Human Pharmacology of Antipsychotic and Antidepressant Drugs

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Abstract
Behavioral and other psychological effects of these drugs are quite poor predictors of their therapeutic, potential or clinical responses. Although personality factors in the patient may have some importance in influencing the clinical actions, these appear to be less important than for most drugs which affect subjective experiences. The limitations of eeg studies in humans have been quite apparent, the paucity of substantial clinical eeg data contrasting greatly with the abundance of electrophysiological studies in animals. Investigation of drug metabolism has indicated that most have a cumulative action, that clinical effects are more dependent upon tissue levels than blood levels, and that patterns of metabolism still cannot be linked to differential clinical responses to drugs. The extent to which changes in biogenic amines can be measured clinically has limited confirmation of the important role of these amines and the possible importance in their mechanism of action of changes in membrane permeability to them which have been suggested by animal experiments. Investigation of the side effects of these drugs has been more rewarding. The unusual ability of many antipsychotic drugs to evoke extrapyramidal reactions in man has led to an extensive amount of investigation of the neurochemical basis of this disorder and possible new therapies. Depression, a side effect induced by reserpine, soon became a model for chemical studies which evolved into the norepinephrine hypothesis of depression.