Restless legs syndrome as side effect of second generation antidepressants

J Psychiatr Res. 2008 Nov;43(1):70-5. doi: 10.1016/j.jpsychires.2008.02.006. Epub 2008 May 12.


Although of clinical interest, the question is still not fully answered whether antidepressants (AD) can cause or exacerbate restless legs syndrome (RLS). The literature provides contradictory information. This study addresses this problem for the class of second generation AD. In four neurological offices, all patients treated for the first time with an AD were prospectively observed with regard to the question of whether RLS occurred or pre-existing RLS worsened as a result of the medication. Because initial treatment in the participating offices is mainly executed with "modern" selective AD, the study was restricted to these drugs (fluoxetine, paroxetine, citalopram, sertraline, escitalopram, venlafaxine, duloxetine, reboxetine, and mirtazapine). In 9% of patients, RLS was recorded as a side effect related to the administration of AD. The frequency of this side effect varied among the drugs. The problem is most pronounced with mirtazapine provoking or deteriorating RLS in 28% of patients. By contrast, no case occurred during use of reboxetine. As for the other AD, the rate of newly occurred and deteriorated RLS, ranged from 5% to 10%. Typically, RLS occurred during the initial days of treatment.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Adult
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Citalopram / adverse effects
  • Citalopram / therapeutic use
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / psychology
  • Female
  • Humans
  • Male
  • Mianserin / adverse effects
  • Mianserin / analogs & derivatives
  • Mianserin / therapeutic use
  • Middle Aged
  • Mirtazapine
  • Morpholines / adverse effects
  • Morpholines / therapeutic use
  • Prospective Studies
  • Reboxetine
  • Restless Legs Syndrome / chemically induced*
  • Restless Legs Syndrome / diagnosis
  • Restless Legs Syndrome / epidemiology
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use


  • Antidepressive Agents
  • Morpholines
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Mianserin
  • Reboxetine
  • Mirtazapine