Generic Name

Prozac

Mechanism

Prozac selectively inhibits the serotonin transporter (SERT) at presynaptic serotoninergic nerve terminals, boosting extracellular 5‑hydroxytryptamine (5‑HT).
• Selective: minimal activity on norepinephrine or dopamine transporters.
• Non‑competitive: no direct binding to postsynaptic sites.
• Result: increased serotonergic neurotransmission, leading to anxiolytic and antidepressant effects.

Pharmacokinetics

• Absorption: Rapid, high oral bioavailability (~70 %).
• Distribution: Large volume of distribution (~2 L/kg), protein‑bound (~94 %).
• Metabolism: Primarily hepatic via CYP2D6 → 4‑hydroxy‑fluoxetine; minor CYP2C19 contribution.
• Half‑life: Active metabolite t½ ≈ 4–6 days; terminal t½ ≈ 4–6 weeks.
• Excretion: Renal (≈ 70 %) and biliary.
• Drug interactions: Inhibits CYP2D6 → ↑ serum levels of drugs metabolized by this enzyme; induces CYP1A2, affecting clozapine, ciprofloxacin, etc.

Indications

• Major Depressive Disorder (MDD)
• Obsessive‑Compulsive Disorder (OCD)
• Panic Disorder
• Social Anxiety Disorder
• Premenstrual Dysphoric Disorder (PMDD)
• Post‑partum Depression (PPD)
• Chronic pain (in adjunctive role)

Contraindications

• Acute angle‑closure glaucoma (risk of increased intraocular pressure)
• Concurrent MAO inhibitor use (serotonin‑syndrome risk) – require 14‑day washout
• Severe hepatic impairment (significant reduction in metabolism)
• Pregnancy: Category C; limited data—use only if benefits outweigh risks
• Pediatric patients < 12 years: off‑label, careful risk–benefit assessment
• Black‑box warning: increased suicidality in adolescents and young adults (monitor closely)

Dosing

• Administer with or without food; late‑day doses may reduce insomnia.
• Preferred oral formulation (tablet, capsule, syrup).
• If dose is held > 3 days → consider rebound anxiety; taper gradually.

Adverse Effects

• Common
• Nausea, vomiting (often early, improves after 1–2 weeks)
• Headache, dizziness
• Insomnia or, conversely, somnolence (dose‑dependent)
• Sexual dysfunction (decreased libido, anorgasmia)
• Weight change (usually gain in adults, slight loss in adolescents)
• Serious
• Serotonin syndrome (neuromuscular hyperactivity, autonomic instability)
• Suicidal ideation/behavior in adolescents
• Hyponatremia (especially in > 65 yrs, concurrent diuretics)
• Hepatotoxicity (rare; ↑ ALT/AST, jaundice)
• QTc prolongation (rare; monitor if combined with other QT‑prolongers)
• Overdose → CNS depression, seizures, cardiac arrhythmias

Monitoring

• Baseline: CBC, CMP, liver function tests (ALT/AST, bilirubin), ECG (if risk factors)
• Follow‑up:
• Liver enzymes at 1–3 months for chronic therapy
• Serum sodium (especially in elderly, fluid‑censor patients)
• Weight and BMI quarterly
• Mental status & suicidal ideation (every visit for < 25 yrs)
• Toxicolology: CRP, creatinine clearance (if renal impairment)
• Drug interactions: Screen for MAOIs, serotonergic agents (TCAs, tramadol, MDMA), CYP2D6 inhibitors (cimetidine), and cardiac blockers (metoprolol, azithromycin).

Clinical Pearls

• Long half‑life → medication washout persists ≈ 2 weeks; abrupt discontinuation can precipitate rebound anxiety or serotonin withdrawal syndrome.
• CYP2D6 poor metabolizers: ↑ plasma fluoxetine; may need dose reduction or slower titration.
• High potency antagonist of CYP2D6 can elevate co‑administered drugs (e.g., metoprolol) → adjust doses or choose alternative UIAs.
• Insomnia vs. somnolence: split dosing (morning 10 mg + bedtime 10 mg) reduces insomnia while minimizing next‑day sedation.
• Adjunctive use for depression + chronic pain: low‑dose (5 mg) may relieve neuropathic pain without full antidepressant effect.
• Switching strategy: When transitioning from older SSRI (e.g., citalopram) to *Prozac*, maintain overlap for 2–3 weeks due to longer half‑life to avoid serotonin depletion.
• Pregnancy & lactation: Animal studies indicate no major teratogenicity; however, infant serum levels rise when nursing; weigh benefits of maternal mood stability vs. neonatal exposure.
• Weight changes: Monitor as data suggest slight weight gain in adults but pronounced weight loss in pediatric patients; address with diet/exercise counseling.
• Suicidality monitoring: Employ validated scales (e.g., PHQ‑9) at baseline and every 2–4 weeks in young adults.

Prozac remains one of the most prescribed SSRIs due to its favorable side‑effect profile, long half‑life, and versatility across psychiatric disorders. Accurate dose titration, vigilant monitoring, and awareness of drug interactions are essential for optimizing therapeutic outcomes while minimizing risks.