Further Research Needed to Optimize Benefit of Gabapentin, Baclofen in Chronic Cough

Gabapentin and baclofen can help in the treatment of chronic refractory cough due to gastroesophageal reflux disease (GERD), but additional research is needed to screen for patients who can most benefit while avoiding unnecessary adverse effects (AEs), a new study says.

The study, published in the Journal of Thoracic Disease as a review piece for the Third International Cough Conference, is the first to compare the effectiveness of the 2 neuromodulators in the treatment of refractory gastroesophageal reflux–induced chronic cough (GERC). Researchers from the Tonji University School of Medicine in Shanghai, China, found the 2 drugs to be similarly effective, but suggested gabapentin may be preferable due to fewer AEs.

The rate of effectiveness, however, was suboptimal, with more than 40% of participants seeing no improvement in their GERC, according to the study. The authors said further studies are needed to determine which patients would be better served receiving either drug, and they suggested that the limited performance points to heterogeneity in GERC.

Cough is a common symptom of GERD, occurring in 30.5% to 34.9% of patients. GERC, the mechanisms of which are poorly understood, is a subtype of GERD in which cough presents as a prominent symptom among patients.

Treatments for GERC include antacid agents to reduce the acid of refluxates and promotility agents to help clear the esophagus and improve gastric emptying. Standard treatment includes antisecretory agents such as proton pump inhibitors (PPIs) and H2 antagonists, used alone or in combination with promotility agents, although the effectiveness of PPIs is considered controversial, the researchers wrote. The study was initiated because neuromodulators are considered a promising treatment for refractory GERC.

Gabapentin had a 57.3% success rate compared with 53% for baclofen. Both drugs also provided similar improvement in cough sensitivity and other symptoms. However, drowsiness (20.5% vs 35.0%; P = .013) and dizziness (11.1% vs 23.9%; P = .010) were significantly lower for patients administered gabapentin.

The study involved 234 patients. Diagnosis of GERC was arrived at only after excluding other causes of chronic cough. Objective evidence of abnormal reflux was documented by a positive DeMeester score (≥ 14.72) and symptom association probability (≥ 95%) as revealed by multiple-channel intraluminal impedance-pH monitoring. The condition was considered refractory if an 8-week course of treatment with omeprazole and domperidone failed to provide relief from cough.

The researchers had speculated that baclofen would be more effective than gabapentin because of the mechanisms underlying gastroesophageal reflux and because it blocks transient lower esophageal sphincter relaxations; however, the results showed otherwise. In fact, gabapentin may be more superior than shown in the study because the dose can be increased to a maximum of 1800 mg, double the maximum daily dose used in the study. Gabapentin relives cough mainly by inhibiting the hypersensitive cough center, similar to how it inhibits neuropathic pain.

Patients who responded saw resolution during an 8-week course of treatment with either drug followed by a 3-week wean. Only a few patients relapsed.

Despite the limited effectiveness of the neuromodulators, the researchers recommended their use. “Considering the severe negative impact of refractory cough on quality of life, cough resolution (even in a few patients) can be considered to be successful and important in clinical practice,” they wrote.

Reference

Zhang M, Zhu Y, Dong R, Qiu Z. Gabapentin versus baclofen for treatment of refractory gastroesophageal reflux–induced chronic cough. J Thorac Dis. 2020;12(9):5243-5250. doi:10.21037/jtd-2020-icc-002