title: Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Refractory chronic cough causes substantial symptoms and quality-of-life impairment. Similarities between central reflex sensitisation in refractory chronic cough and neuropathic pain suggest that neuromodulators such as gabapentin might be effective for refractory chronic cough. We established the efficacy of gabapentin in patients with refractory chronic cough.
  
  
  METHODS
  This randomised, double-blind, placebo-controlled trial was undertaken at an outpatient clinic in Australia. Adults with refractory chronic cough (>8 weeks' duration) without active respiratory disease or infection were randomly assigned to receive gabapentin (maximum tolerable daily dose of 1800 mg) or matching placebo for 10 weeks. Block randomisation was done with randomisation generator software, stratified by sex. Patients and investigators were masked to assigned treatment. The primary endpoint was change in cough-specific quality of life (Leicester cough questionnaire [LCQ] score) from baseline to 8 weeks of treatment, analysed by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12608000248369.
  
  
  RESULTS
  62 patients were randomly assigned to gabepentin (n=32) or placebo (n=30) and ten patients withdrew before the study end. Gabapentin significantly improved cough-specific quality of life compared with placebo (between-group difference in LCQ score during treatment period 1·80, 95% CI 0·56-3·04; p=0·004; number needed to treat of 3·58). Side-effects occurred in ten patients (31%) given gabapentin (the most common being nausea and fatigue) and three (10%) given placebo.
  
  
  CONCLUSIONS
  The treatment of refractory chronic cough with gabapentin is both effective and well tolerated. These positive effects suggest that central reflex sensitisation is a relevant mechanism in refractory chronic cough.
  
  
  BACKGROUND
  National Health and Medical Research Council of Australia and Hunter Medical Research Institute, Newcastle, Australia.
authors.affiliation: Priority Centre for Asthma and Respiratory Diseases, School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia. nicole.ryan@newcastle.edu.au
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Ryan
authors.forename: Surinder S
authors.initials: SS
authors.lastname: Birring
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D000293:Adolescent; D000328:Adult; D000588:Amines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000927:Anticonvulsants; D002490:Central Nervous System / Q000187:drug effects; D002908:Chronic Disease; D003371:Cough / Q000188:drug therapy* / Q000503:physiopathology; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011788:Quality of Life; D012018:Reflex / Q000187:drug effects; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin