Gabapentin Improves Chronic Cough

Emma Hitt, PhD

August 29, 2012

August 29, 2012 — The neuromodulator gabapentin appears to improve refractory, chronic cough, a new study suggests.

Nicole M. Ryan, PhD, from the School of Medicine and Public Health at the University of Newcastle in New South Wales, Australia, and colleagues reported their findings in an article published online August 28 in the Lancet.

According to the researchers, "gabapentin is effective for neuropathic pain with central sensitisation, and findings from two case series have shown success with gabapentin in chronic cough." Gabapentin is a lipophilic structural analog of the neurotransmitter γ-aminobutyric acid

The current study, conducted in 62 patients with refractory, chronic cough, sought to determine whether gabapentin could improve cough-specific quality of life, as measured by a change in the Leicester cough questionnaire (LCQ) score, and decrease cough severity and frequency.

Patients were randomly assigned to receive 10 weeks of either gabapentin (n = 32), at a maximum tolerable daily dose of 1800 mg, or placebo (n = 30). All patients had had their cough for at least 8 weeks without active respiratory disease or infection. Ten patients withdrew before the study end, leaving 26 evaluable patients in each group.

Participants attended 5 visits over the course of 16 weeks. At the first visit, the researchers assessed the patients' cough assessment and recorded clinical history, drug use, and cough severity. Patients also completed a laryngeal dysfunction questionnaire, a short-form 36 health survey, and a cough-specific quality-of-life questionnaire (LCQ).

Gabapentin significantly improved cough-specific quality of life compared with placebo (between-group difference in LCQ score during treatment period, 1.80; 95% confidence interval [CI], 0.56 - 3.04; P = .004), with a number needed to treat of 3.58. Adverse effects, most often nausea and fatigue, occurred in about one third of patients receiving gabapentin compared with 10% receiving placebo.

The authors also found that the improvement in cough symptoms decreased after withdrawal, further supporting the idea that this agent had an antitussive effect.

"Findings from this trial have shown that gabapentin significantly improved cough-specific quality of life compared with placebo," Dr. Ryan and colleagues conclude. "These results suggest that gabapentin might be an effective therapy for refractory chronic cough."

The authors note that gabapentin might block calcium channels, which would inhibit the release of excitatory neurotransmitters such as substance P that can promote cough, as well as possibly N-methyl-D-aspartate receptors.

In a related comment, Kian Fan Chung, MD, from Imperial College, London, United Kingdom, writes, "[T]hese results suggest that gabapentin is worth trying in patients with refractory chronic cough...[and] should provide the impetus to pursue similar trials of other drugs developed to suppress cough sensitisation pathways or target primary afferent nerves associated with cough, for the benefit of patients with refractory chronic cough."

This study was funded by the National Health and Medical Research Council of Australia (NHMRC) and Hunter Medical Research Institute, Newcastle, Australia. Dr. Ryan held a PhD scholarship funded by the NHMRC Centre for Clinical Excellence in Respiratory and Sleep Medicine and was the recipient of a Hunter Medical Research Institute, Research Higher Degree support scholarship donated by the Greaves family. One coauthor is an NHMRC Practitioner Fellow. The remaining authors have disclosed no relevant financial relationships. Dr. Chung has received honoraria for participation in advisory board meetings about the treatment of cough that were organized by GlaxoSmithKline and served as chair of an international cough symposium funded, in part, by educational grants from GlaxoSmithKline and Procter & Gamble.

Lancet. Published online August 28, 2012. Article abstract, Comment extract