Clinical Neuropharmacology最新文献

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: 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: 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.

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.

Objectives: Postictal psychosis (PIP) is one of the most common psychoses for patients with epilepsy and is defined as psychotic symptoms presenting at least 1 week after a cluster of seizures. This case report illustrates an important example of a clinical presentation of postictal psychosis.

Methods: This case report identifies a 29-year-old male with a medical history of asthma and epilepsy who presented with multiple seizures and delirium. He has had multiple hospital admissions and ED visits over the past 1 to 2 years for recurrent seizure-like activity suggestive of PNES. On previous admissions for seizure-like activity, he has been intubated due to uncooperativeness. On this admission, he presented to the ED after multiple at-home seizures. In the ED, he became increasingly delirious with no return to baseline mental status between seizures. He was then intubated with bilateral wrist restraints for nonsensical speech and agitation.

Results: On day 4 in the ICU, he returned to baseline mental status. The patient was cooperative with medical treatment, alert, aware and attentive, and no longer agitated. The patient was able to remember the previous episode of seizure that led him to the ED. He was discharged on lacosamide 200 mg twice daily.

Conclusions: It is important to consider postictal psychosis as a diagnosis in a patient with epilepsy and changes in affect, mood, or the presence of delusions with no clear lucid interval to ensure timely and effective treatment and limit potential future complications.

Introduction: Montelukast has been associated with neuropsychiatric adverse events including mood disorders, suicidality, and anxiety disorders. Studies have shown a possible association between montelukast and delirium; however, most of this research has been focused on children and adolescents.

Case report: A 59-year-old female was admitted for management of spinal osteomyelitis, psoas abscess, epidural abscess, and bacteremia. On hospital day 19, she had new onset of encephalopathy, and workup revealed no clear etiology. On hospital day 41, her home dose of montelukast was stopped, and her mentation improved over the next several days. This improvement in cognition was sustained even though other medical factors continued to fluctuate.

Discussion: There were many factors that may have contributed to this patient's encephalopathy, but the temporal relationship between cessation of montelukast and improvement in her mentation suggests an association between this medication and her symptoms.

Conclusion: We present a hospitalized patient with acute encephalopathy, which resolved after discontinuing montelukast.

Objectives: Scraping is a nondrug treatment method of traditional Chinese medicine, which has potential advantages for treating nervous system disorders.

Methods: To confirm the clinical effect of drug therapy combined with scraping on primary PD, 120 patients with primary PD from March 2020 to March 2022 were chosen as the research objects. The control group (n=60) was treated with simple Traditional Western Pharmacological Treatment. In the combined treatment group (n=60), scraping therapy was added based on drug therapy. The MDS-UPDRS Ⅲ score, nonmotor symptom scale (NMSS) score, IL-6 and IL-1β levels, and clinical efficacy were compared between the 2 groups to determine the advantages of combined treatment. After 3 courses of treatment, the MDS-UPDRS Ⅲ scores, NMSS scores, and the expression of IL-1β and IL-6 were lower than those before treatment ( P <0.05).

Results: This result was also confirmed by analyzing the results at 1 month of follow-up. At the same time, the scores of MDS-UPDRS Ⅲ and NMSS and the levels of IL-1β and IL-6 in the combined treatment patients were lower than those in the control group ( P <0.05).

Conclusions: The combined treatment group's clinical effect was better after treatment than the control group. These findings represent preliminary evidence that scraping in combination with medication can be beneficial for the treatment of primary PD in the early to middle stages. Although it's promising to show overall improvements in motor dysfunction and nonmotor symptoms, further investigation with larger studies is needed to evaluate these effects further.