Fluoxetine
PROZAC
What it isSerotonin reuptake inhibitor with 5-HT2C antagonism; depression, OCD, bulimia, panic disorder and PMDD.
Why this oneLong persistence makes missed doses and discontinuation easier, but delayed interaction washout is the price.
What limits itActivation, insomnia and sexual dysfunction often limit it. CYP2D6 inhibition compromises tamoxifen; allow the extended MAOI washout.
FDA-approved for
- depression (1987)
- OCD (1994)
- bulimia nervosa (1994)
- panic disorder (2000)
- PMDD (2000)
Off-label
- premature ejaculation
- fibromyalgia
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Major depressive disorder | Adults | 20 mg QD (AM) | 20 mg QD | 80 mg/day |
| Major depressive disorder | Peds (children/adolescents) | 10–20 mg QD | 20 mg QD | 20 mg QD |
| Obsessive compulsive disorder | Adults | 20 mg QD (AM) | 20–60 mg/day | 80 mg/day |
| Obsessive compulsive disorder | Peds (children/adolescents) | 10 mg QD | 20–60 mg/day | 60 mg/day |
| Bulimia nervosa | Adults | 60 mg QD (AM) | 60 mg QD | 60 mg/day |
| Panic disorder | Adults | 10 mg QD, then 20 mg QD after 1 week | 20 mg/day | 60 mg/day |
| Bipolar I depression (with oral olanzapine) | Adults | 20 mg fluoxetine + 5 mg olanzapine QHS | fluoxetine 20–50 mg + olanzapine 5–12.5 mg | 75 mg fluoxetine / 18 mg olanzapine (safety limit) |
| Bipolar I depression (with oral olanzapine) | Peds 10–17y | 20 mg fluoxetine + 2.5 mg olanzapine QHS | per efficacy/tolerability | 50 mg fluoxetine / 12 mg olanzapine (safety limit) |
| Treatment-resistant depression (with oral olanzapine) | Adults | 20 mg fluoxetine + 5 mg olanzapine QHS | fluoxetine 20–50 mg + olanzapine 5–20 mg | 75 mg fluoxetine / 18 mg olanzapine (safety limit) |
Titration Increase after several weeks if response inadequate (pediatric MDD: after 1 week at 10 mg; pediatric OCD: after 2 weeks)
Renal Undefined
Hepatic Use a lower or less frequent dose (e.g., in cirrhosis)
Instructions
- Administer in the morning; doses >20 mg/day may be given once in AM or split (morning and noon)
- When combined with olanzapine, dose once daily in the evening
- Taper rather than stop abruptly to reduce discontinuation symptoms
- Do not use an MAOI within 14 days before, or for 5 weeks after, fluoxetine
Contraindications
- MAOIs (concurrently or within 14 days of stopping MAOI); allow 5 weeks after stopping fluoxetine before starting an MAOI due to risk of serotonin syndrome
- Pimozide (QT prolongation; fluoxetine raises pimozide levels via CYP2D6)
- Thioridazine (QT prolongation; do not use within 5 weeks of stopping fluoxetine)
Cautions
- Serotonin syndrome
- Suicidal thoughts and behaviors
- Allergic reactions and rash
- Activation of mania/hypomania; screen for bipolar disorder
- Seizures
- Altered appetite and weight
- Increased risk of bleeding (with NSAIDs/aspirin/warfarin)
- Angle-closure glaucoma
- Hyponatremia / SIADH
- QT prolongation
- Long half-life — dose changes take weeks to reflect in plasma
- Sexual dysfunction
Adverse reactions
- Nausea
- Insomnia
- Headache
- Anxiety
- Nervousness
- Somnolence
- Tremor
- Diarrhea
- Anorexia
- Dry mouth
- Asthenia
- Decreased libido
- Sweating
Pregnancy Published data have not established an increased risk of major birth defects or miscarriage; possible increased postpartum hemorrhage and poor neonatal adaptation/PPHN with third-trimester exposure.
Lactation Fluoxetine and norfluoxetine present in human milk; monitor the infant for agitation, irritability, poor feeding, and poor weight gain.
⚠ BOXED WARNING
- Suicidal thoughts and behaviors in patients under 25
Cost, est. cash$4–$80/month
Generic entry2001
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityLong half-life and CYP2D6 inhibition create persistent interactions; activation and serotonin toxicity are possible.
Active metabolites
Mechanism of action: Fluoxetine ballicule
Open Fluoxetine in the interactive console ↗
Memory aids: mascots and interaction avatars
Fluffer inHibitor (fluoxetine, fluvoxamine, fluconazole)
#20 → 20 mg usual starting dose
