Morphine for the symptomatic reduction of chronic breathlessness: The case for controlled release

Purpose of review Clinicians who seek to reduce the symptomatic burden of chronic breathlessness by initiating regular lowdose morphine has the choice of immediate or sustained-release formulations-which will be better for this often frail population, and which has the more robust evidence to inform its prescription? Both formulations can be used. Recent findings For chronic breathlessness, three factors consistently favour the use of regular, low-dose, sustained-release morphine over immediate-release formulations: (1) Pharmacokinetics in steady state demonstrates lower peak and higher trough concentrations than immediate-release formulations. From first principles, this profile is more likely to minimize harms and maximize benefits. (2) Metaanalyses studying patients who were treated to steady state in randomized, placebo-controlled studies for the indication of chronic breathlessness are almost all done with sustained and not immediaterelease formulations. (3) Studies consistently show patients' preferences for the least frequent dosing, with concomitant increases of up to 50% in otherwise poor medication compliance. Summary As the evidence base expands for the symptomatic reduction of chronic breathlessness, pharmacological interventions will play a part. Using the best available evidence underpins patient-centred approaches that seek to predictably maximize the net effect. As such, the weight of evidence in patient-centred clinical care favours the use of regular, low-dose sustained-release morphine for the symptomatic reduction of chronic breathlessness.