Clinical Neuropharmacology最新文献

Objectives: This is a case series and a review of the literature of therapeutic outcomes of botulinum toxin (BT) injections for anterocollis.

Methods: Data collected included gender, age, age at onset, muscles targeted, and doses injected. Routine forms were filled out during each visit: Patient Global Impression of Change, Clinician Global Impression of Severity, Tsui scale. The effect duration and side effects (SEs) of the previous treatment were noted.

Results: We described 4 patients (3 men, 13 visits) with anterocollis, as primary postural abnormality of the neck, emphasizing the therapeutic response to BT injection. Mean age at onset was 75.3 ± 7.0 years, age at first injection was 80.7 ± 3.5 years. The mean total dose per treatment was 290.0 ± 95.6 units. Patient Global Impression of Change with any grade of favorable effect was reported in 27.3% of the treatments. In objective assessment, Global Impression of Severity and Tsui scores did not show a consistent tendency of improvement. Neck weakness was prevalent in 18.2% of the visits of the anterocollis group while no other SEs were noted. We found 15 articles describing experience with BT for anterocollis in 67 patients (19 in deep and 48 in superficial neck muscles).

Conclusions: This case series describes the poor outcome of BT treatment for anterocollis, with low efficacy and bothersome SE. Levator scapulae injection for anterocollis is not effective and is highly associated with head drop and should perhaps be abandoned. Injection to the longus colli might give some benefit in non-responders.

Objectives: Medical cannabis (MC) has recently garnered interest as a potential treatment for neurologic diseases, including Parkinson's disease (PD). A retrospective chart review was conducted to explore the impact of MC on the symptomatic treatment of patients with PD.

Methods: Patients with PD treated with MC in the normal course of clinical practice were included (n = 69). Data collected from patient charts included MC ratio/formulation changes, PD symptom changes after initiation of MC, and adverse events (AEs) from MC use. Information regarding changes in concomitant medications after MC initiation, including opioids, benzodiazepines, muscle relaxants, and PD medications, was also collected.

Results: Most patients were initially certified for a 1:1 (∆ 9 -tetrahydrocannabinol:cannabidiol) tincture. Eight-seven percent of patients (n = 60) were noted to exhibit an improvement in any PD symptom after starting MC. Symptoms with the highest incidence of improvement included cramping/dystonia, pain, spasticity, lack of appetite, dyskinesia, and tremor. After starting MC, 56% of opioid users (n = 14) were able to decrease or discontinue opioid use with an average daily morphine milligram equivalent change from 31 at baseline to 22 at the last follow-up visit. The MC was well-tolerated with no severe AEs reported and low rate of MC discontinuation due to AEs (n = 4).

Conclusions: The MC may improve motor and nonmotor symptoms in patients with PD and may allow for reduction of concomitant opioid medication use. Large, placebo-controlled, randomized studies of MC use in patients with PD are required.

Objective: Research points to exercise having a positive effect in fighting relapse and use of drugs of abuse. Through conducting this research, differences have been observed in the effects of exercise on drug abuse between sexes. Many of the studies found that exercise tends to cause a more profound effect in blocking drug relapse or reinstatement in males when compared with females.

Methods: Our hypothesis is that these differences in response to drugs of abuse after an exercise regimen could in part be attributed to variations in testosterone levels between males and females.

Results: Testosterone has been shown to have a modulatory impact on the dopaminergic activity in the brain, causing an effect on the brain's response to drugs of abuse. Exercise has demonstrated a causal effect on increasing testosterone levels in males, whereas drugs of abuse decrease testosterone levels in males.

Conclusions: Thus, exercise raising testosterone levels in males helps to decrease the dopaminergic response in the brain to drugs of abuse causing attenuation to drugs. To find sex-specific exercise treatments for drugs of abuse, it is important to continue researching exercise's efficacy against drugs of abuse.

Abstract: Cabergoline is a dopamine 2 receptor agonist used as first-line treatment of pituitary prolactinomas. Here, we describe the case of a 32-year-old woman with a pituitary prolactinoma who was treated with cabergoline for 1 year, during which time she developed delusions. We also discuss the use of aripiprazole to mitigate the psychotic symptoms, while maintaining the efficacy of cabergoline treatment.

Objectives: The aim was to develop a prototype of an application (app) that identifies the significance of discovered genes for further consideration in the treatment plan of patients with epilepsy (precision medicine).

Methods: MEDLINE was systematically searched for related publications from inception to April 1, 2022. The following search strategy was implemented (title/abstract): "epilepsy" AND "precision" AND "medicine." The following data were extracted: genes, phenotypes associated with those genes, and the recommended treatments. Two other databases were searched to cross-check the retrieved data and add to the data: https://www.genecards.org and https://medlineplus.gov/genetics . Also, the original articles of the identified genes were retrieved. Genes with specific treatment strategies (ie, any specific drug to be selected or to be avoided and also any other specific therapies [eg, diets, supplements, etc]) were selected.

Results: A database of 93 genes, which are associated with various epilepsy syndromes and for which specific treatment strategies have been suggested, was developed.

Conclusions: A Web-based app (a search engine) was developed accordingly that is freely available at http://get.yektaparnian.ir/ , GET (Gene, Epilepsy, Treatment). When a patient comes to the clinic with a genetic diagnosis and a specific gene is identified, the physician enters the gene name into the search box, and the app shows whether this genetic epilepsy needs a specific treatment. This endeavor would benefit from input by experts in the field, and the Web site should be developed more comprehensively.

Objective: Major depressive disorder (MDD) often coexists with hypertension (HYT). DNA methylation has elicited vital functionality in their development. Angiotensin-converting enzyme (ACE) is a vital enzyme in blood pressure. This study investigated the effect of ACE methylation on depression and HYT severity in patients with comorbid MDD and HYT (MDD + HYT).

Methods: A total of 119 patients (41 men, 78 women, average age: 56.8 ± 9.1 years) with MDD + HYT were enrolled, with 89 healthy subjects (29 men, 60 women, average age: 57.4 ± 9.7 years) were enrolled. The Hamilton Depression Rating Scale-17 and self-rating depression scale scoring scales were used to assess the depression degree of patients, serum ACE methylation level in MDD + HYT patients was measured by means of bisulfite sequencing polymerase chain reaction, with subsequent analysis of the diagnostic efficacy of ACE methylation for MDD + HYT. The independent risk factors for sMDD + HYT were explored.

Results: Serum ACE methylation levels were significantly increased in MDD + HYT patients. The area under the curve of serum ACE methylation level for accurate diagnosis of MDD + HYT was 0.8471, and the cut-off value was 26.9 (sensitivity 83.19%, specificity 73.03%). ACE methylation was an independent risk factor for sMDD + HYT (P = 0.014; odds ratio, 1.071; 95% confidence interval = 1.014-1.131).

Conclusion: The elevated serum ACE methylation level (P < 0.001) in patients with MDD + HYT elicited definite diagnostic values for MDD + HYT, and ACE methylation level was independently correlated with sMDD + HYT (P < 0.05).

Objectives: Major depressive disorder (MDD) is a chronic and debilitating disease influenced by inflammatory processes in the brain. Some evidence has represented the adding curcumin as a complementary regime to the standard medication in treating depressive symptoms. However, limited clinical trials have been conducted on the antidepressants effects of curcumin in MDD patients. Therefore, this study aimed to investigate the effectiveness of curcumin in the treatment of MDD.

Methods: In a randomized, double-blind clinical trial, 45 severe MDD patients referred to the psychiatric clinic of Ibn-e-Sina Hospital, Mashhad, Iran, during 2016 were selected. Patients were randomly divided into 2 groups who received sertraline plus curcumin or placebo at a dose of 40 mg/d for 8 weeks. The patients were evaluated using Beck Anxiety and Depression Surveys at the beginning of the study, fourth, and eighth weeks by a psychiatry resident. The data analyzed aiding SPSS software.

Results: While depression and anxiety significantly decreased during the 8 weeks of the study, there was no significant difference between the 2 groups (P > 0.05). However, the anxiety score was lower in the intervention group. Moreover, no severe adverse events were observed in all patients.

Conclusions: Adding 40 mg/d of SinaCurcumin to sertraline as a routine medical regimen did not improve the depression and anxiety levels in severe MDD patients. However, the anxiety score was lower in the intervention group than in the placebo receiver, which suggests curcumin may have a more effect on anxiety.

Objectives: Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up.

Methods: This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021.

Results: A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1-3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening (P = 0.843, Mann-Whitney U test) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects.

Conclusion: Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.

Objectives: Levodopa (LD) administered with dopa decarboxylase inhibitor is predominantly metabolized in the periphery by catechol- O -methyltransferase (COMT) to 3- O -methyldopa (3-OMD). Catechol- O -methyltransferase inhibition can improve treatment outcomes by decreasing variability in circulating LD concentrations. Opicapone is a once-daily COMT inhibitor approved in the US adjunctive to carbidopa (CD)/LD in patients with Parkinson disease experiencing "OFF" episodes. This study aimed to evaluate the pharmacokinetics and pharmacodynamics of once-daily opicapone 50 mg adjunctive to CD/LD in patients with stable Parkinson disease.

Methods: Once-daily opicapone 50 mg was administered the evenings of days 1 to 14. Participants were randomized to receive CD/LD (25/100 mg) every 3 or 4 hours (Q3H or Q4H). Participants received Q3H or Q4H CD/LD on days 1, 2, and 15 and their usual CD/LD regimen on other days. Serial blood samples were collected to determine plasma opicapone, LD, and 3-OMD concentrations and erythrocyte soluble COMT (S-COMT) activity. The effects of opicapone on S-COMT, LD, and 3-OMD were assessed. Mean (SD) values are presented.

Results: Sixteen participants were enrolled. At steady-state (day 14), opicapone Cmax (peak plasma concentration) and AUC 0-last (area under the curve-time curve) were 459 ± 252 ng/mL and 2022 ± 783 ng/mL·h, respectively. Maximum COMT inhibition was 83.4 ± 4.9% of baseline on day 14. After opicapone administration, LD total AUC, peak concentration, and trough concentration increased; peak-to-trough fluctuation index decreased. Correspondingly, 3-OMD total AUC, peak concentration, and trough concentration decreased.

Conclusions: Adding once-daily opicapone 50 mg to LD resulted in marked and extended COMT inhibition, which increased systemic exposure to LD. These changes translated into higher trough concentrations and decreased peak-to-trough fluctuations for LD.

Abstract: Oral levodopa is the most effective treatment for Parkinson disease, but OFF periods emerge over time. Gastrointestinal dysfunction and food effects impact levodopa absorption, contributing to unpredictable control of OFF periods. Inhaled levodopa powder (Inbrija) is approved for on-demand treatment of OFF periods in patients receiving oral levodopa-dopa decarboxylase inhibitors. The 84-mg dose is administered via a breath-actuated inhaler. It provides pulmonary delivery of levodopa to the systemic circulation and is taken when a patient has an OFF period in between doses of regular oral levodopa medication. The pivotal SPAN-PD trial in patients experiencing OFF periods on oral dopaminergic therapy showed that levodopa inhalation powder 84 mg produced significant improvement in Unified Parkinson Disease Rating Scale Part III score, as measured 30 minutes postdose at week 12, and improvement was seen as early as 10 minutes. More patients in the levodopa inhalation powder group turned ON within 60 minutes of treatment and remained ON at 60 minutes than in the placebo group. Levodopa inhalation powder can also be used to treat early-morning OFF periods and, when used for up to 12 months, produced no clinically significant differences in pulmonary function compared with an untreated cohort. Levodopa inhalation powder 84 mg increased plasma levodopa concentration rapidly and with less variability than oral levodopa/carbidopa (25/100 mg). Most common adverse event associated with levodopa inhalation powder is cough, found in ~15% of patients in the SPAN-PD trial; otherwise, reported adverse events were consistent with those known to be associated with oral levodopa.