Role of Serotonin Transporter in Antidepressant-Induced Diabetes Mellitus: A Pharmacoepidemiological–Pharmacodynamic Study in VigiBase®
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The association between antidepressant exposure and type 2 diabetes mellitus is still debated. Moreover, the pharmacological mechanisms remain unknown.
The objective of this study was to investigate this putative relationship with the role of antidepressant pharmacological targets using the ‘pharmacoepidemiological–pharmacodynamic’ method.
First, we performed case/non-case analyses in VigiBase® (the World Health Organization international database of suspected adverse drug reactions) to examine a signal of increased type 2 diabetes reporting (expressed as the reporting odds ratio and its 95% confidence interval) for antidepressants in general; examine and rank type 2 diabetes signals between the different pharmacological classes of antidepressants and the different antidepressants (58 in total). Second, we performed linear regression analyses to explore the association between the type 2 diabetes signal ranked between antidepressants and their binding affinities for nine targets (serotonin, norepinephrine, dopamine transporters, 5-HT2C serotonin, D2 dopamine, α1, α2 adrenergic, M3 muscarinic and H1 histamine receptors).
A significant type 2 diabetes signal was found for antidepressants in general, three classes of antidepressants (tricyclic antidepressants, serotonin reuptake inhibitors and “other” antidepressants) and 15 individual antidepressants in particular. Among the antidepressants, three serotonin reuptake inhibitors [escitalopram (adjusted reporting odds ratio 1.15 [1.07–1.25]), paroxetine (1.15 [1.07–1.23]), sertraline (1.23 [1.17–1.31])] and three “other” antidepressants [duloxetine (1.15 [1.07–1.23]), trazodone (1.20 [1.09–1.32]), venlafaxine (1.15 [1.08–1.23])] were the antidepressants most frequently reported with type 2 diabetes. We found a significant correlation between the type 2 diabetes signal and serotonin transporter affinity (slope = 0.14 [0.06–0.23], p = 0.003, R2 = 0.43) but not the other targets.
The present study suggests a potential role for serotonin transporter in antidepressant-induced type 2 diabetes.
The authors thank the Uppsala Monitoring Centre in general, and in particular Ms. Camilla Westerberg, research pharmacist, and the VigiBase® custom search services team for providing and giving permission to use the VigiBase® data. Despite the use of the World Health Organization database, the present study results and conclusions are those of the authors and not necessarily those of the Uppsala Monitoring Centre, National Centres or the World Health Organization.
Thi Thu Ha Nguyen, Anne Roussin, Vanessa Rousseau, Jean-Louis Montastruc and François Montastruc designed the study and wrote the protocol. Thi Thu Ha Nguyen performed the experiments. Thi Thu Ha Nguyen and Vanessa Rousseau analysed the data. Thi Thu Ha Nguyen, Anne Roussin, Vanessa Rousseau, Jean-Louis Montastruc and François Montastruc contributed to the interpretation of the data. Thi Thu Ha Nguyen wrote the first draft of the manuscript and Anne Roussin, Vanessa Rousseau, Jean-Louis Montastruc and François Montastruc critically revised the manuscript for important intellectual content. All authors contributed to and have approved the final manuscript.
Compliance with Ethical Standards
Thi Thu Ha Nguyen was supported by a research grant for her PhD (of which this study is a part) from the Pierre Fabre Foundation, France and the French Embassy in Hanoi, Vietnam.
Conflict of interest
Thi Thu Ha Nguyen, Anne Roussin, Vanessa Rousseau, Jean-Louis Montastruc and François Montastruc have no conflicts of interest that are directly relevant to the content of this study.
This article does not contain any studies with human participants or animals performed by any of the authors.
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