Selective serotonin reuptake inhibitors (SSRIs) discontinuation syndrome

• 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
  • antidepressants differ in their propensity to cause discontinuation symptoms
    • among the SSRIs several prospective studies have shown that paroxetine is associated with the highest incidence of discontinuation symptoms and fluoxetine the lowest
      • analysis of frequency of discontination reactions (Yellow Cards sent to Committee on Safety of Medicines up until 1994) formed a greater proportion of all reports received on paroxetine (5.1%) than on sertraline (0.9%), fluvoxamine (0.4%) and fluoxetine (0.06%)
    • 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 (4):
      • 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
      
      
• Differentiating between withdrawal and relapse
  • patients experiencing antidepressant withdrawal can easily be misdiagnosed as suffering from a relapse of their original mental health condition. This is because of similarity of psychological symptoms between the two, and because of poor understanding of the typical length and severity of withdrawal symptoms. Strategies to differentiate between withdrawal and relapse include (5):
    • identifying if the patient is experiencing physical symptoms of withdrawal that are unlikely to be a feature of depressive relapse, such as sensory disturbances, muscle pain, or nausea;
    • establishing the symptom timeline
      • withdrawal typically begins within days of antidepressant cessation,
      • relapse takes weeks to months

Reference:

• 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.
• Haddad PM, Anderson IM. Advances in Psychiatric Treatment 2007; 13: 447-457
• Haddad, PMThe SSRI discontinuation syndrome. Journal of Psychopharmacology 1998; 12: 305-313.
• Hennsler J et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. Lanet Psychiatry June 5th 2024.
• Palmer EG et al. Withdrawing from SSRI antidepressants: advice for primary care.British Journal of General Practice 2023; 73 (728): 138-140. DOI: 10.3399/bjgp23X732273