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CNS Drugs

Tristram A Lett, Henrik Walter, Eva J Brandl
Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment...
October 17, 2016: CNS Drugs
Wolfgang Löscher, Michel Gillard, Zara A Sands, Rafal M Kaminski, Henrik Klitgaard
The synaptic vesicle glycoprotein SV2A belongs to the major facilitator superfamily (MFS) of transporters and is an integral constituent of synaptic vesicle membranes. SV2A has been demonstrated to be involved in vesicle trafficking and exocytosis, processes crucial for neurotransmission. The anti-seizure drug levetiracetam was the first ligand to target SV2A and displays a broad spectrum of anti-seizure activity in various preclinical models. Several lines of preclinical and clinical evidence, including genetics and protein expression changes, support an important role of SV2A in epilepsy pathophysiology...
October 17, 2016: CNS Drugs
Maria Eliza Freitas, Marta Ruiz-Lopez, Susan H Fox
Levodopa remains the most effective treatment for Parkinson's disease and is considered the gold standard therapy. However, disease progression and changes in the gastrointestinal tract result in a declining window of treatment response in a majority of patients. Efforts have been made recently to improve levodopa bioavailability either by developing more effective oral formulations or by innovating routes of administration (intestinal infusion, transcutaneous or inhaled levodopa). IPX066 is a novel levodopa-carbidopa (LD/CD) oral formulation combining immediate-release (IR) and extended-release (ER) LD/CD recently approved in the USA and the EU...
October 14, 2016: CNS Drugs
Ian Wadsworth, Thomas Jaki, Graeme J Sills, Richard Appleton, J Helen Cross, Anthony G Marson, Tim Martland, Ailsa McLellan, Philip E M Smith, John M Pellock, Lisa V Hampson
Data from clinical trials in adults, extrapolated to predict benefits in paediatric patients, could result in fewer or smaller trials being required to obtain a new drug licence for paediatrics. This article outlines the place of such extrapolation in the development of drugs for use in paediatric epilepsies. Based on consensus expert opinion, a proposal is presented for a new paradigm for the clinical development of drugs for focal epilepsies. Phase I data should continue to be collected in adults, and phase II and III trials should simultaneously recruit adults and paediatric patients aged above 2 years...
September 13, 2016: CNS Drugs
Kim S J Lao, Ying He, Ian C K Wong, Frank M C Besag, Esther W Chan
BACKGROUND: Cariprazine is a novel antipsychotic agent recently approved for treating schizophrenia and bipolar mania in the USA. The sample sizes of published randomized controlled trials (RCTs) of the drug are small; previous meta-analyses included few RCTs and did not specifically investigate the tolerability/safety profile of cariprazine. OBJECTIVE: Our objective was to conduct a meta-analysis of published RCTs to systematically review the tolerability and safety of cariprazine versus placebo...
August 22, 2016: CNS Drugs
Mark Zimmerman, Carolina Guzman Holst, Heather L Clark, Matthew Multach, Emily Walsh, Lia K Rosenstein, Douglas Gazarian
BACKGROUND: Concerns about the generalizability of pharmacotherapy efficacy trials to "real-world" patients have been raised for more than 40 years. Almost all of this literature has focused on treatment studies of major depressive disorder (MDD). OBJECTIVE: The aim of the study was to review the psychiatric inclusion and exclusion criteria used in placebo-controlled trials that assessed the efficacy of medications for bipolar depression (bipolar disorder efficacy trials [BDETs]) and compare the criteria used in BDETs with those used in efficacy trials of antidepressants to treat MDD (antidepressant efficacy trials [AETs])...
August 19, 2016: CNS Drugs
Richard C Chou, Michael Kane, Sanjay Ghimire, Shiva Gautam, Jiang Gui
INTRODUCTION: It is increasingly becoming accepted that inflammation may play an important role in the pathogenesis of Alzheimer's disease (AD), as several immune-related genes have been associated with AD. Among these is tumor necrosis factor (TNF)-α, a proinflammatory cytokine known to play an important role in autoimmune disorders, including rheumatoid arthritis (RA). Although AD and RA appear to involve similar pathological mechanisms through the production of TNF-α, the relationship between AD and RA remains unknown...
July 28, 2016: CNS Drugs
Gin S Malhi, Tim Outhred
Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium-along with the reuptake of lithium in clinical practice...
October 2016: CNS Drugs
Andrew T Lambarth
No abstract text is available yet for this article.
October 2016: CNS Drugs
Karin Wirdefeldt, Per Odin, Dag Nyholm
No abstract text is available yet for this article.
October 2016: CNS Drugs
Diogo Mendes, Carlos Alves, Francisco Batel-Marques
OBJECTIVE: This study aimed to test the number needed to treat to benefit (NNTB) and to harm (NNTH), and the likelihood to be helped or harmed (LHH) when assessing benefits, risks, and benefit-risk ratios of disease-modifying treatments (DMTs) approved for relapsing-remitting multiple sclerosis (RRMS). METHODS: In May 2016, we conducted a systematic review using the PubMed and Cochrane Central Register of Controlled Trials databases to identify phase III, randomized controlled trials with a duration of ≥2 years that assessed first-line (dimethyl fumarate [DMF], glatiramer acetate [GA], β-interferons [IFN], and teriflunomide) or second-line (alemtuzumab, fingolimod, and natalizumab) DMTs in patients with RRMS...
October 2016: CNS Drugs
Evelina A Zimovetz, Stephen M Beard, Paul Hodgkins, Matthias Bischof, Josephine A Mauskopf, Juliana Setyawan
BACKGROUND: An economic analysis from the perspective of the UK National Health Service (NHS) evaluated the cost effectiveness of lisdexamfetamine dimesylate (LDX) compared with atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder who have had an inadequate response to methylphenidate. METHODS: A 1-year decision-analytic model was constructed, with the health outcomes "response", "nonresponse", and "unable to tolerate". Clinical data were taken from a head-to-head, randomized controlled trial in inadequate responders to methylphenidate...
October 2016: CNS Drugs
Emma Beard, Lion Shahab, Damian M Cummings, Susan Michie, Robert West
A wide range of support is available to help smokers to quit and to aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications with (1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and (2) 24 alternative products: cytisine (novel outside Central and Eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e...
October 2016: CNS Drugs
Yanwei Li, Lin Li, Christian Hölscher
Central neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are one of the biggest health problems worldwide. Currently, there is no cure for these diseases. The Gardenia jasminoides fruit is a common herbal medicine in traditional Chinese medicine (TCM), and a variety of preparations are used as treatments for central nervous system (CNS) diseases. Pharmacokinetic studies suggest genipin is one of the main effective ingredients of G. jasminoides fruit extract (GFE). Accumulated research data show that genipin possesses a range of key pharmacological properties, such as anti-inflammatory, neuroprotective, neurogenic, antidiabetic, and antidepressant effects...
October 2016: CNS Drugs
Alp Üçok, Ugur Çıkrıkçılı, Ceylan Ergül, Öznur Tabak, Ada Salaj, Sercan Karabulut, Christoph U Correll
BACKGROUND: Earlier commencement of clozapine has been related to a better response in treatment-resistant schizophrenia. OBJECTIVES: To identify variables that predict clozapine use after a first episode of schizophrenia (FES). METHODS: Patients with FES and ≤15 days of lifetime antipsychotic treatment were followed up during naturalistic treatment, and the patients who were initiated on clozapine were compared with those receiving non-clozapine antipsychotics for ≥24 months regarding demographic and clinical baseline characteristics, adherence, and relapse patterns during follow-up...
October 2016: CNS Drugs
Tingting Xiao, Bin Jiao, Weiwei Zhang, Beisha Tang, Lu Shen
BACKGROUND: Differential responses to donepezil treatment in patients with Alzheimer's disease (AD) have been observed in clinical practice. It remains controversial whether, and to what extent, individual variation in the genes responsible for drug metabolism (CYP2D6) or those associated with AD pathogenesis (APOE) modulate the response to donepezil treatment. OBJECTIVE: The aim of this study was to better understand the potential link between donepezil treatment response and CYP2D6 or APOE polymorphisms...
October 2016: CNS Drugs
Joanne Kacperski, Andrew D Hershey
Treatment of pediatric migraine remains an unmet medical need. There continues to be a paucity of pediatric randomized controlled trials for the treatment of migraine, both in the acute and preventive settings. Pediatric studies are often complicated by high placebo-response rates and much of our current practice is based on adult trials. This lack of significant pediatric studies results in a wide variation in migraine management both amongst clinicians and between institutions, and evidence-based treatments are not always administered...
September 2016: CNS Drugs
Julia Höfler, Alexandra Rohracher, Gudrun Kalss, Georg Zimmermann, Judith Dobesberger, Georg Pilz, Markus Leitinger, Giorgi Kuchukhidze, Kevin Butz, Alexandra Taylor, Helmut Novak, Eugen Trinka
OBJECTIVE: The aim was to describe the safety and efficacy of (S)-ketamine [(S)-KET] in a series of patients with refractory and super-refractory status epilepticus (RSE and SRSE) in a specialized neurological intensive care unit (NICU). METHODS: We retrospectively analyzed the data of patients with RSE and SRSE treated with (S)-KET in the NICU, Salzburg, Austria, from 2011 to 2015. Data collection included demographic features, clinical presentation, diagnosis, electroencephalogram (EEG) data, anticonvulsant treatment, timing, and duration of treatment with (S)-KET...
September 2016: CNS Drugs
Jennifer B Levin, Anna Krivenko, Molly Howland, Rebecca Schlachet, Martha Sajatovic
Poor medication adherence is a pervasive problem that causes disability and suffering as well as extensive financial costs among individuals with bipolar disorder (BD). Barriers to adherence are numerous and cross multiple levels, including factors related to bipolar pathology and those unique to an individual's circumstances. External factors, including treatment setting, healthcare system, and broader health policies, can also affect medication adherence in people with BD. Fortunately, advances in research have suggested avenues for improving adherence...
September 2016: CNS Drugs
Chiara Bernagie, Marina Danckaerts, Martien Wampers, Marc De Hert
BACKGROUND: Both the US FDA and the European Medicines Agency (EMA) have approved aripiprazole for use in adolescents for specific indications. Given the assumed favorable side-effect profile of aripiprazole, its use in children and adolescents has increased for both official and off-label indications (anxiety disorders, eating disorders, personality disorders). However, several cases of children and adolescents with new-onset extrapyramidal symptoms (EPS) after commencing treatment with aripiprazole have been reported, and a more systematic appraisal of this possible risk is lacking...
September 2016: CNS Drugs
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