Clinical Neuropharmacology最新文献

Objectives: Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of dopaminergic medications. Given the metabolic and functional reserves and the comorbidities in older adults, NMS may show an atypical course.

Methods: The medical records of patients with neurodegenerative diseases leading to dementia between 2013 and 2020 were reviewed for the diagnosis of NMS. Demographic and clinical characteristics of the patients were obtained from the records of laboratory parameters, management, and length of stay.

Results: Fifteen older adults (19 episodes) diagnosed with NMS were included. The median age was 76 years, and 5 were female. Ten of 15 NMS patients were atypical. Most of them had an infection accompanying NMS. Neuroleptic malignant syndrome was caused by antidopaminergic agents (5 antipsychotics, 1 metoclopramide) in 6 episodes and discontinuation of a dopaminergic agent, l -DOPA, in 12 episodes. In 1 patient, it was associated with simultaneous use of domperidone and amantadine withdrawal. Rigidity in NMS due to l -DOPA discontinuation was higher than in those due to antipsychotic use ( P = 0.027). Two of our patients needed intensive care, and 1 died.

Conclusions: This study highlights the high frequency of atypical NMS and the importance of early recognition of this potentially fatal syndrome, which can accompany neurodegenerative diseases and infections in older adults.

Objective: Fatigue is a chronic and debilitating symptom of many long-term neurological conditions (LTNCs). Although methylphenidate provides some promise in alleviating fatigue in other clinical groups, little work has explored its potential utility within LTNCs. The current systematic review and meta-analysis evaluates the utility of methylphenidate for symptoms of fatigue in LTNCs.

Methods: Five databases (PsycINFO, MEDLINE, Embase, Scopus, and Cochrane Library) were searched for relevant articles from their inception to February 2022. A purpose-developed evaluation tool was used to assess each study's research quality (QuEST:F).

Results: Of the 1698 articles identified, 11 articles were included within this review (n = 370). Meta-analytical findings reported an overall significant benefit of methylphenidate for symptoms of fatigue across a mixed neurological sample ( g = -0.44; 95% confidence interval, -0.77 to -0.11). Subgroup analyses identified a significantly greater benefit ( P < 0.001) of methylphenidate for fatigue in LTNCs with static pathogenic trajectories (eg, traumatic brain injury) (number needed to treat = 2.5) compared with progressive conditions (eg, multiple sclerosis) (number needed to treat = 40.2).

Conclusions: Methylphenidate may pose an effective intervention for the treatment of fatigue in a number of LTNCs. Nonetheless, given the quality of the current evidence base, there exists a clear need for further robust assessment of the utility of methylphenidate-with a focus on subgroup-specific variability.

Objectives: Randomized controlled trials (RCTs) have established the efficacy of galcanezumab, an antibody binding calcitonin gene-related peptide (CGRP) ligand, in the preventive treatment of migraine. The objective was to summarize real-world data evaluating galcanezumab in the preventive treatment of migraine, to complement RCT results with evidence observed in clinical practice.

Methods: A literature search was conducted to identify real-world studies evaluating galcanezumab in the treatment for patients with migraine.

Results: Twenty-five studies were identified; some only evaluated galcanezumab, and others used pooled data from multiple anti-CGRP antibodies. The studies recruited diverse patient populations, including patients who had failed multiple prior preventive therapies. Treatment was associated with significant reductions from baseline in monthly migraine days and monthly headache days by 4.3 to 12.9 and 3.1 to 13.9, respectively. These values were numerically greater than those reported in most galcanezumab RCTs. Significant decreases from baseline were evident within the first month of treatment, and efficacy was maintained throughout the follow-up periods, ranging from 3 to 12 months. Galcanezumab was also associated with improvements in other efficacy end points, including decreased headache pain intensity, reduction in analgesic use, and improvements in daily functioning and quality of life. Functionality scores, as assessed by the Migraine Disability Assessment Scale questionnaire, decreased by 27 to 75 points from baseline at 3 to 12 months. Galcanezumab was associated with a low discontinuation rate and higher rates of persistence compared with standard migraine preventive treatments.

Conclusions: The results provide complementary data that galcanezumab is effective across the diverse patient populations observed in routine clinical practice.

Objective: In this case report, we discuss the rare manifestation of prolonged neuromuscular blockade in a patient with history of small cell lung cancer and undiagnosed Lambert-Eaton myasthenic syndrome (LEMS) who had previously received succinylcholine for general anesthesia without incident but subsequently exhibited prolonged neuromuscular blockade during a laparoscopic procedure. We aimed to emphasize the importance of reversal agent safety and precision as well as vigilant perioperative and postoperative care.

Methods: We used the patient's electronic medical record, direct patient care experiences, and comprehensive literature review for this case report.

Results: Sugammadex was administered with mild improvement. Suspecting undiagnosed LEMS, neostigmine was administered, yielding satisfactory muscle strength and successful extubation. In retrospect, the patient reported history of weakness when lifting weights that improved upon exertion.

Conclusions: Sugammadex is an efficient and effective agent for reversal of neuromuscular blockade. However, proper monitoring of the depth and recovery of blockade is imperative to when using sugammadex with optimal safety and precision in all patients. Perioperative care teams must remain vigilant with a high index of suspicion for neuromuscular junction pathology to properly plan perioperative care for patients at risk, especially those with small cell lung cancer who may have undiagnosed LEMS.

Objectives: Acute traumatic brain injury is one of the most common causes of death and disability. Reduction in the level of consciousness is a significant complication that can impact morbidity. Glasgow Coma Scale (GCS) is the most widely used method of assessing the level of consciousness. Neurostimulants such as amantadine and modafinil are common pharmacologic agents that increase GCS in patients with brain trauma. This study aimed to compare the effectiveness of these 2 drugs.

Methods: This systematic review obtained articles from Google Scholar, PubMed, Scopus, Embase, and MEDLINE databases. Extensive searches were conducted separately by 4 individuals in 3 stages. Ultimately, 16 clinical trials, cohort studies, case reports, and case series articles were obtained after reading the title, abstract, and full text and considering the exclusion criteria. The data of the final article were entered into the analysis table. This study was registered with PROSPERO (registration number CRD42022334409) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: Amantadine seems to be associated with a higher overall response rate. In contrast, modafinil is associated with the most remarkable change in GCS score during treatment. However, the number of clinical trials with high quality and sample size has not been satisfactory to compare the effectiveness of these 2 drugs and their potential side effects.

Conclusions: The authors recommend additional double-blind clinical trials are needed to be conducted with a larger sample size, comparing amantadine with modafinil to delineate the efficacy and adverse effects, both short and long term.

Background: Intravenous application of amantadine sulfate induces a rapid improvement of motor behavior in patients with Parkinson disease.

Objectives: To determine efficacy of daily infusion of 200 mg amantadine sulfate on scored motor symptoms and performance of standardized movement sequences with components of low and high cognitive efforts.

Methods: Thirty-one participants received infusions of amantadine sulfate in addition to their previous stable drug regimens on 3 consecutive days. Motor symptoms of upper limbs were determined with selected items of the part motor examination of the Unified Parkinson's Disease Rating Scale. Instrumental tasks were executed under cued conditions before and after the infusions.

Results: Scored motor symptoms and components with a need for a higher cognitive load became better. Performance of motion series, characterized by an automated set with low cognitive efforts, did not improve.

Conclusion: Our trial outcomes suggest that the amantadine has a positive impact on cognitive abilities, drive, and vigilance, all of which are necessary for carrying out of higher brain functions.

Objective: Depressive disorders constitute a series of debilitating diseases. This study investigated the therapeutic effect of agomelatine (AG) combined with aerobic exercise (AE) on patients with moderate-severe depression (MSD) and the changes of the serum C-reactive protein (CRP) level in patients after treatment as well as its significance.

Methods: A total of 178 MSD patients were randomly assigned to the AG group (N = 90) and AG + AE group (N = 88). The severity of depressive disorders and anhedonia was assessed using the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores. The serum CRP level in MSD patients was detected by turbidity assay. Patients were defined as remitters, responders, and nonresponders according to the HAM-D 17 score, and the treatment efficacy was analyzed, followed by evaluation of the serum CRP level in patients with different treatment responses. Finally, the adverse reactions of patients during treatment were statistically analyzed.

Results: After treatment, the HAM-D, Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores and the serum CRP level of the 2 groups were reduced, and changes in the AG + AE group was more significant than that in the AG group. The clinical efficacy of the AG + AE group was better than that of the AG group. After treatment, the serum levels of CRP in remitters and responders were reduced, but not significantly in nonresponders. The incidence of adverse events in the AG + AE group was lower than that in the AG group.

Conclusion: AG + AE reduced the serum level of CRP in MSD patients and had good therapeutic effects on MSD patients.

Objectives: This study was aimed at investigating the prevalence of obesity in drug-naive first-episode (DNFE) patients with schizophrenia and its association with metabolic parameters, psychopathological symptoms, and cognitive function.

Methods: We collected general information on 411 DNFE schizophrenia patients and divided them into obese and nonobese groups according to body mass index (BMI). Glucolipid metabolic parameters of patients were collected. Positive and Negative Syndrome Scale was performed for assessing patients' psychopathological symptoms. Cognitive function was observed and evaluated in both groups. Pearson correlation analysis was applied to assess factors related to BMI, while we conducted multiple stepwise regression analysis for determining risk factors for obesity.

Results: Obesity occurred in 60.34% of DNFE patients with schizophrenia, whereas the obese group had notably higher BMI value and waist-to-hip ratio than the nonobese group ( P < 0.05). Obese patients had markedly higher levels of blood glucose, insulin, apolipoprotein B, total triglycerides, low-density lipoprotein cholesterol, and total cholesterol versus nonobese patients ( P < 0.05). Besides, the disease severity and cognitive function were dramatically lower in the obese group. Results of multiple stepwise regression analysis demonstrated negative symptoms, low-density lipoprotein cholesterol, triglycerides, and blood glucose levels as the risk factors for comorbid obesity in DNFE patients with schizophrenia.

Conclusions: The detection rate of obesity was high in DNFE patients with schizophrenia, and there was an intrinsic association between obesity and glucolipid metabolism, clinical symptoms, and cognitive function among them. Our study will provide a theoretical foundation for the diagnosis of obesity in DNFE patients with schizophrenia and the development of effective early interventions.

Abstract: In persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing history of narcolepsy type 1 complaining of recurrent short sudden episodes of whole-body paralysis, with preserved consciousness and memory. Episodes started an hour after her family invited her to celebrate Mother's Day. One week prior, patient had abruptly discontinued duloxetine. Cataplectic episodes resolved within 24 hours after resumption of duloxetine and treatment of hypokalemia. Status cataplecticus has been reported after withdrawal of venlafaxine, fluoxetine, and clomipramine. This is the first report of status cataplecticus due to duloxetine withdrawal. We review the pathophysiology of antidepressant withdrawal-induced status cataplecticus. In persons with narcolepsy type 1, physicians discontinuing any antidepressant should counsel on adverse effects of antidepressant withdrawal and reduce the dose in tapering manner.

Objectives: The aim of this study was to determine how amantadine was used in a movement disorders clinic and how effective it was.

Methods: A chart review over a 2-month period in 2022 of all patients in a movement disorders clinic who had ever taken amantadine was undertaken.

Results: One hundred six charts were included. Amantadine was initiated primarily for tremor and secondly for l -dopa-induced dyskinesias (LIDs). Sixty-two percent of tremor patients improved and tolerated amantadine; 74% of those with LID improved and tolerated the drug. Hallucinations occurred in 23%. Initiating amantadine as a syrup allowed a more conservative titration than other formulations, which is attractive given the high percentage of hallucinations that may occur. Patients who tolerated drug initiation were generally kept on the drug for many years.

Conclusions: Amantadine should be considered as adjunctive therapy in Parkinson disease patients with refractory tremor as well as for LIDs.