Approach

Non-pharmacological therapy forms the cornerstone of the management of acute muscle cramps. There is scant evidence for the effectiveness of non-pharmacological and pharmacological therapies for ongoing prevention of muscle cramps. If cramps are symptoms of an organic disease, then treatment of the underlying abnormality or disease should ameliorate them.[1] Otherwise, trials of various medications used for symptomatic benefit are reasonable.

Acute cramp management

Stretching of the affected muscle(s) will relieve cramps in most cases.[1][3]​​[52] Both passive and active stretching are effective.

Passive stretching involves relief of the tension on the affected muscle(s) by, for example, rubbing and postural changes (e.g., for cramps of the calf muscle, the patient should stand on the foot of the affected side and bring the heel down hard to the ground).[52] In passive stretching, the anti-stretch reflex is induced by efferents from the Golgi organs in tendons, mediating an inhibitory reflex designed to prevent rupture of contracted muscle(s).[52]

Active stretching involves contraction of the antagonist muscle(s), leading to a spinal cord reflex evoking reciprocal inhibition of the cramping muscle (e.g., ankle dorsiflexion during calf muscle cramps).[1][52]

Certain cramps associated with underlying conditions require specific acute management, as described in the sections below. In other associated conditions that are not readily corrected immediately, acute management is supportive.

Ongoing prevention of cramps

Most cramps (around 90%) are considered a nuisance by patients, with only a minority considered to be troublesome or fulminant.[97] The decision about whether to start active preventative therapy depends on the patient's view of the symptoms, and a full assessment of the benefits versus risks of the various options available. 

Examples of non-pharmacological therapy include raising the foot off the bed by 9 inches (23 cm) and sleeping with the foot dorsiflexed, although evidence for the benefit of this strategy is limited.[81] Foot splints can be used to keep the foot dorsiflexed, but these increase the risk of falls when patients mobilise at night.[16] Although muscle strengthening training has been advocated, there is no evidence to support benefit in reduction of cramp risk.[16]

If cramps are symptomatic of a metabolic abnormality or systemic disease, treatment of the underlying abnormality or disease (if possible) should be beneficial.[1]

Therapeutic trials of various medications are reasonable for preventing idiopathic cramps, but the list of potentially useful drugs is long, implying that the efficacy of individual agents is low and variable at best.[1] Suggested drug treatments for cramps associated with specific conditions are described in the sections below.

Issues related to quinine

Despite some evidence for the effectiveness of quinine for prevention of idiopathic cramps, examination of the data has cast doubt on its efficacy and safety.[98][99][100][101]​ Quinine salts can be toxic, with adverse effects including cinchonism (tinnitus, nausea, vasodilation and sweating, headache, dizziness, blurred vision, and altered colour perception), blindness, serious hypersensitivity reactions, hepatotoxicity, diarrhoea, thrombocytopenia, prolongation of the corrected QT interval (predisposing to polymorphous ventricular tachycardia and ventricular fibrillation), and hypoglycaemia.​[98][102]

There are also concerns about the possibility of serious drug-drug interactions, particularly in older adults.[102] Quinine is not recommended for leg cramps in countries such as Australia. In the US, the Food and Drug Administration (FDA) has issued a warning against using quinine for this purpose. FDA: drug safety information for quinine sulfate Opens in new window

The American Academy of Neurology (AAN) recommends that quinine use should be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and where adverse effects can be carefully monitored. The patient must be informed of the potentially serious adverse effects before consenting to treatments.[98]

In other countries, such as the UK, quinine preparations are more readily available for the treatment of leg cramps, but the safety concerns are such that quinine should not be considered the drug of choice for the prevention of cramps.

Idiopathic cramps

Acute management

Management of acute cramps of unknown aetiology (e.g., ordinary or idiopathic cramps) is supportive, with stretching of the affected muscle(s).

Ongoing prevention

Approaches to preventing idiopathic cramps have engendered controversy for many years. Data to support therapeutic choices are sparse. Although stretching exercises are recommended as a treatment for acute cramp, there is no direct evidence of their benefit in the ongoing prevention of idiopathic cramp.

Choices of pharmacological therapy, based on available data, include verapamil (preferred), diltiazem (preferred), vitamin B complex (preferred), naftidrofuryl, selected muscle relaxants (e.g., carisoprodol), or gabapentin.[103][104][105][106] However, one 2010 evidence-based review by the AAN recommended only 3 possibly effective drugs: naftidrofuryl, vitamin B complex, and diltiazem.[98]

One 2020 Cochrane review concluded that it is unlikely that magnesium supplementation provides clinically meaningful cramp prophylaxis to older adults with skeletal muscle cramps.[107]

There is low-quality evidence that quinine significantly reduces the number of cramps and cramp days, and moderate-quality evidence that quinine reduces cramp intensity, but quinine should not be considered the drug of choice for idiopathic cramps (see above).[108] [ Cochrane Clinical Answers logo ]

Exercise-associated cramps

Acute management

Severe exercise-associated muscle cramps (EAMC) are characterised by severe or generalised cramping in muscles not subjected to exercise, or localised cramping associated with altered consciousness, altered body temperature, anuria, and/or myoglobinuria. They are not defined as true exercise cramps. Immediate admission to an emergency department is necessary for further assessment and management.[42]

For true EAMC, rest in a comfortable environment (in terms of temperature and ventilation), along with stretching of the affected muscle(s), is paramount. Oral rehydration with balanced electrolyte solutions (or use of sports drinks plus foods containing sodium) is important if the urine is dark or scant during the first hours.[16][42]

Frictional icing massage of the affected muscle(s) should be considered as a form of analgaesia if cramp pain is severe.[42]

Drug therapy is not recommended.[42]

Ongoing prevention

Ongoing prevention of EAMC involves education. Athletes should be in a well-conditioned state for an event and adequately hydrated. It has been recommended that at-risk muscle groups are well stretched before activity begins, but there is inadequate evidence to support this. An appropriate diet, incorporating sufficient carbohydrates, is necessary to prevent premature muscle fatigue.[28]

Hypoglycaemia-associated cramps in diabetes mellitus

Acute management

Immediate resolution of hypoglycaemia is paramount for the resolution of acute cramps, usually by ingestion of simple sugar by mouth.[64][74]​​[75][109]​ Drug therapy specifically for cramp relief is not recommended.

Ongoing prevention

Optimisation of blood sugar control to avoid recurrent hypoglycaemia is mandatory to prevent further episodes. This may involve adjustments to diet (including snacks to cover at-risk time periods and adequate carbohydrates to cover exercise periods), avoiding alcohol, and adjustment of injectable and/or oral antidiabetic therapies. Intensive glycaemic control in diabetes is associated with an increased risk of hypoglycaemia as compared with conventional treatment.[110][111]

Pregnancy-associated cramps

Acute management

Management of acute cramp is supportive with stretching of the affected muscle(s).

Ongoing prevention

Data regarding the efficacy of therapies for the prevention of recurrent cramps in pregnancy are conflicting. It is unclear whether oral magnesium, calcium, vitamin B, or vitamin C are effective preventative treatments.[35][107] However, magnesium salts (most commonly oxide, citrate, or hydroxide) are safe and worthy of a trial as agents of first choice.[112] Diarrhoea may be a dose-limiting adverse effect. Should this therapy prove inadequate, a trial of a combination of vitamins B1 (thiamine) and B6 (pyridoxine) is probably worthwhile.[98][113] Calcium salts and sodium chloride are of no benefit and should not be used.[37][38] Other drug therapies have not been evaluated in pregnancy-associated cramps and may lead to adverse fetal outcomes.[114] Pregnancy-associated cramps significantly remit after delivery.[17]

Dialysis-associated cramps

Acute management

Procedural methods employed by nephrologists concerning alteration of ultrafiltration rate and administration of hypertonic intravenous fluids for the treatment of acute cramp during haemodialysis sessions in people with end-stage renal failure are beyond the scope of this topic.

Ongoing prevention

Patients undergoing haemodialysis may be able to undergo pre-emptive measures to avoid the development of intradialytic cramps. Most of these measures are undertaken by nephrologists. If these measures are inadequate, a combination of vitamin E plus vitamin C is reasonable.[115] Vitamin E at bedtime has been shown to be effective in an open-label trial, and in a comparative trial with quinine.[116][117]

Creatine monohydrate is thought to improve muscle metabolism by increasing the creatine phosphate stores in the muscle, which, in turn, donate high-energy phosphate groups to adenosine diphosphate to create adenosine triphosphate. This has been documented in athletes receiving creatine supplementation.[118] It may be beneficial in the reduction of cramps associated with haemodialysis.[119]

There is evidence that quinine is effective in significantly reducing cramp frequency and cramp severity in patients using haemodialysis or continuous ambulatory peritoneal dialysis.[117][120] However, in some countries, quinine therapy should be considered only if vitamin therapy has not produced the desired results. In Australia it is not recommended for the treatment of leg cramps. In the US, the FDA has issued a warning against using quinine for leg cramps. FDA: drug safety information for quinine sulfate Opens in new window The AAN recommends that quinine use be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and where adverse effects can be carefully monitored. The patient must be informed of the potentially serious adverse effects before consenting to treatment.[98] In countries such as the UK, quinine preparations are readily available for the treatment of leg cramps, but the safety concerns are such that quinine should not be considered the drug of choice for leg cramps. Physicians should consult local formularies for advice on local availability and indications.

Using low-dose prazosin is not recommended because of the risk of hypotension, which may necessitate the administration of volume or discontinuation of the dialysis session.[121]

Cirrhosis-associated cramps

Acute management

Management of acute cramp is supportive with stretching of the affected muscle(s).

Ongoing prevention

Oral zinc sulfate, at least in patients with low serum zinc concentrations at baseline, is a reasonable first-line agent.[122]

Vitamin E, particularly in patients with low serum vitamin E concentrations at baseline, is another reasonable first-line agent.[123] One small, randomised, double-blind, placebo-controlled trial reported that quinidine was effective in reducing the occurrence of muscle cramps in patients with cirrhosis.[124] However, there are safety concerns about quinidine or quinine therapy. In the US, there is a warning against using quinine or quinidine at all for this indication. FDA: drug safety information for quinine sulfate Opens in new window The AAN recommends that the use of quinine derivatives for muscle cramps should be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and where adverse effects can be carefully monitored. In addition, the patient must be informed of the potentially serious adverse effects before consenting to treatment.[98] In countries such as the UK, quinine preparations are readily available for the treatment of leg cramps, but the safety concerns are such that quinine should not be considered the drug of choice for leg cramps. Physicians should consult local formularies for advice on local availability and indications. 

Intravenous human serum albumin and oral Niuche-Shen-Qi-Wan (TJ-107; a complementary and alternative medication), should not be used because of the paucity of supporting efficacy data for both agents, known adverse effect potential of albumin, and unknown long-term tolerability for Niuche-Shen-Qi-Wan.[26][125]

Multiple sclerosis- and lower motor neuron disease-associated cramps

Acute management

Management of acute cramp is supportive with stretching of the affected muscle(s).

Ongoing prevention

All evidence supporting the use of a variety of drugs for the prevention of cramps associated with multiple sclerosis and lower motor neuron diseases is from case reports and case series. These include gabapentin for severe leg cramps in people with multiple sclerosis; levetiracetam for people with slowly progressive motor neuron disease and amyotrophic lateral sclerosis (ALS); and mexiletine for people with Machado-Joseph disease.[126][127][128] Carbamazepine may also be effective.[129] One 2009 AAN guideline update and one 2012 Cochrane review concluded that there is a lack of evidence to either support, or refute, any specific intervention for the treatment of muscle cramps in patients with ALS.[130][131] 

In a survey of 6 ALS treatment centres in the US, neurologists rated their top 4 drugs used for cramp relief as quinine (35%), baclofen (19%), phenytoin (10%), and gabapentin (7%).[132] In the US, the FDA have issued a warning against using quinine at all for this indication. FDA: drug safety information for quinine sulfate Opens in new window The AAN recommends that quinine use for muscle cramps should be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and where adverse effects can be carefully monitored. In addition, the patient must be informed of the potentially serious adverse effects before consenting to treatment.[98] In countries such as the UK, quinine preparations are readily available for the treatment of leg cramps, but the safety concerns are such that quinine should not be considered the drug of choice for leg cramps. Physicians should consult local formularies for advice on local availability and indications.

Familial syndrome-associated cramps

Acute management

Management of acute cramp is supportive with stretching of the affected muscle(s).

Ongoing prevention

All evidence supporting the use of a variety of drugs for the prevention of cramps associated with familial syndromes is from case reports and case series. These include botulinum toxin type A injection in inherited autosomal dominant benign cramp-fasciculation syndrome; phenytoin in Isaac's syndrome, the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy; vitamin B6 in McArdle's disease; and gabapentin in myokymia-cramp syndrome.[133][134][135][136][137][138] Carbamazepine may also be effective.[129]

In the US, the FDA has issued a warning against using quinine for leg cramps. FDA: drug safety information for quinine sulfate Opens in new window The AAN recommends that quinine use should be considered only if symptoms are very disabling, no other agents have relieved symptoms (or can be tolerated), and where adverse effects can be carefully monitored. The patient must be informed of the potentially serious adverse effects before consenting to treatment.[98] In countries such as the UK, quinine preparations are readily available for the treatment of leg cramps, but the safety concerns are such that quinine should not be considered the drug of choice for leg cramps. Physicians should consult local medicine formularies for advice on local availability and indications.

Medication-associated cramps

Acute management

Management of acute cramp is supportive with stretching of the affected muscle(s).

Ongoing prevention

If possible, all drugs potentially contributing to or causing cramps should be discontinued, being cognisant of the potential for dangerous drug withdrawal reactions. It may be necessary to stage withdrawal of single agents at a time, starting with those associated with the highest risks of cramp. In some cases, dose reduction may be reasonable before resorting to discontinuation, with the realisation that dose reduction may compromise drug efficacy.

Drug substitution within the same therapeutic class may provide a solution for some patients (e.g., substituting non-intrinsic sympathomimetic activity [ISA] beta-blockers for the ISA agents pindolol and carteolol).[50][51]

For patients taking the anticancer drug imatinib:

  • Dose reduction may be impossible without serious compromise of efficacy.

  • Calcium and/or magnesium supplementation, even in the presence of normocalcaemia and normomagnesaemia, can ameliorate imatinib-associated cramps.[48]

  • Quinine should not be used due to its ability to inhibit cytochrome P450 isoenzymes, leading to increased imatinib serum concentrations and, hence, toxicity risk.[48] 

  • There is limited evidence for the efficacy of low-dose chlordiazepoxide in suppressing imatinib-associated cramps.[139]

For patients taking statins:

  • Creatine (loading followed by maintenance therapy) may suppress the triad of statin-induced myalgias, weakness, and cramping.[140]

  • Serum creatine kinase (CK) ≥10-fold of the upper limit of the normal range mandates statin discontinuation.[54][141]​​

  • If serum CK is in the normal range or <10-fold above the upper limit of the normal range and symptoms are tolerable, statin therapy can continue with frequent monitoring (may be candidate for creatine therapy).[54]

  • If serum CK is in the normal range or <10-fold above the upper limit of the normal range and symptoms are intolerable, therapy should be changed to another statin or alternative hypolipidaemic therapy.[54]

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