Harms of Morphine for Chronic Breathlessness in Relation to Dose, Duration and Titration Phase

Ekström, Magnus; Alameri, Fatima; Chang, Sungwon; Ferreira, Diana; Johnson, Miriam J.; Currow, David C.

Abstract

Context: Morphine to treat severe chronic breathlessness might increase adverse events (AEs). Objectives: We aimed to evaluate the risk of AEs in relation to dose, duration and titration phase of regular, low-dose sustained-release (SR) oral morphine for chronic breathlessness in people with chronic obstructive pulmonary disease (COPD). Methods: Secondary analysis of a double-blind, randomized, trial of SR morphine titrated to 0–32 mg/day over three weeks in people with COPD and chronic breathlessness. Risk of AEs by morphine or placebo dose, duration and titration phase (initiation, stable dose or up-titration) was analyzed using multivariable generalized estimating equation (GEE) models. Results: We included 156 people (49% female) of whom 100 (64%) experienced any AE during week 1: 64% of those on 8 mg/morphine/day; 78% on 16 mg/morphine/day; and 48% on placebo. In multivariable analysis, the AE risk was highest the first week of morphine treatment and decreased in week two (adjusted rate ratio [aRR] 0.71; 95% confidence interval (CI) 0.54, 0.94) and week three (aRR 0.49; 95% CI 0.37, 0.67). Over the three weeks, the AE risk was similar between titration phases, and there was no statistically significant trend with higher morphine doses (P-values>0.10). Most AEs did not require treatment discontinuation or dose reduction and resolved by the end of titration. Conclusion: In people with COPD and severe chronic breathlessness, the risk of AEs was highest during the first week of treatment in a dose-related fashion but did not differ by titration phase or by dose of once-daily SR morphine between 8 and 32 mg/day. Trial registration NCT02720822.

Citation

Ekström, M., Alameri, F., Chang, S., Ferreira, D., Johnson, M. J., & Currow, D. C. (in press). Harms of Morphine for Chronic Breathlessness in Relation to Dose, Duration and Titration Phase. Journal of pain and symptom management, https://doi.org/10.1016/j.jpainsymman.2025.02.020

• Journal Article Type: Article
• Acceptance Date: Feb 19, 2025
• Online Publication Date: Feb 24, 2025
• Deposit Date: Mar 13, 2025
• Publicly Available Date: Mar 14, 2025
• Journal: Journal of Pain and Symptom Management
• Print ISSN: 0885-3924
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/j.jpainsymman.2025.02.020
• Keywords: Opioids; Breathlessness; COPD; Adverse events; Randomized controlled trial; Placebo controlled trial
• Public URL: https://hull-repository.worktribe.com/output/5078647