Association between dextromethorphan/bupropion with diabetes mellitus and hyperglycemia: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS)
13 affiliations
- 1Brain and Cognition Discovery Foundation, Canada
- 2University of Toronto Institute of Medical Science, Canada
- 3University Health Network, Canada
- 4University of Toronto Department of Pharmacology & Toxicology, Canada
- 5University of Ottawa Faculty of Medicine, Canada
- 6National University of Singapore Yong Loo Lin School of Medicine, Singapore
- 7National University of Singapore Institute for Health Innovation & Technology, Singapore
- 8The Hong Kong University of Science and Technology School of Science Division of, Hong Kong
- 9Psychiatry, Yale University School of Medicine, USA
- 10University of Connecticut School of Medicine, USA
- 11Department of Psychiatry and Mental Health, Pontificia Universidad Javeriana, Colombia
- 12Center for Clinical and Translational Research, Universidad Simon Bolivar, Venezuela
- 13Department of Psychiatry, University of Toronto, Canada
Abstract
Dextromethorphan/bupropion (DXM/BUP) is the first orally administered antidepressant combining dextromethorphan, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, and bupropion, a CYP2D6 inhibitor and antidepressant. DXM/BUP was approved by the United States Food and Drug Administration for Major Depressive Disorder (MDD) in adults in August 2022. Given that select psychotropic agents prescribed for MDD may alter glucose and insulin homeostasis, we investigated whether DXM/BUP was associated with disproportionate reporting of diabetes mellitus or hyperglycemia. Disproportionality analyses were conducted using reporting odds ratios (RORs), with DXM/BUP and comparator agents evaluated relative to a reference agent (acetaminophen). Data were obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the year of approval to April 26, 2026. A sensitivity analysis was performed on a restricted dataset from January 1, 2022, to April 30, 2026. Statistical significance was defined as a 95% confidence interval (CI) excluding 1.0. DXM/BUP was not associated with disproportionate reporting of diabetes mellitus (ROR = 0.33, 95% CI [0.07, 1.65], p = 0.18) or hyperglycemia (ROR = 0.10, 95% CI [0.01, 1.67], p = 0.11) relative to acetaminophen. Findings from the restricted 2022–2026 analysis were directionally consistent with the primary analysis. Given the sparse number of reports and wide CIs, these findings should be interpreted as preliminary and underpowered, rather than evidence of metabolic neutrality. Continued pharmacovigilance and prospective investigation are needed to further characterize the metabolic profile of DXM/BUP.
Related
- Bridging Nonconsecutive Esketamine Weeks with Bupropion and Over-the-Counter Dextromethorphan
- Off-Label Dextromethorphan/Bupropion for Emotional Lability Following Resection of an IDH-Mutant Astrocytoma: A Case Report.
- Psychiatric and Behavioral Adverse Event Reporting Patterns Among Dopamine Agonists in Parkinson’s Disease Using the Food and Drug Administration Adverse Event Reporting System
- Association between the stress hyperglycemia ratio and neovascular glaucoma in patients with proliferative diabetic retinopathy
- Association of Postoperative Stress Hyperglycemia Ratio with Suspected Infection, Culture Positivity, Sepsis, and Septic Shock in 1408 Patients After Cranial Neurosurgery
BibTeX
@article{zheng2026association,
title = {{Association between dextromethorphan/bupropion with diabetes mellitus and hyperglycemia: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS)}},
author = {Yang Jing Zheng and Sabrina Wong and Gia Han Le and Angela T. H. Kwan and Christine E. Dri and Roger Ho and Taeho Greg Rhee and Hernan F. Guillen-Burgos and Roger S. McIntyre},
journal = {CNS Spectrums},
year = {2026},
month = aug,
doi = {10.1017/s1092852926101163},
url = {https://doi.org/10.1017/s1092852926101163},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Association between dextromethorphan/bupropion with diabetes mellitus and hyperglycemia: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS)
AU - Yang Jing Zheng
AU - Sabrina Wong
AU - Gia Han Le
AU - Angela T. H. Kwan
AU - Christine E. Dri
AU - Roger Ho
AU - Taeho Greg Rhee
AU - Hernan F. Guillen-Burgos
AU - Roger S. McIntyre
PY - 2026
DA - 2026/08/07
JO - CNS Spectrums
DO - 10.1017/s1092852926101163
UR - https://doi.org/10.1017/s1092852926101163
AB - Dextromethorphan/bupropion (DXM/BUP) is the first orally administered antidepressant combining dextromethorphan, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, and bupropion, a CYP2D6 inhibitor and antidepressant. DXM/BUP was approved by the United States Food and Drug Administration for Major Depressive Disorder (MDD) in adults in August 2022. Given that select psychotropic agents prescribed for MDD may alter glucose and insulin homeostasis, we investigated whether DXM/BUP was associated with disproportionate reporting of diabetes mellitus or hyperglycemia. Disproportionality analyses were conducted using reporting odds ratios (RORs), with DXM/BUP and comparator agents evaluated relative to a reference agent (acetaminophen). Data were obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the year of approval to April 26, 2026. A sensitivity analysis was performed on a restricted dataset from January 1, 2022, to April 30, 2026. Statistical significance was defined as a 95% confidence interval (CI) excluding 1.0. DXM/BUP was not associated with disproportionate reporting of diabetes mellitus (ROR = 0.33, 95% CI [0.07, 1.65], p = 0.18) or hyperglycemia (ROR = 0.10, 95% CI [0.01, 1.67], p = 0.11) relative to acetaminophen. Findings from the restricted 2022–2026 analysis were directionally consistent with the primary analysis. Given the sparse number of reports and wide CIs, these findings should be interpreted as preliminary and underpowered, rather than evidence of metabolic neutrality. Continued pharmacovigilance and prospective investigation are needed to further characterize the metabolic profile of DXM/BUP.
SN - 1092-8529
SN - 2165-6509
ER -