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How Does Quinine Help Restless Legs

Quinine is an old remedy for malarial fever. It is also a long-standing remedy for nightly muscle cramps. Given the similarities between restless leg syndrome and nocturnal muscle cramps, some people do take quinine for restless legs. Is quinine any good for restless legs? If so, why did the FDA strongly advise against this off-label use of quinine and what are the risks identified? Read on to find out for yourself.
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What is Quinine?

Quinine is a plant-derived alkaloid. Once extracted, it is available in white crystalline form and it has a bitter taste.

This alkaloid is renowned for its antimalarial properties. Other medicinal properties of quinine include its ability to reduce pain and inflammation as well as its effectiveness in relieving fever.

Since its discovery in the bark of cinchona tree and its first therapeutic use as an antimalarial in the 17th century, quinine has been synthesized in the laboratory as demand for it rose during the world wars. Yet, extracting quinine from natural sources is the only economically viable means of obtaining the alkaloid.

Currently, quinine has been replaced by new groups of antimalarial drugs but most of its replacements are derivatives of the alkaloid. However, quinine is still the drug of choice for severe malaria that does not respond to new antimalarial drugs.

Because it is also cheap, it is the antimalarial drug of choice in the poorest parts of the world.

Although, it is now rarely used, quinine is still available as a prescription drug and in over-the-counter tonic solution. Besides drug-resistant malaria, quinine is still used in the treatment of lupus and arthritis.

There are a few off-label use of quinine and one of these is in the treatment of restless leg syndrome. However, the FDA (Food and Drug Administration) has since banned quinine for this use.

Besides its medicinal use, quinine is also included in some beverages as a bittering agent. However, most countries set a limit to the amount of quinine that can be added to soft drinks and tonic water.

The quinine included in most brands of tonic water is not obtained from cinchona bark but from the bark of a related plant, remijia. Remijia bark contains 0.5 – 2% quinine and it is preferred in tonic water because it is a cheaper source of the alkaloid and has a more intense taste.

The most common side effect of quinine is hearing impairment. This impairment affects high-frequency sounds and is reversible if quinine is withdrawn immediately. Other common side effects of quinine are diarrhea, hypotension, constipation and erectile dysfunction.

However, a condition known as cinchonism or quinism is the most popular adverse effect of quinine.

Cinchonism can be caused by both therapeutic doses and overdoses of quinine. Early symptoms of cinchonism include ringing in the ear, hearing impairment, profuse sweating, blurry vision, flushed skin, headache, mental confusion, dizziness, vertigo, rash, abdominal pain, nausea, vomiting and diarrhea.

These symptoms of mild cinchonism are reversible and they disappear soon after quinine is withdrawn.

In severe cases, cinchonism can cause permanent damage such as deafness, blindness, toxicity to the heart and death.

Quinine injection can also cause severe and sudden adverse reactions. Therefore, patients receiving this injection should be monitored for blood glucose levels and cardiac signs especially blood pressure and heart rhythm.

What is Restless Leg Syndrome?

Restless leg syndrome is a neurological disorder that presents with an uncontrollable urge to move in order to relieve uncomfortable sensations in different parts of the body. The movement, however, only provides temporary relief and soon the repetitive pattern of movement becomes restlessness.

Restless leg syndrome mostly affects the limbs especially the legs. The uncomfortable sensations felt may include painful, achy, itching, tickling or crawly feelings.

Although the presentations of restless leg syndrome may make the condition look harmless, most clinicians now agree that it is a valid neurological disorder and not a psychological trick of the mind.

The defining characteristics, besides the irresistible urge to move and the restlessness it causes, also includes the worsening of symptoms following relaxation; the worsening of symptoms during the evening and at night; and the improvement of symptoms immediately following some activity in the affected limb.

Restless leg syndrome can either be primary or secondary.

Primary restless leg syndrome has no known cause and it usually starts before the age of 40. The odd sensations felt in the affected limb are only mild at the beginning but then they worsen with age.

In contrast, secondary restless leg syndrome usually appears in people who are over 40 years of age. The onset is sudden and there are specific causes for this type of the syndrome.

Restless leg syndrome is hereditary. However, not every case is a result of inherited genes.

Other causes of restless leg syndrome include drugs such as antidepressants, antihistamines, antipsychotics, anticonvulsants and antiemetics. Drugs or medical conditions that reduce the amounts of dopamine and iron in the brain can cause restless leg syndrome.

Furthermore, neurodegenerative diseases such as Parkinson’s disease and fibromyalgia as well as autoimmune diseases such as diabetes, celiac disease, rheumatoid disease and Sjorgen’s syndrome can cause restless leg syndrome. Other known disorders that can serve as an underlying cause of restless leg syndrome are sleep disorder, peripheral neuropathy, venous reflux as well as folate and magnesium deficiencies.

If the cause of a patient’s restless leg syndrome is known, a doctor can simply withdraw the offending drug or treat the underlying medical condition.

Mild restless leg syndrome may not even need medications. Some people experience some relief from walking, stretching the muscles of the limb affected, lying down on one’s face, taking hot or cold showers and getting monochromatic infra-red light therapy.

Iron supplements can also provide significant relief especially in cases where iron deficiency is a major contributory factor.

Drugs that increase the amount and/or the activity of dopamine in the brain can also provide lasting relief for this disorders. Other effective drugs, besides those that affect the dopamine system in the brain, include gabapentin and opioids such as methadone

Besides these, diazepam can be recommended to helps sufferers sleep; and some anticonvulsants may be given to reduce pain due to muscle spasms.

However, there are other drugs used to treat restless leg syndrome that are not strictly recommended for the disorder. Quinine is a good example of such drugs used off-label for this syndrome.

Quinine and Restless Legs

For more than 100 years, physicians have prescribed quinine for benign nocturnal muscle cramps. The drug works even when other alternatives fail.

Some of the clinical trials that support the use of quinine for the treatment of muscle cramp include a 1989 study published in The Western Journal of Medicine.

Although this is a small study, there are other positive studies that arrive at similar conclusions.

In 1995, a review of past studies was done on the subject. The meta-analysis was published in the medical journal, BMJ and it concluded that quinine was effective but that it causes some side effects. Therefore, the researchers recommended that physicians should weigh the benefits against the potential risks when recommending quinine for benign nocturnal muscle cramps especially in the elderly.

A bigger systematic review published in the Cochrane Database in 2010 reached the same conclusions.

The Cochrane review agreed that quinine reduces the frequency, intensity and duration of muscle cramps at dosages between 200 mg/day and 500 mg/day.

Since muscle cramps and nightly occurrence are some of the features of restless leg syndrome, many have also used quinine to calm their restless legs.

However, while benign nocturnal muscle cramp is a musculoskeletal disorder, restless leg syndrome is a neurological disorder. Still, some users find quinine effective for this off-label use even though there is no scientific evidence to back this.

The two mechanisms by which quinine relieves muscle cramps and improve restless legs are:

  • Acting as a muscle relaxant
  • Improving blood flow to the muscles

By relaxing the muscles, quinine can reduce the odd sensations triggering restlessness in the affected limbs. And by dilating the blood vessels, quinine allows the vessels to pump more oxygen and nutrient-rich blood to muscles. This prevents cramping and muscle aches.

The FDA Ban

In 2006, the FDA banned the use of quinine for restless leg syndrome and strongly advised against its off-label use for this syndrome. The ban was introduced after years of warnings about the potentially lethal side effects of quinine.

The FDA argues that quinine can cause

  • blood disorders such as thrombocytopenia
  • low blood sugar
  • electrolyte imbalance
  • abnormal heartbeat rhythm and other cardiac problems
  • eye and hearing problems
  • kidney failure
  • hypersensitivity reactions including rash

In addition, quinine interferes with a long list of drugs including those used in treating cardiac disorders as well as many hereditary and autoimmune diseases.

Given the breadth of these contraindications, adverse effects and drug reactions, there should be an unusually large number of cases of complications with quinine.

Currently, the FDA only allows one brand of quinine on the market. This brand is known as Qualaquin. It contains quinine sulfate and it is recommended for the treatment of untreated malaria caused by Plasmodium falciparum.

However, many still take Qualaquin to treat restless leg syndrome although this off-label use is not approved by the FDA. For example, more than two-thirds of the reports of serious side effects received by the FDA between 2005 and 2008 were from patients who took Qualaquin for restless legs or muscle cramps.

To stop this trend, the FDA mandated the manufacturers of Qualaquin to mention the risks of taking quinine for off-label uses on the drug’s label.

Despite this warning, most physicians still recommend the off-label use of quinine for relieving restless legs. This is because some doctors do not believe that quinine poses a big enough risks at the doses in which it is being prescribed.

Ultimately, it rests on the physician to weigh the risks and access the benefits of quinine for their patients.

Self-medication with quinine should however be avoided especially because there are no standard doses for restless leg syndrome, and because the side effects of the drug can be life-threatening.

Sources


http://www.nhs.uk/Conditions/Restless-leg-syndrome/Pages/Treatment.aspx

http://www.ncbi.nlm.nih.gov/pubmed/7827545

http://www.ncbi.nlm.nih.gov/pubmed/2669346

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