Clinical question: Does low-dose, long-acting oral morphine improve self-reported breathlessness at 28 days for adult patients with moderate to severe chronic breathlessness?
Background: Chronic breathlessness is a debilitating symptom for which opioids, and particularly morphine, have long been used for treatment. Most evidence of benefit arises from laboratory-based exercise studies, while at-home pragmatic studies have not demonstrated a significant effect on breathlessness outcomes.
Study design: Double-blind, parallel-group, randomized, placebo-controlled trial
Setting: 11 clinical centers in the U.K.
Synopsis: 143 patients with cardiorespiratory disease and a modified Medical Research Council breathlessness scale grade of at least 3 were randomized to 5 mg of modified-release oral morphine twice daily versus placebo for 56 days. Dose titration to 10 mg twice daily was performed for patients without improvement over baseline by day seven and with acceptable harms. No difference was detected in the primary outcome of worst breathlessness on a self-reported numerical rating scale at day 28 (adjusted mean difference 0.09; 95% CI, -0.57 to 0.75), nor at any other time point assessed.
An increase in activity by several measures (calories, steps, moderate to vigorous activity, reduced sedentary activity) was noted with morphine, although the measures are imprecise and failed to meet significance. More adverse events were seen in the morphine group, but they were mostly mild. Limitations include a predominance of chronic lung disease (98%) despite broader eligibility criteria, and under-representation of females and non-white patients.
Bottom line: Low-dose morphine was well tolerated but did not improve chronic breathlessness at 28 days, although additional study is needed to understand the potential benefit to patients of improved activity tolerance under the same burden of breathlessness.
Citation: Johnson, MJ, et. al. Morphine for chronic breathlessness (MABEL) in the UK: A multi-site, parallel-group, dose titration, double-blind, randomised, placebo-controlled trial. The Lancet Respiratory Medicine 2025;13(11):967-77.
Dr. Fried
Dr. Fried is a hospitalist and assistant professor of internal medicine at the University of North Carolina in Chapel Hill, N.C.