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Iranian Journal of Psychiatry Jul 2022Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating... (Review)
Review
Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating effects of glutamate receptor modulators in treating patients with resistant depression. The study protocol was registered in PROSPERO (CRD42021225516). Scopus, ISI Web of Science, Embase, Cochrane Library, Google Scholar, and three trial registries were searched up to September 2020 to find RCTs evaluating glutamate receptor modulators for resistant depression. The difference between intervention and control groups in changing depression scores from baseline to endpoint was considered the primary outcome. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the RCTs. No funding was received. Thirty-eight RCTs were included. Based on the included studies, compelling evidence was found for ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657); the results for MK-0657, amantadine, and nitrous oxide were only based on one study for each. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results for efficacy, and, riluzole, and 7-chlorokynurenic acid were mostly comparable to placebo. A limited number of studies were available that addressed drugs other than ketamine. The study cannot determine the difference between statistical and clinical significance between the agents and placebo due to high heterogeneity among the RCTs. Nevertheless, ketamine could be used as an efficacious drug in TRD; still, additional studies are needed to delineate the optimum dosage, duration of efficacy, and intervals. Further studies are also recommended on the effectiveness of glutamatergic system modulators other than ketamine on treatment-resistant depression.
PubMed: 36474699
DOI: 10.18502/ijps.v17i3.9733 -
BMJ Clinical Evidence Mar 2009During the autumn-winter months (influenza seasons), influenza circulates more frequently, causing a greater proportion of influenza-like illness, and sometimes serious... (Review)
Review
INTRODUCTION
During the autumn-winter months (influenza seasons), influenza circulates more frequently, causing a greater proportion of influenza-like illness, and sometimes serious seasonal epidemics. The incidence of infection depends on the underlying immunity of the population.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of vaccines to prevent influenza? What are the effects of antiviral chemoprophylaxis of influenza? What are the effects of antiviral medications to treat influenza? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: vaccines, amantadine, oseltamivir, zanamivir, rimantadine.
Topics: Acute Disease; Administration, Inhalation; Humans; Incidence; Influenza Vaccines; Influenza, Human; Oseltamivir; Rimantadine; Zanamivir
PubMed: 19445759
DOI: No ID Found -
The Canadian Journal of Neurological... May 2017Apathy is highly prevalent in Alzheimer's disease (AD), but whether pharmacotherapy is effective in managing apathy is unclear. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Apathy is highly prevalent in Alzheimer's disease (AD), but whether pharmacotherapy is effective in managing apathy is unclear.
METHODS
To assess the efficacy of pharmacotherapy for apathy in AD we searched for randomized controlled trials (RCT) and aggregate data reporting on apathy in several search engines, reference lists of articles, and reviews. Demographic characteristics and relevant data were extracted to assess apathy.
RESULTS
Fifteen RCTs' were examined, and 11 were used in aggregate meta-analytic statistics. Drugs included were cholinesterase inhibitors, memantine, and psycho-stimulants. We found no significant treatment effect in favour of any of the drugs, and the effect-size estimates under a random effect model were heterogeneous. Most RCTs had a high attrition rate and used the NPI apathy subscale to measure apathy.
CONCLUSION
The lack of an effect could be explained by methodological limitations, publication bias, and heterogeneity.
Topics: Alzheimer Disease; Apathy; Central Nervous System Stimulants; Cholinesterase Inhibitors; Clinical Trials as Topic; Excitatory Amino Acid Antagonists; Humans; Memantine
PubMed: 28148339
DOI: 10.1017/cjn.2016.426 -
Age and Ageing Jan 2013in 2007 the National Institute of Health and Clinical Excellence (NICE) restricted the use of acetylcholinesterase inhibitors and memantine. (Meta-Analysis)
Meta-Analysis Review
Evolution of the evidence on the effectiveness and cost-effectiveness of acetylcholinesterase inhibitors and memantine for Alzheimer's disease: systematic review and economic model.
INTRODUCTION
in 2007 the National Institute of Health and Clinical Excellence (NICE) restricted the use of acetylcholinesterase inhibitors and memantine.
METHODS
we conducted a health technology assessment (HTA) of the effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of AD to re-consider and up-date the evidence base used to inform the 2007 NICE decision. The systematic review of effectiveness targeted randomised controlled trials. A comprehensive search, including MEDLINE, Embase and the Cochrane Library, was conducted from January 2004 to March 2010. All key review steps were done by two reviewers. Random effects meta-analysis was conducted. The cost-effectiveness was assessed using a cohort-based model with three health states: pre-institutionalised, institutionalised and dead. The perspective was NHS and Personal Social Services and the cost year 2009.
RESULTS
confidence about the size and statistical significance of the estimates of effect of galantamine, rivastigmine and memantine improved on function and global impact in particular. Cost-effectiveness also changed. For donepezil, galantamine and rivastigmine, the incremental cost per quality-adjusted life year (QALY) in 2004 was above £50,000; in 2010 the same drugs 'dominated' best supportive care (improved clinical outcome at reduced cost). This was primarily because of changes in the modelled costs of introducing the drugs. For memantine, the cost-effectiveness also improved from a range of £37-53,000 per QALY gained to a base-case of £32,000.
CONCLUSION
there has been a change in the evidence base between 2004 and 2010 consistent with the change in NICE guidance. Further evolution in cost-effectiveness estimates is possible particularly if there are changes in drug prices.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Cost-Benefit Analysis; Evidence-Based Medicine; Humans; Memantine; Models, Economic; Quality-Adjusted Life Years; Receptors, N-Methyl-D-Aspartate; United Kingdom
PubMed: 23179169
DOI: 10.1093/ageing/afs165 -
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 -
Pharmacological Research Jun 2010The term neuroenhancement refers to improvement in the cognitive, emotional and motivational functions of healthy individuals through, inter alia, the use of drugs. Of... (Review)
Review
The term neuroenhancement refers to improvement in the cognitive, emotional and motivational functions of healthy individuals through, inter alia, the use of drugs. Of known interventions, psychopharmacology provides readily available options, such as the anti-dementia drugs, e.g. acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Based on a systematic review we found that expectations about the potential of these drugs exceed their actual effects, as has been demonstrated in randomised controlled trials. Both single and repeated dose trials were included in the systematic review, however repeated dose trials have only been conducted for donepezil. In six small trials lasting 14-42 days, the following results emerged: donepezil improved the retention of training on complex aviation tasks and verbal memory for semantically processed words. In one study episodic memory was improved, whereas in others it remained unaffected by donepezil. In a sleep deprivation trial, donepezil reduced the memory and attention deficits resulting from 24h of sleep deprivation. Two studies reported even transient negative effects. Regarding the safety profile of donepezil, these studies found that it was rather well tolerated. In any case, since large longitudinal studies are not available no conclusions can be drawn. Seven small studies about the effects of a single dose of memantine, and one study with a single dose of rivastigmine have been reported. Again, these studies are not adequate to answer our research question. If, as here and elsewhere suggested, the concept of pharmaceutical neuroenhancement is not to be rejected in principle, the decision of healthy individuals to take drugs for the purpose of neuroenhancement should be based on exhaustive information. At the moment, the research that would support or oppose the use of acetylcholinesterase inhibitors and memantine for neuroenhancement by healthy individuals has not yet been performed.
Topics: Cholinesterase Inhibitors; Cognition; Donepezil; Emotions; Excitatory Amino Acid Antagonists; Humans; Indans; Memantine; Motivation; Phenylcarbamates; Piperidines; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate; Rivastigmine
PubMed: 20193764
DOI: 10.1016/j.phrs.2010.02.009 -
Drugs & Aging 2006Alzheimer's disease (AD) is the most common form of dementia and is characterised by a worsening of cognition, functional ability, and behaviour and mood. The objective... (Review)
Review
Alzheimer's disease (AD) is the most common form of dementia and is characterised by a worsening of cognition, functional ability, and behaviour and mood. The objective of this study was to review the clinical and cost-effectiveness of memantine for the treatment of patients with moderately severe to severe AD. To achieve this, a systematic search and review of the clinical and cost effectiveness literature for memantine was undertaken. The literature search covered the period from the inception of MEDLINE, Cochrane Library, EMBASE and other electronic databases until July 2004. The search included randomised controlled trials (RCTs) and full economic evaluations that assessed the use of memantine in patients with moderately severe to severe AD. Two published RCTs were included in this review; in one of these trials the participants were already being treated with donepezil. The two RCTs showed benefit for patients receiving memantine compared with placebo on the outcome measures of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory modified for severe dementia, the Clinician's Interview-Based Impression of Change Plus Caregiver Input, and the Severe Impairment Battery, and that memantine appeared to be slightly more effective in patients already receiving a stable dose of donepezil. Five cost-effectiveness studies were included in the review. Although these studies reported cost reductions and improved outcomes with memantine, the evaluations were based on a number of assumptions. In conclusion, memantine appears to be beneficial when assessed using functional and global measurements. However, the effect of memantine on cognitive scores and behaviour and mood outcomes is less clear. Cost-effectiveness is dependent upon assumptions surrounding clinical effect and context-specific cost data.
Topics: Aged; Alzheimer Disease; Behavior; Clinical Trials as Topic; Cost-Benefit Analysis; Dopamine Agents; Humans; Memantine; Models, Economic; Outcome Assessment, Health Care; Quality-Adjusted Life Years; Treatment Outcome
PubMed: 16608378
DOI: 10.2165/00002512-200623030-00005 -
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 -
Microbial Pathogenesis Feb 2018This systematic review and meta-analysis was conducted to consolidate the information on the prevalence of the human influenza virus, including H1N1 and H3N2 as well as... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis was conducted to consolidate the information on the prevalence of the human influenza virus, including H1N1 and H3N2 as well as B-type influenza across Iran from 2000 to December 2016. The literature search was based on keywords including "influenza and Iran", "human influenza", "prevalence", "relative frequency", "incidence", and "drug" in MEDLINE (PubMed), Web of Science, Scopus, ScienceDirect, the Iranian Research Institute for Information Science and Technology (IranDoc), the Regional Information Centre for Science & Technology (RICeST), and the Scientific Information Database (SID). The literature search revealed 25 prevalence and seven drug resistance studies. In order to investigate the publication bias among studies, funnel plots and Egger's test were used. Additionally, the statistical tests of I, Chi, and Tau were computed, and the results were visualized with forest plots. A high level of I and Chi were obtained among studies, which are representative of the high variation and remarkable heterogeneity between studies. This may be because of various methodologies applied in the studies such as study design, age groups, and different populations. The prevalence of influenza H1N1, H3N2, and B in Iran have not yet been well evaluated. The heterogeneity among studies reveals that more attention should be paid to considering various factors, including gender, population size, and underlying conditions.
Topics: Amantadine; Antiviral Agents; Drug Resistance, Viral; Female; Humans; Incidence; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza B virus; Influenza, Human; Iran; Male; Oseltamivir; Prevalence; Zanamivir
PubMed: 29284132
DOI: 10.1016/j.micpath.2017.12.064 -
Health Technology Assessment... 2012Alzheimer’s disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK. (Review)
Review
The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model.
BACKGROUND
Alzheimer’s disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK.
OBJECTIVES
Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009).
DATA SOURCES
Electronic databases were searched for systematic reviews and/or metaanalyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases--Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases--NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects.
REVIEW METHODS
The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE).
INTERVENTIONS
mild AD (MMSE 21-26)--donepezil, galantamine and rivastigmine; moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE < 10)--memantine. Comparators: mild AD (MMSE 21-26)--placebo or best supportive care (BSC); moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine, memantine, placebo or BSC; severe AD (MMSE < 10)--placebo or BSC. The outcomes were clinical, global, functional, behavioural, quality of life, adverse events, costs and cost-effectiveness. Where appropriate, data were pooled using pair-wise meta-analysis, multiple outcome measures, metaregression and mixedtreatment comparisons. The decision model was based broadly on the structure of the three-state Markov model described in the previous technology assessment report, based upon time to institutionalisation, parameterised with updated estimates of effectiveness, costs and utilities.
RESULTS
Notwithstanding the uncertainty of our results, we found in the base case that the AChEIs are probably cost saving at a willingness-to-pay (WTP) of £’30,000 per qualityadjusted life-year (QALY) for people with mild-to-moderate AD. For this class of drugs, there is a > 99% probability that the AChEIs are more cost-effective than BSC. These analyses assume that the AChEIs have no effect on survival. For the AChEIs, in people with mild to moderate AD, the probabilistic sensitivity analyses suggested that donepezil is the most cost-effective, with a 28% probability of being the most cost-effective option at a WTP of £’30,000 per QALY (27% at a WTP of £’20,000 per QALY). In the deterministic results, donepezil dominates the other drugs and BSC, which, along with rivastigmine patches, are associated with greater costs and fewer QALYs. Thus, although galantamine has a slightly cheaper total cost than donepezil (£’69,592 vs £’69,624), the slightly greater QALY gains from donepezil (1.616 vs 1.617) are enough for donepezil to dominate galantamine.The probability that memantine is cost-effective in a moderate to severe cohort compared with BSC at a WTP of £’30,000 per QALY is 38% (and 28% at a WTP of £’20,000 per QALY). The deterministic ICER for memantine is £’32,100 per/QALY and the probabilistic ICER is £’36,700 per/QALY.
LIMITATIONS
Trials were of 6 months maximum follow-up, lacked reporting of key outcomes, provided no subgroup analyses and used insensitive measures. Searches were limited to English language, The model does not include behavioural symptoms and there is uncertainty about the model structure and parameters.
CONCLUSIONS
The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms, although there is debate about the magnitude of the effect. Although there is also new evidence on the effectiveness of memantine, it remains less supportive of this drug’s use than the evidence for AChEIs. The conclusions concerning cost-effectiveness are quite different from the previous assessment. This is because both the changes in effectiveness and costs between drug use and non-drug use underlying the ICERs are very small. This leads to highly uncertain results, which are very sensitive to change. RESEARCH PRIORITIES: RCTs to include mortality, time to institutionalisation and quality of life, powered for subgroup analysis.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Cholinesterase Inhibitors; Cost-Benefit Analysis; Donepezil; Dopamine Agents; Female; Galantamine; Humans; Indans; Male; Memantine; Middle Aged; Models, Economic; Phenylcarbamates; Piperidines; Rivastigmine; Technology Assessment, Biomedical
PubMed: 22541366
DOI: 10.3310/hta16210