Antidepressants Reduce Mortality For Patients With Diabetes And Depression

Both type 1 and type 2 diabetes increase the risk of depression; can antidepressants reduce mortality for people with comorbid diabetes and depression?

Depression affects an average of 8% of Americans aged 20 years or older. Patients with type 1 diabetes are about three times more likely, and patients with type 2 diabetes are about twice as likely, to battle depression than those without diabetes. Both diabetes and depression independently increase mortality rate; there is great concern for patients with comorbid diabetes and depression.   

A recent study sought to assess the impact of antidepressants on mortality in patients with comorbid diabetes and depression. Previous studies have shown that antidepressant use in chronic obstructive pulmonary disease (COPD) decreased rate of mortality, while studies focused on cardiovascular disorders displayed a negative effect of antidepressants on mortality. 

This population-based cohort study analyzed data from the National Health Insurance Research Database in Taiwan from 2000 to 2013. The subset of data included patients who had at least one psychiatric admission or three psychiatric outpatient visits, and the diagnosis of depression (major depressive disorder or dysthymic disorder [persistent depressive disorder]) was made by physicians using ICD 9 codes. All subjects included were diagnosed with depression following their diagnosis of diabetes. The population included 50,532 people taking antidepressants (SSRI, SNRI, mirtazapine, trazodone, TCA and reversible inhibitor of monoamine oxidase or RIMA) and 2,880 people not taking antidepressants for a total of 53,412 enrollees. Each category of antidepressants was divided into 3 groups by cumulative defined daily dose (cDDD). 

Risk of mortality was analyzed by comparing the high dose antidepressant group to the low dose group. Differences between the antidepressant group and the non-antidepressant group were thought to be affected greatly by patient demographics including access to care and insufficient drug adherence. The results displayed a statistically significant difference in mortality between the antidepressant group compared to the non-antidepressant group. The incidence rate of death events ranged from 1113.7 per 100,000 person-years (95% CI: 1078.4-1150.3) in the highest dose group, to 1963.7 per 100,000 person-years (95% CI:1876.8-2054.7) in the lowest dose group (p=<0.001). After adjustment for covariates, it was concluded that as the total cumulative dose of antidepressants increased, the rate of total mortality decreased. Significance was displayed at a cDDD of more than 28 (HR=0.91, CI=0.83-1.00) and the statistical significance was even greater at doses ≥84 (HR=0.65, CI=0.59-0.71). 

Further analyses showed several other factors that affected mortality in patients with diabetes and depression. Males were at greater risk for mortality compared to females (HR=1.71, CI=1.63-1.80). Those living in urban areas had a lower risk for mortality compared to participants living in rural areas (HR=0.75, CI=0.69-0.83). Heart failure, ESRD, COPD and malignancy each contributed to increased mortality (p=<0.05). 

While this study examined a large population with many covariates and outcomes data, several limitations hinder this data. The causes of death were not documented; this information could have led to an understanding of how antidepressant therapy decreases mortality in patients with diabetes. Among patients with depression, suicide is a major concern and is especially relevant when discussing mortality; this data was not recorded. Also, comorbid conditions outside of heart failure, ESRD, COPD and malignancy were not recorded. 

The mechanism by which antidepressants improve mortality is unclear, but researchers have hypothesized that modulation of neurotransmitters including serotonin, dopamine, and glutamate affects inflammatory systems leading to improved cardiovascular outcomes. Another theory involves the potential relationship between diabetes and hypercoagulation; SSRIs and SNRIs have been shown to inhibit platelet adhesion and benefit the atherosclerotic pathway. 

This study provides evidence that screening and treating depression in patients with diabetes is important and can improve survival. Although it is currently unclear exactly how antidepressant therapy impacts mortality, clinicians should recognize the correlation. 

Practice Pearls:

• A recent study displayed a significant decrease in mortality from antidepressant therapy among patients with comorbid diabetes and depression. 
• Within this study, cause of death was not documented; therefore, there is not a clear understanding regarding how antidepressants reduce mortality. 
• It is important for clinicians to screen and treat for depression in patients with diabetes. 

References: Antidepressants Reduce Mortality For Patients With Diabetes And Depression

Chen, Hong-Ming, et al. “Antidepressants Reduced Risk of Mortality in Patients with Diabetes Mellitus: a Population-Based Cohort Study in Taiwan.” The Journal of Clinical Endocrinology & Metabolism, 2019, doi:10.1210/jc.2018-02362.

Roy, Tapash, and Cathy E. Lloyd. “Epidemiology of Depression and Diabetes: A Systematic Review.” Journal of Affective Disorders, vol. 142, 2012, doi:10.1016/s0165-0327(12)70004-6.

“Products – Data Briefs – Number 303 – February 2018.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/nchs/products/databriefs/db303.htm.]

Amber Satz, PharmD Candidate, LECOM School of Pharmacy