A 34-year-old woman stops her antidepressant abruptly and three days later develops dizziness, nausea, insomnia, irritability, and electric shock sensations in her limbs. Her physician notes that this agent carries the highest risk of discontinuation symptoms among SSRIs because it has:
- A The longest elimination half-life among SSRIs
- B The shortest elimination half-life among SSRIs, with no long-lived active metabolite ✓
- C Potent CYP2D6 induction
- D Irreversible monoamine oxidase inhibition
Correct answer: B. The shortest elimination half-life among SSRIs, with no long-lived active metabolite
Explanation
Paroxetine has the shortest half-life of the SSRIs, roughly 21 hours, and lacks an active metabolite, so receptor-level serotonergic withdrawal emerges rapidly after abrupt cessation. Fluoxetine sits at the opposite extreme, with a half-life of several days plus the long-lived metabolite norfluoxetine, making it essentially self-tapering and the usual choice when switching or stopping. Paroxetine is a CYP2D6 inhibitor, not an inducer.
Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.
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