Prozac (Fluoxetine): Uses and Prescription Guidelines
Prozac (fluoxetine) is FDA-approved for treating major depressive disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, panic disorder, and bipolar depression (in combination with olanzapine), with dosing typically starting at 20mg daily for adults. 1
FDA-Approved Indications
Adults:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
- Bulimia Nervosa
- Panic Disorder
- Premenstrual Dysphoric Disorder
- Bipolar Depression (in combination with olanzapine)
Children and Adolescents:
- Depression (≥8 years)
- OCD (≥8 years)
Dosing Guidelines
Standard Dosing:
- Major Depression: 20mg once daily, can be increased to 40mg daily after several weeks if needed
- OCD: 20-40mg daily, with treatment-resistant cases potentially requiring 60-80mg 2
- Bulimia Nervosa: 60mg daily
- Panic Disorder: 10-20mg daily initially, increasing to 20mg daily
Special Populations:
- Children (8-18 years): Lower initial doses (10mg daily) with gradual titration
- Elderly: Consider starting at 10mg daily
- Patients with panic disorder: May benefit from starting at lower doses (5-10mg) and gradually increasing to avoid initial activation 3
Mechanism of Action
Fluoxetine selectively inhibits presynaptic serotonin reuptake in the brain, increasing serotonin availability at the synaptic cleft. Over time, it downregulates inhibitory serotonin autoreceptors, enhancing its therapeutic effect 2.
Treatment Duration and Monitoring
- Depression: Minimum 6-12 months after symptom resolution
- OCD: Minimum 12-24 months after achieving remission 2
- Bulimia Nervosa: Long-term treatment efficacy demonstrated for up to 52 weeks 1
Safety Considerations and Adverse Effects
Major Safety Concerns:
- Black Box Warning: Increased risk of suicidality in children, adolescents, and young adults 2
- QT Prolongation: Use with caution in patients with congenital long QT syndrome, history of QT prolongation, family history of long QT syndrome or sudden cardiac death 4
- Serotonin Syndrome: Risk increases with concurrent use of other serotonergic medications 2
Common Side Effects:
- Insomnia
- Headache
- Nausea
- Sexual dysfunction
- Nervousness or agitation (particularly early in treatment)
Pharmacokinetic Considerations:
- Long half-life (1-3 days for fluoxetine, 7 days for active metabolite norfluoxetine)
- Metabolized primarily through CYP2D6 4
- CYP2D6 poor metabolizers may experience higher plasma concentrations and increased risk of adverse effects 4
Special Prescribing Considerations
Drug Interactions:
- Avoid concurrent use with MAOIs (must wait 5 weeks after stopping fluoxetine before starting an MAOI)
- Use caution with other medications metabolized by CYP2D6
- Fluoxetine itself inhibits CYP2D6, potentially affecting other medications 4
Genetic Considerations:
- CYP2D6 poor metabolizers have higher plasma concentrations and may require lower doses 4
- Genetic testing may be considered in cases of treatment failure or unusual side effects 4
Discontinuation:
- Gradual tapering recommended, though less critical than with other SSRIs due to long half-life 5
- Monitor for discontinuation symptoms despite the medication's long half-life
Clinical Pearls
- Fluoxetine's long half-life makes it more forgiving of missed doses compared to other antidepressants 5
- Initial nervousness or insomnia may predict good response to treatment 6
- For panic disorder patients, starting at lower doses (5mg) may improve tolerability 3
- Higher doses are often required for OCD compared to depression 6
- Fluoxetine has demonstrated efficacy for comorbid depression and anxiety disorders 7
Fluoxetine's established efficacy across multiple psychiatric conditions, relatively favorable side effect profile, and once-daily dosing make it a commonly prescribed first-line antidepressant, though individual response and tolerability should guide treatment decisions.