Common Side Effects of Fluoxetine
The most common side effects of fluoxetine include gastrointestinal effects (nausea, vomiting, diarrhea), neurological effects (headache, dizziness, insomnia, somnolence), and sexual dysfunction. 1, 2
Gastrointestinal Side Effects
- Nausea and vomiting are the most common reasons for discontinuation of fluoxetine in clinical trials 1
- Diarrhea occurs more frequently with fluoxetine than with placebo 1
- Dry mouth and indigestion may also occur 2
Neurological Side Effects
- Headache, dizziness, and fatigue are commonly reported 2
- Sleep disturbances including insomnia and somnolence are frequent 1, 2
- Nervousness, anxiety, and agitation may occur, particularly during the first few weeks of treatment 2, 3
- Tremor may be experienced by some patients 1
Sexual Side Effects
- Sexual dysfunction is a common side effect of fluoxetine 2
- Paroxetine has higher rates of sexual dysfunction than fluoxetine 2
Other Common Side Effects
- Increased sweating is frequently reported 2
- Weight changes (usually weight loss initially) may occur 4
- Fatigue and asthenia (weakness) are reported in clinical trials 1
Potentially Serious Side Effects
- QT interval prolongation may occur, particularly in patients with pre-existing cardiac conditions or those who are CYP2D6 poor metabolizers 2
- Serotonin syndrome risk increases when combined with other serotonergic medications 2
- Increased risk for nonfatal suicide attempts has been reported, particularly during the initial treatment period 2
- Seizures may occur, especially in overdose situations 1
- Hyponatremia (low sodium levels) has been reported 2
Side Effect Patterns Over Time
- Most common side effects that occur early in treatment (first 4 weeks) decrease significantly in frequency with continued treatment 3
- No adverse events become more common with continued treatment over 6 months 3
- Nausea, insomnia, nervousness, and somnolence typically resolve in the majority of patients with continued treatment 3
Risk Factors for Increased Side Effects
- CYP2D6 poor metabolizers may experience higher plasma concentrations of fluoxetine and more side effects 2
- Long-term use of fluoxetine can convert normal metabolizers to poor metabolizers through enzyme inhibition 2
- Patients with pre-existing cardiac conditions may be at higher risk for QT prolongation 2
- Concomitant use of other medications metabolized by CYP2D6 may increase the risk of side effects 2
Overdose Effects
- Seizures, somnolence, nausea, tachycardia, and vomiting are the most common signs of non-fatal overdose 1
- Other effects in overdose include coma, delirium, ECG abnormalities, hypotension, mania, and syncope 1
- Fluoxetine overdose is generally less dangerous than tricyclic antidepressant overdose 4, 5
Remember that most side effects are dose-related and may be minimized by starting at lower doses and gradually increasing as tolerated 3, 6.