Fluoxetine

Fluoxetine

Prozac Sarafem Rapiflux Selfemra

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Updated: December 06, 2025

Overview

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant first approved by the FDA in 1987. It is widely used for the treatment of major depressive disorder and various other psychiatric conditions due to its favorable side effect profile compared to older antidepressants. Fluoxetine works by increasing serotonin levels in the synaptic cleft, which helps regulate mood, emotions, and behavior. It has a long half-life and active metabolite, making it suitable for once-daily dosing and having a lower risk of withdrawal symptoms upon discontinuation compared to shorter-acting SSRIs.

Drug Class

Selective serotonin reuptake inhibitor (SSRI) Therapeutic category: Antidepressant

Mechanism of Action

Fluoxetine selectively inhibits serotonin reuptake at the presynaptic neuronal membrane by blocking the serotonin transporter (SERT). • Increases synaptic serotonin concentration • Enhances serotonergic neurotransmission • Downregulates postsynaptic serotonin receptors with chronic use

Pharmacokinetics

Absorption: Well absorbed (70-90% bioavailability), not significantly affected by food Distribution: Extensive tissue distribution (Vd = 20-45 L/kg), 94% protein bound Metabolism: Hepatic via CYP2D6 and CYP3A4 to active metabolite norfluoxetine Excretion: Primarily renal (80%), 15% fecal Half-life: Fluoxetine: 1-3 days (acute), 4-6 days (chronic) Norfluoxetine: 7-9 days

Pharmacodynamics

• Increases synaptic serotonin levels within hours • Therapeutic antidepressant effects typically require 2-4 weeks • Downregulates 5-HT1A autoreceptors over time • Minimal affinity for histaminic, cholinergic, or adrenergic receptors

Indications

• Major depressive disorder: Treatment of acute episodes and maintenance therapy • Obsessive-compulsive disorder (OCD): Reduces frequency/intensity of obsessions/compulsions • Bulimia nervosa: Decreases binge-eating and purging behaviors • Panic disorder: Prevents panic attacks with/without agoraphobia • Premenstrual dysphoric disorder (PMDD): Brand Sarafem specifically approved for this indication

Contraindications

Absolute: • Concurrent use with MAOIs or within 14 days of MAOI discontinuation • Known hypersensitivity to fluoxetine Relative: • Uncontrolled seizure disorders • Bipolar disorder (may induce mania) • Severe hepatic impairment • Concurrent use of other serotonergic drugs

Dosage & Administration

Major depressive disorder: Initial 20 mg daily AM, may increase to 60 mg/day OCD: Initial 20 mg daily, target range 20-60 mg/day Bulimia nervosa: 60 mg daily (may start at 20 mg and titrate) Panic disorder: Start at 10 mg daily, increase to 20 mg/day after 1 week PMDD: 20 mg daily continuously or luteal phase dosing

Special Populations

Pediatric: FDA-approved for MDD (≥8 years) and OCD (≥7 years) Start with 10 mg daily, max 20 mg/day for children <12 years Geriatric: Consider lower starting dose (10 mg), slower titration Renal impairment: No significant adjustment needed Hepatic impairment: Reduce dose or frequency (half-life prolonged 2-3x)

Adverse Effects

Common (>10%): • Nausea, diarrhea, anorexia • Headache, nervousness • Insomnia, somnolence • Dry mouth, sweating Serious (<1%): • Serotonin syndrome • Suicidal ideation (especially <25 years) • Seizures • QT prolongation • Hyponatremia/SIADH

Drug Interactions

• MAOIs: Risk of serotonin syndrome (contraindicated) • Other serotonergic drugs (tramadol, triptans): Increased serotonin toxicity risk • Warfarin: Increased bleeding risk (monitor INR) • CYP2D6 substrates (tricyclics, antipsychotics): Increased levels of co-administered drugs • QTc-prolonging agents: Additive QT prolongation risk

Warnings & Precautions

• Black box warning: Increased risk of suicidal thinking/behavior in children/adolescents/young adults • Monitor for activation of mania/hypomania • Risk of bleeding (especially with anticoagulants) • Potential for seizures at higher doses • Discontinuation syndrome possible (taper recommended)

Pregnancy & Lactation

Pregnancy: Category C • Potential neonatal complications if used in third trimester • Weigh risks vs benefits of treatment Lactation: Excreted in breast milk • Concentrations in milk approximately 25% of maternal serum • Consider monitoring infant for irritability/feeding difficulties

Monitoring Parameters

• Mental status and suicide risk assessment • Signs of serotonin syndrome (hyperthermia, rigidity, autonomic instability) • Weight/BMI in pediatric patients • Electrolytes in elderly (hyponatremia risk) • Liver function tests in hepatic impairment • Therapeutic drug monitoring not routinely required

Patient Counseling

• Take in morning to avoid insomnia • Therapeutic effects may take 2-4 weeks • Do not stop abruptly without medical supervision • Report worsening depression or suicidal thoughts • Avoid alcohol consumption • Use caution when driving until effects are known • Notify providers of all medications/supplements being taken

Storage & Stability

• Store at 20-25°C (68-77°F) • Protect from light • Oral solution stable for 14 days after dilution • Capsules/tablets stable in original packaging

Clinical Pearls

• Consider long half-life when switching to/from other antidepressants • Norfluoxetine contributes to prolonged activity after discontinuation • Often preferred in patients with fatigue (activating properties) • Lower sexual side effects compared to some other SSRIs • Useful in patients with poor compliance due to long half-life

References

• FDA Prescribing Information: Prozac (fluoxetine) Label • Stahl SM. Essential Psychopharmacology (4th ed) • UpToDate: Fluoxetine Drug Information • Drug Facts and Comparisons (2023 ed) • Haddad PM, et al. SSRI discontinuation syndrome. CNS Drugs. 2016

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