Results of a clinical trial do not support the use of daily low-dose, extended-release morphine to relieve severe chronic breathlessness in people with COPD. The intensity of the worst breathlessness was not significantly improved in the randomized trial after the first week of morphine compared with placebo.
Participants received oral extended-release morphine 8 or 16 mg per day or placebo during the first week of treatment. At the start of both weeks 2 and 3, participants in all 3 groups were randomized to receive an 8 mg per day increase in dose or placebo (thus, people could be on placebo during some or all of the 3 weeks or on morphine doses of 8, 16, or 24 mg in week 2 and up to 32 mg per day during week 3.
Based on a primary outcome of the change in intensity of the worst breathlessness after the first week of treatment, the investigators found: “The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, −0.3 [95% CI, −0.9 to 0.4]) or between the 16 mg/d of morphine group and the placebo group (mean difference, −0.3 [95%, CI, −1.0 to 0.4]). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, −1453 [95% CI, −3310 to 405]), between the 16 mg/d of morphine group and the placebo group (mean difference, −1312 [95% CI, −3220 to 596]), between the 24 mg/d of morphine group and the placebo group (mean difference, −692 [95% CI, −2553 to 1170]), or between the 32 mg/d of morphine group and the placebo group (mean difference, −1924 [95% CI, −47,699 to 921]).”
Editorial: “[This study] makes a strong argument against the routine use of daily low-dose, extended-release opiates for patients with COPD and exertional dyspnea. Ongoing assessment of pharmacological and nonpharmacological interventions for this often-debilitating symptom may benefit from controlled measures of dyspnea during exercise at a fixed intensity to help distinguish physiological effects from behavioral outcomes, such as activity level, and may elucidate the complex interaction among physiological, psychological, and social factors in dyspnea.”