Side Effects of Prozac (Fluoxetine)
Prozac (fluoxetine) commonly causes gastrointestinal disturbances, sexual dysfunction, sleep disturbances, and nervous system effects, with nausea and vomiting being the most common reasons for discontinuation. 1
Common Side Effects
Fluoxetine is associated with several common adverse effects that patients should be aware of:
Gastrointestinal effects:
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Anorexia (decreased appetite)
Nervous system effects:
- Headache
- Dizziness
- Nervousness
- Anxiety
- Insomnia
- Somnolence (drowsiness)
- Tremors
Sexual dysfunction:
- Although fluoxetine has lower rates of sexual dysfunction compared to some other SSRIs (particularly paroxetine), it can still cause sexual side effects 1
- These effects are often underreported by patients
Timing and Resolution of Side Effects
Most side effects associated with fluoxetine:
- Appear early in treatment
- Decrease significantly in frequency over time with continued treatment
- Often resolve within the first 6 months of therapy 2
The long half-life of fluoxetine and its active metabolite (norfluoxetine) means:
- Side effects may not manifest for a few weeks after starting treatment 1
- Withdrawal symptoms are less likely compared to other antidepressants 3
Severe Adverse Effects
Suicidality
- SSRIs including fluoxetine may increase the risk for nonfatal suicide attempts, particularly early in treatment 1
- Patients should be monitored for emergence of suicidal thoughts, especially during initial treatment or dose changes 4
Discontinuation Symptoms
When stopping fluoxetine, patients may experience:
- Dysphoric mood
- Irritability
- Agitation
- Dizziness
- Sensory disturbances (e.g., paresthesias such as electric shock sensations)
- Anxiety
- Confusion
- Headache
- Emotional lability
A gradual reduction in dose rather than abrupt cessation is recommended to minimize these symptoms 4
Other Serious Concerns
- Abnormal bleeding: Increased risk when combined with NSAIDs, aspirin, warfarin, or other drugs affecting coagulation 4
- Hyponatremia: May occur as a result of SIADH (syndrome of inappropriate antidiuretic hormone secretion) 4
- Activation of mania/hypomania: Reported in 0.1% of patients with major depressive disorder 4
- Seizures: Reported in approximately 0.2% of patients taking fluoxetine 4
- Serotonin syndrome: Risk increases when combined with other serotonergic medications 4
Drug Interactions
Fluoxetine is an inhibitor of cytochrome P450 (CYP) 2D6 and other CYP enzymes, which increases the potential for drug interactions 3. Key interactions include:
- MAOIs: Potentially fatal serotonin syndrome can occur
- Other serotonergic drugs: Increased risk of serotonin syndrome
- Drugs metabolized by CYP2D6: May have increased plasma levels when taken with fluoxetine
- Anticoagulants: Increased risk of bleeding
Monitoring Recommendations
- Monitor for emergence of suicidal thoughts, especially during initial treatment or dose changes
- Watch for signs of serotonin syndrome when combining with other serotonergic medications
- Assess for sexual dysfunction, as it may be underreported
- Monitor for bleeding risk, especially if combined with anticoagulants or antiplatelet drugs
- Be alert for hyponatremia, particularly in elderly patients
Advantages Over Older Antidepressants
Fluoxetine has several advantages over tricyclic antidepressants:
- Does not have the anticholinergic effects of tricyclic antidepressants
- No significant hypotensive effects
- Less sedating than many other antidepressants
- No particular cardiovascular effects in patients without pre-existing cardiovascular disease
- Overdoses generally do not cause serious toxic effects 5