A Case of Prolonged Serotonin Toxicity After Fluoxetine Ingestion in an Adolescent Patient

Selective serotonin reuptake inhibitors (SSRIs), indicated for many disorders, have nuanced pharmacology. Half-lives of fluoxetine and its active metabolite, norfluoxetine, are 7 days and up to 17.5 days, respectively. Norfluoxetine inhibits CYP2D6, which metabolizes fluoxetine. A single substance ingestion could cause prolonged serotonin toxicity. CYP2D6 genotyping may identify patients at increased risk. In fluoxetine overdose, clinicians can expect prolonged hospitalization requiring aggressive sedation as in this case. A 16-year-old female with anxiety, depression, and headaches on no prescribed medications presented to emergency care after ingesting fluoxetine, benztropine, trimethoprim-sulfamethoxazole (TMP-SMX), gabapentin, omeprazole, and atorvastatin. She was intubated, sedated with propofol and fentanyl, and transported to higher-level care. In the pediatric intensive care unit (PICU), she had examination findings suggestive of serotonin toxicity. She was extubated hospital day (HD) 2 but required sedation for persistent agitation. Her mental status improved 24 hours after receiving cyproheptadine HD8, but she remained hyperthermic until HD10. She was externally cooled for maximum temperature 40.1°C. Peak creatine kinase level was 827 international units/L (reference, 27-140 units/L). Fluoxetine and norfluoxetine concentrations obtained HD8 were 350 ng/mL and 280 ng/mL (therapeutic steady-state range, 72-258 ng/mL for norfluoxetine and 91-302 ng/mL for fluoxetine). CYP2D6 metabolizer phenotype was normal. The patient was discharged home at neurologic baseline HD19.