Antidepressants are one of the most widely prescribed drugs in the global north. However, little is known about the health consequences of long-term treatment.
Researchers from Bristol’s Centre for Academic Mental Health wanted to know if long-term antidepressant usage (over five and ten years) was linked to the development of six health issues: diabetes, high blood pressure, coronary heart disease, stroke, and related syndromes, and two mortality outcomes (death from cardiovascular disease and any cause).
They used data from UK Biobank, a large-scale biomedical database and research resource containing anonymized genetic, lifestyle and health information from half a million UK participants. They then linked comprehensive health data with prescription and disease data (using GP records) on 222,121 adults aged between 40 to 69 years old.
Once pre-existing risk variables were considered, the researchers discovered that long-term antidepressant usage was linked to an increased risk of coronary heart disease and an increased risk of mortality from cardiovascular disease and any cause. Non-SSRI antidepressants (mirtazapine, venlafaxine, duloxetine, and trazodone) posed the most significant dangers, with the usage of these medications linked to a two-fold increased risk of coronary heart disease, cardiovascular death, and all-cause mortality at ten years.
There was also some evidence that antidepressants, particularly SSRIs, were associated with a reduced risk (23 to 32 percent lower) of developing high blood pressure and diabetes. The reasons for these paradoxical findings are unclear. Further work is needed to understand the extent to which differences are due to the severity of the underlying depression or the way the different drugs work.
Dr. Narinder Bansal, the study’s lead author and Honorary Research Fellow at Bristol’s Centre for Academic Mental Health and Centre for Academic Primary Care, said: “While we have taken into account a wide range of pre-existing risk factors for cardiovascular disease, including those that are linked to depression such as excess weight, smoking, and low physical activity, it is difficult to fully control for the effects of depression in this kind of study, partly because there is considerable variability in the recording of depression severity in primary care.”
“This is important because many people taking antidepressants such as mirtazapine, venlafaxine, duloxetine, and trazodone may have more severe depression. This makes it difficult to fully separate the effects of depression from the effects of medication. Further research is needed to assess whether the associations we have seen are genuinely due to the drugs and why this might be.”
“Meanwhile, our message for clinicians is that prescribing antidepressants in the long term may not be harm-free. We hope that this study will help doctors and patients have more informed conversations when weighing up the potential risks and benefits of treatments for depression.”
“Regardless of whether the drugs are the underlying cause of these problems, our findings emphasize the importance of proactive cardiovascular monitoring and prevention in patients who have depression and are on antidepressants, given that both have been associated with higher risks.”
“For anyone with concerns about their long-term use of antidepressants, we urge them to talk to their GP before they stop taking the medication. It is essential they do not stop taking them suddenly.”
- Narinder Bansal et al. Antidepressant use and risk of adverse outcomes: population-based cohort study. BJPsych. DOI: 10.1192/bjo.2022.563