Human pharmacology of antidepressives.

As both the tricyclic antidepressives and the monoamine oxidase (MAO) inhibitors were discovered accidently, their pharmacology has been established on an empirical basis only. There are no convincing models of depression in the normal human. The classification of depression remains controversial; also the relationship between clinical depression, depressive reactions and pessimistic personality traits is unresolved. Antidepressive effects are demonstrable in lugubrious normals. Pharmacokinetic and drug interaction data are important in the usage of a drug and are available from studies in normals. Secondary psychotropic effects such as sedation can be readily studied both in normals and in patients. The antidepressives produce characteristic changes in the electroencephalogram (EEG). Unwanted effects are often related to autonomic actions which can be readily quantified, salivation being most extensively studied. Psychological impairment is dose related in normals but lessens over a course of treatment in patients. Biochemical measures have been little explored despite their obvious relevance. MAO activity in platelets is diminished by MAO inhibitors. Tricyclic drugs inhibit the uptake of amines into neurones and platelets, and this inhibition can be assessed in various ways. Drug experiments in normal subjects provide data which complement, amplify and elucidate observations in patients without ever substituting for them.