Antidepressant Adherence Linked With Lower Risk of Advanced Diabetic Complications

Regular use of selective serotonin reuptake inhibitors or tricyclic or tetracyclic antidepressants was associated with a reduced risk of all-cause mortality in patients with diabetes.

Antidepressant adherence is associated with a lower risk of advanced diabetic complications compared with low adherence, according to a study published in The Journal of Clinical Endocrinology & Metabolism.

Antidepressants may decrease the effect of depression on diabetes, but they can increase the risk of cardiometabolic adverse effects, and this can vary among different classes of antidepressants. The aim of the current study was to research the relationship between antidepressant treatment and advanced diabetic outcomes (ie, macrovascular and microvascular complications) and mortality among patients with both conditions, as well as how various antidepressant classes impacted diabetic outcomes.

The nationwide retrospective cohort study used data from Taiwan’s National Health Insurance (NHI) program—which covers approximately 99% of the Taiwanese population—to study 36,276 patients with depression and newly treated type 2 diabetes (T2D) between 2001 and 2014. Patients with T2D had at least 1 claim with the diagnosis and at least 1 prescription for an antidiabetic drug. Patients with T2D and depressive disorders were included if they had at least 2 ambulatory or 1 inpatient diagnosis of depressive disorder within 1 year before entering the study.

Patients were followed from 6 months after the study began to whenever the study endpoints occurred or the end of 2014.

Most patients in the study were female (61.80%) and between 45 and 64 of age (55.62%). Most had comorbidities, including:

  • 41.75% with hypertension
  • 37.5% with dyslipidemia
  • 6.73% with comorbid chronic liver diseases
  • 11.12% with chronic obstructive pulmonary diseases

In addition, 20.26% had been hospitalized in the past year.

The study found that the risk of macrovascular complications and all-cause mortality in patients with T2D dropped when antidepressants were used regularly. Specifically, adherence to antidepressants was linked with a 0.92-fold decreased risk of macrovascular complications (95% CI, 0.84-1.00; P =.04) and a 0.86-fold decreased risk of all-cause mortality (95% CI, 0.75-0.98).

However, antidepressants were not linked to any reduction in microvascular complications.

By drug class, regular use of SSRIs were linked with a reduced risk of macrovascular complications (adjusted HR [aHR] = 0.83; 95% CI, 0.74-0.94) and all-cause mortality (aHR = 0.75; 95% CI, 0.62-0.91). Regular use of TCAs was also associated with a reduced risk of all-cause mortality. But antidepressant polypharmacy was linked with a higher risk of macrovascular complications (aHR = 1.27, 95% CI, 1.03-1.57) and all-cause mortality (aHR = 1.53; 95% CI,1.15-2.03).

Benzodiazepines were choses as a negative control; regular use of this class of medication was not linked with any T2D outcomes.

In explaining the findings, the researchers noted that depression is linked with poor prognosis in T2D and that their study, in line with previous ones, found that partial use of antidepressants was not linked with a reduced risk of subpar diabetic outcomes. They also had hypothesized that “the anti-inflammatory effect of the antidepressant itself might have played a role in the recovery of the endothelial and vascular damage among patients with depression” but their results showed no difference when it came to microvascular complications.

Additionally, the research showed varying risks of developing advanced diabetic complications among different antidepressants. Individual antidepressants had different effects on treating depression, and each had specific adverse effects. Since the sample sizes were small for the antidepressant classes, the varying risks of individual antidepressants for diabetic complications needs further investigation.

“Clinicians should emphasize antidepressant treatment adherence among patients with depression and diabetes mellitus,” the study authors concluded. “Such findings need to be replicated and confirmed in further investigations.”


Wu CS, Hsu LY, Pan YJ, Wang SH. Associations between antidepressant use and advanced diabetes outcomes in patients with depression and diabetes mellitus. J Clin Endocrinol Metab. Published online July 14, 2021. doi:10.1210/clinem/dgab443

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