Citalopram overdose and severe serotonin syndrome in an intermediate metabolizing patient

• Published in: The American journal of emergency medicine 2019-10, Vol.37 (10), p.1993.e5-1993.e6
• Main Authors: Schult, Rachel F., Morris, Anna J., Picard, Lindsey, Wiegand, Timothy J.
• Format: Article
• Language: English
• Subjects: Adult; Anesthesia; Antidepressants; Case reports; Citalopram; Citalopram - pharmacokinetics; Citalopram - poisoning; CYP2C19; Cytochrome P-450 CYP2C19 - genetics; Drug dosages; Drug Overdose; Emergency medical care; Enzymes; Female; Genetics; Genotype; Genotypes; Humans; Hyperthermia; Inactivation; Ingestion; Metabolism; Metabolites; Overdose; Patients; Pharmacogenomic Variants - genetics; Pharmacogenomics; Seizures; Serotonin; Serotonin syndrome; Serotonin Syndrome - genetics; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - pharmacokinetics; Serotonin Uptake Inhibitors - poisoning; Suicide, Attempted; Tachycardia; Toxicity; Treatment Outcome
• ISSN: 0735-6757; 1532-8171
• DOI: 10.1016/j.ajem.2019.06.038

Citalopram is a selective serotonin reuptake inhibitor used for treatment of depression. Metabolism is primarily through CYP3A4 and CYP2C19; activity of the latter can vary depending on genetics. Although rare after single agent exposure, large citalopram ingestions can lead to serotonin syndrome. We report a case of citalopram overdose in an intermediate CYP2C19 metabolizer complicated by severe serotonin syndrome. A 25-year-old female presented after intentional citalopram overdose with seizures, tachycardia, persistent neuromuscular findings, and severe hyperthermia requiring aggressive sedation and cooling. Protracted symptoms required critical care services throughout a 14 day hospital stay despite traditional treatment of serotonin syndrome. Pharmacogenomic studies revealed intermediate CYP2C19 metabolism which reduces citalopram inactivation and may cause increased levels and toxicity. In the majority of serotonin syndrome cases, symptoms resolve rapidly after treatment initiation and discontinuation of the offending agents. Severe cases are typically associated with ingestion of multiple serotonergic agents. Our patient had severe toxicity after single agent ingestion. Pharmacogenetic testing identified abnormal CYP2C19 activity and previous cases have associated enzyme dysfunction and citalopram toxicity. Citalopram overdose may be associated with severe serotonin syndrome and further investigation is warranted to understand the impact of enzyme genotype on toxicity.