CNS drugs最新文献

Background: Although recurrent ischemic stroke (IS) is associated with higher rates of mortality and comorbidities as well as an increased economic burden than the first attack, the choice of first-line antihypertensive agent for secondary prevention remains controversial. This study examined the efficacy of various antihypertensive agents for the secondary prevention of recurrent ischemic stroke in a real-world context.

Methods: Using the National Health Insurance Research Database, patients with first acute IS from 1 January 2000 to 31 December 2020 were enrolled. Using propensity score-based probability of treatment weighting, all participants were divided into other antihypertensive drugs (OHTND), angiotensin-converting-enzyme-inhibitors/angiotensin II-receptor-blockers (ACEI/ARB), and calcium-channel-blockers (CCB) cohorts. Primary outcome was difference in risk of recurrent IS, and secondary outcomes were all-cause mortality, stroke-related death, and major adverse cardiac and cerebrovascular events (MACCEs). Cox proportional hazards models were used to estimate the adjusted hazard ratio and 95% confidence intervals.

Results: Compared with the OHTND cohort, individuals in the ACEI/ARB and CCB cohorts had a 14% (p < 0.001) and 15% (p < 0.001) lower risk of recurrent IS, respectively. Individuals in the CCB cohort had a 37% (p = 0.006) higher risk of acute myocardial infarction compared with the OHTND cohort. Compared with ACEI users, ARB users experienced a 22% lower risk of recurrent IS, while ARB users had a 46% lower risk of stroke-related death.

Conclusions: The use of ACEI/ARB following acute IS was associated with a lower risk of recurrent IS. Our results not only corresponded to pre-existing randomized controlled trials (RCTs) but also addressed the knowledge gap regarding the choice of first-line antihypertensive agents following acute IS.

Both pediatric and adult patients can develop low-grade glioma (World Health Organization [WHO] grade 2), a type of primary brain tumor that can impact neurologic function and limit one's ability to thrive and survive. Traditionally, the treatment of low-grade gliomas mirrored recommendations for patients with higher-grade gliomas, such as glioblastoma. The diagnosis and categorization of primary brain tumors, including low-grade gliomas, were transformed in 2021 with an update of the World Health Organization classification system for pediatric and adult diffuse gliomas. In the pediatric population, there is recognition that a majority of low-grade gliomas have alterations in the mitogen-activated protein kinase (MAPK) pathway (BRAF mutations and rearrangements and other alterations in genes in this pathway); whereas in the adult population, mutations in isocitrate dehydrogenase (IDH), a key enzyme of the Krebs cycle, define diffuse low-grade glioma, namely oligodendroglioma and astrocytoma. Parallel to the advancements in diagnosis and tumor classification, the treatment has advanced to develop targeted therapies for patients with diffuse low-grade glioma. This review will highlight the molecular and genetic underpinnings of these tumors and how targeted therapeutic strategies led to the US Food and Drug Administration's approvals of combination therapy with dabrafenib and trametinib for pediatric patients with BRAF V600E mutant low-grade glioma; tovorafenib, a pan-RAF inhibitor, for pediatric BRAF mutant glioma; and vorasidenib, an inhibitor of mutant IDH1/2 enzymes, for patients with mutant IDH low-grade glioma. Integration of these targeted therapies into currently accepted treatment paradigms remains to be fully understood, along with the long-term impact on patient quality of life and prognosis.

Ketamine, an anaesthetic and sedative drug, has emerged as a promising therapeutic option for the management of chronic refractory pain, but is used off-label in this indication and known for its psychomimetic side-effects. The primary objective of this manuscript is to synthesize the current evidence on ketamine efficacy and safety for chronic refractory pain. Furthermore, it aims to identify critical knowledge gaps and propose a framework for its rational and safe clinical application. This narrative review analyses key findings from randomised and non-randomised clinical trials investigating ketamine's use in chronic pain conditions. It also examines existing clinical guidelines and expert consensus statements to reach a comprehensive clinical perspective. Current evidence demonstrates that ketamine can provide significant short-term analgesia, especially in neuropathic pain, and is fairly well-tolerated in patients with severe refractory pain. However, long-term data on efficacy, cognitive impact, addiction risk and optimal dosing are severely lacking. The intravenous route remains the most studied, while alternatives are still underexplored. Ketamine is not a first-line treatment for pain and must be prescribed and supervised by trained specialists within a structured standard of care. Its future role in pain management hinges on collaborative translational research to define optimal administration routes, establish phenotyping strategies (on the basis of pain type, comorbidities and comedication), and conduct long-term studies assessing mood, quality of life and cognitive function to ensure both efficacy and safety.

Background: Individuals with schizophrenia and comorbid substance use disorder (SUD) often experience poor treatment adherence, leading to worse clinical outcomes. However, high-quality evidence from randomized trials on the preferred mode of antipsychotic treatment in this population remains limited.

Aims: The aim was to examine whether long-acting injectable (LAI) antipsychotic treatment reduces the risk of all-cause discontinuation (ACD) compared with oral antipsychotics in individuals with early phase schizophrenia and comorbid SUD.

Methods: This study was a secondary analysis of the European Long-Acting Antipsychotics in Schizophrenia Trial (EULAST), a multisite, randomized, open-label trial conducted across multiple European healthcare settings. A total of 471 individuals with early phase schizophrenia were included in this secondary analysis, stratified by presence (n = 143) or absence (n = 328) of comorbid SUD. The observation period lasted 18 months. Participants were randomly assigned to second-generation LAI or oral second-generation antipsychotic treatment. The primary outcome was ACD, an indirect measure of treatment efficacy, defined as discontinuation of the initially assigned treatment for any reason. Hazard ratios (HRs) were estimated using Cox proportional hazards regression models, adjusted for relevant covariates.

Results: Among 143 individuals with schizophrenia and SUD, LAI treatment was associated with a 36% lower risk of ACD compared with oral antipsychotics (adjusted HR = 0.641; 95% CI, 0.438-0.938; P = 0.022). Kaplan-Meier curves showed longer median time to ACD for LAI treatment (158 days) versus oral antipsychotics (97 days). By contrast, among the 328 individuals without SUD, LAI treatment did not significantly reduce ACD risk (P = 0.282). Crude HRs were also assessed, replicating the adjusted hazard findings.

Conclusions: LAI antipsychotics significantly delayed treatment discontinuation compared with oral antipsychotics in participants with early phase schizophrenia and comorbid SUD but not in those without SUD. While these findings provide robust evidence supporting the use of LAIs in people with schizophrenia and comorbid SUD, future studies are needed to more precisely quantify the potential clinical benefits and tolerability of LAIs in this high-risk population. EULAST was registered at ClinicalTrials.gov (NCT02146547).

Cerebral aspergillosis is a well-recognized and particularly severe manifestation of invasive aspergillosis, primarily affecting immunocompromised individuals. The condition is associated with high morbidity and mortality, largely due to diagnostic challenges and limited treatment options. This review examines the epidemiology, risk factors, and diagnostic issues before focusing on drug treatment, including the pharmacokinetics and pharmacodynamics of antifungal agents in the central nervous system. Resistance to current antifungal therapies is also discussed, along with future research directions.

Background and objectives: Glaucoma is one of the leading causes of irreversible blindness worldwide and is increasingly recognized as a potential adverse effect of various pharmacological agents. It has been suggested that psychotropic medications influence glaucoma risk, but findings across studies have remained inconsistent. We aimed to clarify the association between psychotropic drug use and glaucoma through a Bayesian meta-analysis.

Methods: We conducted a systematic literature search up to December 2024. Studies that examined the relationship between psychotropic medications and glaucoma or intraocular pressure (IOP), and reported odds ratios (ORs), relative risks (RRs), or mean differences, were eligible. Bayesian random-effects models were applied using informative priors based on existing evidence for specific compounds. Estimates were reported as pooled ORs and Hedges' g with corresponding 95% credible intervals (CrIs).

Results: A total of 22 observational studies, including 293,228 users of psychotropic medications, met the inclusion criteria. Selective serotonin reuptake inhibitors (SSRIs) were associated with a modestly reduced risk of open-angle glaucoma (OR = 0.832, 95% CrI: 0.753-0.921) and a small but consistent reduction in IOP (Hedges' g = -0.332, 95% CrI: -0.487 to -0.179). Although tricyclic antidepressants were expected to have a direct causative effect, results did not show a significant association with glaucoma risk (OR = 1.466, 95% CrI: 0.700-3.338). Benzodiazepines were associated with a significantly increased risk of glaucoma (OR = 1.550, 95% CrI: 1.436-1.674), with consistent effects across both short- and long-acting compounds. Topiramate demonstrated a strong association with acute angle-closure glaucoma (OR = 3.930, 95% CrI: 1.784-11.465), in accordance with its known mechanism of inducing anterior displacement of the lens-iris diaphragm. Studies on methylphenidate, limited to pediatric populations, suggested a modest but non-significant reduction in IOP compared with untreated individuals. Evidence on antipsychotics was inconsistent, precluding any quantitative synthesis.

Conclusions: While some drug classes (e.g., benzodiazepines, topiramate) show a strong association with glaucoma, results for other compounds must be taken judiciously. The high level of heterogeneity, and the presence of special populations suggest caution when moving to real-life scenarios. Nonetheless, our results highlight the importance of ophthalmologic monitoring in patients prescribed with psychiatric drugs (e.g., benzodiazepines or topiramate), at risk for angle closure.

Background: Prolactin elevation associated with antipsychotic use significantly affects medication adherence and long-term treatment outcomes in patients with schizophrenia. The currently available data are insufficient to guide the monitoring and management of elevated prolactin levels in patients on antipsychotic medications. This study aimed to explore the patterns of prolactin level elevation associated with nine second-generation antipsychotics (SGAs) in a real-world setting and compare the associated risks.

Methods: This retrospective cohort study utilized data from the inpatient electronic medical records of a large mental health center in China from 2007 to 2019. The study included patients diagnosed with schizophrenia (ICD-10 criteria) who received SGA therapy and whose serum prolactin levels were measured. Exposures were the use of nine specific SGAs (amisulpride, risperidone, paliperidone, ziprasidone, olanzapine, perospirone, quetiapine, clozapine, or aripiprazole), including polytherapy and monotherapy. The primary outcome was incident prolactin elevation in patients during hospitalization. An adjusted stratified Cox proportional hazards regression analysis was used to compare the hazard ratios (HRs) of prolactin level elevation across the nine SGAs. In addition, a dose-response analysis of these SGAs was conducted using the defined daily dose (DDD) method. Dose categories were as follows: < 0.6 DDDs/day (low dose), 0.6 to < 1.1 DDDs/day (medium dose), and ≥ 1.1 DDDs/day (high dose).

Results: This study included 6489 patients with schizophrenia (mean [SD] age, 35.1 [14.2] years; 3396 males [52.3%]). Compared with the nonexposure, amisulpride (HR 2.76, 95% confidence interval [CI] 2.12-3.59), risperidone (HR 2.70, 95% CI 2.30-3.16), paliperidone (HR 1.84, 95% CI 1.37-2.46), and ziprasidone (HR 1.36, 95% CI 1.06-1.76) were associated with the highest risk of prolactin elevation. In contrast, quetiapine (HR 0.73, 95% CI 0.61-0.87), clozapine (HR 0.59, 95% CI 0.46-0.76), and aripiprazole (HR 0.30, 95% CI 0.23-0.37) were associated with the lowest risk. Amisulpride posed the highest risk among male patients, whereas risperidone posed the highest risk among female patients. Different types of dose-response associations were detected in seven SGAs.

Conclusion: This cohort study, conducted in an inpatient setting, identified different risks of prolactin elevation associated with SGAs, along with their dose-response curves. Sex and age must be considered when prolactin elevation is analyzed in patients with schizophrenia who are treated with SGAs.

Trial registration: ClinicalTrials.gov identifier: NCT04002258.