-
Journal of Clinical PsychopharmacologyObsessive-compulsive disorder (OCD) affects 2% to 3% of adults worldwide. Although serotonin reuptake inhibitors (SRIs) reliably demonstrate efficacy for this condition,... (Review)
Review
BACKGROUND
Obsessive-compulsive disorder (OCD) affects 2% to 3% of adults worldwide. Although serotonin reuptake inhibitors (SRIs) reliably demonstrate efficacy for this condition, 40% to 60% of patients only achieve partial recovery. The purpose of this systematic review was to assess the efficacy of other agents that may be used as augmentation agents for patients who are partial responders to SRI monotherapy.
METHODS
Using PRISMA-P guidelines, PubMed and Embase were searched using the randomized controlled trial (RCT) filter and the key word "obsessive-compulsive disorder." To be considered for analysis, a potential augmentation agent needed to have at least 2 RCTs. This review specifically analyzes the effect of each augmentation agent on OCD symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale.
RESULTS
The augmentation agents analyzed in this review are d -cycloserine (2 RCTs), memantine (4 RCTs), N -acetylcysteine (5 RCTs), lamotrigine (2 RCTs), topiramate (3 RCTs), riluzole (2 RCTs), ondansetron (2 RCTs), celecoxib (2 RCTs), aripiprazole (5 RCTs), risperidone (7 RCTs), quetiapine (9 RCTs), and olanzapine (3 RCTs).
IMPLICATIONS
The augmentation agents most supported by this review for OCD that is only a partial response to SRI monotherapy are lamotrigine, memantine, and aripiprazole. If an antipsychotic must be used and aripiprazole is not tolerated, risperidone may be considered as an alternative. Unlike the SRI class effect for OCD symptom reduction, augmentation agents demonstrate considerable intraclass variability.
Topics: Adult; Humans; Selective Serotonin Reuptake Inhibitors; Risperidone; Aripiprazole; Lamotrigine; Memantine; Drug Therapy, Combination; Systematic Reviews as Topic; Meta-Analysis as Topic; Antipsychotic Agents; Obsessive-Compulsive Disorder; Anticonvulsants; Treatment Outcome
PubMed: 37335203
DOI: 10.1097/JCP.0000000000001716 -
Cells Jun 2023Memantine is an FDA-approved, non-competitive NMDA-receptor antagonist that has been shown to have mitochondrial protective effects, improve cell viability and enhance...
Memantine is an FDA-approved, non-competitive NMDA-receptor antagonist that has been shown to have mitochondrial protective effects, improve cell viability and enhance clearance of Aβ peptide. Currently, there are uncertainties regarding the precise molecular targets as well as the most favourable treatment concentrations of memantine. Here, we made use of an imaging-based approach to investigate the concentration-dependent effects of memantine on mitochondrial fission and fusion dynamics, autophagy and mitochondrial quality control using a neuronal model of CCCP-induced mitochondrial injury so as to better unpack how memantine aids in promoting neuronal health. GT1-7 murine hypothalamic cells were cultured under standard conditions, treated with a relatively high and low concentration (100 µM and 50 µM) of memantine for 48 h. Images were acquired using a Zeiss 780 PS1 platform. Utilising the mitochondrial event localiser (MEL), we demonstrated clear concentration-dependent effects of memantine causing a protective response to mitochondrial injury. Both concentrations maintained the mitochondrial network volume whilst the low concentration caused an increase in mitochondrial number as well as increased fission and fusion events following CCCP-induced injury. Additionally, we made use of a customised Python-based image processing and analysis pipeline to quantitatively assess memantine-dependent changes in the autophagosomal and lysosomal compartments. Our results revealed that memantine elicits a differential, concentration-dependent effect on autophagy pathway intermediates. Intriguingly, low but not high concentrations of memantine lead to the induction of mitophagy. Taken together, our findings have shown that memantine is able to protect the mitochondrial network by preserving its volume upon mitochondrial injury with high concentrations of memantine inducing macroautophagy, whereas low concentrations lead to the induction of mitophagy.
Topics: Mice; Animals; Mitophagy; Memantine; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Autophagy; Mitochondria
PubMed: 37443760
DOI: 10.3390/cells12131726 -
Molecular Pharmaceutics May 2022Alzheimer's disease is a chronic disease, and the long-term treatment of chronic diseases has always been a concern. Memantine (Mem) is approved by the US Food and Drug...
Alzheimer's disease is a chronic disease, and the long-term treatment of chronic diseases has always been a concern. Memantine (Mem) is approved by the US Food and Drug Administration for the treatment of moderate to severe Alzheimer's disease. In this study, reactions of memantine (Mem) with pamoic acid (Pam) were carried out to form insoluble salts (Mem-Pam). Four polymorphic forms (Forms I-IV) of Mem-Pam were successfully obtained through polymorphic screening, which were systematically characterized by X-ray powder diffraction (PXRD), thermal analysis (TGA and DSC), single-crystal X-ray diffraction (SXRD), and solid-state fluorescence. Compared with the hydrochloride form, the dissolution and release rates of these four forms are lower. The presence of pamoic acid reduces the release rate of memantine and makes it possible to achieve a sustained release of the drug. Interestingly, because of the presence of memantine, each polymorphic solid crystal of Mem-Pam has unique fluorescence emission. Therefore, memantine and pamoic acid have a synergistic effect on the fluorescence performance and can be expected to be used for real-time monitoring in continuous and controlled release drug delivery systems. In addition, the polymorphic solid crystals also exhibit reversible mechanochromic luminescence under the fumigation of acetonitrile vapor, which has a guiding role in the fluorescence design and synthesis of Pam substances and is expected to be used for information security, visual inspection of organic substances, etc.
Topics: Alzheimer Disease; Humans; Memantine; Powders; Sodium Chloride; X-Ray Diffraction
PubMed: 35230851
DOI: 10.1021/acs.molpharmaceut.1c00931 -
Neuropharmacology Feb 2024The great potential for NMDA receptor modulators as druggable targets in neurodegenerative disorders has been met with limited success. Considered one of the rare... (Review)
Review
The great potential for NMDA receptor modulators as druggable targets in neurodegenerative disorders has been met with limited success. Considered one of the rare exceptions, memantine has consistently demonstrated restorative and prophylactic properties in many AD models. In clinical trials memantine slows the decline in cognitive performance associated with AD. Here, we provide an overview of the basic properties including pharmacological targets, toxicology and cellular effects of memantine. Evidence demonstrating reductions in molecular, physiological and behavioural indices of AD-like impairments associated with memantine treatment are also discussed. This represents both an extension and homage to Dr. Chris Parson's considerable contributions to our fundamental understanding of a success story in the AD treatment landscape.
Topics: Humans; Memantine; Alzheimer Disease; Receptors, N-Methyl-D-Aspartate; Cognition
PubMed: 37832633
DOI: 10.1016/j.neuropharm.2023.109737 -
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 -
Journal of Molecular Medicine (Berlin,... Mar 2021Memantine is used in Alzheimer's disease treatment as a non-competitive modern-affinity strong voltage-dependent N-methyl-D-aspartate receptor antagonist. The... (Review)
Review
Memantine is used in Alzheimer's disease treatment as a non-competitive modern-affinity strong voltage-dependent N-methyl-D-aspartate receptor antagonist. The fundamental role of these receptors is to bind glutamate: the main excitatory neurotransmitter in the brain, believed to play a crucial role in neuronal plasticity and learning mechanisms. Glutamate transmission plays an important role in all internal CNS structures and maintains the physiological state of the brain. Excessive glutamate transmission can lead to enlarged calcium ion current which may cause neurotoxicity; however, insufficient transmission can drastically alter the information flow in neurons and the brain, potentially causing schizophrenia-like symptoms by replacing lost information with completely new stimuli. Hence, it is possible that the modulation of NMDA activity may give rise to pathophysiological states. Available literature and clinical trials indicate that memantine is well tolerated by patients, with very few and light side effects. There is a belief that memantine may also benefit other conditions such as schizophrenia and depression.
Topics: Alzheimer Disease; Antidepressive Agents; Antipsychotic Agents; Clinical Trials as Topic; Depression; Drug Repositioning; Excitatory Amino Acid Antagonists; Glutamic Acid; Humans; Memantine; N-Methylaspartate; Neuronal Plasticity; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Serotonin 5-HT3 Receptor Antagonists
PubMed: 33447926
DOI: 10.1007/s00109-020-01982-z -
Journal of Affective Disorders Jun 2022To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis Review
The efficacy and tolerability of memantine for depressive symptoms in major mental diseases: A systematic review and updated meta-analysis of double-blind randomized controlled trials.
OBJECTIVE
To date, there is limited evidence on the antidepressant effects of memantine in patients with major mental diseases. We conducted a systematic review and meta-analysis to assess the efficacy of memantine in such populations.
METHODS
A literature search was performed for randomized controlled trials (RCTs) from the date of their inception until September 28, 2021, using PubMed, Medline, Embase, and the Cochrane Library. Changes in depression scores were the primary outcome. The response rate and remission rate to the treatment were secondary outcomes. We also assessed the dropout rate for tolerance.
RESULTS
Eleven double-blind RCTs were included with 899 participants. Memantine significantly reduced depressive symptom scores compared with the control group (k = 11, n = 899, Hedges' g = -0.17, 95% confidence interval [CI] = -0.30 to -0.04, p = 0.009) with a small effect size. For secondary outcomes, memantine did not show a significant effect on response rate nor remission rate. In the subgroup analysis, memantine significantly reduced depressive symptom scores in patients with mood disorders (k = 8, n = 673, Hedges' g = -0.17, 95% CI = -0.32 to -0.01, p = 0.035) with a small effect size, but not in patients with schizophrenia.
CONCLUSION
The present meta-analysis indicates that memantine effectively alleviates depressive symptoms in patients with mood disorders with a small effect size. Furthermore, memantine is well-tolerated and acceptable.
Topics: Antidepressive Agents; Depression; Humans; Memantine; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 35331821
DOI: 10.1016/j.jad.2022.03.047 -
Journal of Personalized Medicine May 2022Donepezil and memantine are the most common drugs used for Alzheimer's disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to...
Donepezil and memantine are the most common drugs used for Alzheimer's disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to identify Single Nucleotide Polymorphisms (SNPs) associated with pharmacokinetics, pharmacodynamics, and the safety of donepezil and memantine. For this regard, 25 volunteers enrolled in a bioequivalence clinical trial were genotyped for 67 SNPs in 21 genes with a ThermoFisher QuantStudio 12K Flex OpenArray. The statistical strategy included a univariate analysis that analyzed the association of these SNPs with pharmacokinetic parameters or the development of adverse drug reactions (ADRs) followed by a Bonferroni-corrected multivariate regression. Statistical analyses were performed with SPSS software v.21 and R commander (version v3.6.3). In the univariate analysis, fourteen and sixteen SNPs showed a significant association with memantine's and donepezil's pharmacokinetic parameters, respectively. Rs20417 () was associated with the development of at least one ADR. However, none of these associations reached the significance threshold in the Bonferroni-corrected multivariate analysis. In conclusion, we did not observe any significant association of the SNPs analyzed with memantine and donepezil pharmacokinetics or ADRs. Current evidence on memantine and donepezil pharmacogenetics does not justify their inclusion in pharmacogenetic guidelines.
PubMed: 35629210
DOI: 10.3390/jpm12050788 -
Science Advances Dec 2023Cortical spreading depolarization (CSD) is a promising target for neuroprotective therapy in traumatic brain injury (TBI). We explored the effect of NMDA receptor...
Cortical spreading depolarization (CSD) is a promising target for neuroprotective therapy in traumatic brain injury (TBI). We explored the effect of NMDA receptor antagonism on electrically triggered CSDs in healthy and brain-injured animals. Rats received either one moderate or four daily repetitive mild closed head impacts (rmTBI). Ninety-three animals underwent craniectomy with electrocorticographic (ECoG) and local blood flow monitoring. In brain-injured animals, ketamine or memantine inhibited CSDs in 44 to 88% and 50 to 67% of cases, respectively. Near-DC/AC-ECoG amplitude was reduced by 44 to 75% and 52 to 67%, and duration by 39 to 87% and 61 to 78%, respectively. Daily memantine significantly reduced spreading depression and oligemia following CSD. Animals ( = 31) were randomized to either memantine (10 mg/kg) or saline with daily neurobehavioral testing. Memantine-treated animals had higher neurological scores. We demonstrate that memantine improved neurovascular function following CSD in sham and brain-injured animals. Memantine also prevented neurological decline in a blinded, preclinical randomized rmTBI trial.
Topics: Rats; Animals; Memantine; Brain Injuries, Traumatic; Brain; Electrocorticography; Receptors, N-Methyl-D-Aspartate
PubMed: 38091390
DOI: 10.1126/sciadv.adj2417 -
Recent Patents on Biotechnology 2022Alzheimer's disease (AD) is a kind of neuropsychiatric illness that affects the central nervous system. In this disease, the accumulation of amyloid-beta increases, and... (Review)
Review
Alzheimer's disease (AD) is a kind of neuropsychiatric illness that affects the central nervous system. In this disease, the accumulation of amyloid-beta increases, and phosphorylated tau (P-tau) protein is one of the ways to treat this disease is to reduce the accumulation of amyloid-beta. Various studies have demonstrated that pharmacological approaches have considerable effects in the treatment of AD, despite the side effects and challenges. Cholinesterase inhibitors and the NMDA receptor antagonist memantine are presently authorized therapies for AD. Memantine and Donepezil are the most common drugs for the prevention and therapy of AD with mechanisms such as lessened β-amyloid plaque, affecting N-Methyl-D-aspartate (NMDA) receptors. Diminution glutamate and elevated acetylcholine are some of the influences of medications administrated to treat AD, and drugs can also play a role in slowing the progression of cognitive and memory impairment. A new pharmacological approach and strategy are required to control the future of AD. This review appraises the effects of memantine, donepezil, rivastigmine, and aducanumab in clinical trials, in vitro and animal model studies that have explored how these drugs versus AD development and also discuss possible mechanisms of influence on the brain. Research in clinical trials has substantial findings that support the role of these medications in AD treatment and ameliorate the safety and efficacy of AD therapy, although more clinical trials are required to prove their effectiveness.
Topics: Alzheimer Disease; Animals; Antibodies, Monoclonal, Humanized; Donepezil; Indans; Memantine; Patents as Topic; Piperidines; Rivastigmine
PubMed: 35236274
DOI: 10.2174/1872208316666220302115901