Prolonged Serotonin Toxicity after Massive Duloxetine Overdose

Document Type

Conference Proceeding

Publication Date


Publication Title

Journal of Medical Toxicology


Background: Duloxetine is a second-generation serotoninnorepinephrine reuptake inhibitor prescribed for treatment of both psychiatric disorders and neuropathic pain. Duloxetine overdose overall is uncommon, with a total of 6281 cases involving the drug reported in 2020 by the American Association of Poison Control Centers. Survival after massive overdose has previously been reported, however prior case reviews have typically described resolution of symptoms within 24 hours.

Methods: This is a case report obtained via retrospective chart review.

Results: A 74-year-old female who presented to the emergency department after intentional ingestion of an unknown quantity of duloxetine and cephalexin. After an unremarkable initial workup, the patient was admitted medically for observation. She was noted by the hospitalist team 13 hours after ingestion to have mild generalized tremors and nystagmus. The next day the patient developed severe agitation, jerking body movements, and worsening horizontal nystagmus. After not responding to initial therapy, psychology and neurology were consulted. Ultimately, the patient was diagnosed with opsoclonus-myoclonus syndrome secondary to serotonin toxicity 64 hours after her initial ingestion. A duloxetine level was drawn 81 hours post-ingestion and returned a serum level of 3300 ng/mL. The majority of the patient's neurologic symptoms resolved five days after her admission.

Conclusions: This case highlights the potential for both delayed onset as well as prolonged serotonin toxicity in cases of massive duloxetine overdose. Few case reports outside of postmortem studies have identified serum concentrations above 2000 ng/mL. This patient's level returned at 3300 ng/ mL more than three days after her initial ingestion. Several mechanisms may have delayed clearance and prolonged toxicity in this case including delayed absorption secondary to diabetic gastroparesis, inhibition of CYP2D6 by duloxetine, and reversal of CYP1A2 induction by smoking cessation upon admission.





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