Discontinuation syndromes with antidepressants

• can occur with any antidepressant
  
  
• generally start abruptly with a few days of stopping the antidepressant - usually resolve within 24 hours if the drug is restarted (1)
  
• terms 'antidepressant discontinuation symptom' and 'antidepressant withdrawal symptom' are used interchangeably in the literature
  • discontinuation is preferred by some authorities, as it does not imply that antidepressants are addictive or cause a dependence syndrome, whereas the term 'withdrawal' may imply this
    
    
• SSRIs can, in some cases, be associated with a withdrawal/discontinuation reaction upon cessation of regular use
  • in addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances
  • psychological symptoms have also been documented, usually developing within 1-7 days following SSRI discontinuation
  • characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs (1)
    
    
• in the majority of patients
  • discontinuation symptoms are self-limiting, of short duration and mild
    • in a minority of cases they can be severe, last several weeks and cause significant morbidity
      • examples of featurs of SSRI discontinuation reactions include ataxia leading to falls, fatigue causing difficulty walking and electric-shock-like sensations impairing walking and driving
        
        
  • there is no accepted definition of an antidepressant discontinuation syndrome (1,2)
    
    
• Incidence
  • a systematic review and meta-analysis states that incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication (3):
    • desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms
      
      
• Time of Onset
  • symptoms usually appear within a few days of stopping an antidepressant or, less commonly, reducing the dose
  • onset of symptoms after more than 1 week is unusual
    
    
• Duration
  • the majority of antidepressant discontinuation reactions are of short duration, resolving spontaneously between 1 day and 3 weeks after onset
    
    
• Effect of Restarting medication
  • discontinuation symptoms usually resolve fully within 24 h if the original antidepressant is recommenced
    
    
• Primary SSRI discontinuation syndrome
  
  
  • features of this have been suggested as (2):
    • Sensory symptoms
      • Paraesthesia
      • Numbness
      • Electric-shock-like sensations
      • Rushing noise 'in head'
      • Palinopsia (visual trails)
    • Disequilibrium
      • Light-headedness
      • Dizziness
      • Vertigo
    • General somatic symptoms
      • Lethargy
      • headache
      • Tremor
      • Sweating
      • Anorexia
    • Affective symptoms
      • Irritability
      • Anxiety/agitation
      • Low mood
      • Tearfulness
    • Gastrointestinal symptoms
      • Nausea
      • Vomiting
      • Diarrhoea
    • Sleep disturbance
      • Insomnia
      • Nightmares
      • Excessive dreaming
  • most common symptoms are dizziness, nausea, lethargy and headache (4)
    • some patients experience sensory symptoms (e.g. sensations resembling electric shocks) or symptoms of disequilibrium (e.g. dizziness) in brief bursts when they move their head or eyes
      
      
• Primary TCA discontinuation syndrome
  • Has been suggested that characteristically features may include (2):
    • General somatic symptoms
      • Lethargy
      • headache
      • Tremor
      • Sweating
      • Anorexia
    • Affective symptoms
      • Irritability
      • Anxiety/agitation
      • Low mood
      • Tearfulness
    • Gastrointestinal symptoms
      • Nausea
      • Vomiting
      • Diarrhoea
    • Sleep disturbance
      • Insomnia
      • Nightmares
      • Excessive dreaming
        
        
• MAOI discontinuation syndrome
  • reactions to MAOI discontinuation, particularly those reported with tranylcypromine, tend to be more severe than with other antidepressants (2)
    • features may include:
      • (i) a worsening of depressive symptoms, exceeding the severity of the state that originally led to treatment
      • (ii) an acute confusional state with disorientation, paranoid delusions and hallucinations
      • (iii) anxiety symptoms, including hyperacusis and depersonalisation

Reference:

• Drug and Therapeutics Bulletin (1999), 37 (7), 49-52.
• Renoir T. Selective Serotonin Reuptake Inhibitor Antidepressant Treatment Discontinuation Syndrome: A Review of the Clinical Evidence and the Possible Mechanisms Involved. Front Pharmacol. 2013; 4: 45.
• Henssler J et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lancet Psychiatry June 5th 2024.
• Haddad PM, Anderson IM. Advances in Psychiatric Treatment 2007; 13: 447-457