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CNS Drugs

Jeremy Hobart, Tjalf Ziemssen, Peter Feys, Michael Linnebank, Andrew D Goodman, Rachel Farrell, Raymond Hupperts, Andrew R Blight, Veronica Englishby, Manjit McNeill, Ih Chang, Gabriel Lima, Jacob Elkins
BACKGROUND: Walking impairment is a hallmark of multiple sclerosis (MS). It affects > 90% of individuals over time, reducing independence and negatively impacting health-related quality of life, productivity, and daily activities. Walking impairment is consistently reported as one of the most distressing impairments by individuals with MS. Prolonged-release (PR)-fampridine previously has been shown to improve objectively measured walking speed in walking-impaired adults with MS...
December 10, 2018: CNS Drugs
Susan L McElroy, Anna I Guerdjikova, Nicole Mori, Francisco Romo-Nava
This paper reviews past and current progress in developing pharmacologic agents for the treatment of individuals with bulimia nervosa (BN). We searched the literature and clinical trial registries for compounds studied in BN, the related condition, binge eating disorder (BED), and preclinical models of binge-eating behavior. Drug classes evaluated included antidepressants, antiepileptic drugs, stimulants and other medications for attention-deficit/hyperactivity disorder, opioid antagonists, and weight loss agents, among others...
December 6, 2018: CNS Drugs
A George Awad
Schizophrenia is a long-term psychiatric disorder that impacts important mental functions and requires indefinite treatment, as well as psychosocial and economic support. The introduction of chlorpromazine, the first antipsychotic, and the subsequent development of a long list of similar dopamine-blocking antipsychotic medications, has changed the treatment of schizophrenia as medications have become the cornerstone of clinical management. The enthusiasm that greeted the introduction of antipsychotics was soon tempered by the realisation that they induced significant side effects, such as extrapyramidal and autonomic symptoms...
December 3, 2018: CNS Drugs
Andre F Batista, Victor Bodart-Santos, Fernanda G De Felice, Sergio T Ferreira
The current absence of effective treatments for Alzheimer's disease (AD) and Parkinson's disease (PD) reflects an incomplete knowledge of the underlying disease processes. Considerable efforts have been made to investigate the central pathological features of these diseases, giving rise to numerous attempts to develop compounds that interfere with such features. However, further characterization of the molecular targets within the interconnected AD and PD pathways is still required. Impaired brain insulin signaling has emerged as a feature that contributes to neuronal dysfunction in both AD and PD, leading to strategies aiming at restoring this pathway in the brain...
December 3, 2018: CNS Drugs
Jacoline C Bouvy, Pall Jonsson, Diana O'Rourke, Antonella Santuccione Chadha, Niklas Hedberg, Amr Makady, Entela Xoxi, Christine Gispen-de Wied, Anja Schiel, Raj Long, John Gallacher
Although there are a growing number of well-reported, late-stage clinical trial failures in Alzheimer's disease, the introduction of a disease-modifying therapy within the next 5 years may be anticipated. These treatments are likely to target Alzheimer's disease in the earlier disease stages, unlike drugs that are currently available that treat symptoms of moderate-to-severe dementia. Therefore, there is a need to establish a consensus on regulatory and health technology assessment requirements for Alzheimer's disease, as a new drug will need to undergo regulatory and health technology assessments before it becomes available to patients...
November 22, 2018: CNS Drugs
Tristan T Sands, Shahryar Rahdari, Michael S Oldham, Eduardo Caminha Nunes, Nicole Tilton, Maria Roberta Cilio
BACKGROUND: Purified cannabidiol is a new antiepileptic drug that has recently been approved for use in patients with Lennox-Gastaut and Dravet syndromes, but most published studies have not extended beyond 12-16 weeks. OBJECTIVE: The objective of this study was to evaluate the long-term safety, tolerability, and efficacy of cannabidiol in children with epilepsy. METHODS: Patients aged 1-17 years with refractory epilepsy were enrolled in an open-label prospective study through individual patient and expanded access programs between April 2013 and December 2014...
November 20, 2018: CNS Drugs
Rita Khoury, George T Grossberg
The relationship between antidepressants and Alzheimer's disease (AD) is very complex, and the literature is mixed regarding the effect of these medications on the trajectory of the disease. This paper reviews findings from relevant clinical studies that have assessed the impact of antidepressants on AD onset and disease progression. To date, these medications seem to attenuate the risk of developing the disease without affecting the rate of progression. However, most evidence stems from observational studies that are subject to methodological bias...
November 19, 2018: CNS Drugs
Susanna Every-Palmer, Stephen J Inns, Eve Grant, Pete M Ellis
BACKGROUND: Gastrointestinal hypomotility in people taking clozapine is common, poorly understood and potentially dangerous. It causes distress and sometimes sudden death, with greater associated morbidity than the better known adverse effect of clozapine, agranulocytosis. Neither the mechanism nor prevalence of clozapine-induced gastrointestinal hypomotility is well understood. Previous studies show clozapine impedes colon transit, likely owing to anticholinergic and anti-serotonergic properties...
November 19, 2018: CNS Drugs
Parnika P Saxena, J Alexander Bodkin
Research concerning psychiatric issues relating to opioid drugs currently focuses primarily on their role in reinforcing addictive behaviors, given the recent proliferation of lethal abuse of illicit opiates in the United States and around the world. In contrast, this article will review the mechanism of action of opioids in affective disorders and the available evidence and potential for their use, especially in the treatment of resistant major depression. Buprenorphine is the opioid derivative of special interest; we review this and other opioid derivatives, highlighting the growing role of opioids in treating depressive illnesses and other related psychopathologies...
November 15, 2018: CNS Drugs
John A Hey, Petr Kocis, Jakub Hort, Susan Abushakra, Aidan Power, Martin Vyhnálek, Jeremy Y Yu, Martin Tolar
Page 856: Fig. 6 was an incorrect duplication of Fig. 5. The correct figure is given below.
November 12, 2018: CNS Drugs
Juliane Gust, Agne Taraseviciute, Cameron J Turtle
Neurotoxicity is an important and common complication of chimeric antigen receptor-T cell therapies. Acute neurologic signs and/or symptoms occur in a significant proportion of patients treated with CD19-directed chimeric antigen receptor-T cells for B-cell malignancies. Clinical manifestations include headache, confusion, delirium, language disturbance, seizures and rarely, acute cerebral edema. Neurotoxicity is associated with cytokine release syndrome, which occurs in the setting of in-vivo chimeric antigen receptor-T cell activation and proliferation...
November 1, 2018: CNS Drugs
Maira Aguiar Werneck, Guilherme Trevizan Kortas, Arthur Guerra de Andrade, João Mauricio Castaldelli-Maia
BACKGROUND: About 30% of regular cannabis users report withdrawal symptoms on cessation of prolonged use, such as irritability, insomnia, decreased appetite, depressed mood, anxiety, and restlessness. However, among highly dependent and/or in-treatment users, the incidence of withdrawal can be even higher, reaching up to 50-95% of individuals. This syndrome was only recognized by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) as a diagnosis with specific criteria in 2013...
October 25, 2018: CNS Drugs
Arjun Tarakad, Joohi Jimenez-Shahed
The basal ganglia and dopaminergic pathways play a central role in hyperkinetic movement disorders. Vesicular monoamine transporter 2 (VMAT2) inhibitors, which deplete dopamine at presynaptic striatal nerve terminals, are a class of drugs that have long been used to treat hyperkinetic movement disorders, but have recently gained more attention following their development for specific indications in the United States. At present, there are three commercially available VMAT2 inhibitors: tetrabenazine, deutetrabenazine, and valbenazine...
October 10, 2018: CNS Drugs
Alexander Klistorner, Yi Chai, Letizia Leocani, Philipp Albrecht, Orhan Aktas, Helmut Butzkueven, Tjalf Ziemssen, Focke Ziemssen, Jette Frederiksen, Lei Xu, Diego Cadavid
BACKGROUND: Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies. OBJECTIVE: MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants...
September 28, 2018: CNS Drugs
Mark Gudesblatt, Karl Wissemann, Myassar Zarif, Barbara Bumstead, Lori Fafard, Jeffrey Wilken, Karen Blitz, Marijean Buhse, Sourav Santra, Christophe Hotermans, Lily Lee
An Online First version of this article was made available online at on 24 August 2018. An error was subsequently identified in the article, and the following correction should be noted.
September 22, 2018: CNS Drugs
Pierre Ellul, Richard Delorme, Samuele Cortese
BACKGROUND: Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs. OBJECTIVE: The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs. METHODS: Based on a pre-registered protocol (PROSPERO-CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials...
September 20, 2018: CNS Drugs
Lesley Taylor, Barry Gidal, Graham Blakey, Bola Tayo, Gilmour Morrison
BACKGROUND: A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety and tolerability of CBD, the maximum tolerated dose, and to examine the effect of food on CBD PK parameters. OBJECTIVE: This trial assessed the safety, tolerability and PK of CBD oral solution in healthy adult volunteers, as well as the effect of food on CBD PK parameters. METHODS: The study consisted of three arms: single ascending dose (1500, 3000, 4500 or 6000 mg CBD [n = 6 per group]/placebo [n = 8; 2 per CBD dose group]), multiple dose (750 or 1500 mg CBD [n = 9 per group]/placebo [n = 6; 3 per CBD dose group] twice daily), and food effect (1500 mg CBD single dose [n = 12])...
November 2018: CNS Drugs
Stefanie Kuerten, Leila J Jackson, Joel Kaye, Timothy L Vollmer
Growing evidence indicates that B cells play a key role in the pathogenesis of multiple sclerosis (MS). B cells occupy distinct central nervous system (CNS) compartments in MS, including the cerebrospinal fluid and white matter lesions. Also, it is now known that, in addition to entering the CNS, B cells can circulate into the periphery via a functional lymphatic system. Data suggest that the role of B cells in MS mainly involves their in situ activation in demyelinating lesions, leading to altered pro- and anti-inflammatory cytokine secretion, and a highly effective antigen-presenting cell function, resulting in activation of memory or naïve T cells...
November 2018: CNS Drugs
Marcelo E Bigal, Alan M Rapoport, Stephen D Silberstein, Sarah Walter, Richard J Hargreaves, Ernesto Aycardi
Calcitonin gene-related peptide (CGRP) is a neuropeptide of importance in migraine pathogenesis. Its central role in migraine was proven pharmacologically by the development of CGRP receptor antagonists. Monoclonal antibodies targeting CGRP or its receptor are effective in the preventive treatment of episodic and chronic migraine and are considered potential breakthroughs in their treatment. Fremanezumab (previously known as TEV-48125, LBR-101, or RN-307) is a humanized IgG2a monoclonal antibody that binds to CGRP...
November 2018: CNS Drugs
Kevin P Jensen, Elise E DeVito, Sarah Yip, Kathleen M Carroll, Mehmet Sofuoglu
Opioid overdoses recently became the leading cause of accidental death in the US, marking an increase in the severity of the opioid use disorder (OUD) epidemic that is impacting global health. Current treatment protocols for OUD are limited to opioid medications, including methadone, buprenorphine, and naltrexone. While these medications are effective in many cases, new treatments are required to more effectively address the rising societal and interpersonal costs associated with OUD. In this article, we review the opioid and cholinergic systems, and examine the potential of acetylcholine (ACh) as a treatment target for OUD...
November 2018: CNS Drugs
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