Which SSRI is associated with the most frequent and severe antidepressant discontinuation syndrome, and what property accounts for this?

• A Fluoxetine, due to irreversible inhibition of serotonin reuptake
• B Sertraline, due to its sigma receptor affinity
• C Paroxetine, due to having the shortest elimination half-life among SSRIs ✓
• D Citalopram, due to its strong CYP2D6 inhibition

Explanation

Paroxetine has a half-life of roughly 20 hours with no active metabolite, so missed doses rapidly drop brain serotonin levels and produce dizziness, electric shock sensations, insomnia and irritability. Fluoxetine sits at the opposite extreme: its half-life of several days, extended further by the active metabolite norfluoxetine, makes it self-tapering and gives it the lowest risk of discontinuation symptoms, which kills option A. Sertraline and citalopram are intermediate and neither property listed determines withdrawal risk.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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