title: Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?
abstract: OBJECTIVE
  Antidepressants, among the most commonly prescribed medications, trigger symptoms of REM sleep behavior disorder (RBD) in up to 6% of users. Idiopathic RBD is a very strong prodromal marker of Parkinson disease and other synuclein-mediated neurodegenerative syndromes. It is therefore critically important to understand whether antidepressant-associated RBD is an independent pharmacologic syndrome or a sign of possible prodromal neurodegeneration.
  
  
  METHODS
  Prospective cohort study.
  
  
  METHODS
  Tertiary sleep disorders center.
  
  
  METHODS
  100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls.
  
  
  RESULTS
  Of 100 patients, 27 were taking antidepressants. Compared to matched controls, RBD patients taking antidepressants demonstrated significant abnormalities of 12/14 neurodegenerative markers tested, including olfaction (P = 0.007), color vision (P = 0.004), Unified Parkinson Disease Rating Scale II and III (P < 0.001 and 0.007), timed up-and-go (P = 0.003), alternate tap test (P = 0.002), Purdue Pegboard (P = 0.007), systolic blood pressure drop (P = 0.029), erectile dysfunction (P = 0.002), constipation (P = 0.003), depression indices (P < 0.001), and prevalence of mild cognitive impairment (13% vs. 60%, P < 0.001). All these abnormalities were indistinguishable in severity from RBD patients not taking antidepressants. However, on prospective follow-up, RBD patients taking antidepressants had a lower risk of developing neurodegenerative disease than those without antidepressant use (5-year risk = 22% vs. 59%, RR = 0.22, 95%CI = 0.06, 0.74).
  
  
  CONCLUSIONS
  Although patients with antidepressant-associated RBD have a lower risk of neurodegeneration than patients with "purely-idiopathic" RBD, markers of prodromal neurodegeneration are still clearly present. Development of RBD with antidepressants can be an early signal of an underlying neurodegenerative disease.
authors.affiliation: Department of Neurology, McGill University, Montreal General Hospital, Montreal, Québec, Canada ; Centre d'Études Avancées en Médecine du Sommeil, Hôpital du Sacré-Cœur de Montréal, Montréal, Québec, Canada.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Postuma
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Gagnon
authors.forename: Maria
authors.initials: M
authors.lastname: Tuineaig
authors.forename: Josie-Anne
authors.initials: JA
authors.lastname: Bertrand
authors.forename: Veronique
authors.initials: V
authors.lastname: Latreille
authors.forename: Catherine
authors.initials: C
authors.lastname: Desjardins
authors.forename: Jacques Y
authors.initials: JY
authors.lastname: Montplaisir
mesh_terms: D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D003118:Color Perception / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000175:diagnosis; D010302:Parkinson Disease, Secondary / Q000175:diagnosis / Q000209:etiology; D062706:Prodromal Symptoms; D011446:Prospective Studies; D020187:REM Sleep Behavior Disorder / Q000139:chemically induced*; D012307:Risk Factors; D012903:Smell / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents
keywords: Parkinson disease; REM sleep behavior disorder; antidepressants