title: The efficacy of specific neuromodulators on human refractory chronic cough: a systematic review and meta-analysis.
abstract: BACKGROUND
  There have been several published reports on the use of orally administered, specific centrally acting medicines for the treatment of idiopathic cough; however, there is no extant systematic review of randomized controlled trials (RCTs) that evaluated their efficacy and safety for the treatment of idiopathic cough in human beings.
  
  
  METHODS
  We conducted a series of definitive systematic reviews and meta-analyses of RCTs. Claims data from the MEDLINE, EMBASE, LILACS, CBM, CNKI, VIP, Wan Fang, and Cochrane Library databases were used. We also reviewed articles and reference lists of relevant articles pertaining to human subjects published prior to March 26, 2016. No language restrictions were imposed. Two authors independently reviewed the titles and abstracts of the retrieved studies, which were matched using Review Manager 5.3 software. Disagreements were resolved by consensus. The outcome data were the number of subjects whose symptoms declined, measured by cough or Leicester Cough Questionnaire (LCQ) score. Random effect meta-analyses were used to pool the findings. Publication bias was assessed using funnel plots.
  
  
  RESULTS
  Three RCTs, regarding the medicines baclofen, amitriptyline, and gabapentin, were conducted involving 92 persons in total. Our reviews confirmed that baclofen, amitriptyline, and gabapentin show promise in the treatment of cough for select cases of refractory chronic cough. After-treatment relief of cough symptoms was significant (risk ratio =2.41; 95% CI: 1.15-5.04, n=84). Each of the medicines was well tolerated with minimal side effects. Methodological biases in the design and execution of cluster randomized trials might contribute to any selection bias in this review.
  
  
  CONCLUSIONS
  Baclofen, amitriptyline, and gabapentin may be effective 'non-specific' antitussives in clinical settings, although none of them are used in medical assessments or routinely included in the anatomic diagnostic protocol.
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Ruilin
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Yangzi
authors.initials: Y
authors.lastname: ZhangTong
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Qiu
keywords: Cough; anti-depressive agents; drug therapy; neurotransmitter agents; oral medicine; randomized controlled trial (RCT)