A recent phase III trial revealed disappointing results regarding the use of mirtazapine, an inexpensive antidepressant, in alleviating severe, persistent breathlessness in patients suffering from chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD). The study, led by Irene Higginson, BMBS, PhD, from Kings College London, found that after 56 days of treatment, patients who received mirtazapine showed no significant improvement in their “worst breathlessness” compared to those who received a placebo. This lack of efficacy was measured using a 0-10 numeric rating scale, with a mean difference of 0.105 (95% CI -0.407 to 0.618, P=0.69) between the two groups.
Despite previous case reports and a small feasibility study suggesting the potential benefits of mirtazapine in reducing feelings of panic associated with severe breathlessness, the current trial failed to demonstrate any advantage of the antidepressant. Furthermore, Higginson highlighted that the use of mirtazapine may lead to adverse reactions and increased healthcare utilization, making it an unsuitable option for managing severe breathlessness in COPD and ILD patients. This information challenges the common practice of prescribing off-label medications like opioids, benzodiazepines, or antidepressants for breathlessness relief.
The Need for Caution in Off-Label Drug Use
Higginson cautioned against the indiscriminate use of off-label medicines, emphasizing the importance of evidence-based approaches to treatment. She noted that relying on drugs without proper clinical support could potentially harm patients and undermine their overall care. The editorial accompanying the study, written by Kris Mooren, MD, PhD, and Huib Kerstjens, MD, PhD, echoed this sentiment, urging healthcare professionals to adopt individualized care strategies that address the physical, psychological, social, and spiritual aspects of breathlessness.
The international randomized trial, known as BETTER-B, involved 225 patients with severe breathlessness from COPD, ILD, or both. Participants were randomly assigned to receive daily doses of mirtazapine or a placebo, with assessments conducted over a 56-day period. Despite some promising rationale for the study and the anxiolytic effects of tricyclic and tetracyclic antidepressants, no significant differences were observed between the mirtazapine and placebo groups in terms of breathlessness severity and healthcare utilization.
Recommendations for Future Research and Care
Mooren and Kerstjens emphasized the need for personalized approaches to breathlessness management, taking into account the diverse needs of patients in different clinical settings. They highlighted the importance of multidisciplinary care teams and comprehensive breathlessness support services to address the complex nature of this symptom. Moving forward, healthcare professionals should prioritize evidence-based interventions that target the underlying causes of breathlessness while acknowledging the limitations of drug-based therapies.
The findings of the BETTER-B trial shed light on the ineffectiveness of mirtazapine as a treatment option for severe breathlessness in COPD and ILD patients. This study underscores the importance of evidence-based practice and individualized care in addressing complex symptoms like breathlessness. As researchers and clinicians continue to explore alternative treatment modalities, a holistic approach to breathlessness management remains crucial in providing optimal care for patients with chronic respiratory conditions.
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