Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications

Abstract

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 < 90 mmHg] (15 [8%] vs. one; p = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180–4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3–18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12–31 h; p = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (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.

Keywords:

• Duloxetine
• selective serotonin reuptake inhibition
• norepinephrine reuptake inhibition
• antidepressant
• drug overdose
• toxicity

Acknowledgments

The authors acknowledge the assistance of the medical and nursing staff at the Calvary Mater Newcastle emergency department. We also thank the Clinical Toxicology Research Group research staff members for data entry, maintenance of the toxicology database, and for obtaining medical records for study participants.

Author contributions

GI, JC, KI, RP designed the study; GI, KI and RP identified patients; GI and KI did the data extraction; GI carried out the analysis of the data; RP, MK and GI did the literature review; GI drafted the manuscript. All authors read and approved the final manuscript. GI is guarantor of the paper.

Disclosure statement

All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

Additional information

Funding

Geoff Isbister is funded by an NHMRC Senior Research Fellowship ID1154503.