A new study from King’s College London shows that off-label prescriptions of a common antidepressant doesn’t help breathlessness in patients with respiratory disease – and may cause side effects.
Researchers warn prescribing medicines for a use which it has not been licensed could make things worse, even though the prescriber was trying to help.
The findings, presented at the ERS Congress in Vienna and published today in The Lancet Respiratory Medicine, show the desperate need for options to treat the symptoms of severe breathlessness, as there are no drugs licensed for this in the UK or most countries.
The severe breathlessness caused by chronic respiratory diseases greatly impacts patient’s quality of life. As well as creating substantial clinical challenges and health care costs. Most patients with diseases like this have few options to help with their symptoms.
Ahead of the trial, researchers surveyed doctors in respiratory and palliative medicine and found doctors were often using off-label prescribing – where a clinician prescribes a medicine for use in a different way than that stated in its licence. Various off-label prescriptions were being used, including common anti-anxiety and anti-depressant drugs like benzodiazepines and SSRIs.
Mirtazapine, a common antidepressant, was one of the types of drugs being prescribed. Case series and early studies showed it had potential. However, in this international trial, the first large-scale study to be done, researchers found that mirtazapine does not improve breathlessness in patients with respiratory disease compared with placebo. They also found that patients receiving mirtazapine had slightly more side effects and needed more care from hospitals and family members.
Chronic respiratory diseases affect 454.6 million people worldwide, with numbers predicted to increase with an aging population. Over 217 million people globally have Chronic Obstructive Pulmonary Disease (COPD) or Interstitial Lung Disease (ILD), both of which can cause severe breathlessness as they progress.
Off-label use can be as safe as on-label use if based on good evidence. It is often used when symptoms can't be controlled with licenced medicines, particularly in serious illnesses. This is common in severe breathlessness care, making proper evaluation of medicines vital. Off-label prescribing doesn't mean a doctor is making a mistake; it often happens when there are no other options to manage symptoms like breathlessness.
First author Professor Irene Higginson, King’s College London said: “Breathlessness is a widespread issue in palliative care as a symptom of respiratory diseases, heart disease and some cancers. When severe, it’s distressing for patients, as well as their caregivers, family and friends. It diminishes people’s quality of life and often leads to considerable health and social care use, including driving emergency hospital admissions.
“Despite being a widespread issue we still don’t have effective treatments available. As such, many doctors turn to off-label prescribing, trying to help their patients.
“Our earlier survey found that 19% of respiratory and 11% of palliative physicians frequently recommend antidepressants for severe breathlessness in COPD, so these medicines are already being used off-label. This new trial concludes that mirtazapine is not recommended for the treatment of breathlessness, that the use of unlicensed medicines should be approached with caution and that it’s crucial to subject medicines in palliative care to rigorous trials.
“We need further research into potential therapies for severe breathlessness. In the meantime, we recommend clinicians use early identification and non-pharmacological approaches, such as those offered from breathlessness support services, to treat the symptom.”
The paper is published in The Lancet Respiratory Medicine on September 9th 2024.
ENDS
Funding information
This project received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 825319. Additional support was from the Cicely Saunders International (Registered Charity No. 1087195) Breathlessness Programme and the National Institute for Health and Care Research (NIHR) Applied Research Collaboration South London.
About King’s College London
King’s College London is amongst the top 40 universities in the world and top 10 in Europe (THE World University Rankings 2024), and one of England’s oldest and most prestigious universities. With an outstanding reputation for world-class teaching and cutting-edge research, King’s maintained its sixth position for ‘research power’ in the UK (2021 Research Excellence Framework).
King's has more than 33,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and 8,500 staff.
For nearly 200 years, King’s students and staff have used their knowledge and insight to make a positive impact on people, society and the planet. Focused on delivering positive change at home in London, across the UK and around the world, King’s is building on its history of addressing the world’s most urgent challenges head on to accelerate progress, make discoveries and pioneer innovation. Visit the website to find out more about Vision 2029, which sets out bold ambitions for the future of King’s as we look towards our 200th anniversary.
World-changing ideas. Life-changing impact: kcl.ac.uk/news
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;
- Attracting, 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 international development funding from the UK government.
Journal
The Lancet Respiratory Medicine