Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study

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Currow, David Christopher
McDonald, Christine
Oaten, Sheila
Kenny, Bernadette
Allcroft, Peter
Frith, Peter Anthony
Briffa, Michael
Johnson, Miriam J
Abernethy, Amy Pickar
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© 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Context Randomised controlled trials (RCTs) can answer questions of efficacy, but rarely generate a complete safety profile. Long term pharmacovigilance studies complement RCTs. Objectives Level I evidence supports short term efficacy of opioids in reducing refractory dyspnoea. This study aims to determine: the minimum effective daily dose of sustained release morphine to reduce refractory breathlessness; and whether net clinical benefits are sustained safely. Methods In a phase II dose increment study, 10mg sustained release morphine was administered daily, and increased by 10mg daily each week to a maximum of 30mg daily. The participant was withdrawn if there were unacceptable side-effects or no response to maximum dose. If participants had a 10% improvement in dyspnoea over their own baseline, they joined a long-term phase IV effectiveness/safety study at that dose. Complying with STROBE guidelines for reporting observational studies, response and side-effects are described, with demographic and clinical characteristics of responders. Results Eighty five participants (65 males, mean age 74, 59% with chronic obstructive pulmonary disease (COPD) provided >30 patient-years of data. Fifty three participants derived ≥10% benefit (35.4% improvement over baseline) giving a response rate of 62% (number needed to treat of 1.6); for 70%, this dose was 10mg/24hours. Benefit was maintained at three months for 28 (33%) people. Breathlessness was reduced significantly (p<0.001) but constipation increased (p<0.001) despite aperients. There were no severe adverse events including no respiratory depression nor hospitalisations. Conclusion Ten mg of sustained release oral morphine daily is safe in this population, and effective for most people.
Palliative care, Pain management
Currow, D.C., McDonald, C., Oaten, S., Kenny, B., Allcroft, P., Frith, P., Briffa, M., Johnson, M.J. and Abernethy, A.P., 2011. Once-daily opioids for chronic dyspnea: a dose increment and pharmacovigilance study. Journal of Pain and Symptom Management, 42(3), 388-399.