Correlation between EEG changes indicative of sedation and subjective responses

The central activity of ketotifen ( Zaditen ), a benzocycloheptathiophene derivative for use in the prophylaxis of asthma, was determined by quantitative pharmaco-EEG in 7 healthy volunteers in a single-blind trial. During the 1st week of the trial, placebo was given twice daily followed by ketotifen 1 mg twice daily for 3 weeks. Placebo was again given for a further week. 15-min resting EEGs were taken immediately before and 3 and 6 h after medication on 8 defined days during the study, and the subjects were asked for side effects. Lead O2-Cz was analyzed by spectral analysis, and the relative power of the delta, theta, and fast and slow alpha bands as well as the dominant alpha frequency were calculated. The mean of each of these parameters was calculated per subject for each of the three measurements on each study day and compared with the baseline by means of one-way analysis of variance. A statistically significant slowing of the dominant alpha frequency, a decrease of the relative power of the fast alpha activity, and an increase of the relative power of the theta rhythm were found. These effects, indicative of a mild sedation, were highest during the 1st week of treatment with ketotifen, with a peak at the 3rd day, and gradually decreased thereafter. In contrast to the sensitive pharmaco-EEG method, none of the subjects complained of sedation or tiredness while taking ketotifen.