Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial

Ryan, Nicole; Birring, Surinder S.; Gibson, Peter G.

doi:10.1016/s0140-6736(12)60776-4

Cited by 401 publications

(384 citation statements)

References 29 publications

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“…Similar to the Gabapentin study [89], there was no significant difference between morphine and placebo for the citric acid cough challenge test supporting its central mechanism.…”

Section: Resultssupporting

confidence: 53%

“…Blurred vision, cognitive changes, dizziness, and weight gain were significantly greater in the PREG + SPT group while sleep disturbance and headache were significantly greater for the PLAC + SPT group. The incidence of AEs for this study was much higher than the gabapentin study (31%) [89]. The risk/benefit of pregabalin versus gabapentin for the treatment of refractory CC needs to be carefully considered.…”

Section: Resultsmentioning

confidence: 94%

“…No comparator group. Small sample size.Ryan et al, 2012 [89]Randomized, double-blind, placebo-controlled parallel trial62 Gabapentin 6 capsules (1800 mg) daily ( n = 32) versus matching placebo 6 capsules daily ( n = 30). *Primary outcome was cough QOL measured by the LCQ.Secondary outcomes were cough severity (VAS), cough frequency (LCM®).…”

Section: Resultsmentioning

confidence: 99%

“…The effectiveness of gabapentin treatment for refractory CC was investigated in a placebo-controlled randomized trial by Ryan et al [89] (Table 4). The primary efficacy outcome was cough quality of life measured by the LCQ.…”

Section: Resultsmentioning

confidence: 99%

“…This analysis included the the Jeyakumar et al (Amitriptyline) study [86], the Morice et al (morphine sulfate) study [88], the Ryan et al (Gabapentin) study [89], and the Vertigan et al (Pregabalin + Speech Pathology) study [90]. As the Jeyakumar et al study used a different measure of cough QOL to the other studies, we converted continuous outcome data into Standardized Mean Difference (SMDs) and presented these with 95% CIs.…”

Section: Methodsmentioning

confidence: 99%

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An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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Introduction: Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain.Areas covered: The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible.Expert opinion: Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.

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“…Similar to the Gabapentin study [89], there was no significant difference between morphine and placebo for the citric acid cough challenge test supporting its central mechanism.…”

Section: Resultssupporting

confidence: 53%

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough

Kum,

Patel,

Diab

et al. 2023

JAMA

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ImportanceGefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.ObjectiveTo evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.Data SourcesMEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.Study SelectionTwo reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.Data Extraction and SynthesisTwo reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).Main Outcomes and MeasuresCough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.ResultsNine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, −6.2 mm [95% CI, −4.1 to −8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).Conclusions and RelevanceCompared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.

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Unilateral Laryngoscopic Findings Associated With Response to Gabapentin in Patients With Chronic Cough

Giliberto

Dibildox²,

Meratı

2017

JAMA Otolaryngol Head Neck Surg

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Gabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial

Cited by 401 publications

References 29 publications

An update and systematic review on drug therapies for the treatment of refractory chronic cough

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough

Unilateral Laryngoscopic Findings Associated With Response to Gabapentin in Patients With Chronic Cough

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