Fluoxetine (Prozac) ​

Fluoxetine (Prozac) Overview
​Fluoxetine, marketed as Prozac, is a selective serotonin reuptake inhibitor (SSRI) used to treat various mood and anxiety disorders. It was the first SSRI approved by the FDA and remains widely prescribed due to its efficacy and tolerability.
Mechanism of Action
  • Selective Serotonin Reuptake Inhibition:
    Fluoxetine inhibits the serotonin transporter (SERT), preventing the reabsorption of serotonin (5-HT) into presynaptic neurons. This increases serotonin availability in the synaptic cleft, enhancing serotonergic neurotransmission.
  • Delayed Adaptive Changes:
    Chronic use leads to downstream changes in serotonin receptor sensitivity and enhanced neuroplasticity, which contribute to its therapeutic effects.
  • Half-Life:
    Fluoxetine has a long half-life (~4-6 days), and its active metabolite, norfluoxetine, lasts even longer (~7-15 days). This results in a gradual tapering effect and reduces withdrawal symptoms compared to other SSRIs.
Clinical Benefits
  1. Major Depressive Disorder (MDD):
    • Reduces symptoms of depression, including low mood, fatigue, and cognitive dysfunction.
  2. Obsessive-Compulsive Disorder (OCD):
    • Decreases obsessive thoughts and compulsive behaviors.
  3. Panic Disorder:
    • Reduces the frequency and severity of panic attacks.
  4. Bulimia Nervosa:
    • Helps reduce binge-eating and purging behaviors.
  5. Premenstrual Dysphoric Disorder (PMDD):
    • Alleviates mood swings, irritability, and physical symptoms associated with the luteal phase.
  6. Off-Label Uses:
    • Includes generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and bipolar depression (as adjunct therapy).

Dosage
  1. Forms:
    • Capsules, tablets, and liquid solutions.
  2. Dosing Guidelines:
    • MDD and OCD: Start at 20 mg/day; may increase to a maximum of 80 mg/day.
    • Panic Disorder: Start at 10 mg/day; increase to 20 mg/day after 1 week, up to 60 mg/day.
    • Bulimia Nervosa: Typically 60 mg/day.
    • PMDD: 20–30 mg/day continuously or during the luteal phase only.
  3. Administration:
    • Taken once daily, with or without food.
    • Morning dosing is preferred due to the potential for insomnia.

Prevalence of Side Effects
​Fluoxetine is generally well-tolerated but may cause side effects, particularly during the initial weeks of treatment.
Common Side Effects (10–30% of patients):
  • Neurological: Headache, insomnia, drowsiness, dizziness.
  • Gastrointestinal: Nausea, diarrhea, dry mouth.
  • Other: Sweating, appetite changes, weight changes (usually loss initially).
Less Common Side Effects:
  • Sexual dysfunction (e.g., decreased libido, anorgasmia).
  • Anxiety, restlessness, or jitteriness.
Rare but Serious Side Effects:
  1. Serotonin Syndrome:
    • Symptoms include agitation, confusion, rapid heart rate, and tremors (especially when combined with other serotonergic drugs).
  2. QT Prolongation:
    • May increase the risk of abnormal heart rhythms in predisposed individuals.
  3. Increased Risk of Suicidal Thoughts:
    • Most notable in children, adolescents, and young adults during the initial treatment phase.
  4. Hyponatremia:
    • More common in older adults or those on diuretics.
  5. Mania/Hypomania:
    • Can occur in individuals with undiagnosed bipolar disorder.

Efficacy
  • Fluoxetine is highly effective in treating depressive and anxiety disorders, with response rates comparable to other SSRIs.
  • Its long half-life provides smoother discontinuation compared to other SSRIs.
  • Combined treatment with psychotherapy enhances outcomes for most disorders, particularly OCD and MDD.

Special Considerations
  • Drug Interactions:
    • Potent inhibitor of CYP2D6, which can affect the metabolism of other medications.
    • Avoid combining with MAOIs, other serotonergic drugs, or St. John’s Wort.
  • Pregnancy and Breastfeeding:
    • Use with caution during pregnancy. May be associated with neonatal adaptation syndrome.
    • Small amounts are excreted in breast milk but are generally considered safe.
  • Gradual Onset:
    • Therapeutic effects typically take 4–6 weeks to become fully evident.
  • 1. Official Prescribing Information
  • Fluoxetine (Prozac) FDA-approved package insert and labeling.
    Available at FDA.gov.
  • 2. Clinical Pharmacology and Pharmacotherapy References
  • Brunton, L. L., Knollmann, B. C., & Hilal-Dandan, R. (2017). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education.
  • Stahl, S. M. (2013). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed.). Cambridge University Press.
  • 3. Peer-Reviewed Journals
  • Cipriani, A., et al. (2018). "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." The Lancet.
    DOI: 10.1016/S0140-6736(17)32802-7.
  • 4. Clinical Guidelines
  • American Psychiatric Association (APA). (2010). Practice Guidelines for the Treatment of Patients with Major Depressive Disorder.
    Available at psychiatry.org.
  • 5. Drug Information Databases
  • Lexicomp Online, Fluoxetine Monograph.
    Subscription available at Wolters Kluwer.
  • Micromedex Solutions. "Fluoxetine Drug Summary."
    Subscription required at IBM Micromedex.
  • 6. UpToDate
  • Articles on "Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects" and "Unipolar major depression in adults: Choosing initial treatment."
    Available at www.uptodate.com.
  • 7. MedlinePlus
  • Consumer information on fluoxetine, including uses, dosage, and side effects.
    Available at MedlinePlus.gov.
  • 8. National Institute of Mental Health (NIMH)
  • Overview of antidepressant use in depression and anxiety.
    Available at NIMH.nih.gov.