What are the side effects of Prozac (fluoxetine)?

Prozac (Fluoxetine) Side Effects

Prozac causes common gastrointestinal and neurological side effects that typically resolve within weeks, but carries serious risks including increased suicidal thinking in young patients, serotonin syndrome when combined with other serotonergic drugs, and bleeding complications, particularly when used with NSAIDs or anticoagulants. 1, 2

Common Side Effects

Gastrointestinal Effects

• Nausea, vomiting, diarrhea, and constipation are the most frequently reported gastrointestinal side effects 1
• Anorexia (decreased appetite) occurs in 11% of patients with depression, 17% with OCD, and 8% with bulimia nervosa 2
• These gastrointestinal symptoms typically decrease significantly over time and resolve in the majority of patients during the first 6 months of treatment 3

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 2
• Fluoxetine should be introduced with care in patients with a history of seizures 2

Psychiatric Effects

• Insomnia, nervousness, anxiety, and agitation are frequently reported, particularly during initial treatment 1
• In depression trials, 12-16% of patients experienced anxiety/nervousness compared to 7-9% on placebo 2
• Insomnia occurred in 28% of OCD patients and 33% of bulimia patients on fluoxetine 2
• These psychiatric symptoms typically resolve over time, with all events occurring in >5% of patients early in treatment decreasing significantly by 6 months 3

Sexual Dysfunction

• Decreased libido and difficulties with sexual performance are potential side effects 1
• Sexual dysfunction is a common reason for treatment discontinuation 1

Weight Changes

• Weight loss may occur, particularly in underweight depressed or bulimic patients 2
• Patients on 60 mg lost an average of 0.45 kg compared to 0.16 kg gain on placebo in bulimia trials 2
• Weight should be monitored throughout therapy 2

Serious Adverse Events

Suicidal Thinking and Behavior

• There is an increased risk of suicidal thinking and behavior, particularly during the initial treatment period, 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 should be monitored closely for emergence of anxiety, agitation, panic attacks, irritability, hostility, aggressiveness, impulsivity, and worsening depression, particularly early in treatment and during dose adjustments 2

Serotonin Syndrome

• Serotonin syndrome, characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, can occur when fluoxetine is combined with other serotonergic medications 1
• Combining fluoxetine with MAOIs is absolutely contraindicated due to this risk 1
• Other high-risk combinations include triptans, tramadol, and other serotonergic agents 2

Bleeding Complications

• SSRIs including fluoxetine increase the risk of bleeding events, ranging from ecchymoses and epistaxis to life-threatening hemorrhages 2
• Concomitant use with NSAIDs, aspirin, warfarin, or other anticoagulants significantly increases bleeding risk 2
• Patients should be cautioned about this risk and monitored appropriately 2

Hyponatremia

• Hyponatremia may occur due to SIADH (syndrome of inappropriate antidiuretic hormone secretion) 2
• Cases with serum sodium lower than 110 mmol/L have been reported 2
• Elderly patients and those taking diuretics or who are volume depleted are at greater risk 2
• Signs include headache, confusion, memory impairment, weakness, unsteadiness, and in severe cases, seizures, coma, or death 2

Mania/Hypomania Activation

• Mania or hypomania was reported in 0.7% of patients across all clinical trials 2
• This risk exists in patients with bipolar disorder or those predisposed to mood cycling 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

• Elderly patients are more sensitive to adverse effects and have higher risk for hyponatremia 1
• Alternative medications such as citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion may be preferred 1

Patients with Hepatic Impairment

• In patients with cirrhosis, clearance of fluoxetine and norfluoxetine is decreased, increasing elimination half-lives 2
• A lower or less frequent dose should be used in cirrhotic patients 2

Patients with Diabetes

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

Drug Interactions

Critical Interactions

• MAOIs are absolutely contraindicated due to serotonin syndrome risk 1
• Fluoxetine increases levels of drugs metabolized by CYP2D6, including tricyclic antidepressants, requiring careful monitoring 1
• The long elimination half-life (4 days for fluoxetine, 7 days for norfluoxetine) means drug interactions can persist for weeks after discontinuation 2

Discontinuation Syndrome

Withdrawal Symptoms

• Abrupt discontinuation can cause dysphoric mood, irritability, agitation, dizziness, sensory disturbances (electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania 2
• A gradual dose reduction rather than abrupt cessation is recommended whenever possible 2
• The long half-life of fluoxetine may minimize discontinuation symptoms compared to other SSRIs 2

Overdose Considerations

• Among 633 adult overdoses with fluoxetine alone, 34 were fatal 2
• The most common overdose symptoms are seizures, somnolence, nausea, tachycardia, and vomiting 2
• Serious complications can include coma, delirium, QT prolongation, ventricular tachycardia (including torsades de pointes), and neuroleptic malignant syndrome-like events 2
• There is no specific antidote; treatment is supportive with activated charcoal if administered soon after ingestion 2