The received wisdom is that there is no known effective treatment for psychopathic disorders. Although outcome studies have not identified an effective programmatic treatment for psychopathic disorders, such studies tend to leave the question open. If behavioral science has not established that psychopathic disorders respond to a particular programmatic approach, neither are psychopathic disorders convincingly proven to be absolutely resistant to treatment. If no treatment is known to be effective in psychopathic disorders, then any treatment seems to squander resources. What is often missing from the discussion is effective therapeutic measures to treat other behaviors that often co-occur, if they do not represent a domain of pathology of psychopathic disorders, such as impulsive aggression. After a brief summary of results of programmatic treatment of psychopathic offenders, this review focuses on the pharmacotherapy of impulsive aggression in psychopathic disorders. If the impulsive aggression that occurs with psychopathic disorders can be better controlled, treatment can have substantial benefits and would be most appropriate.

Introduction: Selective serotonin reuptake inhibitors are considered the most effective and well-established pharmacotherapy for the treatment of obsessive-compulsive disorder (OCD), a chronic and disabling condition. However, ~40% of patients do not have a significant improvement, suggesting that new medications are needed. This study was designed to investigate the treatment response to escitalopram in OCD patients.

Methods: This open-label study involved 11 adult OCD outpatients diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders. Data were collected and the treatment response was assessed by an experienced psychiatrist by using the Yale-Brown Obsessive-Compulsive Scale. Subjects received escitalopram 30 mg/day for 12 weeks starting at 10 mg/day. Dosage adjustments were made within 2 weeks, depending on the tolerability of the patient.

Results: Six of the 11 patients (54.5%) presented a reduction of at least 40% in the baseline total Yale-Brown Obsessive-Compulsive Scale scores.

Conclusion: Despite the small sample size and the open-label nature of this trial, these data suggest that escitalopram may be a useful option for patients with OCD.

Combination pharmacotherapy has proven effective in a number of psychiatric disorders, including depression and schizophrenia. However, compared with other affective disorders, few studies have explored the use of combination therapy in alcoholism, and the majority have been limited to animal models. There is evidence to support a role for combination therapy in alcoholism. For example, several neurochemical systems, including the dopaminergic, serotonergic, and opioidergic, appear to affect alcohol intake. Studies in several different types of alcohol-preferring rats have suggested that coadministration of agents to target more than one of these systems simultaneously may produce beneficial effects on alcohol intake, while avoiding problematic effects, such as alterations in food or water intake. Data from preliminary clinical studies have shown trends toward combination therapy reducing alcohol intake in humans. While such findings are encouraging, they must be explored further in larger, randomized, double-blind trials.

It has been well known for a number of years that abrupt withdrawal from alcohol following chronic use is associated with adverse consequences, ranging from mild tremors to withdrawal seizures. The overall purposes of treating alcohol withdrawal (AW) are to relieve patient discomfort, to prevent the development of more serious withdrawal symptoms, and to initiate long-term alcohol rehabilitation. Several areas of controversy exist in the clinical management of AW, including the optimal treatment setting, the need for pharmacologic management, and the most appropriate agent to prescribe when medication is deemed necessary. This article reviews the clinical features, general management, and treatment of AW.

Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHD. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders.

In this expert roundtable supplement, Timothy E. Wilens, MD, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MD, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MD, reviews stimulant treatment of adult ADHD, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD.

Personalizing medicine by understanding the unique properties of each patient's genome has the potential of predicting what drug to prescribe for that individual. This approach has already proven useful for several drugs in medicine and promises to become a strategy for selection of therapeutics in psychiatry soon. Understanding some of the key concepts, strategies, and advances in the field of pharmacogenomics can set the stage for adapting emerging findings to the practice of psychopharmacology.

Introduction: Because major depressive disorder (MDD) is often chronic and recurrent, even pediatric patients who are treated successfully during an acute episode may need longer-term treatment. Yet, data on long-term treatment with antidepressants in pediatric MDD are limited.

Objective: To evaluate long-term effectiveness and safety of treatment with venlafaxine extended-release (ER) in children and adolescents with MDD.

Methods: Subjects (n=86) 7–17 years of age with MDD entered a multicenter, open-label study of flexible-dose venlafaxine ER for 6 weeks of acute treatment, followed by continuation treatment for up to 6 months total treatment. The primary efficacy variable was the Children's Depression Rating Scale-Revised (CDRS-R) total score (intent-to-treat population).

Results: Mean CDRS-R total score decreased from 60.1±10.0 at baseline to 36.3±13.1 at week 6, and to 33.8±15.0 at 6 months (last observation carried forward). Among completers (n=36), the mean CDRS-R total score was 24.3±7.6 at the end of 6 months of treatment. The most frequent treatment-emergent adverse events were headache (53%), nausea (26%), infection (24%), abdominal pain (22%), vomiting (21%), and pharyngitis (19%). Fifteen (17%) participants discontinued due to adverse events, 9 of whom did so within the first 6 weeks. Serious adverse events (suicide attempt [two], hostility [two], hallucinations, depression, and pharyngitis) occurred in seven patients. There were no suicides.

Conclusion: Most improvement with venlafaxine ER occurs during the first 6 weeks of treatment. Prescribers should be alert to signs of suicidal ideation and hostility in pediatric patients.

Sexual health is important to overall health and quality of life. Sexual problems have been associated with relationship problems and may interfere with overall health and they may also be a marker for other undiagnosed comorbid medical conditions. In order for healthcare professionals to manage the sexual health concerns of their patients, it is important for them to understand what constitutes good sexual health. To that end, it is necessary to have a working knowledge of the evolving theoretical models offered to describe a healthy sexual response as well as an understanding of the neurobiology of sexual function. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised lists six primary female sexual disorders: hypoactive sexual desire disorder, sexual aversion disorder, female sexual arousal disorder, female orgasmic disorder,dyspareunia, and vaginismus. Despite a growing awareness of the high prevalence of sexual disorders they are not typically identified nor treated. There are a number of reasons why clinicians fail to identify and treat sexual problems including insufficient training in sexual medicine and communication skills, time-constraints, and embarrassment. Treatment for female sexual problems is usually individualized and may include a combination of office-based education and basic counseling, cognitive-behavioral psychotherapy, pharmacotherapy, and treatment of concomitant medical conditions.

Successful treatment of pediatric disorders has necessitated the development of alternative medication formulations, as children may prefer alternative dosage forms to tablets or capsules. This is especially true for attention-deficit/hyperactivity disorder (ADHD), which is one of the most common chronic pediatric conditions and often involves children with a variety of overlapping physical, psychological, or neurodevelopmental disorders. A special challenge for developing alternative dosage forms for ADHD treatment is the incorporation of a once-daily long-acting formulation. Traditional ADHD medication formulations have been limited, and issues surrounding prescribed dosing regimens—including poor medication adherence, difficulty swallowing, and the lack of dosing titration options—persist in ADHD treatment. In other disease areas, the development of alternative formulations has provided options for patients who have issues with consuming solid dosage forms, particularly children and individuals with developmental disorders. In the light of these new developments, several alternative formulations for ADHD medications are under development or have recently become available. This article reviews the various strategies for developing alternative dosage forms in other disease areas and discusses the application of these strategies in ADHD treatment. Alternative dosage forms may increase medication adherence, compliance, and patient preference and, therefore, improve the overall treatment for ADHD.

Evidence-based medicine (EBM) enables clinicians to justify decision making, enhances the quality of medical practice, identifies unanswered research questions, and ensures the efficient practice of medicine. Implementation of evidence-based mental health programs requires education, time, and improved effort by administration, regulatory, and clinical professionals. Essential to these efforts are consistent incentives for change, effective training materials, and clear clinical guidelines. Guidelines exist within the framework of EBM. Good guidelines are simple, specific, and user friendly, focus on key clinical decisions, are based on research evidence, and present evidence and recommendations in a concise and accessible format. Potential limitations of guidelines to improve clinical outcomes in anxiety disorders are the widespread distribution of anxiety symptoms in primary care, health inequalities across patient groups, persistent misconceptions regarding psychotropic drugs, and low confidence in using simple psychological treatments. Clinical guidelines generally specify therapeutic areas covered and not covered, but often there is no mention of cost or cost effectiveness of treatment. Guidelines can inform clinical decision making, but administrators of drug formularies may regard themselves as being primarily responsible for limiting costs and access to certain medications, even if these decisions are at odds with guideline recommendations.

Mixed states in bipolar disorder have been neglected, and the data concerning treatment of these conditions have been relatively obscure. To address this, we systematically reviewed published pharmacological treatment data for “mixed states/episodes” in mood disorders, including “with mixed features” in DSM–5. We searched PubMed, MEDLINE, The Cochrane Library, clinicaltrials.gov, and controlled-trials.com (with different combinations of the following keywords: “mixed states/features,” “bipolar,” “depressive symptoms/bipolar depression,” “manic symptoms,” “treatment,” “DSM–5”) through to October 2016. We applied a quality-of-evidence approach: first-degree evidence=randomized placebo-controlled studies of pharmacological interventions used as monotherapy; second-degree evidence=a similar design in the absence of a placebo or of a combination therapy as a comparative group; third-degree evidence=case reports, case series, and reviews of published studies. We found very few primary double-blind, placebo-controlled studies on the treatment of mixed states: the preponderance of available data derives from subgroup analysis performed on studies that originally involved manic patients. Future research should study the effects of treatments in mixed states defined using current criteria.

In this second of two articles on second messenger/signal transduction cascades in major mood disorders, we will review the evidence in support of intracellular dysfunction and its rectification in the etiopathogenesis and treatment of bipolar disorder (BD). The importance of these cascades is highlighted by lithium's (the gold standard in BD psychopharmacology) ability to inhibit multiple critical loci in second messenger/signal transduction cascades including protein kinase C (involved in the IP3/PIP2 pathway) and GSK-3β (canonically identified in the Wnt/Fz/Dvl/GSK-3β cascade). As a result, and like major depressive disorder (MDD), more recent pathophysiological studies and rational therapeutic targets have been directed at these and other intracellular mediators. Even in the past decade, intracellular dysfunction in numerous neuroprotective/apoptotic cascades appears important in the pathophysiology and may be a future target for pharmacological interventions of BD.

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder characterized by inattention, impulsivity, and overactivity that begins in childhood. While considerable research has focused on the neurobiological substrates of this disorder, the specific nature of the brain dysfunction in ADHD has remained elusive. However, early data from pharmacological treatment studies, as well as from basic research in animals and humans, initially led several investigators to develop neurobiological models of ADHD. These models of ADHD and more recent evidence from neuropsychological, neuroimaging, neurochemical, and genetic research are briefly reviewed. While not completely consistent, the empirical data suggest that dysfunction in prefrontal-striatal neural circuits, as well as in brain stem catecholamine systems that innervate these circuits, may underlie the executive function deficits in ADHD.

Williams syndrome is a neurodevelopmental disorder that results from the deletion of ~25-30 genes spanning about 1.5 megabases in the q11.23 region of chromosome 7. Patients with this syndrome present with a combination of a distinctive elfin-like facial appearance; growth retardation; mild mental retardation; an inconsistent cognitive profile that includes visuospatial impairments with good facial discrimination and relatively preserved expressive language skills; and cardiovascular abnormalities. In addition, a striking behavioral feature of the syndrome is the high sociability and empathy that these patients show for others. The study of patients with “partial” deletions of the chromosome band 7q11.23, mutated genes in this region and knockout mice with deletions of specific genes in the homologous G1–G2 region of mouse chromosome 5 are clarifying some genotype/phenotype relationships. Futhermore, genes located in this region that are prominently expressed have been implicated in brain development and function.The neuropsychological profile of patients with Williams syndrome is heterogeneous, highlights important dissociations between cognitive functions and suggests that the behavioral dimensions of sociability, empathy, engageability, and talkativeness may be independent of, or not easily explained by, the cognitive deficits. Williams syndrome has enormous heuristic value because its pathological feature of heightened “sociability” can be a “deficit” symptom of major complex neuropsychiatrie disorders, such as schizophrenia and autism. Data consistent with a core inability of patients with Williams syndrome to inhibit social approach suggest that this disorder may afford an opportunity to study the biological basis of the “drive” toward socialization. From a research perspective, the syndrome lends itself to neurobiological studies of sociability as a dimension that varies independently of cognition (or at least many separable cognitive processes). Importantly, from a clinical perspective, the syndrome challenges us to administer strategic psychosocial interventions that take advantage of the opportunities that “pathological” sociability provide, while avoiding its threats. An illustrative example of an effective strategically planned psychosocial intervention for a patient with Williams syndrome is briefly presented.