Which antidepressant mechanism is most associated with causing a discontinuation syndrome characterised by 'brain zaps', dizziness, flu-like symptoms, and sensory disturbances when abruptly stopped?

• A Norepinephrine-dopamine reuptake inhibition (bupropion)
• B Tricyclic anticholinergic blockade (amitriptyline)
• C Serotonin reuptake inhibition with short half-life (paroxetine, venlafaxine) ✓
• D MAO inhibition (phenelzine)

Explanation

SSRI/SNRI discontinuation syndrome occurs most severely with agents that have short half-lives (paroxetine t½ ~21 h; venlafaxine t½ ~5 h) because rapid plasma level falls cause sudden serotonergic withdrawal. Symptoms include dizziness, flu-like malaise, electric shock-like 'brain zaps', and paresthesias (FINISH mnemonic). Fluoxetine, with its active metabolite norfluoxetine (t½ ~4–6 days), is least likely to cause this syndrome. Bupropion acts on norepinephrine/dopamine with minimal serotonergic action, and MAOIs have a different withdrawal profile.

Reference: Kaplan & Sadock's Synopsis of Psychiatry, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.