After reading this article, you will be familiar with:
• Pathogenesis of restless legs syndrome (RLS)
• Comorbidity of RLS and psychiatric disorders
• Treatment options for RLS in patients with psychiatric disorders
Who will benefit from reading this article?
Psychiatrists, geriatric psychiatrists, psychologists, primary care physicians, nurse practitioners, and other health care professionals. To determine whether this article meets the continuing education requirements of your specialty, please contact your state licensing and certification boards.
Restless legs syndrome (RLS) is a neurosensory disorder first described by Sir Thomas Willis in 1672. As early as the 19th century, Theodor Wittmaack1 observed the comorbidity of RLS with depression and anxiety. He termed this condition “anxietas tibiarum” and believed it to be a form of hysteria.
Once thought to be rare, data now suggest that RLS is relatively common but underrecognized and undertreated.2 Several clinical and population-based studies have reported a high prevalence of psychiatric comorbidities—particularly depression and anxiety—in patients with RLS.3 Thus, for psychiatrists, understanding the clinical features and treatment of RLS has become critical in their daily practice. The symptomatic overlap between RLS and mood disorders and the potential impact of psychiatric medications on RLS symptoms make RLS a diagnostic and treatment challenge.
This article provides an overview of the clinical features of and treatment strategies for RLS. It also offers a survey of the current literature on issues in the diagnosis and treatment of RLS among psychiatric patients.
Clinical features and diagnosis
The case vignette illustrates the importance of evaluating for RLS symptoms in patients with major depressive disorder (MDD) who complain of insomnia.
Lisa is a 45-year-old married woman who came to see a psychiatrist initially for depressive symptoms. During the initial evaluation, she complained of difficulty in falling asleep and other depressive symptoms such as low mood, difficulty with concentration, poor appetite, and low energy along with daytime fatigue. Depression was diagnosed. An SSRI was prescribed on an as-needed basis, and the patient was advised to take a nightly dose of diphenhydramine to help her sleep.
Three days later—after staying up nearly all night—Lisa called her doctor in despair and complained of worsening insomnia. On more detailed questioning about the insomnia, Lisa revealed that for the past 2 years, she has experienced leg discomfort when she gets into bed. She is so uncomfortable that she needs to walk or ride on her exercise bike past 2 or 3 am until the discomfort subsides. While not painful, this leg discomfort sometimes prevents her from relaxing and watching television because she just “has to move” her legs.
Lisa describes a deep uncomfortable sensation that feels like “bugs crawling in her legs.” She also reveals that her mother used to suffer from similar nighttime leg restlessness. For the past 3 nights, Lisa’s leg discomfort has been more intense and has lasted most of the night.
After secondary causes of RLS, such as iron deficiency anemia, pregnancy, uremia, and neuropathy, were ruled out, a diagnosis of RLS was made. SSRI and diphenhydramine therapy were stopped. Low-dose dopamine agonist therapy was started, after which the symptoms subsided. However, despite resolution of the RLS symptoms, her depressive symptoms continued. Titrated bupropion was given until the depressive symptoms fully resolved.
The RLS diagnosis and epidemiology workshop at the NIH established 4 criteria for diagnosis of RLS4:
1. An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs
2. The urge to move or unpleasant sensations that begin or worsen during periods of rest or inactivity, such as lying or sitting
3. The urge to move or unpleasant sensations that are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues
4. The urge to move or unpleasant sensations that are worse in the evening or night than during the day or only occur in the evening or night
A diagnostically supportive but not essential feature of RLS includes a history of the disorder in first-degree relatives. A polygenetic disorder with its phenotype contributed by a number of variants, RLS is a highly familial trait with heritability estimates of about 50%.5 Recent linkage studies in families with RLS revealed several loci but have not led to the identification of disease-causing sequence variants.6,7
Another supportive diagnostic feature is a history of positive response to dopaminergic therapy, such as levodopa (L-dopa) or a dopamine receptor agonist.4 Periodic limb movements during sleep (PLMS), although not specific to RLS, occur in at least 80% of RLS patients and correlate with clinical ratings of RLS severity.8 While polysomnography or actigraphy evidence of PLMS is not necessary for diagnosis, PLMS supports the diagnosis of RLS and provides an objective, indirect measure of RLS severity.4 In more severe cases, symptoms of RLS occur during the daytime, disrupting restful activities such as sitting or trying to nap. Ascertaining the degree of interference with daytime activities may provide a measure of RLS severity.
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