ISSUE:Reports of rapid-onset but short-duration antidepressant effects in patients with treatment-resistant mood disorders after intravenous administration of ketamine have prompted efforts to find an agent with ketamine's properties that can be administered orally in repeated doses in order to sustain that action. One candidate for this is dextromethorphan, and here the pharmacologic mechanism of action is compared and contrasted with that of ketamine.

ISSUE:The low incidence of extrapyramidal side effects associated with the atypical antipsychotic iloperidone may be linked to its unique binding profile of high affinity antagonism of both α1 adrenergic receptors and serotonin 2A receptors.

ISSUE:Standards for the practice of medicine are increasingly being confused with standards for the sale and reimbursement of medicines. Authority for prescribing of psychotropic drugs, whether on-label or off-label, is determined by the standard of medical care set by practitioners, not by regulators of the pharmaceutical industry.

ISSUE:Current psychiatric diagnoses are defined “top-down” based upon clinical phenomenology, but may give way to defining mental illnesses “bottom-up” based upon genetic and molecular factors that regulate information processing in neuronal circuits, and that can be visualized with neuroimaging techniques.

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.

ISSUE:Ketamine induces rapid-onset and short-duration improvement in depressive and suicidal symptoms in both treatment-resistant unipolar depression and bipolar depression, and also reduces chronic pain after short intravenous infusions. In order to develop long-acting oral agents with the same clinical effects, the pharmacologic mechanism of action must be understood, and the leading hypotheses are discussed here.

The goal of this brief review is to explain the role of monoamine oxidase enzymes in the neurobiology, etiology, and presentation of psychiatric illnesses, primarily major depressive disorder. This article will initially focus on the basic science and function of the monoamine oxidase system and some proposed neuropsychiatric symptoms that may arise if this enzyme system is altered by genetic predisposition. These findings and theories will next be translationally discussed in regard to clinical application pertaining to enzyme inhibition and the treatment of major depressive and other psychiatric disorders.

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.

Opioid use disorder (OUD) is a major public health problem in the United States. It has resulted in devastating consequences for people with this condition, including psychosocial and legal problems, in addition to contraction of infectious diseases such as HIV and hepatitis B and C. Furthermore, this disease can cause fatalities from drug overdoses and drug–drug interactions. OUD shatters families and destroys relationships. Effective treatment is crucial in order to curtail the consequences of this condition. The objective of this article is to provide a review of the pharmacotherapies currently being used to treat OUD.

Jealousy is a complex emotion characterized by the perception of a threat of loss of something that the person values, particularly in reference to a relationship with a loved one, which includes affective, cognitive, and behavioral components. Neural systems and cognitive processes underlying jealousy are relatively unclear, and only a few neuroimaging studies have investigated them. The current article discusses recent empirical findings on delusional jealousy, which is the most severe form of this feeling, in neurodegenerative diseases. After reviewing empirical findings on neurological and psychiatric disorders with delusional jealousy, and after considering its high prevalence in patients with Parkinson's disease under dopamine agonist treatment, we propose a core neural network and core cognitive processes at the basis of (delusional) jealousy, characterizing this symptom as possible endophenotype. In any case, empirical investigation of the neural bases of jealousy is just beginning, and further studies are strongly needed to elucidate the biological roots of this complex emotion.

The etiopathogenesis and treatment of major mood disorders have historically focused on modulation of monoaminergic (serotonin, norepinephrine, dopamine) and amino acid [γ-aminobutyric acid (GABA), glutamate] receptors at the plasma membrane. Although the activation and inhibition of these receptors acutely alter local neurotransmitter levels, their neuropsychiatric effects are not immediately observed. This time lag implicates intracellular neuroplasticity as primary in the mechanism of action of antidepressants and mood stabilizers. The modulation of intracellular second messenger/signal transduction cascades affects neurotrophic pathways that are both necessary and sufficient for monoaminergic and amino acid–based treatments. In this review, we will discuss the evidence in support of intracellular mediators in the pathophysiology and treatment of preclinical models of despair and major depressive disorder (MDD). More specifically, we will focus on the following pathways: cAMP/PKA/CREB, neurotrophin-mediated (MAPK and others), p11, Wnt/Fz/Dvl/GSK3β, and NFκB/ΔFosB. We will also discuss recent discoveries with rapidly acting antidepressants, which activate the mammalian target of rapamycin (mTOR) and release of inhibition on local translation via elongation factor stimulation. Throughout this discourse, we will highlight potential intracellular targets for therapeutic intervention. Finally, future clinical implications are discussed.

Depressive symptoms and episodes dominate the long-term course of bipolar disorder and are associated with high levels of disability and an increased risk of suicide. However, the treatment of bipolar depression has been poorly investigated in comparison with that of manic episodes and unipolar major depressive disorder. The goal of treatment in bipolar depression is not only to achieve full remission of acute symptoms, but also to avoid long-term mood destabilization and to prevent relapses. A depressive presentation of bipolar disorder may often delay the appropriate management and, thus, worsen the long-term outcome. In these cases, an accurate screening for diagnostic indicators of a possible bipolar course of the illness should guide the therapeutic choices, and lead to prognostic improvement. Antidepressant use is still the most controversial issue in the treatment of bipolar depression. Despite inconclusive evidence of efficacy and tolerability, this class of agents is commonly prescribed in acute and long-term treatment, often in combination with mood stabilizers. In this article, we review available treatment options for bipolar depression, and we shall provide some suggestions for the management of the different presentations of depression in the course of bipolar disorder.

There are several investigational drugs in development for the treatment of depression. Some of the novel antidepressants in development target monoaminergic neurotransmission in accordance with the “monoamine hypothesis of depression.” However, the current conceptualization of antidepressant actions is that it is the downstream effects on protein synthesis and neuroplasticity that account for therapeutic efficacy, rather than the immediate effects on synaptic monoamine levels. Thus, a number of novel agents in development directly target components of this “neuroplasticity hypothesis of depression,” including hypothetically overactive glutamatergic neurotransmission and dysfunctional hypothalamic–pituitary–adrenal (HPA) axis functioning.

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.