Depression and RLS John W. Winkelman MD, PhD Departments of Psychiatry and Neurology Massachusetts General Hospital Associate Professor of Psychiatry Harvard Medical School
A 42 year old man has a three year history of leg restlessness in the evening associated with pulling feelings deep in his lower leg, which are relieved by movement. These symptoms originally produced substantial difficulties with sleep onset and occasional awakenings. Clonazepam (0.5 mg) was prescribed for nightly use, with initial relief of the restlessness and sleep disturbance. After a year, he needed to increase the dose to 1.0 mg to maintain relief. He also reports a long history of dysthymia, for which he began citalopram 20 mg roughly two years before the current visit. The citalopram was associated with some initial worsening of his RLS. His medical history is unremarkable. He does not have symptoms of other sleep disorders, including snoring and excess daytime sleepiness. He does share a bottle of wine with his wife three times per week. He now reports that his RLS has worsened again, with a return of insomnia and of some symptoms of depression, including loss of enthusiasm for work, guilty preoccupation, mild fatigue, and mild difficulty with concentration. He also reports some mild word-finding difficulties which he attributes to the clonazepam.
Depression symptoms are common in neurological and sleep disorders Parkinson s disease Traumatic brain injury Epilepsy Stroke Alzheimer s disease Multiple sclerosis Restless Legs Syndrome Obstructive sleep apnea Insomnia
RLS and symptoms of depression/anxiety have been linked since 19 th century when Wittmaack called RLS anxietas tibiarum.
Major Depressive Disorder ++ Depressed mood or a loss of interest or pleasure in daily activities for more than two weeks Specific symptoms, at least 5 of these 9, present nearly every day: Depressed mood or irritable most of the day, nearly every day Decreased interest or pleasure in most activities, most of each day Significant weight change (5%) or change in appetite Change in sleep: Insomnia or hypersomnia Change in activity: Psychomotor agitation or retardation Fatigue or loss of energy Guilt/worthlessness: Feelings of worthlessness or excessive or inappropriate guilt Concentration: diminished ability to think or concentrate, or more indecisiveness Suicidality: Thoughts of death or suicide, or has suicide plan
RLS and Major Depressive Disorder (MDD) Both have prevalence rates of 5-10% Both disorders are diagnosed by subjective report Risk of both disorders is roughly double for women compared to men Both have strong genetic influence Both have diurnal variation Both have powerful placebo treatment responses
Epidemiologic studies of RLS and depression symptoms From Li et al, Am J Epidem 2012
Prevalence of depressive disorders in RLS 20-40% of those with RLS meet DSM criteria for MDD or dysthymia Most people with both RLS and MDD report that the RLS occurred first
RLS increases risk of new onset MDD in women over 6 years of follow up
RL S
but depressive symptoms increase risk of new onset RLS
Bidirectional association between RLS and depression + RLS Depression +
Treatment of RLS probably improves depression symptoms Ropinirole, pramipexole, gabapentin enacarbil
Do SSRIs worsen/produce RLS? SSRIs were a risk factor in RLS by automated phone interview (N=18,980): OR=3.11, 1.66-5.79) Another study found no difference in RLS prevalence in those taking SSRIs vs those not taking these medications
Antidepressants produce PLMS OR of PLMI >20 = 5.15 (2.09-12.68) for SSRIs compared to controls (no antidepressant) Yang C et al., Biol Psychiatry 2005
What is the mechanism of the association between RLS and depression? RLS? Depression
Is sleep the key mediator of the RLSdepression association? RLS Sleep disturbance Depression symptoms
Treatment Algorithm for Depression with RLS Depression Mild depression or dysthymia) Treat RLS first If depression persists, add bupropion or other non-ssri Severe depression + Optimize sleep quality & quantity Treat both depression and RLS Adapted from Picchetti D, Winkelman JW. Sleep. 2005 and Hornyak CNS Drugs 2010.
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