Sustained-Release Morphine Safe in Chronic Breathlessness

By Reuters Staff

December 27, 2019

NEW YORK (Reuters Health) - Regular low-dose sustained-release oral morphine appears to be a safe treatment for chronic breathlessness, according to findings from a randomized clinical trial.

Emerging evidence suggests that oral morphine can improve symptoms in people with disabling breathlessness despite optimal treatment of its underlying cause, but respiratory depression associated with morphine use remains a significant concern.

Dr. Miriam J. Johnson of the Wolfson Palliative Care Research Center at Hull York Medical School, University of Hull, UK, and colleagues used data from phase 3 trial of sustained-release morphine for chronic breathlessness to evaluate treatment-emergent adverse events (TEAEs) in the morphine and placebo groups.

Overall, there were 1,449 TEAEs affecting 138 (97%) participants in the morphine group and 132 (96%) participants in the placebo group. Ten percent of these events were severe, with no significant difference between the groups.

Significantly more participants receiving morphine reported constipation (56% vs. 43%) and vomiting (37% vs. 23%), but there were no significant differences in mean change from baseline of any measurement of respiratory harm in either group.

Potentially opioid-related symptoms (collected in the trial as TEAEs of special interest) affected similar fractions of the morphine group (91%) and placebo group (95%), the researchers reported in BMJ Supported and Palliative Care.

The only factor significantly associated with severe TEAEs of special interest was sex, with the odds for a severe TEAE being 4.27-fold higher among women than men.

"Clinicians can treat chronically breathless opioid-naive patients confidently with this starting dose of regular, low-dose, oral sustained-release morphine in the context of careful patient selection and ongoing appropriate monitoring," the authors conclude. "The absence of an identified subgroup at greater risk of harms gives further confidence in the careful use of this drug in this formulation."

"However," they add, "it is notable that twice as many participants with severe TEAE in the morphine arm withdrew from the study than in the placebo arm, although the absolute numbers are small. Although we found no association by study arm, it is good practice to assess and manage morphine-related harms such as constipation rigorously and expertly from morphine initiation."

The study did not have external funding. Two of the authors reported ties to companies selling pain medicines.

Dr. Johnson did not respond to a request for comments.

SOURCE: BMJ Supportive and Palliative Care, online November 12, 2019.