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fluoxetine

Brand: Prozac, Sarafem, Selfemra

⚠ BBW Prototype Drug
Drug Class: antidepressant
Drug Family: antidepressant
Subclass: selective serotonin reuptake inhibitor (SSRI)
Organ Systems: cns

Mechanism of Action

Selectively inhibits the presynaptic serotonin reuptake transporter (SERT), increasing synaptic serotonin concentrations; minimal effects on norepinephrine or dopamine transporters; also a potent CYP2D6 inhibitor.

serotonin reuptake transporter (SERT)

Indications

  • major depressive disorder
  • obsessive-compulsive disorder
  • panic disorder
  • bulimia nervosa
  • premenstrual dysphoric disorder (Sarafem)
  • bipolar I depression (with olanzapine)

Contraindications

  • concurrent MAOIs (allow 14-day washout)
  • concurrent thioridazine or pimozide (CYP2D6 inhibition risk)
  • concurrent linezolid or IV methylene blue

Adverse Effects

Common

  • nausea
  • insomnia
  • headache
  • sexual dysfunction (anorgasmia, delayed ejaculation)
  • anxiety
  • weight changes

Serious

  • serotonin syndrome
  • suicidal ideation (black box; particularly in patients <24 years)
  • bleeding (GI, surgical)
  • QTc prolongation
  • hyponatremia (SIADH)

Pharmacokinetics (ADME)

Absorption Well absorbed (~72%); not significantly affected by food
Distribution Highly protein-bound (94%); Vd 20–45 L/kg; crosses BBB
Metabolism CYP2C9 and CYP2D6 to active metabolite norfluoxetine (also a potent CYP2D6 inhibitor)
Excretion Renal (~60%) and fecal; hepatic dose adjustment needed
Half-life 1–3 days (fluoxetine); 4–16 days (norfluoxetine) — longest half-life of all SSRIs
Onset Antidepressant effect: 2–4 weeks
Peak 6–8 hours
Duration Weeks after discontinuation due to long half-life
Protein Binding 94%
Vd 20–45 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
MAOIs serotonin syndrome — potentially fatal; 14-day washout required before MAOI; 5-week washout after stopping fluoxetine major
tricyclic antidepressants CYP2D6 inhibition increases TCA levels major
warfarin CYP2C9 inhibition increases warfarin levels; bleeding risk major

Nursing Considerations

  1. Monitor for suicidal ideation, especially in first 4 weeks of therapy and after dose changes; schedule follow-up within 1 week of initiation in young adults
  2. Due to long half-life, discontinuation syndrome is less likely than with other SSRIs; however, a 5-week washout is required before starting an MAOI
  3. Monitor for signs of serotonin syndrome: hyperthermia, agitation, clonus, hyperreflexia, diaphoresis — medical emergency
  4. Assess baseline sexual function; sexual dysfunction is common and often a reason for nonadherence — counsel patients and consider dose reduction or drug holiday strategy

Clinical Pearls

  • Fluoxetine's extremely long half-life (1–6 weeks for parent + metabolite) is both an advantage (missed doses matter less, no discontinuation syndrome) and a disadvantage (5-week MAOI washout needed, drug interactions persist weeks after stopping)
  • Fluoxetine/olanzapine combination (Symbyax) is FDA-approved for bipolar I depression — an uncommon but important indication

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

Antidepressant Bipolar I Depression (with Olanzapine) Bulimia Nervosa Major Depressive Disorder Obsessive-compulsive Disorder Panic Disorder Premenstrual Dysphoric Disorder (Sarafem)
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