CNS drugs最新文献

{"title":"Intervening in the Premonitory Phase to Prevent Migraine: Prospects for Pharmacotherapy.","authors":"Nazia Karsan, Peter J Goadsby","doi":"10.1007/s40263-024-01091-2","DOIUrl":"10.1007/s40263-024-01091-2","url":null,"abstract":"<p><p>Migraine is a common brain condition characterised by disabling attacks of headache with sensory sensitivities. Despite increasing understanding of migraine neurobiology and the impacts of this on therapeutic developments, there remains a need for treatment options for patients underserved by currently available therapies. The first specific drugs developed to treat migraine acutely, the serotonin-5-hydroxytryptamine [5-HT_1B/1D] receptor agonists (triptans), seem to require headache onset in order to have an effect, while early treatment during mild pain before headache escalation improves short-term and long-term outcomes. Some patients find treating in the early window once headache has started but not escalated difficult, and migraine can arise from sleep or in the early hours of the morning, making prompt treatment after pain onset challenging. Triptans may be deemed unsuitable for use in patients with vascular disease and in those of older age and may not be effective in a proportion of patients. Headache is also increasingly recognised as being just one of the many facets of the migraine attack, and for some patients it is not the most disabling symptom. In many patients, painless symptoms can start prior to headache onset and can reliably warn of impending headache. There is, therefore, a need to identify therapeutic targets and agents that may be used as early as possible in the course of the attack, to prevent headache onset before it starts, and to reduce both headache and non-headache related attack burden. Early small studies using domperidone, naratriptan and dihydroergotamine have suggested that this approach could be useful; these studies were methodologically less rigorous than modern day treatment studies, of small sample size, and have not since been replicated. The emergence of novel targeted migraine treatments more recently, specifically calcitonin gene-related peptide (CGRP) receptor antagonists (gepants), has reignited interest in this strategy, with encouraging results. This review summarises historical and emerging data in this area, supporting use of the premonitory phase as an opportunity to intervene as early as possible in migraine to prevent attack-related morbidity.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"533-546"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141183872","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":"Sex Differences Between Female and Male Individuals in Antipsychotic Efficacy and Adverse Effects in the Treatment of Schizophrenia.","authors":"Megan Galbally, Karen Wynter, Dan Siskind, Christoph U Correll, Korinne Northwood, Susanna Every-Palmer","doi":"10.1007/s40263-024-01089-w","DOIUrl":"10.1007/s40263-024-01089-w","url":null,"abstract":"<p><strong>Background and objective: </strong>Antipsychotics are core treatments for people living with psychotic disorders. Understanding individualised factors that influence both efficacy and adverse responses will improve outcomes. The objective of this study was to examine sex differences in antipsychotic-related efficacy and tolerability.</p><p><strong>Methods: </strong>This was a secondary analysis of data from phase 1 and 1a of Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE); participants with schizophrenia were randomly assigned to double-blinded treatment with oral olanzapine, quetiapine, risperidone, ziprasidone or perphenazine. Measures included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions (CGI) scale and Calgary Depression Rating Scale, as well as self-reported side effects, medication compliance, dosage, weight measurements and various blood parameters.</p><p><strong>Results: </strong>There were 1460 participants including 380 female and 1080 male individuals. Very few differences existed between male and female participants in response, adverse reactions, compliance or antipsychotic dosage. However, significantly more female participants than male participants reported constipation (28% vs 16%), dry mouth (50% vs 38%), gynecomastia/galactorrhea (11% vs 3%), incontinence/nocturia (16% vs 8%) and self reported weight gain (37% vs 24%) [all p < 0.001]. Within the risperidone treatment group, there was a significantly greater increase in prolactin levels (p < 0.001) among female participants (n = 61) than male participants (n = 159). No overall differences in clinician-rated measures, weight gain or other laboratory indicators were found.</p><p><strong>Conclusions: </strong>While overall sex differences were limited across efficacy and tolerability for antipsychotic treatment, there were some specific findings with risperidone. Further examination of sex differences within antipsychotic trials will be important to improve efficacy and reduce adverse responses across as well as individualising care for people with schizophrenia.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"559-570"},"PeriodicalIF":7.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852893","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":"Targeting Biometals in Alzheimer's Disease with Metal Chelating Agents Including Coumarin Derivatives.","authors":"Adrián Gucký, Slávka Hamuľaková","doi":"10.1007/s40263-024-01093-0","DOIUrl":"10.1007/s40263-024-01093-0","url":null,"abstract":"<p><p>Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer's disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"507-532"},"PeriodicalIF":6.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199629","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":"FcRn Inhibitor Therapies in Neurologic Diseases.","authors":"Nouf Alfaidi, Salama Karmastaji, Alexandria Matic, Vera Bril","doi":"10.1007/s40263-024-01090-3","DOIUrl":"10.1007/s40263-024-01090-3","url":null,"abstract":"<p><p>In the last decade, the landscape of treating autoimmune diseases has evolved with the emergence and approval of novel targeted therapies. Several new biological agents offer selective and target-specific immunotherapy and therefore fewer side effects, such as neonatal Fc receptor (FcRn)-targeting therapy. Neonatal Fc receptor-targeted therapies are engineered to selectively target FcRn through various methods, such as Fc fragments or monoclonal anti-FcRn antibodies. These approaches enhance the breakdown of autoantibodies by blocking the immunoglobulin G recycling pathway. This mechanism reduces overall plasma immunoglobulin levels, including the levels of pathogenic autoantibodies, without affecting the other immunoglobulin class immunoglobulin A, immunoglobulin E, immunoglobulin M, and immunoglobulin D levels. Drugs that inhibit FcRn include efgartigimod, rozanolixizumab, batoclimab, and nipocalimab. These medications can be administered either intravenously or subcutaneously. Numerous clinical trials are currently underway to investigate their effectiveness, safety, and tolerability in various neurological conditions, including myasthenia gravis and other neurological disorders such as chronic inflammatory demyelinating polyneuropathy, myositis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein antibody disease. Positive results from clinical trials of efgartigimod and rozanolixizumab led to their approval for the treatment of generalized myasthenia gravis. Additional clinical trials are still ongoing. Neonatal Fc receptor inhibitor agents seem to be well tolerated. Reported adverse events include headache (most commonly observed with efgartigimod and rozanolixizumab), upper respiratory tract infection, urinary tract infection, diarrhea, pyrexia, and nausea. Additionally, some of these agents may cause transient hypoalbuminemia and hypercholesterolemia notably reported with batoclimab and nipocalimab. In this review, we discuss the available clinical data for FcRN inhibitor agents in treating different neurological autoimmune diseases.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"425-441"},"PeriodicalIF":6.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897610","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 Effect of Levetiracetam Compared with Enzyme-Inducing Antiseizure Medications on Apixaban and Rivaroxaban Peak Plasma Concentrations.","authors":"Rachel Goldstein, Natalie Rabkin, Noa Buchman, Aviya R Jacobs, Khaled Sandouka, Bruria Raccah, Tamar Fisher Negev, Ilan Matok, Meir Bialer, Mordechai Muszkat","doi":"10.1007/s40263-024-01077-0","DOIUrl":"10.1007/s40263-024-01077-0","url":null,"abstract":"<p><strong>Background and objective: </strong>Post-stroke epilepsy represents an important clinical challenge as it often requires both treatment with direct oral anticoagulants (DOACs) and antiseizure medications (ASMs). Levetiracetam (LEV), an ASM not known to induce metabolizing enzymes, has been suggested as a safer alternative to enzyme-inducing (EI)-ASMs in patients treated with DOACs; however, current clinical guidelines suggest caution when LEV is used with DOACs because of possible P-glycoprotein induction and competition (based on preclinical studies). We investigated whether LEV affects apixaban and rivaroxaban concentrations compared with two control groups: (a) patients treated with EI-ASMs and (b) patients not treated with any ASM.</p><p><strong>Methods: </strong>In this retrospective observational study, we monitored apixaban and rivaroxaban peak plasma concentrations (C_max) in 203 patients treated with LEV (n = 28) and with EI-ASM (n = 33), and in patients not treated with any ASM (n = 142). Enzyme-inducing ASMs included carbamazepine, phenytoin, phenobarbital, primidone, and oxcarbazepine. We collected clinical and laboratory data for analysis, and DOAC C_max of patients taking LEV were compared with the other two groups.</p><p><strong>Results: </strong>In 203 patients, 55% were female and the mean age was 78 ± 0.8 years. One hundred and eighty-six patients received apixaban and 17 patients received rivaroxaban. The proportion of patients with DOAC C_max below their therapeutic range was 7.1% in the LEV group, 10.6% in the non-ASM group, and 36.4% in the EI-ASM group (p < 0.001). The odds of having DOAC C_max below the therapeutic range (compared with control groups) was not significantly different in patients taking LEV (adjusted odds ratio 0.70, 95% confidence interval 0.19-2.67, p = 0.61), but it was 12.7-fold higher in patients taking EI-ASM (p < 0.001). In an analysis in patients treated with apixaban, there was no difference in apixaban C_max between patients treated with LEV and non-ASM controls, and LEV clinical use was not associated with variability in apixaban C_max in a multivariate linear regression.</p><p><strong>Conclusions: </strong>In this study, we show that unlike EI-ASMs, LEV clinical use was not significantly associated with lower apixaban C_max and was similar to that in patients not treated with any ASM. Our findings suggest that the combination of LEV with apixaban and rivaroxaban may not be associated with decreased apixaban and rivaroxaban C_max. Therefore, prospective controlled studies are required to examine the possible non-pharmacokinetic mechanism of the effect of the LEV-apixaban or LEV-rivaroxaban combination on patients' outcomes.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":"399-408"},"PeriodicalIF":7.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11026229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193519","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":"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}