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Depression, Its Treatment, and Diabetes Risk

Aug 31, 2021
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Macrina Ghali, PharmD Candidate 2021, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences

Loss of healthy behaviors due to depression may increase the risk of the development of type 2 diabetes.

Diabetes is related to many risk factors such as a sedentary lifestyle, poor diet, and obesity. Previous studies have shown that depression might increase the risk of type 2 diabetes development. However, studies have been inconsistent and underlying pathophysiology has not been explained. Depression may result in a loss of self-care practices, leading to overeating, diminished physical activity, smoking, and increased alcohol intake. The use of antidepressants has improved over the past few years, making them one of the most prescribed medication classes. Antidepressants, however, may lead to impaired glucose homeostasis and weight gain, increasing the risk of type 2 diabetes development. Unfortunately, current literature has not explained a detailed understanding of the mechanisms and causal relationships. Therefore, researchers performed a population-based retrospective cohort study in Taiwan to determine the association of depression, antidepressant medications, and the risk of type 2 diabetes.   


Patient data was taken from the Taiwan National Health Insurance Research Database (NHIRD) and included 46,201 patients without a history of type 2 diabetes from 2000 – 2013. The primary outcome was newly diagnosed type 2 diabetes, and patients on one antidepressant were included to assess the direct, causal relationship of different medications.  Statistical analysis was conducted utilizing chi-square and two-sample t-tests. A statistically significantly higher number of patients in the depression group had comorbidities (P < 0.001). Furthermore, researchers equally balanced age and gender between both groups to exclude any age/sex-related differences. Among these patients, 29.71% received SSRIs, 6.29% received TCAs, and 9.65% received heterocyclic antidepressants. Patients were followed up for a median duration of over seven years in both the depression and comparison cohorts.

Results found that the depression group had a statistically significant higher rate of type 2 diabetes development (p = 0.002). The incidence rate was 4.21 and 3.68 per 1,000 person-years in the depression and comparison cohort, respectively. Moreover, female patients with depression had a higher risk of type 2 diabetes incidence when compared to women without depression (HR 1.25, 95% CI 1.17 – 1.33). Among age group sub-analysis, patients with depression had a higher risk of type 2 diabetes in all three groups, with hazard ratios being 1.14, 1.15, and 1.15 in the less than 49 years old, between 50 to 64 years old, and 65 years or more groups, respectively. When comparing antidepressants, SSRIs, TCAs, heterocyclic antidepressants, and other antidepressants, all had significantly lower risks of type 2 diabetes with hazard ratios of 0.67, 0.63, 0.90. and 0.69, respectively.

Overall, patients with depression and no antidepressant medications had a higher risk of developing type 2 diabetes. The underlying mechanism may be due to a disruption in the hypothalamus-pituitary-adrenal axis leading to increased corticotropin-releasing hormone levels and the subsequent occurrence of diabetes. In contrast, patients on antidepressants, especially those treated with SSRIs, had a lower risk of new-onset diabetes. This may be due to the effect of antidepressants on elevating mood and enabling patients with a depressive disorder to engage in healthy behaviors. Strengths of this study are the long duration of follow-up and large population size, increasing power. However, this study’s limitation is the primarily Taiwanese population, limiting generalizability to other areas of the world.

Furthermore, several risk factors for type 2 diabetes, such as alcohol and tobacco consumption, family history, dietary intake, and body mass index, were missing from the NHIRD database, preventing the analysis of confounding factors. Moreover, analysts did not include data on the patients’ fasting blood glucose and HbA1c to assess the full extent of depression and antidepressants on glycemic control. In conclusion, the study demonstrated that depression was associated with a higher risk of type 2 diabetes, while antidepressants significantly reduced the occurrence of new-onset diabetes.

Practice Pearls:

  • Healthcare professionals should educate patients on the impact depression may have on diabetes occurrence.
  • Adherence to proper lifestyle and antidepressant medications should be encouraged to reduce the risk of type 2 diabetes among patients with depression.
  • Future studies should be conducted to determine the exact mechanism of reduced diabetes risk among patients receiving antidepressants.


Fang, Yi-Jen et al. “Association between Depression, Antidepression Medications, and the Risk of Developing Type 2 Diabetes Mellitus: A Nationwide Population-Based Retrospective Cohort Study in Taiwan.” BioMed research international vol. 2021 8857230. January 7, 2021.

Björntorp, “Visceral fat accumulation: the missing link between psychosocial factors and cardiovascular disease?,” Journal of Internal Medicine, vol. 230, no. 3, pp. 195–201, 1991.


Macrina Ghali, PharmD Candidate 2021, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences