Newer Formulations of Risperidone: Role in the Management of Psychotic Disorders
AbstractAntipsychotic long-acting injections improve relapse prevention in psychotic disorders. Three new risperidone formulations have been developed that offer advantages over currently available risperidone-based long-acting injections. Risperidone ISM® is a monthly intramuscular injection that does not require loading doses or concurrent oral risperidone. RBP-7000 is a monthly subcutaneous injection not requiring loading or oral supplementation. BB0817 is a 6-monthly implant of risperidone injected subcutaneously. All three preparations have been shown to be effective and well tolerated in clinical trials. A fourth...
Source: CNS Drugs - May 27, 2020 Category: Neurology Source Type: research

Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer ’s Disease
AbstractAlzheimer ’s disease (AD) is the most prevalent dementia in the world. Its cause(s) are presently largely unknown. The most common explanation for AD, now, is the amyloid cascade hypothesis, which states that the cause of AD is senile plaque formation by the amyloid β peptide, and the formation of neurofib rillary tangles by hyperphosphorylated tau. A second, burgeoning theory by which to explain AD is based on the infection hypothesis. Much experimental and epidemiological data support the involvement of infections in the development of dementia. According to this mechanism, the infection either dire ct...
Source: CNS Drugs - May 26, 2020 Category: Neurology Source Type: research

Pharmacotherapeutic Options for Managing Pain in Multiple Sclerosis
AbstractPain is a major matter for patients with multiple sclerosis; treatment response is frequently inadequate, with a significant impact on quality of life. The estimated prevalence of pain in multiple sclerosis ranges widely (26 –86%), and different subtypes of pain, mediated by specific pathophysiological mechanisms, are described. The aim of this narrative review, performed using a systematic search methodology, was to provide current, evidence-based, knowledge about the pharmacological treatment of the different kinds of pain in multiple sclerosis. We searched for relevant papers within PubMed, EMBASE, the Coc...
Source: CNS Drugs - May 8, 2020 Category: Neurology Source Type: research

Cognitive Efficacy of Pharmacologic Treatments in Multiple Sclerosis: A Systematic Review
ConclusionsHigher-quality randomized controlled trials are needed to establish the cognitive efficacy of pharmacologic treatments for MS-related cognitive dysfunction, with cognition as the primary endpoint. Researchers are urged to use standardized criteria (such as the AAN criteria) to guide their research designs. Clinicians should consider effect sizes of studies before deciding whether to prescribe certain medications to ameliorate cognitive symptoms. (Source: CNS Drugs)
Source: CNS Drugs - May 2, 2020 Category: Neurology Source Type: research

A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug –Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy
ConclusionsThe clinical relevance of the increase in stiripentol exposure is unknown; patients receiving cannabidiol and stiripentol concomitantly should be monitored for adverse reactions as individual patient responses may vary. Coadministration of cannabidiol did not affect the pharmacokinetics of valproate or its metabolite, 4-ene-VPA, in adult patients with epilepsy. Safety results were consistent with the known safety profile of cannabidiol at a dose of 20 mg/kg/day.Clinicaltrials.gov: NCT02607891. (Source: CNS Drugs)
Source: CNS Drugs - April 30, 2020 Category: Neurology Source Type: research

The Efficacy and Safety of Concomitant Psychotropic Medication and Electroconvulsive Therapy (ECT)
AbstractElectroconvulsive therapy (ECT) is an effective treatment for severe psychiatric disorders. Patients referred to ECT are often taking multiple medications, many of which can potentially affect the safety and efficacy of their course of ECT. This review evaluates the impact of a variety of psychotropic medications often used in conjunction with ECT and examines strategies to optimize their management. The review encompasses mood stabilizers, antidepressants, benzodiazepines, antiepileptics, antipsychotics, and other commonly used psychotropics. (Source: CNS Drugs)
Source: CNS Drugs - April 27, 2020 Category: Neurology Source Type: research

Associations of Prescribed ADHD Medication in Pregnancy with Pregnancy-Related and Offspring Outcomes: A Systematic Review
ConclusionThe current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman ’s specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate speci...
Source: CNS Drugs - April 24, 2020 Category: Neurology Source Type: research

Tapering with Pharmaceutical GHB or Benzodiazepines for Detoxification in GHB-Dependent Patients: A Matched-Subject Observational Study of Treatment-as-Usual in Belgium and The Netherlands
ConclusionsThese results support earlier work that BZD tapering might not always sufficiently dampen withdrawal in GHB-dependent patients. However, it needs to be taken into account that both treatments were assessed in separate countries. Based on the current findings, tapering with pharmaceutical GHB could be considered for patients with GHB dependence during detoxification, as it has potentially less severe withdrawal and fewer complications than BZD tapering. (Source: CNS Drugs)
Source: CNS Drugs - April 21, 2020 Category: Neurology Source Type: research

Predicted Cellular and Molecular Actions of Lithium in the Treatment of Bipolar Disorder: An In Silico Study
ConclusionsThe predicted cellular and molecular events in this study could be considered as mechanisms and also determinants of lithium responsiveness in BD. (Source: CNS Drugs)
Source: CNS Drugs - April 18, 2020 Category: Neurology Source Type: research

Dose Adjustment of Stimulants for Children with Attention-Deficit/Hyperactivity Disorder: A Retrospective Chart Review of the Impact of Exceeding Recommended Doses
AbstractBackgroundWhen children with attention-deficit/hyperactivity disorder (ADHD) are treated with stimulant medication, the dose is established clinically by dose adjustment over time. Little is known about children who are not adequately treated when they reach a designated maximum dose, or the consequences of exceeding this dose.ObjectiveThe aim of this study was to determine the characteristics of and side effects observed in children optimised to high dose (HD) versus regular dose (RD) stimulants.MethodChildren treated by one paediatrician (AP) in Western Sydney, Australia with HD stimulants (n = 52) ...
Source: CNS Drugs - April 16, 2020 Category: Neurology Source Type: research

Preclinical Evaluation of Vaccines to Treat Opioid Use Disorders: How Close are We to a Clinically Viable Therapeutic?
AbstractThe ongoing opioid crisis, now into its second decade, represents a global public health challenge. Moreover, the opioid crisis has manifested despite clinical access to three approved opioid use disorder medications: the  full opioid agonist methadone, the partial opioid agonist buprenorphine, and the opioid antagonist naltrexone. Although current opioid use disorder medications are underutilized, the ongoing opioid crisis has also identified the need for basic research to develop both safer and more effective opi oid use disorder medications. Emerging preclinical evidence suggests that opioid-targeted v...
Source: CNS Drugs - April 4, 2020 Category: Neurology Source Type: research

Potential of Glial Cell Modulators in the Management of Substance Use Disorders
This article presents a brief overview of the effects of each of the major classes of addictive drugs on glia. Next, the paper reviews the pre-clinical and clinical studies assessing the effects that glial modulators have on abuse -related behavioral effects, such as pleasure, withdrawal, and motivation. There is a strong body of pre-clinical literature demonstrating the general effectiveness of several glia-modulating drugs in models of reward and relapse. Clinical studies have also yielded promising results, though not as r obust. There is still much to disentangle regarding the integration between addictive drugs and gl...
Source: CNS Drugs - April 4, 2020 Category: Neurology Source Type: research

Comparative Tolerability of Dopamine D2/3 Receptor Partial Agonists for Schizophrenia
AbstractAripiprazole, brexpiprazole and cariprazine differ from all other second-generation antipsychotics due to partial agonism at the dopamine D2 and D3 receptors. In contrast to aripiprazole, brexpiprazole has lower intrinsic dopamine D2 activity and higher affinity for the serotonin 5-HT1A and 5-HT2A receptors, while cariprazine has the highest affinity for the dopamine D3 receptor, and the longest half-life. The main adverse effect of dopamine receptor partial agonists (DRPAs) is akathisia of low-to-moderate severity, which occurs in a small proportion of patients, usually in the first few weeks of treatment. While d...
Source: CNS Drugs - April 3, 2020 Category: Neurology Source Type: research

Transnasal Revolution? The Promise of Midazolam Spray to Prevent Seizure Clusters
(Source: CNS Drugs)
Source: CNS Drugs - April 3, 2020 Category: Neurology Source Type: research

Changes in Anti-JCV Antibody Status in a Large Population of Multiple Sclerosis Patients Treated with Natalizumab
ConclusionOur data confirmed that a high percentage of patients shift to or remain in a positive JCV status during NTZ treatment and after discontinuation. NTZ suspension seems not to be able to interfere on JCV status modification over an extended period. The choice of alternative treatment as exit strategy after NTZ discontinuation should be carefully considered because it could negatively influence the PML risk stratification of patients. (Source: CNS Drugs)
Source: CNS Drugs - March 27, 2020 Category: Neurology Source Type: research

Adherence to Oral Antipsychotics Measured by Electronic Adherence Monitoring in Schizophrenia: A Systematic Review and Meta-analysis
ConclusionsOral antipsychotic adherence rates in schizophrenia, defined as a continuous variable and measured by EAM, were in the range of 70%, lower than the 80% threshold used widely to define satisfactory adherence. (Source: CNS Drugs)
Source: CNS Drugs - March 26, 2020 Category: Neurology Source Type: research

Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring
This study aimed to examine the efficacy, tolerability, and safety of intranasal midazolam (in-MDZ) spray in clinical practice.MethodsIn this retrospective, multicenter observational study, we evaluated all patients with peri-ictal application of in-MDZ during video-EEG monitoring at the epilepsy centers in Frankfurt and Marburg between 2 014 and 2017. For every patient, we analyzed the recurrence of any seizure or generalized tonic –clonic seizures after index seizures with and without in-MDZ administration. Treatment-emergent adverse events (TEAEs) were also evaluated.ResultsIn-MDZ was used in 243 patients with e...
Source: CNS Drugs - March 26, 2020 Category: Neurology Source Type: research

Impact of Pharmacological Treatments for Opioid Use Disorder on Mortality
AbstractThe use of pharmacological treatments for opioid use disorders, including methadone, buprenorphine and naltrexone has been associated with a reduction in mortality compared with illicit opioid use. However, these treatments can also contribute significantly to the risk of death. The opioid agonists methadone and buprenorphine achieve clinical efficacy in patients with an opioid use disorder through suppressing craving and diminishing the effectiveness of illicit opioid doses, while the antagonist naltrexone blocks the action of opioids. Pharmacological differences between opioid pharmacotherapies then create differ...
Source: CNS Drugs - March 25, 2020 Category: Neurology Source Type: research

Safety and Efficacy of Ubrogepant for the Acute Treatment of Episodic Migraine: A Meta-Analysis of Randomized Clinical Trials
ConclusionsThe use of ubrogepant as an acute treatment of episodic migraine in adults led to a greater percentage of freedom from pain and absence of the most bothersome symptoms at 2 h post-dose. Short-term use of ubrogepant was not related to an increased risk for adverse events. Further studies are needed to evaluate efficacy and safety for long-term use and in specific subgroups of patients. (Source: CNS Drugs)
Source: CNS Drugs - March 19, 2020 Category: Neurology Source Type: research

Fingolimod and Dimethyl-Fumarate-Derived Lymphopenia is not Associated with Short-Term Treatment Response and Risk of Infections in a Real-Life MS Population
The objective of this study was to assess whether lymphopenia is associated with short-term treatment response and infection rate in a real-life multiple sclerosis population treated with fingolimod and dimethyl-fumarate. We assessed the associations between baseline absolute lymphocyte count and the lymphocyte mean percentage decrease at 6 and 12  months with treatment response and the occurrence of adverse events over 12 months in the entire cohort of patients and in the two treatment groups separately.MethodsThis is a retrospective observational real-world study of patients with multiple sclerosis treated with...
Source: CNS Drugs - March 19, 2020 Category: Neurology Source Type: research

Pharmacological Treatment of Methamphetamine/Amphetamine Dependence: A Systematic Review
ConclusionsNo pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention. (Source: CNS Drugs)
Source: CNS Drugs - March 17, 2020 Category: Neurology Source Type: research

Safety of OnabotulinumtoxinA with Concomitant Antithrombotic Therapy in Patients with Muscle Spasticity: A Retrospective Pooled Analysis of Randomized Double-Blind Studies
The objective of this study was to determine the risk of bleeding complications in patients with post-stroke spasticity receiving antithrombotic therapy and intramuscular onabotulinumtoxinA.MethodsWe conducted a retrospective analysis of pooled safety data from 16 randomized, double-blind, placebo-controlled Allergan-sponsored studies of onabotulinumtoxinA for the treatment of post-stroke upper or lower limb muscle spasticity, including adult patients with at least moderate upper or lower limb spasticity and receiving at least one dose of the study drug. Bleeding-related adverse events starting within 4  weeks of stud...
Source: CNS Drugs - March 13, 2020 Category: Neurology Source Type: research

Correction to: Cladribine Tablets: In Relapsing-Remitting Multiple Sclerosis
During the creation of the HTML version of the article, incorrect body text (including all tables and figures) and an incorrect Additional Information section were uploaded; the PDF version was correct. The HTML version has now been corrected. (Source: CNS Drugs)
Source: CNS Drugs - March 9, 2020 Category: Neurology Source Type: research

Genetic Influence on Efficacy of Pharmacotherapy for Pediatric Attention-Deficit/Hyperactivity Disorder: Overview and Current Status of Research
This article reviews childhood ADHD pharmacogenomics efficacy studies published during the last decade (2009 –2019), which have largely focused on pharmacodynamic candidate gene investigations of methylphenidate and atomoxetine response, with a smaller number investigating pharmacokinetic candidate genes and genome-wide approaches. Findings from studies which have advanced the field of ADHD pharmacogenom ics through investigation of meta-analytic approaches and gene–gene interactions are also overviewed. Despite recent progress, no one genetic variant or currently available pharmacogenomics test has demonstrate...
Source: CNS Drugs - March 4, 2020 Category: Neurology Source Type: research

Sleep Disorders in Children and Adolescents with Autism Spectrum Disorder: Diagnosis, Epidemiology, and Management
AbstractSleep problems are a common complaint in children/adolescents with autism spectrum disorder (ASD). Correctly diagnosing and treating sleep problems in individuals with ASD is key, as they can add to the psychosocial burden of the disorder and exacerbate associated symptoms, such as inattention or irritability. Here, we provide an overview of the epidemiology, diagnosis, and management of sleep problems/disorders in children and adolescents with ASD. This narrative review is mainly informed by a systematic search in PubMed and PsycInfo (last search: 10 October 2019) of available pertinent meta-analyses. We also sear...
Source: CNS Drugs - February 27, 2020 Category: Neurology Source Type: research

Achieving Smoking Cessation Among Persons with Opioid Use Disorder
AbstractWhile prevalence of tobacco use in the US general population is declining, prevalence among those with opioid use disorder (OUD) remains high and results in excessive tobacco-related disease and premature mortality. Among smokers with OUD, tobacco cessation rates are negligible without treatment. However, both low-intensity behavioral interventions and more intensive motivational interventions yield negligible cessation rates. While contingency management has potent short-term cessation effects, effects are not maintained at post-intervention follow-up. Evidence-based smoking cessation pharmacotherapies, such as ni...
Source: CNS Drugs - February 27, 2020 Category: Neurology Source Type: research

Targeting BK Ca Channels in Migraine: Rationale and Perspectives
AbstractLarge (big)-conductance calcium-activated potassium (BKCa) channels are expressed in migraine-related structures such as the cranial arteries, trigeminal ganglion and trigeminal spinal nucleus, and they play a substantial role in vascular tonus and neuronal excitability. Using synthetic BKCa channels openers was associated with headache as a frequent adverse effect in healthy volunteers. Additionally, BKCa channels are downstream molecules in migraine signalling pathways that are activated by several compounds known to provoke migraine, including calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-a...
Source: CNS Drugs - February 14, 2020 Category: Neurology Source Type: research

Management of Dementia-Related Psychosis, Agitation and Aggression: A Review of the Pharmacology and Clinical Effects of Potential Drug Candidates
AbstractAlong with cognitive decline, 90% of patients with dementia experience behavioral and psychological symptoms of dementia, such as psychosis, aggression, agitation, and depression. Atypical antipsychotics are commonly prescribed off-label to manage certain symptoms, despite warnings from the regulatory agencies regarding the increased risk of mortality associated with their use in elderly patients. Moreover, these compounds display a limited clinical efficacy, mostly owing to the fact that they were developed to treat schizophrenia, a disease characterized by neurobiological deficits. Thus, to improve clinical effic...
Source: CNS Drugs - February 12, 2020 Category: Neurology Source Type: research

Born to Protect: Leveraging BDNF Against Cognitive Deficit in Alzheimer ’s Disease
AbstractAlzheimer ’s disease is a chronic neurodegenerative devastating disorder affecting a high percentage of the population over 65 years of age and causing a relevant emotional, social, and economic burden. Clinically, it is characterized by a prominent cognitive deficit associated with language and behavioral impairments. The molecular pathogenesis of Alzheimer’s disease is multifaceted and involves changes in neurotransmitter levels together with alterations of inflammatory, oxidative, hormonal, and synaptic pathways, which may represent a drug target for both prevention and treatment; however, an ef...
Source: CNS Drugs - February 12, 2020 Category: Neurology Source Type: research

Adjunctive Cannabidiol in Patients with Dravet Syndrome: A Systematic Review and Meta-Analysis of Efficacy and Safety
ConclusionsAdjunctive CBD resulted in a greater reduction in convulsive seizure frequency than placebo and a higher rate of AEs in patients with DS presenting with seizures uncontrolled by concomitant antiepileptic therapy. (Source: CNS Drugs)
Source: CNS Drugs - February 10, 2020 Category: Neurology Source Type: research

Pitolisant: A Review in Narcolepsy with or without Cataplexy
AbstractPitolisant (Wakix®), an orally available, first-in-class antagonist/inverse agonist of the histamine 3 receptor, is approved in the EU (as of March 2016) for the treatment of narcolepsy with or without cataplexy in adults and in the USA (as of August 2019) for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy. Pitolisant was demonstrated to have minimal risk of abuse in preclinical and clinical studies, and is the only anti-narcoleptic drug not scheduled as a controlled substance in the USA. The totality of evidence from pivotal and supportive phase III trials suggests that pitolisan...
Source: CNS Drugs - January 29, 2020 Category: Neurology Source Type: research

Pharmacotherapy for Cluster Headache
AbstractCluster headache is characterised by attacks of excruciating unilateral headache or facial pain lasting 15  min to 3 h and is seen as one of the most intense forms of pain. Cluster headache attacks are accompanied by ipsilateral autonomic symptoms such as ptosis, miosis, redness or flushing of the face, nasal congestion, rhinorrhoea, peri-orbital swelling and/or restlessness or agitation. Cluster heada che treatment entails fast-acting abortive treatment, transitional treatment and preventive treatment. The primary goal of prophylactic and transitional treatment is to achieve attack freedom, although this...
Source: CNS Drugs - January 29, 2020 Category: Neurology Source Type: research

Cardiac Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: Results from the Clinical Development Program
AbstractBackgroundAn intranasal formulation of esketamine, combined with an oral antidepressant, is approved in the USA and the European Union for adults with treatment-resistant depression (TRD). Transient cardiovascular stimulatory effects have been reported with ketamine.MethodsCardiovascular effects of esketamine nasal spray, combined with an oral antidepressant, were evaluated in 1708 esketamine-treated adults with TRD in six trials (five double-blind, placebo-controlled (486 placebo-treated patients); one open-label) of 4 –52 weeks’ duration. Patients with established cardiovascular disease, includin...
Source: CNS Drugs - January 29, 2020 Category: Neurology Source Type: research

Anti-CD20 Monoclonal Antibodies for Relapsing and Progressive Multiple Sclerosis
AbstractMultiple sclerosis (MS) was previously thought to be a T-cell-mediated, demyelinating disease of the central nervous system. Disease-modifying therapies targeting T cells have, indeed, shown remarkable efficacy in patients with relapsing-remitting MS. However, these therapies do also target B cells, and a B-cell-depleting monoclonal antibody (ocrelizumab) has recently been approved for MS therapy and is efficacious not only in relapsing forms of MS but also in some patients with primary progressive MS. This suggests that B cells may play a more important role in the pathogenesis of MS than previously appreciated. W...
Source: CNS Drugs - January 28, 2020 Category: Neurology Source Type: research

Multiple-Ascending Dose Study in Healthy Subjects to Assess the Pharmacokinetics, Tolerability, and CYP3A4 Interaction Potential of the T-Type Calcium Channel Blocker ACT-709478, A Potential New Antiepileptic Drug
ConclusionsACT-709478 exhibits good tolerability up to 100  mg once daily using an up-titration regimen and pharmacokinetic properties that support further clinical investigations. A weak induction of gastrointestinal cytochrome P450 3A4 activity was observed, unlikely to be of clinical relevance.ClinicalTrials.gov IdentifierNCT03165097. (Source: CNS Drugs)
Source: CNS Drugs - January 28, 2020 Category: Neurology Source Type: research

Pharmacological Management of the Genetic Generalised Epilepsies in Adolescents and Adults
AbstractCommon genetic generalised epilepsy syndromes encountered by clinicians include childhood and juvenile absence epilepsies, juvenile myoclonic epilepsy and generalised tonic –clonic seizures on awakening. Treatment of these syndromes involves largely the use of broad-spectrum antiseizure drugs. Those effective for the generalised epilepsies include sodium valproate, phenobarbital, ethosuximide, clobazam, clonazepam, lamotrigine, levetiracetam, topiramate, zonisamide a nd, more recently, perampanel and brivaracetam. Results from the few rigorous studies comparing outcomes with drugs for genetic generalised epil...
Source: CNS Drugs - January 25, 2020 Category: Neurology Source Type: research

Recently Approved and Upcoming Treatments for Narcolepsy
AbstractNarcolepsy is a chronic, disabling neurologic disorder characterised by excessive daytime sleepiness (EDS) and, in up to 60% of patients, cataplexy. Treatments for narcolepsy are aimed at improving wakefulness (e.g. modafinil, armodafinil, stimulants), reducing cataplexy attacks (e.g. sodium oxybate, venlafaxine), and treating the symptoms of disturbed nocturnal sleep, sleep paralysis and sleep-related hallucinations (e.g. sodium oxybate). In general, medications that increase the release, or inhibit the reuptake, of norepinephrine or dopamine have wake-promoting effects and are useful in managing EDS, whereas medi...
Source: CNS Drugs - January 17, 2020 Category: Neurology Source Type: research

Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing –Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study
ConclusionsDRF demonstrated an improved gastrointestinal tolerability profile compared with DMF, with less severe gastrointestinal events and fewer days of self-assessed gastrointestinal symptoms, fewer gastrointestinal adverse events, and lower discontinuation rates because of gastrointestinal adverse events.Clinical Trials RegistrationClinicalTrials.gov (NCT03093324). (Source: CNS Drugs)
Source: CNS Drugs - January 17, 2020 Category: Neurology Source Type: research

Recent Advances in the Treatment of Huntington ’s Disease: Targeting DNA and RNA
AbstractHuntington ’s disease is a dominantly inherited neurodegenerative disease caused by an unstable expanded trinucleotide repeat at the short end of the fourth chromosome. Central nervous system pathology begins in the striatum, eventually affecting the entire brain and occurs consequent to multiple intracellul ar derangements. The proximate cause is a mutant protein with an elongated polyglutamine tract. Pharmacological approaches targeting multiple domains of intracellular functions have universally been disappointing. However, recent developments in gene therapy, including antisense oligonucleotides, sm all i...
Source: CNS Drugs - January 13, 2020 Category: Neurology Source Type: research

Potential of Glioblastoma-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy
AbstractDespite the established efficacy of chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies, translating CAR T therapy to solid tumors has remained investigational. Glioblastoma, the most aggressive and lethal form of primary brain tumor, has recently been among the malignancies being trialed clinically with CAR T cells. Glioblastoma in particular holds several unique features that have hindered clinical translation, including its vast intertumoral and intratumoral heterogeneity, associated immunosuppressive environment, and lack of clear experimental models to predict response and analyze resist...
Source: CNS Drugs - January 8, 2020 Category: Neurology Source Type: research

Mortality Risk Associated with Haloperidol Use Compared with Other Antipsychotics: An 11-Year Population-Based Propensity-Score-Matched Cohort Study
ConclusionHaloperidol was associated with increased overall mortality when compared with other antipsychotics in long-term follow-up. Treatment with haloperidol should be carefully considered, especially in older patients and patients at risk of CVD or pneumonia, since the risk of death appears to be lower with non-haloperidol agents. (Source: CNS Drugs)
Source: CNS Drugs - January 8, 2020 Category: Neurology Source Type: research

Efficacy and Safety of Oral Therapies for Relapsing-Remitting Multiple Sclerosis
AbstractDisease-modifying therapies have now become standard treatment for multiple sclerosis. These include five oral therapies for relapsing-remitting multiple sclerosis, namely fingolimod, dimethyl fumarate, teriflunomide, cladribine, and siponimod, although there is some discrepancy on the relative efficacy and safety of these agents. To gain further insight on these oral agents in relapsing-remitting multiple sclerosis, we performed a narrative review of fingolimod, dimethyl fumarate, teriflunomide, cladribine, and siponimod. We limited the analysis to randomized clinical studies in which a comparator was used (i.e., ...
Source: CNS Drugs - January 2, 2020 Category: Neurology Source Type: research

Long-Term Safety and Efficacy of Blonanserin Transdermal Patches in Japanese Patients with Schizophrenia: A 52-Week Open-Label, Multicenter Study
ConclusionsBlonanserin transdermal patches are safe and effective in the long-term treatment of schizophrenia.ClinicalTrials.gov registrationNCT02335658. (Source: CNS Drugs)
Source: CNS Drugs - December 27, 2019 Category: Neurology Source Type: research

Pharmacotherapy for Pediatric Convulsive Status Epilepticus
AbstractConvulsive status epilepticus (CSE) is one of the most common pediatric neurological emergencies. Ongoing seizure activity is a dynamic process and may be associated with progressive impairment of gamma-aminobutyric acid (GABA)-mediated inhibition due to rapid internalization of GABAA receptors. Further hyperexcitability may be caused by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-d-aspartic acid) receptors moving from subsynaptic sites to the synaptic membrane. Receptor trafficking during prolonged seizures may contribute to difficulties treating seizures of longer duration a...
Source: CNS Drugs - December 26, 2019 Category: Neurology Source Type: research

Prescription of Valproate-Containing Medicines in Women of Childbearing Potential who have Psychiatric Disorders: Is It Worth the Risk?
AbstractValproate-containing medicines have long been used in psychiatric practice, principally in the treatment of acute manic episodes, as augmentation agents in the treatment of bipolar and unipolar depressive episodes, and in the prophylaxis of bipolar affective disorder. Many babies are still being born with the adverse consequences of valproate exposure in utero, which include congenital malformations, neurodevelopmental delay, and increased risks of attention-deficit hyperactivity disorder and autism spectrum disorder. Previous measures designed to better inform women about the risks associated with valproate have n...
Source: CNS Drugs - December 16, 2019 Category: Neurology Source Type: research

Cognitive Impairment in Patients with Bipolar Disorder: Impact of Pharmacological Treatment
AbstractBipolar disorder is an illness characterised by periods of elated and depressed mood. These mood episodes are associated with changes in cognitive function and there is evidence to suggest that cognitive dysfunction persists during euthymia. The extent to which this is a function of the illness or a result of treatment is less clear. In this narrative review, we explore the impact of commonly used medications for bipolar disorder on cognitive function. Specific impairments in executive function and verbal memory have been noted in bipolar disorder. The impact of pharmacological treatments upon cognitive function is...
Source: CNS Drugs - December 5, 2019 Category: Neurology Source Type: research

Clinically Significant Drug –Drug Interactions with Agents for Attention-Deficit/Hyperactivity Disorder
This article provides an overview of the pharmacokinetic drug –drug interactions (DDIs) for agents prescribed for attention-deficit/hyperactivity disorder (ADHD). Polypharmacy in the treatment of patients with ADHD leads to high exposures to DDIs and possibly adverse safety outcomes. We performed a systematic search of DDI reports for ADHD agents in Embase a nd Medline. We also searched for agents in the pharmacological pipeline, which include (1) mazindol, molindone and viloxazine, which were previously prescribed for other indications; (2) centanafadine and AR-08, never before approved; and (3) two extracts (Polyga...
Source: CNS Drugs - November 27, 2019 Category: Neurology Source Type: research

Novel IDH1-Targeted Glioma Therapies
AbstractMutations in the isocitrate dehydrogenase (IDH) 1 gene are commonly found in human glioma, with the majority of low-grade gliomas harboring a recurrent point mutation (IDH1 R132H). Mutant IDH reveals an altered enzymatic activity leading to the synthesis of 2-hydroxyglutarate, which has been implicated in epigenetic mechanisms of oncogenesis. Nevertheless, it is unclear exactly how IDH mutations drive glioma initiation and progression, and it is also not clear why tumors with this mutation generally have a better prognosis than IDH wild-type tumors. Recognition of the high frequency of IDH mutations in glioma [and ...
Source: CNS Drugs - November 25, 2019 Category: Neurology Source Type: research

Psychostimulants/Atomoxetine and Serious Cardiovascular Events in Children with ADHD or Autism Spectrum Disorder
ConclusionUsing large US claims data, we found no evidence of increased SCV risk in children and adolescents with ADHD or ASD exposed to ADHD medications. (Source: CNS Drugs)
Source: CNS Drugs - November 25, 2019 Category: Neurology Source Type: research

Achieving the Lowest Effective Antipsychotic Dose for Patients with Remitted Psychosis: A Proposed Guided Dose-Reduction Algorithm
AbstractContinuing antipsychotic treatment in patients with schizophrenia under clinical remission remains controversial. Even though the mainstream opinion declares an outweighed balance against medication discontinuation, recent reviews and critiques suggest that some patients may remain symptom free and well functioning after stopping antipsychotics, but few predictors can identify who can try medication discontinuation, whilst no guidelines exist for reducing medication to reach the lowest effective dose safely. Analyzing the findings from studies employing different methodologies, adopting evidence from pharmacodynami...
Source: CNS Drugs - November 18, 2019 Category: Neurology Source Type: research