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The Annals of Pharmacotherapy Nov 2014To describe the current data evaluating the efficacy and safety of memantine for the prevention of primary headache disorders. (Review)
Review
OBJECTIVE
To describe the current data evaluating the efficacy and safety of memantine for the prevention of primary headache disorders.
DATA SOURCES
A literature search using MEDLINE (1966-July 2014) and EMBASE (1973-July 2014) was conducted using the search terms memantine, headache, migraine, glutamate, and NMDA. References of identified articles were reviewed for additional, relevant citations.
STUDY SELECTION AND DATA EXTRACTION
All English-language articles dealing with the use of memantine for prevention of primary headache disorders were included.
DATA SYNTHESIS
Data from several retrospective reports and 2 prospective clinical trials suggest that memantine may be a useful treatment option for the prevention of primary headache disorders. The majority of available literature focuses specifically on chronic migraine prevention in refractory patients who had failed multiple previous prophylactic therapies. In these patients, 10 to 20 mg of memantine daily reduced the frequency and intensity of migraine headaches and was generally well tolerated, with few adverse events. Data regarding the efficacy of memantine for other primary headache disorders such as chronic tension type and cluster headaches are limited.
CONCLUSION
Although further studies evaluating the efficacy of memantine for prevention of primary headache disorders are warranted, memantine may be a reasonable option, used either as monotherapy or adjunctive therapy, in the refractory chronic migraine prophylaxis setting.
Topics: Analgesics; Clinical Trials as Topic; Headache Disorders, Primary; Humans; Memantine; Migraine Disorders
PubMed: 25159002
DOI: 10.1177/1060028014548872 -
Biomolecules Jul 2020Memantine, an -methyl-d-aspartate (NMDA) receptor antagonist approved for treating Alzheimer's disease, has a good safety profile and is increasingly being studied for... (Review)
Review
Memantine, an -methyl-d-aspartate (NMDA) receptor antagonist approved for treating Alzheimer's disease, has a good safety profile and is increasingly being studied for possible use in a variety of non-dementia psychiatric disorders. There is an abundance of basic and clinical data that support the hypothesis that NMDA receptor hypofunction contributes to the pathophysiology of schizophrenia. However, there are numerous randomized, double-blind, placebo-controlled clinical trials showing that add-on treatment with memantine improves negative and cognitive symptoms, particularly the negative symptoms of schizophrenia, indicating that memantine as adjunctive therapy in schizophrenia helps to ameliorate negative symptoms and cognitive deficits. It remains unclear why memantine does not show undesirable central nervous system (CNS) side effects in humans unlike other NMDA receptor antagonists, such as phencyclidine and ketamine. However, the answer could lie in the fact that it would appear that memantine works as a low-affinity, fast off-rate, voltage-dependent, and uncompetitive antagonist with preferential inhibition of extrasynaptic receptors. It is reasonable to assume that the effects of memantine as adjunctive therapy on negative symptoms and cognitive deficits in schizophrenia may derive primarily, if not totally, from its NMDA receptor antagonist activity at NMDA receptors including extrasynaptic receptors in the CNS.
Topics: Animals; Antipsychotic Agents; Drug Combinations; Excitatory Amino Acid Antagonists; Humans; Memantine; Receptors, N-Methyl-D-Aspartate; Schizophrenia
PubMed: 32751985
DOI: 10.3390/biom10081134 -
The American Journal of Geriatric... Apr 2015To clarify whether memantine is more efficacious in several outcomes and safer than placebo in patients with Lewy body disorders, we performed a meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To clarify whether memantine is more efficacious in several outcomes and safer than placebo in patients with Lewy body disorders, we performed a meta-analysis of memantine in patients with Lewy body disorders.
METHODS
The meta-analysis included randomized controlled trials of memantine for Lewy body disorders in all patients with Lewy body disorders. Motor function, activities of daily living, Neuropsychiatric Inventory, Mini-Mental State Exam, discontinuation rate, and individual side effects were evaluated.
RESULTS
No significant effects of memantine on motor function scores, Mini-Mental State Exam scores, Neuropsychiatric Inventory scores, and activity of daily living scores were found. However, memantine was superior to placebo in Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change scores (standardized mean difference: -0.26; 95% confidence interval: -0.51 to -0.02; z = 2.08; p = 0.04; two studies; N = 258). Dropout due to all causes, inefficacy, or adverse events were similar in both groups. Moreover, no significant differences in serious adverse events, somnolence/tiredness, stroke, dizziness/vertigo, and confusion were found between the groups.
CONCLUSION
Our results suggest that memantine did not have a benefit for the treatment of Lewy body disorders in cognition and motor function. However, memantine may be superior to placebo for the overall impression of the disorders. Further, memantine is well tolerated.
Topics: Excitatory Amino Acid Antagonists; Humans; Lewy Body Disease; Memantine; Patient Dropouts
PubMed: 24406251
DOI: 10.1016/j.jagp.2013.11.007 -
European Archives of Psychiatry and... Oct 2023This review article presents select recent studies that form the basis for the development of esmethadone into a potential new drug. Esmethadone is a promising member of... (Review)
Review
This review article presents select recent studies that form the basis for the development of esmethadone into a potential new drug. Esmethadone is a promising member of the pharmacological class of uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists that have shown efficacy for major depressive disorder (MDD) and other diseases and disorders, such as Alzheimer's dementia and pseudobulbar affect. The other drugs in the novel class of NMDAR antagonists with therapeutic uses that are discussed for comparative purposes in this review are esketamine, ketamine, dextromethorphan, and memantine. We present in silico, in vitro, in vivo, and clinical data for esmethadone and other uncompetitive NMDAR antagonists that may advance our understanding of the role of these receptors in neural plasticity in health and disease. The efficacy of NMDAR antagonists as rapid antidepressants may advance our understanding of the neurobiology of MDD and other neuropsychiatric diseases and disorders.
Topics: Humans; Excitatory Amino Acid Antagonists; Depressive Disorder, Major; Memantine; Antidepressive Agents; Alzheimer Disease
PubMed: 36890259
DOI: 10.1007/s00406-023-01571-4 -
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 -
Journal of Pain & Palliative Care... Dec 2016Phantom limb pain (PLP) occurs in up to 85% of patients who have undergone an amputation and remains difficult to treat. Memantine is a N-Methyl-d-aspartate receptor... (Review)
Review
Phantom limb pain (PLP) occurs in up to 85% of patients who have undergone an amputation and remains difficult to treat. Memantine is a N-Methyl-d-aspartate receptor antagonist that has shown benefit in pain syndromes. The objective of this systematic review is to evaluate the evidence for the use of memantine in the treatment of acute and chronic PLP. MEDLINE (1956 to May 2016) and Embase (1957 to May 2016) were queried for articles that characterized the clinical outcomes of patient(s) treated with memantine for PLP. The initial search identified 185 studies and case reports. After screening, eight articles were included. One prospective study, a case report, and two case series demonstrated benefit with memantine in the treatment of acute PLP. However, in chronic PLP that persisted for over 1 year, four prospective studies failed to demonstrate significant analgesic effects with memantine. Memantine was well tolerated in all studies. Memantine appears to be a reasonable option to trial in a patient with a recent amputation or who has failed or cannot tolerate other analgesics. Additional research is needed to further determine the role of memantine in the treatment and prevention of PLP and to identify the population most likely to gain benefit.
Topics: Acute Disease; Chronic Disease; Excitatory Amino Acid Antagonists; Humans; Memantine; Phantom Limb
PubMed: 27813692
DOI: 10.1080/15360288.2016.1241334 -
PloS One 2015We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD).
METHODS
The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes.
RESULTS
Nine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI=-0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17¬ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups.
CONCLUSIONS
Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.
Topics: Activities of Daily Living; Alzheimer Disease; Humans; Memantine; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25860130
DOI: 10.1371/journal.pone.0123289 -
Fundamental & Clinical Pharmacology Feb 2018Neuropathic pain (NP) is difficult to treat and is associated with a decline in quality of life. NP aetiologies are numerous and a number of pathologies display... (Review)
Review
Neuropathic pain (NP) is difficult to treat and is associated with a decline in quality of life. NP aetiologies are numerous and a number of pathologies display neuropathic characteristics. Of the various N-methyl-d-aspartate antagonists that are alternatives to be recommended in first-line NP treatment, memantine has the safest side-effect profile and has long been approved in Alzheimer's disease. The review covers memantine studies in postherpetic neuralgia, diabetic pain, postoperative pain, complex regional pain syndrome, chronic phantom limb pain, opioid-refractory pain and fibromyalgia. Results were inconclusive because of studies with poor levels of evidence, paucity of trials and small samples. Two recent randomized trials, however, showed significant efficacy of memantine: one demonstrated prophylactic effects against postoperative neuralgia and pain-associated psychological impairment; in the other, memantine improved pain and cognition in fibromyalgia. Both studies found no side effects or adverse events. Given the high rate of therapeutic failure in chronic states, often because of adverse events, the excellent benefit/risk ratio of memantine in these pilot studies encourages further exploration of this drug in NP prevention and in fibromyalgia in larger-scale studies.
Topics: Analgesics; Animals; Excitatory Amino Acid Antagonists; Humans; Memantine; Neuralgia; Pain Measurement; Treatment Outcome
PubMed: 28802070
DOI: 10.1111/fcp.12316 -
Progress in Neuro-psychopharmacology &... Dec 2021The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic... (Review)
Review
The deleterious effects of the drug addiction epidemic are compounded by treatment strategies that are only marginally efficacious. Memantine is a unique glutamatergic medication with proven ability to attenuate drug addiction in preclinical models. However, clinical translational studies are inconsistent. In this review, we summarize preclinical evidences and clinical trials that investigated the efficacy of memantine in treating patients with alcohol, opiate, cocaine, and nicotine use disorders and discuss the results from a mechanistic point of view. Memantine has shown efficacy in reducing alcohol and opiate craving, consumption, and withdrawal severity. However, in cocaine and nicotine use disorders, memantine did not have significant effect on cravings or consumption. Additionally, memantine was associated with increased subjective effects of alcohol, cocaine, and nicotine. We discuss possible mechanisms behind this variability. Since memantine transiently blocks NMDA receptors and protects neurons from overstimulation by excessive synaptic glutamate, its efficacy should be observed in drug phases that cause hyperglutamatergic states, while hypoglutamatergic drug use states would not resolve with blocking NMDA receptors. Second, memantine pharmacokinetic studies have been done in rodents and healthy volunteers, but not in patients with substance use disorder. Memantine, opiates, cocaine, and nicotine share the same transporter family at the blood brain barrier. This shared transport mechanism could impact brain concentrations of memantine and its effects. In conclusion, memantine remains an intriguing compound in our pharmacopeia with controversial results in treating certain aspects of drug addiction. Further studies are needed to understand the clinical and biological correlates of its efficacy.
Topics: Animals; Brain; Cocaine; Ethanol; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Memantine; Neurons; Opiate Alkaloids; Receptors, N-Methyl-D-Aspartate; Substance-Related Disorders
PubMed: 34324921
DOI: 10.1016/j.pnpbp.2021.110409 -
American Journal of Alzheimer's Disease... 2004Alzheimer's disease (AD) is the most common form of dementia in occidental countries. Currently approved treatments for AD provide mainly symptomatic benefits without... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia in occidental countries. Currently approved treatments for AD provide mainly symptomatic benefits without clear evidence of neuroprotection. N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential in several central nervous system disorders, including neuroprotective treatment in chronic neurodegenerative diseases, and symptomatic treatment in other neurologic diseases. Memantine, an NMDA antagonist, has been recently approved for the treatment of advanced AD. Due to its mechanism of action, memantine is considered a neuroprotective drug, whose utility has been demonstrated in preclinical studies. In addition, memantine is a useful symptomatic treatment for AD and vascular dementia. This paper reviews both aspects of memantine as well as some basic mechanisms mediating cognition and glutamatergic neurodegeneration.
Topics: Clinical Trials as Topic; Dementia; Excitatory Amino Acid Antagonists; Humans; Memantine; Molecular Structure
PubMed: 15002339
DOI: 10.1177/153331750401900103