Clinical Neuropharmacology最新文献

Objective: Intractable hiccups, which are hiccups that can last longer than 1 month, may be very debilitating for patients. With limited evidence and a lack of treatment guidelines, refractory hiccups can be difficult to manage. We aim to present a case of refractory idiopathic intractable hiccups treated with amitriptyline in conjunction with other medications shown to produce hiccups relief.

Materials and methods: The patient's electronic health record, direct patient care experiences, and a systematic literature review were used for this case report. We report a 53-year-old male patient with refractory idiopathic intractable hiccups. Treatment was improved with the addition of amitriptyline to his regimen of medications used for hiccups management. Medline and PubMed were searched using the key terms "hiccup" or "singultus" and "amitriptyline."

Results: The literature search yielded 3 unique articles, which resulted in 4 unique cases with intractable hiccups responding to amitriptyline therapy. In all cases, patients tried multiple medications before amitriptyline initiation.

Conclusions: This is the first case in over 30 years providing additional evidence for amitriptyline use in the relief of intractable hiccups. Amitriptyline may be more useful in patients experiencing intractable hiccups with comorbid mood disorders and in cases of suspected psychogenic origin.

Objectives: To prevent the adverse effects, deprescribing is a structured approach aimed at reducing anticholinergic burden and improving clinical outcomes, particularly in those with cognitive impairment. The objective of this study was to ascertain the impact of alterations in the total number of medications and the Drug Burden Index (DBI) score on cognitive tests and Activity of Daily Living (ADL) scores during a 6-month follow-up period in older patients with major neurocognitive impairment.

Methods: A total of 232 older patients with major neurocognitive impairment were enrolled in this study, which was retrospectively designed and followed up. The alterations in the total number of medications and the DBI scores were evaluated at baseline and at the end of the sixth month, which were compared with the changes in cognitive tests and ADL scores.

Results: Comparing baseline and end-of-six-month Mini-Mental State Examination (MMSE) scores revealed a significant decrease in MMSE scores in patients with elevated DBI scores and those with increased medication intake ( P =0.001 and P =0.034, respectively). A subsequent comparison of the change in MMSE score across the groups revealed a significant decrease only among the group with decreased DBI score (Δ=0.45±3.29 and P <0.001). In the linear regression analysis, a 1-unit increase in DBI score and drug number was associated with a decrease in MMSE scores ( B : -0.245 vs. -0.197).

Conclusions: The 6-month follow-up study demonstrated that deprescribing should prioritize the comprehensive evaluation of medication quantity and anticholinergic burden to enhance the efficacy of dementia care in older adults.

Background: Alzheimer disease is the most common cause of dementia and a major global health concern with a significant impact on elderly individuals and society. Gantenerumab, a monoclonal antibody that targets aggregated amyloid beta and removes Aβ plaques, could potentially treat Alzheimer disease.

Objectives: To systematically evaluate the safety of gantenerumab in patients with Alzheimer disease through a meta-analysis of available clinical studies.

Materials and methods: A comprehensive literature search was conducted, and six studies were included. Extracted data included study year, location, sample size, age, gender, gantenerumab dosage, APOE4 status, cognitive scores, CSF biomarkers, PET-SUVr, Changes in mental function, hippocampal volume, PET-SUVr, adverse effects, and mortality. Analysis was done using the R software.

Results: ADAS scores increased less in the gantenerumab group than in the placebo group (MD=-1.25, 95% CI:-1.40 to -1.10, P<0.00001, I²=88%). The increase in the FAQ score was also smaller (MD=-0.82, 95% CI: -0.92 to -0.72, P<0.00001, I²=87%). Hippocampal volumes significantly improved (right: MD=11.93, P=0.01; left: MD=12.24, P=0.008). However, gantenerumab was linked to higher rates of ARIA-E (OR=25.62, P<0.00001) and ARIA-H (OR=1.80, P<0.00001).

Conclusion: In conclusion, patients with Alzheimer disease treated with gantenerumab showed significant improvement in the ADAS score, FAQ score, hippocampal volume, and CSF biomarkers compared with those treated with placebo. However, the use of gantenerumab is associated with a higher incidence of ARIA-E and ARIA-H.

Objectives: Dihydropyridine calcium channel blockers (DHPCCBs) are widely employed in managing cardiovascular diseases. Although some studies suggest a potential link to psychiatric adverse events (PAEs), a systematic investigation is lacking.

Methods: Adverse event reports for seven DHPCCBs marketed in the United States were collected from the FDA Adverse Event Reporting System (FAERS). PAEs were extracted from these reports and then performed using disproportionality analysis.

Results: A total of 9164 PAEs associated with 7 DHPCCBs were identified, revealing 18 positive signal associations. For amlodipine, 18 positive signals were detected, with "completed suicide," "suicide attempt," and "mental status changes" being the most frequent. In contrast, nifedipine showed only 2 positive signals, which overlapped with amlodipine. No positive signals were found for the remaining five DHPCCBs. PAEs typically occur within the first 30 days of treatment. After adjusting for sex and age, 13 positive signals remained, 11 of which were related to suicidal behaviors.

Conclusions: The disproportionality analysis identified signal associations between DHPCCBs and PAEs. These findings should be interpreted as hypothesis-generating signals requiring further validation through controlled studies. Clinicians may consider monitoring psychiatric symptoms in high-risk patients, particularly given the conflicting evidence from previous studies.

Objectives: To report the first documented case of anxiety and depression related to superficial siderosis that responded to electroconvulsive therapy (ECT).

Methods: A 58-year-old man with traumatic superficial siderosis presented with panic attacks and major depressive disorder unresponsive to multiple pharmacologic trials. Brain MRI revealed hemosiderin deposition in cerebellar-limbic structures. A course of bifrontal brief-pulse ECT (8 sessions) was administered.

Results: After 8 sessions, the patient experienced full remission of panic attacks and functional recovery. The PHQ-9 score decreased from 21 to 7, and the GAD-7 score decreased from 19 to 6, with sustained improvement at the six-week follow-up.

Conclusions: This case suggests that ECT can safely and effectively target cerebellar-limbic circuit dysfunction in superficial siderosis and supports further investigation into neuromodulation for refractory psychiatric symptoms in this population.

Objectives: The APOΕ3 Christchurch (APOΕ3Ch) variant, characterized by an R136S substitution, confers protection against Alzheimer disease (AD) by reducing apolipoprotein E (ApoE) binding to heparan sulfate proteoglycans (HSPGs), thereby limiting tau propagation. While antibody-based strategies mimicking this variant have shown promise, small-molecule approaches to disrupt the ApoE-HSPG interaction remain underexplored.

Methods: We conducted a structure-guided molecular docking study targeting the ApoE HSPG-binding domain centered on Arg136, using AutoDock Vina within the SAMSON platform. The ligand benzene-1,3-disulfonic acid tiron, a small, anionic molecule with structural similarity to sulfated glycosaminoglycans, was docked to the cationic surface of ApoΕ3. Binding affinity, interaction pose, and root-mean-square deviation (RMSD) were assessed. Pharmacokinetic and toxicity predictions were performed using the pkCSM web server.

Results: Benzene-1,3-disulfonic acid exhibited strong binding to the Arg136-containing pocket with a top docking score of -5.93 kcal/mol and an estimated inhibition constant (Ki) of 44.6 µmol. The top-ranked pose revealed stabilizing electrostatic interactions and hydrogen bonds with Arg136 and neighboring basic residues. pkCSM profiling predicted poor oral absorption and limited blood-brain barrier permeability, but a favorable safety profile, including no predicted hepatotoxicity, hERG inhibition (cardiac toxicity), or mutagenicity.

Conclusions: These findings establish the feasibility of targeting the ApoE-HSPG interface with small molecules and identify benzene-1,3-disulfonic acid as a candidate Christchurch mimetic. While pharmacokinetic limitations preclude systemic use, intranasal delivery or ligand optimization may overcome brain access barriers. This study provides a foundation for developing novel small-molecule therapeutics to disrupt ApoE-mediated tau pathology in AD.

Herman Melville's Moby-Dick or The White Whale is a literary classic and historical account of 19th-century American whaling. Depictions of New Bedford, Nantucket, and life aboard the Pequod capture the whaling industry. Readers experience the whale hunt from sighting atop the ship's masts with shouts of "Thar she blows!" to excision of blubber and extraction of oil. Relationships are described, such as Ishmael, the novel's narrator, and Queequeg, a Pacific Islander harpooner reared as a prince among idolatrous cannibals. Captain Ahab's monomaniacal pursuit of Moby Dick, his hated nemesis, is the book's major plot. The novel's story is interrupted with descriptions of Sperm Whale anatomy and scattered observations of its behavior. Sperm Whales are social mammals, possessing the largest brain of all mammalian species, and capable of complex socio-cognitive computations and social communication. Sperm Whales use socially learned vocalization codas to "identify" matrilineally-defined social groups and "non-identity codas" to communicate between different social units sharing overlapping ocean habitats. Interestingly, Sperm Whales possess neurons morphologically similar to von Economo neurons (VENs) found in humans and other hominids. In higher primates, VENs support social behavior, higher socio-cognitive functions, and social communication. Thus, questions arise as to whether these morphologically similar "von Economo-like" neurons in Sperm Whales represent convergent evolution supporting complex socio-cognitive computations and social communication. In summary, Sperm Whales are an ethological model of social behavior, socio-cognitive functioning and social communication with translational relevance for man.

Objectives: This study aims to evaluate the efficacy of Botulinum toxin type A (BTX-A) in patients with postherpetic neuralgia (PHN) and to identify key prognostic factors associated with treatment response.

Methods: This prospective, randomized controlled trial enrolled patients with PHN from November 2023 to January 2024. Sixty patients were randomized into 2 groups: the BTX-A group (standard care plus BTX-A injections) and the control group (standard care alone). The primary outcome was the change in pain intensity, assessed using the Visual Analog Scale (VAS) before and after treatment. Secondary outcomes included changes in inflammatory factor levels, the use of analgesics, and the occurrence of adverse events.

Results: Compared with the control group, the BTX-A group showed significantly lower VAS scores and decreased inflammatory markers (P<0.001). After 1 month, the frequency of analgesic use decreased in both groups (P<0.001), but there was no difference between the groups. Multivariate logistic regression results showed that BTX-A was the only significant factor associated with pain reduction in PHN patients (P<0.001). Cox regression prognostic model results identified Gabapentin frequency, IL-6, and C-reactive protein as significant predictors of BTX-A treatment response (P<0.05). ROC analysis further showed that IL-6 was a strong predictor of BTX-A treatment response (AUC=0.804, P=0.034). Adverse events were rare and similar between groups.

Conclusions: BTX-A may offer benefit in relieving pain and reducing inflammation in PHN patients compared with standard treatment, and IL-6 may be a strong predictor of efficacy.

Objectives: High treatment costs remain a major barrier for people with epilepsy (PWE), leading to significant treatment gaps. At the University of Malaya Medical Centre (UMMC), levetiracetam (LEV) is sold at a retail price (self-paying), but some patients receive subsidization. This study aimed to study the impact of medication costs on adherence, dosing, and quality of life among self-paying versus subsidized patients.

Methods: This cross-sectional study was conducted at a tertiary care center in Kuala Lumpur, Malaysia. A structured questionnaire was used to assess the medication adherence, dosing, and quality of life among patients prescribed LEV, incorporating the Malaysian Medication Adherence Scale (MALMAS) and the Quality of Life in Epilepsy Inventory (QOLIE-31).

Results: Among the 172 respondents, those under the subsidization scheme (86, 50%) had a higher mean maximum dose (2055.2 mg vs. 1688.4 mg, P=0.013) and were less likely to reduce LEV intake due to cost concerns (7.7% vs. 23.7%, P=0.021). In the self-paying group, more patients had low adherence (23.3% vs. 17.6%), the seizure-free rate was lower (22.1% vs. 29.1%), and the mean QOLIE-31 score was lower (60.5 vs. 62.4) than the subsidized group, but the differences were not statistically significant.

Conclusions: Financial support is crucial in optimizing LEV dosing and adherence, with subsidized patients receiving higher doses and being less likely to reduce intake due to cost.

Objective: Due to the boom in the use of certain psychedelics in different neuropsychiatric conditions, the objective was to synthesize the available information on the use of psilocybin (a psychedelic) in the population with autism spectrum disorder (ASD; a developmental neuropsychiatric condition).

Methods: Scoping review. Question framework: Population: people with ASD-Concept: Psilocybin-Context: use, prescription, outcomes and pharmacological variables. The databases Medline (Pubmed), EMBASE, SCOPUS, LILACS, Web of Science and additional resources were searched until June 2024. Controlled and free terms combined with Boolean operators were used to find documents in English, Spanish and Portuguese. Screening was performed by title and abstract, full text and extraction independently by two reviewers. The analysis was descriptive and with emphasis on drug use. Protocol was registered in OSF (DOI code: 10.17605/OSF.IO/GPBVZ).

Results: Four studies were included. Indications for psilocybin prescription in ASD patients were related to cognitive rigidity, exacerbated fear, behavioral/social difficulties, and inability to generate mental imagery. Two studies mentioned specific psilocybin administration, identifying microdoses and dosing intervals. Results were grouped into increased empathy and emotionality/sociability, reduction of symptoms associated with their condition or comorbidity and changes compared with other populations. All the studies were of acceptable quality with low evidence level.

Conclusions: Descriptive findings of a therapeutic signal were observed in some subjects with ASD at low doses, not associated with toxic or disruptive effects. As restrictions on psilocybin use are lifted, studies with a higher level of evidence should be conducted.