Planning of pharmacodynamic trials: I. Specificity and possible solutions. II. Stability considerations under placebo and interpretation of drug effects on EEG.

This workshop deals with the concept of quantitative electroencephalography (QEEG) to characterize the central effects of drugs. For proper interpretation, the circumstances under which data are obtained play an important role. To infer the size of variability in standard practice, we elaborated some computations for "placebo-treatment" in healthy volunteers, which helps to determine the threshold of drug effect detection. Simple rules for interpretation of multiple statistical comparisons were proposed and validation of dose effects were carried out with accepted reference compounds. Furthermore, psychotropic agents with comparable therapeutic indications often present similar modifications in EEG spectral composition (pharmaco-EEG profile). To extrapolate this concept, quantified wake-EEG is a rapid, validated technique for early psychopharmacological investigation of new psychotropic compounds (Phase I, healthy volunteers). Classification of drug-induced changes in cerebral activity at this stage forms a useful decision instrument in planning the long-term clinical scenario of drug development (Phases II and higher).