Introduction
Prozac (fluoxetine hydrochloride) is a selective serotonin reuptake inhibitor (SSRI) antidepressant approved by the FDA in 1987. It was the first SSRI to be marketed in the United States and remains one of the most widely prescribed antidepressants worldwide. Prozac is indicated for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder, bulimia nervosa, and premenstrual dysphoric disorder (PMDD).
Mechanism of Action
Prozac exerts its therapeutic effects primarily through potent inhibition of serotonin reuptake at the presynaptic neuronal membrane. By blocking the serotonin transporter (SERT), fluoxetine increases synaptic concentrations of serotonin in the central nervous system, enhancing serotonergic neurotransmission. This action is believed to underlie its antidepressant and anxiolytic effects. Fluoxetine has minimal affinity for adrenergic, cholinergic, GABA, dopamine, or histaminergic receptors.
Indications
FDA-approved indications:
- Major depressive disorder (MDD) in adults and pediatric patients (≥8 years)
- Obsessive-compulsive disorder (OCD) in adults and pediatric patients (≥7 years)
- Panic disorder with or without agoraphobia
- Bulimia nervosa
- Premenstrual dysphoric disorder (PMDD)
Off-label uses (with supporting evidence):
- Social anxiety disorder
- Posttraumatic stress disorder (PTSD)
- Generalized anxiety disorder
- Treatment-resistant depression (often in combination)
Dosage and Administration
Standard dosing:- Depression: 20 mg daily initially, may increase after several weeks (max 80 mg/day)
- OCD: 20 mg daily initially, may increase (max 80 mg/day)
- Panic disorder: 10 mg daily initially, may increase (max 60 mg/day)
- Bulimia: 60 mg daily
- PMDD: 20 mg daily
- Usually administered in the morning
- May be taken with or without food
- Available as capsules, tablets, liquid, and delayed-release formulations
- Hepatic impairment: Reduced dose or less frequent dosing
- Renal impairment: Caution advised
- Elderly: Consider lower starting doses
- Pediatrics: Weight-based dosing recommended
Pharmacokinetics
Absorption: Well absorbed orally, bioavailability ~70-80%, peak concentrations in 6-8 hours Distribution: Volume of distribution 20-45 L/kg, 94.5% protein bound Metabolism: Extensive hepatic metabolism via CYP2D6 and CYP2C9 to active metabolite norfluoxetine Elimination: Half-life of fluoxetine 2-3 days, norfluoxetine 7-9 days; primarily renal excretionContraindications
- Hypersensitivity to fluoxetine or any component
- Concomitant use with MAOIs or within 14 days of MAOI use
- Concomitant use with pimozide or thioridazine
- Uncontrolled narrow-angle glaucoma
Warnings and Precautions
Black Box Warnings:- Increased risk of suicidal thinking and behavior in children, adolescents, and young adults
- Monitor for clinical worsening and emergence of suicidal thoughts
- Serotonin syndrome risk
- Increased bleeding risk
- Activation of mania/hypomania
- QT prolongation
- Discontinuation syndrome
- Hyponatremia/SIADH
- Bone fractures
Drug Interactions
Major interactions:- MAOIs: Risk of serotonin syndrome (contraindicated)
- Other serotonergic drugs: Increased serotonin syndrome risk
- CYP2D6 substrates: Increased levels of drugs metabolized by CYP2D6
- Warfarin: Increased anticoagulant effect
- Triptans: Increased serotonin syndrome risk
- NSAIDs/aspirin: Increased bleeding risk
- TCAs: Increased tricyclic levels
Adverse Effects
Common (≥10%):- Headache
- Nausea
- Insomnia
- Fatigue
- Diarrhea
- Dry mouth
- Anxiety
- Serotonin syndrome
- Suicidal ideation
- Seizures
- Mania
- Hyponatremia
- Bleeding events
- QT prolongation
Monitoring Parameters
- Mental status and suicidal ideation (especially during initiation)
- Therapeutic response and side effects
- Blood pressure and heart rate
- Electrolytes (particularly sodium)
- Liver function tests
- Bleeding parameters if on anticoagulants
- Weight changes (pediatrics)
- Signs of serotonin syndrome
Patient Education
- Take medication as prescribed; do not stop abruptly
- Therapeutic effects may take 4-6 weeks
- Report worsening depression or suicidal thoughts immediately
- Avoid alcohol consumption
- Use caution when driving or operating machinery
- Inform all healthcare providers about Prozac use
- Report unusual bleeding or bruising
- Notify provider if pregnant or planning pregnancy
- Use reliable contraception
- Be aware of potential sexual side effects
References
1. FDA Prescribing Information: Prozac (fluoxetine hydrochloride) 2. Stahl SM. Essential Psychopharmacology: The Prescriber's Guide. 6th ed. Cambridge University Press; 2017. 3. Hirsch M, Birnbaum RJ. Fluoxetine: pharmacology and administration. UpToDate; 2023. 4. Cipriani A, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357-1366. 5. Hiemke C, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018;51(1-02):9-62. 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder. 3rd ed. 2010.