[Pharmacopsychologic studies on normal subjects for the prediction of the therapeutic efficiency of psychotropic drugs].

The paper deals with some basic problems and possibilities of predicting the therapeutic efficiency of psychotropic drugs from studies in normal humans. Comparing drug studies with normal subjects and patients it seems evident that from a methodological and economical point of view studies with normal subjects have many advantages. However, the practical importance of drug studies with normal subjects is limited unless the therapeutic efficiency of a drug can be predicted. There are some arguments which deny the possibility of prediction, e.g. referring to the lack of comparability of dosages, administration regimens, situational parameters and psychosomatic states between normal subjects and patients. Discussing such arguments it is pointed out that perfect comparability of all these factors is not a necessary prerequisite of prediction. A number of theoretically possible models for predicting therapeutic efficiency is suggested. For some of them there already exists some empirical evidence. The first model takes into account the inter- and intra- individual variability of behavior. It is suggested that a state corresponding to the psychosomatic state of patients be approximated, or simulated, in the normal subjects by suitable selection procedures of subjects or by manipulation of the experimental conditions. The usefulness of such a model for predicting therapeutic efficiency has been shown in many studies with anti-anxiety agents. In another model the drug profiles of normal subjects and patients are compared and the prediction is based upon drug effects in normal subjects which can also be seen in patients and which have a high correlation to the patients' improvement. A further model assumes that improvement is partly the result of learning processes. The prediction of therapeutic efficiency is, therefore, based upon the properties of a drug to facilitate or inhibit learning processes. The final two models proposed, predict limitations of therapeutic efficiency. The one model takes into account side-effects; the other the variability of drug response due to situational and person-parameters.