Effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy

Laryngoscope. 2006 Dec;116(12):2108-12. doi: 10.1097/01.mlg.0000244377.60334.e3.


Objective: The objective of this prospective, randomized, controlled study (N = 28) was to evaluate the effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy.

Methods: Patients were selected based on a clinical history consistent with postviral vagal neuropathy and a history of an antecedent upper respiratory tract infection. All patients had been tried on antireflux medication (proton pump inhibitors) and had a negative chest x-ray before presentation. All were nonsmokers without a history of asthma. Patients on angiotensin-converting enzyme inhibitors were excluded from the study. All patients completed a pretreatment, validated cough-specific quality-of-life (QOL) survey. Patients were randomized by chart numbers to either 10 mg amitriptyline at bedtime or 10 to 100 mg/5 mL, 10 mL codeine/guaifenesin every 6 hours standing dose while awake. Both groups were instructed to complete 10 days of therapy and then asked to subjectively rate the reduction in the frequency and severity of their cough by 100%, 75%, 50%, 25%, or 0% as well as completing the posttreatment cough QOL questionnaire. Those patients experiencing a 75% to 100% reduction were recorded as having a complete response, 25% to 50% a partial response, and 0% as having no response. Final results and the cough QOL survey were recorded and used for statistical analysis.

Results: A majority of patients in the amitriptyline group achieved a complete response on the initial dose of 10 mg. None of the codeine/guaifenesin group achieved a complete response. The data were analyzed using a logistic regression model, and amitriptyline was found to be a highly significant predictor of a greater than 50% response when compared with codeine/guaifenesin (P = .0007). The same data were analyzed using a proportional odds model and similar results were noted.

Conclusions: Chronic cough can have a profound impact on the psychosocial function of patients. The most common causes of a persisting cough in the absence of infection or chronic smoking are laryngopharyngeal reflux, asthma, particularly the cough variant, allergy, rhinosinusitis, bronchitis, and medications, in particular angiotensin-converting enzyme inhibitors. Currently, there are few effective treatments for cough with an acceptable therapeutic ratio and more selective drugs with a more favorable side effect profile are needed. This is this first prospective, randomized, controlled study comparing the effectiveness of amitriptyline versus codeine/guaifenesin for select cases of chronic cough resulting from suspected postviral vagal neuropathy.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Amitriptyline / therapeutic use*
  • Antitussive Agents / therapeutic use*
  • Chronic Disease
  • Codeine / therapeutic use*
  • Cough / drug therapy*
  • Cough / etiology*
  • Drug Combinations
  • Expectorants / therapeutic use*
  • Female
  • Guaifenesin / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Quality of Life
  • Vagus Nerve Diseases / complications*
  • Vagus Nerve Diseases / virology


  • Antitussive Agents
  • Drug Combinations
  • Expectorants
  • Amitriptyline
  • Guaifenesin
  • Codeine