Prozac

(fluoxetine)

Prozac (fluoxetine); not controlled

Summary

Prozac is a selective serotonin reuptake inhibitor approved for major depressive disorder from 8 years of age and for obsessive-compulsive disorder from 7 years. Response is judged over weeks of continuous dosing. Its half-life is the longest in the class, so it is effectively self-tapering and forgiving of a missed dose. Not controlled; brand and generic.

Forms & Strengths

• Capsules, immediate release: 10 mg, 20 mg, 40 mg
• Tablets: 10 mg, 20 mg, 60 mg
• Oral solution: 20 mg/5 mL (4 mg/mL)
• Capsule, delayed release, once weekly: 90 mg. A separate label; NEVER studied in children
• Olanzapine and fluoxetine capsules: fluoxetine 25 mg or 50 mg with olanzapine 3, 6 or 12 mg

Dosing

• Age:
  • MDD: 8 y/o and older
  • OCD: 7 y/o and older
  • Bipolar I depression, with olanzapine: 10 y/o and older
• Onset: 4 weeks or longer in MDD; 5 weeks or longer in OCD
• Duration: continuous with once-daily dosing
• Initial Dose:
  • Pediatric MDD: 10 or 20 mg/day; 10 mg/day if lower weight
  • Pediatric OCD: 10 mg/day at any weight
  • Adults: 20 mg/day
• Titration:
  • Pediatric MDD: to 20 mg/day after 1 week; OCD: to 20 mg/day after 2 weeks
  • Further increases only after several more weeks, never weekly
• Max Dose:
  • Ceiling at any age or indication: 80 mg/day
  • Pediatric OCD: 60 mg/day, or 30 mg/day if lower weight
  • Pediatric MDD: no separate maximum; trials used 10 to 20 mg/day
• Considerations: Give in the morning; a dose above 20 mg/day may be split between morning and noon. Use a lower or less frequent dose in cirrhosis.

Pharmacology

• Mechanism: Blocks presynaptic serotonin reuptake at SERT, without the tricyclics' anticholinergic and sedative burden
• Delivery / Release: immediate release; food does not affect bioavailability
• Metabolism: hepatic via CYP2D6 to active norfluoxetine. Half-life 4 to 6 days on chronic dosing, norfluoxetine 4 to 16 days, steady state at 4 to 5 weeks
• Class Positioning: a POTENT CYP2D6 inhibitor persisting up to 5 weeks after the last dose, unlike Zoloft. The only SSRI with a pediatric MDD indication

Indications

• Major Depressive Disorder (ICD-10: F32.x, F33.x): 8 y/o and older
• Obsessive-Compulsive Disorder (ICD-10: F42.x): 7 y/o and older
• Bulimia Nervosa (ICD-10: F50.2): adults only, at 60 mg/day
• Panic Disorder (ICD-10: F41.0): adults only
• Bipolar I depression, with olanzapine only (ICD-10: F31.x): 10 y/o and older
• Treatment-resistant depression, with olanzapine only: adults

Off-Label Uses

• Pediatric anxiety disorders (ICD-10: F41.1, F40.10, F93.0): supported; AHRQ graded SSRIs moderate to high, with CBT outperforming fluoxetine (AHRQ 2017). On-label alternative: Cymbalta from 7 y/o
• MDD in CHILDREN rather than adolescents (ICD-10: F32.x): graded low in adolescents, INSUFFICIENT in children (AACAP 2023)
• Bulimia nervosa in adolescents (ICD-10: F50.2): insufficient at any dose

Contraindications & Warnings

• Boxed Warning: SUICIDAL THOUGHTS AND BEHAVIORS in children, adolescents and young adults.
  • Monitor closely for worsening and emergent suicidality in the initial few months and at every dose change, up or down.
  • Observation must include DAILY observation at home. Dispense the smallest quantity consistent with good management.
• Contraindicated:
  • An MAOI concurrently, within 5 WEEKS of stopping Prozac, or Prozac within 14 days of an MAOI. That 5-week exit washout is longer than the rest of the class, set by norfluoxetine's half-life.
  • Linezolid or intravenous methylene blue.
  • Pimozide and thioridazine; fluoxetine raises both via CYP2D6 and all three prolong QT.
• Use with caution:
  • Seizure history; long QT, hypokalemia, hypomagnesemia, recent myocardial infarction, heart failure, bradyarrhythmias.
  • Narrow angles without a patent iridectomy; diabetes; cirrhosis, needing a lower dose.
  • Underweight patients; NSAIDs, aspirin, anticoagulants, diuretics; prior rash on fluoxetine.
• Screen before starting:
  • Personal and family history of bipolar disorder, mania or hypomania; baseline height, weight and sexual function.
  • QT risk factors, and a medication list for CYP2D6 substrates, MAOIs and anticoagulants.

Drug Interactions

• MAOIs (phenelzine, selegiline, linezolid, methylene blue): contraindicated. 14 days before starting Prozac, 5 WEEKS after stopping it
• CYP2D6 substrates including atomoxetine (Strattera, TCAs, antipsychotics): start low, and treat anyone dosed within the previous 5 weeks as still on fluoxetine.
  • For atomoxetine, lengthen the titration interval to 4 weeks rather than lowering the target dose.
  • This pair, and Qelbree, stack two pediatric suicidality boxed warnings.
• Bupropion (Wellbutrin XL): doubles 2D6 inhibition and stacks seizure cautions
• Other serotonergic drugs (SSRIs, SNRIs, triptans, tramadol, lithium, AMPHETAMINES): serotonin syndrome. Stop all for agitation, hyperthermia, rigidity or myoclonus
• Tricyclics, phenytoin, carbamazepine: levels rise for weeks; check when fluoxetine starts and stops
• NSAIDs, aspirin, warfarin: bleeding; check the INR at both ends
• QT-prolonging drugs (ziprasidone, erythromycin, amiodarone, methadone): avoid, or obtain an ECG before each increase

Administration

• Give once daily in the morning; split a dose above 20 mg for daytime nausea rather than reducing it.
• With or without food. Swallow capsules and tablets whole; the oral solution is the only form delivering below 10 mg.
• Missed dose: resume at the next dose; do not double up.
• Never use the 90 mg once-weekly capsule in a pediatric patient or in place of daily dosing.
• Switching to an MAOI: allow 5 weeks off fluoxetine. From an MAOI: allow 14 days.

Side Effects

• Common: nausea, insomnia, nervousness, somnolence, anxiety, diarrhea, anorexia, dry mouth, tremor, asthenia.
  • Pediatric trials add thirst, hyperkinesia, agitation, epistaxis, urinary frequency and menorrhagia.
• Serious:
  • Suicidal thoughts and behavior: the boxed warning. Change the regimen, including stopping, if suicidality emerges.
  • Serotonin syndrome: stop every serotonergic agent immediately and treat supportively.
  • Mania or hypomania, in 2.6% of pediatric patients. Stop and reassess for bipolar disorder.
  • Rash and systemic hypersensitivity. Discontinue on any unexplained rash.
  • Hyponatremia and SIADH; QT prolongation and torsades; seizures.
  • Growth lag: 1.1 cm and 1.1 kg below placebo at 19 weeks.
  • Bleeding; angle-closure glaucoma; sexual dysfunction.

Monitoring & Labs

• Suicidality: every visit for 3 months, at every dose change in either direction, then every 3 months. Instruct the family in DAILY home observation for the first month
• Activation and mania: screen for bipolar history before the first dose, then ask about reduced sleep need, pressured speech and elevated mood every 3 months
• Growth: plot height and weight at baseline, every 3 months for the first year, then every 6 months
• Hyponatremia: check sodium for new headache, confusion or unsteadiness, or when a diuretic is started
• Bleeding: ask about bruising and nosebleeds every 3 months; check the INR on warfarin
• Response: do not judge efficacy before 4 weeks in MDD or 5 weeks in OCD; reassess every 6 months, with sexual function

Discontinuation & Taper

• Effectively self-tapering: both fluoxetine and norfluoxetine fall gradually at the end of therapy, minimizing discontinuation symptoms.
• The contrast that drives drug choice: Zoloft has a 26-hour half-life and must be reduced gradually. Where adherence is unreliable, fluoxetine is safer.
• A gradual reduction is still preferred; reactions include dysphoric mood, irritability, dizziness, electric shock sensations and insomnia. If they follow a decrease, resume the previous dose.
• Drug holidays are not appropriate; steady state takes 4 to 5 weeks, so a break resets the clock.
• Interactions outlast the drug: for 5 weeks an MAOI and thioridazine stay contraindicated.

Pregnancy & Lactation

• Pregnancy: decades of data have not established increased risk of major birth defects or miscarriage.
  • Later exposure may raise the risk of persistent pulmonary hypertension of the newborn; third-trimester exposure has produced respiratory distress, feeding difficulty, hypotonia and irritability.
  • Weigh rather than abstain: women who stopped antidepressants in pregnancy relapsed more often.
• Lactation: present in human milk; agitation, irritability, poor feeding and poor weight gain reported.
  • Milk levels run HIGHER than most other SSRIs, relative infant dose roughly 2.4% to 7%, with no adverse developmental effects to 5 years (LactMed 2026).
  • Zoloft is the lower-exposure choice when starting an SSRI while nursing.
• Exposure Registry: National Pregnancy Registry for Antidepressants, 1-844-405-6185, womensmentalhealth.org

Counseling Points

• Counsel the family on:

  • Nothing much happening for two weeks. Name the review point aloud: 4 weeks for depression, 5 for OCD.
  • Taking it in the morning, and splitting a dose above 20 mg if nausea is the problem.
  • A missed dose being forgiving here, and a dose increase taking weeks to show for the same reason.
  • Never accepting a 90 mg once-weekly capsule; it has never been studied in children.
  • Telling every future prescriber about fluoxetine taken within the last 5 weeks.
  • Daily home observation for the first month for out-of-character behaviour.

• Advise them to call for:

  • New or worsening talk of self-harm, or any abrupt mood change after a dose change.
  • Days without needing sleep, much faster speech, or a jump in energy.
  • Any rash or hives, particularly with fever or joint swelling.
  • Shivering, twitching, stiffness, racing heart, sweating and confusion together.
  • Nosebleeds that will not stop, unexplained bruising, or black stools.
  • Fainting, irregular heartbeat, or a seizure.

References

1. DailyMed. Prozac (fluoxetine) capsule. Dista Products Company. 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c88f33ed-6dfb-4c5e-bc01-d8e36dd97299
2. DailyMed. Fluoxetine delayed release capsule, 90 mg weekly. Dr. Reddy's. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=887fc670-db67-4cfe-967b-46b38375dae5
3. LactMed. Fluoxetine. 2026. https://www.ncbi.nlm.nih.gov/books/NBK501186/
4. AHRQ. Anxiety in children. CER No. 192, 17-EHC023-EF. 2017. https://www.ncbi.nlm.nih.gov/books/NBK476277/
5. AACAP. Depressive disorders practice guideline. 2023. PMID 36273673. https://www.jaacap.org/article/S0890-8567(22)01852-4/fulltext
6. FDA. NDC Directory, openFDA, generic name fluoxetine. 2026. https://api.fda.gov/drug/ndc.json?search=generic_name:%22fluoxetine%22&limit=1000