N-of-1 double-blind, randomized controlled trial of tramadol to treat chronic cough

Abstract

Background: Chronic cough caused by interstitial pneumopathy can present a therapeutic dilemma, and the use of tramadol in the treatment of this symptom might be an alternative to improve the quality of life in patients. The present study describes a patient with rheumatoid arthritis and interstitial lung disease lasting 11 years who developed dry cough secondary to interstitial pneumopathy but was nonresponsive to several treatments (codeine 20 mg q6h; clobutinol 240 mg/d; and dextromethorphan 10 mg q4h). Objective: The purpose of this study was to investigate, for an individual patient, the effectiveness of tramadol 50 mg compared with placebo, and whether tramadol provided any antitussive benefit. Methods: This was an N-of-1 double-blind, randomized controlled trial of tramadol against placebo. Treatment was administered in 3 pairs, each consisting of 2 periods in which either tramadol 50 mg BID or placebo was administered for 6 days, followed by a 2-day washout period, and then the administration of the alternate for 6 days. A 2-day washout period was also carried out after pairs 1 and 2. Per pair, the sequence of treatments was randomized. Outcome measures were: the intensity of daytime and nighttime cough, assessed by a visual analog scale (VAS) ranging from 0 to 5 (0 = no cough, 5 = distressing cough); and the patient's perception regarding her health state (better, same, or worse). Results: A 55-year-old black woman (height, 153 cm; weight, 71 kg) was in the study. In all treatment pairs, cough intensity, as reported by the patient using the VAS, was significantly lower with tramadol compared with placebo (P < 0.001), both in the daytime (2 vs 5, respectively) and at nighttime (1 vs 4). Regarding the patient's health state, in all periods in which tramadol was administered, the patient reported feeling better than when placebo was administered. At the begin- ning of pair 2, the use of rescue tramadol 50 mg (un-blinded) was permitted due to cough intensity. In the remaining treatment periods in which placebo was administered, rescue tramadol was administered, whereas rescue tramadol was not needed during the periods in which tramadol was administered. Conclusions: Tramadol appeared to be effective in controlling cough in this patient. Because no similar report was found in the literature, further studies assessing the efficacy of tramadol as an antitussive agent are warranted. © 2009 Excerpta Medica Inc. All rights reserved.