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BMJ Open Apr 2022To examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer's dementia (AD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer's dementia (AD).
DESIGN
Systematic review and individual patient data (IPD) network meta-analysis (NMA) based on our previously published systematic review and aggregate data NMA.
DATA SOURCES
MEDLINE, Embase, Cochrane Methodology Register, CINAHL, AgeLine and Cochrane Central Register of Controlled Trials up to March 2016.
PARTICIPANTS
80 randomised controlled trials (RCTs) including 21 138 adults with AD, and 12 RCTs with IPD including 6906 patients.
INTERVENTIONS
Cognitive enhancers (donepezil, rivastigmine, galantamine and memantine) alone or in any combination against other cognitive enhancers or placebo.
DATA EXTRACTION AND SYNTHESIS
We requested IPD from authors, sponsors and data sharing platforms. When IPD were not available, we used aggregate data. We appraised study quality with the Cochrane risk-of-bias. We conducted a two-stage random-effects IPD-NMA, and assessed their findings using CINeMA (Confidence in Network Meta-Analysis).
PRIMARY AND SECONDARY OUTCOMES
We included trials assessing cognition with the Mini-Mental State Examination (MMSE), and adverse events.
RESULTS
Our IPD-NMA compared nine treatments (including placebo). Donepezil (mean difference (MD)=1.41, 95% CI: 0.51 to 2.32) and donepezil +memantine (MD=2.57, 95% CI: 0.07 to 5.07) improved MMSE score (56 RCTs, 11 619 participants; CINeMA score: moderate) compared with placebo. According to P-score, oral rivastigmine (OR=1.26, 95% CI: 0.82 to 1.94, P-score=16%) and donepezil (OR=1.08, 95% CI: 0.87 to 1.35, P-score=30%) had the least favourable safety profile, but none of the estimated treatment effects were sufficiently precise when compared with placebo (45 RCTs, 15 649 patients; CINeMA score: moderate to high). For moderate-to-severe impairment, donepezil, memantine and their combination performed best, but for mild-to-moderate impairment donepezil and transdermal rivastigmine ranked best. Adjusting for MMSE baseline differences, oral rivastigmine and galantamine improved MMSE score, whereas when adjusting for comorbidities only oral rivastigmine was effective.
CONCLUSIONS
The choice among the different cognitive enhancers may depend on patient's characteristics. The MDs of all cognitive enhancer regimens except for single-agent oral rivastigmine, galantamine and memantine, against placebo were clinically important for cognition (MD larger than 1.40 MMSE points), but results were quite imprecise. However, two-thirds of the published RCTs were associated with high risk of bias for incomplete outcome data, and IPD were only available for 15% of the included RCTs.
PROSPERO REGISTRATION NUMBER
CRD42015023507.
Topics: Adult; Alzheimer Disease; Donepezil; Galantamine; Humans; Memantine; Network Meta-Analysis; Nootropic Agents; Rivastigmine
PubMed: 35473731
DOI: 10.1136/bmjopen-2021-053012 -
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 -
Human Psychopharmacology Sep 2022The United States Food and Drug Administration has approved drugs that address only autism-related symptoms rather than the underlying impairments. N-Methyl-D-Aspartate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The United States Food and Drug Administration has approved drugs that address only autism-related symptoms rather than the underlying impairments. N-Methyl-D-Aspartate receptor antagonists have recently emerged as a promising treatment option for a variety of neurologic and developmental problems, including autism.
AIMS
To review (systematically), for the first time, the medical literature that explores the safety in and efficacy of memantine in autism.
METHODS AND PROCEDURES
A comprehensive electronic search for relevant randomized controlled trials was conducted in four databases. Using RevMan software, we extracted and pooled data as a risk ratio (RR) or normalized mean differences in an inverse variance strategy.
RESULTS
This systematic review and meta-analysis includes five trials. There was no difference in enhancing social responsiveness when compared to placebo, though memantine lowered the likelihood of anxiety (RR = 0.25; 95% Confidence interval: [0.07; 0.87], p = 0.03). However, memantine aggravated impulsive behaviors. Additionally, in another trial that compared memantine added to risperidone versus risperidone added to placebo, memantine was found to be effective and safe.
CONCLUSION
Memantine showed safety in reducing acute symptoms of anxiety and other symptoms encountered in pediatric patients with autism spectrum disorders. However, memantine does not improve the core symptoms of autism. Nevertheless, further long-term trials are needed to explore its potential efficacy.
Topics: Anxiety Disorders; Autism Spectrum Disorder; Child; Excitatory Amino Acid Antagonists; Humans; Memantine; Risperidone
PubMed: 35315131
DOI: 10.1002/hup.2841 -
International Journal of Environmental... Feb 2022Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) is the second most common cause of optic nerve-related permanent visual loss in adults.
AIM
We aimed to analyze the efficacy of the noninvasive and minimally invasive therapeutic options of NAION.
METHODS
We performed a systematic literature search in MEDLINE, EMBASE, and CENTRAL from inception to 10 June 2019 to identify the studies that report on the effect of different therapies on visual acuity (VA) and visual field (VF). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated for these outcomes. The efficacy of steroids was investigated in quantitative, oxygen, steroid plus erythropoietin (EPO), levodopa/carbidopa, memantine, and heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP) therapies and other therapeutic modalities in qualitative synthesis.
RESULTS
Thirty-two studies were found to be eligible. We found that steroid therapy compared to control did not improve VA ( = 0.182, WMD = 0.14, 95% CI: -0.07, 0.35) or VF ( = 0.853, WMD = 0.16, 95% CI: -1.54, 1.86). Qualitative analysis could be performed for oxygen, steroid plus EPO, and HELP as well, however, none of them showed VA and VF benefit. Two individual studies found memantine and levodopa beneficial regarding VA.
CONCLUSION
Our systematic review did not reveal any effective treatment. Further investigations are needed to find therapy for NAION.
Topics: Adult; Humans; Levodopa; Memantine; Optic Neuropathy, Ischemic; Oxygen; Steroids; Visual Acuity
PubMed: 35270411
DOI: 10.3390/ijerph19052718 -
Acta Psychiatrica Scandinavica Apr 2022The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT.
METHODS
Electronic databases of Pubmed, PsycInfo, Embase and Scopus were searched from inception through 1 April, 2021, using terms for ECT (e.g. electroconvulsive therapy), cognitive outcome (e.g. cogni*) and pharmacological intervention (e.g. calcium channel blocker and general terms, like protein). Original studies with humans receiving ECT were included, which applied pharmacological interventions in comparison with placebo or no additive intervention to diminish cognitive side effects. Data quality was assessed using Risk of Bias and GRADE. Random-effects models were used. PROSPERO registration number was CRD42021212773.
RESULTS
Qualitative synthesis (systematic review) showed 52 studies reporting sixteen pharmacological intervention-types. Quantitative synthesis (meta-analysis) included 26 studies (1387 patients) describing twelve pharmacological intervention-types. Low-quality evidence of efficacy was established for memantine (large effect size) and liothyronine (medium effect size). Very low-quality evidence shows effect of acetylcholine inhibitors, piracetam and melatonin in some cognitive domains. Evidence of no efficacy was revealed for ketamine (very low-quality), herbal preparations with anti-inflammatory properties (very low to low-quality) and opioid receptor agonists (low-quality).
CONCLUSION
Memantine and liothyronine are promising for further research and future application. Quality of evidence was low because of differences in ECT techniques, study populations and cognitive measurements. These findings provide a guide for rational choices of potential pharmacological intervention research targets to decrease the burden of cognitive side effects of ECT. Future research should be more uniform in design and attempt to clarify pathophysiological mechanisms of cognitive side effects of ECT.
Topics: Cognition; Electroconvulsive Therapy; Humans; Ketamine; Memantine; Triiodothyronine
PubMed: 35075641
DOI: 10.1111/acps.13397 -
Ageing Research Reviews Mar 2022Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial... (Meta-Analysis)
Meta-Analysis Review
Psychotic symptoms of dementia are highly prevalent and lead to poor medical outcomes and substantial dysfunction. To date, which drug to use remains controversial without a summary of all direct or indirect comparisons of pharmacotherapy. Therefore, we conducted a systematic review with pairwise and network meta-analysis to examine efficacy and tolerability outcomes of pharmacological treatments in dementia patients. MEDLINE, Cochrane Library, EMBASE, and PubMed were searched systematically up to August 31, 2020. We included trials of cholinesterase inhibitors (ChEIs), memantine, antipsychotics, antidepressants, and mood stabilizers, with final approval from the U.S. Food and Drug Administration. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. This analysis is based on 34 trials, which included 10,415 patients randomly assigned to 15 commonly used drug regimens. Donepezil (standardized mean difference [SMD] -0.30, 95% credible interval [CrI] -0.50 to -0.12; SUCRA, 0.85), memantine (SMD -0.20, 95%CrI -0.34 to -0.07; SUCRA, 0.68) and aripiprazole (SMD -0.17, 95% CrI -0.32 to -0.02; SUCRA, 0.62) showed greater benefit than placebo, and with relatively good tolerability in network meta-analyses. Risperidone was also found to be more efficacious than placebo (SMD -0.16, 95% CrI -0.28 to -0.05; SUCRA, 0.60), but with poor tolerability (odds ratios [OR] 1.50, 95% CrI 1.06-2.26). Donepezil, memantine, haloperidol, aripiprazole and risperidone were more efficacious than quetiapine (SMDs ranged from -0.36 to -0.22). Besides, donepezil, memantine and mirtazapine were more efficacious than sertraline (SMDs ranged from -0.47 to -0.36). Most of the results were rated as "low" to "very low". Several effective treatment choices for psychotic symptoms are available across drug classes. Donepezil, memantine and aripiprazole are probably the appropriate options to consider when a pharmacological treatment is indicated. Given the limitations of the meta-analytic approach and the low methodological quality of the majority of studies, our results should be cautiously interpreted.
Topics: Aripiprazole; Dementia; Donepezil; Humans; Memantine; Network Meta-Analysis; Risperidone; United States
PubMed: 35051646
DOI: 10.1016/j.arr.2022.101568 -
Current Neuropharmacology 2022Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient...
BACKGROUND
Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient treatment, the poor adherence in advanced patients, and varied response. Proper intake of medications regarding food and managing drug-food interactions may optimize Parkinson's disease treatment.
OBJECTIVES
We investigated potential effects that food, beverages, and dietary supplements may have on the pharmacokinetics and pharmacodynamics of drugs used by parkinsonian patients; identified the most probable interactions; and shaped recommendations for the optimal intake of drugs regarding food.
METHODS
We performed a systematic review in adherence to PRISMA guidelines, and included a total of 81 studies in the qualitative synthesis.
RESULTS AND CONCLUSION
We found evidence for levodopa positive interaction with coffee, fiber and vitamin C, as well as for the potential beneficial impact of low-fat and protein redistribution diet. Contrastingly, high-protein diet and ferrous sulfate supplements can negatively affect levodopa pharmacokinetics and effectiveness. For other drugs, the data of food impact are scarce. Based on the available limited evidence, all dopamine agonists (bromocriptine, cabergoline, ropinirole), tolcapone, rasagiline, selegiline in tablets, safinamide, amantadine and pimavanserin can be taken with or without a meal. Opicapone and orally disintegrating selegiline tablets should be administered on an empty stomach. Of monoamine oxidase B inhibitors, safinamide is the least susceptible for interaction with the tyramine-rich food, whereas selegiline and rasagiline may lose selectivity to monoamine oxidase B when administered in supratherapeutic doses. The level of presented evidence is low due to the poor studies design, their insufficient actuality, and missing data.
Topics: Antiparkinson Agents; Dietary Supplements; Humans; Levodopa; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34784871
DOI: 10.2174/1570159X19666211116142806 -
Systematic Reviews Oct 2021The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in... (Review)
Review
PURPOSE
The aim of this study was to review the scientific evidence and describe the ocular treatment-emergent adverse events (TEAEs) related to pharmacological treatment in patients with multiple sclerosis.
METHODS
A systematic review of literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines in the MEDLINE, LILACS, EMBASE, and COCHRANE databases. Articles were filtered based on title and abstract considering the selection criteria and subsequently filtered by full-text reading. The resulting articles were evaluated using the Joanna Briggs Institute Quality Tools. Study characteristics and results were extracted and presented in structured tables to conduct a narrative synthesis.
RESULTS
A total of 2852 published articles were extracted using our strategy. After removing duplicates, 2841 articles were screened based on title and abstract, 102 articles were evaluated using quality tools, and 69 articles were filtered by full-text reading. Through this search strategy, 60 articles met all the inclusion criteria and seven articles, through a search update conducted in the same manner, were included. This resulted in 67 articles meeting the inclusion criteria, of which 11 were experimental and 56 were observational. The therapies related to ocular TEAEs were alemtuzumab, amantadine, fingolimod, steroids, CTLA-4 Ig, estriol, interferon β, natalizumab, hyperbaric oxygen, rituximab, siponimod, teriflunomide, and tovaxin. Fingolimod and siponimod were commonly associated with macular edema, interferon β was associated with retinopathy, alemtuzumab was associated with thyroid eye disease, amantadine was associated with corneal edema, and steroids were associated with acute retinal necrosis. Opportunistic infections were also found, and there was one life-threatening case.
CONCLUSIONS
Our search revealed different methodological assessments of the topic. However, longitudinal studies regarding ocular TEAEs related to multiple sclerosis therapy are necessary to provide evidence-based recommendations, especially in understudied regions such as Latin America and Africa. Physicians should monitor ocular symptoms in patients being treated for multiple sclerosis and consider an interdisciplinary approach.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO ID CRD42020106886.
Topics: Africa; Humans; Multiple Sclerosis
PubMed: 34711264
DOI: 10.1186/s13643-021-01782-7 -
Journal of Geriatric Psychiatry and... Jul 2022Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy...
IMPORTANCE
Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear.
OBJECTIVE
To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy.
METHODS
The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020.
RESULTS
Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research.
CONCLUSION
Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Drug Therapy, Combination; Humans; Indans; Memantine; Piperidines
PubMed: 34476990
DOI: 10.1177/08919887211044746 -
Headache Sep 2021The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine.
OBJECTIVE
The purpose of this systematic review is to assess the efficacy and safety of memantine for the prophylactic treatment of episodic migraine.
BACKGROUND
Migraine is a prevalent chronic disease with significant costs to the health care system. Although various prophylactic treatment options are available, these medications have limitations based on efficacy, potential side effects, and patient preference. Memantine is an N-methyl-d-aspartate receptor antagonist used in dementia treatment that may have potential benefit for migraine prophylaxis.
METHODS
A systematic search of PubMed, Embase, and CENTRAL databases was conducted to identify relevant published studies through December 2020 using the search terms: migraine disorders, migraine, headache disorders, or headache and memantine. Studies selected for the systematic review included prospective, interventional designs and evaluated memantine for prophylaxis of migraine. Animal studies, case reports, abstracts, review articles, protocols without results, and studies not written in English were excluded. Data were extracted using a standardized systematic process and included author, publication date, study design, sample size, patient characteristics, treatment regimen, clinical efficacy outcomes, and adverse drug effects.
RESULTS
Four articles were identified for inclusion representing two prospective open-label studies and two randomized, double-blind trials, evaluating 183 patients on memantine overall. A reduction in number of migraine days and headache severity were shown in all four studies in the participants treated with memantine. The most common adverse effects included somnolence, sedation, and nausea, none of which were severe.
CONCLUSION
The studies in this review establish that memantine has the potential for use as a treatment option for episodic migraine. Additional long-term studies using an active comparator would be useful to further elucidate its role.
Topics: Excitatory Amino Acid Antagonists; Humans; Memantine; Migraine Disorders; Outcome Assessment, Health Care; Receptors, N-Methyl-D-Aspartate
PubMed: 34352118
DOI: 10.1111/head.14186