Antidepressant Withdrawal

Aka: Antidepressant Withdrawal, Antidepressant Discontinuation Syndrome, SSRI Discontinuation Syndrome

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II. Epidemiology

  1. Withdrawal symptoms may occur in up to 50% of patients on stopping their Antidepressant
    1. Davies (2019) Addict Behav 97:111-21 [PubMed]

III. Pathophysiology

  1. Occurs with sudden Antidepressant Withdrawal
    1. Selective Serotonin Reuptake Inhibitor (SSRI)
    2. Tricyclic Antidepressant
    3. MAO Inhibitor
  2. Symptom onset occurs within 24 hours to 2-3 weeks
  3. Likely results from Cholinergic overdrive
    1. Symptoms similar to Organophosphate Poisoning

IV. Risk Factors

  1. Highest Withdrawal Risk (most common with Shorter Half-Life Medications)
    1. Fluvoxamine (Luvox)
    2. Paroxetine (Paxil)
    3. Venlafaxine (Effexor) or Desvenlafaxine (Pristiq)
    4. Imipramine
    5. Nortriptyline
  2. Moderate Withdrawal Risk
    1. Duloxetine (Cymbalta)
    2. Citalopram (Celexa) or Escitalopram (Lexapro)
    3. Sertraline (Zoloft)
    4. Trazodone
    5. Vortioxetine
    6. Amitriptyline
    7. Clomipramine
    8. Desipramine
    9. Doxepin
  3. Lowest Withdrawal Risk
    1. Fluoxetine (Prozac, naturally tapers)
    2. Bupropion
    3. Mirtazapine (Remeron)
    4. Milnacipran
    5. Vilazodone

V. Symptoms

  1. Mnemonic: FINISH
    1. Flu-like Symptoms, Insomnia, Nausea, Imbalance, Sensory disturbance, hyperarousal
  2. Cholinergic rebound (See Cholinergic Toxicity)
    1. Diaphoresis
    2. Nausea or Vomiting
    3. Diarrhea
  3. Non-specific Withdrawal symptoms
    1. Dizziness
    2. Anxiety
    3. Headache
    4. Malaise
    5. Myalgias
    6. Weakness
    7. Sleep Disturbance
  4. Extrapyramidal Effects
    1. Paresthesias
    2. Restless legs

VI. Differential Diagnosis

  1. Bipolar Disorder with Antidepressant-induced mania

VII. Management: Approach

  1. Mild Symptoms: Resolve spontaneously
    1. Withhold treatment
    2. Reassurance and observe
  2. Moderate to severe symptoms
    1. Restart medication and then slowly taper
      1. See specific medications for taper schedule
    2. Symptoms abate soon after restarting medication

VIII. Management: Specific Withdrawal Symptoms

  1. Cholinergic rebound symptoms (See above)
    1. Atropine 0.8 mg PO tid to qid
    2. Cogentin 0.5 to 4 mg PO qd
    3. Artane 1-4 mg PO tid to qid
    4. Donnatal 2 tablets PO tid-qid
  2. Anxiety
    1. Lorazepam 0.5 to 1 mg PO tid prn
  3. Dizziness
    1. Antivert 12.5 to 25 mg PO q6 hours prn
    2. Dramamine 50 mg PO q6 hours prn

IX. Prevention

  1. Slowly taper off Antidepressants
    1. Decrease dose by 25% every 4 weeks or 12.5% every 2 weeks (stopping medication over 3-4 months)

X. Reference

  1. Henssler (2019) Dtsch Arztebl Int 116(20):355-61+PMID: 31288917 [PubMed]
  2. Kovich (2023) Am Fam Physician 107(2): 173-81 [PubMed]
  3. Wolfe (1997) Am Fam Physician 56(2):455-461 [PubMed]
  4. Zwiebel (2022) Cleve Clin J Med 89(1): 18-26 [PubMed]

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Related Topics in Pharmacology

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