Prozac
fluoxetine
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial treatment.
Overview
Fluoxetine was the first SSRI approved in the US and remains one of the most widely prescribed antidepressants. It is approved for major depressive disorder, OCD, panic disorder, bulimia nervosa, and bipolar depression (in combination with olanzapine).
10mg, 20mg, 40mg, 60mg
Capsules: 10mg, 20mg, 40mg; Tablets: 10mg, 20mg, 60mg; Oral solution: 20mg/5mL; Delayed-release capsules (weekly): 90mg
Category C (risk cannot be ruled out)
Mechanism of Action
Selective serotonin reuptake inhibitor (SSRI) that blocks the serotonin transporter (SERT). Its active metabolite norfluoxetine is also a potent SSRI, contributing to an extremely long effective half-life.
Taper Notes
Very long half-life makes it the easiest SSRI to taper. Sometimes used as a bridge for tapering other SSRIs/SNRIs.
Maudsley Deprescribing Guidance
Long half-life provides built-in buffering. Still recommended to taper gradually rather than abrupt stop.
Common Withdrawal Symptoms
Interactions & Safety
Drug Interactions
- MAOIs — contraindicated (allow 5 weeks washout due to long half-life)
- Thioridazine — contraindicated (QT prolongation)
- Pimozide — contraindicated
Food Interactions
- No significant food effect on absorption
- Grapefruit juice may modestly increase levels
- Avoid alcohol during treatment
Contraindications
- MAOIs within 14 days (5 weeks washout before starting MAOI)
- Thioridazine
- Pimozide
Toxicity
Serotonin syndrome at supratherapeutic doses. QT prolongation rarely reported. Lower toxicity in overdose compared to TCAs.
Pharmacokinetics
ADME Profile
Well absorbed after oral administration. Bioavailability ~72%. Tmax 6–8 hours. Food slightly delays absorption but does not affect overall extent.
~20–45 L/kg
Hepatic via CYP2D6 (primary) and CYP2C9 to the active metabolite norfluoxetine. Fluoxetine is a potent CYP2D6 inhibitor.
Renal (~80%, with ~2.5% as unchanged fluoxetine and ~10% as norfluoxetine). Fecal (~15%).
~94.5%
Apparent oral clearance ~600 mL/min; decreases with chronic dosing due to CYP2D6 inhibition.
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