Fluoxetine

1. Drug Class

Fluoxetine is an antidepressant belonging to the class of Selective Serotonin Reuptake Inhibitors (SSRIs).

2. Mechanism of Action

Fluoxetine works by selectively inhibiting the reuptake of serotonin (5-HT) in the central nervous system.

• It blocks the serotonin transporter (SERT) in presynaptic neurons
• This leads to increased serotonin levels in the synaptic cleft
• Enhanced serotonergic neurotransmission improves mood and emotional stability

Additionally:

• Mild activity on 5-HT2 receptors may contribute to activating effects
• Minimal effect on norepinephrine compared to other antidepressants

3. Pharmacokinetics

• Absorption: Well absorbed orally (bioavailability ~70–90%)
• Peak levels: 6–8 hours after administration
• Protein binding: ~94%
• Half-life:
  • Fluoxetine: 2–4 days
  • Active metabolite (norfluoxetine): 7–14 days
• Onset of action: Typically 2–4 weeks

The long half-life reduces withdrawal risk but prolongs drug interactions.

4. Indications

FDA-Approved Uses

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Panic Disorder (± agoraphobia)
• Bulimia Nervosa
• Bipolar depression (with olanzapine)
• Treatment-resistant depression (with olanzapine)

Common Off-Label Uses

• Premenstrual dysphoric disorder (PMDD)
• Generalized anxiety disorder (GAD)
• Post-traumatic stress disorder (PTSD)
• Social anxiety disorder
• Binge eating disorder

5. Dosage and Administration

• Typical starting dose: 20 mg once daily
• Effective range: 20–40 mg/day (may increase if needed)
• Maximum dose: up to 80 mg/day (depending on indication)
• Can be taken with or without food

Also available as:

• Capsules, tablets, oral solution
• Weekly delayed-release formulation (90 mg)

6. Adverse Effects

Common Side Effects

• Nausea, diarrhea
• Insomnia or nervousness
• Headache
• Dry mouth
• Loss of appetite (anorexia)
• Sweating
• Sexual dysfunction (↓ libido, delayed ejaculation)

Serious Adverse Effects

• Suicidal ideation (especially in young adults)
• Serotonin syndrome (life-threatening)
• QT interval prolongation (rare)
• Seizures (rare)
• Mania activation (in bipolar disorder)

7. Contraindications

Fluoxetine should NOT be used in:

• Hypersensitivity to fluoxetine
• Concomitant use with MAO inhibitors (or within 14 days)
• Use with pimozide or thioridazine (risk of QT prolongation)

8. Drug Interactions

• Strong inhibitor of CYP2D6 enzyme
• Increases levels of:
  • Tricyclic antidepressants
  • Antipsychotics
  • Antiarrhythmics
• Risk of serotonin syndrome with other serotonergic drugs
• Increased bleeding risk with NSAIDs or anticoagulants

9. Warnings and Precautions

• Monitor for behavioral changes and suicidality
• Use cautiously in:
  • Seizure disorders
  • Elderly patients
  • Hepatic impairment
• Avoid abrupt discontinuation (taper gradually)

10. Toxicity & Overdose

• Usually not fatal alone, but dangerous with:
  • Alcohol
  • Other serotonergic drugs
• Overdose may cause:
  • Agitation
  • Tachycardia
  • Serotonin syndrome
• Management is supportive care

Patient Disclaimer

This information is for educational purposes only and does not replace medical advice. Fluoxetine should only be used under the supervision of a qualified healthcare professional. Patients must not start, stop, or change the dose without consulting their doctor. Seek immediate medical attention if severe side effects occur, such as suicidal thoughts, severe agitation, or symptoms of serotonin syndrome (e.g., confusion, fever, muscle stiffness).