Antidepressant withdrawal reactions

Am Fam Physician. 1997 Aug;56(2):455-62.


Antidepressants can cause a variety of withdrawal reactions, starting within a few days to a few weeks of ceasing the drug and persisting for days to weeks. Both tricyclic antidepressants and selective serotonin reuptake inhibitors cause similar syndromes, most commonly characterized by gastrointestinal or somatic distress, sleep disturbances, mood fluctuations and movement disorders. Most symptoms related to tricyclic antidepressant withdrawal are believed to be caused by rebound excess of cholinergic activity after prolonged anticholinergic effect on cholinergic receptors. (This situation is analogous to the adrenergic rebound that occurs after beta-blocker withdrawal.) Treatment involves restarting the antidepressant and tapering it more slowly. Alternatively, tricyclic antidepressant withdrawal symptoms often respond to anticholinergics, such as atropine or benztropine mesylate. Three case reports of antidepressant withdrawal are presented, including one featuring akathisia (motor restlessness) related to withdrawal of venlafaxine.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Amitriptyline / adverse effects
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Clomipramine / adverse effects
  • Cyclohexanols / adverse effects
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Monoamine Oxidase Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Substance Withdrawal Syndrome* / diagnosis
  • Substance Withdrawal Syndrome* / drug therapy
  • Trazodone / adverse effects
  • Venlafaxine Hydrochloride


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Cyclohexanols
  • Monoamine Oxidase Inhibitors
  • Serotonin Uptake Inhibitors
  • Amitriptyline
  • Venlafaxine Hydrochloride
  • Clomipramine
  • Trazodone