Introduction. Migraine is a common, debilitating primary headache. Memantine is a non-competitive N-methyl D-aspartate (NMDA) antagonist that lowers neuronal excitability that could prevent migraine attacks. This study aimed to determine the efficacy and safety of memantine in patients with episodic migraine attacks using a systematic review and meta-analysis.

Methods. We searched CENTRAL, MEDLINE, Scopus, Cochrane, LILACS, ClinicalTrials.gov, HERDIN and Google Scholar for relevant studies until July 31, 2020. Prespecified screening and eligibility criteria for inclusion were applied. Included studies underwent methodological quality assessment. Study design, patient characteristics, interventions given, and relevant outcomes were extracted and synthesized.

Results. This review included five relevant articles - two randomized controlled trials (RCT) and three non randomized studies (one retrospective records review and survey, two prospective open-label single-arm trials). There were 109 patients included in the RCTs and 197 patients reported in the non-randomized studies. Pooled data from the two RCTs showed that memantine at 10 mg/day significantly decreased the monthly number of migraine days at 12 weeks compared to placebo with a mean difference of -1.58 [95% confidence interval (CI) -1.84, -1.32]. Non-randomized studies also showed a decrease in migraine days per month with memantine (5 to 20 mg/day) after 12 weeks [95% CI]: -9.1 [-11, -7.23], -7.2 [-8.85, -5.55], and -4.9 [-6.29, -3.51]. Adverse drug events (ADE) did not differ significantly between patients treated with memantine compared to placebo.

Conclusion. Memantine may be effective and well-tolerated as prophylaxis for episodic migraine.

Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer's disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.
Alzheimer Disease ; Animals ; Axons ; Brain ; Calcium ; Cerebral Cortex ; Cognition ; Computational Biology ; Cytoskeleton ; Hippocampus ; Learning ; Memantine ; Memory ; Mice ; Mice, Transgenic ; N-Methylaspartate ; Proteome ; Ribosomes ; Water

Memantine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNF α)genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.
Acoustics ; Animals ; Auditory Cortex ; Brain Stem ; Evoked Potentials, Auditory, Brain Stem ; Genes, Immediate-Early ; Glutamic Acid ; Immunohistochemistry ; Integrin alpha2 ; Memantine ; Models, Animal ; N-Methylaspartate ; Neurons ; Noise ; Prepulse Inhibition ; Rats ; Reflex, Startle ; Tinnitus ; Tumor Necrosis Factor-alpha

BACKGROUND: Alzheimer's dementia is the most common dementia. However, recently, choline alfoscerate is prescribed for treating Alzheimer's dementia, although it is not a treatment for this disease. PURPOSE: To analyze the prescription patterns of choline alfoscerate as a dementia treatment for patients with Alzheimer's disease and to analyze, as well as the factors affecting choline alfoscerate prescription. METHOD: The 2016 HIRA-NPS data was used in this study. The code of Alzheimer's dementia is F00 in the ICD-10 disease classification code. We analyzed the demographic, clinical, and regional characteristics associated with donepezil, rivastigmine, galantamine, memantine, and choline alfoscerate prescriptions. All statistical and data analyse were conducted by SAS 9.4 and Excel. RESULTS: For patients with Alzheimer's disease, choline alfoscerate was the second most prescribed after donepezil. Analysis results showed that choline alfoscerate was more likely to be prescribed to men than to women, and more likely to be prescribed by local health centers than by medical institutions. Moreover, choline alfoscerate was highly likely to be prescribed at neurosurgical departments, among medical departments. CONCLUSION: This study confirmed that choline alfoscerate was prescribed considerably for patients with Alzheimer's dementia. Further studies valuating its clinical validity should be performed to clarify whether choline alfoscerate prescription is appropriate for treating Alzheimer's dementia.
Alzheimer Disease ; Choline ; Classification ; Dementia ; Female ; Galantamine ; Glycerylphosphorylcholine ; Humans ; International Classification of Diseases ; Male ; Memantine ; Methods ; Prescriptions ; Rivastigmine

Dementia is a clinical syndrome characterized by a cluster of symptoms and signs that manifest as difficulties in cognitive functions such as memory, psychological and psychiatric changes, and impairments in activities of daily living. As a result of worldwide trends of population aging, dementia has had a huge impact on public health in almost all countries. Disease modification therapies for dementia have not yet been developed. However, pharmacotherapy is essential in patients with dementia to combat delays in their cognitive and functional decline. In this article, we review the current pharmacotherapy for dementia. Three acetylcholinesterase inhibitors—donepezil, rivastigmine, galantamine—and memantine are the only medications that have been approved for the treatment of dementia. We present the indications, dose recommendations, side effects, and criteria for National Health Insurance coverage in Korea of these medications for dementia treatment. Although the Ministry of Food and Drug Safety in Korea has not approved any medications for managing the behavioral and psychological symptoms of dementia, some antipsychotics and antidepressants have been studied and used clinically for those purposes. Clinicians may consider vitamin E, Ginkgo biloba extract, choline alfoscerate, or omega-3 fatty acids as additional treatment options. Non-steroid anti-inflammatory drugs, estrogen hormone therapy, and statins are not generally recommended for dementia treatment. We believe that our findings will aid clinicians in the treatment of patients with cognitive decline.
Acetylcholinesterase ; Activities of Daily Living ; Aging ; Antidepressive Agents ; Antipsychotic Agents ; Cholinesterase Inhibitors ; Cognition ; Dementia ; Drug Therapy ; Estrogens ; Fatty Acids, Omega-3 ; Ginkgo biloba ; Glycerylphosphorylcholine ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Memantine ; Memory ; National Health Programs ; Public Health ; Rivastigmine ; Vitamin E ; Vitamins

Delayed carbon monoxide (CO) encephalopathy patients can show cognitive impairment, aphasia, affective and personality changes and behavioral symptoms. The prognosis of them is sometimes poor or irreversible. We present a case of 61-year-old woman who visited us at 56 days after CO intoxication and showed moderate to severe cognitive impairment and behavioral problems. We prescribed the donepezil (5 mg/d), memantine (5 mg/d), choline alfoscerate (800 mg/d) and ziprasidone (20 mg/d), based on previous case reports and performed the cognitive rehabilitation. After 30 days treatment in hospital, she showed dramatic improvement in cognitive functions and behavioral problems. This case suggests that adequate pharmacological and cognitive treatment could improve the moderate to severe symptoms of delayed CO encephalopathy even about 2 months later after CO intoxication.
Aphasia ; Behavioral Symptoms ; Brain Diseases* ; Carbon Monoxide* ; Carbon* ; Cognition ; Cognition Disorders ; Female ; Glycerylphosphorylcholine ; Humans ; Memantine ; Middle Aged ; Problem Behavior ; Prognosis ; Rehabilitation

OBJECTIVE: Autophagy is one of the key responses of cells to programmed cell death. Memantine, an approved anti-dementia drug, has an antiproliferative effect on cancer cells but the mechanism is poorly understood. The aim of the present study was to test the possibility of induction of autophagic cell death by memantine in glioma cell lines. METHODS: Glioma cell lines (T-98 G and U-251 MG) were used for this study. RESULTS: The antiproliferative effect of memantine was shown on T-98 G cells, which expressed N-methyl-D-aspartate 1 receptor (NMDAR1). Memantine increased the autophagic-related proteins as the conversion ratio of light chain protein 3-II (LC3-II)-/LC3-I and the expression of beclin-1. Memantine also increased formation of autophagic vacuoles observed under a transmission electron microscope. Transfection of small interfering RNA (siRNA) to knock down NMDAR1 in the glioma cells induced resistance to memantine and decreased the LC3-II/LC3-I ratio in T-98 G cells. CONCLUSION: Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.
Autophagy* ; Cell Death ; Cell Line ; Gastrin-Secreting Cells ; Glioma* ; Memantine* ; N-Methylaspartate ; RNA, Small Interfering ; Transfection ; Vacuoles

Pharmacotherapy has been constantly chosen by the clinician among the available treatment options for tinnitus. Medications that have been prescribed off-label to treat tinnitus can be grouped into several categories: benzodiazepines, antidepressants, anticonvulsants, N-methyl-D-aspartate (NMDA) receptor antagonists, dopamine receptor modulators, muscle relaxants, and others. In this article, a wide variety of compounds once used in the treatment of tinnitus and evidenced by clinical trials are reviewed with respect to the mechanisms of action and the drug efficacy. Only a few of the various pharmacological interventions investigated have some beneficial effects against tinnitus: clonazepam, acamprosate, neramexan, and sulpiride. Sertraline and pramipexole were effective in subgroups of patients with psychiatric symptoms or presbycusis. However, no agents have been identified to provide a reproducible long-term reduction of tinnitus in excess of placebo effects. In rodent tinnitus models, L-baclofen, memantine, and KCNQ2/3 channel activators have been demonstrated to reduce tinnitus development. Limitation of the use of an effective high dosage during a longer treatment duration due to dose-dependent side effects of the centrally acting drugs may influence the results in clinical studies. More effective and safer innovative agents should be developed based on the further understanding of tinnitus neural mechanisms and valid animal models, and should be supported by improved clinical trial methodology. The management of tinnitus patients through a tailored treatment approach depending on the detailed classification of tinnitus subtypes will also lead to better treatment outcomes.
Anticonvulsants ; Antidepressive Agents ; Benzodiazepines ; Classification ; Clonazepam ; Dopamine Agonists ; Dopamine Antagonists ; Drug Therapy ; Humans ; Memantine ; Models, Animal ; N-Methylaspartate ; Placebo Effect ; Presbycusis ; Rodentia ; Sertraline ; Sulpiride ; Tinnitus*

Schizophrenia is considered a neurodevelopmental disorder; however, all the available treatment options are used when the disease becomes clinically significant in adolescence or early adulthood. Using a developmental rat model of schizophrenia, we examined whether neonatal treatment with memantine, an NMDA receptor modulator, can improve schizophrenic-like symptoms in adulthood. Early maternal deprivation in rats produces deficits in social interaction behaviors in adulthood. In contrast, memantine administrated in neonatal rats subjected to early maternal deprivation significantly reduces deficits in social interaction behaviors in adulthood. These results raise the possibility that pharmacological treatment with memantine at the early developmental stage helps people with a risk to develop schizophrenic-like symptoms.
Adolescent ; Adult* ; Animals ; Cognition* ; Glutamic Acid ; Humans ; Interpersonal Relations ; Maternal Deprivation* ; Memantine* ; Models, Animal ; N-Methylaspartate ; Neurodevelopmental Disorders ; Neuropharmacology ; Rats* ; Schizophrenia

BACKGROUND AND PURPOSE: Although the treatment efficacy of memantine in Parkinson's disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using (99m)Tc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT). METHODS: A total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD. RESULTS: The PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR (p=0.32), sum of box of CDR (p=0.49), MMSE (p=0.61), GDS (p=0.79), and NPI (p=0.23) were not significant in the PDD patients. CONCLUSIONS: Our findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.
Brain ; Cerebrovascular Circulation ; Cognition ; Dementia* ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Memantine* ; Parkinson Disease ; Perfusion* ; Prospective Studies* ; Tomography, Emission-Computed, Single-Photon* ; Treatment Outcome