What are the side effects of Prozac (fluoxetine)?

Prozac (Fluoxetine) Side Effects

Prozac (fluoxetine) is generally well-tolerated but has common side effects including gastrointestinal issues, sexual dysfunction, and potential risk for suicidal thinking in young patients, with most side effects emerging within the first few weeks of treatment and diminishing over time. 1, 2

Common Side Effects

Fluoxetine commonly causes several side effects that patients should be aware of:

• Gastrointestinal effects:

  • Nausea, diarrhea, dry mouth, heartburn 3
  • Anorexia (decreased appetite) and potential weight loss 1

• Neurological effects:

  • Headache, dizziness, somnolence, insomnia 3
  • Nervousness, anxiety, tremor 3, 2
  • Vivid dreams 3

• Other common effects:

  • Fatigue 3
  • Diaphoresis (excessive sweating) 3
  • Bruxism (teeth grinding) 3
  • Sexual dysfunction 2

Potentially Serious Side Effects

Several more serious adverse effects require monitoring and potential intervention:

• Suicidal thinking and behavior:

  • Boxed warning for increased risk through age 24 years 3
  • Close monitoring recommended, especially in first months of treatment 3
  • Risk difference of 0.7% compared to placebo 3

• Behavioral activation/agitation:

  • Can include motor/mental restlessness, insomnia, impulsiveness, talkativeness, disinhibition, aggression 3
  • More common in younger children than adolescents 3
  • More common in anxiety disorders than depressive disorders 3

• Hypomania/mania:

  • Reported in 0.7% of patients across clinical trials 1
  • Can be difficult to distinguish from behavioral activation 3

• Serotonin syndrome:

  • Risk increases when combined with other serotonergic medications 2
  • Symptoms include mental status changes, neuromuscular hyperactivity, autonomic instability 2

• Abnormal bleeding:

  • Increased risk when combined with NSAIDs, aspirin, warfarin, or other anticoagulants 1
  • Bleeding events range from minor (ecchymoses, petechiae) to life-threatening hemorrhages 1

• Seizures:

  • Reported in approximately 0.2% of patients 1
  • Use with caution in patients with a history of seizures 1

• Hyponatremia:

  • May occur due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1
  • Higher risk in elderly patients and those taking diuretics 1
  • Symptoms include headache, difficulty concentrating, memory impairment, confusion, weakness 1

Discontinuation Effects

Abrupt discontinuation of fluoxetine may lead to withdrawal symptoms, including:

• Dysphoric mood, irritability, agitation 1
• Dizziness, sensory disturbances (e.g., electric shock sensations) 1
• Anxiety, confusion, headache, lethargy 1
• Emotional lability, insomnia, hypomania 1

A gradual reduction in dose rather than abrupt cessation is recommended 1. However, fluoxetine's long half-life (1-3 days) and its active metabolite norfluoxetine (7 days) essentially preclude a withdrawal phenomenon compared to other SSRIs 4.

Time Course of Side Effects

Most adverse effects emerge within the first few weeks of treatment 3, 5. A study following patients for 6 months found that all common side effects (occurring in >5% of patients) decreased in frequency over time, and no new common side effects emerged during continuation therapy 5. This suggests that patients who experience initial side effects may find them resolving with continued treatment.

Special Considerations

• Overdose: Symptoms can include seizures, somnolence, nausea, tachycardia, vomiting, and in severe cases, ECG abnormalities, hypotension, and coma 1

• Drug interactions: Fluoxetine inhibits cytochrome P450 (CYP) 2D6 and other CYP enzymes, increasing potential for drug interactions, though most are not clinically important 4

• Diabetes: May alter glycemic control; insulin or oral hypoglycemic dosage may need adjustment 1

• Liver impairment: Lower or less frequent dosing recommended for patients with cirrhosis 1

Monitoring Recommendations

• Monitor closely for suicidality, especially in the first months of treatment and following dosage adjustments 3, 1
• Watch for signs of behavioral activation/agitation, particularly in younger patients 3
• Be alert for symptoms of serotonin syndrome when combining with other serotonergic medications 2
• Monitor weight and appetite changes 1
• In patients with diabetes, monitor glycemic control 1

Fluoxetine's side effect profile is generally more favorable than older antidepressants like tricyclics, with fewer anticholinergic effects and greater safety in overdose 6, 7.