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Adverse health outcomes associated with long-term antidepressant use

Press release issued: 29 September 2022

Regular review of treatment plans for patients on long-term antidepressants, recommend researchers

Long-term antidepressant use may double the risk of heart disease, finds the most comprehensive epidemiological study to date to investigate the health consequences from using the medication over ten years. The University of Bristol-led study, published in the British Journal of Psychiatry Open, analysed data on over 200,000 people.

Antidepressants are one of the most widely prescribed drugs in England. In 2018, over 70-million antidepressant prescriptions were dispensed. The striking rise in prescribing (nearly doubling in a decade) is due mainly to long-term treatment rather than increased diagnosis. However, little is known about the health consequences of long-term use of these medicines.

About the study

Researchers from Bristol’s Centre for Academic Mental Health aimed to find out if long-term antidepressant use (over five and ten years) was associated with the onset of six health problems: diabetes, high blood pressure, coronary heart disease, stroke and related syndromes, and two mortality outcomes (death from cardiovascular disease and from any cause).

Using data from 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) on 222,121 adults aged between 40 to 69 years old.

They 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 in England over ten years. These were categorised 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.

Key findings

The researchers found that, once pre-existing risk factors had been taken into account, long-term antidepressant use was associated with an increased risk of coronary heart disease, and an increased risk of death from cardiovascular disease and from any cause. The risks were greater for non-SSRI antidepressants (mirtazapine, venlafaxine, duloxetine, trazodone), with the use of such drugs associated with a two-fold increased risk of coronary heart disease, cardiovascular mortality, and all-cause mortality at ten years.

There was also some evidence that antidepressants, and particularly SSRI’s, were associated with a reduced risk (23 to 32% lower risk) of developing high blood pressure and diabetes. The reasons for these apparently paradoxical findings are unclear and further work is needed to understand the extent to which differences are due to severity of the underlying depression or due to 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, 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 a more severe depression. This makes it difficult to fully separate the effects of the 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 if so why this might be.

“Meanwhile, our message for clinicians is that prescribing of 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 emphasise 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 any concerns about their long-term use of antidepressants, we urge them to talk to their GP first before they stop taking the medication. It is very important they do not stop taking them suddenly.”


The study was funded by the National Institute of Health and Care (NIHR) Research School for Primary Care Research (NIHR SPCR) through the Centre for Academic Primary Care, University of Bristol, and was also supported by the National Institute of Health and Care (NIHR) Bristol Biomedical Research Centre (NIHR Bristol BRC) a partnership between University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol.

Read the paper

Paper: Antidepressant use and risk of adverse outcomes: a population-based cohort study by Narinder Bansal et al. in the British Journal of Psychiatry [open access].

Further information

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 health and wealth of the nation through research. We do this by:

  • Funding high quality, timely research that benefits the NHS, public health and social care;
  • Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;
  • Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;
  • tracting, training and supporting the best researchers to tackle complex health and social care challenges;
  • Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
  • Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.

NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK Aid from the UK government.

About UK Biobank
UK Biobank is a large-scale biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. UK Biobank’s database, which includes blood samples, heart and brain scans and genetic data of the volunteer participants, is globally accessible to approved researchers who are undertaking health-related research that’s in the public interest.

UK Biobank recruited 500,000 people aged between 40-69 years in 2006-2010 from across the UK. With their consent, they provided detailed information about their lifestyle, physical measures and had blood, urine and saliva samples collected and stored for future analysis.

UK Biobank’s research resource is a major contributor in the advancement of modern medicine and treatment, enabling better understanding of the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses – including cancer, heart diseases and stroke. Since the
UK Biobank resource was opened for research use in April 2012 and since then 30,000 researchers from 100 countries have been approved to use it and more than 5,000 peer-reviewed papers that used the resource have now been published.

UK Biobank is generously supported by its founding funders 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 organisation has over 200 dedicated members of staff, based in multiple locations across the UK.

You can find out more about UK Biobank at

About the Centre for Academic Primary Care, University of Bristol
The Centre for Academic Primary Care (CAPC) at the University of Bristol is a leading centre for primary care research in the UK, one of nine forming the NIHR School for Primary Care Research. It sits within Bristol Medical School, an internationally recognised centre of excellence for population health research and teaching.

About the National Institute for Health and Care Research Bristol Biomedical Research Centre (NIHR Bristol BRC)
The National Institute for Health and Care Research Bristol Biomedical Research Centre’s (NIHR Bristol BRC) innovative biomedical research takes science from the laboratory bench or computer and develops it into new drugs, treatments or health advice. Its world-leading scientists work on many aspects of health, from the role played by individual genes and proteins to analysing large collections of data on hundreds of thousands of people. Bristol BRC is unique among the NIHR’s 20 BRCs across England, thanks to its expertise in ground-breaking population health research.

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