A 34-year-old woman stops paroxetine abruptly after two years of treatment. Three days later she has dizziness, electric shock sensations, insomnia, irritability, and flu-like symptoms. Which property of paroxetine makes it the SSRI most likely to produce this picture?

• A Longest elimination half-life among SSRIs
• B Potent CYP2D6 inhibition combined with a short half-life ✓
• C Active metabolite with a half-life exceeding one week
• D Strong sigma receptor affinity causing physical dependence

Explanation

SSRI discontinuation syndrome is most frequent and severe with agents having short half-lives and no active metabolites. Paroxetine has the shortest half-life of the SSRIs and is a potent CYP2D6 inhibitor, so levels fall rapidly on stopping. Fluoxetine, with a half-life of days and an active metabolite norfluoxetine lasting one to two weeks, is least likely to cause it, which kills option A. Symptoms typically begin within 2 to 4 days.

Reference: Kaplan and Sadock's Synopsis of Psychiatry, 12th ed.

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