Morphine is not effective for chronic breathlessness and raises safety concerns

Morphine failed to improve breathlessness scores compared with placebo in patients with chronic breathlessness from cardiopulmonary diseases or cancer, while increasing safety risks.

MABEL (EudraCT 2019-002479-33) was a phase-3, parallel-group, double-blind, placebo-controlled trial in patients with moderate-to-severe breathlessness due to cardiorespiratory conditions and cancer (Medical Research Council breathlessness score ≥3). Participants were randomised to receive morphine 5-10 mg twice daily (possible up-titration at day 15) or placebo for 56 days. The primary endpoint was the numerical rating scale for breathlessness at day 28. In total, MABEL included 140 participants.

Prof. Miriam Johnson (University of Hull, UK) presented the results. Dose escalation was required in 29% of the participants in the morphine group and 36% of the participants in the placebo group. Analysis of the primary outcome at day 28 showed no significant difference between groups, with an adjusted mean difference of 0.09 (95% CI -0.57 to 0.75; P=0.781) for morphine versus placebo. However, participants in the morphine group experienced higher rates of adverse events, serious adverse events, and treatment withdrawals. Among secondary endpoints, morphine produced significant improvements only in cough scores and physical activity [1].

In summary, “morphine did not improve the worst breathlessness intensity over 24 hours,” said Prof. Johnson, “and further research is needed to determine if there is any role for morphine in chronic breathlessness.”

1. Johnson M, et al. Morphine for chronic breathlessness (MABEL): a multi-site, parallel group, dose titration, double-blind, randomised, placebo-controlled trial. ERS Congress, 27 September–1 October 2025, Amsterdam, the Netherlands.

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Posted on 30 October 202530 October 2025