In pharmacotherapy, you always have to balance the pros and cons. Many side effects cause symptoms observed by the patient and therefore the dose is reduced or the medicine changed. Some of the adverse effects are asymptomatic but may cause complications in the long run. Antidepressants are often associated with weight gain and, consequently, the risk of developing type 2 diabetes. The first symptoms of this are an increase in HbA1c levels in a blood test.
Austin-Zimmermann and colleagues have studied the effect of CYP2D6 and CYP2C19 metabolic rate on HbA1c levels. The data has been collected from the UK Biobank. The study found that paroxetine users had HbA1c 2.3 mmol/L higher CYP2D6 in slow metabolisers than normal metabolisers. In these patients, higher than normal drug concentrations may predispose to diabetes. A similar association was observed with venlafaxine. Both venlafaxine and paroxetine have been associated with an increased risk of diabetes in previous studies. In the same study, diabetics taking venlafaxine with CYP2D6 slow metabolisers had HbA1c 10.15 mmol/L higher than normal metabolisers.
Based on the study, it can be thought that paroxetine and venlafaxine users could potentially reduce the incidence of type 2 diabetes associated with an antidepressant by individualised administration based on the CYP2D6 result.
Austin-Zimmerman, Isabelle, Marta Wronska, Baihan Wang, Haritz Irizar, Johan Hilge Thygesen, Anjali Bhat, Spiros Denaxas et al. “The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics.” medRxiv (2021).
https://www.medrxiv.org/content/10.1101/2021.07.07.21259926v2.full.pdf
“Figure 1 Frequency table of identified antipsychotics (blue bars) and antidepressants (green bars) in UK Biobank.” by Austin-Zimmermann et al https://doi.org/10.1101/2021.07.07.21259926, used under CC BY https://creativecommons.org/licenses/by/4.0/legalcode
