A recent phase III trial has revealed that the inexpensive antidepressant, mirtazapine, is no more effective than a placebo in alleviating severe, persisting breathlessness caused by 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, there was no difference in the “worst breathlessness” experienced by patients who received mirtazapine compared to those who received a placebo. This disappointing outcome was based on a 0-10 numeric rating scale, with a mean difference of 0.105 (95% CI -0.407 to 0.618, P=0.69).
Severe breathlessness is a common issue affecting 75 million individuals worldwide, with limited medication options available for relief. As a result, healthcare providers often resort to off-label use of medications such as opioids, benzodiazepines, or antidepressants. Mirtazapine, specifically, was considered a potential treatment option due to its ability to reduce feelings of panic often associated with severe breathlessness. However, despite some biological plausibility and previous case reports suggesting its efficacy, the trial demonstrated no significant benefit in treating breathlessness.
Despite the desire to alleviate symptoms, Higginson emphasized the importance of caution when using off-label medications. She highlighted the fact that prescribing drugs for purposes beyond their approved indications could lead to adverse reactions and increased healthcare utilization. The study results indicate that mirtazapine not only failed to improve breathlessness but also resulted in higher rates of acute hospital visits, outpatient visits, and hours of family care compared to the placebo group.
In light of the study findings, it is clear that a one-size-fits-all approach to treating severe breathlessness is unlikely to be effective. While awaiting more effective therapies, healthcare providers are urged to adopt individualized approaches to care that address the physical, psychological, social, and spiritual aspects of breathlessness. Kris Mooren, MD, PhD, and Huib Kerstjens, MD, PhD, emphasized the importance of multidisciplinary care in supporting patients with severe breathlessness.
The BETTER-B trial, which enrolled 225 patients with COPD, ILD, or both, shed light on the limitations of using antidepressants like mirtazapine for the treatment of severe breathlessness. Despite the strong rationale for studying the use of antidepressants in this population, including their anxiolytic effects and mood-modulating properties, the trial results were underwhelming. It is clear that more research is needed to identify effective treatments for this challenging symptom.
The study’s findings underscore the importance of evidence-based prescribing practices and the need for individualized care in managing severe breathlessness. While mirtazapine may have shown promise in case reports and feasibility studies, the results of the phase III trial indicate that it is not a viable option for alleviating breathlessness in patients with COPD or ILD. Further research is needed to explore alternative treatment options that address the complex nature of this debilitating symptom.
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