Short‐ and Long‐term Effects of Neuromodulators for Unexplained Chronic Cough

Abstract

Objective To evaluate the short- and long-term effects of tricyclic antidepressants (TCAs) and gabapentin in the treatment of unexplained chronic cough (UCC). Study Design Prospective cohort. Setting Tertiary care hospital. Subjects and Methods Patients seen between July 2016 and March 2017 were included following a formal workup and clinical evaluation indicative of UCC. Patients were placed on either a TCA (amitriptyline or nortriptyline) or gabapentin. Leicester Cough Questionnaire (LCQ) and percentage improvement scores were obtained prior to treatment initiation and at 2 and 6 months of neuromodulator treatment. A linear mixed model assessed the change in LCQ score between the 2 treatment time points and baseline scores. Results Twenty-eight patients completed a total of 37 neuromodulator trials. Gabapentin demonstrated statistically significant improvement in LCQ scores at 2 months (2.48 points, P≤ .01) and 6 months (5.40 points, P = .01) of treatment as compared with baseline. Patients taking TCAs demonstrated statistically significant improvement of LCQ scores at 2 months of treatment (3.46 points, P≤ .01). However, the majority of patients discontinued treatment, most commonly secondary to the development of tachyphylaxis after 2 months, precluding analysis at 6 months. Conclusion While both neuromodulator classes demonstrated short-term benefit, the majority of patients discontinue treatment prior to 6 months, with patients taking TCAs discontinuing more frequently than patients on gabapentin. Future investigations are warranted evaluating tachyphylaxis and the utility of dual treatment therapies designed to address peripheral and central sensory pathways involved in UCC.

Chronic Cough in Adults: Make the Diagnosis and Make a Difference

“…Neuroplasticity occurs because of the inflammation and hyperresponsiveness of the airway from the inciting causes that are not resolved, subsequent tissue remodeling and nerve sensitization, all of which lead to an enhanced cough reflex that maintains the cough even though the inciting cause has resolved [33]. Similarities have been demonstrated between neuropathic pain and chronic cough, and centrally acting neuromodulators such as tricyclic antidepressants (amitriptyline, nortriptyline), gabapentin, and pregabalin have shown benefit in improving cough (albeit with risk of side effects) [34][35][36]. Consider the potential side effects and the risk-benefit profile of these medications and again at 6 months before continuing the drug (Fig.…”

A cough that won’t go away: Evaluation and treatment in 2 patients

“…plained chronic cough and should be one of the fi rst considerations for this patient, given his lack of benefi t from a multispecialty workup. 21 A major limitation of this treatment approach is that we cannot predict the patient in front of us will respond to any particular medication at any given dose or frequency.…”

“…As such, gabapentin is an effective and well-tolerated treatment in chronic cough, and several prospective case series and cohort studies support its effi cacy. 21,22 Similarly, the effectiveness of amitriptyline was assessed in a single randomized clinical trial 23 in 28 patients randomized to receive either amitriptyline or codeine-guaifenesin. Eleven (73%) of the 15 patients in the amitriptyline group achieved a complete response, compared with none of the patients in the codeine-guaifenesin group, indicating that amitriptyline may also be an effective treatment in chronic cough.…”

Treatment of Chronic Refractory Cough in Adults: Focus on Neuromodulators and Other Therapeutic Modalities

“…Bowen et al 56 conducted a prospective study with 16 cohorts (mean age = 61 years, 57% female) to evaluate the short-and long-term effectiveness of amitriptyline in the treatment of unexplained chronic cough. After 2 months, there was a significant improvement in mean LCQ scores (P < 0.01), but a marked dropout of patients (83%) from the treatment regimen secondary to diminished benefits inhibited a valid analysis at 6 months.…”