Opioid Prescription Method for Breathlessness Due to Non-Cancer Chronic Respiratory Diseases: A Systematic Review

A previous pooled analysis demonstrated significant relief of breathlessness following opioid administration in patients with chronic obstructive pulmonary disease. However, in clinical practice, it is important to know the characteristics of patients responding to opioids, the best prescription methods, and the evaluation measures that can sufficiently reflect these effects. Thus, we performed a systematic review of systemic opioids for non-cancer chronic respiratory diseases. Fifteen randomized controlled studies (RCTs), four non-randomized studies, two observational studies, and five retrospective studies were included. Recent RCTs suggested that regular oral opioid use would decrease the worst breathlessness in patients with a modified Medical Research Council score ≥ 3 by a degree of 1.0 or less on a scale of 1-10. Ergometer or treadmill tests indicated mostly consistent significant acute effects of morphine or codeine. In two non-randomized studies, about 60% of patients responded to opioids and showed definite improvement in symptoms and quality of life. Furthermore, titration of opioids in these studies suggested that a major proportion of these responders had benefits after administration of approximately 10 mg/day of morphine. However, more studies are needed to clarify the prescription method to reduce withdrawal due to adverse effects, which would lead to significant improvements in overall well-being.