Pharmacotherapeutic Options for Chronic Refractory Cough

Chronic refractory cough (CRC) is more than a persistent cough, but can cause serious impairment to quality of life. Through remarkable advances in our understanding of the neurobiology of cough, there is realization that CRC can be controlled by novel drugs that target cough reflex pathways.The authors present an overview of the clinical trials of antitussives for CRC, and ongoing clinical trials of novel drugs. They discuss the potential strengths and limitations of each medication, as well as knowledge gaps and uncertainties that should be addressed by future trials of putative CRC treatments.Currently-available antitussive drugs (i.e., opioids and gabapentin) are centrally-acting drugs primarily used for pain and neuropathic conditions; they were not designed for cough and have limitations with respect to efficacy and safety. Due to the success of gefapixant, a first-in-class P2X3 antagonist, early phase trials with different therapeutic targets in the cough reflex pathways have been conducted; these are expected to control cough hypersensitivity, while preserving protective cough reflex. However, the reported effects of antitussive drugs depend on the clinical context, cough outcome measures or cough characteristics. Further biomarkers are needed to accurately predict responders to different antitussive drugs.