CITALOPRAM AND RELATED AGENTS
- USES: Selective serotonin reuptake inhibitors (SSRIs) used to treat major depressive disorder. Also used for treating obsessive-compulsive disorder, panic disorder, premenstrual dysphoric syndrome, anxiety disorder, and posttraumatic stress disorder. PHARMACOLOGY: Selectively inhibits the presynaptic reuptake of serotonin. Stimulation of postsynaptic 5-HT1 receptors results in the antidepressant and anxiolytic effects. TOXICOLOGY: Many of the toxic effects are mediated by stimulation of the 5-HT2 receptors causing excessive serotonin effect or serotonin syndrome. EPIDEMIOLOGY: Overdose is becoming increasingly frequent. Overdose of a single SSRI is usually well tolerated with mild to moderate severity. More severe toxicity (serotonin syndrome) may develop when another agent that increases CNS serotonin is ingested in addition to citalopram. MILD TO MODERATE TOXICITY: Agitation, confusion, tremor, nausea, vomiting, hyperreflexia, occasional clonus and myoclonus, hypoglycemia, hypertension, and bradycardia. SEVERE TOXICITY: Seizure, rigidity, hyperthermia, hypertension or hypotension, QRS and QTc interval prolongation, coma, and rarely, death. Serotonin syndrome may develop and is characterized by mental status changes (confusion, hypomania), agitation, myoclonus, hyperreflexia, diaphoresis, shivering, tremor, diarrhea, incoordination, and fever. Wide complex tachyarrhythmias, torsade de pointes, and cardiac arrest have all been observed after massive citalopram overdose, sometimes occurring quite late after the ingestion. Neuroleptic malignant syndrome has been reported following a citalopram overdose. ADVERSE EFFECTS: COMMON: Nausea, vomiting, dry mouth, somnolence, insomnia, sweating, tremor, diarrhea, dyspepsia, anxiety, decreased libido, asthenia, myalgia, rash, and weight gain. ADVERSE EFFECTS: SEVERE: Suicidality, worsening depression, serotonin syndrome, mania, seizure, elevated liver enzymes, hyponatremia, SIADH, priapism, anaphylactoid reaction, hypoglycemia, extrapyramidal reaction, tachycardia, abnormal platelet aggregation, and hepatitis. Abrupt cessation can result in withdrawal syndrome. Escitalopram is the S(+)-enantiomer of citalopram, and the adverse effects profile is similar to that of citalopram.
Range of Toxicity:
CITALOPRAM AND RELATED AGENTS
- TOXICITY: Acute ingestion of up to 100 mg citalopram or 50 mg escitalopram is not expected to result in toxicity. Serotonin toxicity may develop at therapeutic doses, particularly if another medication that increases CNS serotonin is used concomitantly. Minor toxicity develops with overdose less than 600 mg citalopram. Ingestion of more than 600 mg citalopram or more than 300 mg escitalopram requires cardiac monitoring for 8 hours (11 hours if the patient did not receive activated charcoal within 4 hours of ingestion). Ingestion of more than 1000 mg citalopram or more than 500 mg escitalopram requires cardiac monitoring for 13 hours. At the end of the observation period, if the QTc is less than 450 msec, the monitoring can be discontinued, and the patient may be discharged if asymptomatic. Patients with symptoms of toxicity or a QTc of greater than 450 msec at the end of the observation period should be admitted for continued cardiac monitoring. Seizures have been reported after ingestions of more than 600 mg citalopram, and serious toxicity after ingestion of 800 mg or more. PEDIATRIC: QTc prolongation has been reported after ingestion of escitalopram 200 mg. THERAPEUTIC DOSE: ADULT: Citalopram: Initially, 20 mg/day orally; max dose 40 mg/day. Escitalopram: 10 to 20 mg/day orally; max dose 20 mg/day. PEDIATRIC: Safety and effectiveness in children have not been established.
CITALOPRAM AND RELATED AGENTS
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Most patients require only supportive care. Control agitation and confusion with either benzodiazepines or serotonin antagonist such as cyproheptadine or chlorpromazine. Hypertension and tachycardia are generally mild and well tolerated, and do not require specific treatment. MANAGEMENT OF SEVERE TOXICITY: Early intubation, neuromuscular paralysis, ventilation assistance, and aggressive cooling should be performed if the patient presents with respiratory depression, severe muscle rigidity, and severe hyperthermia. Adequate circulatory support with IV fluids and vasopressors (if needed) should be assured if patient presents with circulatory collapse. Treat seizures with benzodiazepines; use barbiturates or propofol for recurrent seizures. Patients with wide-complex dysrhythmias should be treated with hypertonic sodium bicarbonate boluses. Although QTc interval prolongation is well described, torsade de pointes is rare. If torsade de pointes occurs, patients should be treated using standard interventions (magnesium sulfate 2 g IV, external or internal cardiac pacing).
- Decontamination: PREHOSPITAL: Activated charcoal can be considered within the first hour after large ingestion (greater than 600 mg citalopram), if the patient has an appropriate level of consciousness, has a patent airway, and is able to drink the charcoal. HOSPITAL: Administer activated charcoal if the patient presents early after large ingestion (greater than 600 mg citalopram), if the patient has an appropriate level of consciousness, patent airway and can drink the charcoal, or if the patient is intubated. Severe toxicity is rare; gastric lavage is rarely, if ever, warranted.
- Airway management: Perform early with neuromuscular paralysis if the patient presents with respiratory or CNS depression, severe muscle rigidity, or severe hyperthermia.
- Antidote: CYPROHEPTADINE: A serotonin antagonist with high affinity for the 5-HT2 receptors; effective for milder cases of serotonin syndrome. Dose: ADULT: 12 mg orally or nasogastric tube, followed by 4 to 8 mg every 4 to 6 hours. CHILD: 0.25 mg/kg/day orally or nasogastric tube divided every 6 hours, maximum dose 12 mg/day. CHLORPROMAZINE: A phenothiazine antipsychotic with 5-HT2 antagonist activity; indicated in severe serotonin syndrome cases. Dose: 12.5 to 50 mg IV, followed by 25 to 50 mg every 6 hours. It is NOT generally recommended because it may cause severe hypotension.
- Seizure: IV benzodiazepines, barbiturates, or propofol for recurrent seizures.
- Serotonin syndrome: IV benzodiazepines, cooling measures. Cyproheptadine may be considered (ADULT: 12 mg orally or nasogastric (NG) tube, followed by 4 to 8 mg orally or NG tube every 4 to 6 hours if symptoms persist, up to a maximum of 32 mg in 24 hours. CHILD: 0.25 mg/kg/day divided every 6 hours, maximum dose 12 mg/day). Severe cases have been managed with benzodiazepine sedation and neuromuscular paralysis with nondepolarizing agents.
- Torsades de pointes: Hemodynamically unstable patients require electrical cardioversion. Emergent treatment with magnesium or atrial overdrive pacing is indicated. Detect and correct underlying electrolyte abnormalities.
- Monitoring of patient: Monitor vital signs (including temperature) and mental status. Monitor serum electrolytes (including potassium, bicarbonate) following significant overdose. Obtain baseline ECG, continuous cardiac monitoring, and serial ECGs following a significant exposure. Monitor serial blood glucose, especially in patients with depressed mental status; severe hypoglycemia has been reported after citalopram overdose. Plasma concentration is not readily available and does not correlate well with therapeutic or adverse effects. It is not indicated for the acute management of overdose.
- Enhanced elimination procedure: Hemodialysis and hemoperfusion are NOT of value due to the large volume of distribution.
- Patient disposition: HOME CRITERIA: Children and adults with mild symptoms (eg, vomiting, mydriasis, diaphoresis, mild somnolence) following an inadvertent ingestion of up to 100 mg citalopram or 50 mg escitalopram can be managed at home with instructions to call the poison center, if symptoms develop. For patients already on citalopram or escitalopram, those with inadvertent ingestions of up to 5 times their own single therapeutic dose can be observed at home with instructions to call the poison center back if symptoms develop. OBSERVATION CRITERIA: Patients with deliberate ingestions, those with more than mild symptoms, and ingestions of more than 100 mg citalopram or 50 mg escitalopram should be sent to a health care facility. Patients on chronic citalopram or escitalopram therapy should be sent to a healthcare facility if they ingest more than 5 time their own single therapeutic dose. Ingestion of more than 600 mg citalopram or more than 300 mg escitalopram requires cardiac monitoring for 8 hours (11 hours if the patient did not receive activated charcoal within 4 hours of ingestion). Ingestion of more than 1000 mg citalopram or more than 500 mg escitalopram requires cardiac monitoring for 13 hours. At the end of the observation period, if the QTc is less than 450 msec, the monitoring can be discontinued, and the patient may be discharged if asymptomatic. Patients with symptoms of toxicity or a QTc of greater than 450 msec at the end of the observation period should be admitted for continued cardiac monitoring. ADMISSION CRITERIA: Patients with mild to moderate toxicity after intentional overdose need to be monitored for prolonged QTc for at least 13 hours. Patients with severe toxicity need to be admitted to an intensive care unit. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or an unclear diagnosis.