The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

This article reviews scientific advances in the prevention and treatment of substance-use disorder and related developments in public policy. In the past two decades, research has increasingly supported the view that addiction is a disease of the brain. Although the brain disease model of addiction has yielded effective preventive measures, treatment interventions, and public health policies to address substance-use disorders, the underlying concept of substance abuse as a brain disease continues to be questioned, perhaps because the aberrant, impulsive, and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology. Here we review recent advances in the neurobiology of addiction to clarify the link between addiction and brain function and to broaden the understanding of addiction as a brain disease. We review findings on the desensitization of reward circuits, which dampens the ability to feel pleasure and the motivation to pursue everyday activities; the increasing strength of conditioned responses and stress reactivity, which results in increased cravings for alcohol and other drugs and negative emotions when these cravings are not sated; and the weakening of the brain regions involved in executive functions such as decision making, inhibitory control, and self-regulation that leads to repeated relapse. We also review the ways in which social environments, developmental stages, and genetics are intimately linked to and influence vulnerability and recovery. We conclude that neuroscience continues to support the brain disease model of addiction. Neuroscience research in this area not only offers new opportunities for the prevention and treatment of substance addictions and related behavioral addictions (e.g., to food, sex, and gambling) but may also improve our understanding of the fundamental biologic processes involved in voluntary behavioral control. In the United States, 8 to 10% of people 12 years of age or older, or 20 to 22 million people, are addicted to alcohol or other drugs. 1 The abuse of tobacco, alcohol, and illicit drugs in the United States exacts more than $700 billion annually in costs related to crime, lost work productivity, and health care. 2-4 After centuries of efforts to reduce addiction and its related costs by punishing addictive behaviors failed to produce adequate results, recent basic and clinical research has provided clear evidence that addiction might be better considered and treated as an acquired disease of the brain (see Box 1 for definitions of substance-use disorder and addiction). Research guided by the brain disease model of addiction has led to the development of more effective methods of prevention and treatment and to more informed public health policies. Notable examples include the Mental Health Parity and Addiction Equity Act of 2008, which requires medical insurance plans to provide the same coverage for substance-use disorders and other mental illnesses that is provided for other illnesses, 5 and the proposed bipartisan Senate legislation that From the National Institute on Drug Abuse (N.D.V.) and the National Institute of Alcohol Abuse and Alcoholism (G.F.K.) — both in Bethesda, MD; and the Treatment Research Institute, Philadelphia (A.T.M.). Address reprint requests to Dr. Volkow at the National Institute on Drug Abuse, 6001 Executive Bld., Rm. 5274, Bethesda, MD 20892, or at nvolkow@ nida . nih . gov.

Review Article: Neurobiologic Advances from the Brain Disease Model of Addiction

Linking Research and Service Delivery: The Unique Mission of the Substance Abuse and Mental Health Services Administration: (495882006-006)

Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.

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Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice.

/pdf/recommendations-for-daytime-evening-and-nighttime-indoor-3f73uft1.pdf

Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults

Background Bright light therapy has demonstrated efficacy and is an accepted treatment for seasonal depression. It has been suggested that bright light therapy may have efficacy in nonseasonal depressions. Also, there is evidence that bright light therapy may improve responsiveness to antidepressant pharmacotherapy. Data sources We searched PubMed/MEDLINE, PsycINFO, PsycARTICLES, CINAHL, EMBASE, Scopus, and Academic OneFile for English-language literature published between January 1998 and April 2016, using the keywords bright light therapy AND major depression, bright light therapy AND depress*, bright light therapy AND bipolar depression, bright light therapy AND affective disorders, circadian rhythm AND major depression, circadian rhythm AND depress*, and circadian rhythm AND affective disorder. Study selection and data extraction Studies that reported randomized trials comparing antidepressant pharmacotherapy with bright light therapy ≥ 5,000 lux for ≥ 30 minutes to antidepressant pharmacotherapy without bright light therapy for the treatment of nonseasonal depression were included. Studies of seasonal depression were excluded. Following review of the initial 112 returns, 2 of the authors independently judged each trial, applying the inclusionary and exclusionary criteria. Ten studies were selected as meeting these criteria. Subjects in these studies were pooled using standard techniques of meta-analysis. Results Ten studies involving 458 patients showed improvement using bright light therapy augmentation versus antidepressant pharmacotherapy alone. The effect size was similar to that of other accepted augmentation strategies, roughly 0.5. Conclusions Analysis of pooled data from randomized trials provides evidence for the efficacy of use of bright light therapy ≥ 5,000 lux for periods ≥ 30 minutes when used as augmentation to standard antidepressant pharmacotherapy in the treatment of major depressive disorder and bipolar depression without a seasonal pattern.

Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis.

Recent years have seen a widespread increase in kratom use, not just for the purpose of easing opioid withdrawal, but also for management of emotional and mental health concerns by individuals without histories of opioid use. Chronic use can lead to dependence, tolerance, and withdrawal on cessation, and clinicians are seeing an increasing number of presentations involving the latter. Although there is literature discussing the use of kratom to assist in opioid withdrawal, this article comprehensively examines independent withdrawal from kratom. We systematically review existing evidence and provide our own clinical cases. Clinicians need to be aware of the withdrawal symptomatology and implement a similar approach as for opioid withdrawal with long-term maintenance to prevent relapse.

Kratom Withdrawal: A Systematic Review with Case Series.

The article entitled, “The Behavioral Profile of Methylenedioxypyrovalerone (MDPV) and α– pyrrolidinopentiophenone (PVP) - A Systematic Review”, submitted in Current Drug Abuse Reviews (CDAR) by Dr. Cornel N Stanciu has been withdrawn from the journal in accordance with BSP Editorial Policies.

Withdrawn: The Behavioral Profile of methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (PVP) - A Systematic Review.

Loperamide is widely available as an inexpensive, over-the-counter remedy commonly used for management of diarrhea. Although an opioid, at therapeutic doses it acts primarily on the gastrointestinal tissues; however, larger than recommended amounts facilitate central nervous system (CNS) penetration. Such high doses of loperamide have recently gained popularity among users of opioids to manage withdrawal symptomatology and, less frequently, to achieve psychoactive effects. Chronic loperamide use can result in development of tolerance and, upon abrupt cessation of use, withdrawal. With increasing prevalence of use, side-effects are noted, one particularly being life-threatening cardiac arrhythmias. Users are often not forthcoming and routine drug screens do not detect loperamide, so providers need to be alert to such practices in order to recognize intoxication, be able to screen for use, and facilitate entry into treatment.

Cornel N. Stanciu

Papers

Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis.

Kratom Withdrawal: A Systematic Review with Case Series.

Withdrawn: The Behavioral Profile of methylenedioxypyrovalerone (MDPV) and α-pyrrolidinopentiophenone (PVP) - A Systematic Review.

Loperamide, the "Poor Man's Methadone": Brief Review.

Use of Buprenorphine in treatment of refractory depression-A review of current literature.