By Seema Gupta, MD, MSPH
Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV
SYNOPSIS: Long-term antidepressant use could lead to elevated risks of coronary heart disease, along with higher cardiovascular disease mortality and all-cause mortality rates.
SOURCE: Bansal N, Hudda M, Payne RA, et al. Antidepressant use and risk of adverse outcomes: Population-based cohort study. BJPsych Open 2022;8:e164.
Antidepressants are one of the most widely prescribed medications across the United States. More than one out of eight Americans older than age 18 years have taken one recently.1 While studies have shown that many patients continue to stay on antidepressants for years once initiated, the long-term health consequences are not well understood.
The authors of previous studies have found associations between antidepressant use and several adverse events in older patients, such as falls, hyponatremia, stroke, and attempted suicide.2 Similarly, in patients age 20 to 64 years, antidepressants have been found to be associated with significantly higher fracture rates and increased risks of falls.3 The authors of a meta-analysis found selective serotonin reuptake inhibitors (SSRIs) were associated with a higher risk of cerebrovascular disease (relative risk, 1.24; 95% CI, 1.15-1.34).4 However, the analysis did not include a distinction between the effects of antidepressants and depression itself. Since the disease of depression is strongly associated with adverse risk profiles, such as excess adiposity, diabetes, smoking, poor diet, physical inactivity, and cardiovascular morbidity and mortality, it is important to understand the contributions of antidepressant medications, if any, to cardiovascular morbidity/mortality as well as all-cause mortality.
Bansal et al studied data from UK Biobank participants whose data were linked to primary care records and investigated the association between antidepressant use and adverse events. The study team compared the risk of developing adverse health outcomes between those who had not taken antidepressants and those who had been treated with the most commonly prescribed antidepressants over 10 years. They assessed the association between various drug classes (SSRIs and non-SSRIs) and four morbidity outcomes (diabetes, hypertension, coronary heart disease [CHD], and cerebrovascular disease) as well as two mortality outcomes (cardiovascular disease [CVD] and all-cause) at five- and 10-year follow-ups. The cohort was restricted to 222,121 qualifying participants, age 40 to 69 years, who were recruited to the UK Biobank between 2006 and 2010.
The researchers found that at 10-year follow-up, SSRI treatment was associated with increased risks of cerebrovascular disease (HR, 1.34; 95% CI, 1.02-1.77), CVD mortality (HR, 1.87; 95% CI, 1.38-2.53), and all-cause mortality (HR, 1.73; 95% CI, 1.48-2.03). Non-SSRI treatment was associated with a higher risk of CHD (HR, 1.99; 95% CI, 1.31-3.01), CVD (HR, 1.86; 95% CI, 1.10-3.15), and all-cause mortality (HR, 2.20; 95% CI, 1.71-2.84). Researchers also found some evidence indicating antidepressant use, particularly SSRIs, was associated with a lower risk of developing high blood pressure and diabetes.
COMMENTARY
The prevalence of depression has been spreading globally, with depressive disorders listed as one of the leading causes of disability over the last three decades. Similarly, the prevalence of depression among young adults also has become worse. As more patients are prescribed antidepressants for longer periods, it is critical to better understand the morbidity and mortality that may result from their use. Bansal et al found long-term antidepressant use was associated with a higher risk of CHD, CVD, and all-cause mortality. Specifically, the risk was found to be much worse for non-SSRI types of antidepressants, such as mirtazapine, venlafaxine, duloxetine, and trazodone, as the use of such drugs was associated with approximately a two-fold increased risk of CHD, CVD, and all-cause mortality at 10 years. Concurrently, there seems to be evidence suggesting SSRIs may be associated with a lower risk of developing hypertension and diabetes.
Many patients taking non-SSRI antidepressants may be living with more severe depression to begin with, which makes it even more difficult to fully differentiate the long-term risks of depression from the adverse effects of medication. Therefore, it becomes even more critical that clinicians discuss with their patients the risks of antidepressant use. The most relevant message may be that antidepressants for long-term use are not without significant risks. A conversation may help not only address the medications’ adverse effects, but also other options for managing depression.
REFERENCES
1. Brody DJ, Gu Q. Antidepressant use among adults: United States, 2015-2018. National Center for Health Statistics. September 2020.
2. Coupland CA, Dhiman P, Barton G, et al. A study of the safety and harms of antidepressant drugs for older people: A cohort study using a large primary care database. Health Technol Assess 2011;15:1-202, iii-iv.
3. Coupland C, Hill T, Morriss R, et al. Antidepressant use and risk of adverse outcomes in people aged 20-64 years: Cohort study using a primary care database. BMC Med 2018;16:36.
4. Biffi A, Scotti L, Corrao G. Use of antidepressants and the risk of cardiovascular and cerebrovascular disease: A meta-analysis of observational studies. Eur J Clin Pharmacol 2017;73:487-497.
Long-term antidepressant use could lead to elevated risks of coronary heart disease, along with higher cardiovascular disease mortality and all-cause mortality rates.
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