Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea
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Objective To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated. Design Randomised, double blind, placebo controlled crossover study. Setting Four outpatient clinics at a hospital in South Australia. Participants 48 participants who had not previously been treated with opioids (mean age 76, SD 5) with predominantly chronic obstructive pulmonary disease (42, 88%) were randomised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo, or vice versa. Laxatives were provided as needed. Main outcome measures Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale, quality of sleep, wellbeing, performance on physical exertion, and side effects as measured at the end of the four day treatment period. Results 38 participants completed the study; three withdrew because of definite and two because of possible side effects of morphine (nausea, vomiting, and sedation). Participants reported significantly different dyspnoea scores when treated with morphine: an improvement of 6.6 mm (95% confidence interval 1.6 mm to 11.6 mm) in the morning and of 9.5 mm (3.0 mm to 16.1 mm) in the evening (P = 0.011 and P = 0.006, respectively). During the period in which they were taking morphine participants also reported better sleep (P = 0.039). More participants reported distressing constipation while taking morphine (9 v 1, P = 0.021) in spite of using laxatives. All other side effects were not significantly worse with morphine, although the study was not powered to address side effects. Conclusions Sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting.
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Opioids provide benefit of only borderline clinical significance for breathlessness.
“Even opioids, with most evidence to support their use, provide benefit of only borderline clinical significance.”
From The Breathing, Thinking, Functioning clinical model: a proposal to facilitate evidence-based breathlessness management in chronic respiratory disease (2017) · cites this paper as [19]
The Discussion reports a modest 7–10 mm improvement in breathlessness and calls it clinically significant. The Limitations section acknowledges that the clinical significance of that change may be questioned, but describes a 5–10% improvement as welcome. These passages support a modest benefit, not the categorical claim that opioids provide benefit of only borderline clinical significance. (LLM, conf=0.82)
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- Authors
- Abernethy, A. P., Currow, D. C., Frith, P., Fazekas, B. S., McHugh, A., & Bui, C.
- Affiliations
- Flinders University (AU)
- Repatriation General Hospital (AU)
- Nepean Hospital (AU)
- Corresponding author
- Currow, David C
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2003-09-04
- Volume
- 327
- Issue
- 7414
- Pages
- 523-528
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC192892
- OpenAlex
- W2157851934
- Cited by
- 521
- References
- 26
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 10 · 2023: 11 · 2022: 17 · 2021: 20 · 2020: 22 · 2019: 19 · 2018: 38 · 2017: 34 · 2016: 38 · 2015: 44 · 2014: 26 · 2013: 25 · 2012: 40
- FWCI
- 11.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Flinders Academic Commons (Flinders University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative Care and End-of-Life Issues
- Keywords
- sustained-release morphine, oral morphine, chronic obstructive pulmonary disease, opioid therapy, dyspnea, sleep quality, constipation, opioid side effects, palliative care, community-based treatment
- MeSH terms
- Administration, Oral, Aged, Chronic Disease, Delayed-Action Preparations, Double-Blind Method, Dyspnea, Female, Humans, Male, Morphine, Narcotics, Cross-Over Studies, Pulmonary Disease, Chronic Obstructive
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