Off-label drugs prescribed for shortness of breath could do more harm than good, scientists warn

A new study from King’s College London shows that off-label prescribing of a commonly used antidepressant does not help shortness of breath in patients with respiratory conditions – and can cause side effects.

Researchers warn that prescribing drugs for an unlicensed use could make matters worse, even if the prescriber tried to help.

The findings, presented at the ERS Congress in Vienna and published in The Lancet Respiratory Medicineshow the desperate need for options to treat the symptoms of severe breathlessness as there are no drugs registered for it in Britain and most countries.

The severe shortness of breath caused by chronic respiratory diseases has a major impact on a patient’s quality of life. In addition to creating substantial clinical challenges and healthcare costs. Most patients with such diseases have few options to help relieve their symptoms.

Ahead of the trial, researchers surveyed doctors in respiratory and palliative medicine and found that doctors often prescribe off-label – where a doctor prescribes a drug for use in a different way than stated in the license. Several off-label prescriptions were used, including common anti-anxiety and antidepressant medications such as benzodiazepines and SSRIs.

Mirtazapine, a common antidepressant, was one of the types of medications prescribed. Case series and early studies showed it had potential. However, in this international study, the first large-scale study conducted, researchers found that mirtazapine does not improve shortness of breath in patients with respiratory disease compared to placebo. They also found that patients given mirtazapine had slightly more side effects and required more care from hospitals and family members.

Chronic respiratory diseases affect 454.6 million people worldwide, and this number is expected to increase as the population ages. More than 217 million people worldwide suffer from chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD), both of which can cause severe shortness of breath as the disease progresses.

Off-label use can be just as safe as on-label use, if based on good evidence. It is often used when symptoms cannot be controlled with approved medications, especially in serious diseases. This is common when caring for severe shortness of breath, making proper evaluation of medications critical. Off-label prescribing does not mean a doctor makes a mistake; it often happens when there are no other options to manage symptoms such as shortness of breath.

First author Professor Irene Higginson, King’s College London said: “Breathlessness is a widespread problem in palliative care as a symptom of respiratory disease, heart disease and some cancers. When severe it is distressing for patients, as well as their carers , family and friends. It reduces people’s quality of life and often leads to significant use of health and social care, including emergency hospital admissions.

“Despite it being a widespread problem, we still have no effective treatments available. That’s why many doctors are turning to off-label prescribing in an effort to help their patients.

Our previous research found that 19% of respiratory physicians and 11% of palliative physicians often recommend antidepressants for severe shortness of breath in COPD, so these medications are already used off-label.

“This new study 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 is 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 that clinicians use early identification and non-pharmacological approaches, such as those offered by breathlessness support services, to treat the symptom.”