Restless Legs with Antidepressants?

Which of the following antidepressant is known to be associated with higher rates of restless legs syndrome and periodic limb movements, causing significant disruption in sleep?

Restless leg syndrome is defined as having following four essential clinical consensus criteria:

  • (a) Compelling urge to move the legs with or caused by uncomfortable sensations inside the legs.
  • (b) Symptoms begin or worsen with rest or inactivity.
  • (c) Symptoms are partially or totally relieved by movement; and
  • (d) Symptoms are worse in the evening or at night.

In addition to these four essential criteria, following three criterias can support the RLS diagnosis:

  • family history
  • response to dopaminergic treatment, and
  • presence of periodic leg movements in sleep

Several medications have been implicated in onset of restless leg syndrome, with antidepressants having the most evidence (2).

Answer to the above question: Mirtazapine is known to have the highest risk of RLS (Restless Leg Syndrome) and PLM (Periodic Limb Movements).


Read the following two chapters from our Academy:

  1. Restless Legs Syndrome/Periodic Limb Movements: Diagnosis & Management.
  2. Antidepressants & risk of RLS (Restless Leg Syndrome) and PLM (Periodic Limb Movements):

(1) Restless Legs Syndrome/Periodic Limb Movements: Diagnosis & Management

  1. Diagnosis of RLS
  2. Laboratory Workup
  3. Treatment for intermittent RLS
  4. Treatment for daily RLS
  5. Treatment for refractory RLS

(2) Antidepressants & risk of RLS (Restless Leg Syndrome) and PLM (Periodic Limb Movements):

  1. Higher risk antidepressants
  2. Moderate risk antidepressants
  3. Lower risk antidepressants
  4. No risk/preferred antidepressants


  1. Winkelman, J. Restless Legs Syndrome. History of Neurology: Seminal Citations. Arch Neurol. 1999;56(12):1526-1527.
  2. Kolla BP, Mansukhani MP, Bostwick JM. The influence of antidepressants on restless legs syndrome and periodic limb movements: A systematic review. Sleep Med Rev. 2018;38:131-140. 
  3. Allen RP, Picchietti DL, Auerbach M, et al. Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis-Ekbom disease in adults and children: an IRLSSG task force report. Sleep Med. 2018;41:27-44. doi:10.1016/j.sleep.2017.11.1126



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