Table 1

Multiple dosing studies of opioids for dyspnoea among patients with COPD

StudyPopulationOpioid dose regimen (vs placebo)SettingDuration of follow-upOutcome measureOverall effect on dyspnoeaSide effects
Eiser et al 199130n = 18 (pink puffer, mean FEV1 36%)Diamorphine 2.5 or 5 mg orally qidPre and 2 week exercise testing in study centre2 weeks ×3, crossover, no washoutVAS for dyspnoea 6 min walkNS4 withdrew (chest infection, itching, constipation, headache), mild nausea: ‘several’ constipation or vomiting:3/14
Poole et al 199822n = 16 (FEV1 <1.5 l)Morphine SR 10–20 mg od or bidPre and 6 week exercise testing in study centre6 weeks ×2, plus 2 week washoutCRQ for quality of life, 6 min walkNS overall, but mastery scale favored placebo; 6 min walk test worse with morphineOpioid withdrawal syndrome:4/16; patients on morphine “more likely to report nausea, anorexia, constipation or drowsiness” (p = 0.004)
Johnson et al 198332n = 19 (FEV1 <1.2, MRC ⩾3)Dihydrocodeine 15 mg orally 30 min pre-exercise, up to tidPre and 1 week pedometer testing in the homeWeekly, cross over×3 (third week alternate day codeine)VAS for dyspnoea Pedometer distanceDyspnoea reduced by18%, walk distance up 17%Similar in placebo and treated groups
Woodcock et al 198123n = 12 (MRC >3)Dihydrocodeine 1 mg/kg orally od vs oxygen, alcohol or caffeine 45 min before exerciseExercise testing (treadmill, in hospital)4 consecutive daysVAS for dyspnoea20% reduction in dyspnoea, 18% increase in exercise tolerance 45 min after codeineNausea and vomiting 5/16; constipated/drowsy 2/16
Woodcock et al 198231n = 16 (mean FEV1 0.75)Dihydrocodeine 30 mg or 60 mg tidExercise testing at 2 weeks in study centres2 weeks crossover ×3Oxygen consumption (bicycle ergometer), 6 min walk“A few patients reported considerable benefit”, Lower oxygen consumption (p<0.05)5 withdrew (nausea and vomiting). Opioid withdrawal syndrome (2 on 60 mg dose), constipation (2/11)
Abernethy et al 200325n = 48 (COPD n = 42)Morphine SR 4-day crossover versus placeboClinical study in the community4 daysVAS for dyspnoea at day 4Better dyspnoea scores both mornings (p = 0.01) and evening (p<0.05)More constipation with morphine. Other side effects not significant
Currow et al 200934n = 68 (48 with COPD, modified MRC ⩾2)Morphine SR 10–20–30 mg odOpen-label dose-finding long-term clinical study in the communityMean 3 months; 18.5 patient years of dataVAS for dyspnoea51% of patients found sufficient benefit over long term to choose to continueConstipation 6%, nausea 6%, confusion/drowsiness/lethargy/dizziness 12%
  • bid, twice a day; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 s; MRC, Medical Research Council; NS, not significant; od, once daily; SR, sustained release; tid, three times a day; VAS, visual analogue scale.