Codeine is generally accepted as the standard
antitussive against which new
antitussive medications are compared. This presents a problem because the support for
codeine's
antitussive activity comes from studies on
cough in animals, and chronic and induced
cough models in man, whereas
antitussives are almost exclusively used for the treatment of
cough associated with acute
upper respiratory tract infection (URTI). The aims of this study were twofold. Firstly, to study the
antitussive efficacy of
codeine in
cough associated with URTI and, secondly, to validate a sound meter as tool for quantifying
cough. The efficacy of
codeine was assessed in a double-blind, stratified, placebo-controlled, parallel-group, clinical trial using three different measures of
cough:
cough sound-pressure levels (CSPLs) measured on a sound meter; subjective scores of
cough severity; and
cough frequency recorded by means of a microphone connected to an ink-pen recorder. A group of 82 subjects (51 females and 31 males; mean age 23.5 years, range 18-46 years) with
cough owing to acute URTI were included in the study. The study took place on two separate study days. On study day 1
cough measurements were made before and 90 min
after treatment with a single dose of either 50 mg
codeine or matched placebo in
capsule form. The same three measures of
cough were repeated 2-5 days later (study day 2). On study day 1 a highly significant (P < 0.0001) decrease in all three measures of
cough was found
after treatment with both placebo and
codeine yet there was no significant difference between the treatment groups. A highly significant (P < 0.0001) decrease in the three measures of
cough was also found between days 1 and 2. The results demonstrate that
codeine is no more effective than placebo in reducing
cough associated with acute URTI, as measured by CSPLs,
cough frequency or subjective symptom scores. This result might be explained on the basis of two central pathways for
cough; a reflex pathway via the brain-stem which is sensitive to
codeine and a voluntary pathway via the cortex which is unaffected by
codeine. The results also demonstrate that the sound-level meter appears to be a potentially useful investigative tool for the assessment of
cough and
antitussive efficacy.