Gabapentin for the cough of idiopathic pulmonary fibrosis

Design

single-centre randomised, double-blind, placebo-controlled trial, 12 weeks treatment with 4 weeks follow-up, 1:1 allocation

Population

68 randomised patients with guideline-diagnosed idiopathic pulmonary fibrosis, cough over 8 weeks and cough VAS at least 40 mm

Primary outcome

cough relief rate at end of treatment — at least 50% reduction in total Cough Symptom Score from baseline

Effect

73.5% vs 26.5%, placebo-adjusted difference 47.1 percentage points (95% CI 26.1-68.0), P < 0.001; adverse events 32.4% vs 8.8%

Cough in idiopathic pulmonary fibrosis is common, wrecks quality of life, and has almost nothing licensed to treat it. This trial randomised 68 patients with fibrosis diagnosed to ATS/ERS/JRS/ALAT criteria and cough for more than eight weeks with a visual analogue score of at least 40 mm, to gabapentin titrated to a maximum 900 mg daily or matching placebo for 12 weeks, double-blind, with four weeks of follow-up.

The result is unusually clear-cut for a symptom trial. Cough relief — defined in advance as at least a 50% reduction in total Cough Symptom Score — occurred in 73.5% on gabapentin against 26.5% on placebo, a placebo-adjusted absolute difference of 47.1 percentage points (95% CI 26.1 to 68.0, P < 0.001). Adverse events occurred in 32.4% against 8.8%, and were the expected ones: drowsiness, fatigue, dizziness.

Two qualifications, neither fatal. This was a single centre with 68 patients, so the effect size is likely to shrink in wider use, and the population was Chinese, which matters for gabapentin dose tolerance. And the maximum dose was 900 mg daily — lower than is often used for neuropathic pain, which is good news for tolerability and means there is no need to push higher to reproduce the result. Against a symptom with essentially no alternatives, a cheap, widely available, off-patent drug with a 47-point absolute benefit and a known side-effect profile is worth offering, with a clear plan to stop if drowsiness outweighs the relief.

• Titrate to a maximum of 900 mg daily — the dose that produced this result, not a neuropathic-pain dose
• Warn about drowsiness, fatigue and dizziness before starting; a third had an adverse event
• Set a review point and stop the drug if cough has not meaningfully improved by the end of titration
• Reduce the dose in renal impairment, common in this older population, as gabapentin is renally cleared
• Gabapentin is cheap and widely available in India, which makes this one of the few IPF interventions not limited by cost

The statistics, in plain English

An absolute difference of 47.1 percentage points means that for roughly every two patients treated, one gained meaningful cough relief they would not otherwise have had — an unusually large effect for a symptom trial. The confidence interval (26.1 to 68.0) is wide because only 68 patients were randomised, so the true benefit could plausibly be half the headline figure and would still be worth having. A responder endpoint like this one is easier to interpret than a mean change but discards information about how much better the responders got, and single-centre trials of this size typically report larger effects than later multicentre replication finds.

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