Reference | [1]. Ann Clin Psychiatry. 2018 Aug;30(3):234-248.<br />
The use of memantine in neuropsychiatric disorders: An overview.<br />
Lu S(1), Nasrallah HA.<br />
Author information: (1)Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine, St. Louis, MO 63104 USA; E-MAIL: [email protected].<br />
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.<br />
PMID: 30028898 [Indexed for MEDLINE]<br />
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[2]. J Alzheimers Dis. 2017;60(2):401-425. doi: 10.3233/JAD-170424.<br />
Memantine for Alzheimer's Disease: An Updated Systematic Review and Meta-analysis.<br />
Kishi T(1), Matsunaga S(1), Oya K(1), Nomura I(1), Ikuta T(2), Iwata N(1).<br />
Author information: (1)Department of Psychiatry, Fujita Health University School of Medicine, Kutsukake-cho, Toyoake, Aichi, Japan. (2)Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University MS, USA.<br />
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.<br />
DOI: 10.3233/JAD-170424 PMID: 28922160 [Indexed for MEDLINE]<br />
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[3]. J Alzheimers Dis. 2017;57(1):113-121. doi: 10.3233/JAD-161251.<br />
A Meta-Analysis of Memantine for Depression.<br />
Kishi T, Matsunaga S, Iwata N.<br />
We conducted a systematic review and meta-analysis on whether memantine was beneficial for the treatment of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). The analysis included double-blind, randomized, placebo-controlled trials of memantine in MDD and BD. The primary outcome measures for efficacy and safety were response rate and all-cause discontinuation, respectively. Risk ratio (RR) and standardized mean difference with 95% confidence intervals (95% CI) were calculated. We identified six trials including 451 patients: MDD, four trials (n = 189), three of which studied memantine augmentation for antidepressants; BD, two trials (n = 262), both on memantine augmentation for mood stabilizers. The mean study duration was 8.33 weeks, and the mean age of patients was 39.9 years. Memantine was not superior to placebo with regard to response rate (RR = 0.92, 95% CI = 0.70-1.20, I2 = 72%), remission rate, improvement of depressive symptoms scale score, all-cause discontinuation (RR = 0.84, 95% CI = 0.60-1.18, I2 = 0%), discontinuation due to inefficacy and adverse events, or incidence of individual adverse events including decreased appetite, dizziness, nausea, and sedation. Although we conducted sensitivity analyses of the response rate to determine the reasons for the heterogeneity (diagnosis, age of patients, memantine dose, memantine augmentation, geographical region, and statistical population), we did not seek confounding factors. Memantine did not improve the treatment efficacy for depressive symptoms in MDD and BD patients. Long-term study of memantine for depression is required.<br />
DOI: 10.3233/JAD-161251 PMID: 28222534 [Indexed for MEDLINE]<br />
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[4]. PLoS One. 2015 Apr 10;10(4):e0123289. doi: 10.1371/journal.pone.0123289. eCollection 2015.<br />
Memantine monotherapy for Alzheimer's disease: a systematic review and meta-analysis.<br />
Matsunaga S(1), Kishi T(1), Iwata N(1).<br />
Author information: (1)Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.<br />
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.<br />
DOI: 10.1371/journal.pone.0123289 PMCID: PMC4393306 PMID: 25860130 [Indexed for MEDLINE]<br />
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[5]. J Clin Psychiatry. 2019 Dec 3;80(6):19f13163. doi: 10.4088/JCP.19f13163.<br />
Augmentation With Memantine in Obsessive-Compulsive Disorder.<br />
Andrade C(1).<br />
Author information: (1)Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India. [email protected].<br />
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.<br />
DOI: 10.4088/JCP.19f13163 PMID: 31846244 [Indexed for MEDLINE]
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