Combining speech pathology breathing therapy with the neuropathic pain drug pregabalin (Lyrica) was more effective than speech pathology therapy alone for chronic cough refractory to other treatments, according to results of a randomized controlled trial.
The mean difference in cough-related quality of life based on the Leicester Cough Questionnaire (LCQ) between the dual and single therapy groups was 3.5 (95% CI of difference 1.1-5.8), while the mean difference in using a visual analog scale (coughVAS) was 25.1 (95% CI of difference 10.6-39.6), reported Anne E. Vertigan, PhD, of the University of Newcastle New South Wales in Australia, and colleagues
Cough severity, cough frequency, and cough-related quality of life (QOL) all improved in both groups during active treatment and follow-up, but the improvement was significantly greater in patients receiving both the drug and speech pathology training (SPT), they wrote in Chest.
Chronic Cough
Chronic cough is responsible for an estimated 30 million physician visits each year in the U.S. alone, noted Kenneth W. Altman, MD, of Baylor College of Medicine in Houston, who was not involved with the study.
"Even when it is not a sign of serious disease, chronic cough is associated with significant impairment of quality of life, and this is largely unrecognized," Altman told MedPage Today.
Altman served on an expert panel that reported early in 2016 on assessment and treatment practices regarding unexplained chronic cough. The panel recommended that adults with chronic cough undergo objective testing for bronchial hyper-responsiveness and eosinophilic bronchitis.
The panel also recommended a therapeutic trial of multimodality speech pathology therapy in patients with refractory unexplained chronic cough and a therapeutic trial of gabapentin, "as long as the potential side effects and the risk-benefit profile are discussed with patients before use of the medication, and there is a reassessment of the risk-benefit profile at six months before continuing the drug."
Serious lung disease, gastrointestinal-reflux disease (GERD), allergy and asthma, and use of ACE inhibitor hypertension drugs are all common causes of chronic cough, but a significant percentage of patients have no obvious cause, or have chronic cough refractory to treatment for these conditions.
"Most patients with significant symptoms have been extensively examined and have tried a variety of asthma, COPD, and cough medications," wrote Eva Millqvist, MD, PhD, of Sweden's University of Gothenburg in an accompanying editorial. "Treatment failure is more the rule than the exception, despite evident links between a number of respiratory conditions and aspects of coughing."
Millqvist noted that the relatively new term cough hypersensitivity syndrome (CHS) refers to patients with chronic cough often triggered by "low levels of thermal, mechanical or chemical exposure with or without pathological medical findings."
"The key to successful management of chronic cough may be to disregard old concepts (e.g., use of asthma medications such as β2-agonists and inhaled steroids) as cures for unexplained chronic cough," she wrote.
The anti-seizure and neuropathic pain drug gabapentin has been shown in recent studies to be effective and well tolerated in the treatment of chronic cough, as has respiratory retraining speech pathology.
Study Details
In the current study, the researchers explored the efficacy of pregabalin for the treatment of chronic refractory cough. They noted that pregabalin may be better tolerated in CRC than gabapentin because it can be prescribed in lower doses.
All patients in the trial received SPT in addition to pregabalin or placebo, because neuropathic pain drugs do not address the issue of reflex hypersensitivity.
In an interview with MedPage Today, voice and swallowing disorder specialist Thomas Murry, MD, of Loma Linda University in Loma Linda, Calif., said the goal of speech pathology treatment in patients with chronic refectory cough is to better coordinate breathing patterns with vocal folds.
"People with chronic cough often have irritated or inflamed vocal cords," he said. "In chronic cough and some other conditions, vocal folds tend to want to close when they are supposed to be open and this irregular motion causes irritation."
The trial included 40 patients with chronic refractory cough randomized to receive either combined SPT and pregabalin (300 mg daily) or combined SPT and placebo. The majority of participants (60%) in both groups had never smoked. The mean duration of cough was 94 months in the study arm and 141 months in the placebo arm.
Primary outcomes included cough frequency and cough-related QOL.
The authors reported no significant difference in improvement in cough frequency between groups, and no deterioration in symptoms once pregabalin was withdrawn. Median capsaicin cough sensitivity improved from 15.7 to 47.5 μM with combined SPT and pregabalin and from 3.92 to 15.7 μM with SPT alone.
Adverse effects were reported by 75% of participants from each group but blurred vision, cognitive changes, dizziness, and weight gain were significantly greater in the patients treated with pregabalin. Also, sleep disturbance and headache were significantly greater for the SPT plus placebo group.
However, the authors pointed out that "these side effects were not treatment limiting (i.e., participants did not withdraw because of them), but are common, and patients receiving this therapy need to be informed about the likely side effects."
The mean depression scores did not change between treatment groups (P=0.280).
The authors noted that "these findings are in contrast with previous studies of gabapentin, in which the treatment effect was not maintained once the medication was withdrawn. It is possible that SPT was responsible for the sustained response; however, direct comparison with a group receiving pregabalin alone would be needed to test this hypothesis."
Although gabapentin and pregabalin have similar methods of action, pregabalin has more rapid absorption, the researchers noted, adding that more study is needed to determine if one drug is superior to another for the treatment of chronic refractory cough.
Study limitations included the low recruitment rate and the need for more data to determine if the findings apply to a broader population.
The authors also cautioned that pregabalin has been associated with dizziness and falls, especially in seniors. Given this side effect, they suggested that pregabalin may be best for patients should be reserved for patients with more severe cough symptoms, they said. It's also possible that lower doses of pregabalin may offer similar efficacy with less adverse events, they added.
The study was funded by the John Hunter Hospital and the National Health and Medical Research Council, New South Wales, Australia.
Vertigan and co-authors disclosed no relevant relationships with industry.
Millqvist disclosed no relevant relationships with industry.
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