Relationship between plasma-levels of chlorpromazine and effects on EEG and evoked potentials in healthy volunteers.

The effect of chlorpromazine (CPZ) was studied at four different doses in a group of 10 normal subjects. Blood levels of CPZ were assayed by gas chromatography and showed wide interindividual variations. Spontaneous brain electrical activity (EEG) was recorded from 8 leads and submitted to spectral analysis. Evoked responses (ER) to flashes, pattern reversals and clicks were averaged, and measured by their amplitude and variability. Several subjects presented marked side-effects (responders, R) and showed differences in many EEG parameters with respect to subjects without side-effects (non-responders, NR). A cluster analysis permitted to distinguish very clearly these two groups of subjects. The differences in the effects of CPZ between the R and NR groups involved mainly EEG, and appeared with a systematic topography over the scalp. Within the R group, many differences were observed as a function of the dose of CPZ; they consisted mainly in a decrease of alpha and an increase of theta activity in the EEG, decrease of amplitude and increase of variability in the ER measures. These modifications had also a typical topography over the scalp. Finally, many variables of EEG (relative power only) were correlated with plasma level of CPZ, while no such correlation appeared for ER. These results are discussed in terms of individual sensitivity to drugs, relationships between EEG parameters and plasma level, and topographical differences in the effect of CPZ.