What are the effects of a fluoxetine (selective serotonin reuptake inhibitor - SSRI) overdose?

From the Guidelines

Fluoxetine overdose is a medical emergency that requires immediate attention, as it can lead to severe symptoms, including serotonin syndrome, and even death, especially with very large ingestions 1.

Key Considerations

• Fluoxetine has a relatively high margin of safety in overdose compared to other antidepressants, but deaths have been reported following very large ingestions 1.
• Symptoms of fluoxetine overdose include agitation, restlessness, nausea, vomiting, tremor, seizures, rapid heartbeat, confusion, hallucinations, and in severe cases, serotonin syndrome.
• The long half-life of fluoxetine (2-3 days for the parent compound and 7-9 days for its active metabolite) means that symptoms can persist longer than with other antidepressants.

Treatment and Management

• If an overdose is suspected, call emergency services (911) or poison control (1-800-222-1222) immediately.
• While waiting for emergency services, do not induce vomiting unless instructed by medical professionals.
• Provide the emergency responders with information about the amount ingested, time of ingestion, and the person's medical history.
• Treatment typically occurs in a hospital setting and may include activated charcoal to prevent further absorption, supportive care for symptoms, and monitoring of vital signs.

Special Considerations

• Serotonin syndrome is a particular concern with fluoxetine overdose due to its serotonergic effects, and can be triggered by combining fluoxetine with other serotonergic medications 1.
• Symptoms of serotonin syndrome include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity, and can lead to fatalities if left untreated.
• Treatment for serotonin syndrome includes discontinuation of all serotonergic agents and supportive care with continuous cardiac monitoring 1.

From the FDA Drug Label

Of the 1578 cases of overdose involving fluoxetine hydrochloride, alone or with other drugs, reported from this population, there were 195 deaths Among 633 adult patients who overdosed on fluoxetine hydrochloride alone, 34 resulted in a fatal outcome, 378 completely recovered, and 15 patients experienced sequelae after overdosage, including abnormal accommodation, abnormal gait, confusion, unresponsiveness, nervousness, pulmonary dysfunction, vertigo, tremor, elevated blood pressure, impotence, movement disorder, and hypomania The most common signs and symptoms associated with non–fatal overdosage were seizures, somnolence, nausea, tachycardia, and vomiting Among pediatric patients (ages 3 months to 17 years), there were 156 cases of overdose involving fluoxetine alone or in combination with other drugs Six patients died, 127 patients completely recovered, 1 patient experienced renal failure, and 22 patients had an unknown outcome Other important adverse events reported with fluoxetine overdose (single or multiple drugs) include coma, delirium, ECG abnormalities (such as QT interval prolongation and ventricular tachycardia, including torsades de pointes–type arrhythmias), hypotension, mania, neuroleptic malignant syndrome–like events, pyrexia, stupor, and syncope

The effects of a fluoxetine overdose can be severe and potentially life-threatening. Common symptoms of overdose include:

• Seizures
• Somnolence
• Nausea
• Tachycardia
• Vomiting Less common but serious symptoms include:
• Abnormal accommodation
• Abnormal gait
• Confusion
• Unresponsiveness
• Nervousness
• Pulmonary dysfunction
• Vertigo
• Tremor
• Elevated blood pressure
• Impotence
• Movement disorder
• Hypomania
• Coma
• Delirium
• ECG abnormalities
• Hypotension
• Mania
• Neuroleptic malignant syndrome-like events
• Pyrexia
• Stupor
• Syncope 2

From the Research

Effects of Fluoxetine Overdose

The effects of a fluoxetine overdose can vary, but several studies have reported the following:

• Most patients remain asymptomatic or experience minor symptoms, such as drowsiness, tachycardia, tremor, vomiting, or nausea 3, 4, 5
• Some patients may experience more severe symptoms, including serotonin syndrome, seizure, and rhabdomyolysis, especially at high doses 6, 7
• Electrocardiogram abnormalities, such as QTc interval prolongation and Torsades de Pointes, can occur, especially in cases of multiple drug overdose or high doses of fluoxetine 6
• Vital sign abnormalities, such as elevated heart rate and diastolic blood pressure, can also occur 4

Severity and Outcome

The severity and outcome of a fluoxetine overdose depend on various factors, including:

• Dose: Higher doses are associated with more severe symptoms and a higher risk of complications 6, 7
• Co-ingested drugs: The presence of other drugs, such as ethanol, can increase the risk of adverse effects 4, 5
• Age: Children and adolescents may be more susceptible to severe symptoms, such as serotonin syndrome and seizure 7
• Time to treatment: Delayed treatment can increase the risk of complications, such as rhabdomyolysis 7

Management

The management of a fluoxetine overdose typically involves:

• Supportive care, including monitoring of vital signs and cardiac rhythm 3, 4, 5
• Treatment of symptoms, such as serotonin syndrome and seizure, with medications like magnesium sulphate 6, 7
• Intravenous fluids and analgesia for patients with rhabdomyolysis 7