ISSUE:Psychotropic drugs are traditionally classified by the first disorder they are proven to target (eg, as antidepressants or antipsychotics). However, these names are becoming increasingly confusing, as many drugs have multiple therapeutic actions. A more rational nomenclature categorizes psychotropic drugs by their pharmacologic mode of action.

Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990–2012.

Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described.

Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.

Alzheimer's disease (AD) is an urgent public health challenge that is rapidly approaching epidemic proportions. New therapies that defer or prevent the onset, delay the decline, or improve the symptoms are urgently needed. All phase 3 drug development programs for disease-modifying agents have failed thus far. New approaches to drug development are needed. Translational neuroscience focuses on the linkages between basic neuroscience and the development of new diagnostic and therapeutic products that will improve the lives of patients or prevent the occurrence of brain disorders. Translational neuroscience includes new preclinical models that may better predict human efficacy and safety, improved clinical trial designs and outcomes that will accelerate drug development, and the use of biomarkers to more rapidly provide information regarding the effects of drugs on the underlying disease biology. Early translational research is complemented by later stage translational approaches regarding how best to use evidence to impact clinical practice and to assess the influence of new treatments on the public health. Funding of translational research is evolving with an increased emphasis on academic and NIH involvement in drug development. Translational neuroscience provides a framework for advancing development of new therapies for AD patients.

We discuss the importance of cognitive abnormalities in unipolar depression, drawing the distinction between “hot” (emotion-laden) and “cold” (emotion-independent) cognition. “Cold” cognitive impairments are present reliably in unipolar depression, underscored by their presence in the diagnostic criteria for major depressive episodes. There is good evidence that some “cold” cognitive abnormalities do not disappear completely upon remission, and that they predict poor response to antidepressant drug treatment. However, in many studies the degree of impairment is moderately related to symptoms. We suggest that “cold” cognitive deficits in unipolar depression may in part be explicable in terms of alterations in “hot” processing, particularly on tasks that utilize feedback, on which depressed patients have been reported to exhibit a “catastrophic response to perceived failure.” Other abnormalities in “hot” cognition are commonly observed on tasks utilizing emotionally valenced stimuli, with numerous studies reporting mood-congruent processing biases in depression across a range of cognitive domains. Additionally, an emerging literature indicates reliable reward and punishment processing abnormalities in depression, which are especially relevant for hard-to-treat symptoms such as anhedonia. Both emotional and reward biases are strongly influenced by manipulations of the neurochemical systems targeted by antidepressant drugs. Such a pattern of “hot” and “cold” cognitive abnormalities is consistent with our cognitive neuropsychological model of depression, which proposes central roles for cognitive abnormalities in the generation, maintenance, and treatment of depressive symptoms. Future work should examine in greater detail the role that “hot” and “cold” cognitive processes play in mediating symptomatic improvement following pharmacological, psychological, and novel brain circuit-level interventions.

Guidelines for treating various conditions can be helpful in setting practice standards, but the presence of several sets of guidelines from different countries, experts, and settings, written at different times, can also create confusion. Here we provide a “guideline of guidelines” for the treatment of schizophrenia, or “meta-guidelines,” which not only reconcile the various existing standards but also update them to include the use of several newer agents, most of which were marketed following the publication of existing standards.