Clinical Neuropharmacology最新文献

Objective: N -methyl- d -aspartate (NMDA) receptor antagonism in the central nervous system has been described. More data are needed regarding its clinical impact on the cardiovascular system. In this study, we assess the cardiovascular impact of NMDA receptor antagonism with amantadine on patients with primary or secondary parkinsonism.

Methods: To conduct this retrospective cohort analysis, we queried the TriNetX Global database on January 13, 2024 to identify patients 18 years old or older with Parkinsonism between January 2003 and December 2023 and divided them into 2 groups based on amantadine use. We conducted propensity score matched (PSM) analysis for sociodemographics, cardiovascular comorbidities and medications, and antiparkinsonian agents.

Results: After PSM, relative risks (RRs) were used to compare outcomes over a 5-year follow-up period. After PSM, both groups had 28,461 patients each. Amantadine use in patients with parkinsonism was associated with a 13% reduction in 3-point major adverse cardiovascular and cerebrovascular events (RR: 0.867, 95% confidence interval [CI]: 0.836-0.900, P < 0.0001), as well as a significantly lower risk of all-cause mortality (RR: 0.877, 95% CI: 0.844-0.912, P < 0.0001), AMI (RR: 0.790, 95% CI: 0.709-0.881, P < 0.0001), and cerebral infarction (RR: 0.868, 95% CI: 0.791-0.952, P = 0.0026). It was also associated with lower rates of heart failure, atrial arrhythmias, bradycardia, atrioventricular blocks, ventricular tachycardia, syncope and collapse, and peripheral edema. Amantadine use was however associated with a higher risk of orthostatic hypotension.

Conclusions: NMDA antagonism with amantadine in patients with primary or secondary parkinsonism is associated with a significantly reduced risk of all-cause mortality, AMI, cerebral infarction, heart failure, and arrhythmias.

Objectives: This cohort study aimed to better understand the relationship between attention deficit hyperactivity disorder (ADHD) severity predating the COVID-19 outbreak, in children with ADHD, and the severity of ADHD symptoms during the COVID-19 lockdowns.

Methods: Age and clinical data, including ADHD-Rating Scale scores, of 30 children and adolescents with ADHD, aged 7-18 years, were collected from medical files, for the 6-month period that predated the COVID-19 outbreak. During the COVID-19 lockdowns, the children's ADHD severity was evaluated by the mothers using the Clinical Global Impression-Severity scale (CGI-S). The correlations of CGI-S scores with age and above-mentioned ADHD-Rating Scale scores that were collected before COVID-19 were then assessed.

Results: Significant correlation was found between age of participants and CGI-S scores ( P = 0.034). Additionally, participants who continued ADHD pharmacological treatment ( P = 0.02) and used remote clinical treatment ( P = 0.008) demonstrated lower mother reported CGI-S scores.

Conclusions: In children with ADHD, younger age, ongoing stimulant-treatment and ongoing remote visits with a caretaker, seem to correlate with lower ADHD-symptom severity during COVID-19 lockdowns.

Objectives: Malnutrition is common in dementia patients and can lead to poor outcomes. Also, these patients are often prescribed medications with sedative and anticholinergic effects for various reasons. Thus, we aimed to explore the relationship between drug burden index (DBI), anticholinergic burden (ACB), and nutrition status in community-dwelling older adults with dementia.

Method: A total of 415 outpatients with dementia, evaluated by Mini Nutrition Assessment, and whose drug information is registered are included in study. DBI score was calculated by summing the scores of regularly used anticholinergic and/or sedative drugs taken for at least four weeks prior to admission.

Results: The mean age of participants was 77.4 ± 6.3 years, and the majority were female (64.3%). The most prevalent type of dementia (71.6%) was Alzheimer's dementia. The prevalence of malnutrition is 23.6%. Polypharmacy was present in approximately half of the participants (47.5). In total, 57.0% of the participants were using anticholinergic drugs, and 77% of the participants had drug exposure. In the fully adjusted multivariate models, an increase in DBI score raised the risk of "malnutrition" by 2.12 times (OR, 2.12; 95% CI, 1.15-4.01; P = 0.02), whereas no relationship was determined between ACB score and "malnutrition" (OR, 1.21; 95% CI, 0.98-1.49; P = 0.07).

Conclusions: Older adults with dementia are frequently exposed to drugs with sedative and anticholinergic properties. Considering the relationship between DBI and malnutrition, these drugs and doses should be optimized to prevent malnutrition and its adverse outcomes in this vulnerable population.

Objectives: Intractable headaches are a common occurrence in patients experiencing an aneurysmal subarachnoid hemorrhage (aSAH). Utilization of multimodal pain management regimens has become the standard of care for the treatment of acute and chronic pain. The primary objective of this study was to evaluate the use of a new multimodal pain regimen for headache in patients who have experienced aSAH.

Methods: This was an Institutional Review Board approved study evaluating the use of a multimodal pain regimen for treatment of headache pain in 104 patients who experienced aSAH in a neuro intensive care unit. Patients diagnosed with aSAH from January 2017 to December 2019, which was prior to the implementation of the multimodal pain regimen, were compared to aSAH patients from March 2020 through 2022, who were treated with the multimodal pain regimen. The primary endpoint was morphine milligram equivalent usage during the first 5 days of admission before and after the implementation of the multimodal pain regimen. The secondary endpoints were pain scores during the first 5 days of admission.

Results: As compared to those who did not receive the aSAH headache pathway (n = 39, premultimodal regimen), those who did receive the pathway (n = 65, multimodal regimen) received significantly more morphine milligram equivalents over the first 5 days of admission (30.0 [0, 97.5] vs 82.5 [15, 135]); P = 0.0053. There was no difference in the median average pain score.

Conclusions: The MM pain pathway did not reduce the total morphine equivalents utilized for the treatment of aSAH-associated headache.

Objectives: The relationship of older antiseizure drugs with congenital malformations has been known for many years. Studies are mostly limited to major malformations and few studies have investigated minor malformations. In recent years, the long-term cognitive and behavioral effects of these drugs have also come to the fore. The aim of our study was to evaluate the incidence of major and minor congenital malformations and neurodevelopmental outcomes in children prenatally exposed to levetiracetam (LEV), lamotrigine (LTG), and carbamazepine (CBZ) monotherapy.

Methods: This was a prospective observational study conducted in two university hospital epilepsy centers. It included 32 pregnant women who were continuously treated with LEV, LTG, or CBZ from conception throughout pregnancy. Children were followed up from birth until 18 months. Neurodevelopmental outcomes were evaluated with the Ages and Stages Questionnaire and Denver Developmental Screening Test.

Results: Eighteen of the patients were on LEV, 10 were on LTG, and 4 were on CBZ. Diaphragmatic hernia was detected in a child. At least one minor anomaly was observed in 58.1% of the patients. More than 80% of children were normal in the Ages and Stages Questionnaire.

Conclusions: The risk of major congenital malformations is lower with newer antiseizure drugs. We found a high incidence of minor ones. However, because the population prevalence of minor malformations is also variable, more studies are needed to confirm the results. Neurodevelopmental outcomes were favorable with LTG and LEV and slightly unfavorable with CBZ. Longer-term follow-up with large groups of children is required to reach more reliable results.

Objective: Eslicarbazepine acetate (ESL) is a third-generation antiseizure medication (ASM) approved for the treatment of focal seizures. Because of the delayed approval of ESL in Asian countries, there is limited information on the clinical usefulness of ESL in the Asian population. We performed a retrospective analysis of retention rate and seizure outcomes for ESL treatment in Korean epilepsy patients.

Methods: A 2-year retrospective observational study was conducted, in which 160 epilepsy patients (82 males; age range, 17-81 years) were treated with ESL. The starting dose of ESL was 400 mg/d, and optimal dose adjustments were made based on individual clinical responses. We analyzed efficacy and tolerability during the 2-year follow-up period.

Results: This study found that the overall retention rate was 81.5% at 1 year and 76.1% at 2 years. The retention rate at 2 years was 86.5% in the monotherapy group and 69.8% in the adjunctive therapy group. Adverse events, mostly dizziness/somnolence and skin eruption, were reported in 38 (23.8%) of patients, leading to discontinuation of ESL in 24 patients. Laboratory hyponatremia was noted in 2 patients, but neither of them experienced symptomatic hyponatremia. Switching from other dibenzazepine ASMs, carbamazepine and oxcarbazepine, was performed in 31 patients (19.4%), and most patients (26 of 31 patients, 83.9%) continued to take ESL until their last follow-up.

Conclusions: Our study demonstrates that treatment with ESL results in favorable retention rates and tolerability among Korean epilepsy patients, which is consistent with data from Western countries. Additionally, our findings suggest that ESL-induced hyponatremia is infrequent and largely asymptomatic when used cautiously and switching from other dibenzazepine ASMs may be a useful option for selected patients.

Objective: This study aimed to explore the changes in brain functional activity before and after acceptance and commitment therapy (ACT) treatment in patients with major depressive disorder (MDD) and the correlation between brain functional changes and clinical symptoms.

Methods: We recruited 12 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for MDD. Patients underwent clinical assessments and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after ACT intervention. The amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) maps were obtained after data preprocessing, and the ALFF/fALFF values of patients were extracted and compared. Pearson correlation analysis was used to analyze the correlation between fALFF/ALFF values and clinical symptoms.

Results: A total of nine MDD patients completed the study. The results showed that, following treatment, there was an improvement in psychological flexibility, along with a reduction in depressive symptoms. Additionally, MDD patients exhibited increased ALFF in the left inferior frontal gyrus and triangle, as well as increased fALFF in the left medial superior frontal gyrus following symptom remission. Pearson correlation analysis showed that fALFF of the left medial superior frontal gyrus at baseline was negatively correlated with the rate of Acceptance and Action Questionnaire, Second Edition (AAQ-II), change ( r = -0.76, P < 0.05).

Conclusions: We observed alterations in spontaneous activity in regions of the prefrontal cortex in MDD patients following ACT, providing preliminary relevant insights into understanding the neural mechanisms underlying the treatment of MDD by ACT.

Objective: This study aimed to investigate the effects of preoperative low-dose esketamine and dexmedetomidine nasal administration on the incidence of postoperative emergence delirium in children undergoing fiber bronchoscopy.

Methods: A total of 129 patients, of any gender, aged 1 to 6 years, with ASA grades I and II, who were scheduled for fiber bronchoscopy, were randomly divided into three groups (n = 43) using a random number table method: 1.0 mg/kg of esketamine, 1.0 μg/kg of dexmedetomidine, and an equal volume of normal saline (group control). The respective dose of the drug or normal saline was rapidly instilled through both nostrils using a 1-mL syringe. The primary outcome measure was the incidence of emergence delirium. The secondary outcome measures included postoperative pain intensity, time to awaken and open eyes in the postanesthesia care unit, incidence of postoperative adverse behavior, hemodynamics, and duration of stay in the postanesthesia care unit.

Results: A total of 126 patients completed the study, and compared with the group control (48.78%), the 1.0 mg/kg esketamine (7.14%) and 1.0 μg/kg dexmedetomidine (18.6%) had a lower incidence of postoperative emergence delirium ( P < 0.01), as well as lower postoperative pain intensity ( P < 0.01). However, compared with the group control, the 1.0 μg/kg dexmedetomidine had a prolonged time to awaken and open eyes in the postanesthesia care unit ( P < 0.05). The duration of hemodynamics, oral secretion volume, and stay in the postanesthesia care unit were similar among the three groups.

Conclusions: The findings suggest that low-dose esketamine and dexmedetomidine can reduce the incidence of emergence delirium.

Objectives: Proton pump inhibitors (PPIs) are widely used to reduce gastric acid levels and are often prescribed with antiplatelet agents in patients with stroke. However, the interactions and differences among various PPIs remain unclear. Therefore, we aimed to compare the differences between esomeprazole and ilaprazole in patients with and without stroke. We also compared the effects of aspirin use in the ilaprazole group.

Methods: We retrospectively analyzed 580 patients with neurological disorders who responded to the Gastroesophageal Reflux Disease Questionnaire at a tertiary hospital between October 2020 and December 2023. Comparative and subgroup analyses were performed using the chi-squared test, Fisher's exact test, and t tests.

Results: In the overall patient cohort, patients using esomeprazole had lower rates of dyslipidemia and lower white blood cell, hemoglobin, triglyceride, and low-density lipoprotein cholesterol levels, compared to ilaprazole users. However, among patients with stroke, esomeprazole users had higher rates of atrial fibrillation and lower triglyceride, hemoglobin, and uric acid levels, compared to ilaprazole users. In the ilaprazole group, nonaspirin users were younger and had fewer stroke episodes and higher total cholesterol levels, compared to aspirin users. Furthermore, patients using antiplatelet and PPI therapies and antacids had lower hemoglobin levels, compared to antacid nonusers.

Conclusions: Significant differences existed between esomeprazole and ilaprazole users and among ilaprazole users based on aspirin use. Therefore, careful monitoring of PPI use with antiplatelet agents and antacids is recommended in patients with neurological disorders. However, further research is needed to understand these differences and their clinical impact.