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The Cochrane Database of Systematic... Aug 2022Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness.
OBJECTIVES
To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence).
AUTHORS' CONCLUSIONS
It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Female; Humans; Male; Memantine; Odds Ratio; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36006807
DOI: 10.1002/14651858.CD013845.pub2 -
Emergency Medicine Clinics of North... May 2021Chronic brain failure, also known as dementia or major neurocognitive disorder, is a syndrome of progressive functional decline characterized by both cognitive and... (Review)
Review
Chronic brain failure, also known as dementia or major neurocognitive disorder, is a syndrome of progressive functional decline characterized by both cognitive and neuropsychiatric symptoms. It can be conceptualized like other organ failure syndromes and its impact on quality of life can be mitigated with proper treatment. Dementia is a risk factor for delirium, and their symptoms can be similar. Patients with dementia can present with agitation that can lead to injury. Logic and reason are rarely successful when attempting to redirect someone with advanced dementia. Interactions that offer a sense of choice are more likely to succeed.
Topics: Aged; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Cholinesterase Inhibitors; Delirium; Dementia; Diagnosis, Differential; Emergency Medicine; Humans; Incidence; Memantine; Mental Competency; Neurocognitive Disorders; Neuropsychological Tests; Pain; Prevalence; Psychomotor Agitation
PubMed: 33863461
DOI: 10.1016/j.emc.2021.01.008 -
ACS Omega Oct 2023Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established...
Sepsis-associated encephalopathy (SAE) is the most common complication of sepsis, with increased morbidity and mortality. To date, there has still been no established pharmacological therapy. Memantine, as an NMDA (-methyl-d-aspartate) receptor antagonist, exhibited neuroprotective effects against cognitive and emotional dysfunction in many disorders. We performed cecal ligation and puncture (CLP) inducing sepsis as the ideal animal model of SAE. CLP-induced septic mice were given a memantine treatment through intragastric administration. The novel object recognition test indicated that memantine significantly improved cognitive dysfunction in septic mice. The open field test revealed that the anxiety-like behaviors and locomotion ability of septic mice were relieved by memantine. The pole test further confirmed the protective effects of memantine against immobility. Memantine significantly inhibited the excessive glutamate production and improved impaired neurogenesis on first and seventh day after sepsis, accompanying with reducing proinflammatory cytokines production (tumor necrosis factor alpha (TNF-α), interleukin (IL)-1beta (IL-1β), and IL-10) and microglia activation in the brain of SAE. In addition, memantine treatment also reducing sepsis-induced brain blood barrier disruption via inhibiting the expression of metalloproteinase-9 (MMP-9). In conclusion, memantine exerted neuro-protective effects against cognitive and emotional defects, which might be considered as a promising therapy for SAE.
PubMed: 37929090
DOI: 10.1021/acsomega.3c06250 -
International Journal of Molecular... Jun 2023Tau protein aggregations are important contributors to the etiology of Alzheimer's disease (AD). Hydromethylthionine (HMT) is a potent inhibitor of tau aggregation in...
Tau protein aggregations are important contributors to the etiology of Alzheimer's disease (AD). Hydromethylthionine (HMT) is a potent inhibitor of tau aggregation in vitro and in vivo and is being developed as a possible anti-dementia medication. HMT was also shown to affect the cholinergic system and to interact with mitochondria. Here, we used tau-transgenic (L1 and L66) and wild-type NMRI mice that were treated with HMT, rivastigmine and memantine and with combinations thereof, for 2-4 weeks. We measured HMT concentrations in both brain homogenates and isolated mitochondria and concentrations of glucose, lactate and pyruvate in brain by microdialysis. In isolated brain mitochondria, we recorded oxygen consumption of mitochondrial complexes by respirometry. While rivastigmine and memantine lowered mitochondrial respiration, HMT did not affect respiration in wild-type animals and increased respiration in tau-transgenic L1 mice. Glucose and lactate levels were not affected by HMT administration. The presence of HMT in isolated mitochondria was established. In summary, traditional anti-dementia drugs impair mitochondrial function while HMT has no adverse effects on mitochondrial respiration in tau-transgenic mice. These results support the further development of HMT as an anti-dementia drug.
Topics: Mice; Animals; Rivastigmine; Memantine; tau Proteins; Mice, Transgenic; Cholinesterase Inhibitors; Alzheimer Disease; Mitochondria
PubMed: 37445987
DOI: 10.3390/ijms241310810 -
Naunyn-Schmiedeberg's Archives of... Jul 2023Migraine is a debilitating disorder affecting females more frequently than males. There is some evidence that drugs targeting glutamate receptors: memantine and ketamine... (Review)
Review
Migraine is a debilitating disorder affecting females more frequently than males. There is some evidence that drugs targeting glutamate receptors: memantine and ketamine might be beneficial in the therapy of this entity. Therefore, the purpose of this work is to present NMDA receptor antagonists, memantine and ketamine, as potential anti-migraine agents. We searched PubMed/MEDLINE, Embase, and clinical trials submitted to ClinicalTrials.gov to find publications describing eligible trials published between database inception and December 31, 2021. This comprehensive literature review summarizes data on the use of the NMDA receptor antagonists memantine and ketamine in the pharmacotherapy of migraine. Results from 20 previous and recent preclinical experiments are discussed and correlated with 19 clinical trials (including case series, open-label, and randomized placebo-controlled trials). For the purposes of this review, the authors hypothesized that the propagation of SD is a major mechanism in the pathophysiology of migraine. In several animal studies and in vitro studies, memantine and ketamine inhibited or reduced propagation of the SD. In addition, the results of clinical trials suggest that memantine or ketamine may be an effective treatment option for migraine. However, most studies on these agents lack control group. Although further clinical trials are needed, the results suggest that ketamine or memantine may be promising molecules for the treatment of severe migraine. Particular attention should be paid to people who have a treatment-resistant form of migraine with aura or have exhausted existing treatment options. For them, the drugs under discussion could represent an interesting alternative in the future.
Topics: Male; Animals; Female; Memantine; Ketamine; Excitatory Amino Acid Antagonists; Receptors, N-Methyl-D-Aspartate; Migraine Disorders
PubMed: 36869904
DOI: 10.1007/s00210-023-02444-2 -
Psychopharmacology Bulletin Feb 2023Memenatine is USFDA approved for dementia of Alzheimer's disease. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of... (Review)
Review
BACKGROUND
Memenatine is USFDA approved for dementia of Alzheimer's disease. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of disorders.
STUDY QUESTION
Memantine remains one of only few psychotropic drugs with antiglutamate activity. This might impart it a therapeutic potential in treatment-resistant major psychiatric disorders characterized by neuroprogression. We reviewed memantine basic pharmacology and its diversifying clinical indications while examining the extant evidence.
METHODS
EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant studies up to date of November, 2022.
RESULTS
Sound evidence supports use of memantine for major neuro-cognitive disorder due to Alzheimer's disease and severe vascular dementia, obsessive-compulsive disorder, treatment-resistant schizophrenia, and, ADHD. Modicum evidence supports use of memantine for PTSD, GAD and pathological gambling. Less compelling evidence is present for use in catatonia. No evidence supports use for core symptoms of autism spectrum disorder.
CONCLUSIONS
Memantine is an important addition to the psychopharmacological armamentarium. Level of evidence supporting the use of memantine in these off-label indications is highly variable, and hence, sound clinical judgment is necessary for its proper use and placement in real-life psychiatric practice and psychopharmacotherapy algorithms.
Topics: Humans; Memantine; Alzheimer Disease; Autism Spectrum Disorder; Psychiatry; Off-Label Use
PubMed: 36873917
DOI: No ID Found -
The Journal of Clinical Psychiatry Dec 2019Patients with obsessive-compulsive disorder (OCD) who do not respond adequately to serotonin reuptake inhibitor (SRI) therapy and cognitive behavioral therapy commonly... (Meta-Analysis)
Meta-Analysis Review
Patients with obsessive-compulsive disorder (OCD) who do not respond adequately to serotonin reuptake inhibitor (SRI) therapy and cognitive behavioral therapy commonly receive SRI augmentation in the form of an atypical antipsychotic drug. Memantine is another augmentation strategy that has been trialed. A recent systematic review and meta-analysis found very large improvements associated with memantine augmentation in OCD. Specifically, in 4 randomized controlled trials (RCTs), the response rate was 81% in 67 memantine-treated patients vs only 19% in 68 placebo-treated patients. The weighted mean difference between memantine and placebo groups was nearly 8 points on the Yale-Brown Obsessive Compulsive Scale. Such striking differences for intervention vs placebo in a difficult-to-treat disorder demand scrutiny. An examination of the RCTs on which the meta-analysis was based showed that all 4 RCTs emerged from the same geographical area, limiting the generalizability of the findings. Of greater concern, all 4 RCTs presented what were effectively completer analyses of data, compromising the scientific validity of the findings. There were several other concerns about the individual studies and about the meta-analysis, itself. Therefore, a reasonable conclusion is that, when the internal and external validity of studies in a meta-analysis are compromised, the findings and conclusions of the meta-analysis cannot be considered sound. It is concluded that, despite the very large benefits reportedly associated with memantine augmentation, the routine use of memantine as an augmentation agent for OCD cannot as yet be recommended.
Topics: Cognitive Behavioral Therapy; Combined Modality Therapy; Drug Therapy, Combination; Humans; Memantine; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 31846244
DOI: 10.4088/JCP.19f13163 -
European Journal of Pharmacology Nov 2021Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that was initially indicated for the treatment of moderate to severe Alzheimer's disease.... (Review)
Review
Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that was initially indicated for the treatment of moderate to severe Alzheimer's disease. It is now also considered for a variety of other pathologies in which activation of NMDA receptors apparently contributes to the pathogenesis and progression of disease. In addition to the central nervous system (CNS), NMDA receptors can be found in non-neuronal cells and tissues that recently have become an interesting research focus. Some studies have shown that glutamate signaling plays a role in cell transformation and cancer progression. In addition, these receptors may play a role in cardiovascular disorders. In this review, we focus on the most recent findings for memantine with respect to its pharmacological effects in a range of diseases, including inflammatory disorders, cardiovascular diseases, cancer, neuropathy, as well as retinopathy.
Topics: Animals; Cardiovascular Diseases; Excitatory Amino Acid Antagonists; Humans; Inflammation; Memantine; Neoplasms; Nervous System Diseases; Oxidative Stress; Receptors, N-Methyl-D-Aspartate; Retinal Diseases
PubMed: 34461125
DOI: 10.1016/j.ejphar.2021.174455 -
International Journal of Pharmaceutical... 2023Memantine hydrochloride is commonly prescribed for Alzheimer's disease and vascular dementia. However, the drug is only available in tablet form, a dosage form which...
Memantine hydrochloride is commonly prescribed for Alzheimer's disease and vascular dementia. However, the drug is only available in tablet form, a dosage form which is difficult for geriatrics to swallow. This problem is especially difficult for those patients diagnosed with Alzheimer's. This study was therefore aimed to develop and characterize an oral disintegrating film containing memantine hydrochloride using different types and concentrations of polymers. Using the solvent casting method, twelve formulations were developed, which involved manipulations on the type and concentration of the polymer. Afterwards, six formulations were selected to undergo characterization tests. These tests evaluated the films' tensile strength, Young's Modulus, percent elongation, folding endurance, disintegration and dissolution time, content uniformity, moisture loss, and moisture uptake. Polymers such as polyvinyl alcohol, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, and pullulan gum were respectively incorporated at different concentrations. The study found that only hydroxypropyl methylcellulose and polyvinyl alcohol formulations developed into acceptable oral disintegrating films. Formulation E (hydroxypropyl methylcellulose 50-mg/film), which exhibited optimal mechanical strength, fast disintegration and dissolution, and excellent content uniformity, was identified as the best formula. Although polyvinyl alcohol showed higher mechanical strength, hydroxypropyl methylcellulose films were better at fulfilling the optimal characteristics of an oral disintegrating film. The study showed that the mechanical strength increased proportionally to the polymer concentration in the polyvinyl alcohol film. However, for the hydroxypropyl methylcellulose film, the mechanical strength increased only when hydroxypropyl methylcellulose's concentration was increased from a 40-mg/film to a 50-mg/film but decreased with a 60-mg/film. To summarize, orally disintegrating films containing memantine hydrochloride was developed, characterized, and reasoned to have high potential to be marketed and to increase medication compliance among geriatrics suffering from Alzheimer's disease.
Topics: Humans; Aged; Chemistry, Pharmaceutical; Memantine; Polyvinyl Alcohol; Alzheimer Disease; Administration, Oral; Hypromellose Derivatives; Solubility; Polymers; Drug Compounding
PubMed: 38100669
DOI: No ID Found -
Frontiers in Neuroscience 2023The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and,... (Review)
Review
The primary mechanism for neuron death after an ischemic stroke is excitotoxic injury. Excessive depolarization leads to NMDA-mediated calcium entry to the neuron and, subsequently, cellular death. Therefore, the inhibition of the NMDA channel has been proposed as a neuroprotective measure in ischemic stroke. The high morbimortality associated with stroke warrants new therapies that can improve the functional prognosis of patients. Memantine is a non-competitive NMDA receptor antagonist which has gained attention as a potential drug for ischemic stroke. Here we analyze the available preclinical and clinical evidence concerning the use of memantine following an ischemic stroke. Preclinical evidence shows inhibition of the excitotoxic cascade, as well as improved outcomes in terms of motor and sensory function with the use of memantine. The available clinical trials of high-dose memantine in patients poststroke have found that it can improve patients' NIHSS and Barthel index and help patients with poststroke aphasia and intracranial hemorrhage. These results suggest that memantine has a clinically relevant neuroprotective effect; however, small sample sizes and other study shortcomings limit the impact of these findings. Even so, current studies show promising results that should serve as a basis to promote future research to conclusively determine if memantine does improve the outcomes of patients' post-ischemic stroke. We anticipate that future trials will fill current gaps in knowledge, and these latter results will broaden the therapeutic arsenal for clinicians looking to improve the prognosis of patients poststroke.
PubMed: 36743806
DOI: 10.3389/fnins.2023.1096372