Treatment of Chronic, Refractory Cough with Baclofen

Abstract

Chronic, nonproductive cough may result from enhanced sensitivity of the cough reflex. Often, this debilitating symptom is refractory to standard antitussive therapy. Baclofen, an agonist of γ-aminobutyric acid (GABA), has been shown, in animals, to have antitussive activity via a central mechanism. Recently, in normal subjects, we have demonstrated the ability of baclofen to inhibit capsaicin-induced cough, as well as cough due to angiotensin-converting enzyme (ACE) inhibitors. Herein, we describe two patients with chronic, refractory cough who obtained symptomatic improvement after a 14-day course of low-dose, oral baclofen, administered in a double-blind, placebo-controlled manner. In addition, both subjects demonstrated significant increases in cough threshold to inhaled capsaicin after treatment with baclofen.

The efficacy of specific neuromodulators on human refractory chronic cough: a systematic review and meta-analysis

“…However, the positive effects were not maintained 2 to 4 weeks after drug cessation according to the same study measurements. Cough frequency eventually returned to the previous baseline levels (4,5), and even cough severity (VAS score) significantly increased to greater than baseline values (4) (Figure 4), suggesting a possible treatment-byperiod interaction.…”

“…After the placebo treatment period, a reduction of cough sensitivity to inhaled capsaicin was not sustained after treatment in both studies (4,5). After 14 days of baclofen therapy, the capsaicin cough threshold increased by three to five doubling concentrations (8-to 32-fold) in the subjects (5) (Figure 7).…”

“…Ten participants withdrew from the study, and 82 completed it. The effective fill participants were 84 person-times [arm of specific neuromodulators, n=49; arm of control medicine Codeine/Guaifenesin (3), n=13; arm of control medicine placebo (4,5), n=32]. Of all patients screened and randomized, four withdrew because of possible side-effects, two were lost to follow-up after the first treatment period, two perceived lack of efficacy, one received treatment for comorbidity and one withdrew for personal reasons.…”

Successful Resolution of Refractory Chronic Cough Induced by Gastroesophageal Reflux With Treatment of Baclofen

“…In addition, baclofen has also been recognized for a long time to have a nonspecific antitussive activity both in animals [10] and in humans [11,12]. There have been several lines of evidence illustrating baclofen can treat the cough caused by angiotensin-converting enzyme inhibitors [13] and refractory chronic cough with unknown cause [14]. Our observations revealed that 2-4 week course of baclofen was needed for the significant alleviation of cough, and the complete resolution was generally achieved in the 2-3 months.…”

Gastroesophageal Reflux Disease

“…Lesogaberan, Baclofen ile aynı mekanizmaları kullanmasına karşın santral sinir sistemi yerine periferik aktiviteye sahip olduğundan yan etkiler daha azdır. Baclofen'in reflüyü inhibe ederek [62] ve/ veya öksürük refleksinin duyarlılığını azaltarak kronik öksü-rüğü olan hastalarda semptomları düzelttiği düşünülmektedir [63][64][65]. Yakın zamanda yapılmış bir çalışmanın preklinik verilerine göre deneysel oluşturulmuş öksürükte Lesogaberan'ın periferik etkilerden ziyade Baclofen'e benzer inhibitör etkiye sahip olduğu belirtilmektedir [66].…”