Usage
Fluoxetine is primarily prescribed for the treatment of:
- Major Depressive Disorder (MDD): For acute and maintenance treatment.
- Obsessive-Compulsive Disorder (OCD): For acute and maintenance treatment of obsessions and compulsions.
- Bulimia Nervosa: For acute and maintenance treatment of binge-eating and purging behaviors.
- Panic Disorder: For acute treatment of panic disorder, with or without agoraphobia.
- Premenstrual Dysphoric Disorder (PMDD): To manage symptoms of PMDD.
Pharmacological Classification: Fluoxetine is classified as a selective serotonin reuptake inhibitor (SSRI).
Mechanism of Action: Fluoxetine selectively inhibits the reuptake of serotonin in the synaptic cleft, increasing the extracellular concentration of serotonin and enhancing serotonergic neurotransmission.
Alternate Names
Fluoxetine is also known by its popular brand name, Prozac. Other brand names may exist internationally and regionally.
How It Works
Pharmacodynamics: Fluoxetine’s primary effect is to increase serotonergic activity in the central nervous system. This leads to mood elevation, decreased anxiety, and improved control of obsessive thoughts and compulsive behaviors.
Pharmacokinetics:
- Absorption: Fluoxetine is well-absorbed orally.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2D6, to norfluoxetine (also an active metabolite).
- Elimination: Primarily eliminated renally. The half-life of fluoxetine is 1-3 days, while norfluoxetine has a half-life of 4-16 days.
Mode of Action: Fluoxetine binds to the serotonin transporter (SERT) on presynaptic neurons, blocking the reuptake of serotonin. This increases the concentration of serotonin in the synaptic cleft.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Fluoxetine primarily acts by inhibiting SERT. It may also have weak effects on other neurotransmitter systems, but its primary therapeutic effect is mediated through serotonin modulation.
Elimination Pathways: Fluoxetine and its metabolites are primarily excreted in the urine. Hepatic metabolism plays a role in the conversion of fluoxetine to norfluoxetine.
Dosage
Standard Dosage
Adults:
- MDD, OCD: Initial dose is 20 mg orally once daily, usually in the morning. The dose may be gradually increased after several weeks if necessary, to a maximum of 80 mg/day. Once-weekly delayed-release capsules (90 mg) can be used after achieving a stable dose on daily fluoxetine.
- Bulimia: 60 mg orally once daily.
- Panic Disorder: Initial dose is 10 mg orally once daily for the first week, then increased to 20 mg/day. May be increased gradually to a maximum of 60 mg/day if needed.
- PMDD: 20 mg orally daily continuously or 20 mg orally daily starting 14 days before menstruation and through the first full day of menses (repeat each cycle).
Children:
- MDD (8 years and older), OCD (7 years and older): Initial dose is 10 mg orally once daily. May increase to 20 mg/day after several weeks. Adolescents and higher-weight children may require a higher dose (20-60 mg/day). Lower-weight children should be started on a lower dose (10mg/day, increase after several weeks) and maintained on a lower dose (20-30 mg/day). Maximum dose generally not to exceed 60 mg/day.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 10 mg/day) and titrate cautiously, generally not exceeding 40 mg/day.
- Patients with Renal Impairment: No dosage adjustment is typically required.
- Patients with Hepatic Dysfunction: Use lower doses (up to 50% reduction) or less frequent dosing.
- Patients with Comorbid Conditions: Dose adjustments may be needed based on specific comorbid conditions (e.g., diabetes, cardiovascular disease) and potential drug interactions. Consult specialized resources for guidance.
Clinical Use Cases
Fluoxetine is not typically indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest. Other medications are more suitable for these scenarios. While some research suggests potential neuroprotective effects of fluoxetine after cardiac arrest, it is not a standard treatment. For depression after status epilepticus, consider other treatments.
Dosage Adjustments
Dosage adjustments may be needed based on individual patient response and tolerability. Consider lower or less frequent dosing for elderly patients, patients with hepatic impairment, and patients taking multiple medications. Monitor for drug interactions, particularly with CYP2D6 inhibitors and inducers.
Side Effects
Common Side Effects:
Nausea, insomnia, headache, drowsiness, anxiety, sexual dysfunction, decreased libido, tremor, dry mouth, and sweating.
Rare but Serious Side Effects:
Serotonin syndrome (high fever, muscle rigidity, confusion, seizures), suicidal thoughts or behaviors (particularly in children and young adults), mania/hypomania, allergic reactions, bleeding disorders, hyponatremia, and seizures.
Long-Term Effects:
Weight changes, sexual dysfunction, and potential withdrawal symptoms upon discontinuation.
Adverse Drug Reactions (ADR):
Serotonin syndrome, severe allergic reactions (anaphylaxis), and suicidal ideation/behavior require immediate medical attention.
Contraindications
- Hypersensitivity to fluoxetine.
- Concurrent use of MAOIs or within 14 days of discontinuing MAOIs.
- Unstable seizure disorders.
Drug Interactions
Fluoxetine is primarily metabolized by CYP2D6 and can interact with other drugs metabolized by this enzyme. Significant interactions can occur with MAOIs, tricyclic antidepressants, NSAIDs, warfarin, and other medications. Consult a comprehensive drug interaction resource for a complete list. Alcohol, smoking, and certain foods (e.g., grapefruit juice) may also interact with fluoxetine.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Fluoxetine is generally considered Pregnancy Category C.
- Fetal Risks: Potential for neonatal withdrawal symptoms, persistent pulmonary hypertension of the newborn (PPHN), and other complications.
- Breastfeeding: Fluoxetine is excreted in breast milk. Weigh the risks and benefits of breastfeeding while taking fluoxetine.
Drug Profile Summary
- Mechanism of Action: SSRI.
- Side Effects: Nausea, insomnia, headache, sexual dysfunction, serotonin syndrome (rare).
- Contraindications: Hypersensitivity, concurrent MAOI use.
- Drug Interactions: CYP2D6 inhibitors/inducers, MAOIs, TCAs.
- Pregnancy & Breastfeeding: Use with caution; potential neonatal effects.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Monitor for mood changes, suicidal thoughts, and side effects.
Popular Combinations
Fluoxetine is sometimes used in combination with olanzapine for treatment-resistant depression and depressive episodes in bipolar I disorder (Symbyax).
Precautions
- Screen for bipolar disorder, suicidality, and bleeding disorders.
- Caution in patients with hepatic impairment, seizure disorders, and diabetes.
- Avoid abrupt discontinuation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluoxetine?
A: See detailed dosage section above.
Q2: What are the common side effects of Fluoxetine?
A: Common side effects include nausea, insomnia, headache, drowsiness, anxiety, sexual dysfunction, and tremor.
Q3: What are the serious side effects of Fluoxetine?
A: Serious side effects include serotonin syndrome, suicidal thoughts/behaviors, and mania/hypomania.
Q4: What are the contraindications for Fluoxetine?
A: Contraindications include hypersensitivity to fluoxetine and concurrent use of MAOIs.
Q5: Can Fluoxetine be used during pregnancy?
A: Fluoxetine should be used with caution during pregnancy. Discuss the risks and benefits with your doctor.
Q6: How long does it take for Fluoxetine to work?
A: It can take several weeks (4-6 weeks or longer) for Fluoxetine to reach full therapeutic effect.
Q7: What should I do if I miss a dose of Fluoxetine?
A: If you miss a dose, take it as soon as you remember. If it is close to the time for your next dose, skip the missed dose and take your next dose as scheduled.
Q8: Can Fluoxetine be used in children?
A: Yes, Fluoxetine can be used in children 8 years and older for MDD and 7 years and older for OCD. Dosing needs to be adjusted for pediatric patients.
Q9: Does Fluoxetine have any drug interactions?
A: Yes, Fluoxetine can interact with various medications, including MAOIs, TCAs, and other drugs metabolized by CYP2D6. Consult a comprehensive drug interaction resource.
Q10: What are the withdrawal symptoms of Fluoxetine?
A: Withdrawal symptoms can include dizziness, nausea, headache, irritability, and anxiety. Taper the dose gradually to minimize withdrawal effects.
