- USES: Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) and is used for depressive disorder, obsessive-compulsive disorder, panic attack, and bulimia nervosa. PHARMACOLOGY: Fluoxetine and its active metabolite norfluoxetine inhibit reuptake of serotonin from the synaptic cleft, therefore increasing serotonergic neurotransmission. TOXICOLOGY: Severe toxicity is not common, but may develop from excessive serotonergic effects, particularly when fluoxetine is ingested with another agent that increases CNS serotonin. EPIDEMIOLOGY: Poisoning with fluoxetine and other SSRIs are common. Life threatening toxicity is rare, and patients usually recover without sequelae. MILD TO MODERATE POISONING: Somnolence, dizziness, nausea, and vomiting are common; QTc prolongation may occur even in therapeutic or mild overdose. SEVERE POISONING: Significant CNS depression, seizures, and QTc prolongation. Ventricular dysrhythmias have rarely been reported. Serotonin toxicity (autonomic instability, altered mental status, seizures, muscle rigidity, hyperreflexia, and hyperthermia) may occur; however most reported cases involve patients using multiple serotonergic agents. ADVERSE EFFECTS: Somnolence, dizziness, insomnia, nervousness, headache, nausea, vomiting, and diarrhea are often reported. Hyponatremia, due to inappropriate secretion of antidiuretic hormone (SIADH), may be observed.
Range of Toxicity:
- TOXICITY: Acute ingestion of up to 100 mg is not expected to cause toxicity. Expect mild toxicity in fluoxetine naive patients after ingestion of more than 100 mg. Adding fluoxetine to an established therapy with serotonergic agents may lead to serotonin toxicity. There have been rare reports of fatalities to fluoxetine alone. THERAPEUTIC DOSE: ADULTS: Bulimia nervosa: 20 to 60 mg orally once daily. Depression: 20 to 80 mg orally once daily. Begin with 20 mg and titrate dose slowly within weeks. CHILDREN (more than 7 years): Depression: 10 to 40 mg once daily. Begin with 10 mg and titrate dose within weeks.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Primarily supportive care; a single dose of activated charcoal may be helpful in patients presenting shortly after ingestion. MANAGEMENT OF SEVERE TOXICITY: Consider a single dose of activated charcoal if patients present early after ingestion. In case of significant CNS depression, perform orotracheal intubation for airway protection prior to giving charcoal. Use primarily benzodiazepines for serotonin toxicity. In case of autonomic instability, severe muscle rigidity, and significant hyperthermia consider intubation and muscle paralysis.
- Decontamination: PREHOSPITAL: GI decontamination is not recommended because of potential for somnolence and seizures. HOSPITAL: Single dose activated charcoal if recent, substantial ingestion, and patient is able to protect airway.
- Airway management: Early orotracheal intubation in patients with signs of severe intoxication (CNS depression, seizures, severe serotonin toxicity).
- Antidote: None.
- Seizure: Use IV benzodiazepines or barbiturates as needed.
- Serotonin syndrome: Treat with benzodiazepines. In severe cases cyproheptadine is sometimes used. Cyproheptadine, Adult: 12 mg orally initially followed by 2 mg every 2 hours if symptoms persist, maximum 32 mg/day, maintenance dose 8 mg every 6 hours. Pediatric: 0.25 mg/kg/day divided every 6 hours, maximum 12 mg/day.
- Monitoring of patient: Monitor vital signs and mental status. Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity (CNS depression, seizures, serotonin toxicity). Monitor serum electrolytes and creatinine phosphokinase concentrations in patients with seizures or prolonged CNS depression. Fluoxetine plasma levels are not clinically useful or widely available. No specific lab work is needed in most patients.
- Enhanced elimination procedure: There is no role for repeat-dose activated charcoal, hemodialysis or hemoperfusion.
- Patient disposition: HOME CRITERIA: Children and adults with mild symptoms (eg, vomiting, mydriasis, diaphoresis, mild somnolence) with inadvertent ingestions of up to 100 mg fluoxetine can be managed at home. A patient on chronic fluoxetine therapy may be managed at home if there are only mild symptoms, the ingestion is inadvertent and less than 5 times that patient’s single therapeutic dose. OBSERVATION CRITERIA: Any patient who overdoses in suicidal attempt or who develops more than mild symptoms should be sent to a healthcare facility for evaluation and treatment. For fluoxetine naive patients with ingestion more than 100 mg and for patients on chronic fluoxetine therapy with an ingestion of more than five times that patient’s single therapeutic dose, prompt referral to a healthcare facility is necessary for evaluation and treatment. Patients should be observed for 6 hours. With ingestion of extended-release formulations, absorption is delayed by 1 to 2 hours at therapeutic doses and may warrant longer observation times (8 to 12 hours). ADMISSION CRITERIA: Patients with persistent mental status changes, seizures or dysrhythmias should be admitted. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in decision making whether or not admission is advisable, managing patients with severe toxicity (CNS depression, seizures, serotonin toxicity), or in whom the diagnosis is not clear.