A case of serotonin syndrome following the reintroduction of aripiprazole after dextromethorphan overdose

PCN Rep. 2025 Jul 15;4(3):e70162. doi: 10.1002/pcn5.70162. eCollection 2025 Sep.

ABSTRACT

BACKGROUND: Serotonin syndrome is a potentially life-threatening condition that arises from excessive serotonergic activity. Dextromethorphan (DXM), commonly used as a non-prescription antitussive, can induce serotonin syndrome when taken in high doses or in combination with other serotonergic agents. At supratherapeutic levels, DXM acts as a serotonin reuptake inhibitor and N-methyl-D-aspartate (NMDA) receptor antagonist, thereby significantly increasing the risk of serotonin toxicity.

CASE PRESENTATION: We present the case of an 18-year-old female diagnosed with attention-deficit/hyperactivity disorder (ADHD) and comorbid depressive symptoms who developed serotonin syndrome after the reinitiation of aripiprazole in the context of recent DXM overdose. Following ingestion of an estimated 600 mg of DXM, the patient exhibited signs of toxicity. The subsequent administration of aripiprazole was temporally associated with the emergence of serotonin syndrome, evidenced by hyperreflexia, hypertonia, and fever, in accordance with the Hunter Serotonin Toxicity Criteria.

CONCLUSION: This case illustrates the necessity of cautious reintroduction of serotonergic or dopaminergic medications following DXM overdose. Given the potential for prolonged metabolism and interaction-especially in individuals with reduced CYP2D6 activity-clinicians should allow for adequate washout periods before restarting psychotropic agents, such as aripiprazole.

PMID:40673125 | PMC:PMC12264311 | DOI:10.1002/pcn5.70162