium orally twice daily for 2 weeks and in this group good clinical improvement was achieved (p less than 0.001). The treatment increased the total serum calcium concentration from 2.25 mmol/l to 2.30 mmol/l but did not alter the ionized serum calcium concentration. Twenty-one untreated patients had the same frequency of cramps and showed no change in serum calcium concentrations throughout the investigation.

In an open-labeled trial with eight elderly patients (aged 62 to 87 years) suffering from nocturnal leg cramps refractory to treatment with quinine sulfate, we ruled out other active disease processes and substituted verapamil hydrochloride therapy (120 mg at bedtime). Response to treatment was assessed by biweekly observations by the primary care physician and nightly by the research registered nurse for the entire duration of the trial, lasting eight weeks. Observations made and clinical conditions reported were indicative of improvement and disappearance of cramping when therapy was changed from quinine to verapamil. This noteworthy improvement in patients with recumbent nocturnal leg cramps is an important finding and merits further investigation.

A prospective, double-blind, placebo-controlled crossover study of the use of quinine for nocturnal leg cramps was carried out in 8 elderly volunteer patients. The patients were randomly assigned to receive either placebo or 200 mg of quinine sulfate by mouth at bedtime. After 4 weeks of treatment and after a one-week washout period, the group taking quinine switched to placebo and vice versa for another 4 weeks. The differences in the number, duration, and severity of cramps and the side effects were compared. All of the patients had fewer cramps and decreased severity and duration of attacks while receiving quinine. Mild side effects developed in only 2 patients, and these subsided without treatment or discontinuing the medication. We conclude that quinine was effective in relieving nocturnal leg cramps in a selected group of elderly patients.

Organic causes for nocturnal or recumbency leg cramps as venous, arterial, statical, nervous, rheumatical and metabolic diseases such as tetany, diabetes and gout must be excluded. This means also electrolyte disturbances during a medical treatment, for example with diuretics. In addition there is a very high portion of idiopathic cramps. In 22 patients with nocturnal leg cramps a four week double blind study with a combination of quinine sulphate and aminophylline (Limptar) was started. Unequivocally, Limptar significantly reduced the number and the intensity of nocturnal or recumbency leg cramps. There was no influence on angiological and biochemical parameters. Side effects appeared very seldom.