The possibility that pharmacological response might help to refine psychiatric nosology has been the subject of recurrent speculation, but few clear-cut results have been obtained. Only bipolar depressives and several other minor patient subgroups manifest consistent drug responses in association with characteristic psychobiological features. The presence of multiple intervening variables, such as individual differences in drug metabolism, drug-taking behaviour and biological sensitivity to drugs, may mitigate against the reliable identification of clinically distinguishable drugresponding subgroups. Furthermore, the majority of available psychoactive drugs have either multiple or broad spectrum effects inconsistent with hypotheses utilizing the mechanism or site of drug action to argue for a diagnosis-specific biological disorder at such sites.
Nonetheless the successful use of drug-response models in other areas of medicine suggests a rationale for continued exploration in this area, and a number of recent advances make this approach potentially more productive. Pharmacological developments have rendered it possible to assess the biological availability of drugs in potential responders, thus eliminating some of the confounding intervening variables. Further consideration should also be given to the use of drugs with more specific neurochemical effects, even when they themselves are not necessarily therapeutic. The comparison of drug responder and non-responder groups has also been made more meaningful by the availability of more reliable methods of assessing clinical phenomena, more sophisticated diagnostic models and the introduction of other biological measures. Combining several of these approaches may allow the use of one to validate the other.