CNS drugs最新文献

{"title":"The effects of Lysergic Acid Diethylamide (LSD) on the Positive Valence Systems: A Research Domain Criteria (RDoC)-Informed Systematic Review.","authors":"Niloufar Pouyan, Farnaz Younesi Sisi, Alireza Kargar, Milan Scheidegger, Roger S McIntyre, Jonathan D Morrow","doi":"10.1007/s40263-023-01044-1","DOIUrl":"10.1007/s40263-023-01044-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research Domain Criteria (RDoC) framework, as proposed by the National Institute of Mental Health, we aim to synthesize the existing literature concerning the impact of lysergic acid diethylamide (LSD) on the RDoC's Positive Valence Systems (PVS) domain, and to identify potential avenues for further research.</p><p><strong>Methods: </strong>Two LSD-related terms (lysergic acid diethylamide and LSD) and 13 PVS-related terms (reward, happiness, bliss, motivation, reinforcement learning, operant, conditioning, satisfaction, decision making, habit, valence, affect, mood) were used to search electronic databases such as PubMed, Scopus, PsychINFO, and Web of Science for relevant articles. A manual search of the reference list resulted in nine additional articles. After screening, articles and data were evaluated and included based on their relevance to the objective of investigating the effects of LSD on the PVS. Articles and data were excluded if they did not provide information about the PVS, were observational in nature, lacked comparators or reference groups, or were duplicates. A risk of bias assessment was performed using the National Toxicology Program's Office of Health Assessment and Translation (NTP OHAT) risk of bias (RoB) tool. Data from the included articles were collected and structured based on the RDoC bio-behavioral matrix, specifically focusing on the PVS domain and its three constituent constructs: reward responsiveness, reward learning, and reward valuation.</p><p><strong>Results: </strong>We reviewed 28 clinical studies with 477 participants. Lysergic acid diethylamide, assessed at self-report (23 studies), molecular (5 studies), circuit (4 studies), and paradigm (3 studies) levels, exhibited dose-dependent mood improvement (20 short-term and 3 long-term studies). The subjective and neural effects of LSD were linked to the 5-HT<sub>2A</sub> receptor (molecular). Animal studies (14 studies) suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential associative learning enhancements. Reward valuation measures indicated potential reductions in effort expenditure for other reinforcers.</p><p><strong>Conclusion: </strong>Our findings are consistent with our previous work, which indicated classical psychedelics, primarily serotonin 2A receptor agonists, enhanced reward responsiveness in healthy individuals and patient populations. Lysergic acid diethylamide exhibits a unique profile in the reward learning and valuation constructs. Using the RDoC-based framework, we identified areas for future research, enhancing our understanding of the impact of LSD on reward processing. However, applying RDoC to p","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1027-1063"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10703966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298588","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":"Levetiracetam Interaction with Direct Oral Anticoagulants: A Pharmacovigilance Study.","authors":"Mohammed Abou Kaoud, Ran Nissan, Amitai Segev, Avi Sabbag, David Orion, Elad Maor","doi":"10.1007/s40263-023-01052-1","DOIUrl":"10.1007/s40263-023-01052-1","url":null,"abstract":"<p><strong>Background: </strong>Levetiracetam is widely used in post-stroke epilepsy. However, it is suspected to possess P-glycoprotein (P-gp) induction properties, and therefore, a potentially significant interaction with direct oral anticoagulants (DOACs). We aimed to search for ischemic stroke signals with levetiracetam and the DOACs.</p><p><strong>Methods: </strong>In this retrospective pharmacovigilance study, we used the FAERS database to identify ischemic stroke events associated with DOACs and concomitant use of levetiracetam. We evaluated disproportionate reporting by the adjusted reporting odds ratio (adjROR) and the lower bound of the shrinkage 95% confidence interval. When shrinkage is positive, an increased risk of a specific adverse event occurrence is emphasized over the sum of the individual risks when these same drugs are used separately.</p><p><strong>Results: </strong>We identified 1841 (1.5%), 3731 (5.3%), 338 (4.9%), and 1723 (1.3%) ischemic stroke reports with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. The adjROR of the interaction effect was 3.57 (95% CI 2.81-4.58) between DOACs and levetiracetam. The shrinkage analysis detected an interaction between each of the DOACs and levetiracetam. The logistic model and shrinkage analysis failed to detect an interaction when queried for hemorrhagic stroke. A significant signal in the classical enzyme inducer, carbamazepine, strengthened our results (adjROR; 8.47, 95% CI 5.37-13.36).</p><p><strong>Conclusions: </strong>Our study shows a strong signal for the levetiracetam interaction with the DOACs. Our findings suggest implementation of a drug monitoring strategy.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1111-1121"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290546","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":"Context is a Critical for Psychoactive Drug Effects.","authors":"Kyle T Greenway","doi":"10.1007/s40263-023-01053-0","DOIUrl":"10.1007/s40263-023-01053-0","url":null,"abstract":"","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1065-1068"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298586","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":"Effect of BI 1358894 on Cholecystokinin-Tetrapeptide (CCK-4)-Induced Anxiety, Panic Symptoms, and Stress Biomarkers: A Phase I Randomized Trial in Healthy Males.","authors":"Markus Goettel, Rene Fuertig, Salome Rebecca Mack, Stefan Just, Vikas Sharma, Andreas Wunder, Johan den Boer","doi":"10.1007/s40263-023-01042-3","DOIUrl":"10.1007/s40263-023-01042-3","url":null,"abstract":"<p><strong>Introduction: </strong>Depression, anxiety, and/or panic disorder are often comorbid and have a complex etiology mediated through the same neuronal network. Cholecystokinin-tetrapeptide (CCK-4), a synthetic analog of the endogenous neuropeptide cholecystokinin (CCK), is thought to be implicated in this network. The CCK-4 challenge model is an accepted method of investigating the pathophysiology of panic and has been shown to mediate neuronal activation via the transient receptor potential canonical (TRPC) ion channels.</p><p><strong>Objectives: </strong>This study aimed to assess the pharmacodynamic effects of BI 1358894, a small-molecule inhibitor of TRPC ion channel members 4 and 5 (TRPC4/5), on CCK-4-induced anxiety/panic-like symptoms and evaluate circuit engagement.</p><p><strong>Methods: </strong>Twenty healthy male CCK-4-sensitive volunteers entered a Phase I, double blind, randomized, two-way cross-over, single dose, placebo-controlled trial. Randomization was to oral BI 1358894 100 mg in the fed state followed by oral placebo in the fed state, or vice versa. Treatments were administered 5 h prior to intravenous CCK-4 50 µg. The primary endpoint was maximum change from baseline of the Panic Symptom Scale (PSS) sum intensity score after CCK-4 injection. Further endpoints included the emotional faces visual analog score (EVAS), the Spielberger State-Trait Anxiety Inventory (STAI), plasma adrenocorticotropic hormone (ACTH), and serum cortisol values. The safety and tolerability of BI 1358894 was assessed based on a number of parameters including occurrence of adverse events (AEs). All pharmacodynamic, pharmacokinetic, and safety endpoints were analyzed using descriptive statistics.</p><p><strong>Results: </strong>Single oral doses of BI 1358894 were generally well tolerated by the healthy male volunteers included in this study. Adjusted mean maximum change from baseline in PSS sum intensity score was 24.4 % lower in volunteers treated with BI 1358894 versus placebo, while adjusted mean maximum change from baseline of EVAS was reduced by 19.2 % (BI 1358894 vs placebo). The STAI total score before CCK-4 injection was similar in both groups (placebo: 25.1; BI 1358894: 24.3). Relative to placebo, BI 1358894 reduced CCK-4-induced mean maximum plasma ACTH and serum cortisol values by 58.6 % and 27.3 %, respectively. Investigator-assessed drug-related AEs were reported for 13/20 participants (65.0 %). There were no serious or severe AEs, AEs of special interest, AEs leading to discontinuation of trial medication, or deaths.</p><p><strong>Conclusions: </strong>Overall, BI 1358894 reduced psychological and physiological responses to CCK-4 compared with placebo, as measured by PSS, subjective EVAS and objectively measured stress biomarkers. BI 1358894 had a positive safety profile, and single oral doses were well tolerated by the healthy volunteers. This trial (NCT03904576/1402-0005) was registered on Clinicaltrials.gov on 05.04.19.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1099-1109"},"PeriodicalIF":7.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10703963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451118","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":"Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study.","authors":"Valeria Caponnetto, Antonio Russo, Marcello Silvestro, Alessandro Tessitore, Roberto De Icco, Gloria Vaghi, Grazia Sances, Cristina Tassorelli, Carlo Baraldi, Flavia Lo Castro, Simona Guerzoni, Maria Pia Prudenzano, Adriana Fallacara, Martino Gentile, Raffaele Ornello, Agnese Onofri, Andrea Burgalassi, Alberto Chiarugi, Francesco De Cesaris, Antonio Granato, Alfonsina Casalena, Marina De Tommaso, Edoardo Mampreso, Paola Merlo, Gianluca Coppola, Stefania Battistini, Valentina Rebecchi, Innocenzo Rainero, Federica Nicoletta Sepe, Giorgio Dalla Volta, Simona Sacco, Pierangelo Geppetti, Luigi Francesco Iannone","doi":"10.1007/s40263-023-01050-3","DOIUrl":"10.1007/s40263-023-01050-3","url":null,"abstract":"<p><strong>Background: </strong>Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up.</p><p><strong>Objective: </strong>We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine.</p><p><strong>Methods: </strong>This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed.</p><p><strong>Results: </strong>A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events.</p><p><strong>Conclusions: </strong>This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1069-1080"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10703741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298587","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":"Effects of Single and Multiple Ascending Doses of BI 1358894 in Healthy Male Volunteers on Safety, Tolerability and Pharmacokinetics: Two Phase I Partially Randomised Studies.","authors":"René Fuertig, Markus Goettel, Lena Herich, Josef Hoefler, Sabrina T Wiebe, Vikas Sharma","doi":"10.1007/s40263-023-01041-4","DOIUrl":"10.1007/s40263-023-01041-4","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;The transient receptor potential canonical (TRPC) ion channels have been implicated in the pathophysiology of major depressive disorder (MDD), and TRPC inhibition has been shown to reduce depressive-like behaviour in rodent models of depression. BI 1358894, a small-molecule inhibitor of TRPC ion channels, is currently being developed for the treatment of MDD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;Two phase I studies assessed the safety, tolerability, and pharmacokinetics (PK) of oral BI 1358894 in fed and fasted states following a single ascending dose (SAD) [NCT03210272/1402-0001] and multiple ascending doses (MAD) [NCT03754959/1402-0002] in healthy male volunteers. In addition, any potential food effect was evaluated after a single dose.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In both studies, eligible healthy male volunteers (aged 18-45 years; body mass index of 18.5-29.9 kg/m&lt;sup&gt;2&lt;/sup&gt;) were allocated to receive BI 1358894 or placebo. In the SAD study (1402-0001), volunteers were randomised 3:1 to receive BI 1358894 or placebo in fasted (3, 6, 10, 25, 50, 100, or 200 mg) and fed states (200 mg). The food effect part was conducted as an open-label, randomised, two-way crossover study at doses of 50 and 100 mg in fasted and fed states (high-calorie, high-fat breakfast). For the MAD study (1402-0002), volunteers were randomised 4:1 to receive BI 1358894 (10, 25, 50, 100, or 200 mg) or placebo once daily for 14 days under fed conditions. Primary endpoint (both studies): number of volunteers with drug-related adverse events (DRAEs). Secondary PK endpoints for study 1402-0001: area under the concentration-time curve (AUC) from time zero extrapolated to infinity (AUC&lt;sub&gt;∞&lt;/sub&gt;), maximum plasma concentration (C&lt;sub&gt;max&lt;/sub&gt;), and AUC from time zero to the last quantifiable data time point (AUC&lt;sub&gt;0-tz&lt;/sub&gt;). Secondary PK endpoints for study 1402-0002: AUC over 0-24 h (AUC&lt;sub&gt;0-24&lt;/sub&gt;), C&lt;sub&gt;max&lt;/sub&gt; after the first dose, and steady-state AUC and C&lt;sub&gt;max&lt;/sub&gt; over a uniform dosing interval (AUC&lt;sub&gt;τ,ss&lt;/sub&gt; and C&lt;sub&gt;max,ss&lt;/sub&gt;, respectively) after the last dose.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;BI 1358894 was well tolerated at doses ≤ 200 mg under all tested conditions and no dose dependency was observed in DRAE frequency for either study. In the SAD study, BI 1358894 exposure increased dose proportionally across 3-50 mg in the fasted state and across 50-200 mg in the fed state. A positive food effect was observed at the tested doses. In the MAD study, BI 1358894 exposure increased less than dose proportionally across 10-200 mg.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These studies demonstrate that BI 1358894 is well tolerated in healthy male volunteers following single and multiple doses, with no dose dependency observed in DRAE frequency. BI 1358894 exposure increased dose dependently in both the SAD and MAD studies, with higher exposure of BI 1358894 observed in the fed state.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinicaltrials regist","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"1081-1097"},"PeriodicalIF":6.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10703969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451119","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":"A Prospective Longitudinal Study of the Effects of Eslicarbazepine Acetate Treatment on Bone Density and Metabolism in Patients with Focal-Onset Epilepsy.","authors":"Martin Hirsch, Ilka Immisch, Susanne Knake, Andreas Schulze-Bonhage","doi":"10.1007/s40263-023-01045-0","DOIUrl":"10.1007/s40263-023-01045-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Eslicarbazepine acetate (ESL) is a third-generation anti-seizure medication for patients with focal-onset epilepsy. There are known short-term impacts of classic enzyme-inducing drugs on bone health. For oxcarbazepine, which like ESL is a less potent inducer of cytochrome P450 (CYP450) than carbamazepine, some studies have shown that treatment is associated with increased bone metabolic parameters. The effects of ESL on bone health have not been systematically evaluated so the objective of this study was to investigate whether adverse effects of ESL on bone mineral density (BMD) could be measured after a 12-month exposure period. In addition, the effects of ESL on bone turnover were investigated using laboratory indicators of bone metabolism.</p><p><strong>Methods: </strong>BONAPARTE was a prospective, longitudinal, observational study that enrolled patients with focal-onset epilepsy with or without secondary generalization who started treatment with ESL, either as adjunctive treatment or monotherapy, at two tertiary epilepsy centres in Germany between February 2018 and July 2020. Standardised osteodensitometry and biochemical bone metabolism parameters at the time of ESL initiation and 1 year after continuation of therapy were assessed. Comparisons between biochemical and densitometric parameters at baseline and after 12 months of treatment were performed using the paired samples t test.</p><p><strong>Results: </strong>In total, 26 patients (15 male; mean age 41.4 ± 12.5 years) newly treated with ESL were evaluated. Six of these patients had osteopenia at baseline. The mean daily dose of ESL at the 12-month follow-up was 1438 ± 1406 mg. At the group level, there were no significant effects of treatment with ESL on laboratory markers or on BMD. Mean values of BMD in g/cm² at baseline and after 12 months of ESL treatment were 1.17 (± 0.16) and 1.16 (± 0.16) in the lumbar spine, and 0.98 (± 0.15) and 0.96 (± 0.15) in the proximal femur, respectively. Intra-individually, two patients developed de novo osteopenia measured at the femoral neck associated with relevant changes in bone metabolic parameters.</p><p><strong>Conclusion: </strong>Neither osteodensitometry nor bone metabolism parameters showed significant group effects after 1 year of treatment with ESL. Individual fluctuations were observed, however, which may warrant monitoring for longer follow-up periods. The study was registered in the German register for clinical studies under the number DRKS00010430 with the official name BONAPARTE.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"973-980"},"PeriodicalIF":6.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434051","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":"Current Insights into Diagnosing and Treating Neurotuberculosis in Adults.","authors":"Sofiati Dian, Ahmad Rizal Ganiem, Lindsey Hm Te Brake, Arjan van Laarhoven","doi":"10.1007/s40263-023-01047-y","DOIUrl":"10.1007/s40263-023-01047-y","url":null,"abstract":"<p><p>Neurotuberculosis has the highest morbidity and mortality risk of all forms of extrapulmonary tuberculosis (TB). Early treatment is paramount, but establishing diagnosis are challenging in all three forms of neurotuberculosis: tuberculous meningitis (TBM), spinal TB and tuberculomas. Despite advancements in diagnostic tools and ongoing research aimed at improving TB treatment regimens, the mortality rate for neurotuberculosis remains high. While antituberculosis drugs were discovered in the 1940s, TB treatment regimens were designed for and studied in pulmonary TB and remained largely unchanged for decades. However, new antibiotic regimens and host-directed therapies are now being studied to combat drug resistance and contribute to ending the TB epidemic. Clinical trials are necessary to assess the effectiveness and safety of these treatments, addressing paradoxical responses in neurotuberculosis cases and ultimately improving patient outcomes. Pharmacokinetic-pharmacodynamic analyses can inform evidence-based dose selection and exposure optimization. This review provides an update on the diagnosis and treatment of neurotuberculosis, encompassing both sensitive and resistant antituberculosis drug approaches, drawing on evidence from the literature published over the past decade.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"957-972"},"PeriodicalIF":6.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396672","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":"Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.","authors":"Leonore Purwien, Susanne Schubert-Bast, Matthias Kieslich, Michael W Ronellenfitsch, Michael Merker, Marcus Czabanka, Laurent M Willems, Felix Rosenow, Adam Strzelczyk","doi":"10.1007/s40263-023-01049-w","DOIUrl":"10.1007/s40263-023-01049-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Over the last decade, significant advancements have been made in status epilepticus (SE) management, influenced by landmark trials such as ESETT and RAMPART. The objectives of this study were to explore the evolution of drug treatments for patients with SE, to investigate its association with outcomes and mortality, and to evaluate differences in treatment patterns between adults and children for a potential shift in medication trends due to the above mentioned trials.</p><p><strong>Methods: </strong>The medical records of patients with SE treated at University Hospital Frankfurt between 2012 and 2021 were evaluated for medication trends and outcomes. Children and adults were analyzed separately and jointly.</p><p><strong>Results: </strong>This study included 1151 SE episodes in 1021 patients (mean age = 53.3 ± 28.3 years; 52.5 % female [n = 533]). The overall percentage of patients with SE treated prehospital was stable over the last decade. More than half (53.6 %) of children were treated prehospital, compared with less than one-third (26.7 %) of adults. Prehospital midazolam use increased over time, while diazepam use decreased. Lorazepam was the most commonly used benzodiazepine in hospitals in 2012-2013, used in 40.8 % of all episodes. However, its use declined to 27.2 % in 2020-2021, while midazolam use increased to 44.0 %. While the use of older antiseizure medications (ASMs) such as phenobarbital (p = 0.02), phenytoin (p < 0.001), and valproate (p < 0.001) decreased, the use of newer ASMs such as levetiracetam and lacosamide significantly increased (p < 0.001). Propofol and continuous midazolam infusion remained the most used third-line therapy drugs. Overall mortality was 16.5 % at discharge and 18.9 % at 30 days. Mortality rates did not change between 2012 and 2021.</p><p><strong>Conclusion: </strong>Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. The same applies to the increased use of levetiracetam and lacosamide over time in children and adults, while phenobarbital, phenytoin, and valproate use decreased. Continuous midazolam infusion and propofol remain the most frequently used anesthetic drugs. Mortality and outcome remain stable despite changes in medication patterns.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"993-1008"},"PeriodicalIF":6.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396674","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 MAO-B Inhibitors Safinamide and Zonisamide in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Laila Aboulatta, Lara Haidar, Ahmed Abou-Setta, Nicole Askin, Rasheda Rabbani, Alekhya Lavu, Payam Peymani, Ryan Zarychanski, Sherif Eltonsy","doi":"10.1007/s40263-023-01048-x","DOIUrl":"10.1007/s40263-023-01048-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = -  2.18; 95% CI -  2.88 to -  1.49; I &lt;sup&gt;2&lt;/sup&gt; =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = -  2.10; 95% CI -  3.09 to -  1.11; I&lt;sup&gt;2&lt;/sup&gt; = 71%; n = 8 studies) and zonisamide (MD = -  2.31; 95% CI -  3.35 to -  1.27; I&lt;sup&gt;2&lt;/sup&gt; = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were re","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"941-956"},"PeriodicalIF":6.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396673","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}