Clinical Neuropharmacology最新文献

Objective: Phenibut is a widely available gamma-aminobutyric acid B receptor agonist. When taken chronically, phenibut causes dependence and subsequent withdrawal if stopped. Baclofen, a gamma-aminobutyric acid B receptor agonist structurally related to phenibut, has been used to manage phenibut withdrawal (PW), although baclofen doses for PW are not well defined and may exceed Food and Drug Administration-approved doses. Little data described outcomes from baclofen use.

Methods: This case details a patient who experienced a seizure while on baclofen 10 mg thrice daily as monotherapy for PW and highlights a potential risk of underdosing baclofen as monotherapy in the management of PW.

Results: A man in his early 30s with anxiety, depression, and substance use disorder presented to the emergency department by family for lethargy and confusion starting earlier that day. He had been using 25-30 g of phenibut daily for the past 6 months. On arrival, he was hypertensive, tachycardic, tachypneic, and lethargic. The patient received 1 mg of intravenous lorazepam and was admitted to the hospital for presumed PW. His symptoms improved overnight, and he was discharged on 10 mg of baclofen thrice daily. He returned 28 hours later after having a seizure and required intensive care admission in addition to multimodal drug therapy.

Conclusions: Phenibut use is rising, and treatment options for PW, such as baclofen, warrant additional study. Potential risks of underdosing baclofen if used as monotherapy in PW may include seizures as withdrawal progresses. Baclofen's role in therapy may be more appropriate as an adjunct than a cornerstone of therapy. Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk.

Objectives: The reference range for lacosamide (LCM) has been updated from 1 to 10 mg/L to 10 to 20 mg/L. Historically, LCM range was defined from trough-level measurements, but the newer ranges were obtained from peak-level measurements. The purpose of the study was to evaluate the relationship between LCM plasma levels higher than 10 mg/L and the incidence of adverse effects.

Methods: This was a single-center, retrospective, observational study of adult outpatients with epilepsy who were prescribed LCM and had LCM serum concentrations (LCM-SCs) >10 mg/L on drug-fasting samples, measured from June 2017 to December 2020.

Results: A total of 55 LCM-SC samples corresponding to 44 patients (25 women [57%]) were analyzed. The median age was 47 (39-61) years. The median LCM-SC was 13.4 (11.2-17.8) mg/L. Adverse effects were reported in 18 patients (41%). Forty-eight percent (21 of 44) of patients required an LCM dose reduction, with a mean LCM-SC of 16.0 (13.2-18.1) mg/L, whereas, in the remaining patients (23 of 44), LCM dose was not modified, with a mean LCM-SC of 12.2 (10.7-14.2) mg/L ( P = 0.0244). Forty-one percent (18 of 44) of patients reported adverse effects related to LCM, with a mean LCM-SC of 15.6 (12.7-18.4) mg/L, whereas, in the remaining patients (26 of 44), adverse effects did not occur, with a mean LCM-SC of 12.6 (10.7-16.5) mg/L ( P = 0.0495).

Conclusions: The 10 to 20 mg/L reference range clearly increases toxicity in patients treated with LCM. Adjusting the reference range upper limit to 12 mg/L with a routine therapeutic drug monitoring program is suggested, to achieve a reasonable probability of efficacy and decrease toxicity.

Objectives: This report discusses the emergence, clinical appearance, and treatment of the rare entity Capgras syndrome (CS) in an adolescent diagnosed with autism.

Methods: After a brief introduction to the CS, we conduct a detailed description of the case and review, after a search on the PubMed database, the known pathophysiology, psychiatric disorders associated with the onset of this syndrome, and the management of CS.

Results: Capgras syndrome generally emerges during the course of delusional disorder, schizophrenia, or mood disorders, and for reasons such as neurological, infectious, or endocrinological diseases, drug intoxications, or deprivation. We encountered no previous reports of CS developing during the course of autism. There are no prospective studies concerning the treatment of the syndrome. However, antipsychotic drug use is primarily recommended in treatment. Antipsychotic drug therapy was therefore planned for the treatment of delusion, a psychotic symptom, in this case. The atypical antipsychotic aripiprazole was used based on the presence of accompanying diagnosis of autism, and the patient's body mass index and age. A relatively high dose of aripiprazole was required for the first psychotic attack in our patient. However, a good level of response was achieved within the expected time frame. In addition, no marked adverse effects were observed.

Conclusions: Aripiprazole seems to be an effective and well-tolerated antipsychotic drug in the treatment of CS accompanying autism.

Objectives: The aim of this study was to assess the safety and efficacy of perampanel in patients with refractory essential tremor (ET).

Methods: We recruited patients from our movement disorders clinic with the diagnosis of severe refractory ET, and perampanel 4 mg at night was initiated.Assessments were conducted at baseline and after 1 month of treatment with perampanel 4 mg/d. Details about tolerance and effectiveness were collected. Clinical evaluation was conducted with the Fahn-Tolosa-Marín scale, and statistical analysis was carried out with Wilcoxon matched pairs signed rank test.

Results: This study included 18 patients with severe ET (11 females, 7 males; mean age: 75.1 ± 12.03 years; mean duration of ET: 17.4 ± 17.03 years). Perampanel significantly improved patients' average score with refractory ET ( P ≤ 0.0001). This improvement has been occasionally quite relevant. However, a proportion of patients did not tolerate perampanel because of several adverse effects including dizziness, ataxia, irritability, and instability.

Conclusions: Perampanel had a markedly positive antitremor effect in patients with ET and could be an alternative treatment. However, this drug is not devoid of adverse effects.

Objectives: The present research aimed to evaluate the effect of adding l -carnitine to risperidone in treating children and adolescents with autism spectrum disorder (ASD).

Methods: In this randomized controlled clinical trial study, 50 ASD children and adolescents were divided into 2 groups: those receiving l -carnitine and risperidone (n = 25) and those receiving placebo and risperidone (n = 25). Treatment continued for 8 weeks, and participants were assessed at the beginning of the study, in the fourth and eighth weeks, by the Aberrant Behavior Checklist (ABC).

Results: l -Carnitine add-on therapy reduced the scores of total ABC and subscales of restlessness, lethargy and social isolation, stereotypic behavior, and inappropriate speech at weeks 4 and 8. There was a significant difference between the 2 groups in the score of total ABC and subscale of lethargy and social isolation.

Conclusions: According to the present study, adding l -carnitine to risperidone improves ASD symptoms.

Objectives: Intravenous thrombolysis and mechanical endovascular thrombectomy are recommended for patients whose stroke onsets are within the first 6 hours; however, patients beyond this time window have very limited options. Dl-3-n-butylphthalide (NBP) and human urinary kallidinogenase (HUK) have shown potential clinical benefits in the treatment of acute ischemic stroke (AIS) patients. This research aims to investigate the efficacy and safety of NBP combined with HUK in the treatment of ischemic stroke patients.

Patients and methods: We reviewed the 215 AIS patients registered in the database of the Fifth Affiliated Hospital of Sun Yat-sen University from April 2019 to October 2020. Among them, 65 patients received NBP sodium chloride injection treatment, 55 patients received HUK treatment, and 95 patients received NBP sodium chloride injection combined with HUK treatment. The recovery of neural function was evaluated by the National Institutes of Health Stroke Scale (NIHSS), and the recovery of daily function was evaluated by the modified Rankin Scale (mRS). The NIHSS and mRS scores after the 7-day treatment, 6-month independency rate (6-month mRS score ≤1), and related factors were compared among the 3 groups. The safety was monitored by recording adverse events.

Results: The NIHSS and mRS scores of 7-day and 6-month treatment in the NBP combined with HUK group were lower than the monotherapy ( P < 0.05). In addition, the NBP combined with HUK treatment achieved an independency rate of 82.1%, whereas NBP and HUK treatments achieved only 53.8% and 63.6%, respectively ( P < 0.001). Binary logistic regression showed that NBP combined with HUK therapy treatment could lead to a 5.28 times higher rate of patients' 6-month independency after AIS occurrence. No serious adverse events occurred in both the combined therapy and monotherapy.

Conclusions: Dl-3-n-butylphthalide combined with HUK is safe to treat AIS patients. It can significantly improve the neural function and the 6-month recovery of AIS patients.

Objective: Botulinum toxin type A is widely used for the treatment of spasticity, focal dystonia, hemifacial spasm, hyperhidrosis, strabismus, chronic migraine, and also cosmetic purposes. Therapeutic use is commonly effective and safe. However, if toxin enters the vascular space and gets through to peripheral cholinergic nerve terminals, it may lead to iatrogenic botulism.

Method: We presented a patient who is diagnosed as iatrogenic botulism and treated with antitoxin at the 15th day of the exposure.

Results: After the antitoxin administration, dramatical response to the treatment was observed.

Conclusions: In this report, we want to evaluate a new case of iatrogenic botulism and emphasize the importance of antitoxin administration regardless the timing of the exposure for patients with progressing paralysis.

Objective: Lance-Adams syndrome is a rare but devastating disorder characterized by rest, action, and stimulus-sensitive myoclonus after cardiorespiratory arrest. We aimed to present a case of multidrug-resistant Lance-Adams syndrome that was successfully treated with oral phenobarbital therapy.

Method and results: We report a previously healthy 11-year, 6-month-old boy was referred to our pediatric intensive care unit because of severe hypoxic ischemic brain injury due to sudden cardiorespiratory arrest. On the 15th day of hospitalization, he developed myoclonic jerks involving his limbs, trunk, and eyes. Despite many antiseizure medications in different combinations, myoclonic jerks persisted. Then, phenobarbital was started, and myoclonic jerks disappeared the next day. At the final evaluation, additional phenobarbital treatment was continued for 6 months and the patient remained myoclonus-free during this time.

Conclusions: To the best of our knowledge, this case is the first report describing significant improvement with phenobarbital in a patient with multidrug-resistant Lance-Adams syndrome. We suggest that phenobarbital is an effective option and should be kept in mind in patients with multidrug-resistant Lance-Adams syndrome.

Objectives: The present review describes stroke pathophysiology in brief and discusses the spectrum of available treatments with different promising interventions that are in clinical settings or are in clinical trials.

Methods: Relevant articles were searched using Google Scholar, Cochrane Library, and PubMed. Keywords for the search included ischemic stroke, mechanisms, stroke interventions, clinical trials, and stem cell therapy.

Results and conclusion: Stroke accounts to a high burden of mortality and morbidity around the globe. Time is an important factor in treating stroke. Treatment options are limited; however, agents with considerable efficacy and tolerability are being continuously explored. With the advances in stroke interventions, new therapies are being formulated with a hope that these may aid the ongoing protective and reparative processes. Such therapies may have an extended therapeutic time window in hours, days, weeks, or longer and may have the advantage to be accessible by a majority of the patients.