Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) indicated for the management of major depressive disorder, obsessive-compulsive disorder, panic disorder, and bulimia nervosa in adults. As one of the most extensively studied antidepressants worldwide, it offers a well-established efficacy and safety profile supported by decades of clinical use and post-marketing surveillance. Its mechanism of action involves potent inhibition of serotonin reuptake in the central nervous system, leading to increased synaptic serotonin concentrations and subsequent improvement in mood, anxiety, and compulsive symptoms.

Features

• Active ingredient: Fluoxetine hydrochloride
• Available formulations: Capsules (10 mg, 20 mg, 40 mg), delayed-release capsules (90 mg), oral solution (20 mg/5 mL)
• Pharmacologic class: Selective serotonin reuptake inhibitor (SSRI)
• Half-life: 2–3 days (norfluoxetine metabolite: 7–9 days)
• Bioavailability: Approximately 72%
• Protein binding: 94.5%
• Metabolism: Hepatic, primarily via CYP2D6 and CYP2C9 isoenzymes
• Excretion: Primarily renal (60%), with 15% fecal elimination

Benefits

• Demonstrated efficacy in reducing symptoms of major depressive disorder within 2–4 weeks of initiation
• Reduction in frequency and severity of obsessive-compulsive behaviors and panic attacks
• Decreased binge-eating and purging behaviors in bulimia nervosa
• Long half-life allows for once-daily dosing and reduces withdrawal symptoms upon discontinuation
• Lower anticholinergic and cardiovascular side effect profile compared to tricyclic antidepressants
• FDA-approved for pediatric use in depression and OCD (ages 8 and older)

Common use

Fluoxetine is primarily prescribed for the treatment of major depressive disorder (MDD) in adults and pediatric patients aged 8 years and older. It is also FDA-approved for obsessive-compulsive disorder (both adult and pediatric populations), panic disorder with or without agoraphobia, and acute and maintenance treatment of bulimia nervosa. Off-label uses include treatment of premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), and certain anxiety spectrum disorders. Clinical response typically emerges within 1–4 weeks, with full therapeutic effects often requiring 8–12 weeks of continuous therapy.

Dosage and direction

Initial dosing:

• Depression: 20 mg once daily in the morning
• OCD: 20 mg daily (may increase to 60 mg maximum)
• Panic disorder: Start with 10 mg daily, increase to 20 mg after one week
• Bulimia nervosa: 60 mg daily (may start with 20 mg and titrate)
• Pediatric dosing (ages 8–18): Start with 10–20 mg daily

Administration:
Take with or without food. Swallow capsules whole; do not crush or chew. For once-weekly formulation (90 mg), take exactly 7 days after last daily dose. Dosage adjustments required in hepatic impairment and CYP2D6 poor metabolizers. Avoid abrupt discontinuation; taper gradually over at least 2 weeks.

Precautions

Monitor for clinical worsening and suicide risk, especially during initial treatment and dosage adjustments. Use caution in patients with history of seizures, mania, or hyponatremia. May increase risk of bleeding, particularly when combined with NSAIDs or anticoagulants. Screen for angle-closure glaucoma prior to initiation. Use with caution in elderly patients due to potential for hyponatremia and falls. Regular monitoring of weight and growth parameters recommended in pediatric patients.

Contraindications

Absolute contraindications include:

• Concomitant use with MAOIs or within 14 days of MAOI discontinuation
• Known hypersensitivity to fluoxetine or any component of the formulation
• Concomitant use with pimozide or thioridazine
• Uncontrolled narrow-angle glaucoma

Relative contraindications include:

• Severe hepatic impairment (Child-Pugh C)
• QT prolongation or risk factors for QT prolongation
• History of serotonin syndrome
• Pregnancy (unless clearly needed—Category C risk)

Possible side effect

Common (≥1%):

• Headache (21%), insomnia (14%), nausea (12%)
• Diarrhea (8%), dry mouth (6%), fatigue (5%)
• Anxiety (5%), dizziness (5%), decreased libido (4%)

Serious (<1%):

• Serotonin syndrome
• Suicidal ideation (particularly in young adults)
• QT prolongation and ventricular arrhythmias
• Severe cutaneous adverse reactions (SCARs)
• Syndrome of inappropriate antidiuretic hormone (SIADH)
• Manic episodes
• Seizures
• Bleeding events

Drug interaction

Major interactions:

• MAOIs: Risk of serotonin syndrome (contraindicated)
• CYP2D6 substrates: Increased concentrations of drugs like codeine, tamoxifen
• Anticoagulants: Increased bleeding risk
• Triptans: Enhanced serotonergic effects
• Tricyclic antidepressants: Significantly increased TCA levels
• Antiarrhythmics: QT prolongation risk with flecainide, propafenone

Moderate interactions:

• NSAIDs: Additive bleeding risk
• Other serotonergic drugs: Possible serotonin syndrome
• CYP2D6 inhibitors: May increase fluoxetine levels

Missed dose

If a dose is missed, take it as soon as remembered unless it is close to the next scheduled dose. Do not double the dose to make up for a missed one. For once-weekly formulation: If missed, take as soon as remembered, then resume regular weekly schedule. Do not take more than one capsule within 7 days.

Overdose

Symptoms: Nausea, vomiting, agitation, restlessness, hypomania, seizures, ECG changes (including QT prolongation). Serotonin syndrome may occur with severe overdose.
Management: Supportive care with gastric lavage if presented early. Activated charcoal may be beneficial. No specific antidote exists. Monitor cardiac function for at least 24 hours. Benzodiazepines for agitation; anticonvulsants for seizures. Serotonin syndrome may require cyproheptadine and intensive care support.

Storage

Store at 20–25°C (68–77°F); excursions permitted to 15–30°C (59–86°F). Keep container tightly closed. Protect from light and moisture. Do not freeze oral solution. Keep out of reach of children. Dispose of unused medication via drug take-back programs.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Always consult a healthcare professional before starting or changing any medication regimen. Individual response to fluoxetine may vary. Not all uses described may be approved in your country. Full prescribing information should be reviewed before administration.

Reviews

Clinical Psychiatry News: “Fluoxetine remains a cornerstone in antidepressant therapy due to its predictable pharmacokinetics and extensive safety database.”
Journal of Affective Disorders: “Meta-analyses confirm fluoxetine’s superiority over placebo in moderate-to-severe depression with NNT of 6.”
Pediatric Pharmacology Journal: “The only SSRI with FDA approval for depression in children aged 8+,