Morphine improves chronic breathlessness in patients with COPD

In certain patients with COPD, regular, low-dose, oral sustained-release morphine treatment for 4 weeks improved several disease outcomes without causing respiratory adverse effects, a randomized clinical trial showed.

The findings, published in JAMA Internal Medicine, closely align with previous studies conducted among smaller cohorts that used different scales to measure outcomes, according to researchers.

“Physicians remain reluctant to prescribe opioids for breathlessness in COPD for fear of respiratory depression,” Cornelia A. Verberkt, MSc, of the faculty of health, medicine and life sciences at Maastricht University in the Netherlands, and colleagues wrote.

Researchers randomly assigned 124 outpatients with moderate to severe breathlessness stemming from COPD in a 1:1 ratio to receive either a capsule of 10 mg of regular, oral sustained-release morphine or placebo up to three times daily for 4 weeks. The mean age of the 111 patients (60 men) who completed the trial was 65 years.

Verbekt and colleagues reported a 2.18-point improvement in COPD Assessment Test (arterial partial pressure of carbon dioxide) scores among the morphine recipients (95% CI, –4.14 to –0.22 points; P = .03). The difference in arterial partial pressure of carbon dioxide was 1.19 mm Hg higher, but not statistically significant, among morphine recipients (95% CI, –2.7 to 5.07 mm Hg, P = .55). Breathlessness remained unchanged. Among a subgroup of morphine recipients with higher modified Medical Research Council (severe COPD-related dyspnea) grades, worst breathlessness scores improved 1.33 points on a numeric rating scale (95% CI, –2.5 to –0.16 points; P = .03).

Five of the 54 morphine recipients and one of the 57 placebo recipients withdrew from the trial prior to completion due to adverse events (constipation, nausea, dizziness, abdominal pain, vomiting, changes in heart rate and/or hallucinations). No morphine-related hospital admissions or deaths occurred.

“Our study clearly illustrates that fear of respiratory depression or other respiratory adverse effects cannot be substantiated,” Verberkt and colleagues wrote. “A larger randomized clinical trial with longer follow-up in patients with [modified Medical Research Council] grades 3 to 4 is warranted.”

In a related editorial, Eric W. Widera, MD, of the department of geriatrics at the University of California, San Francisco, wrote that the current trial was intended to detect a “clinically important difference” of 3.8 points in COPD Assessment Test scores. However, these researchers accepted the 2.18-point difference as relevant, pointing to a 2017 study that drew the same conclusion.

“It is reasonable to use the most current evidence to help interpret findings,” Widera wrote. “However, lowering the threshold that defines a clinically meaningful difference at the end of the study suggests that the role of opioids on health status is likely small for the population studied.”

References:

• Verberkt CA, et al. JAMA Intern Med. 2020;doi:10.1001/jamainternmed.2020.3134.
• Widera EW. JAMA Intern Med. 2020;doi:10.1001/jamainternmed.2020.3133.