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Antidepressant discontinuation syndrome (ADS) is the cluster of physical and psychological symptoms that can emerge when an antidepressant dose is rapidly reduced, missed, or stopped altogether after at least several weeks of regular use. It reflects the brain’s adaptive response to the sudden absence of a drug that has been modulating monoamine neurotransmission, most commonly serotonin and noradrenaline. Although often called “withdrawal,” the preferred clinical term is ADS because the symptoms are usually self-limited and not driven by craving or compulsive drug-seeking behaviour [1]–[3].
Core clinical picture
• Onset: Typically 1–3 days (sometimes up to a week) after abrupt cessation or a large dose reduction [1], [2].
• Duration: Most cases resolve within 1–3 weeks, but 10–15 % may last months or longer, especially after long-term use or with short half-life drugs [3], [5].
• Symptoms: Remember the FINISH mnemonic—Flu-like symptoms, Insomnia, Nausea, Imbalance (dizziness, vertigo), Sensory disturbances (electric-shock “brain zaps”, paresthesia), and Hyperarousal (anxiety, irritability) [1]. Other features include headache, vivid dreams, crying spells, fatigue, and, less commonly, cholinergic rebound (sweating, diarrhea) or movement disorders [2], [4].
Drugs most often implicated
Prevalence is higher with short half-life selective serotonin reuptake inhibitors (SSRIs) and serotonin–noradrenaline reuptake inhibitors (SNRIs) such as paroxetine, venlafaxine, desvenlafaxine, and duloxetine. Longer half-life agents (e.g., fluoxetine) and tricyclic antidepressants cause fewer or milder symptoms, although ADS can occur with any antidepressant class, including MAOIs and atypical agents such as mirtazapine [1], [3].
Risk factors
• Abrupt cessation or large dose reductions
• Longer duration of treatment (>6–8 weeks; risk rises further after months/years)
• High maintenance dose
• Previous episodes of ADS
• Concomitant substances that induce hepatic metabolism (which shorten half-life) [2], [3].
Pathophysiology (brief)
Chronic antidepressant use down-regulates postsynaptic receptors and alters transporter densities. When the drug is suddenly withdrawn, synaptic serotonin and noradrenaline signaling fall abruptly before receptors can readjust, producing the characteristic symptoms. Neuro-adaptations in cholinergic, glutamatergic, and GABAergic systems may also contribute [4], [5].
Differential diagnosis
• Relapse of the underlying mood or anxiety disorder (relapse appears gradually over weeks and reproduces pre-treatment symptoms).
• Physical illness (e.g., viral infection, vestibular disorder).
ADS is suggested by the close temporal link with stopping the drug, the FINISH symptom profile, and rapid relief within hours to days after re-instating the antidepressant (“re-challenge”) [3].
Prevention and management
• Patient education before initiation and again before tapering.
• Gradual dose reduction—guidelines recommend reducing by 5–10 % of the current dose every 1–4 weeks, with slower tapering for high-risk drugs or long-term users [3].
• Consider switching to fluoxetine (long half-life) before tapering if using short half-life SSRIs/SNRIs [1].
• Symptomatic relief: antiemetics, NSAIDs, short-term hypnotics or benzodiazepines, vestibular suppressants as required.
• If severe, reinstate the previous effective dose and restart taper at a slower pace [2], [3].
When appropriately recognized and managed, ADS is rarely dangerous, but failure to anticipate it can lead to significant distress, misdiagnosis of relapse, and unnecessary long-term drug continuation.
Sources
[1] Harvard Health Publishing. “Going off antidepressants—how to do it right.” The source explains onset, typical symptoms (FINISH), and higher risk with paroxetine and venlafaxine. https://www.health.harvard.edu/diseases-and-conditions/going-off-antidepressants
View: Practical patient-focused overview; emphasizes gradual taper and role of half-life.
[2] Royal College of Psychiatrists. “Stopping antidepressants: information for patients” (2024). Details timing, symptom spectrum, risk factors, and taper strategies. https://www.rcpsych.ac.uk/docs/default-source/mental-health/treatments-and-wellbeing/print-outs/stopping-antidepressants-information-resource-print-version-18-03-24.pdf
View: Authoritative patient leaflet; stresses FINISH mnemonic and personalised tapering.
[3] Horowitz MA & Taylor D. “Tapering of SSRI treatment to mitigate withdrawal symptoms.” Therapeutic Advances in Psychopharmacology 2021; 11:1-22. https://pmc.ncbi.nlm.nih.gov/articles/PMC7970174
View: Systematic clinical review; describes incidence, risk factors, protracted withdrawal, and proposes hyperbolic taper method.
[4] Fava GA et al. “The potential role of discontinuation syndrome in antidepressant tapering.” CNS Drugs 2015 (full text via CORE). https://core.ac.uk/reader/195308748?utm_source=linkout
View: Discusses neurobiological mechanisms and differentiates ADS from relapse.
[5] Chouinard G & Chouinard V-A. “Antidepressant discontinuation syndrome and its management.” Postgraduate Medicine 2015 (open access summary in PMC). https://pmc.ncbi.nlm.nih.gov/articles/PMC8061160/
View: Reviews prevalence, pathophysiology, and clinical management; notes persistence beyond 3 weeks in a subset of patients.