Antistress properties of antidepressant drugs and their clinical implications

Stress, in its different forms, represents a major environmental component for increased susceptibility to mental illness and, indeed, stressful life events serve as significant predictors of depression. With this respect, since antidepressant drugs may be effective in a variety of conditions that are triggered by, or associated with, exposure to stress, it is important to establish to what extent drug treatment can interfere with behavioral, functional and molecular alterations induced by stress exposure. The aim of this article is to examine the evidence supporting the ability of antidepressant treatment to reverse or modulate stress-induced alterations in humans and animals. Biologically, there is accumulating evidence that antidepressants can modify not only the neuroendocrine response to stress, but also mechanisms that regulate neuronal plasticity and that may play a key role in structural and functional changes associated with major depression. We believe that a detailed analysis of pharmacotherapy effects on stress-induced alterations may be important to define the ability and potency of different antidepressants to 'normalize' alterations that are central to the disease, in order to differentiate them with respect to the pathologic phenotype. This may lead to the identification of new pharmacological targets and contribute to the development of novel and more effective agents, which may eventually achieve higher rates of remission.