Opioids Do Not Relieve Persistent Breathlessness among COPD patients, suggests study
One of the most prevalent and impactful symptoms in COPD is persistent dyspnoea, occurring in the majority of patients with advanced COPD. Opioids, mostly morphine, have been investigated and suggested as treatment in palliative care guidelines. However, in recent years multiple trials on morphine for persistent dyspnoea have shown no clinical benefit, and there are concerns regarding adverse events. Transdermal fentanyl has not yet been investigated for this indication.
They performed a multicentre, crossover, double-dummy randomised controlled trial, investigating transdermal fentanyl (12 μg·h−1), morphine (10 mg per os twice daily) and placebo, during three treatment periods of 2 weeks (including a 3-day washout period). Patients with persistent dyspnoea despite optimal therapy and modified Medical Research Council dyspnoea scale score ≥3 caused by COPD, forced expiratory volume in 1 s (FEV1) <50% predicted and stable disease were included. The primary end-point was change in mean daily dyspnoea score on a Numeric Rating Scale (NRS). Secondary outcomes were change in worst daily dyspnoea (NRS), health status (Clinical COPD Questionnaire), anxiety (Hospital Anxiety and Depression Scale-Anxiety), hypercapnia (capillary blood gas), mastery (Chronic Respiratory Questionnaire-Mastery) and sleep quality (NRS).
Between April 2019 and November 2024, 59 randomisations were performed in 58 participants (mean±sd 69±7 years; 54% female; FEV1 33±10% predicted); 37 participants completed the study. The main reasons for study discontinuation were exacerbations (n=13) and side-effects (n=7). There were no significant differences between both fentanyl and morphine compared to placebo for mean and worst dyspnoea, sleep, health status, mastery, anxiety, hypercapnia or side-effects (except for a possible difference in vomiting).
This study demonstrated no positive effect of transdermal fentanyl nor oral morphine compared to placebo in the treatment of persistent dyspnoea in COPD.
Reference:
van Dijk, M., Mooren, K. J. M., van Beurden-Moeskops, W., et al. (2026). Fentanyl or morphine for persistent dyspnoea in COPD: A multicentre randomised crossover trial. European Respiratory Journal, 68(2), 2501431. https://doi.org/10.1183/13993003.01431-2025
Keywords:
Opioids, Relieve, Persistent, Breathlessness, COPD patients, study, van Dijk, M., Mooren, K. J. M., van Beurden-Moeskops, W
