Clinical Neuropharmacology最新文献

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: Metformin is the first-line treatment for type 2 diabetes (T2D), yet interindividual variability in glycemic response remains poorly understood. Preclinical studies demonstrate that low-dose metformin lowers glucose via Rap1 signaling in ventromedial hypothalamic neurons, a pathway not required for sulfonylurea or thiazolidinedione efficacy. We investigated whether a common intronic RAP1A variant (rs7525578) modifies glycemic response to metformin in humans.

Methods: We analyzed men with T2D and HbA1c >6% in the UK Biobank who were prescribed metformin (n=7002), pioglitazone (n=587), or gliclazide (n=2654). Genotypes were obtained from imputed array data. The mean HbA1c by genotype (CC, CT, and TT) was compared within each drug cohort using 1-way ANOVA with Tukey post hoc tests. Effect sizes were quantified using eta-squared (η2).

Results: Among men prescribed metformin, rs7525578 was significantly associated with HbA1c (F=5.644, P=0.004, η2=0.0016). Heterozygotes (CT) had a higher mean HbA1c (7.52%) than CC homozygotes (7.39%, P=0.002). No significant associations were observed among pioglitazone (P=0.444) or gliclazide (P=0.233) users, and no effects were detected in women. The metformin-specific association remained after adjustment for combination therapy.

Conclusions: The RAP1A variant rs7525578 is associated with modestly higher HbA1c among men treated with metformin, but not with pioglitazone or gliclazide. This drug-specific pharmacogenetic association mirrors mechanistic data in mice, supporting a role for Rap1 signaling in metformin action and highlighting pathway-based approaches to T2D pharmacogenetics.

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, I ²=88%). The increase in the FAQ score was also smaller (MD=-0.82, 95% CI: -0.92 to -0.72, P <0.00001, I ²=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: This systematic review characterizes drug-induced aseptic meningitis (DIAM), a rare but clinically significant adverse drug reaction. The study synthesizes data from published case reports and case series to enhance diagnostic accuracy and guide management strategies.

Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Embase, Cochrane Library, ClinicalTrials.gov, and gray literature following PRISMA guidelines. Cases with detailed clinical and therapeutic data were included.

Results: A total of 98 reports involving 108 patients were analyzed. The mean patient age was 47 years, with a slight female predominance (55%). The most commonly implicated drugs were nonsteroidal anti-inflammatory drugs, antibiotics, and monoclonal antibodies. Symptoms typically included headache (78%), fever (65%), and neck stiffness (56%), with severe neurological manifestations in 17%. Cerebrospinal fluid analysis showed pleocytosis in 65% and elevated protein in 60%. Magnetic resonance imaging findings were variable. Drug discontinuation led to symptom resolution in all cases, with corticosteroids used in severe presentations.

Conclusions: DIAM mimics infectious meningitis, making early recognition critical. A thorough patient history, including medication exposure, is essential for diagnosis. This review underscores the need for clinician awareness to facilitate prompt identification and management. Future research should explore the immunopathogenesis and evidence-based treatment strategies for DIAM.

Background: There is no direct guidance on the optimal clopidogrel loading dose (LD) strategy when starting dual antiplatelet therapy (DAPT) in patients diagnosed with mild to moderate acute ischemic stroke (AIS) or high-risk transient ischemic attacks (TIA).

Objectives: Determine whether a specific clopidogrel LD influences the rate of recurrent stroke or bleeding events in patients with high-risk TIA or mild-moderate acute ischemic stroke.

Methods: This is a multicenter, retrospective cohort study that included patients with mild-moderate AIS or high-risk TIA, treated with either a clopidogrel LD of 300 mg or 600 mg. The primary outcome was the incidence of recurrent ischemic stroke or TIA. The secondary outcomes assessed bleeding events, intracranial hemorrhage, myocardial infarction, mortality, and length of stay.

Results: Recurrent stroke (P = 0.16) occurred in 3% and 7% of the 300 mg and 600 mg groups, respectively. Recurrent TIA (P = 0.58) occurred in 1% and 3% of the 300 mg and 600 mg groups, respectively. Severe bleeding (P = 0.09) and moderate bleeding (P = 0.67) between the 300 mg and 600 mg LD groups were insignificant.

Conclusion: This study represents the first evaluation of the effects of the clopidogrel LD on recurrent ischemic strokes and TIA. While the optimal duration of 21 days of DAPT therapy has been established and recommended in guidelines, the optimal loading dose has yet to be established. These results highlight the need for additional research to evaluate the true outcomes associated with the use of a 300 or 600 mg LD within this patient population.

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.

Objectives: Trichotillomania is a psychiatric disorder characterized by the compulsive pulling of one's own hair, eyelashes, or eyebrows. Depression and obsessive-compulsive disorder comorbidity is frequently observed in patients with trichotillomania. In this case series, we will report how a patient diagnosed with trichotillomania was successfully treated with transcranial magnetic stimulation (TMS) therapy in our clinic.

Methods: The TMS protocol was delivered using the MagVenture X100 device, with treatment intensity calibrated to 100% of each participant's motor threshold. Following the established treatment protocol for trichotillomania, patients received repetitive TMS at 1 Hz, with each train lasting 300 seconds and a 60-second intertrain interval, for a total of 1200 pulses per session. The bilateral supplementary motor area (SMA) was targeted as the site of stimulation.

Results: The efficacy of TMS in reducing hair-pulling behaviors in patients with trichotillomania was evaluated in a case series of 3 patients who underwent 20 TMS sessions. The findings demonstrated a significant reduction in hair-pulling behaviors post-treatment. According to the Massachusetts General Hospital Hair Pulling Scale (MGH-HP), over 50% improvement was observed in all patients.

Conclusions: The findings suggest that TMS may serve as a promising intervention for trichotillomania, warranting further exploration in larger, controlled trials. The utilization of the MGH-HP scale provided a robust measure for assessing behavioral changes, highlighting the potential of TMS in managing compulsive disorders.

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: Available treatment strategies for attention-deficit/hyperactivity disorder (ADHD) encounter significant limitations and, thus, necessitate novel therapeutic approaches. In this regard, this study investigated the effects of sulforaphane due to its neuroprotective, anti-inflammatory, and antioxidant properties.

Methods: Seventy ADHD outpatients aged 6 to 11 were equally assigned to receive methylphenidate (0.3 to 1.5 mg/kg/d) plus either sulforaphane 30 mg/d or matched placebo for 8 weeks. The teacher and parent ADHD rating scale (ADHD-RS) was used to assess their symptoms at baseline and weeks 4 and 8. The patients were also evaluated for side effects.

Results: Thirty-two patients in the sulforaphane group and 31 in the placebo group completed the study with comparable baseline demographic and clinical characteristics (Ps>0.05). There were significant time-treatment interaction effects on the ADHD-RS total, inattention, and hyperactivity-impulsivity scores rated by teachers (=0.245, 0.203, and 0.246, respectively) and parents (=0.265, 0.283, and 0.159, respectively). Affirmatively, their reductions were significantly greater in the sulforaphane group until the endpoint rated by teachers (Cohen ds=1.192, 1.055, and 1.220, respectively) and parents (Cohen's ds=1.344, 1.446, and 0.966, respectively). Better response to treatment (≥40% reduction in ADHD-RS total scores), robust improvement (≥50% reduction in ADHD-RS total scores), and remission (an ADHD-RS total score of ≤18) rates were obtained in the sulforaphane group until the endpoint (Ps<0.001). The side effect frequencies were comparable between the groups (Ps>0.05).

Conclusions: Sulforaphane adjunct to methylphenidate was beneficial for inattention, hyperactivity-impulsivity, and total symptoms of children with ADHD safely and tolerably.