A recent phase III trial conducted by Irene Higginson, BMBS, PhD, of Kings College London, revealed that mirtazapine, an inexpensive antidepressant, did not perform better than a placebo in alleviating severe, persisting breathlessness in patients with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD). The study’s primary outcome, which measured the “worst breathlessness” over the past 24 hours on a 0-10 numeric rating scale (NRS), showed no significant difference between patients who received mirtazapine and those who received a placebo after 56 days of treatment.
Mirtazapine, a tetracyclic antidepressant known for reducing feelings of panic that often accompany severe breathlessness, was chosen for the study based on its biological plausibility and previous case reports and feasibility studies. However, the results of this trial indicated that mirtazapine failed to provide any significant benefit in reducing breathlessness. The study’s authors cautioned against the off-label use of medications like mirtazapine for conditions such as severe breathlessness.
In an editorial accompanying the study publication, Kris Mooren, MD, PhD, and Huib Kerstjens, MD, PhD, highlighted the rationale for the study and the lack of prior research on the use of antidepressants in patients with severe breathlessness. While the study did not show any benefit of mirtazapine, the editorialists emphasized the importance of individualized care approaches that address the physical, psychological, social, and spiritual aspects of breathlessness.
The BETTER-B trial, a double-blind study that randomized 225 patients with severe breathlessness from COPD, ILD, or both, compared the effectiveness of daily mirtazapine to a placebo. Patients in the trial had a mean age of 74 years, with the majority being men and having comorbidities. The results of the study showed no significant differences in secondary outcomes such as healthcare usage, changes in quality of life measures, and symptom severity between the mirtazapine and placebo groups.
While adverse events in the study were relatively mild, the mirtazapine group had higher rates of healthcare utilization and informal care use compared to the placebo group. The most common side effects observed with mirtazapine were dry mouth, somnolence, fatigue, and sedation. The study was also limited by factors such as the COVID-19 pandemic and Brexit, which led to an incomplete enrollment of participants, making it underpowered to detect significant differences between the treatment groups.
The study on the use of mirtazapine in alleviating severe breathlessness in COPD and ILD patients did not yield favorable results. The findings suggest that the off-label use of antidepressants like mirtazapine may not be effective in managing breathlessness and could lead to increased healthcare utilization and adverse events. Moving forward, a more comprehensive and personalized approach to care that addresses the multiple dimensions of breathlessness is warranted for these patient populations.
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