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Tremor and Other Hyperkinetic Movements... 2024Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval,...
BACKGROUND
Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus.
METHODS
Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies.
RESULTS
The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus.
CONCLUSION
Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.
Topics: Humans; Male; Amantadine; Multiple System Atrophy; Ocular Motility Disorders; Aged
PubMed: 38737300
DOI: 10.5334/tohm.832 -
Medicine Apr 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
OBJECTIVE
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
METHODS
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
RESULTS
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
CONCLUSION
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
Topics: Humans; Alzheimer Disease; Donepezil; Galantamine; Memantine; Molecular Docking Simulation; Cholinesterase Inhibitors; Rivastigmine
PubMed: 38640313
DOI: 10.1097/MD.0000000000037799 -
Brain & Spine 2024TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on... (Review)
Review
INTRODUCTION
TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness. It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition. The current study will synthesize the current available evidence and show the effect of Amantadine in functional improvement after TBI.
RESEARCH QUESTION
Does Amantadine have an effect on functional improvement of TBI patients?
MATERIAL AND METHODS
This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores.
RESULTS
Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores.
DISCUSSION AND CONCLUSION
Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.
PubMed: 38465280
DOI: 10.1016/j.bas.2024.102773 -
Clinical NeuropharmacologyAcute 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...
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.
Topics: Humans; Modafinil; Consciousness; Brain Injuries, Traumatic; Amantadine; Brain Injuries; Randomized Controlled Trials as Topic
PubMed: 37962310
DOI: 10.1097/WNF.0000000000000577 -
Frontiers in Pharmacology 2023Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still...
Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.
PubMed: 37426819
DOI: 10.3389/fphar.2023.1199794 -
Neurology Aug 2023Comprehensive guidelines for the diagnosis, prognosis, and treatment of disorders of consciousness (DoC) in pediatric patients have not yet been released. We aimed to... (Review)
Review
BACKGROUND AND OBJECTIVES
Comprehensive guidelines for the diagnosis, prognosis, and treatment of disorders of consciousness (DoC) in pediatric patients have not yet been released. We aimed to summarize available evidence for DoC with >14 days duration to support the future development of guidelines for children, adolescents and young adults aged 6 months-18 years.
METHODS
This scoping review was reported based on Preferred Reporting Items for Systematic reviews and Meta-Analyses-extension for Scoping Reviews guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3 blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated.
RESULTS
On November 9, 2022, 2,167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the past 5 years. Overall, 2,161 individuals met the inclusion criteria; female patients were 527 of 1,554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%) and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near-Coma Scale, Level of Cognitive Functioning Assessment Scale, and Post-Acute Level of Consciousness scale. EEG, event-related potentials, structural CT, and MRI were the most frequently used instrumental techniques. In 29/53 (54.7%) cases, DoC improvement was observed, which was associated with treatment with amantadine.
DISCUSSION
The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence and have limited validity and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to the diagnosis, prognosis, and treatment of pediatric DoC.
Topics: Adolescent; Humans; Female; Child; Consciousness; Consciousness Disorders; Coma; Prognosis; Randomized Controlled Trials as Topic
PubMed: 37308301
DOI: 10.1212/WNL.0000000000207473 -
Cureus Apr 2023Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective... (Review)
Review
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective serotonin reuptake inhibitor (SSRI) or serotonin reuptake inhibitor (SRI) treatment along with cognitive behavioral therapy (CBT). Nearly 25%-30% of OCD patients do not respond to SSRIs. Glutamatergic agents are currently being studied for the treatment of OCD due to the glutamatergic pathway in the brain, related to OCD, and the role of the cortico-striato-thalamic circuit (CSTC). This review assesses the clinical effectiveness of N-methyl-D-aspartate (NMDA) antagonists, ketamine/esketamine, memantine, and amantadine, for adult patients with OCD. Inclusion criteria include human studies published within the last 15 years, with patients diagnosed with OCD, aged over 18 years, with only psychiatric comorbidities, and full-text articles. Papers that included interventions other than CBT, exposure with response prevention (ERP), and SSRI/SRI were excluded. Articles were searched for using PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online, GeorgiA LIbrary LEarning Online, EBSCO Information Services, OpenAthens, Multidisciplinary Digital Publishing Institute, and Google Scholar databases, last searched on December 2, 2022. The risk of bias was assessed using Cochrane Risk of Bias tools, the Scale for the Assessment of Narrative Review Articles (SANRA) checklist for literature reviews, and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for quasi-experimental studies. Results were presented and synthesized by Excel spreadsheet analysis. The database search yielded 4,221 articles, which was cut down to 18 articles by inclusion/exclusion criteria, including duplications. 80% of the ketamine studies resulted in a significant reduction of obsessions and compulsions based on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and each of the memantine and amantadine studies displayed clinical effectiveness, also. Limitations include the small number of amantadine studies and the limited availability of other NMDA receptor (NMDAR) antagonist-focused studies. This systematic review shows that ketamine is an effective drug for the treatment of non-refractory, mild to moderate OCD, and memantine and amantadine are effective augmentation agents for the treatment of mild to severe OCD.
PubMed: 37213965
DOI: 10.7759/cureus.37833 -
Therapeutic Advances in Rare Disease 2022The rare inherited autosomal recessive disease Friedreich ataxia (FA) causes progressive neurodegenerative changes and disability in patients. A systematic literature... (Review)
Review
OBJECTIVES
The rare inherited autosomal recessive disease Friedreich ataxia (FA) causes progressive neurodegenerative changes and disability in patients. A systematic literature review (SLR) was carried out to understand and summarize the published efficacy and safety of therapeutic interventions in this disease.
METHODS
Database searches were carried out in MEDLINE, Embase, and Cochrane by two independent reviewers. In addition, trial registries and conference proceedings were hand-searched.
RESULTS
Thirty-two publications were deemed eligible according to PICOS criteria. Twenty-four publications detail randomized controlled trials. The most frequently identified therapeutic intervention was idebenone ( = 11), followed by recombinant erythropoietin ( = 6), omaveloxolone ( = 3), and amantadine hydrochloride ( = 2). Other therapeutic interventions were investigated in one publication: A0001, CoQ10, creatine, deferiprone, interferon-γ-1b, the L-carnitine levorotatory form of 5-hydroxytryptophan, luvadaxistat, resveratrol, RT001, and vatiquinone (EPI-743). These studies included patients from 8 to 73 years old, and disease duration varied from 4.7 to 19 years. Disease severity as per the mean GAA1 and GAA2 allele repeat length ranged from 350 to 930 and 620 to 987 nucleotides, respectively. Most frequently reported efficacy outcomes were the International Cooperative Ataxia Rating Scale (ICARS, = 10), the Friedreich Ataxia Rating Scale (modified FARS and FARS-neuro, = 12), the Scale for Assessment and Rating of Ataxia (SARA, = 7), and the Activities of Daily Living scale (ADL, = 8). Each of these assesses the severity of disability in FA patients. In many studies, patients with FA deteriorated according to these severity scales regardless of treatment, or inconclusive results were found. Generally, these therapeutic interventions were well-tolerated and safe. Serious adverse events were atrial fibrillation ( = 1), craniocerebral injury ( = 1), and ventricular tachycardia ( = 1).
CONCLUSION
Identified literature showed a considerable unmet need for therapeutic interventions that halt or slow the deteriorating nature of FA. Novel efficacious drugs should be investigated that aim to improve symptoms or slow disease progression.
PubMed: 37180421
DOI: 10.1177/26330040221139872 -
Iranian Journal of Psychiatry Jul 2022Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating... (Review)
Review
Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating effects of glutamate receptor modulators in treating patients with resistant depression. The study protocol was registered in PROSPERO (CRD42021225516). Scopus, ISI Web of Science, Embase, Cochrane Library, Google Scholar, and three trial registries were searched up to September 2020 to find RCTs evaluating glutamate receptor modulators for resistant depression. The difference between intervention and control groups in changing depression scores from baseline to endpoint was considered the primary outcome. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the RCTs. No funding was received. Thirty-eight RCTs were included. Based on the included studies, compelling evidence was found for ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657); the results for MK-0657, amantadine, and nitrous oxide were only based on one study for each. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results for efficacy, and, riluzole, and 7-chlorokynurenic acid were mostly comparable to placebo. A limited number of studies were available that addressed drugs other than ketamine. The study cannot determine the difference between statistical and clinical significance between the agents and placebo due to high heterogeneity among the RCTs. Nevertheless, ketamine could be used as an efficacious drug in TRD; still, additional studies are needed to delineate the optimum dosage, duration of efficacy, and intervals. Further studies are also recommended on the effectiveness of glutamatergic system modulators other than ketamine on treatment-resistant depression.
PubMed: 36474699
DOI: 10.18502/ijps.v17i3.9733 -
Asian Journal of Psychiatry Jan 2023To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for... (Meta-Analysis)
Meta-Analysis
Pharmacological and nonpharmacological augmentation treatments for clozapine-resistant schizophrenia: A systematic review and network meta-analysis with normalized entropy assessment.
OBJECTIVE
To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS).
METHODS
Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking.
RESULTS
We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93).
CONCLUSION
Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).
Topics: Humans; Clozapine; Network Meta-Analysis; Entropy; Memantine; Mirtazapine; Antipsychotic Agents; Schizophrenia
PubMed: 36470132
DOI: 10.1016/j.ajp.2022.103375