The case for an individual approach to the treatment of depression.

Early reports of the discovery of antidepressants in the 1950s have remained as little-known findings. Had the discovery of isoniazid, an agent with no clear action on monoamine systems, and that of reserpine, which depletes monoamines, been more widely known, then the monoamine lesion theories of depression, as proposed by Schildkraut in 1965, may not have been written. If the lesion in depression is lowered brain monoamine levels, then antidepressant agents that increase monoamine levels should work for all patients. If this were the case, optimizing treatment effect sizes with a minimum of side effects and some demonstrable specificity to depressive disorders would be possible. This is not the profile of antidepressants in clinical practice. Alternatively, if antidepressants act on constitutional types to provide appropriate therapeutic principles, then the efficacy would stem from an ability to suppress symptoms and to elicit or maintain conditions that allow recovery in a subgroup of patients who would otherwise remain nonresponsive. Current monoamine selective antidepressant principles embody "get-up-and-go" (noradrenergic) and emotional reactivity-reducing (serotonergic) principles. Different antidepressants are, therefore, likely to have different treatment effect sizes in different constitutional types. A further important aspect of antidepressant selectivity will lie in the extent to which these agents promote a sense of well-being during the maintenance phase of treatment.