The cost of drug repurposing: parallel economic evaluation of mirtazapine for severe breathlessness in the multinational BETTER-B trial

Breathlessness is a prevalent, distressing symptom in advanced respiratory disease. Proven treatments are lacking. Mirtazapine, an antidepressant, is increasingly prescribed. The placebo-controlled BETTER-B trial did not find significant clinical benefit of mirtazapine for severe breathlessness, and patient experiences were mixed. Given mirtazapine’s low cost and wide availability, it is important to understand effects more broadly. We conducted a parallel cost-effectiveness analysis of mirtazapine versus placebo. BETTER-B recruited 225 adults with chronic obstructive pulmonary disease and/or Interstitial Lung Diseases in seven countries between 2021 and 2023. We calculated quality-adjusted life years (QALYs) using EuroQoL EQ-5D-5 L and national value sets, and combined self-reported healthcare and informal care frequencies with unit costs. Primary trial endpoint was at day 56, with sensitivity analysis at day 180 (trial exit). In primary analysis mirtazapine reduced QALYs (-0.006 (95% confidence interval (CI): -0.012 to -0.001)) and was associated with higher total costs (+€231 (95% CI: -218 to + 680)). For willingness-to-pay thresholds of €20,000-€40,000 per QALY, mirtazapine had a 1%-2% likelihood of being cost-effective. These findings were substantively unaffected by sensitivity analyses to timeframe, perspective, outcome measurement, and modelling strategy. Repurposing mirtazapine to treat severe breathlessness negatively impacted patient outcomes while being associated with higher formal and informal costs, and should be discouraged. Off-label prescribing of repurposed medicines without robust evidence risks unnecessary strain on healthcare systems and families. Economic evaluation within testing of repurposed medicines is important. Parallel cost-effectiveness analyses can deliver high-value information even when the efficacy trial finds no effect.

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Journal
BMC Health Services Research
Published
2025-11-04
DOI
https://doi.org/10.1186/s12913-025-13605-9
Primary Topic
Chronic Obstructive Pulmonary Disease (COPD) Research
Type
article
Field-Weighted Citation Impact
0.00

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article

The cost of drug repurposing: parallel economic evaluation of mirtazapine for severe breathlessness in the multinational BETTER-B trial

Sabrina Bajwah, Peter May, David C. Currow, Matthew M Maddocks et al.
BMC Health Services Research
Chronic Obstructive Pulmonary Disease (COPD) Research
article

The cost of drug repurposing: parallel economic evaluation of mirtazapine for severe breathlessness in the multinational BETTER-B trial

Sabrina Bajwah, Peter May, David C. Currow, Matthew M Maddocks, Simon P. Hart, Piotr Janowiak, Caroline J. Jolley, Silvia Tanzi, Julia Brown, Samantha Smith, Charles Normand, Massimo Costantini, Małgorzata Krajnik, H M Mather, Kathrin Kahnert, Charlotte E. Bolton, Elena Turola, Steffen T. Simon, Luca Ghirotto, Miriam J. Johnson, Bobbie Farsides, Adejoke O Oluyase, Geraldine Murden, Irene J Higginson, Karen Ryan, Sarah Brown
article en

Abstract

Breathlessness is a prevalent, distressing symptom in advanced respiratory disease. Proven treatments are lacking. Mirtazapine, an antidepressant, is increasingly prescribed. The placebo-controlled BETTER-B trial did not find significant clinical benefit of mirtazapine for severe breathlessness, and patient experiences were mixed. Given mirtazapine’s low cost and wide availability, it is important to understand effects more broadly. We conducted a parallel cost-effectiveness analysis of mirtazapine versus placebo. BETTER-B recruited 225 adults with chronic obstructive pulmonary disease and/or Interstitial Lung Diseases in seven countries between 2021 and 2023. We calculated quality-adjusted life years (QALYs) using EuroQoL EQ-5D-5 L and national value sets, and combined self-reported healthcare and informal care frequencies with unit costs. Primary trial endpoint was at day 56, with sensitivity analysis at day 180 (trial exit). In primary analysis mirtazapine reduced QALYs (-0.006 (95% confidence interval (CI): -0.012 to -0.001)) and was associated with higher total costs (+€231 (95% CI: -218 to + 680)). For willingness-to-pay thresholds of €20,000-€40,000 per QALY, mirtazapine had a 1%-2% likelihood of being cost-effective. These findings were substantively unaffected by sensitivity analyses to timeframe, perspective, outcome measurement, and modelling strategy. Repurposing mirtazapine to treat severe breathlessness negatively impacted patient outcomes while being associated with higher formal and informal costs, and should be discouraged. Off-label prescribing of repurposed medicines without robust evidence risks unnecessary strain on healthcare systems and families. Economic evaluation within testing of repurposed medicines is important. Parallel cost-effectiveness analyses can deliver high-value information even when the efficacy trial finds no effect.

BMC Health Services ResearchVol. 25(1)
Brighton and Sussex Medical School (GB), University of Leeds (GB), University of Sussex (GB), Flinders University (AU), University of Cologne (DE), King's College London (GB), University of Hull (GB), Trinity College Dublin (IE), Mater Misericordiae University Hospital (IE), LMU Klinikum (DE), Nicolaus Copernicus University (PL), Leeds Trinity University (GB), Düsseldorf University Hospital (DE), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), King's College Hospital NHS Foundation Trust (GB), Cicely Saunders International (GB), Nottingham Biomedical Research Centre (GB), Collegium Medicum in Bydgoszcz (PL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University Hospital Cologne (DE), Heinrich Heine University Düsseldorf (DE), Hull York Medical School (GB), Gdańsk Medical University (PL), Ludwig-Maximilians-Universität München (DE)
European Respiratory Society, University of Nottingham, National Health and Medical Research Council
Openalex Percentile: Top 54%
Chronic Obstructive Pulmonary Disease (COPD) Research
DOIOpen Access PDFOpenAlex
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