The assertion that the clinical efficacy of antide-pressants is comparable between – and within – the classes1 may

be true from a statistical viewpoint, but is of limited value in practice. Indeed, depression is, clinically and biologically, a heterogeneous check details illness and several lines of evidence suggest that the response to a Inhibitors,research,lifescience,medical pharmacological treatment depends on the patient’s biological state.2 Despite advances in psychopharmacology, more than one-third of patients do not respond to the drug of first choice.3 Therefore, a major issue is not only to have efficacious drugs, but also to optimize their use. During the past years, there has been Increasing Interest In the Identification of predictors of outcome in depression. However, Inhibitors,research,lifescience,medical there is little consensus regarding which clinical and biological variables influence the therapeutic response to antidepressants.4,5 Among the possible predictors, those derived from neuroendocrine investigations have been extensively studied. These predictors can be measured at baseline (ie, after a sufficient drugwithdrawal period) and/or during the course of treatment. It is beyond the scope of this Inhibitors,research,lifescience,medical article

to detail the numerous endocrine indicators that can be used as potential biological predictors of outcome. Rather, this paper illustrates, through selected examples, the usefulness of some pertinent neuroendocrine investigations. HPA axis Considerable research findings have accumulated over Inhibitors,research,lifescience,medical the last four decades regarding the role of the hypothalamicpituitary-adrenal (HPA) axis in the psychobiology of depression.6 Increased Cortisol secretion and failure to suppress Cortisol in response

to dexamethasone, a glucocorticoid agonist, have been consistently Inhibitors,research,lifescience,medical associated with severe, melancholic, and psychotic depression.7-9 It has been hypothesized that this stress axis overdrive is primarily a reflection of abnormal limbic-hypothalamic activation, with increased secretion of hypothalamic corticotropin-releasing hormone (CRH) and consequent excessive adrenal Cortisol secretion. However, it remains uncertain whether the hypercortisolism is an epiphenomenon or directly TCL contributes to depressive symptomatology and to the biochemical alterations seen in major depression (Figure 1).10 Figure 1. Overview of the relationships between the monoamine systems and the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes. 5-HT, serotonin; NA, noradrenaline; DA, dopamine; monoamine receptors, 5-HT1A, α2-adrenoreceptor, …