Rachel F Schult1, Anna J Morris2, Lindsey Picard3, Timothy J Wiegand3. 1. Department of Pharmacy, University of Rochester Medical Center, 601 Elmwood Ave. Box 638, Rochester, NY 14642, United States of America; Department of Emergency Medicine, University of Rochester Medical Center, 601 Elmwood Ave. Box 655, Rochester, NY 14642, United States of America. Electronic address: rachel_schult@urmc.rochester.edu. 2. St. John Fisher College, Wegmans School of Pharmacy, 3690 East Ave., Rochester, NY 14618, United States of America. 3. Department of Emergency Medicine, University of Rochester Medical Center, 601 Elmwood Ave. Box 655, Rochester, NY 14642, United States of America.
Abstract
INTRODUCTION: 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. CASE DETAILS: 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. DISCUSSION: 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. CONCLUSION: Citalopram overdose may be associated with severe serotonin syndrome and further investigation is warranted to understand the impact of enzyme genotype on toxicity.
INTRODUCTION: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 citalopramoverdose in an intermediate CYP2C19 metabolizer complicated by severe serotonin syndrome. CASE DETAILS: A 25-year-old female presented after intentional citalopramoverdose 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. DISCUSSION: 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 citalopramtoxicity. CONCLUSION:Citalopramoverdose may be associated with severe serotonin syndrome and further investigation is warranted to understand the impact of enzyme genotype on toxicity.
Authors: Farzin Zobdeh; Ivan I Eremenko; Mikail A Akan; Vadim V Tarasov; Vladimir N Chubarev; Helgi B Schiöth; Jessica Mwinyi Journal: Pharmaceutics Date: 2022-06-01 Impact factor: 6.525