Clinical Neuropharmacology最新文献

Objective: Bipolar disorder (BD) patients remain symptomatic. As lipid-lowering drug targets have been linked to BD risk, we used Mendelian randomization (MR) to assess their therapeutic potential.

Methods: We conducted MR analyses utilizing genetic variants associated with lipid traits and variants in genes encoding the protein targets of various classes of lipid-lowering drugs. The specific drug classes investigated included 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-Like 1 (NPC1L1). To determine the effects on BD risk, we meta-analyzed MR estimates for regional variants using data from 2 large sample sets. The genetic variants were weighted based on their associations with low-density LDL-c. For lipid-modifying drug targets that exhibited suggestive significance, we further used eQTL data. In addition, we performed colocalization analysis to assess genetic confounding.

Results: Genetically proxied inhibition of PCSK9 was strongly associated with a lower risk of developing BD (IVW MR OR=0.82, 95% CI=0.74-0.91, P=2.12e-04, SD reduction in LDL-c) in PGC data set, and in UK Biobank data set (P=0.03). Sensitivity analyses yielded no statistically significant evidence of bias arising from pleiotropy or genetic confounding. The posterior probability for a common causal variant between PCSK9 inhibition and BD risk was 80.8%.

Conclusions: It was observed that PCSK9 showed significant associations with BD risk. These findings indicate that PCSK9 inhibitors have the potential to serve for the treatment of BD.

Objective: This case report describes the clinically underrecognized manifestation of delayed-onset akathisia induced by cariprazine occurring 10 weeks after treatment initiation. The secondary objective was to discuss potential pharmacokinetic and pharmacodynamic mechanisms of the drug-induced side effects.

Methods: A retrospective review of the patient's medical and psychiatric history was performed in addition to a comprehensive literature review.

Results: A 42-year-old female with bipolar disorder and generalized anxiety disorder presented to the emergency department on 3 separate occasions with severe restlessness and insomnia, commonly attributed to her previous history of anxiety. Although initial treatment with lorazepam provided subjective symptom relief, the underlying cause persisted. Psychiatry consultation led to a diagnosis of antipsychotic-induced akathisia and administration of diphenhydramine resulted in rapid improvement. The offending agent, cariprazine, was discontinued, resulting in sustained symptom resolution.

Conclusions: This case highlights the challenge of distinguishing akathisia from primary anxiety disorders, in addition to considering this diagnosis beyond the initial treatment period. Akathisia symptoms most commonly present within 4 weeks of initiation or titration of antidopaminergic treatment. However, this timeline may be delayed with cariprazine due to its pharmacokinetic and pharmacodynamic properties.

Objectives: Treatment-resistant depression (TRD) is a serious public health burden in the United States and comes with an extremely high suicide risk relative to the general population. Lamotrigine, though approved for use only in bipolar disorder, has been found to augment the effects of an antidepressant in treatment-resistant individuals. However, studies showing an antisuicidal effect of lamotrigine in the TRD population are limited. The objective of this paper is to describe a case of a 58-year-old male with TRD and chronic suicidality who was treated with lamotrigine augmentation of the serotonin-norepinephrine reuptake inhibitor, duloxetine, and experienced a sustained clinical improvement of his suicidality.

Methods: Clinical changes in depression and suicidality after initiation of lamotrigine are presented.

Results: The patient experienced a brief improvement in depression and sustained improvement in suicidality for 2 years.

Conclusions: While there remains insufficient evidence in the literature for a clinical recommendation of the use of lamotrigine for suicidality in the TRD population, our case report introduces the novel possibility of an antisuicidal effect of lamotrigine at the individual level. We suggest clinicians consider its use when other, more robust treatments for suicidality have failed.

Objectives: Long COVID (LC) is associated with neuropsychiatric disorders (anxiety, depression, and fatigue), an insulin resistance (IR) state, and inflammatory biomarkers. In the present study, IR and inflammatory biomarkers were used to predict the scores of neuropsychiatric disorders.

Methods: The ELISA method was used for measurements of IL-1β, IL-10, IL-18, C-reactive protein (CRP), and insulin in the sera of LC and control subjects. Glucose levels were measured spectrophotometrically. The Hamilton scale for anxiety (HAMA) and depression (HAMD), and the fibro fatigue scale (FFtotal) were used for scoring the neuropsychiatric symptoms. The homeostatic model assessment 2 (HOMA2) calculator was used for computing IR (HOMA2IR), insulin sensitivity (HOMA%S), and pancreatic β-cell function (HOMA%B).

Results: LC is associated with neuropsychiatric diseases (FFtotal, HAMAtotal, and HAMDtotal), insulin resistance biomarkers, and inflammatory biomarkers. These biomarkers are correlated with each other in LC patients. The building of principal components for inflammatory biomarkers (PC_Inflam) and insulin resistance (PC_IR) creates vectors that could surpass individual biomarkers in neuropsychiatric issue prediction in liver cirrhosis patients. Out of the biomarkers investigated, PC_Inflam is the most important predictor for FFtotal (sensitivity and specificity of 71.4%), HAMAtotal (sensitivity and specificity of 70%), and HAMDtotal (sensitivity of 71.2% and specificity of 71.5%).

Conclusions: Neuropsychiatric disorders can be predicted by the principal component built from inflammatory biomarkers (IL-1β, IL-10, IL-18, and CRP). In contrast, PC_IR has a lower predictive value for the neuropsychiatric disorders compared with PC_Inflam. These results indicated the significant role of inflammation in the main symptoms of LC.

Objective: This study is designed to expound the risk factors for symptomatic exacerbation of acute ischemic stroke due to anterior circulation large vessel occlusion (AIS-AC-LVO), aiming to inform strategies for preventing disease progression.

Methods: Two hundred patients with AIS-AC-LVO were retrospectively analyzed. Baseline data included demographics, vascular risk factors, stroke subtype, admission NIHSS score, core infarct volume, blood pressure, serum lipid profile, homocysteine (Hcy), and neutrophil count. Perioperative variables comprised onset-to-door time (ODT), door-to-procedure time (DPT), intravenous thrombolysis, bridging therapy, occlusion site, anesthesia type, procedure duration, intraoperative rescue interventions, recanalization status, and postoperative sedative use. Patients were classified into exacerbated or nonexacerbated groups according to 7-day neurological outcomes. Univariate analysis, multivariate logistic regression, and receiver operating characteristic (ROC) curve analysis were conducted.

Results: Baseline NIHSS score, LDL-C, Hcy, neutrophil count, ODT, procedure duration, core infarct volume, and recanalization rate differed significantly between groups ( P <0.05). Multivariate analysis identified elevated Hcy (OR=2.109, 95% CI: 1.499-2.965), prolonged ODT (OR=1.574, 95% CI: 1.181-2.098), longer procedure duration (OR=1.049, 95% CI: 1.014-1.085), and higher LDL-C (OR=5.398, 95% CI: 1.385-21.036) as independent predictors of symptom worsening. ROC analysis showed strong predictive performance for Hcy (AUC=0.866) and ODT (AUC=0.769) (both P <0.001).

Conclusions: Elevated Hcy, elevated LDL-C, and prolonged ODT and procedure duration independently predict short-term neurological deterioration.

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: 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.

Objectives: Refractory epilepsy remains a major therapeutic challenge, affecting approximately one third of patients with persistent seizures despite treatment with multiple antiseizure medications (ASMs). Cenobamate (CNB), a novel ASM, has shown promising efficacy in both clinical trials and real-world settings. This observational study aimed to evaluate the efficacy, tolerability, and retention of CNB in adults with drug-resistant focal-onset seizures in routine clinical practice.

Methods: A cross-sectional analysis was conducted on 40 patients treated with CNB at Santa Lucía University Hospital between 2022 and 2024. Seizure frequency, CNB discontinuation, adverse effects, and concomitant ASMs were assessed at 1, 3, and 6 months.

Results: We found a significant reduction in mean monthly seizures, from 48.4 at baseline to 12.1 at 6 months ( P =0.0001). At 6 months, 48% of patients had a ≥50% seizure reduction, and 27% were seizure-free. In addition, CNB treatment was associated with a significant reduction in Defined Daily Doses and the number of concomitant ASMs. A 95% retention rate was observed among patients after 6 months on CNB treatment. Only 2 patients discontinued CNB, neither due to adverse effects. Reported adverse effects were mild to moderate, with somnolence (13%) and dizziness (10%) being the most common.

Conclusions: These findings reinforce CNB as a valuable treatment option for patients with focal-onset drug-resistant epilepsy, supporting its integration into clinical practice. Further research is needed to evaluate long-term outcomes and its potential role as a first-line therapy.

Background: Parkinson's disease (PD), the second most common neurodegenerative illness, is thought to have impacted 9.4 million people globally in 2020. The causation framework for Parkinson's disease is a combination of genetics, age, and environment. Iron chelators have been studied as potential treatment agents for Parkinson's disease (PD) because they can reduce oxidative stress and iron accumulation. Deferiprone (DFP) is one such drug.

Objectives: To systematically review and analyze available clinical studies assessing the efficacy and safety of deferiprone in patients with Parkinson's disease, with particular focus on motor outcomes, iron accumulation, and adverse effects.

Materials and methods: A comprehensive search was conducted in PubMed, Scopus, clinicaltrials.gov.in, and Web of Science databases, and a total of 3 studies were included and reviewed. The studies' baseline data included the first author's name, the year of the study, the place of the study, the number of subjects and controls, the mean age, gender, dosage, and route of DFP, the Estimated years of Disease (EYO), the MDS-UPDRS score, the PDQ-39 score, the MOCA score, the MMSE score, MRI T2 changes, and serum ferritin levels. Data regarding adverse effects and deaths were also extracted. A pooled analysis of the collected data was performed using R Studio.

Results: The MDS-UPDRS score increased less in the test group's patients than in the placebo group (SMD=-0.69, 95% CI=-5.64 to 4.25, P =<0.00001, I 2 =98%). However, there was no significant difference between the 2 groups in the serum ferritin levels and the MRI T2 changes in caudate, nigra, pallidum, and putamen.

Conclusion: Deferiprone shows potential in slowing motor symptom progression in Parkinson's disease, although its impact on brain iron levels remains inconclusive. Further large-scale, long-term studies are warranted to establish its clinical efficacy and safety.