What are the side effects of Prozac (fluoxetine)?

Side Effects of Prozac (Fluoxetine)

Prozac (fluoxetine) commonly causes nausea, insomnia, nervousness, headache, diarrhea, sexual dysfunction, and anxiety, with nausea and vomiting being the most common reasons for discontinuation. 1

Common Side Effects

Fluoxetine, as a selective serotonin reuptake inhibitor (SSRI), has a distinct side effect profile that differs from older antidepressants like tricyclics. The most frequently reported adverse events include:

• Gastrointestinal effects:

  • Nausea
  • Diarrhea
  • Vomiting
  • Anorexia (decreased appetite)
  • Weight loss (reported in 1.4% of patients) 1, 2

• Neurological effects:

  • Headache
  • Dizziness
  • Tremor
  • Insomnia (reported in 12-16% of patients) 1, 2

• Psychological effects:

  • Anxiety (12-16% of patients)
  • Nervousness
  • Agitation 1, 2

Severe Adverse Events

Sexual Dysfunction

Sexual adverse events are common with fluoxetine, though often underreported. Fluoxetine has higher rates of sexual dysfunction compared to some other antidepressants like bupropion 1.

Suicidality

While studies show no differences in suicidal thinking among second-generation antidepressants, meta-analyses have indicated that SSRIs may be associated with an increased risk for nonfatal suicide attempts compared to placebo (odds ratio, 2.25 [CI, 3.3 to 4.6]) 1.

Discontinuation Syndrome

Abrupt discontinuation of fluoxetine can lead to withdrawal symptoms including:

• Dysphoric mood
• Irritability
• Agitation
• Dizziness
• Sensory disturbances (e.g., paresthesias, electric shock sensations)
• Anxiety
• Confusion
• Headache
• Lethargy
• Emotional lability
• Insomnia
• Hypomania 2

Serotonin Syndrome

Though rare with fluoxetine alone, serotonin syndrome can occur, especially when combined with other serotonergic medications. Symptoms include:

• Changes in mental status (agitation, confusion)
• Autonomic hyperactivity (fever, tachycardia, tachypnea, diaphoresis, mydriasis)
• Neuromuscular abnormalities (tremor, clonus, hyperreflexia, hypertonia) 1

Other Serious Adverse Events

• Hyponatremia: May occur as a result of syndrome of inappropriate antidiuretic hormone secretion (SIADH) 2
• Activation of mania/hypomania: Reported in 0.1% of patients with major depressive disorder 2
• Seizures: Reported in 0.2% of patients, similar to other antidepressants 2
• Abnormal bleeding: SSRIs may increase the risk of bleeding events, especially when combined with NSAIDs, aspirin, or anticoagulants 2

Special Populations

Pregnancy

Third-trimester use of fluoxetine and other SSRIs has been linked to neonatal complications including:

• Continuous crying
• Irritability
• Jitteriness
• Tremors
• Hypertonia or rigidity
• Tachypnea or respiratory distress
• Feeding difficulty
• Sleep disturbance
• Hypoglycemia
• Seizures 1

These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 1.

Elderly Patients

Older patients may be at greater risk for developing hyponatremia with SSRIs. Preferred agents for older patients with depression include citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion. Fluoxetine should generally be avoided in this population due to its long half-life and potential for drug interactions 1.

Overdose Considerations

In cases of overdose, fluoxetine may cause:

• Seizures
• Somnolence
• Tachycardia
• Vomiting
• ECG abnormalities (QT interval prolongation and ventricular tachycardia)
• Hypotension
• Mania
• Neuroleptic malignant syndrome-like events
• Pyrexia
• Stupor
• Syncope 2

Clinical Recommendations

When prescribing fluoxetine:

1. Start at a low dose (10-20 mg daily) and titrate as needed 1
2. Monitor for side effects, particularly during the first few weeks of treatment
3. Consider gradual dose reduction when discontinuing to minimize withdrawal symptoms 2
4. Be cautious when using fluoxetine with other medications that affect serotonin levels to avoid serotonin syndrome 2
5. Monitor for increased bleeding risk when combined with NSAIDs, aspirin, or anticoagulants 2

Comparison to Other Antidepressants

Compared to tricyclic antidepressants, fluoxetine has:

• Fewer anticholinergic effects
• Less sedation
• Minimal cardiovascular effects
• Lower risk of serious toxicity in overdose 3, 4

However, it has higher rates of:

• Nausea
• Nervousness
• Insomnia 4

Understanding these side effects is crucial for appropriate patient selection, monitoring, and management to optimize treatment outcomes while minimizing adverse events.