Extended-release morphine didn't improve breathlessness in COPD

Extended-release morphine did not improve chronic breathlessness in patients with chronic obstructive pulmonary disease (COPD), an Australian trial found.

The trial randomized 160 patients with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) at 20 centers in Australia to 8 mg or 16 mg of oral extended-release morphine daily or placebo during week 1. At the start of weeks 2 and 3, patients received either 8 mg of extended-release morphine per day added to the prior week's dose or placebo. The primary outcome was change in the intensity of worst breathlessness on a rating scale from 0 (none) to 10 (worst or most intense). Results were published by JAMA on Nov. 22.

Of the 160 patients randomized, 156 were included in the primary analyses (median age, 72 years; 48% women). A total of 138 (88%) completed week 1, and the change in the intensity of worst breathlessness from baseline to week 1 was not significantly different between either of the doses and placebo. There was also no significant difference in the secondary outcome of change in mean daily step count at week 3. “The unchanged total step count does not support the hypothesis that the lack of efficacy on breathlessness was due to people increasing their physical activity (thereby masking a true symptom improvement),” the authors noted. They concluded that the study's findings do not support the use of these doses of extended-release morphine to relieve breathlessness.

The authors cautioned that the results “may not be applicable to people with very advanced COPD and breathlessness who are in palliative care or near the end of life, at which time treatment with opioids may be useful to provide relief of severe dyspnea.” Limitations of the study include that the number of participants decreased each week of the trial; only 42% completed treatment at week 3.

An accompanying editorial noted additional limitations affecting the applicability of the findings, including that the study didn't address whether the patients had dyspnea at rest. “The absence of dyspnea at rest would call into question the premise for use of daily long-acting opiates instead of rapid-onset, short-acting opiates as needed prior to planned exertion. Such a strategy would minimize the adverse events associated with opiate use,” said the editorialist. It is also useful to assess change in dyspnea while patients are performing a controlled exercise, which allows evaluation of the effects of an intervention such as opioids and helps to “elucidate the complex interaction among physiological, psychological, and social factors in dyspnea,” the editorial said.