The cost of drug repurposing: parallel economic evaluation of mirtazapine for severe breathlessness in the multinational BETTER-B trial
Year: 2025
Type: article
Abstract: BACKGROUND: 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. METHODS: 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). FINDINGS: 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. INTERPRETATION: 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.
Source: BMC Health Services Research
Authors: Peter May, Charles Normand, Adejoke O. Oluyase, Samantha Smith, Sarah T. Brown, Matthew Maddocks, Massimo Costantini, Sabrina Bajwah, Kathrin Kahnert, Steffen T. Simon, Karen Ryan, David C. Currow, Miriam J. Johnson, Simon P. Hart, Małgorzata Krajnik, Silvia Tanzi, Charlotte E. Bolton, Piotr Janowiak, Elena Turola, Caroline J. Jolley, Hannah Mather, Geraldine Murden, Luca Ghirotto, Bobbie Farsides, Julia M. Brown, Irene J. Higginson
Institutions: King's College London, Trinity College Dublin, University of Leeds, King's College Hospital NHS Foundation Trust, LMU Klinikum, Ludwig-Maximilians-Universität München, University of Cologne, University Hospital Cologne, University College Dublin, Mater Misericordiae University Hospital, Flinders University, University of Hull, Hull York Medical School, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz, University of Nottingham, Nottingham Biomedical Research Centre, Gdańsk Medical University, Brighton and Sussex Medical School, University of Sussex
Language: English
Subfield: Economics and Econometrics
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $3,290
OpenAlex ID: W4415854669