A 30-year-old woman stops paroxetine abruptly after two years of therapy. Three days later she develops dizziness, electric shock sensations, insomnia, irritability, and flu-like symptoms. Which pharmacokinetic property of paroxetine best explains why these symptoms are most severe with this particular SSRI?
- A Longest half-life among SSRIs
- B Irreversible enzyme inhibition
- C Shortest half-life among SSRIs with no active metabolite ✓
- D Active metabolite with cumulative accumulation
Correct answer: C. Shortest half-life among SSRIs with no active metabolite
Explanation
SSRI discontinuation syndrome is most frequent and severe with agents having short half-lives and no active metabolites, and paroxetine is the classic offender; fluvoxamine is similar. In contrast, fluoxetine has a very long half-life plus the long-lived active metabolite norfluoxetine, so it essentially self-tapers and rarely causes withdrawal symptoms. The syndrome reflects cholinergic rebound and serotonergic instability rather than dependence. Management is reinstitution followed by slow tapering.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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