Fluoxetine (Prozac)
The original SSRI antidepressant and still one of the most prescribed. Fluoxetine has a very long half-life, which means fewer withdrawal issues when stopping, but also means drug interactions can persist for weeks.
What it's used for
Major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, bulimia nervosa, and premenstrual dysphoric disorder (PMDD). Sometimes used off-label for anxiety, PTSD, and binge eating disorder.
Typical dosing (adults)
- Depression: Start at 20 mg once daily in the morning; may increase to 40–80 mg daily.
- OCD: 20–60 mg daily (sometimes up to 80 mg).
- Panic disorder: Start at 10 mg daily, increase to 20 mg after one week.
- Can be taken with or without food. Takes 4–6 weeks for full antidepressant effect.
Key interactions
- MAO inhibitors (phenelzine, tranylcypromine, selegiline): major — risk of fatal serotonin syndrome; must wait at least 5 weeks after stopping fluoxetine before starting an MAOI.
- Other serotonergic drugs (tramadol, triptans, St. John's Wort): major — increased risk of serotonin syndrome (agitation, tremor, high temperature).
- NSAIDs and blood thinners (warfarin, aspirin): moderate — SSRIs impair platelet function, increasing bleeding risk.
- Metoprolol and other CYP2D6 substrates: moderate — fluoxetine is a strong CYP2D6 inhibitor, raising levels of many drugs.
- Tamoxifen: major — fluoxetine blocks conversion of tamoxifen to its active form, potentially reducing breast cancer protection.
Common side effects
Nausea (most common early on), headache, insomnia or drowsiness, anxiety or nervousness (may worsen in first 1–2 weeks), sexual dysfunction (reduced libido, delayed orgasm), decreased appetite, and dry mouth. Weight changes vary. Rare but serious: serotonin syndrome, increased suicidal thoughts in young adults under 25 (FDA black box warning — monitor closely in early weeks).
Who should be cautious
- Children and young adults under 25 (increased risk of suicidal thinking in early treatment).
- Bipolar disorder (can trigger manic episodes if used without a mood stabilizer).
- History of seizures (slightly lowers seizure threshold).
- Liver disease (fluoxetine is extensively metabolized by the liver).
- Taking tamoxifen for breast cancer (choose a different antidepressant).
What to ask your pharmacist
- How long before I notice an improvement in my mood?
- I'm also taking ibuprofen regularly — does that increase bleeding risk?
- Can I take melatonin or herbal supplements with fluoxetine?
- If I miss a dose, should I double up the next day?
- Is it safe to drink alcohol while on fluoxetine?