Antidepressants and RLS/PLMS in the general population

Abstract

Restless Legs Syndrome (RLS) and periodic leg movements during sleep (PLMS) can occur as a primary disorder or as a secondary condition. The claim that antidepressant use induces RLS or PLMS is controversial and has significant implications considering the widespread use of these medications. The aim of this study was to explore the association between antidepressant drugs intake and the frequency of both RLS and PLMS in a large unselected middle-aged general population sample. Data from 5064 subjects (2542 women, mean age 56.7 ± 10.1) participating in an ongoing population-based cohort study (HypnoLaus, Lausanne, Switzerland) was collected. All them completed a series of sleep related questionnaires and 2019 underwent polysomnographic recordings at home. RLS was ascertained by the presence of the 4 basic diagnostic criteria of the International Restless Legs Syndrome Study Group. PLMS index (PLMSI) was determined according to AASM 2007 criteria. A PLMSI > 15/h was considered to be abnormal. Among the 5064 participants, 457 (9%) were taking antidepressive drugs: 291 (5.7%) took SSRIs, 44 (0.8%) tricyclics and 122 (2.4%) other antidepressive drugs (a heterogeneous group including Trazodone, Mirtazapine, Mianserine, Venlafaxine, Bupropion, Duloxetine). Overall, the prevalence of RLS in subjects taking antidepressive drugs was 21% vs 12.1% in the other subjects ( p < 0.001). Analyses of individual antidepressants class revealed an association between RLS and SSRIs (RR = 1.78, CI = 1.32–2.42) and for the group “other antidepressive drugs” (RR = 1.8, CI = 1.14–2.84) but no association was found for tricyclic antidepresants, after adjusting for age, gender, diabetes (yes/no), neuroleptic use (yes/no) and glomerular filtration rate. Among the 2019 participants that underwent PSG, 131 (6.5%) took SSRIs, 18 (0.9%) took tricyclics and 48 (2.4%) took other antidepressive drugs. The prevalence of PLMSI > 15/h in subjects taking antidepressive drugs was 34.4% (vs. 26.1%, p = 0.039). A significant association was found between PLMSI > 15/h and SSRIs (RR = 1.84, CI = 1.23–2.76) and tricyclics (RR = 3.84, CI = 1.44–10.2), but no for the group other antidepressants, after adjusting for confounding factors. RLS and PLMS in the general population are associated with antidepressant use. SSRIs are associated with RLS and PLMS whereas tricyclic are associated only with PLMS. Funding: Fondation Leenaards, FNS, GSK, Ligue Pulmonnaire Vaudoise and CIRS.