Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal?

Sleep. 2013 Nov 1;36(11):1579-85. doi: 10.5665/sleep.3102.


Objectives: 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.

Design: Prospective cohort study.

Setting: Tertiary sleep disorders center.

Participants: 100 patients with idiopathic RBD, all with diagnosis confirmed on polysomnography, stratified to baseline antidepressant use, with 45 matched controls.

Measurements/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.

Keywords: Parkinson disease; REM sleep behavior disorder; antidepressants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antidepressive Agents / adverse effects*
  • Case-Control Studies
  • Color Perception / drug effects
  • Humans
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / chemically induced*
  • Neurodegenerative Diseases / diagnosis
  • Parkinson Disease, Secondary / diagnosis
  • Parkinson Disease, Secondary / etiology
  • Prodromal Symptoms
  • Prospective Studies
  • REM Sleep Behavior Disorder / chemically induced*
  • Risk Factors
  • Smell / drug effects


  • Antidepressive Agents