OBJECTIVE: Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is 
a sensorimotor disorder that can result in considerable sleep disruption. This 
narrative review provides an overview of RLS diagnosis and reports epidemiologic 
evidence for an association between RLS and mood disorders. Possible links 
between RLS, sleep disturbances, and mood disorders are considered, and 
theoretical pathophysiologic pathways are discussed. Finally, pharmacologic 
therapies for RLS are summarized.
DATA SOURCES: A PubMed search was performed using the search term restless legs 
syndrome in combination with affective/anxiety, antidepressants, anxiety/anxiety 
disorder, attention deficit hyperactivity disorder, depression/depressive 
disorder, mood/mood disorder, neuropsychiatric, panic/panic disorder, 
psychiatric disorder, and psychosis. English-language articles published between 
January 1993 and May 2013 were retrieved. Additional studies were identified 
from the reference lists of relevant publications.
STUDY SELECTION: 173 publications were retrieved. Articles related to the 
association between idiopathic RLS and depression, anxiety, and mood disorders 
were reviewed. In total, 32 epidemiologic studies were identified. These studies 
were reviewed in detail and ranked according to quality.
DATA EXTRACTION: Data were extracted on the basis of relevance to the topic. 
Epidemiologic studies were assessed using 3 parameters: methodology, data 
quality, and generalizability of the results. Each factor was scored from 1 
(high quality) to 4 (low quality), giving a total score of between 3 and 12 for 
each study.
RESULTS AND CONCLUSIONS: RLS and mood disorders are frequently comorbid. 
Recognition and appropriate treatment of comorbid RLS are particularly important 
in patients with psychiatric disorders, as RLS is a common medical reason for 
insomnia, and antidepressant use may exacerbate sensory symptoms.