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.

This review aims to shed light on the symptoms of obsessive–compulsive disorder (OCD) with a focus on contamination fears. In addition, we will briefly review the current therapies for OCD and detail what their limitations are. A key focus will be on discussing how smartphone solutions may provide approaches to novel treatments, especially when considering global mental health and the challenges imposed by rural environments and limited resources; as well as restrictions imposed by world-wide pandemics such as COVID-19. In brief, research that questions this review will seek to address include: (1) What are the symptoms of contamination-related OCD? (2) How effective are current OCD therapies and what are their limitations? (3) How can novel technologies help mitigate challenges imposed by global mental health and pandemics/COVID-19.

Cognitive impairment is common in bipolar disorder and is emerging as a therapeutic target to enhance quality of life and function. A systematic search was conducted on PubMed, PsycInfo, Cochrane, clinicaltrials.gov, and Embase databases for blinded or open-label randomized controlled trials evaluating the pro-cognitive effects of pharmacological, neurostimulation, or psychological interventions for bipolar disorder. Twenty-two trials were identified, evaluating a total of 16 different pro-cognitive interventions. The methodological quality of the identified trials were assessed using the Cochrane Risk of Bias tool. Currently, no intervention (i.e., pharmacologic, neurostimulation, cognitive remediation) has demonstrated robust and independent pro-cognitive effects in adults with bipolar disorder. Findings are preliminary and methodological limitations limit the interpretation of results. Methodological considerations including, but not limited to, the enrichment with populations with pre-treatment cognitive impairment, as well as the inclusion of individuals who are in remission are encouraged. Future trials may also consider targeting interventions to specific cognitive subgroups and the use of biomarkers of cognitive function.

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.

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.

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.

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.

Schizophrenia is a complex syndrome of unknown etiology and difficult to manage. Unconjugated bilirubin has been researched as a potential biological marker of this syndrome. The objective of this review article was to gather the studies published to date on the relationship between this molecule and schizophrenia. Broad inclusion criteria have been used (PRISMA) to include as many relevant studies as possible. Fourteen studies were selected: 3 analyzed the effects of unconjugated hyperbilirubinemia in animal models; 6 demonstrated an increased incidence of schizophrenia in patients with increased unconjugated bilirubin; 2 reported an increased incidence of the disease in patients with decreased unconjugated bilirubin; and 3 linked an increased incidence of schizophrenia with an increased excretion of the oxidative product of bilirubin, the so-called biopyrrins. Because of apparently contradictory reported results, the hypothesis that the relationship between schizophrenia and unconjugated bilirubin was not linear and that there was an inflammatory dysfunction explaining this was considered. The 2 most accepted models for the pathophysiology of schizophrenia are described, and the possible role of the molecule in each is clarified. The bilirubin buffer system and its role in antioxidant defense was explored. The average levels of unconjugated bilirubin in patients with schizophrenia, schizoaffective disorder, and bipolar disorder were also compared, having been hypothesized that these diseases could be different points of a same pathological spectrum. Finally, it was concluded that unconjugated bilirubin is a promising molecule that could be used as a possible biological marker for schizophrenia, and the necessity of subsequent efforts for its research was considered.

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.

Our knowledge and understanding of the underlying neurobiology and symptomatic expression of ADHD has advanced dramatically over the past decade. Associated with these advances has been a similar explosion of new treatment options to individualize treatment for our patients.

This article will:

• ∙ review strategies to measure ADHD symptoms and functional difficulties while seeking to achieve full symptomatic remission throughout the day

• ∙ summarize recent findings regarding the management and prioritization of ADHD and comorbid conditions and

• ∙ discuss the various pharmacologic treatment options with a focus on recently developed molecules and novel delivery systems

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.

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.

Alzheimer's disease is a progressive condition characterized by a loss of cognition, altered behavior, and a loss of functional ability, such as bathing, dressing, toileting, and organizing finances. Family and friends provide nearly three quarters of all care for patients with Alzheimer's disease. This informal care results in significant burden to caregivers. Caregiver burden is the set of physical, psychological or emotional, social, and financial problems that family members may experience when caring for impaired older adults. Caregivers of Alzheimer's disease patients report higher rates of physical symptoms, mortality, depression, and fatigue, as well as adverse effects on employment compared with those who are not caregivers for Alzheimer's disease patients. In many cases, the same family members are responsible for both out-of-pocket expenditures and caregiving duties. For this article, a MEDLINE search using the key words “caregiver and Alzheimer's disease” and “cost and Alzheimer's disease” was performed. The purpose of this article is to review the literature on caregiver burden, the components of caregiver burden, effects of caregiving on the health of caregivers, the cost of Alzheimer's disease on the caregiver and society, and the benefits attainable with treatment.

Data regarding the increased incidence of psychiatric illness during midlife in women are still conflicting. However, there is a growing consensus that certain groups of women may in fact be at higher risk for mood symptoms and psychiatric disorders during the perimenopausal transition. Mood symptoms during the perimenopause may be related to mood disorders during other periods of hormonal fluctuation throughout a woman's reproductive lifecycle. Elucidating these associations may advance the understanding of mood disorders during the perimenopausal transition. The epidemiology and treatment of perimenopausal mood symptoms compared with the epidemiology and treatment of mood disorders during the late luteal phase of the menstrual cycle, pregnancy, and postpartum. Common risk factors associated with mood disorders during these periods of hormonal changes or instability include poor lifestyle habits, a history of hormonally related mood disorders, stress and negative life events, ethnicity, and comorbidity. Reproductive-related mood disorders also are subject to an improvement in symptoms in response to treatment with selective serotonin reuptake inhibitors. As the morbidity associated with mood disorders during midlife may be quite significant, and as life expectancy continues to increase, recognition, prevention, and treatment of perimenopausal affective illness is becoming increasingly essential.

An 82-year-old man with treatment-resistant depression and early Alzheimer's disease was started on methylphenidate. Significant obsessive-compulsive behavior ensued but diminished over several weeks when methylphenidate was replaced by fluvoxamine. The patient had no prior psychiatric history, but he had a sister with obsessive-compulsive disorder. It appears that methylphenidate precipitated the patient's pathological behavior.

Obsessive-compulsive disorder (OCD) experienced in childhood or adolescence is often a chronic disorder with high subjective distress and impairment of family and social functioning. An early comprehensive intervention schedule can have a profound effect on outcome in later years. The clinical manifestations of OCD among children and adolescents do not seem to be inherently different from those of adult patients. In younger subjects, the clinical picture tends to be dominated by compulsions, and insight can be poor, with little recognition of the symptoms as a problem.There is often a shift in symptoms over time, with some symptoms being replaced by others, while in adults, the core obsessions and compulsions tend to be more stable. In addition to depression and anxiety disorders, the spectrum of comorbid psychopathology seen in pediatric OCD patients includes tic, disruptive behavior, and specific developmental disorders. The treatment of childhood and adolescent OCD relies on cognitive-behavioral techniques of psychotherapy and pharmacotherapeutic interventions similar to those recommended in adults. The efficacy of exposure and response prevention in pediatric OCD has been shown in numerous open studies, and four controlled trials. Pharmacotherapy relies on serotonergic medication, and all have been demonstrated to be significantly superior to placebo, as reported in a recently published meta-analysis. Current concerns with the use of SSRIs in children and adolescents were explored as regards OCD and anxiety disorders, and there is no evidence for an increase in suicide or related behaviors.