A recent study conducted by King’s College London has raised concerns about the practice of prescribing medications for unapproved uses, particularly for treating breathlessness in patients with chronic respiratory diseases. While doctors often use off-label prescriptions to address unmet clinical needs, the findings suggest that such practices may sometimes do more harm than good (1^✔ ✔Trusted Source
Mirtazapine to alleviate severe breathlessness in patients with COPD or interstitial lung diseases (BETTER-B): an international, multicentre, double-blind, randomised, placebo-controlled, phase 3 mixed-method trial

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Off-label prescription refers to the practice of prescribing a drug for a purpose other than the one it was originally approved for by regulatory authorities. It is commonly used when there are no licensed drugs available to manage certain symptoms or conditions. Off-label use can sometimes be the only option for patients suffering from severe or untreatable symptoms, such as those caused by chronic respiratory diseases.

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Risks of Off-Label Prescribing: Insights from the Mirtazapine Trial

Researchers from King’s College London conducted a large-scale, international trial to explore the effects of mirtazapine, a common antidepressant, on patients with chronic respiratory diseases. This study, published in The Lancet Respiratory Medicine and presented at the European Respiratory Society (ERS) Congress in Vienna, focused on whether mirtazapine could relieve severe breathlessness, a debilitating symptom in many chronic respiratory conditions.

• Mirtazapine does not improve breathlessness in patients with chronic respiratory disease compared to a placebo.
• Patients treated with mirtazapine experienced slightly more side effects than those on placebo.
• Those receiving mirtazapine required more hospital care and assistance from family members, suggesting the drug may lead to increased healthcare burdens.

These results highlight the risks of prescribing medications off-label without sufficient supporting evidence.

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The Growing Need for Breathlessness Treatment Options

Chronic respiratory diseases affect 454.6 million people worldwide, with many suffering from severe breathlessness. Two of the most common diseases, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD), together account for over 217 million cases globally. These conditions progressively worsen over time, severely impacting patients’ quality of life and placing a strain on healthcare systems.

Breathlessness is a particularly distressing symptom for patients and their caregivers, leading to frequent hospital admissions and the need for intensive care. As there are currently no licensed medications in most countries, including the UK, to treat severe breathlessness, doctors often resort to off-label prescriptions in hopes of alleviating symptoms.

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Off-Label Prescribing in Breathlessness Management

Before conducting their clinical trial, the researchers surveyed doctors specializing in respiratory and palliative care. They found that 19% of respiratory doctors and 11% of palliative care physicians frequently recommended antidepressants such as benzodiazepines and Selective Serotonin Reuptake Inhibitors (SSRIs), like mirtazapine, to treat severe breathlessness.

While earlier smaller studies suggested that mirtazapine could potentially reduce breathlessness, this latest research contradicts those findings, indicating that off-label prescriptions in such cases should be approached with extreme caution.

Why Off-Label Prescribing Can Be Risky

Off-label prescriptions are not necessarily unsafe, but they require strong evidence to back their effectiveness in new uses. In the case of mirtazapine, earlier studies and case reports showed potential benefits, but larger, controlled trials have now debunked those claims.

The main risks associated with off-label use include:

• Lack of proven efficacy: Medications prescribed off-label may not be effective for the new condition they are intended to treat.
• Increased side effects: Since the medication is being used in a new context, patients might experience unexpected or more severe side effects, as seen in the mirtazapine trial.
• Higher healthcare costs: Patients using off-label medications may require additional hospital care, increasing the burden on healthcare systems and families.

The King’s College study emphasizes the importance of rigorous clinical trials before recommending off-label use of any medication. The lack of approved drugs for severe breathlessness has led doctors to explore alternative treatments, but this trial demonstrates the potential harm in doing so without proper evidence.

Non-Pharmacological Approaches: An Alternative to Off-Label Prescribing

Given the current lack of effective drug treatments for severe breathlessness, non-pharmacological approaches offer a promising alternative. These interventions include:

• Breathing techniques: Strategies such as controlled breathing exercises and pulmonary rehabilitation programs.
• Oxygen therapy: In some cases, providing supplemental oxygen can help alleviate symptoms.
• Physical activity: Regular, gentle exercise has been shown to improve respiratory function and overall well-being in patients with chronic respiratory diseases.
• Psychological support: Counseling and support for both patients and caregivers can help manage the emotional burden of living with a chronic illness.

While off-label prescribing remains a common practice in many fields of medicine, especially in situations where licensed treatments are lacking, this study from King’s College London raises serious concerns about its safety and efficacy. The findings highlight the need for caution when prescribing medications for unapproved uses and underscore the importance of further research to find effective treatments for severe breathlessness.

For now, clinicians are encouraged to explore non-drug approaches to help alleviate patients’ symptoms and to remain vigilant when considering off-label prescriptions.

Reference:

1. Mirtazapine to alleviate severe breathlessness in patients with COPD or interstitial lung diseases (BETTER-B): an international, multicentre, double-blind, randomised, placebo-controlled, phase 3 mixed-method trial – (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(24)00187-5/fulltext)

Source-Medindia