Long-term use of antidepressants may double the risk of heart disease, according to the most comprehensive epidemiological study to date to examine the health consequences of taking the drug over a decade. The University of Bristol-led study, published in the British Journal of Psychiatry Open, analyzed data from over 200,000 people.
Antidepressants are one of the most commonly prescribed medications in England. In 2018, over 70 million antidepressant medications were prescribed. The striking increase in prescriptions (nearly doubling in a decade) is largely due to long-term treatment rather than increasing diagnosis. However, little is known about the health consequences of long-term use of these drugs.
Researchers at the Bristol Center for Academic Mental Health wanted to find out whether long-term antidepressant use (over five and 10 years) is associated with the occurrence of six health problems: diabetes, hypertension, coronary artery disease, stroke and related syndromes, and two mortality outcomes (death by cardiovascular disease and any cause).
Using data from the UK Biobank, a large-scale biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants, the team linked comprehensive health data with prescription and disease data (using GP records) from 222,121 Adults between the ages of 40 and 69.
They compared the risk of developing health problems between those who had not taken antidepressants and those who had been on the most commonly prescribed antidepressants in England for ten years. These have been categorized by drug class as selective serotonin reuptake inhibitors, often known as SSRIs, called citalopram, sertraline, fluoxetine, and paroxetine, and “other” non-SSRI antidepressants, called mirtazapine, venlafaxine, duloxetine, and trazodone.
The researchers found that after adjusting for pre-existing risk factors, long-term use of antidepressants was associated with an increased risk of coronary artery disease and an increased risk of death from cardiovascular disease and all causes. Risks were greater for non-SSRI antidepressants (mirtazapine, venlafaxine, duloxetine, trazodone), with use of such drugs being associated with a two-fold increased risk of coronary artery disease, cardiovascular mortality, and all-cause mortality at ten years.
There was also evidence that antidepressants, and SSRIs in particular, were associated with a reduced risk (by 23 to 32 percent lower risk) of developing high blood pressure and diabetes. The reasons for these seemingly paradoxical findings are unclear, and further work is needed to understand to what extent the differences are due to the severity of the underlying depression or to the mode of action of the different drugs.
dr Narinder Bansal, lead author of the study and Honorary Research Fellow at Bristol’s Center for Academic Mental Health and Center for Academic Primary Care, said: “We considered a wide range of pre-existing risk factors for cardiovascular disease, including those associated with depression such as obesity, smoking, and low physical activity, it is difficult to fully control for the impact of depression in this type of study, in part because there are significant differences in the primary care assessment of depression severity.
“This is important because many people who take antidepressants such as mirtazapine, venlafaxine, duloxetine and trazodone may have more severe depression. This makes it difficult to completely separate the effects of depression from the effects of medication. More research is needed to assess whether the associations we observed are really due to the drugs, and if so, why this might be the case.
“In the meantime, our message to physicians is that long-term antidepressant prescriptions may not be safe. We hope this study will help physicians and patients have more informed conversations when weighing the potential risks and benefits of treatments for depression. Regardless of whether the medications are the underlying cause of these problems, our results underscore the importance of proactive cardiovascular surveillance and prevention in patients suffering from depression and taking antidepressants, since both are associated with higher risks.
“We urge anyone who has concerns about their long-term use of antidepressants to speak to their GP first before stopping the medication. It is very important that they do not suddenly stop taking it.”
The study was funded by the National Institute of Health and Care (NIHR) Research School for Primary Care Research (NIHR SPCR) and was also supported by the National Institute of Health and Care (NIHR) Bristol Biomedical Research Center (NIHR Bristol BRC) partnership between the University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol.
“Antidepressant use and risk of adverse outcomes: a population-based cohort study” by Narinder Bansal et al. in which British Journal of Psychiatry [open access]
1. “Community Dispensed Prescriptions: England 2005-2015” Health and Social Information Center Prescriptions and Drugs Team [05 July 2016].
2. “NHS prescribed record number of antidepressants last year” by Iacobucci G. et al. in BMJ [2019; 364: l1508]
3. UK biobank: an open access resource for identifying the cause of a wide range of complex diseases of middle and old age, by Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J ., et al. om PLOS medicine [2015; 12(3): e1001779]
Counseling and support for people with mental health problems
About the National Institute for Health and Care Research
The mission of the National Institute for Health and Care Research (NIHR) is to improve the nation’s health and wealth through research. We do this through:
- funding high-quality, timely research that benefits the NHS, public health and social care;
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About UK Biobank
The UK Biobank is a large-scale biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. The UK Biobank database, which includes blood samples, heart and brain scans and genetic data from volunteer participants, is accessible worldwide to accredited researchers conducting health-related research in the public interest.
The UK Biobank recruited 500,000 people aged between 40 and 69 from across the UK between 2006 and 2010. With their consent, they provided detailed information about their lifestyle, physical measurements, and had blood, urine, and saliva samples collected and stored for future analysis.
The UK Biobank research resource makes an important contribution to the advancement of modern medicine and treatment, enabling a better understanding of the prevention, diagnosis and treatment of a wide range of serious and life-threatening diseases – including cancer, heart disease and stroke. Since the
The UK Biobank resource was opened for research in April 2012 and since then 30,000 researchers from 100 countries have been granted permission to use it and over 5,000 peer-reviewed papers using the resource have now been published.
UK Biobank is generously supported by its founding sponsors, the UK Medical Research Council (MRC) and Wellcome, as well as the British Heart Foundation, Cancer Research UK, the National Institute of Health Research (NIHR) and UK Research and Innovation (UKRI). The organization has over 200 dedicated staff at multiple locations across the UK.
For more information about the UK Biobank, visit http://www.ukbiobank.ac.uk
About the National Institute for Health and Care Research Bristol Biomedical Research Center (NIHR Bristol BRC)
The innovative biomedical research at the National Institute for Health and Care Research Bristol Biomedical Research Center (NIHR Bristol BRC) takes science off the bench or computer and develops it into new medicines, treatments or health advice. Its world-leading scientists work on many aspects of health, from the role of individual genes and proteins to analyzing large data sets from hundreds of thousands of people. The Bristol BRC is unique among the NIHR’s 20 BRCs across England thanks to its expertise in pioneering public health research.