Quinine and its derivatives have commonly been used to treat muscle cramps since the 1930s. In 2006, however, the U.S. Food and Drug Administration warned against this off-label use of quinine, noting 665 reports of adverse events from its use.

In a report from the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology, Katzberg and colleagues review the available data and provide recommendations for the treatment of muscle cramps. They conducted a literature search that resulted in 563 articles, of which 24 met the inclusion criteria and were categorized as class I through IV, with I being the most robust.

Evidence indicated that quinine derivatives effectively reduce the frequency but not the severity of muscle cramps. However, routine treatment with quinine isn't recommended because adverse effects, though rare, can be severe. The subcommittee recommends quinine use only for "very disabling" cramps and suggests that patients be informed of the risks and be monitored closely throughout treatment.

There is evidence to show that naftidrofuryl (not available in the United States), vitamin B complex, and diltiazem may be effective in treating muscle cramps; however, these data are from one class II study of each. Two class II studies indicate that magnesium preparations don't effectively treat cramps. Similarly, one study in patients with amyotrophic lateral sclerosis showed a lack of efficacy of gabapentin.

According to the authors, more research is needed to find effective treatments for muscle cramps, including possibly nonpharmacologic interventions.