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Fluoxetine half-life — MRCPsych Paper A MCQ

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ModeratePsychopharmacologyFluoxetine half-lifeMRCPsych Paper A

A 35-year-old woman taking maintenance fluoxetine misses one dose and experiences no withdrawal symptoms. When previously taking paroxetine, missed doses caused dizziness and electric-shock sensations. Which pharmacokinetic property of fluoxetine most directly explains this difference?

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Correct answer: C — Prolonged elimination of fluoxetine and norfluoxetine

The correct answer is C. Fluoxetine has an elimination half-life of approximately 4–6 days and is metabolised to active norfluoxetine, whose half-life is approximately 4–16 days. Active drug exposure therefore falls slowly after a missed dose, reducing the likelihood of an abrupt withdrawal syndrome. Paroxetine has a shorter duration of action and is particularly associated with withdrawal symptoms such as dizziness and electric-shock sensations after missed doses. Fluoxetine does inhibit CYP2D6 and has extensive protein binding, non-linear pharmacokinetics and a large volume of distribution, but none of these properties is the principal explanation for the clinical difference described. The decisive feature is the prolonged elimination of both the parent drug and its active metabolite.

Reference: Electronic Medicines Compendium. Fluoxetine 10 mg hard capsules, Summary of Product Characteristics, sections 4.5 and 5.2; updated 12 April 2024. https://www.medicines.org.uk/emc/product/15589/smpc