Desvenlafaxine overdose and the occurrence of serotonin toxicity, seizures and cardiovascular effects

Abstract

Context: Desvenlafaxine is used to treat major depression. Desvenlafaxine is also the active metabolite of venlafaxine. Venlafaxine overdose can cause serotonin toxicity, seizures and cardiovascular effects, but there is limited information on desvenlafaxine overdose.

Objective: We aimed at investigating the clinical effects and complications from desvenlafaxine overdose.

Materials and methods: This was a retrospective observational study of desvenlafaxine overdoses over a six-year period. Demographic details, dose and timing of the overdose, together with clinical effects, treatment and complications were extracted from a local hospital network database or the medical records of patients following hospital admission with a desvenlafaxine overdose.

Results: There were 182 cases of desvenlafaxine overdose included in the study. From the 182 cases, 75 were desvenlafaxine (± alcohol) only ingestions and 107 included one or more co-ingested drugs. In single-agent desvenlafaxine ingestions, median age was 25 years (range: 13–68 years) with a median ingested dose of 800 mg (range: 250–3500 mg; interquartile range (IQR): 600–1400 mg), and 54/75 (72%) were female. The Glasgow Coma Score (GCS) was 15 in 68/74 (92%) patients, 13–14 in 5/74 (7%), and was seven in one patient following aspiration. Mild hypertension (systolic blood pressure [BP] > 140–180 mmHg) occurred in 23/71 patients (32%), and tachycardia occurred in 29/74 (39%) patients. There were no abnormal QT intervals and no QRS >120 m s. Serotonin toxicity was diagnosed by the treating physician in 7/75 (9%) patients, but only one of these met the Hunter Serotonin Toxicity Criteria. None of the 75 patients who took desvenlafaxine only (± alcohol) had seizures, were admitted to intensive care or died. In comparison, the 107 patients taking desvenlafaxine in overdose with other medications developed more pronounced toxicity. Generalised seizures occurred in 5/107 (5%), but in three of these cases co-ingestants were possible proconvulsants. Fifteen patients had a GCS ≤9 and none had an abnormal QT or QRS. Severe effects appeared to be associated with coingestants.

Conclusion: Desvenlafaxine overdose causes minor effects with mild hypertension and tachycardia. The risk of seizures or serotonin toxicity is low.

Keywords:

• Overdose
• poisoning
• antidepressant
• toxicity
• serotonin syndrome
• seizures

Acknowledgements

We would like to 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. We also thank the New South Wales Poison Information Centre staff for recruiting cases to the study. We thank Dr. Naren Gunja for assisting with the Poison Information Centre recruitment. We thank Prof Nicholas Buckley for his idea to merge the datasets and his review of the manuscript.

Disclosure statement

The authors declare no conflicts of interest.