Protracted escitalopram discontinuation syndrome and serotonin toxicity associated with CYP2C19 poor metabolism: A case report

Serotonin-related adverse drug reactions (ADRs) of selective serotonin reuptake inhibitors, including serotonin toxicity (ST) and antidepressant discontinuation syndrome (ADS), may significantly affect adherence to antidepressant therapy. ST is a rare but potentially serious adverse drug reaction resulting from excessive serotonergic activity, while ADS may occur after the abrupt discontinuation or dose reduction of an antidepressant. Both complications may be influenced by pharmacokinetic and pharmacogenetic (PGx) factors, although research on these relationships is limited. This case report describes a 40-year-old, medically healthy patient identified to be a CYP2C19 *2/*2 poor metabolizer (PM) who potentially experienced ST and prolonged ADS following treatment with escitalopram. After starting escitalopram while on buspirone and stimulant medications, she developed symptoms consistent with ST, including agitation, confusion, diarrhea, and muscle rigidity, leading to discontinuation. A retrial of escitalopram after 3 weeks resulted in similar symptoms. Despite ongoing ST-like symptoms, the patient chooses to continue escitalopram for 2 years, given her perceived benefits with treatment. Upon discontinuation after being on escitalopram for more than 2 years, the patient experienced prolonged withdrawal symptoms consistent with ADS. This case highlights the utility of pre-emptive PGx testing in antidepressant therapy and the importance of interprofessional care in enhancing the patient's self-efficacy.