Side Effects of Prozac (Fluoxetine)
Prozac (fluoxetine) commonly causes nausea, insomnia, nervousness, headache, diarrhea, dizziness, sexual dysfunction, and somnolence, with nausea and vomiting being the most common reasons for discontinuation. 1, 2
Common Side Effects
- Gastrointestinal effects: Nausea, vomiting, diarrhea, and constipation are frequently reported 1, 2
- Neurological effects: Headache, dizziness, tremors, and somnolence 1, 2
- Psychiatric effects: Insomnia, nervousness, anxiety, and agitation 1, 2
- Sexual dysfunction: Decreased libido and difficulties with sexual performance 1
- Weight and appetite changes: Anorexia (decreased appetite) and weight loss may occur 2
Severe Adverse Events
Suicidality
- Risk of increased suicidal thinking and behavior, particularly during initial treatment period 1
- While no evidence indicates an increase in completed suicide risk with SSRIs (odds ratio 0.85), the risk for nonfatal suicide attempts may increase (odds ratio 1.57-2.25) 1
Serotonin Syndrome
- Characterized by mental status changes (agitation, confusion), autonomic hyperactivity (fever, tachycardia, diaphoresis), and neuromuscular abnormalities (tremor, hyperreflexia) 1, 2
- Risk increases when combined with other serotonergic medications 1, 2
Bleeding Risk
- Increased risk of bleeding events, especially when combined with NSAIDs, aspirin, or anticoagulants 2
- Can range from minor bleeding (ecchymoses, epistaxis) to serious hemorrhagic events 2
Discontinuation Syndrome
- Abrupt discontinuation may lead to dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, and insomnia 2
- Gradual dose reduction is recommended to minimize these effects 2
Other Serious Adverse Events
- Hyponatremia: May occur due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) 2
- Seizures: Risk is approximately 0.2% of patients 2
- Activation of mania/hypomania: Reported in approximately 0.1-0.7% of patients 2
- QT prolongation: Rare but potentially serious cardiac effect 2
Special Populations
Pregnancy
- Third-trimester use linked to neonatal complications including continuous crying, irritability, jitteriness, tremors, feeding difficulties, respiratory distress, and sleep disturbance 1
- These neonatal signs typically resolve within 1-2 weeks after birth 1
Elderly Patients
- Higher risk for developing hyponatremia 2
- May be more sensitive to adverse effects; citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion are generally preferred over fluoxetine in older adults 1
Time Course of Side Effects
- Most side effects that occur early in treatment (first 4 weeks) decrease significantly in frequency over time 3
- No adverse events become more frequent with continued treatment over a 6-month period 3
- Most common initial side effects (nausea, insomnia, nervousness, somnolence) resolve in the majority of patients with continued treatment 3
Drug Interactions
- MAOIs: Contraindicated due to risk of serotonin syndrome 1, 2
- Other serotonergic drugs: Increased risk of serotonin syndrome when combined with triptans, tramadol, or other serotonergic agents 2
- Drugs metabolized by CYP2D6: Fluoxetine may increase levels of these medications 1
- Drugs that affect coagulation: Increased bleeding risk when combined with NSAIDs, aspirin, or anticoagulants 2