bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considering Ethnicity and Ethnopharmacology in the Treatment of Patients with Mental Illness
Authors: Nasrallah Henry A. 
Published: August 2016

SummaryThe articles in this supplement demonstrate that ethnicity and ethnopharmacology have emerged as important considerations in the treatment of patients with mental illness. Patients from ethnically diverse backgrounds often demonstrate varying levels of response and tolerability to drugs such as atypical antipsychotics. In part, this response may be due to the particular agent itself, yet metabolic differences between populations may also impact these varied effects. Specific isoforms of the cytochrome P450 enzyme system can dictate the rate at which patients metabolize certain medications, thus genotypic variability among these enzymes predicts the phenotypic response or metabolic rate. For example, patients from certain ethnic groups such as Caucasians and Hispanics tend to be extensive metabolizers, while African Americans and Asians tend to be slower metabolizers.Total dose and resulting plasma drug levels are closely related to adverse effects. Thus, patients exhibiting slow or poor oxidative enzyme activity may face increased drug exposure and potentially higher rates of adverse events. The undesirable antipsychotic-induced side effects include metabolic issues such as weight gain, insulin resistance, and dyslipidemia. Certain ethnic groups are at a higher risk for developing these metabolic problems. Side effects such as extrapyramidal symptoms and tardive dyskinesia, which have traditionally been attributed to conventional antipsychotics, may occur with atypicals although much less frequently. Movement disorders caused by the use of an atypical antipsychotic become particularly apparent when plasma drug levels are high. Patients with a slow metabolism will be exposed to high plasma drug levels, even on standard dosages of an atypical antipsychotic.Therefore, given a genetic predisposition and the potential for metabolic side effects with atypical antipsychotics, a careful risk/benefit assessment is crucial for the successful management of patients with mental illness.Other patient factors as well as clinician factors can influence the response and tolerability of treatment. Provider biases can affect access to certain medications, while misconceptions about how to treat certain ethnic groups can affect the initial choice of medication and dosage. Ultimately, sensitivity and an awareness of pharmacologic issues as they relate to an expanding and ethnically diverse population must become a high priority for clinicians treating patients with atypical antipsychotics. Side effects of these medications can be minimized with vigilance and a thorough understanding of the risks and benefits.Continued research is necessary to further understand the field of ethnopharmacology and to lead psychiatry into the future of individualized, metabolically directed therapies.
Clinical Trials in Schizophrenia with Results for the Real World
Authors: Perkins Diana O. 
Published: August 2016

AbstractMost clinical data for antipsychotics come from studies designed to test the efficacy and safety of the drugs under ideal conditions, in limited subgroups of patients. In contrast, practical clinical trials (PCTs) are designed to test the effectiveness of different treatment options under conditions that more accurately reflect actual clinical practice. Consequently, PCTs are able to provide information that can be utilized by healthcare providers and other decision makers. Characteristics of PCTs include a clinically relevant question, a representative sample of patients and practice settings, sufficient power to identify modest relevant effects, randomization to protect against bias, uncertainty regarding the outcome of treatment, assessment and treatment protocols that enact best clinical practices, simple and relevant outcomes, and limited subject and investigator burden. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) research program is an example of a PCT. The CATIE study illustrates how PCTs, when properly designed, might be helpful in informing clinical decision making. Because the CATIE study was designed to reflect the effectiveness of antipsychotics under naturalistic clinical conditions, its results should have particular applicability to the arena of clinical practice. This article provides a discussion of the differences between efficacy and effectiveness studies. In assessing the practical utility of results from the CATIE study, much can be learned on how to shape future studies of effectiveness so as to better generate data that are applicable to the “real world.”
Implications of the CATIE Trial on Treatment: Extrapyramidal Symptoms
Authors: Casey Daniel E. 
Published: August 2016

AbstractDevelopment of extrapyramidal symptoms (EPS), particularly tardive dyskinesia (TD), has long been a troubling side effect for patients taking antipsychotics. Atypical antipsychotics have been hailed as an improvement over conventional antipsychotics, offering similar efficacy with more favorable EPS profiles. In the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, which compared the conventional antipsychotic perphenazine with atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone in patients with schizophrenia, no significant differences in time to treatment discontinuation due to intolerability were observed between treatment groups. However, perphenazine was associated with a higher rate of patients experiencing EPS as well as a significantly higher rate of discontinuation due to EPS, despite the fact that patients with TD at baseline were excluded from the perphenazine group. Unfortunately, due to short treatment duration, the CATIE study did not have the assay sensitivity to detect differences in TD risk among any of the drugs. Thus, the atypical antipsychotics remain the first line of treatment for most patients, with specific drug selection based on benefit-risk profiles that best fit the individual patient's needs. Frequent monitoring, while noting a patient's subjective experience, remains the best strategy for choosing therapy to maximize symptom relief and minimize the impact of EPS and other side effects over the long-term. This article explores the reported results of the CATIE trial regarding EPS and emphasizes the differentiation of the atypicals from perphenazine on EPS and how these results should be incorporated into daily practice for the clinician.
Neurobiology, Pharmacology, and Emerging Treatment
Authors: Adler Lenard A. 
Published: August 2016

AbstractTreatment of attention-deficit/hyperactivity disorder (ADHD) may positively impact the neurobiology of adult patients with ADHD. Treatment may also minimize impairment from core symptoms and may alter the course of co-morbid disorders such as depression and substance use disorder. However, much of the information on stimulant use in adult ADHD comes from studies conducted in children, and it remains unclear whether there is a difference between children and adults when it comes to the side effects and tolerability of ADHD treatments. It is known that clinical presentation differs between adults and children, with adults demonstrating a higher percentage of mood disorders. Current treatments for adult ADHD include psychosocial therapies and pharmacologic therapies, the latter of which include the stimulants d-methylphenidate extended release (XR), OROS methylphenidate, lisdexamfetamine, and mixed amphetamine salts XR; and the nonstimulant atomoxetine, a selective norepinephrine reuptake inhibitor. There is need for additional study of treatment strategies for adult ADHD. Although all classes of ADHD medications are approved in adults, there are fewer approved formulations for adults than for children. Efficacy in adults is more subjective than in children, which may affect how efficacy rates for adult treatments are calculated. Adults also present a greater diversion risk than children. In addition, there are several new and emerging medication treatments worth considering.This Expert Roundtable Supplement represents part 2 of a 3-part supplement series on adult ADHD led by Lenard A. Adler, MD. In this activity, Thomas J. Spencer, MD, discusses the neurobiology and genetics of adult ADHD; Mark A. Stein, PhD, discusses stimulant therapy; and Jeffrey H. Newcorn, MD, reviews nonstimulants and psychosocial treatments.
Treating Adult ADHD with Stimulants
Authors: Stein Mark A. 
Published: August 2016

AbstractTreatment of attention-deficit/hyperactivity disorder (ADHD) may positively impact the neurobiology of adult patients with ADHD. Treatment may also minimize impairment from core symptoms and may alter the course of co-morbid disorders such as depression and substance use disorder. However, much of the information on stimulant use in adult ADHD comes from studies conducted in children, and it remains unclear whether there is a difference between children and adults when it comes to the side effects and tolerability of ADHD treatments. It is known that clinical presentation differs between adults and children, with adults demonstrating a higher percentage of mood disorders. Current treatments for adult ADHD include psychosocial therapies and pharmacologic therapies, the latter of which include the stimulants d-methylphenidate extended release (XR), OROS methylphenidate, lisdexamfetamine, and mixed amphetamine salts XR; and the nonstimulant atomoxetine, a selective norepinephrine reuptake inhibitor. There is need for additional study of treatment strategies for adult ADHD. Although all classes of ADHD medications are approved in adults, there are fewer approved formulations for adults than for children. Efficacy in adults is more subjective than in children, which may affect how efficacy rates for adult treatments are calculated. Adults also present a greater diversion risk than children. In addition, there are several new and emerging medication treatments worth considering.This Expert Roundtable Supplement represents part 2 of a 3-part supplement series on adult ADHD led by Lenard A. Adler, MD. In this activity, Thomas J. Spencer, MD, discusses the neurobiology and genetics of adult ADHD; Mark A. Stein, PhD, discusses stimulant therapy; and Jeffrey H. Newcorn, MD, reviews nonstimulants and psychosocial treatments.
Anxiety and the Spectrum of Obsessive-Compulsive Disorder
Authors: Black Donald W. 
Published: August 2016

This supplement to CNS Spectrums focuses on the obsessive-compulsive spectrum of disorders and their relationship to anxiety. Hollander and others pioneered the concept of the obsessive-compulsive spectrum in the early 1990s, and have described its breadth and overlap with other psychiatric disorders. While its place in the psychiatric nomenclature is uncertain, the obsessive-compulsive spectrum is intertwined with the anxiety disorders in both its symptoms and biologic substrates.Obsessive-compulsive disorder (OCD) has an important place at the center of the spectrum. While currently classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition as an anxiety disorder, OCD is distinct from these conditions in the International Classification of Diseases. There is a strong rationale for its separation from the anxiety disorders. First, OCD often begins in childhood, whereas other anxiety disorders typically have a later age of onset. OCD has a nearly equal gender distribution, unlike the other anxiety disorders, which are more common in women. Studies of psychiatric comorbidity show that, unlike the other anxiety disorders, persons with OCD generally tend not to have elevated rates of substance misuse. Family studies suggest that first-degree relatives of persons with OCD have an elevated prevalence of OCD-related disorders including body dysmorphic disorder, hypochondriasis, and grooming disorders, but not other anxiety disorders except for generalized anxiety disorder. The brain circuitry that mediates OCD appears to be different from that involved in other anxiety disorders. Lastly, OCD is unique with regard to its specific response to selective serotonin reuptake inhibitors, while noradrenergic medications, effective in the anxiety and mood disorders, are largely ineffective. On the other hand, the benzodiazepines, which have little effect on OCD, are often effective for the other anxiety disorders.
The Overlap of Obsessive-Compulsive Disorder and Social Phobia and its Treatment
Authors: Baldwin David S. , Brandish Emma K. , Meron Daniel 
Published: August 2016

AbstractBoth obsessive-compulsive disorder (OCD) and social phobia are common in community and clinical settings, and it should be expected that a proportion of patients with one of these conditions will also fulfill either current or lifetime criteria for the other condition. However, comorbid social phobia is more common among patients with a primary diagnosis of OCD than is comorbid OCD in patients with a primary diagnosis of social phobia. This article explores the extent of the association of OCD and social phobia in epidemiological studies, and examines the possible role of underlying depression and other disorders in mediating the appearance of the comorbid condition. Although there have been no published randomized controlled trials in patients with this particular pattern of co-morbidity, it seems sensible to adopt pharmacologic and psychologic treatment approaches which have been found efficacious in both OCD and social phobia. Pharmacologic management therefore centers on first-line treatment with a selective serotonin reuptake inhibitor. Psychologic intervention should draw on the range of cognitive and behavioral approaches required for optimal outcomes in OCD and social phobia, as discrete conditions.
Short Clinical Assessments Applicable to Busy Practices
Authors: Nasreddine Ziad 
Published: August 2016

Because biomarkers to detect Alzheimer’s disease (AD) have not yet been validated, physicians must rely on clinical assessments. The Research Committee of the American Neuropsychiatric Association recommended that the ideal cognitive screening instrument have the following characteristics: First, it should take <15 minutes to administer by a clinician at any level of training. Second, it should sample all major cognitive domains, including memory, attention/concentration, executive function, visual-spatial skills, language, and orientation. Third, it should be reliable, having adequate test-retest and inter-rater validity. Finally, it should be able to detect cognitive disorders commonly encountered by neuropsychiatrists.The American Academy of Neurology Practice Parameters from 1994 and 2001 and the Canadian Consensus Guidelines on Dementia from 2007 recommend that physicians screen subjects with suspected dementia or mild cognitive impairment (MCI), since these patients are at increased risk for AD. Currently, there are no data on the utility of screening subjects who are asymptomatic.The most commonly used brief cognitive tests are the Mini-Mental State Examination (MMSE), according to a survey conducted by the International Psychogeriatric Association (IPA) in 2006, followed by the clock-drawing test, the delayed-word recall, the verbal fluency test, the similarities test, and the trail-making test. Clinicians appraised these assessments as the most effective and easiest to administer (Slide 1).
Cholinesterase Inhibitors and Memantine: Best Practices
Authors: Doody Rachelle S. 
Published: August 2016

Today’s therapies must be put in the context of both currently available treatments as well as treatment trials with exciting potential for use in the near future. Current clinical trial methodologies do not allow for clear separation of symptomatic treatments from disease-modifying therapies; it may be unproductive to maintain this distinction given the current range of treatments available. A more currently relevant focus is added value. Therapies should aim to provide added value through incremental benefits above and beyond existing treatments, as well as enduring benefits.Alzheimer’s disease (AD) treatment guidelines are not used by physicians only. Healthcare payers often make use of these guidelines to delimit coverage. Cost concerns will also impact AD treatments after generic cholinesterase inhibitors are made available; it is widely believed that a great number of patients will switch to generics. Therefore, treatment guidelines must account for the possible adverse effects of switching therapies as well as the desirability of persistent treatment. There are many AD treatment guidelines, among them the American Academy of Neurology (AAN) Management of Dementia Guidelines, which are currently being revised. The Institute for the Study on Aging (ISOA) Management of Alzheimer’s Disease in Managed Care Guideline also presents a different approach for a different audience.The first step to creating evidence-based best practices guidelines is to determine what is meant by “evidence.” A system of classification exists for examining forms of evidence: Class I evidence is provided by one or more well-designed, randomized, controlled clinical trials, including overviews or meta-analyses of such trials. Class II evidence is provided by well-designed observational studies with concurrent controls; for example, case-control studies that generate hypotheses about epidemiologic associations. Class III evidence is provided by expert opinion, case series, case reports, and studies with historical controls.
Amyloid-Based Therapeutics: Findings Translated into Novel Treatments
Authors: Aisen Paul S. 
Published: August 2016

For decades following the 1906 identification of Alzheimer’s disease (AD), it was believed that the disorder was untreatable. Only in the late 1970s, with the introduction of the cholinergic hypothesis of the underlying mechanisms of AD, were treatment options considered possible. The first positive treatment study was conducted in 1985. In 1993, tacrine, a cholinesterase inhibitor, was approved for the treatment of AD; three similar drugs soon followed. Memantine, an NMDA receptor antagonist, was approved in 2003, representing a second therapeutic class for AD.Cholinesterase inhibitors were the first therapeutic options successfully employed, and there is strong evidence these agents confer benefits. The addition of memantine to the standard course of therapy can be beneficial as well, particularly at the moderate stages of the disorder (Mini-Mental State Exam score of ≤14). For patients without cardiovascular disease, diabetes, or statin use, 1,000 IU vitamin E BID is a consideration to mitigate the effects of AD. However, there is presently concern over the risks involved in vitamin E therapy. Unfortunately, there are no established treatments for mild cognitive impairment (MCI). Vitamin E is ineffective in treating MCI, and cholinesterase inhibitors, while possibly risky, are only minimally effective. The need for effective treatment remains expansive. The benefits of the available agents are modest, and there are currently no treatments for individuals with memory impairment who do not yet meet the diagnostic criteria for AD.
Depression in the Elderly: The Unique Features Related to Diagnosis and Treatment
Authors: Shear Katherine , Ginsberg David L. , Roose Steven P. , Lenze Eric J. , Alexopoulos George S. , Hollander Eric 
Published: August 2016

AbstractDepression affects 6.5 million of the 35 million Americans ≥65 years of age. While depression usually begins earlier in life and recurs periodically, it can present for the first time in people 80–90 years of age as well. Depression throughout the lifespan has a genetic/biological component but is also very much affected by social environmental factors. As people age, demographic factors, social support, and negative life events remain important to overall mental health, while physical illness and disability begin to take on a much more prominent role. Depression in the elderly is associated with impairment, dependency, disability, and significant distress for the individual and their family. This population is likely to present with concomitant cognitive dysfunction and medical illness, which can complicate the identification and treatment of psychiatric conditions. Bereavement is almost universal in late life and is sometimes a deterrent to appropriate diagnosis and treatment of depression. Physical frailty and diminishing social resources further complicate the treatment of depression in the elderly. Elderly individuals respond well to standard pharmacotherapy and psychotherapy treatments for depression. However, due to the high rate of relapse of depression in this population, continuous treatment is often warranted. This monograph will review depression in the elderly in the context of social disruptions, such as bereavement, caregiver strain, interpersonal conflict, role transitions, and social isolation; late-onset vascular depression and cognitive impairment; and physical illness including disability.
The Pharmacologic Treatment of Patients With Generalized Anxiety Disorder: Where Are We Now and Where Are We Going?
Authors: Baldwin David S. , Tiwari Nupur 
Published: August 2016

AbstractEvidence-based guidelines for the pharmacologic management of patients with generalized anxiety disorder (GAD) recommend initial treatment with either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). However, response rates to initial treatment with an SSRI or SNRI can be disappointing, and it remains impossible to predict reliably which patients will respond positively or negatively to treatment. Due to the dearth of longitudinal studies of outcome in GAD and the relatively small number of placebo-controlled relapse prevention studies, the optimal duration of treatment after a satisfactory response to acute treatment is still uncertain. Furthermore, there have been few studies on the management of patients who do not respond to initial treatment. Also, there is a clear need for further randomized controlled trials of augmentation treatment in patients who do not respond to SSRI, SNRI, or other initial pharmacologic approaches. Future guidelines will be influenced by emerging data with both established and novel drug treatments, and through better identification of patient groups that are likely to respond preferentially to particular interventions.