In the United States, around 17.3 million adults (7.1% of the population) experienced “at least one major depressive episode” in 2017.

Having diabetes increases a person’s chance of developing depression by two to three times, but only 25–50% of those with both conditions receive treatment.

“The reduction of mortality in individuals with [diabetes] remains a critically important and unmet need,” explain Dr. Vincent Chin-Hung Chen — of Chiayi Chang Gung Memorial Hospital and Chang Gung University in Puzi, Taiwan — and colleagues in a recent paper in The Journal of Clinical Endocrinology & Metabolism.

The team set out to investigate whether taking antidepressants affects mortality rates in people who have both diabetes and depression.

Higher doses linked to fewer deaths

“The incidence of major depressive disorder [among] individuals with diabetes is significantly greater than the general population,” says Dr. Chen. “Diabetes and depression each independently contribute to increasing total mortality.”

Dr. Chen and colleagues used data from the Taiwan National Health Insurance Research Database and identified 53,412 people who had first received a diagnosis of diabetes and then an additional diagnosis of depression.

For the purpose of their study, the team defined “depression” as having had at least one psychiatric admission or three psychiatric outpatient visits, and having received a diagnosis from a psychiatrist.

Of all the people in the study, 50,532 used antidepressants.

The scientists divided the people who took antidepressants into three groups based on how much of a particular drug they took each day. The groups were low, medium, and high cumulative daily dose groups.

When the researchers analyzed the data, they found that as the daily dose increased, death rates decreased.

Specifically, the data showed an incident rate of death of 1,963.7 per 100,000 person-years in the low dose group and 1113.7 per 100,000 person-years in the high dose group.

In other words, taking high daily doses of antidepressants was linked to a 35% reduction in mortality when compared with taking low daily doses.

Other factors that increased a person’s risk of death in the study cohort were being male, living in a rural area, having a lower socioeconomic status, and having more severe depression.

‘Further rationale’ for depression screening

Dr. Chen and collagues then looked at the different classes of antidepressants in more detail. They compared the risk of mortality of those in the medium and high groups with that of those in the low group by measuring hazard ratios.

Compared with taking a low daily dose, taking a high daily dose of norepinephrine-dopamine reuptake inhibitors (NDRIs) was associated with an 80% decrease in mortality. Other results included the following:

Taking a high dose of selective serotonin reuptake inhibitors (SSRIs) was associated with a 37% decrease in mortality.

Taking a high dose of serotonin-norepinephrine reuptake inhibitors (SNRIs) was associated with a 42% decrease in mortality.

Taking a high dose of mirtazapine was associated with a 40% decrease in mortality.

Taking a high dose of tricyclic/tetracyclic antidepressants was associated with a 27% decrease in mortality.

Taking a high dose of trazodone was associated with a 48% decrease in mortality.

On the other hand, those taking a medium daily dose of reversible inhibitor of monoamine oxidase A (RIMA) were nearly twice as likely to die, and those in the high daily dose group had a nearly 50% greater mortality rate than those taking a low dose.

Dr. Chen suggests that taking antidepressants may reduce inflammation and, by extension, death risk. Another theory he puts forward in the paper is that the drugs may reduce excessive blood clotting.

According to the American Heart Association (AHA), nearly 80% of people with diabetes die due to blood clot-related complications, such as heart attacks and stroke.

“[These data provide] further rationale for the screening and treating of depression in persons who have diabetes.”

Dr. Vincent Chin-Hung Chen

The study has some limitations, however. For example, the researchers did not have information on the specific causes of death. Dr. Chen also points out that the results may not hold true for populations outside of Taiwan.

The team also did not compare the risk of death in those not taking antidepressants with those who did, instead focusing on hazard ratios between those taking low daily doses of the drugs compared with medium or high daily doses.