Poisonings Caused by Duloxetine Overdose: A Systematic Review

Background/Objectives: Duloxetine is a serotonin–norepinephrine reuptake inhibitor used for psychiatric and chronic pain conditions. It enhances serotonergic and noradrenergic neurotransmission by inhibiting the reuptake of serotonin and norepinephrine. Acute poisoning, most commonly resulting from intentional oral ingestion, may frequently present with neurological and cardiovascular manifestations. Although duloxetine is widely prescribed, evidence regarding acute overdose remains limited, and no validated toxic duloxetine concentration threshold reliably predicts the severity of duloxetine toxicity. This systematic review aimed to synthesize published cases of duloxetine poisoning and characterize clinical manifestations, management strategies, and outcomes. Methods: We searched PubMed and Google Scholar for case reports and case series describing cases of duloxetine poisoning. We included cases of acute duloxetine poisoning with a clearly toxic ingested dose and/or analytically confirmed toxic duloxetine concentrations. Results: A total of 18 publications describing 23 patients were included in this systematic review. Duloxetine intoxication was classified as suicidal in 17 cases (73.9%), accidental in 5 cases (21.7%), and not specified in one case (4.3%). In most cases (78.3%), duloxetine overdoses involved co-ingestion of other central nervous system depressants. The most common clinical manifestation was altered mental status, ranging from somnolence, confusion, disorientation, and drowsiness to impaired consciousness, coma, or unresponsiveness in severe cases. Nearly half of the included duloxetine poisoning cases (47.8%) were fatal. Conclusions: In conclusion, acute duloxetine intoxication is most frequently associated with the co-ingestion of other central nervous system depressants, and early recognition with prompt supportive management is essential to minimize the risk of fatal outcomes.