Antiglucocorticoids in psychiatry†

Many of the current drug treatments in psy chiatry were discovered without any knowledge of the under lying ‘disease processes’ concerned. Theories of the mechanism of drug action were all devel oped post hoc and are predominantly concerned with mono amine neurotransmitter modulation. How­ ever, not all patients are treated successfully by these means and rates of full remission are frequently quite low. Current diagnostic categorisation of psychiatric disorders, such as unipolar depression, bipolar disorder and schizophrenia, is provisional and subject to ongoing revision. Ideally, drug development should be predicated on knowledge of ‘drug targets’ derived from understanding of the pathophysiological processes involved that are important for the illness in question. Although the central pathophysiological components of most psychiatric disorders remain unknown, a large body of evidence indicates that endocrine dysfunction, particularly of the hypothalamic– pituitary–adrenal (HPA) axis, may be important for certain psychiatric illnesses, as indeed is the case for some physical illnesses. Factors related to the HPA axis may partially account for treatment­ resistance (although, of course, a variety of factors contribute) and these may also suggest targets for development of new drugs with novel modes of action.