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Differentiating restless legs syndrome from psychotropic side effects

Subtleties of symptoms can help differentiate restless legs syndrome from medication side effects

Vol. 11, No. 02 / February 2012

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Patients who complain of unpleasant paresthesias present a challenge to psychiatrists who need to differentiate between what could be psychotropic side effects from restless legs syndrome (RLS). Reconizing the differences between the 2 conditions can guide intervention. A previously unknown RLS diagnosis may shed light on a patient’s comorbid sleep disturbances and insomnia.

Signs that suggest RLS

Symptoms consistent with akathisia temporally related to initiating an antipsychotic or antidepressant should not be considered RLS-induced. In less clear cases, subtleties of the symptoms can help you decide.

RLS often presents as discomfort in the legs that patients describe as creeping, crawling, pulling, or itching; movement typically relieves this discomfort. Feelings of akathisia also have been described as an inner restlessness and a need to get up and move to relieve the tension. However, RLS has the following defining characteristics:

  • occurs specifically in the lower extremities
  • has a circadian rhythm and is worse at night
  • can be accompanied by paresthesias and myoclonic jerks while awake.1

Other factors that support an RLS diagnosis are a family history of RLS,1 positive response to dopaminergic drugs,1 and low ferritin levels. Also consider conditions that put patients at risk for RLS, including end stage renal disease, diabetes mellitus, multiple sclerosis, Parkinson’s disease, anemia, rheumatic disease, venous insufficiency, and pregnancy.

3 substances that can worsen RLS

Ask patients about their intake of caffeine, nicotine, and alcohol. Use of these substances is common among psychiatric patients and can worsen RLS symptoms. Making a connection between these substances and RLS symptoms can help motivate patients to temper their use.

In addition to mimicking the subjective experience of RLS, many psychotropics, including antidepressants, neuroleptics, and antihistamines,2-4 can worsen RLS symptoms in patients with a known RLS diagnosis.

The next step

RLS is a clinical diagnosis that’s usually made based on a patient’s medical history. Polysomnography is not necessary to make an RLS diagnosis but may be helpful if a patient is treatment-resistant or to monitor periodic leg movement disorders. Serum ferritin levels should be checked because normal hemoglobin levels do not rule out iron deficiency.


Dr. Baker reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.


1. Allen RP, Picchietti D, Hening WA, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4(2):101-119.

2. Hoque R, Chesson AL, Jr. Pharmacologically induced/exacerbated restless legs syndrome periodic limb movements of sleep, and REM behavior disorder/REM sleep without atonia: literature review, qualitative scoring, and comparative analysis. J Clin Sleep Med. 2010;6(1):79-83.

3. O’Sullivan RL, Greenberg DB. H2 antagonists restless leg syndrome, and movement disorders. Psychosomatics. 1993;34(6):530-532.

4. Terao T, Terao M, Yoshimura R, et al. Restless legs syndrome induced by lithium. Biol Psychiatry. 1991;30(11):1167-1170.

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