-
Journal of Clinical Neuroscience :... Nov 2013Memantine hydrochloride is a first-line therapeutic drug approved by the US Food and Drug Administration for the management of moderate to severe Alzheimer's disease... (Review)
Review
Memantine hydrochloride is a first-line therapeutic drug approved by the US Food and Drug Administration for the management of moderate to severe Alzheimer's disease (AD). We conducted a review of the literature to determine the changes to the central glutamatergic neurotransmitter system in dementia subtypes and the available clinical evidence regarding the use of memantine in the treatment of different dementia subtypes. We conclude from our review that memantine may be an effective therapeutic option in managing AD, frontotemporal dementia, dementia with Lewy bodies, Parkinson's disease dementia and vascular dementia. When a diagnosis of the dementia subtype cannot be clearly identified or when there is no clear therapeutic option, memantine may be simple and safe.
Topics: Alzheimer Disease; Dementia; Excitatory Amino Acid Antagonists; Humans; Memantine; Parkinson Disease
PubMed: 24035650
DOI: 10.1016/j.jocn.2013.02.041 -
Ideggyogyaszati Szemle Nov 2021In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well.... (Review)
Review
In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well. Patients' and caregivers' quality of life and life expectancy are greatly determined by the early diagnosis and the initiation of available symptomatic treatments. Cholinesterase inhibitors and memantine have been the cornerstones of Alzheimer's therapy for approximately two decades and over the years, more and more experience has been gained on their use in non-Alzheimer's dementias too. The aim of our work was to provide a comprehensive summary about the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer's and non-Alzheimers's dementias.
Topics: Alzheimer Disease; Caregivers; Cholinesterase Inhibitors; Humans; Memantine; Quality of Life
PubMed: 34856086
DOI: 10.18071/isz.74.0379 -
JAMA Oct 2019Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million. (Review)
Review
IMPORTANCE
Worldwide, 47 million people live with dementia and, by 2050, the number is expected to increase to 131 million.
OBSERVATIONS
Dementia is an acquired loss of cognition in multiple cognitive domains sufficiently severe to affect social or occupational function. In the United States, Alzheimer disease, one cause of dementia, affects 5.8 million people. Dementia is commonly associated with more than 1 neuropathology, usually Alzheimer disease with cerebrovascular pathology. Diagnosing dementia requires a history evaluating for cognitive decline and impairment in daily activities, with corroboration from a close friend or family member, in addition to a thorough mental status examination by a clinician to delineate impairments in memory, language, attention, visuospatial cognition such as spatial orientation, executive function, and mood. Brief cognitive impairment screening questionnaires can assist in initiating and organizing the cognitive assessment. However, if the assessment is inconclusive (eg, symptoms present, but normal examination findings), neuropsychological testing can help determine whether dementia is present. Physical examination may help identify the etiology of dementia. For example, focal neurologic abnormalities suggest stroke. Brain neuroimaging may demonstrate structural changes including, but not limited to, focal atrophy, infarcts, and tumor, that may not be identified on physical examination. Additional evaluation with cerebrospinal fluid assays or genetic testing may be considered in atypical dementia cases, such as age of onset younger than 65 years, rapid symptom onset, and/or impairment in multiple cognitive domains but not episodic memory. For treatment, patients may benefit from nonpharmacologic approaches, including cognitively engaging activities such as reading, physical exercise such as walking, and socialization such as family gatherings. Pharmacologic approaches can provide modest symptomatic relief. For Alzheimer disease, this includes an acetylcholinesterase inhibitor such as donepezil for mild to severe dementia, and memantine (used alone or as an add-on therapy) for moderate to severe dementia. Rivastigmine can be used to treat symptomatic Parkinson disease dementia.
CONCLUSIONS AND RELEVANCE
Alzheimer disease currently affects 5.8 million persons in the United States and is a common cause of dementia, which is usually accompanied by other neuropathology, often cerebrovascular disease such as brain infarcts. Causes of dementia can be diagnosed by medical history, cognitive and physical examination, laboratory testing, and brain imaging. Management should include both nonpharmacologic and pharmacologic approaches, although efficacy of available treatments remains limited.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Excitatory Amino Acid Antagonists; Humans; Memantine; Neuroimaging; Neuropsychological Tests
PubMed: 31638686
DOI: 10.1001/jama.2019.4782 -
Annals of Clinical Psychiatry :... Aug 2018Memantine is a non-competitive N-methyl-d-aspartate receptor antagonist currently used for the treatment of Alzheimer's disease as an approved indication. However, as... (Review)
Review
BACKGROUND
Memantine is a non-competitive N-methyl-d-aspartate receptor antagonist currently used for the treatment of Alzheimer's disease as an approved indication. However, as knowledge of signaling pathways is increasing, the therapeutic potential of memantine is being applied for the treatment of various psychiatric illnesses.
METHODS
The PubMed online database was searched for the use of memantine in various psychiatric disorders. Case studies, open-label trials, and controlled trials from the search were included.
RESULTS
Memantine monotherapy was found to exert efficacy in several neuropsychiatric conditions, including autism spectrum disorder, binge eating disorder, and attention-deficit/hyperactivity disorder. For posttraumatic stress disorder and generalized anxiety disorder, memantine was found efficacious in augmentation with other medications. In obsessive-compulsive disorder (OCD), memantine was used as both an augmentation to selective serotonin reuptake inhibitors and standalone therapy, and most published studies found it to improve OCD symptoms. For schizophrenia, memantine has been reported to be consistently effective for negative symptoms only. The manic phase of bipolar disorder also appears to benefit from memantine. The depressive phase of bipolar disorder and major depressive disorder did not respond significantly to memantine. Catatonia as a symptom of various disorders improved in several case studies when memantine was used in combination with other medications.
CONCLUSIONS
Memantine may have several therapeutic applications in psychiatry, reflecting the involvement of glutamate pathways in multiple psychiatric disorders.
Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Binge-Eating Disorder; Drug Therapy, Combination; Humans; Memantine; Mood Disorders; Selective Serotonin Reuptake Inhibitors
PubMed: 30028898
DOI: No ID Found -
The American Journal of Psychiatry May 2023Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin, leading to noticeable hair loss or tissue damage. To date there is a severe paucity of evidence-based treatments for these conditions. In this study, the authors sought to determine whether memantine, a glutamate modulator, is more effective than placebo in reducing hair-pulling and skin-picking behavior.
METHODS
One hundred adults with trichotillomania or skin-picking disorder (86 women; mean age, 31.4 years [SD=10.2]) were enrolled in a double-blind trial of memantine (dosing range, 10-20 mg/day) or placebo for 8 weeks. Participants were assessed with measures of pulling and picking severity. Outcomes were examined using a linear mixed-effects model. The prespecified primary outcome measure was treatment-related change on the NIMH Trichotillomania Symptom Severity Scale, modified to include skin picking.
RESULTS
Compared with placebo, memantine treatment was associated with significant improvements in scores on the NIMH scale, Sheehan Disability Scale, and Clinical Global Impressions severity scale in terms of treatment-by-time interactions. At study endpoint, 60.5% of participants in the memantine group were "much or very much improved," compared with 8.3% in the placebo group (number needed to treat=1.9). Adverse events did not differ significantly between the treatment arms.
CONCLUSIONS
This study found that memantine treatment resulted in statistically significant reductions in hair pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on number needed to treat), and was well tolerated. The glutamate system may prove to be a beneficial target in the treatment of compulsive behaviors.
Topics: Adult; Humans; Female; Trichotillomania; Memantine; Double-Blind Method; Glutamates
PubMed: 36856701
DOI: 10.1176/appi.ajp.20220737 -
Journal of Alzheimer's Disease : JAD 2017The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical benefit of memantine for Alzheimer's disease (AD) remains inconclusive.
OBJECTIVE
We performed an updated systematic review and meta-analysis of the efficacy/safety of memantine in AD.
METHODS
We included randomized trials of memantine for AD patients. Cognitive function scores (CF), behavioral disturbances scores (BD), and all-cause discontinuation were used as primary measures. Effect size based on a random-effects model was evaluated in the meta-analyses.
RESULTS
Thirty studies (n = 7,567; memantine versus placebo: N = 11, n = 3,298; memantine + cholinesterase inhibitors (M+ChEIs) versus ChEIs: N = 17, n = 4,175) were identified. Memantine showed a significant improvement in CF [standardized mean difference (SMD) = -0.24, 95% confidence intervals (95% CIs) = -0.34, -0.15, p < 0.00001, I2 = 35% ] and BD (SMD = -0.16, 95% CIs = -0.29, -0.04, p = 0.01, I2 = 52%) compared with placebo. In the sensitivity analysis including only patients with moderate-severe AD, memantine was superior to the placebo in reducing BD without considerable heterogeneity (SMD = -0.20, 95% CIs = -0.34, -0.07, p = 0.003, I2 = 36%). Compared with ChEIs, M+ChEIs showed a greater reduction in BD (SMD = -0.20, 95% CIs = -0.36, -0.03, p = 0.02, I2 = 77%) and a trend of CF improvement (SMD = -0.11, 95% CIs = -0.22, 0.01, p = 0.06, I2 = 56%). However, in the sensitivity analysis of double-blind, placebo-controlled studies only, M+ChEIs showed a significant reduction in BD compared with ChEIs without considerable heterogeneity (SMD = -0.11, 95% CIs = -0.21, -0.01, p = 0.04, I2 = 40%). When performing the sensitivity analysis of donepezil studies only, M+ChEIs was superior to ChEIs in improving CF without considerable heterogeneity (SMD = -0.18, 95% CIs = -0.31, -0.05, p = 0.006, I2 = 49%). No differences were detected in all-cause discontinuation between the groups.
CONCLUSIONS
The meta-analyses suggest the credible efficacy and safety of memantine in treating AD when used alone or in combination with ChEIs.
Topics: Alzheimer Disease; Excitatory Amino Acid Antagonists; Humans; Memantine
PubMed: 28922160
DOI: 10.3233/JAD-170424 -
Brain Injury Feb 2020This comprehensive review discusses clinical studies of patients following brain injuries (traumatic, acquired, or stroke), who have been treated with amantadine or... (Review)
Review
This comprehensive review discusses clinical studies of patients following brain injuries (traumatic, acquired, or stroke), who have been treated with amantadine or memantine. Both amantadine and memantine are commonly used in the acute rehabilitation setting following brain injuries, despite their lack of FDA-approval for neuro-recovery. Given the broad utilization of such agents, there is a need to review the evidence supporting this common off-label prescribing. The purpose of this review is to describe the mechanisms of action for memantine and amantadine, as well as to complete a comprehensive review of the clinical uses of these agents. We included 119 original, clinical research articles from NCBI Medline, published before 2019. We focused on the domains of neuroplasticity, functional recovery, motor recovery, arousal, fatigue, insomnia, behavior, agitation, and cognition. Most of the existing research supporting the use of amantadine and memantine in recovery from brain injuries was done in very small populations, limiting the significance of conclusions. While most studies are positive; small effect sizes are usually reported, or populations are subject to bias. Furthermore, evidence is so limited that this review includes research regarding both acute and chronic acquired brain injury populations. Fortunately, reported short-term side effects generally are modest, and stop soon after amantadine/memantine is discontinued. However, responses are inconsistent, and the phenotype of responders remains elusive.
Topics: Amantadine; Brain Injuries; Humans; Memantine; Neuronal Plasticity; Off-Label Use; Recovery of Function
PubMed: 32078407
DOI: 10.1080/02699052.2020.1723697 -
Pharmacological Reports : PR Jun 2021Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment so far. Our study...
BACKGROUND
Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment so far. Our study aimed to evaluate the potential anti-CHIKV activity of memantine hydrochloride (mtnH), a drug from the class of the aminoadamantanes approved for the treatment of Alzheimer´s disease, as a possible drug to be repurposed to the treatment of Chikungunya fever.
METHODS
MtnH antiviral activity against CHIKV was determined by infecting BHK-21 cells with CHIKV-nanoluc, a virus carrying the marker nanoluciferase reporter, in the presence or absence of mtnH at concentrations ranging from 500 to 1.45 µM. The effective concentration of 50% inhibition (EC) was calculated. Cell viability assay (determination of CC) was also performed employing BHK-21 cells. Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay (Ames test).
RESULTS
MtnH presented a CC of 248.4 ± 31.9 µM and an EC of 32.4 ± 4 µM against CHIKV in vitro. The calculated selectivity index (SI) was 7.67. MtnH did not induce genetic mutation in Salmonella strains with or without an external metabolizing system.
CONCLUSION
With the data herein presented, it is possible to hypothesize mtnH as a viable candidate to be repurposed as an anti-CHIKV drug. Clinical assays are, therefore, encouraged due to the promising in vitro results. The drug memantine hydrochloride is herein personified with a doubt: as a prior regulated drug against Alzheimer, could it follow the path against Chikungunya virus too?
Topics: Antiviral Agents; Cell Line; Cell Survival; Chikungunya Fever; Chikungunya virus; Humans; Memantine
PubMed: 33523405
DOI: 10.1007/s43440-021-00216-4 -
Brain and Behavior Nov 2020Alzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Alzheimer's disease (AD) is a degenerative brain disease that progresses over time, heavily burdening patients, families, and aging societies worldwide. Memantine and donepezil are frequently used in its treatment, both as monotherapy and in combination. This multiple treatment comparison meta-analysis assessed the efficacy of these regimens and placebo in the management of AD.
METHODS
We searched PubMed, Embase, the Cochrane Library, and Wanfang Med Online and China National Knowledge Infrastructure for English and Chinese publications from the first records to 17 April 2020. Two investigators scanned articles for placebo-controlled trials of memantine and donepezil alone and in combination. We extracted data on the following outcomes: cognition, global assessment, daily activities, neuropsychiatric symptoms, adverse events, and the acceptability and cost of these treatment regimens.
RESULTS
Of 936 records screened, we included 54 trials in this analysis. The combination therapy was more effective in improving cognition (mean difference (MD)-5.01, 95% credible interval (95% Crl) -10.73 to 0.86 in the Alzheimer's Disease Assessment Scale-Cognitive Subscale; MD 9.61, 95% Crl 2.29 to 16.97 in the Severe Impairment Battery), global assessment (MD -2.88, 95% Crl -6.04 to 0.40), daily activities (MD 13.06, 95% Crl -34.04 to 58.92), and neuropsychiatric symptoms (MD -6.84, 95% Crl -10.62 to -2.82) compared with placebo. Memantine was more acceptable than placebo (MD 0.93, 95% Crl 0.69 to 1.22).
CONCLUSIONS
Memantine plus donepezil showed superior outcomes for cognition, global assessment, daily activities, and neuropsychiatric symptoms, but lower acceptability than monotherapy and placebo. Combination therapy may be more cost-effective, because memantine slows the progression of AD.
Topics: Alzheimer Disease; China; Donepezil; Humans; Memantine; Network Meta-Analysis
PubMed: 32914577
DOI: 10.1002/brb3.1831 -
Nature Reviews. Drug Discovery Feb 2004
Topics: Aged; Alzheimer Disease; Excitatory Amino Acid Antagonists; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 15040575
DOI: 10.1038/nrd1311