CNS drugs最新文献

{"title":"Sex Differences in Adverse Effects of Antiseizure Medications in Adults with Epilepsy: A Systematic Review","authors":"Loretta Giuliano, Vania Durante, Giulia Battaglia, Sara Gasparini, Elena Zambrelli, Caterina Ermio, Angela La Neve, Barbara Mostacci","doi":"10.1007/s40263-024-01088-x","DOIUrl":"https://doi.org/10.1007/s40263-024-01088-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Sex differences in epilepsy have been described in prevalence, seizure propensity and response to treatment. Therefore, taking into account sex-based differences in epilepsy is important for both diagnostic purposes and therapeutic considerations. However, little is known about sex differences in adverse effects of antiseizure medications (ASMs).</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We performed a systematic review searching for sex differences in adverse effects of ASMs in adult persons with epilepsy (PWE) as part of a wider project aimed to assess sex-based differences in efficacy and adverse effects of ASMs in PWE.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a comprehensive literature search in the PubMed database. The search was conducted with no restriction on publication date, and all results up to April 2020 were included. We included articles written in English, Italian, Spanish, or French that evaluated adverse effects of one or more ASMs in PWE, with specific mention of the two sexes. When appropriate, Newcastle-Ottawa or Jadad scales were used to assess study quality.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of 5164 identified studies, only 167 considered sex in the analysis and were therefore included. Significant sex-related differences were found in 58 of those studies. We found a consistently higher frequency of cutaneous adverse effects in females; higher risk of developing general adverse effects on different ASMs in females; stronger risk of adverse effects on bone metabolism in females, mainly on treatment with enzyme-inducing ASMs; a concordant higher risk of visual field loss was noted in males on vigabatrin; an overall worse lipid profile in males; as well as higher leptin levels and higher body mass index in females treated with various ASMs.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Our analysis has identified some important sex differences in the adverse effects of ASMs. Clinicians should be aware of these differences when informing patients about the risks associated with ASM treatment in PWE.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"25 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140829367","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":"Rapid Metabolism Underlying Subtherapeutic Serum Levels of Atypical Antipsychotics Preceding Clozapine Treatment: A Retrospective Analysis of Real-World Data","authors":"Hasan Çağın Lenk, Robert Løvsletten Smith, Kevin S. O’Connell, Ole A. Andreassen, Espen Molden","doi":"10.1007/s40263-024-01079-y","DOIUrl":"https://doi.org/10.1007/s40263-024-01079-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Adequate antipsychotic treatment intensity is required before diagnosing resistant schizophrenia and initiating clozapine treatment. We aimed to investigate potential rapid drug metabolism underlying low dose-adjusted serum concentration (CD) of non-clozapine atypical antipsychotics preceding clozapine treatment.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Patients using non-clozapine, atypical antipsychotics (aripiprazole, risperidone, olanzapine, or quetiapine) within 1 year before starting clozapine were included in this study from a therapeutic drug monitoring service in Oslo, Norway, between 2005 and 2023. Patients were assigned into low CD (LCD) and normal CD (NCD) subgroups. Using a reference sample with 147,964 antipsychotic measurements, LCD was defined as CDs below the 25th percentile, while patients with NCD exhibited CDs between the 25th and 75th percentile of the respective reference measurements. Metabolic ratios, doses, and frequency of subtherapeutic levels of non-clozapine antipsychotics were compared between LCD and NCD groups.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Preceding clozapine treatment, 110 out of 272 included patients (40.4%) were identified with LCD. Compared with the NCD group, LCD patients exhibited higher metabolic ratios of olanzapine (1.5-fold; <i>p</i> &lt; 0.001), quetiapine (3.0-fold; <i>p</i> &lt; 0.001), and risperidone (6.0-fold; <i>p</i> &lt; 0.001). Metabolic ratio differences were independent of smoking and <i>CYP2D6</i> genotype for olanzapine (<i>p =</i> 0.008) and risperidone (<i>p</i> = 0.016), respectively. Despite higher doses of olanzapine (1.25-fold; <i>p</i> = 0.054) and quetiapine (1.6-fold; <i>p</i> = 0.001) in LCD versus NCD patients, faster metabolism among the former was accompanied by higher frequencies of subtherapeutic levels of olanzapine (3.3-fold; <i>p</i> = 0.044) and quetiapine (1.8-fold; <i>p</i> = 0.005).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>LCD and associated rapid metabolism of non-clozapine antipsychotics is frequent before starting clozapine treatment. For olanzapine and quetiapine, this is associated with significantly increased risk of having subtherapeutic concentrations.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"63 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623600","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":"Ticagrelor Versus Clopidogrel in Acute Large-Vessel Ischemic Stroke: A Randomized Controlled Single-Blinded Trial","authors":"Mohamed G. Zeinhom, Ahmed Elbassiouny, Ahmed Mahmoud Mohamed, Sherihan Rezk Ahmed","doi":"10.1007/s40263-024-01080-5","DOIUrl":"https://doi.org/10.1007/s40263-024-01080-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Large-vessel ischemic stroke represents about 25–40% of all ischemic strokes. Few clinical trials compared ticagrelor versus clopidogrel in ischemic stroke patients; all these studies included only patients with a transient ischemic attack or minor stroke; moreover, none of these studies included patients from North Africa.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>We aimed to compare ticagrelor versus clopidogrel in the first-ever large-vessel occlusion (LVO) acute ischemic stroke in Egypt.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Our trial involved 580 first-ever LVO ischemic stroke patients who were randomly assigned to administer loading and maintenance doses of ticagrelor or clopidogrel. Screening, randomization, and start of treatment occurred during the first 24 hours of the stroke.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>580 patients were included in the intention-to-treat analysis. Thirty patients in the ticagrelor group and 49 patients in the clopidogrel group experienced a new ischemic or hemorrhagic stroke at 90 days (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.38–0.98; <i>p</i>-value = 0.04), 36 patients in the ticagrelor group, and 57 in the clopidogrel group experienced composite of a new stroke, myocardial infarction, or death due to vascular insults (HR 0.56; 95% CI 0.37–0.87; <i>p </i>= 0.009). Patients who received ticagrelor had better clinical outcomes regarding National Institutes of Health Stroke Scale (NIHSS) reduction and a favorable modified Rankin scale (mRS) score. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Patients with acute large-vessel ischemic stroke who received ticagrelor within the first 24 hours after ischemic stroke had better clinical outcomes based on recurrent stroke rates, NIHSS reduction, and favorable mRS rates compared with those who received clopidogrel. There were no differences between ticagrelor and clopidogrel regarding hemorrhagic and non-hemorrhagic complications.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration</h3><p>Clinical trials.gov (NCT06120725).</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"48 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561005","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":"Impulse Control Disorders in Parkinson’s Disease: An Overview of Risk Factors, Pathogenesis and Pharmacological Management","authors":"Federico Carbone, Atbin Djamshidian","doi":"10.1007/s40263-024-01087-y","DOIUrl":"https://doi.org/10.1007/s40263-024-01087-y","url":null,"abstract":"<p>Impulse control disorders in Parkinson’s disease are relatively common drug-induced addictive behaviours that are usually triggered by the dopamine agonists pramipexole, ropinirole and rotigotine. This narrative review aimed to provide a comprehensive overview of the current knowledge of impulse control disorders in Parkinson’s disease. We summarised the prevalence, clinical features, risk factors and potential underlying mechanisms of impulse control disorders in Parkinson’s disease. Moreover, recent advances in behavioural and imaging characteristics and management strategies are discussed. Early detection as well as a tailored multidisciplinary approach, which typically includes careful adjustment of the dopaminergic therapy and the treatment of associated neuropsychiatric symptoms, are necessary. In some cases, a continuous delivery of levodopa via a pump or the dopamine D₁ receptor agonist, apomorphine, can be considered. In selected patients without cognitive or speech impairment, deep brain stimulation of the subthalamic nucleus can also improve addictions. Finding the right balance of tapering dopaminergic dose (usually dopamine agonists) without worsening motor symptoms is essential for a beneficial long-term outcome.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"167 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560904","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":"Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial","authors":"Libat Weizman, Haggai Sharon, Lior Dayan, Joumana Espaniol, Silviu Brill, Hadas Nahman-Averbuch, Talma Hendler, Giris Jacob","doi":"10.1007/s40263-024-01085-0","DOIUrl":"https://doi.org/10.1007/s40263-024-01085-0","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>THC significantly reduced the LF/HF ratio compared with placebo (interaction effect <i>F</i>(1,11) = 20.5; <i>p</i> &lt; 0.005) and significantly improved CPM responses (interaction effect <i>F</i>(1,9) = 5.2; <i>p</i> = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster <i>p</i>-FDR &lt; 0.005].</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation.</p><h3 data-test=\"abstract-sub-heading\">Clinical Trial Registry Number</h3><p>NCT02560545.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"250 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561002","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":"On the Optimal Diagnosis and the Evolving Role of Pimavanserin in Parkinson’s Disease Psychosis","authors":"Fernando L. Pagan, Paul E. Schulz, Yasar Torres-Yaghi, Gregory M. Pontone","doi":"10.1007/s40263-024-01084-1","DOIUrl":"https://doi.org/10.1007/s40263-024-01084-1","url":null,"abstract":"<p>Parkinson’s disease (PD) is associated with the development of psychosis (PDP), including hallucinations and delusions, in more than half of the patient population. Optimal PD management must therefore involve considerations about both motor and non-motor symptoms. Often, clinicians fail to diagnosis psychosis in patients with PD and, when it is recognized, treat it suboptimally, despite the availability of multiple interventions. In this paper, we provide a summary of the current guidelines and clinical evidence for treating PDP with antipsychotics. We also provide recommendations for diagnosis and follow-up. Finally, an updated treatment algorithm for PDP that incorporates the use of pimavanserin, the only US FDA-approved drug for the treatment of PDP, was developed by extrapolating from a limited evidence base to bridge to clinical practice using expert opinion and experience. Because pimavanserin is only approved for the treatment of PDP in the US, in other parts of the world other recommendations and algorithms must be considered.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"45 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561216","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":"Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review","authors":"Amira Salim, Elise Hennessy, Claire Sonneborn, Olivia Hogue, Sudipa Biswas, MaryAnn Mays, Aarushi Suneja, Zubair Ahmed, Ignacio F. Mata","doi":"10.1007/s40263-024-01086-z","DOIUrl":"https://doi.org/10.1007/s40263-024-01086-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency with monotherapy. The burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>The aim of this study was to evaluate the effect of concurrent anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) and onabotulinumtoxinA (onabot) treatment on median monthly migraine days (MMD) in patients with chronic migraine, through a retrospective study.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The electronic medical records of Cleveland Clinic patients either concurrently (dual therapy) or consecutively (monotherapy) treated with anti-CGRP mAbs and onabot between June 2018 and November 2021 were extracted. Only adult patients (≥ 18 years of age) were included in this study. MMDs for 194 concurrently treated (86.6% female and a median [interquartile range] age of 51 [41–61] years) and 229 consecutively treated (88.2% female and median age of 47 [IQR 39–57] years) patients were examined at baseline, after first therapy of either anti-CGRP mAb or onabot, and following dual therapy for 3 consecutive months. The reduction of MMDs for each treatment group were compared. The same approach was utilized to compare consecutive monotherapy at separate times (<i>n</i> = 229) and dual-therapy groups.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The initial treatment of the dual-therapy group reduced the median (IQR) MMDs from 30 (30–30) to 15 (12–30) [<i>p</i> &lt; 0.0001]. After initiation of dual therapy, the median MMDs was further decreased from 15 (12–30) to 8 (3–22) [<i>p</i> &lt; 0.0001]. A majority [132/194 (68.0%)] of the dual-therapy patients reported a ≥ 50% reduction in MMD and 90/194 (46.4%) reported a ≥ 75% reduction. For the consecutive monotherapy group, median MMDs changed from a baseline of 30 (25–30) to 15 (8–25) from onabot monotherapy and decreased from 25 (15–30) to 12 (4–25) after anti-CGRP mAb monotherapy. Almost half (113/229 [49.3%] from onabot, and 104/229 [45.4%] from anti-CGRP mAb) of these patients achieved a ≥ 50% reduction in MMDs and a minority (38/229 [16.6%] from onabot, and 45/229 [19.7%] from anti-CGRP mAb) achieved a reduction of ≥ 75%. Additionally, dual therapy showed significant improvement in MMDs compared with monotherapy of either treatment (<i>p</i> &lt; 0.0001).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Dual therapy of anti-CGRP mAbs and onabot may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"48 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561122","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":"CNS Viral Infections—What to Consider for Improving Drug Treatment: A Plea for Using Mathematical Modeling Approaches","authors":"Ming Sun, Martijn L. Manson, Tingjie Guo, Elizabeth C. M. de Lange","doi":"10.1007/s40263-024-01082-3","DOIUrl":"https://doi.org/10.1007/s40263-024-01082-3","url":null,"abstract":"<p>Neurotropic viruses may cause meningitis, myelitis, encephalitis, or meningoencephalitis. These inflammatory conditions of the central nervous system (CNS) may have serious and devastating consequences if not treated adequately. In this review, we first summarize how neurotropic viruses can enter the CNS by (1) crossing the blood-brain barrier or blood-cerebrospinal fluid barrier; (2) invading the nose via the olfactory route; or (3) invading the peripheral nervous system. Neurotropic viruses may then enter the intracellular space of brain cells via endocytosis and/or membrane fusion. Antiviral drugs are currently used for different viral CNS infections, even though their use and dosing regimens within the CNS, with the exception of acyclovir, are minimally supported by clinical evidence. We therefore provide considerations to optimize drug treatment(s) for these neurotropic viruses. Antiviral drugs should cross the blood–brain barrier/blood cerebrospinal fluid barrier and pass the brain cellular membrane to inhibit these viruses inside the brain cells. Some antiviral drugs may also require intracellular conversion into their active metabolite(s). This illustrates the need to better understand these mechanisms because these processes dictate drug exposure within the CNS that ultimately determine the success of antiviral drugs for CNS infections. Finally, we discuss mathematical model-based approaches for optimizing antiviral treatments. Thereby emphasizing the potential of CNS physiologically based pharmacokinetic models because direct measurement of brain intracellular exposure in living humans faces ethical restrictions. Existing physiologically based pharmacokinetic models combined with in vitro pharmacokinetic/pharmacodynamic information can be used to predict drug exposure and evaluate efficacy of antiviral drugs within the CNS, to ultimately optimize the treatments of CNS viral infections.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"28 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561208","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":"Observation on the Analgesic Effect of Different Doses of a Combination of Esketamine and Dexmedetomidine Administered for Percutaneous Endoscopic Transforaminal Discectomy: A Randomized, Double-Blind Controlled Trial","authors":"Jian-Shun Zhou, Zhen Chen, Ying-Ying Liu, Mao-Lin Zhong, Qiong Zhong, Jun Wei, Qian Hu, Jia-Sheng Wang, Li-Feng Wang","doi":"10.1007/s40263-024-01083-2","DOIUrl":"https://doi.org/10.1007/s40263-024-01083-2","url":null,"abstract":"&lt;h3 data-test=\"abstract-sub-heading\"&gt;Background&lt;/h3&gt;&lt;p&gt;Percutaneous endoscopic transforaminal discectomy (PETD) is an effective method for treating lumbar disc herniation, and is typically performed under local anesthesia. However, inadequate analgesia during the procedure remains a concern, prompting the search for a medication that can provide optimal pain control with minimal impact on the respiratory and circulatory systems.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Objectives&lt;/h3&gt;&lt;p&gt;The aim of this study was to observe the effects of different doses of esketamine combined with dexmedetomidine on reducing visual analog scale (VAS) scores during surgical interventions.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Methods&lt;/h3&gt;&lt;p&gt;One hundred two patients who underwent PETD were randomly divided into a control group (group C: normal saline + dexmedetomidine), an E1 group (0.1 mg kg&lt;sup&gt;−1&lt;/sup&gt; esketamine + dexmedetomidine), and an E2 group (0.2 mg kg&lt;sup&gt;−1&lt;/sup&gt; esketamine + dexmedetomidine). The primary outcome was the maximum visual analogue scale (VAS) (score: 0 = no pain and 10 = worst pain) at six time points. The secondary outcomes included the Assessment of Alertness/Sedation Scale (OAA/S) score and mean arterial pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO&lt;sub&gt;2&lt;/sub&gt;) at 11 time points. The incidence of adverse reactions during and 24 h after the operation and patient satisfaction with the anesthesia were also recorded.&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Results&lt;/h3&gt;&lt;p&gt;Compared with those in group C, the VAS scores of patients in groups E1 and E2 were lower at &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;6&lt;/sub&gt;, &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;7&lt;/sub&gt;, and &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;9&lt;/sub&gt; (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). From &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;4&lt;/sub&gt; to &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;10&lt;/sub&gt;, the OAA/S scores of the E1 and E2 groups were both lower than those of group C (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), and at the &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;4&lt;/sub&gt;–&lt;i&gt;T&lt;/i&gt;&lt;sub&gt;6&lt;/sub&gt; time points, the OAA/S score of the E2 group was lower than that of group E1 (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). At &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;4&lt;/sub&gt; and &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;5&lt;/sub&gt;, the HR and BP of patients in groups E1 and E2 were greater than those in group C (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Compared with those in group C, the incidences of intraoperative illusion, floating sensation, postoperative dizziness, and hyperalgesia in groups E1 and E2 were significantly greater (&lt;i&gt;P&lt;/i&gt; &lt; 0.01). There was no significant difference in patient RR, SpO&lt;sub&gt;2&lt;/sub&gt;, or postoperative satisfaction with anesthesia among the three groups (&lt;i&gt;P&lt;/i&gt; &gt; 0.05).&lt;/p&gt;&lt;h3 data-test=\"abstract-sub-heading\"&gt;Conclusion&lt;/h3&gt;&lt;p&gt;The combination of esketamine and dexmedetomidine can reduce VAS scores during certain stages of this type of surgery; it has minimal impact on respiration and circulation. However, this approach is associated with increased incidences of postoperative dizziness and psychiatric side effects, which may also affect patients’ compliance with surgical instructions from medical staff. Patient sati","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"48 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561211","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":"The Gut Microbiota in Parkinson Disease: Interactions with Drugs and Potential for Therapeutic Applications","authors":"","doi":"10.1007/s40263-024-01073-4","DOIUrl":"https://doi.org/10.1007/s40263-024-01073-4","url":null,"abstract":"<h3>Abstract</h3> <p>The concept of a ‘microbiota-gut-brain axis’ has recently emerged as an important player in the pathophysiology of Parkinson disease (PD), not least because of the reciprocal interaction between gut bacteria and medications. The gut microbiota can influence levodopa kinetics, and conversely, drugs administered for PD can influence gut microbiota composition. Through a two-step enzymatic pathway, gut microbes can decarboxylate levodopa to dopamine in the small intestine and then dehydroxylate it to <em>m</em>-tyramine, thus reducing availability. Inhibition of bacterial decarboxylation pathways could therefore represent a strategy to increase levodopa absorption. Other bacterial perturbations common in PD, such as small intestinal bacterial overgrowth and <em>Helicobacter pylori</em> infection, can also modulate levodopa metabolism, and eradication therapies may improve levodopa absorption. Interventions targeting the gut microbiota offer a novel opportunity to manage disabling motor complications and dopa-unresponsive symptoms. Mediterranean diet-induced changes in gut microbiota composition might improve a range of non-motor symptoms. Prebiotics can increase levels of short-chain fatty acid-producing bacteria and decrease pro-inflammatory species, with positive effects on clinical symptoms and levodopa kinetics. Different formulations of probiotics showed beneficial outcomes on constipation, with some of them improving dopamine levels; however, the most effective dosage and duration and long-term effects of these treatments remain unknown. Data from faecal microbiota transplantation studies are preliminary, but show encouraging trends towards improvement in both motor and non-motor outcomes.</p> <p>This article summarises the most up-to-date knowledge in pharmacomicrobiomics in PD, and discusses how the manipulation of gut microbiota represents a potential new therapeutic avenue for PD.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":"144 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140561028","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}