CNS drugs最新文献

{"title":"Comment on: \"Extended‑Release Viloxazine Compared with Atomoxetine for Attention Deficit Hyperactivity Disorder\".","authors":"Uday Pande, Nitin R Gaikwad, Alok Singh","doi":"10.1007/s40263-023-01034-3","DOIUrl":"10.1007/s40263-023-01034-3","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10128103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials.","authors":"Dania Akbar, Taeho Greg Rhee, Felicia Ceban, Roger Ho, Kayla M Teopiz, Bing Cao, Mehala Subramaniapillai, Angela T H Kwan, Joshua D Rosenblat, Roger S McIntyre","doi":"10.1007/s40263-023-01032-5","DOIUrl":"10.1007/s40263-023-01032-5","url":null,"abstract":"<p><strong>Background: </strong>A significant proportion of adults with major depressive disorder (MDD) do not respond to treatments which are currently used in clinical practice such as first-generation monoamine-based antidepressants.</p><p><strong>Objectives: </strong>The objective of this systematic review was to assess the efficacy, safety, and mechanisms of action of AXS-05, a combination of the NMDA-receptor antagonist dextromethorphan with bupropion, in adults with MDD.</p><p><strong>Methods: </strong>We searched PubMed, Embase, Google Scholar, and ClinicalTrials.gov for current studies reporting on efficacy and/or safety of AXS-05 in patients with MDD. The search terms included: \"AXS-05\" OR \"dextromethorphan and bupropion\" AND \"depression\". Studies from database inception to January 2023 were evaluated. Risk of bias was assessed using the Cochrane Risk of Bias tool.</p><p><strong>Results: </strong>The search yielded 54 studies of which 5 were included. All studies had low risk of bias. Depression severity, measured with the Montgomery-Åsberg Depression Rating Scale (MADRS) significantly decreased as early as 1-week post-treatment from baseline when compared to a placebo-controlled group (LS mean difference 2.2; 95% CI 0.6-3.9; p = 0.007) and at 2 weeks compared to an active control group (LS mean difference 4.7; 95% CI 0.6-8.8; p = 0.024). Treatment efficacy could be maintained for up to 12 months with mean MADRS score reduction of 23 points from baseline. Clinical remission and response rates also improved at week 1 and were maintained for 12 months. The treatment was well-tolerated, with some transient adverse events reported.</p><p><strong>Conclusion: </strong>Current evidence suggests that the combination of dextromethorphan and bupropion is a well-tolerated, rapid-acting treatment option for adults with MDD. Initial success with AXS-05 supports the mechanistic role of glutamatergeric and sigma 1 signaling in the pathophysiology of MDD.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Third-Generation Antiseizure Medication in the Treatment of Benzodiazepine-Refractory Status Epilepticus in Poststroke Epilepsy: A Retrospective Observational Register-Based Study.","authors":"Yaroslav Winter,&nbsp;Katharina Sandner,&nbsp;Thomas Vieth,&nbsp;Gabriel Gonzalez-Escamilla,&nbsp;Sebastian V Stuckrad-Barre,&nbsp;Sergiu Groppa","doi":"10.1007/s40263-023-01039-y","DOIUrl":"10.1007/s40263-023-01039-y","url":null,"abstract":"<p><strong>Background and objective: </strong>Status epilepticus in poststroke epilepsy is a challenging condition because of multiple vascular comorbidities and the advanced age of patients. Data on third-generation antiseizure medication (ASM) in this condition are limited. The aim of this study was to evaluate the efficacy of third-generation ASMs in the second- or third-line therapy of benzodiazepine-refractory status epilepticus in poststroke epilepsy following acute ischemic stroke.</p><p><strong>Methods: </strong>Data on the effectiveness of third-generation ASMs in patients with status epilepticus in poststroke epilepsy were gathered from two German Stroke Registries and the Mainz Epilepsy Registry. We included only cases with epilepsy remote to the ischemic event. No patients with acute symptomatic seizures were included. The following third-generation ASMs were included: brivaracetam, lacosamide, eslicarbazepine, perampanel, topiramate, and zonisamide. The assessment of effectiveness was based on seizure freedom within 48 h since the start of therapy with the respective ASM. Seizure freedom was evaluated both clinically (clinical evaluation at least three times per day) and by daily electroencephalogram records.</p><p><strong>Results: </strong>Of the 138 patients aged 70.8 ± 8.1 years with benzodiazepine-refractory status epilepticus in ischemic poststroke epilepsy, 33 (23.9%) were treated with lacosamide, 24 (17.4%) with brivaracetam, 23 (16.7%) with eslicarbazepine, 21 (15.2%) with perampanel, 20 (14.5%) with topiramate, and 17 (12.3%) with zonisamide. Seizure freedom within 48 h was achieved in 66.7% of patients with lacosamide, 65.2% with eslicarbazepine, 38.1% with perampanel, 37.5% with brivaracetam, 35.0% with topiramate, and 35.3% with zonisamide (p < 0.05 for comparison of lacosamide or eslicarbazepine to other ASMs).</p><p><strong>Conclusions: </strong>Based on these data, lacosamide and eslicarbazepine might be more favorable in the treatment of refractory status epilepticus in poststroke epilepsy, when administered as second- or third-line ASMs before anesthesia. Because of the fact that these ASMs share the same mechanism of action (slow inactivation of sodium channels), our findings could motivate further research on the role that this pharmaceutical mechanism of action has in the treatment of poststroke epilepsy.</p><p><strong>Clinical trial registration: </strong>This study was registered at ClinicalTrials.gov (NCT05267405).</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/e2/40263_2023_Article_1039.PMC10570217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41110872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assisted Reproductive Technology and Disease Management in Infertile Women with Multiple Sclerosis.","authors":"Maddalena Sparaco,&nbsp;Luigi Carbone,&nbsp;Doriana Landi,&nbsp;Ylenia Ingrasciotta,&nbsp;Raffaella Di Girolamo,&nbsp;Giacomo Vitturi,&nbsp;Girolama Alessandra Marfia,&nbsp;Carlo Alviggi,&nbsp;Simona Bonavita","doi":"10.1007/s40263-023-01036-1","DOIUrl":"10.1007/s40263-023-01036-1","url":null,"abstract":"<p><p>Multiple sclerosis (MS) predominantly affects women of fertile age. Various aspects of MS could impact on fertility, such as sexual dysfunction, endocrine alterations, autoimmune imbalances, and disease-modifying therapies (DMTs). The proportion of women with MS (wMS) requesting infertility management and assisted reproductive technology (ART) is increasing over time. In this review, we report on data regarding ART in wMS and address safety issues. We also discuss the clinical aspects to consider when planning a course of treatment for infertility, and provide updated recommendations to guide neurologists in the management of wMS undergoing ART, with the goal of reducing the risk of disease activation after this procedure. According to most studies, there is an increase in relapse rate and magnetic resonance imaging activity after ART. Therefore, to reduce the risk of relapse, ART should be considered in wMS with stable disease. In wMS, especially those with high disease activity, fertility issues should be discussed early as the choice of DMT, and fertility preservation strategies might be proposed in selected cases to ensure both disease control and a safe pregnancy. For patients with stable disease taking DMTs compatible with pregnancy, treatment should not be interrupted before ART. If the ongoing therapy is contraindicated in pregnancy, then it should be switched to a compatible therapy. Prior to beginning fertility treatments in wMS, it would be reasonable to assess vitamin D serum levels, thyroid function and its antibody serum levels; start folic acid supplementation; and ensure smoking and alcohol cessation, adequate sleep, and food hygiene. Cervico-vaginal swabs for Ureaplasma urealyticum, Mycoplasma hominis, and Chlamydia trachomatis, as well as serology for viral hepatitis, HIV, syphilis, and cytomegalovirus, should be performed. Steroids could be administered under specific indications. Although the available data do not clearly show a definite raised relapse risk associated with a specific ART protocol, it seems reasonably safe to prefer the use of gonadotropin-releasing hormone (GnRH) antagonists for ovarian stimulation. Close clinical and radiological monitoring is reasonably recommended, particularly after hormonal stimulation and in case of pregnancy failure.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/fd/40263_2023_Article_1036.PMC10570169.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10553318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Five Broad-Spectrum Antiseizure Medications for Adjunctive Treatment of Refractory Epilepsy: A Systematic Review and Network Meta-analysis.","authors":"Hecheng Wang,&nbsp;Haoran Wang,&nbsp;Yi Liu,&nbsp;Jing Zhao,&nbsp;Xuewen Niu,&nbsp;Lei Zhu,&nbsp;Xiaomin Ma,&nbsp;Yu Zong,&nbsp;Yinglin Huang,&nbsp;Wei Zhang,&nbsp;Yanshuo Han","doi":"10.1007/s40263-023-01029-0","DOIUrl":"10.1007/s40263-023-01029-0","url":null,"abstract":"<p><strong>Background: </strong>Overall, up to one-third of epilepsy patients have drug-resistant epilepsy. However, there was previously no meta-analysis to support the guidelines for broad-spectrum antiseizure medication selection for the adjunctive treatment of refractory epilepsy. In the present meta-analysis, we assessed the efficacy and safety of three second-generation broad-spectrum antiseizure medications, lamotrigine (LTG), levetiracetam (LEV), and topiramate (TPM), and two third-generation broad-spectrum antiseizure medications, perampanel (PER) and lacosamide (LCM), for the adjunctive treatment of refractory epilepsy.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, and CENTRAL from inception to July 15, 2022. The studies included in the meta-analysis were required to meet the following criteria: (1) be randomized, double-blind clinical trials; (2) include patients aged >2 years with a clinical diagnosis of drug-resistant epilepsy; (3) have at least 8 weeks for the treatment period excluding the titration phase; and (4) report the outcomes of seizure response, seizure freedom and the withdrawal rate due to treatment-emergent adverse effects. Data were extracted, and the risk of bias for each study was assessed by two authors independently using RoB2 tools. We performed the network meta-analysis for each outcome through a group of programs in the mvmeta and network packages in Stata. Relative odds ratios with 95% confidence intervals were calculated as the result of the analyses. The surface under the cumulative ranking curve (SUCRA) and mean ranks were used to rank these treatments.</p><p><strong>Results: </strong>Forty-two randomized controlled trials (RCTs) (LTG-placebo: n = 6, LEV-placebo: n = 13, TPM-placebo: n = 9, PER-placebo: n = 6, LCM-placebo: n = 7, LEV-TPM: n = 1) with 10257 participants (LTG = 569, LEV = 1626, TPM = 701, PER = 1734, LCM = 1908, placebo = 3719) were included. Levetiracetam had subequal efficacy in 50 % seizure frequency reduction to TPM [odds ratio (OR) 1.00, 95% confidence interval (CI) 0.73-1.38], and LEV had a higher rate of ≥ 50% seizure frequency reduction than LCM (OR 1.49, 95% CI 1.11-2.01) and PER (OR 1.68, 95% CI 1.24-2.29). Levetiracetam was also related to a higher proportion of seizure freedom participants than TPM (OR 1.87, 95% CI 1.20-2.89), PER (OR 2.23, 95% CI 1.12-4.43), and LCM (OR 2.97, 95% CI 1.46-6.05). In addition, LEV was associated with a lower risk of experiencing at least one treatment-emergent adverse event (TEAE) than PER (OR 0.63, 95% CI 0.46-0.85) and TPM (OR 0.51, 95 % CI 0.36-0.72) and a lower proportion of patients experiencing TEAEs leading to discontinuation than PER (OR 0.51, 95% CI 0.27-0.97) and TPM (OR 0.50, 95 % CI 0.27-0.93).</p><p><strong>Conclusions: </strong>Third-generation drugs (PER and LCM) had no advantages in terms of efficacy and safety for adjunctive treatment of refractory epilepsy compared with several second-generation drugs (L","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10005550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stopping Disease-Modifying Treatments in Multiple Sclerosis: A Systematic Review and Meta-Analysis of Real-World Studies.","authors":"Luca Prosperini,&nbsp;Shalom Haggiag,&nbsp;Serena Ruggieri,&nbsp;Carla Tortorella,&nbsp;Claudio Gasperini","doi":"10.1007/s40263-023-01038-z","DOIUrl":"10.1007/s40263-023-01038-z","url":null,"abstract":"<p><strong>Background: </strong>The question of whether multiple sclerosis requires life-long disease-modifying treatments (DMTs) remains unanswered. Some studies suggest that older patients with stable disease may safely discontinue their DMTs, yet comprehensive evidence-based data are scarce and real-world studies have provided mixed results.</p><p><strong>Objective: </strong>The aim of this study was to assess the rate of disease reactivation and associated risk factors after discontinuation of DMTs in patients with multiple sclerosis.</p><p><strong>Methods: </strong>We searched scientific databases (PubMed/MEDLINE, Scopus and Google Scholar) to identify real-world studies published until 31 July, 2023 that reported the number of patients who experienced relapses and/or disability accrual (outcomes of interest) following a therapy discontinuation longer than 12 months. Magnetic resonance activity and treatment re-start after DMT discontinuation were also considered as additional outcomes. We excluded studies where therapy discontinuation was explicitly related to an unintended or planned pregnancy or preceded a treatment switch. We ran random-effects meta-analyses, subgroup analyses and meta-regression models to provide pooled estimates of post-discontinuation relapse and disability events, and to identify their potential moderators (predictors).</p><p><strong>Results: </strong>After an independent screening, 22 articles met the eligibility criteria, yielding a pooled sample size of 2942 patients followed for 1-7 years after discontinuation (11,689 patient-years). The pooled rates for relapse and disability events were 6.7 and 5.8 per 100 patient-years, respectively. However, available data did not allow us to disentangle isolated disability accrual from relapse-associated worsening. Studies including older patients (β = -0.65, p = 0.006), patients with a longer exposure to DMTs (β = -2.22, p = 0.001) and patients with a longer period of disease stability (β = -2.74, p = 0.002) showed a lower risk of relapse events. According to meta-regression equations, the risk of relapse events after DMT discontinuation became negligible (arbitrarily set at < 1% per year) at approximately 60 years of age, and after either 10 years of DMT exposure, or 8 years of disease stability. Additional analyses showed pooled rates for magnetic resonance imaging activity and re-start events of 16.7 and 17.5 per 100 patient-years, respectively.</p><p><strong>Conclusions: </strong>Based on our quantitative synthesis of real-world data, in the absence of definitive answers from clinical trials, DMT discontinuation appears feasible with a high degree of certainty in selected patients. While our findings are robust regarding relapse events, future efforts are warranted to determine if DMT discontinuation is associated with isolated disability accrual.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41093711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development.","authors":"Emilio Perucca,&nbsp;H Steve White,&nbsp;Meir Bialer","doi":"10.1007/s40263-023-01025-4","DOIUrl":"10.1007/s40263-023-01025-4","url":null,"abstract":"<p><p>The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the modulation of neuronal excitability, and a disruption of GABAergic transmission contributes to the pathogenesis of some seizure disorders. Although many currently available antiseizure medications do act at least in part by potentiating GABAergic transmission, there is an opportunity for further research aimed at developing more innovative GABA-targeting therapies. The present article summarises available evidence on a number of such treatments in clinical development. These can be broadly divided into three groups. The first group consists of positive allosteric modulators of GABA_A receptors and includes Staccato^® alprazolam (an already marketed benzodiazepine being repurposed in epilepsy as a potential rescue inhalation treatment for prolonged and repetitive seizures), the α2/3/5 subtype-selective agents darigabat and ENX-101, and the orally active neurosteroids ETX155 and LPCN 2101. A second group comprises two drugs already marketed for non-neurological indications, which could be repurposed as treatments for seizure disorders. These include bumetanide, a diuretic agent that has undergone clinical trials in phenobarbital-resistant neonatal seizures and for which the rationale for further development in this indication is under debate, and ivermectin, an antiparasitic drug currently investigated in a randomised double-blind trial in focal epilepsy. The last group comprises a series of highly innovative therapies, namely GABAergic interneurons (NRTX-001) delivered via stereotactic cerebral implantation as a treatment for mesial temporal lobe epilepsy, an antisense oligonucleotide (STK-001) aimed at upregulating NaV1.1 currents and restoring the function of GABAergic interneurons, currently tested in a trial in patients with Dravet syndrome, and an adenoviral vector-based gene therapy (ETX-101) scheduled for investigation in Dravet syndrome. Another agent, a subcutaneously administered neuroactive peptide (NRP2945) that reportedly upregulates the expression of GABA_A receptor α and β subunits is being investigated, with Lennox-Gastaut syndrome and other epilepsies as proposed indications. The diversity of the current pipeline underscores a strong interest in the GABA system as a target for new treatment development in epilepsy. To date, limited clinical data are available for these investigational treatments and further studies are required to assess their potential value in addressing unmet needs in epilepsy management.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/2d/40263_2023_Article_1025.PMC10501930.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10320464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Meta-analysis of Different Treatments for Vestibular Migraine.","authors":"Jiann-Jy Chen,&nbsp;Bing-Syuan Zeng,&nbsp;Kuan-Pin Su,&nbsp;Yi-Cheng Wu,&nbsp;Yu-Kang Tu,&nbsp;Brendon Stubbs,&nbsp;Tien-Yu Chen,&nbsp;Bing-Yan Zeng,&nbsp;Yen-Wen Chen,&nbsp;Chih-Wei Hsu,&nbsp;Ping-Tao Tseng","doi":"10.1007/s40263-023-01037-0","DOIUrl":"10.1007/s40263-023-01037-0","url":null,"abstract":"<p><strong>Introduction: </strong>Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.</p><p><strong>Aim: </strong>The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.</p><p><strong>Methods: </strong>The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.</p><p><strong>Results: </strong>Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.</p><p><strong>Conclusions: </strong>The current study provides evidence ","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/e0/40263_2023_Article_1037.PMC10501927.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Over the Counter Supplements for Memory: A Review of Available Evidence.","authors":"Haley Hersant,&nbsp;Sean He,&nbsp;Peter Maliha,&nbsp;George Grossberg","doi":"10.1007/s40263-023-01031-6","DOIUrl":"10.1007/s40263-023-01031-6","url":null,"abstract":"<p><p>In 2021, the Global Brain Health Supplement Industry Market size was valued at US$7.6 billion. It is predicted to increase to US$15.59 billion by 2030. Memory and its enhancement are a segment of the market that comprised the highest global revenue share in 2021. In the USA alone, dietary supplement sales reached US$18 billion in 2018. The US Food and Drug Administration (FDA) does not have the authority to approve dietary supplements' safety, effectiveness, or labeling before products go on the market. The FDA often does not even review supplements before they go to market. Supplement manufacturers are thus responsible for ensuring their products are safe and that their claims are truthful. An extensive review of current supplements on the market was performed by surveying memory products for sale at local and national pharmacies and grocery stores. A list of 103 supplements was compiled and the ingredients in these memory supplements were reviewed. The 18 most common ingredients in these supplements were identified. Each of the supplements included at least one of the 18 most common ingredients. Scientific data relative to these ingredients and their effect on memory was searched using PubMed and Cochrane library databases. Currently, there is no compelling evidence for use of apoaequorin, coenzyme Q10, coffee extracts, L-theanine, omega-3 fatty acids, vitamin B6, vitamin B9, or vitamin B12 supplementation for memory. On the other hand, there is some current evidence for memory benefit from supplementation with ashwagandha, choline, curcumin, ginger, Lion's Mane, polyphenols, phosphatidylserine, and turmeric. There are current studies with mixed results regarding the benefit of carnitine, gingko biloba, Huperzine A, vitamin D, and vitamin E supplementation for memory. Dietary supplements geared toward improving cognition are a billion-dollar industry that continues to grow despite lacking a solid scientific foundation for their marketing claims. More rigorous studies are needed relative to the long-term use of these supplements in homogenous populations with standardized measurements of cognition. Health care providers need to be aware of any and all supplements their older adult patients may be consuming and be educated about their side effects and interactions with prescription medications. Lastly, the FDA needs to take an active position relative to monitoring marketed supplements regarding safety, purity and claims of efficacy.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: I. Role of GABA as a Modulator of Seizure Activity and Recently Approved Medications Acting on the GABA System.","authors":"Emilio Perucca, Meir Bialer, H Steve White","doi":"10.1007/s40263-023-01027-2","DOIUrl":"10.1007/s40263-023-01027-2","url":null,"abstract":"<p><p>γ-Aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter in the mammalian brain and has been found to play an important role in the pathogenesis or the expression of many neurological diseases, including epilepsy. Although GABA can act on different receptor subtypes, the component of the GABA system that is most critical to modulation of seizure activity is the GABA_A-receptor-chloride (Cl^-) channel complex, which controls the movement of Cl^- ions across the neuronal membrane. In the mature brain, binding of GABA to GABA_A receptors evokes a hyperpolarising (anticonvulsant) response, which is mediated by influx of Cl^- into the cell driven by its concentration gradient between extracellular and intracellular fluid. However, in the immature brain and under certain pathological conditions, GABA can exert a paradoxical depolarising (proconvulsant) effect as a result of an efflux of chloride from high intracellular to lower extracellular Cl^- levels. Extensive preclinical and clinical evidence indicates that alterations in GABAergic inhibition caused by drugs, toxins, gene defects or other disease states (including seizures themselves) play a causative or contributing role in facilitating or maintaning seizure activity. Conversely, enhancement of GABAergic transmission through pharmacological modulation of the GABA system is a major mechanism by which different antiseizure medications exert their therapeutic effect. In this article, we review the pharmacology and function of the GABA system and its perturbation in seizure disorders, and highlight how improved understanding of this system offers opportunities to develop more efficacious and better tolerated antiseizure medications. We also review the available data for the two most recently approved antiseizure medications that act, at least in part, through GABAergic mechanisms, namely cenobamate and ganaxolone. Differences in the mode of drug discovery, pharmacological profile, pharmacokinetic properties, drug-drug interaction potential, and clinical efficacy and tolerability of these agents are discussed.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/86/40263_2023_Article_1027.PMC10501955.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10270386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}