Introduction: Although sustained-release (SR) morphine may reduce persistent breathlessness in some people, there is a lack of evidence for its use in interstitial lung disease (ILD).

Aim: To investigate the efficacy and safety of SR morphine for persistent breathlessness in ILD.

Methods: Participants with optimally-treated ILD and a modified Medical Research Council scale score?2 were randomised to 1) one week of SR morphine 20mg, and 2) one week of placebo (or vice-versa), with 1-week washout. Primary outcomes were breathlessness intensity ?now? in the morning and evening (100mm visual analogue scale). Secondary outcomes included other breathlessness measures, perceived quality of sleep, harms, and blinded satisfaction with the medication. Analysis was conducted to inform progression to a larger trial [Cocks & Togerson. J Clin Epidemiol 2013; 66:197-201].

Results: From 2012 to 2021, 88 people were assessed and 35 (39.8%) randomised. Eight participants withdrew, seven while taking morphine; 27 participants completed the study. Breathlessness now was lower on morphine compared with placebo for morning [mean (M)±SD 38.4±23mm vs. 45.7±22mm; effect size [80% CI] = 0.37 (0.1 to 0.6)] and evening [38.8±24mm vs. 43.3±23mm; effect size [80% CI] = 0.20 (-0.1 to 0.5)]. Secondary breathlessness measures were lower with morphine. Morphine was related to more constipation, confusion and nausea, but also better perceived sleep quality. More people were satisfied/very satisfied with morphine compared to placebo (77.3% vs. 44.0%). 

Conclusion: This trial of morphine for breathlessness in ILD had problems recruiting but suggest a potential signal for benefit of morphine, which needs further investigation.