ArticlesGabapentin for refractory chronic cough: a randomised, double-blind, placebo-controlled trial
Introduction
Chronic cough is a common clinical problem for 11–16% of the population,1 affecting physical, psychological, and social domains of health.2 Although many patients are treated successfully,3 cough can persist even after extensive investigation or treatment trials in 20–42% of outpatient referrals. These patients have refractory chronic cough.4, 5
The sensitivity of the cough reflex is increased in chronic cough.4, 6 Hypersensitivity to tussive stimuli such as capsaicin is caused by both peripheral and central mechanisms. Non-tussive stimuli can also trigger cough, which suggests that additional central neuronal mechanisms or central reflex sensitisation are implicated. Peripheral sensitisation (cough reflex hypersensitivity in peripheral nerves) has been shown with enhanced cough responses to inhaled capsaicin4, 6 and increased neural expression of transient receptor potential receptors. The role of central sensitisation in refractory cough has received little attention; however, refractory cough shares similarities with other disorders associated with central sensitisation, such as neuropathic pain.7
The clinical features that indicate central sensitisation in chronic pain, such as paraesthesia (abnormal sensation in the absence of a stimulus), hyperalgesia (pain triggered by a low exposure to a known painful stimulus), and allodynia (pain triggered by a non-painful stimulus), show similarities with the clinical features of refractory chronic cough, such as an abnormal throat sensation or tickle (laryngeal paraesthesia), increased cough sensitivity in response to known tussigens (hypertussia), and cough triggered in response to non-tussive stimuli such as talking or cold air (allotussia).8
The neuromodulator gabapentin is effective for neuropathic pain with central sensitisation, and findings from two case series have shown success with gabapentin in chronic cough.9, 10 We aimed to test whether gabapentin, given to patients with refractory chronic cough, improves cough-specific quality of life and decreases cough severity and frequency.
Section snippets
Study design and participants
In this randomised, double-blind, placebo-controlled trial, we recruited adults with chronic cough lasting longer than 8 weeks from the John Hunter Hospital respiratory outpatient clinic (New Lambton, NSW, Australia), which receives referrals from primary and secondary care. Recruitment took place between October, 2008, and September, 2010. All participants had negative responses to previous investigations or trials of treatments for asthma, gastro-oesophageal reflux disease, and rhinitis
Results
We recruited 65 patients diagnosed with refractory chronic cough. We excluded three patients and randomly assigned the remaining 62 to either gabapentin (n=32) or placebo (n=30). Ten participants withdrew from the study and 52 completed it (gabapentin, n=26; placebo, n=26; figure 1), although one in the placebo group did not receive the full dose of the study drug due to a pharmacy dispensing error.
All patients had received several treatment trials before study entry and their cough was
Discussion
Findings from this trial have shown that gabapentin significantly improved cough-specific quality of life compared with placebo. These results suggest that gabapentin might be an effective therapy for refractory chronic cough (panel).
The onset of action of gabapentin was within 4 weeks, and the effect was maintained during maximal dosing at 8 weeks. However, the improvement in cough-specific quality of life (LCQ score) was not sustained after treatment withdrawal and LCQ score returned to
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