Long Term Antidepressant Use Associated With Increased Morbidity and Mortality

An article recently published in BJ Psych Open investigates the adverse effects of SSRIs and other antidepressants when taken for longer than five years.

Narinder Bansal, Mohammad Hudda, Rupert A. Payne, Daniel J. Smith, David Kessler, and Nicola Wiles utilized over 200,000 individual medical records collected by UK Biobank between 2006 and 2010.

“Antidepressants are one of the most widely prescribed drugs. Seventy million prescriptions were dispensed in 2018, amounting to nearly a doubling of prescriptions in a decade. This striking rise in prescribing is attributed to long-term treatment rather than an increased incidence of depression, and these trends are not limited to the UK,” the authors write. “However, little is known about the health consequences of long-term antidepressant treatment.”

In July, Joanna Moncreiff and Mark Horowitz conducted and published a review of the evidence for the “chemical imbalance theory” of depression, effectively debunking the idea. However, psychotropic medications are still used as the first-line treatment for depression despite questions about their efficacy. Additionally, long-term antidepressant use may have troubling side effects, but public and medical education concerning discontinuation and tapering remain scarce.

Bansal and colleagues sought to document the adverse effects of long-term antidepressant use. The United Kingdom Biobank collected medical records of over 500,000 individuals over four years (2006-2010). After excluding participants for various reasons (eg, the participant was no longer registered with their general practitioners or was on multiple antidepressants at the start of the study), over 200,000 participants between the ages of 40-69 years old remained 96% of whom were White.

The authors then assessed the association between antidepressant use and four different morbidities: diabetes, hypertension, coronary heart disease (CHD), and cerebrovascular disease (CV), and two different mortality outcomes, including cardiovascular disease (CVD) and all-cause mortality. Each morbidity was then assessed utilizing Cox’s proportional hazard model (a regression model commonly used to understand the association between the survival time of patients and one or more predictor variables).

The authors highlight that the experience of the symptoms commonly understood as “depression” is strongly associated with “health risk behaviors” or “cofounders,” such as obesity, smoking, and lack of physical activity, which are also risk factors for both CVD and diabetes. Through multiple statistical analyses, Bansal and colleagues did their best to account for these risk factors.

The authors discuss their findings:

“Our study found that long-term antidepressant use was associated with an increased risk of CHD, CVD, and all-cause mortality. These issues appear to be more problematic for antidepressants other than SSRIs (mirtazapine, venlafaxine, duloxetine, trazodone), with the use of such drugs associated with a two-fold increased risk of CHD, CVD, and all-cause mortality at ten years. However, there was also evidence that antidepressants, particularly SSRIs, were associated with a reduced risk of developing hypertension and diabetes. The findings were particularly evident after ten years of follow-up, where we had larger numbers of events.”

The authors explain why their findings may differ from other studies due to how they accommodated varying cofounders. After the authors adjusted for the risk behaviors that commonly co-occur with symptoms of depression, the increased risk of diabetes seems to be indistinguishable from that of antidepressant use vs. smoking/obesity.

However, the authors note that: “…it was not possible to distinguish between the effects of antidepressants and depression itself.” And that “…long-term antidepressant use was associated with an increased risk of CHD, CVD and all-cause mortality.”

****

Bansal, N., Hudda, M., Payne, R., Smith, D., Kessler, D., & Wiles, N. (2022). Antidepressant use and risk of adverse outcomes: Population-based cohort study. BJPsych Open, 8(5), E164. doi:10.1192/bjo.2022.563 (Link)

Leave a Comment