The clinical pharmacology of depressive states

Antidepressants have good efficacy in the treatment of mood disorders, with effect sizes that have consistently been found to be greater than those of placebo. The more recent antidepressants do not have better efficacy than the compounds discovered 40 to 50 years ago, but they do have a more favorable configuration of side effects, leading to fewer dropouts. This favorable situation has made it possible to prescribe the newer antidepressants in less severe depression and in several anxiety disorders, with considerable benefit to patients. During the last decades, research into the pathophysiology of mood and anxiety disorders has provided much information on the brain circuitry, neurohormones, and neurotransmitters involved in these disorders. In parallel, biological and behavioral work on antidepressants, using animal models and new biochemical techniques, has led to a broader understanding of the mode of action of these drugs. Despite this impressive list of discoveries, much research remains to be done on the clinical, psychological, neuropsychological, physiological, and neurochemical aspects, before we can obtain a coherent description of the pathophysiological mechanisms of depression and its treatment. This will lead to a better ability to predict the quality of drug response and, therefore, to the individualization of treatment.