Pharmakopsychiatrie, Neuro-Psychopharmakologie最新文献

Dynamics and structure of EEG-patterning are highly sensitive indicators of psychotropic drug effects on the regulation of vigilance. Methodological requirements for an adequate evaluation of these effects and appropriate procedures for their measurement are discussed. The kind of information to be obtained by using these strategies is illustrated by the results of comparative investigations concerning the action of Viloxazine, a new antidepressant drug, on the resting activity and on the waking EEG during performance of various tracking tasks.

Assuming already condensed data from the EEG power spectra, problems arising with the statistical analysis of such data in comparative pharmaco-EEG trials are discussed. Since, in general, there is only a limited number of subjects available in a study to evaluate and compare the effects of a number of drugs by means of the EEG, the experimental design is usually of the cross-over type. With respect to this design, the requirements for the application and for the appropriate analysis are stated. Further, the problems are indicated which arise when the number of subjects is not a multiple of the number of drugs and/or when there are missing values. Finally, the topic of repeated null hypothesis testing and the inflation of the overall significance level is treated. Suggestions are made how to at least partly avoid the indicated problems at the present stage of methodological statistical research.

Many studies involving computerized EEG analyses are based on the assumption that normal subjects constitute a homogeneous population, so that under specified conditions across-subject averaging is justified. Quite often EEG signals are processed with little or no concern for the state of the particular person from whom they are obtained. It is the purpose of this discussion to draw attention to the fact that only can normals have different EEG's one from another, but also that the same ones can display markedly different EEGs from recording session to recording session. A consequence of this situation is that there is always a large between-subject variability, and that the source of the signals needs to be carefully documented before generalizations can be made.

The EEG effects of twenty, clinically most frequently used psychotropic drugs and five placebos were studied in 75 male volunteers in five simultaneously designed basic studies. In each of the five studies single oral dosages of five drugs (well known representatives of neuroleptics, antidepressants, anxiolytics and psychostimulants, as well as placebos) were investigated in 15 subjects in a double-blind latin-square research design using the methods of the Quantitative Pharmaco-EEG. The results demonstrated that the therapeutically equivalent effective compounds also have similar effects on human EEG. With a classification rule, based on discriminant function 20, and with a classification rule, based on correlation statistics 19 of 25 compounds could be reclassified into correct clinical-therapeutic psychotropic drug groups. It is suggested that CEEG is an important tool in predicting and describing psychotropic properties of compounds, and should routinely be used in psychotropic drug development.

Quantitative EEG analyses in combination with certain statistical procedures may be utilized in order to classify psychotropic drugs and to determine their cerebral bioavailability. Psychometric tests including evaluation of attention, concentration, psychomotor activity, critical flicker frequency, reaction time, Archimedean spiral, mood and affectivity, may add valuable information about a drug's psychotropic and pharmacodynamic properties. As was seen in studies involving a new pyridodiazepine, short-term drug effects in the EEG of normals are predictive of EEG and clinical effects in patients. Pharmaco-EEG profiles of lopirazepam were found similar in normals and alcoholic patients with an anxiety syndrom as far as the type of changes was concerned, although some quantitative differences were observed. As previously described, quantitative EEG changes during treatment were correlated with clinical improvement or deterioration. Moreover, there is some evidence that single dose effects in the EEG of patients may eventually be utilized to predict therapeutic outcome with a certain drug. Finally, relationships between blood level, quantitative EEG and psychometric changes after administration of phentermine and oxazepam are described and discussed.

This paper reviews older results on EEG and behavioral effects of heroin and opiate antagonists in exaddicts, and presents new findings on the effects of naltrexone in men who have never been addicted. Ten normal volunteers were given on three separate occasions placebo, 50 mg or 100 mg of naltrexone. The average alpha frequency was significantly slower after naltrexone than after placebo. Naltrexone elicited a significant reduction of breathing rate and oral temperature. Those results indicate that naltrexone does not act as a pure narcotic antagonist in non-addicted men.

An objective rule for the classification of psychotropic substances has been developed. Classification is based on data from five basic studies simultaneously designed and performed and involving 75 healthy volunteers who ingested 20 different psychotropic drugs and 5 placebos in single oral dosages. Each volunteer took one psychostimulant, one antidepressant, one neuroleptic, one minor tranquilizer and one placebo in a double-blind Latin square cross-over design. The variables were 6 frequency bands, based on power spectrum estimates and determined by factor analysis, plus total power in the 1.5-30.0 Hz range. An objective classification rule was established by multi-group (5 groups) linear discriminant analysis. Reclassification of the substances by the new rule yielded correct results for 17 out of 20 psychotropic drugs and 4 out of 5 placebos. Of placebos from various studies not used for the establishment of the classification rule, 7/9 were classified correctly. The validity of the rule for other classes of substances will have to be verified in independent studies.

The quantitative EEG profile of a putative antihistaminic drug, terfenadine, was determined in a crossover comparison with diphenhydramine in normal male volunteers. Terfenadine failed to elicit the characteristic EEG or behavioral effects of sedative antihistaminics, and was distinguishable from diphenhydramine. The EEG profile confirmed the lack of CNS effect observed in preclinical and clinical trials.