Janke W, Debus G
Arzneimittelforschung. 1975 Jul;25(7a):1185-94.
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.
本文探讨了通过对正常人的研究来预测精神药物治疗效果的一些基本问题和可能性。比较针对正常受试者和患者的药物研究，从方法学和经济学角度来看，针对正常受试者的研究似乎具有诸多优势。然而，除非能够预测药物的治疗效果，否则针对正常受试者的药物研究的实际重要性是有限的。存在一些观点否认预测的可能性，例如提到正常受试者和患者之间在剂量、给药方案、情境参数和身心状态方面缺乏可比性。在讨论这些观点时指出，所有这些因素的完美可比性并非预测的必要前提。文中提出了一些理论上可能的预测治疗效果的模型。其中一些已经有了一些实证依据。第一个模型考虑了行为的个体间和个体内变异性。建议通过合适的受试者选择程序或操纵实验条件，在正常受试者中近似或模拟与患者身心状态相对应的状态。在许多抗焦虑药物研究中已经证明了这种模型在预测治疗效果方面的有用性。在另一个模型中，比较正常受试者和患者的药物特征，并基于在正常受试者中也能在患者身上看到且与患者病情改善高度相关的药物效应进行预测。另一个模型假设改善部分是学习过程的结果。因此，治疗效果的预测基于药物促进或抑制学习过程的特性。最后提出的两个模型预测治疗效果的局限性。一个模型考虑副作用；另一个模型考虑由于情境和个体参数导致的药物反应变异性。
