Pregabalin and Speech Pathology Combination Therapy for Refractory Chronic Cough

Vertigan, Anne E.; Kapela, Sarah L.; Ryan, Nicole; Birring, Surinder S.; McElduff, Patrick; Gibson, Peter G.

doi:10.1378/chest.15-1271

Cited by 218 publications

(165 citation statements)

References 23 publications

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“…Small sample size. No comparator group.Vertigan et al, 2016 [90]Randomized, double-blind, placebo-controlled parallel trial40Speech pathology (SPT) with 300 mg pregabalin (PREG) treatment ( n = 20) versus SPT with placebo (PLAC) treatment ( n = 20).Primary outcomes were cough QOL measured by the LCQ, cough severity (VAS), cough frequency (LCM®). Secondary outcomes were capsaicin cough reflex sensitivity, urge to cough score and laryngeal function measures.Cough severity, cough frequency and cough QOL improved in both groups.…”

Section: Resultsmentioning

confidence: 99%

“…It acts on central nervous system calcium channels, leading to decreased release of neurotransmitters such as glutamate, noradrenaline, and substance P. Halum et al [102] showed that pregabalin was effective in the treatment of a small number of patients with laryngeal sensory neuropathy. In 2016, Vertigan et al [90] compared a combination treatment of pregabalin (PREG) and SPT to a matching placebo medication (PLAC) and SPT for patients with refractory CC (Table 3). The change in LCQ score from baseline for the PREG + SPT group was mean (SD) 6.6 (4.5) compared to the change in LCQ score from baseline for the PLAC + SPT group, mean (SD) 3.3 (2.3), p = 0.024 [meta-analysis, Figure 3(a,b)].…”

Section: Resultsmentioning

confidence: 99%

“…If we remove the Vertigan et al [90] study from the meta-analysis due to the effect of speech pathology on cough outcomes, there is now a significant pooled-effect from the remaining neuromodulators, gabapentin and amitriptyline (RR 2.11, 95% CI 1.37 to 3.26, p = 0.0007) (Figure 4(b)). There is less effect from the gabapentin treatment but there is more risk of bias for the amitriptyline study.…”

Section: Resultsmentioning

confidence: 99%

“…Conversely in a guinea pig study [118], memantine was found to significantly inhibit capsaicin-induced cough suggesting that the memantine site of action was peripheral. Further, capsaicin cough reflex sensitivity and objective cough frequency outcomes significantly decreased in both the pregabalin with SPT and the placebo with SPT groups from the Vertigan et al [90] study suggesting that speech pathology has an effect on the peripheral component of refractory cough.…”

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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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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Pregabalin and Speech Pathology Combination Therapy for Refractory Chronic Cough

Cited by 218 publications

References 23 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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