Drug-Induced Restless Legs Syndrome

(March 17, 2019; updated October 14, 2021)

It is well-known that long-term use of anti-psychotic drugs can trigger a side effect called "tardive dyskinesia," a movement disorder characterized by twitching or uncontrolled movements in the head, neck, and face, and limbs. (See our article on this topic, referenced below.)

Recently, however, a very common neurological disorder affecting around ten percent of the population, "Restless Legs Syndrome," or RLS, has also been linked to antipsychotics as well as to antidepressants and antihistamines. Public Citizen's Health Research Group's Worst Pills March issue examined the phenomenon of drug-induced restless legs syndrome, and gave advice on what patients should consider when thinking about whether the condition is just an annoyance or needs to be treated.

What is RLS?
"Restless legs syndrome (RLS) causes a powerful urge to move your legs. Your legs become uncomfortable when you are lying down or sitting. Some people describe it as a creeping, crawling, tingling, or burning sensation. Moving makes your legs feel better, but not for long. RLS can make it hard to fall asleep and stay asleep." (from Medline Plus)

Not all leg-related movement disorders are classified as RLS. For example, a movement disorder that only occurs during sleep is called "periodic limb movement disorder" (PLMD). The sleeper's leg or legs move rhythmically with a kick or a jerk every 40 to 60 seconds during the first phase of sleep. Because the person with PLMD isn't aware of the kicking, the condition is often first observed by a bed partner. The bed partner, incidentally, may also suffer from sleep issues as a result of being kept awake by the "kicky" sleeper. RLS sufferers may also have PLMD, but many people have PLMD without having RLS.

For both kinds of leg movement disorders, older adults are affected more often, and the condition may only happen occasionally. Diet changes, such as avoiding alcohol or caffeine near bedtime, can alleviate the problem. Iron deficiencies and pregnancy can also temporarily trigger RLS.

Drug-induced RLS
Drugs that may cause or worsen RLS include antipsychotics, some antidepressants, antiepileptic (seizure drugs), over-the-counter and prescription antihistamines, and nausea drugs. When RLS is severe and needs treatment, and is caused by a medication, the course of treatment decision is difficult.

If you think your drug may be causing or worsening your RLS, Worst Pills recommends first asking your doctor if you can try discontinuing the suspected drug completely or at least reduce the dosage of the drug. In addition, you can try modifying your diet or sleep habits to try to lessen the RLS symptoms.

Because there is no drug approved for drug-induced RLS, any Rx received for that purpose would be considered to be "off-label" and come with its own set of side effects risks. Horizant, an extended release gabapentin, and Mirapex, a dopamine agonist are both approved for treatment of primary RLS, meaning that the RLS is not linked to another cause.

Here are some examples of drugs that may trigger restless legs syndrome, along with links to patient experiences of RLS:

Examples of Drugs That May Cause Restless Legs Syndrome (RLS)
Drug Type of Drug
Benadryl Antihistamine
Risperdal Antipsychotic
Reglan* Migraine/Nausea
Seroquel Antipsychotic
Zyprexa Antipsychotic
Lexapro Antidepressant
Lamictal Anticonvulsant
Cymbalta Antidepressant
Latuda Antipsychotic
Click drug name above to link to patient experiences of RLS.
* Reglan (METOCLOPRAMIDE HYDROCHLORIDE) has FDA black box warning about risk of tardive dyskinesia

There are many more examples in addition to those listed above. From the AskaPatient web site, search for your drug, then click "filter results" and type "RLS restless legs" and check the box "any word" to find out if your drug has patient experience reports for the side effect.

Sources and more reading on this topic:

- "Restless Legs" article on National Library of Medicine's Medline Plus
- "Movement disorder side effects of antipsychotic drugs" article from AskaPatient November 2017. Includes chart of drugs with links to patient examples of movement disorders caused by antipsychotics like Seroquel, nausea drug Reglan, and a few common antidepressants. Movement disorder side effects
- "Drug-induced Restless Legs Syndrome" March 2019. Worst Pills, Best Pills newsletter. (membership required to view) WorstPills.org
- "Sleep Related Movement Disorders" a collection of short articles on the topic, including periodic limb movement disorder. Science Direct
- Some drugs that have been taken by patients for treating restless legs syndrome (not "drug-induced restless leg syndrome") include:
Requip, Mirapex, Neurontin, Ultram, and benzodiazepines like Valium, Xanax, or clonazepam.