Quinine Treatment for RLS or Leg Cramps is Associated with Increased Mortality

By Lynn Marie Trotti, MD, MSc

An excerpt from the Summer 2017 edition of NightWalkers, the Foundation's quarterly magazine

“Association Between Long-Term Quinine Exposure and All-Cause Mortality.” Fardet L, et al. JAMA, May 2017.

The Background:

Nocturnal leg cramps are common, affecting over one-third of adults over age 60 at least occasionally, and over half of adults over age 80. For many years, quinine was used for treatment of cramps, either as a prescription in pill form or through drinking tonic water for its high quinine content.

In 2006, the FDA recommended against the use of quinine for leg cramps because of the potential for serious side effects or death. Despite this warning, use of quinine for the treatment of leg cramps has not ceased.

The Research:

Researchers used a large healthcare database of primary care patients in the United Kingdom to evaluate quinine use and mortality across approximately 175,000 people from 1990 through 2015. Individuals who were prescribed a dose of at least 100 mg per day of quinine for at least one year were each compared to three people who were not prescribed quinine. Those who were prescribed quinine had either cramps (96 percent of the quinine-prescribed group) or restless legs syndrome (4 percent), so controls were chosen with these same diseases (96 percent had cramps and 4 percent had RLS).

People exposed to quinine were, on average, one year older than controls, and were prescribed an average quinine dose of 203 mg per day. There was a 24 percent increase in risk of dying during the study period in the group prescribed quinine. Considering only those people prescribed quinine for RLS, there was still a significant increase in mortality risk in those with a quinine prescription.

The Bottom Line:

Quinine pills are not recommended for the treatment of RLS or leg cramps. It is unclear whether daily use of tonic water, which generally contains less than 100 mg of quinine per liter, also increases mortality risk.

New Questions:

Although there are multiple proven treatments available for RLS, data is very limited on how best to treat nocturnal leg cramps. As quinine is to be avoided, what treatments are effective for nocturnal leg cramps?

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