INTRODUCTION: Persistent breathlessness is a debilitating symptom that is prevalent in the community, particularly in people with chronic and life-limiting illnesses. Treatment includes different steps, including pharmacological treatment aiming to improve the symptom and optimize people's wellbeing. AREAS COVERED: PubMed and Google Scholar were screened using 'chronic breathlessness' OR 'persistent breathlessness,' AND 'pharmacological treatment,' OR 'opioids.' This review focuses on pharmacological treatments to reduce persistent breathlessness and discusses possible mechanisms involved in the process of breathlessness reduction through pharmacotherapy. Research gaps in the field of persistent breathlessness research are outlined, and future research directions are suggested. EXPERT OPINION: Regular, low-dose (≤30 mg/day), sustained-release morphine is recommended as the first-line pharmacological treatment for persistent breathlessness. Inter-individual variation in response needs to be investigated in future studies in order to optimize clinical outcomes. This includes 1) better understanding the centrally mediated mechanisms associated with persisting breathlessness and response to pharmacological therapies, 2) understanding benefit from the perspective of people experiencing persistent breathlessness, small and meaningful gains in physical activity.
