What are the side effects of Prozac (fluoxetine)?

Side Effects of Prozac (Fluoxetine)

Prozac causes common gastrointestinal and neurological side effects that are generally manageable, but carries serious risks including increased suicidal thinking in young patients, serotonin syndrome, and bleeding complications that require careful monitoring.

Common Side Effects

Gastrointestinal Effects

• Nausea, vomiting, diarrhea, and constipation are frequently reported and represent the most common category of adverse effects 1, 2
• Anorexia (decreased appetite) occurs in 11% of patients with major depressive disorder (versus 2% with placebo), 17% with OCD (versus 10% with placebo), and 8% with bulimia (versus 4% with placebo) 2
• Weight loss may occur, particularly problematic in underweight depressed or bulimic patients, though discontinuation due to anorexia or weight loss is rare 2

Neurological Effects

• Headache, dizziness, tremors, and somnolence are common neurological manifestations 1
• Seizures occur in approximately 0.1-0.2% of patients, similar to other antidepressants, and fluoxetine should be used cautiously in patients with seizure history 2

Psychiatric Effects

• Insomnia is reported in 28% of OCD patients (versus 22% placebo) and 33% of bulimia patients on 60mg (versus 13% placebo) 2
• Anxiety, nervousness, and agitation occur in 12-16% of major depressive disorder patients (versus 7-9% placebo) 2
• These symptoms are among the most common reasons for discontinuation 2

Sexual Dysfunction

• Decreased libido and difficulties with sexual performance are potential side effects 1

Serious and Life-Threatening Adverse Events

Suicidal Thinking and Behavior

• There is an increased risk of suicidal thinking and behavior, particularly during initial treatment, with an odds ratio of 1.57-2.25 for nonfatal suicide attempts 1
• This risk is especially concerning in children, adolescents, and young adults 1
• Patients require close monitoring for emergence of suicidal ideation, especially when initiating therapy or adjusting doses 2

Serotonin Syndrome

• Characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities 1
• Occurs when fluoxetine is combined with other serotonergic medications, including MAOIs (which are contraindicated), triptans, or tramadol 1, 2
• Can progress to life-threatening complications 3

Bleeding Complications

• SSRIs increase the risk of bleeding events ranging from ecchymoses and epistaxis to life-threatening hemorrhages 2
• Risk is amplified when combined with NSAIDs, aspirin, warfarin, or other anticoagulants 2
• Gastrointestinal bleeding is particularly associated with concomitant use of drugs interfering with serotonin reuptake 2

Hyponatremia

• May result from syndrome of inappropriate antidiuretic hormone secretion (SIADH) 2
• Cases with serum sodium below 110 mmol/L have been reported 2
• Elderly patients and those taking diuretics or who are volume depleted are at greater risk 2
• Symptoms include headache, confusion, memory impairment, weakness, unsteadiness, and in severe cases, hallucinations, seizures, coma, or death 2

Mania/Hypomania Activation

• Reported in 0.1% of major depressive disorder patients and 0.8% of OCD patients in controlled trials 2
• Overall incidence across all trials was 0.7% of 10,782 patients 2

Special Population Considerations

Pregnancy and Neonatal Effects

• Third-trimester use is linked to neonatal complications including continuous crying, irritability, jitteriness, tremors, feeding difficulties, respiratory distress, and sleep disturbance 1
• These symptoms typically resolve within 1-2 weeks after birth 1

Elderly Patients

• More sensitive to adverse effects with higher risk for hyponatremia 1, 2
• Alternative medications such as citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion may be preferred 1

Patients with Hepatic Impairment

• Clearance of fluoxetine and norfluoxetine is decreased in cirrhosis, increasing elimination half-lives 2
• Lower or less frequent dosing is required 2

Patients with Diabetes

• Fluoxetine may alter glycemic control 2
• Hypoglycemia can occur during therapy; hyperglycemia may develop after discontinuation 2
• Insulin and oral hypoglycemic dosages may require adjustment 2

Drug Interactions

Contraindicated Combinations

• MAOIs are absolutely contraindicated due to risk of serotonin syndrome 1

Significant Interactions Requiring Monitoring

• Fluoxetine increases levels of drugs metabolized by CYP2D6, including tricyclic antidepressants, requiring careful monitoring 1
• Interactions occur with L-dopa, L-tryptophan, anorexiants, anticonvulsants, anxiolytics, calcium channel blockers, cyproheptadine, and lithium 3

Discontinuation Syndrome

• Abrupt discontinuation can cause dysphoric mood, irritability, agitation, dizziness, sensory disturbances (electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania 2
• While generally self-limiting, serious discontinuation symptoms have been reported 2
• Gradual dose reduction is recommended rather than abrupt cessation 2
• Fluoxetine's long half-life may minimize discontinuation risk compared to other SSRIs, though delirium has been reported in rare cases 4

Overdose Considerations

• The largest known adult ingestion was 8 grams with recovery, though fatalities have occurred with doses as low as 520 mg 2
• Most common overdose symptoms include seizures, somnolence, nausea, tachycardia, and vomiting 2
• Cardiac monitoring is essential as QT prolongation and ventricular arrhythmias including torsades de pointes can occur 2

Important Clinical Caveats

• Fluoxetine may impair judgment, thinking, or motor skills; patients should be cautioned about operating hazardous machinery until effects are known 2
• The long elimination half-life (several days for both parent compound and active metabolite) means dose changes take weeks to be fully reflected in plasma levels 2
• Clinical experience is limited in patients with recent myocardial infarction or unstable heart disease, as these patients were excluded from premarket trials 2