Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications

Objective: Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose. Methods: We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database. Results: There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25–48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405–1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; p = 0.040), develop coma (16 [9%] vs. none; p = 0.008) and hypotension [systolic BP 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia. Conclusion: Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose