-
Journal of Alzheimer's Disease : JAD 2023Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the...
BACKGROUND
Perfusion imaging has the potential to identify neurodegenerative disorders in a preclinical stage. However, to correctly interpret perfusion-derived parameters, the impact of perfusion modifiers should be evaluated.
OBJECTIVE
In this systematic review, the impact of acute and chronic intake of four acetylcholinesterase inhibitors (AChEIs) on cerebral perfusion in adults was investigated: physostigmine, donepezil, galantamine, and rivastigmine.
RESULTS
Chronic AChEI treatment results in an increase of cerebral perfusion in treatment-responsive patients with Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease dementia in the frontal, parietal, temporal, and occipital lobes, as well as the cingulate gyrus. These effects appear to be temporary, dose-related, and consistent across populations and different AChEI types. On the contrary, further perfusion decline was reported in patients not receiving AChEIs or not responding to the treatment.
CONCLUSION
AChEIs appear to be a potential perfusion modifier in neurodegenerative patients. More research focused on quantitative perfusion in both patients with and without a cholinergic deficit is needed to draw conclusions on whether AChEI intake should be considered when analyzing perfusion data.
Topics: Humans; Cholinesterase Inhibitors; Acetylcholinesterase; Dementia; Piperidines; Indans; Phenylcarbamates; Parkinson Disease; Rivastigmine; Alzheimer Disease; Galantamine; Cognition; Perfusion; Cerebrovascular Circulation
PubMed: 37182871
DOI: 10.3233/JAD-221125 -
The Cochrane Database of Systematic... Feb 2021Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of... (Review)
Review
BACKGROUND
Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug - cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine - are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment.
OBJECTIVES
To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer-related outcomes.
SEARCH METHODS
We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources.
SELECTION CRITERIA
We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed citations and full-text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3-11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods.
MAIN RESULTS
We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias. Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) -0.42, 95% confidence interval (CI) -0.64 to -0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD -0.40, 95% CI -0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD -0.62; 95% CI -0.94 to -0.31). Data from one longer-term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) -2.09 Standardised Mini-Mental State Examination (SMMSE) points, 95% CI -3.43 to -0.75; moderate certainty). Discontinuation may make little or no difference to functional status in the short term (SMD -0.25, 95% CI -0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD -0.38, 95% CI -0.74 to -0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD -3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI -6.67 to -0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD - 0.48, 95% CI -0.82 to -0.13; 2 studies; low certainty; and SMD -0.27, 95% CI -0.47 to -0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD -0.87 Neuropsychiatric Inventory (NPI) points; 95% CI -8.42 to 6.68; moderate certainty). We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review.
AUTHORS' CONCLUSIONS
This review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well-designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.
Topics: Activities of Daily Living; Alzheimer Disease; Cholinesterase Inhibitors; Dementia; Donepezil; Humans; Memantine; Parkinson Disease; Quality of Life; Rivastigmine
PubMed: 35608903
DOI: 10.1002/14651858.CD009081.pub2 -
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 -
Health Technology Assessment... Jan 2006To provide an update review of the best quality evidence for the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine for mild to... (Review)
Review
OBJECTIVES
To provide an update review of the best quality evidence for the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine for mild to moderately severe Alzheimer's disease (AD) and of memantine for moderately severe to severe AD.
DATA SOURCES
Electronic databases, experts in the field and manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE).
REVIEW METHODS
A systematic review of the literature and an economic evaluation were undertaken. The quality of included randomised controlled trials (RCTs) was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. An outline assessment of economic evaluations was undertaken using a standard checklist. The clinical and cost-effectiveness data were synthesised through a narrative review with full tabulation of the results of included studies. Where appropriate, meta-analysis of data was undertaken.
RESULTS
For mild to moderately severe AD, the results of the study suggested that all three treatments were beneficial when assessed using cognitive outcome measures. Global outcome measures were positive for donepezil and rivastigmine, but mixed for galantamine. Results for measures of function were mixed for donepezil and rivastigmine, but positive for galantamine. Behaviour and mood measures were mixed for donepezil and galantamine, but showed no benefit for rivastigmine. For memantine, two published RCTs were included; in one of these trials the participants were already being treated with donepezil. The results suggest that memantine is beneficial when assessed using functional and global measurements. The effect of memantine on cognitive and behaviour and mood outcomes is, however, less clear. Literature on the cost-effectiveness of donepezil, rivastigmine and galantamine was dominated by industry-sponsored studies, and studies varied in methods and results. Of the three UK studies, two report donepezil as not cost-effective, whereas a third study reports an additional cost (1996 pounds sterling) of between 1200 pounds sterling and 7000 pounds sterling per year in a non-severe AD health state (concerns over these estimates are raised, suggesting that they may underestimate the true cost-effectiveness of donepezil). Cost-effectiveness analysis undertaken in this review suggests that donepezil treatment has a cost per quality-adjusted life-year (QALY) in excess of 80,000 pounds sterling, with donepezil treatment reducing the mean time spent in full-time care (delays progression of AD) by 1.42-1.59 months (over a 5-year period). From four published cost-effectiveness studies, two UK studies report additional costs associated with rivastigmine treatment. Cost-effectiveness analysis undertaken in the current review suggests that rivastigmine treatment has a cost per QALY in excess of 57,000 pounds sterling, with rivastigmine treatment reducing the mean time spent in full-time care (delays progression) by 1.43-1.63 months (over a 5-year period). From five published cost-effectiveness studies, one UK study reports a cost per QALY of 8693 pounds sterling for 16-mg galantamine treatment and 10,051 pounds sterling for 24-mg galantamine treatment (concerns raised suggest that this may underestimate the true cost-effectiveness of galantamine). Cost-effectiveness analysis undertaken in the present review suggests that galantamine treatment has a cost per QALY in excess of 68,000 pounds sterling, with galantamine reducing the time spent in full-time care (delays progression) by 1.42-1.73 months (over a 5-year period). From two published cost-effectiveness studies, one reports analysis for the UK, finding that memantine treatment results in cost savings and benefits in terms of delaying disease progression (concerns raised suggest that this may underestimate the true cost-effectiveness of memantine). In the current review, the cost-effectiveness of memantine has not been modelled separately, but where alternative parameter inputs on the cost structure and utility values have been used in a reanalysis using the industry model, the cost-effectiveness is reported at between 37,000 pounds sterling and 52,000 pounds sterling per QALY, with this alternative analysis still based on what is regarded as an optimistic or favourable effectiveness profile for memantine.
CONCLUSIONS
Although results from the clinical effectiveness review suggest that these treatments may be beneficial, a number of issues need to be considered when assessing the results of the present review, such as the characteristics of the participants included in the individual trials, the outcome measures used, the length of study duration, the effects of attrition and the relationship between statistical significance and clinical significance. Many included trials were sponsored by industry. For donepezil, rivastigmine and galantamine, the cost savings associated with reducing the mean time spent in full-time care do not offset the cost of treatment sufficiently to bring estimated cost-effectiveness to levels generally considered acceptable by NHS policy makers. It is difficult to draw conclusions on the cost-effectiveness of memantine; it is suggested that further amendments to the potentially optimistic industry model (measure of effect) would offer higher cost per QALY estimates. Future research should include: information on the quality of the outcome measures used; development of quality of life instruments for patients and carers; studies assessing the effects of these interventions of durations longer than 12 months; comparisons of benefits between interventions; and research on the prediction of disease progression.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cost-Benefit Analysis; Donepezil; Dopamine Agents; Evidence-Based Medicine; Female; Galantamine; Humans; Indans; Male; Memantine; Neuroprotective Agents; Nootropic Agents; Phenylcarbamates; Piperidines; Rivastigmine; Treatment Outcome; United Kingdom
PubMed: 16409879
DOI: 10.3310/hta10010 -
Frontiers in Aging Neuroscience 2023To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba preparations combined with donepezil hydrochloride vs. donepezil for the treatment of...
OBJECTIVE
To conduct a meta-analysis of the effectiveness and safety of ginkgo biloba preparations combined with donepezil hydrochloride vs. donepezil for the treatment of Alzheimer's disease (AD).
METHODS
Three English databases (Cochrane Library, PubMed, EMBASE), and four Chinese databases [the China National Knowledge Infrastructure (CKNI), the Chinese Biomedical Literature database (CBM), the Chongqing VIP database, and WANFANG DATA)] were manually searched for literature published from the respective dates of inception of the databases to December 2022. The randomized controlled trials (RCTs) of ginkgo biloba preparations with donepezil hydrochloride vs. donepezil for the treatment of AD were included. Relevant literature was screened, and the data in the included studies were extracted for quality assessment according to the Risk of bias tool. The RevMan 5.3 software was used for meta-analysis.
RESULTS
A total of 1,642 participants were enrolled in the 18 RCTs. Of these, 842 were in the experimental group (ginkgo biloba preparations combined with donepezil hydrochloride) and 800 were in the control group (donepezil). The overall methodological quality of the included RCTs is poor due to the high risks of blindness and allocation concealment. The meta-analysis results showed statistically significant differences in several outcomes including Risk Ratio (RR) in change for clinical effectiveness rate (1.23, 95% CI 1.13, 1.34, < 0.00001), mean difference (MD) in change for Mini-Mental State Examination score (3.02, 95% CI 2.14, 3.89, < 0.00001), Activity of Daily Living Scale score (-4.56, 95% CI -5.09, -4.03, < 0.00001), Hasegawa Dementia Scale score (2.04, 95% CI 1.74, 2.34, < 0.00001), Montreal Cognitive Assessment score (2.38, 95% CI 0.72, 4.06, = 0.005), between the experimental and control groups. But there is no statistically significant difference in change for adverse reaction (0.91, 95% CI 0.58, 1.42, = 0.69).
CONCLUSION
Ginkgo biloba preparations plus donepezil can improve clinical effectiveness rate and vocabulary memory outcomes. However, more relevant high-quality RCTs are needed in the future to validate these results.
SYSTEMATIC REVIEW REGISTRATION
Identifier CRD42022378970.
PubMed: 36960422
DOI: 10.3389/fnagi.2023.1124710 -
Cancer Medicine May 2023Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including... (Review)
Review
BACKGROUND
Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours.
METHODS
We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021.
RESULTS
In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention.
CONCLUSION
The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.
Topics: Adult; Humans; Quality of Life; Cognitive Dysfunction; Cognition; Cognition Disorders; Brain Neoplasms
PubMed: 36880363
DOI: 10.1002/cam4.5760 -
The Cochrane Database of Systematic... Jan 2012Antipsychotic medication remains the mainstay of treatment for schizophrenia and has been in use for a long time. As evidenced by ongoing research and partial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic medication remains the mainstay of treatment for schizophrenia and has been in use for a long time. As evidenced by ongoing research and partial effectiveness of the antipsychotics on cognitive and negative symptoms, the search is on for drugs that may improve these domains of functioning for someone suffering from schizophrenia. Acetylcholinesterase inhibitors have long been in use for treating cognitive symptoms of dementia.
OBJECTIVES
The aim of the review was to evaluate the clinical effects, safety and cost effectiveness of acetylcholinesterase inhibitors for treating people with schizophrenia
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Register (February 2009), and inspected the references of all identified studies for further trials.
SELECTION CRITERIA
We included all clinical randomised trials comparing acetylcholinesterase inhibitors with antipsychotics or placebo either alone, or in combination, for schizophrenia and schizophrenia-like psychoses.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat (ITT) basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model.
MAIN RESULTS
The acetylcholinesterase inhibitor plus antipsychotic showed benefit over antipsychotic and placebo in the following outcomes.1. Mental state - PANSS negative symptoms average end point score (2 RCTs, n = 31, MD -1.69 95% CI -2.80 to -0.57), PANSS General Psychopathology average end point score (2 RCTs, n = 31, MD -3.86 95% CI -5.40 to -2.32), and improvement in depressive symptoms showed at least by one short-term study as measured by CDSS scale (data skewed).2. Cognitive domains - attention, (1 RCT, n = 73, MD 1.20 95% CI 0.14 to 2.26), visual memory (2 RCTs, n = 48 , MD 1.90 95% CI 0.52 to 3.28), verbal memory and language (3 RCTs, n = 42, MD 3.46 95% CI 0.67 to 6.26) and executive functioning (1 RCT, n = 24, MD 17.10 95% CI 0.70 to 33.50).3. Tolerability - EPSE: AIMS, (1 RCT, n = 35, MD 1.50 95% CI 1.04 to 1.96).No difference was noted between the two arms in other outcomes. The overall rate of participants leaving studies early was low (13.6 %) and showed no clear difference between the two groups.
AUTHORS' CONCLUSIONS
The results seem to favour the use of acetylcholinesterase inhibitors in combination with antipsychotics on a few domains of mental state and cognition, but because of the various limitations in the studies as mentioned in the main text, the evidence is weak. This review highlights the need for large, independent, well designed, conducted and reported pragmatic randomised studies.
Topics: Antipsychotic Agents; Cholinesterase Inhibitors; Donepezil; Galantamine; Humans; Indans; Phenylcarbamates; Piperidines; Psychotic Disorders; Randomized Controlled Trials as Topic; Rivastigmine; Schizophrenia; Schizophrenic Psychology
PubMed: 22258978
DOI: 10.1002/14651858.CD007967.pub2 -
Journal of the Formosan Medical... Aug 2022Donepezil had been recognized to have impact on sleep quality in demented patients. However, there was insufficient evidences about the actual effect of donepezil in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Donepezil had been recognized to have impact on sleep quality in demented patients. However, there was insufficient evidences about the actual effect of donepezil in the sleep architectures. Our meta-analysis aimed to evaluate the changes of sleep architectures related to donepezil use.
METHODS
Followed the PRISMA2020 and AMSTAR2 guidelines, electronic search had been performed on the databases of PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane CENTRAL, ProQuest, Web of Science, and ClinicalTrials.gov. The outcome measurement was changes of sleep parameters detected by polysomnography. A random-effects meta-analysis was conducted.
RESULTS
Total twelve studies had been involved. The percentage of REM sleep would significantly increase after donepezil treatment (Hedges' g = 0.694, p < 0.001). Compared to placebo/controls, subjects with donepezil would had significantly increased percentage of REM sleep stage (Hedges' g = 0.556, p = 0.018). Furthermore, donepezil was also associated with the decreased stage 2 sleep percentage, sleep efficiency, or total sleep time in different analysis conditions.
CONCLUSION
Our meta-analysis provided detailed changes of sleep architectures related to donepezil treatment. Further larger sample size studies with stricter control of potential moderators are needed to clarify these issues.
Topics: Donepezil; Humans; Indans; Piperidines; Polysomnography; Sleep
PubMed: 34753629
DOI: 10.1016/j.jfma.2021.10.013 -
The Cochrane Database of Systematic... Jan 2009Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome [DS]. Acetylcholine is a chemical found in the brain that has an important... (Review)
Review
BACKGROUND
Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome [DS]. Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Donepezil a reversible inhibitor of acetylcholinesterase, which is thought to maintain levels of acetylcholine, and is reported to have some benefits for people with AD in the general population. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population.
OBJECTIVES
To determine the effectiveness and safety of donepezil for people with DS who develop AD.
SEARCH STRATEGY
CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of donepezil as well as experts in the field, to ask about reports of unpublished or ongoing trials.
SELECTION CRITERIA
Randomised controlled trials of participants with DS and AD in which treatment with donepezil was administered compared with a placebo group.
DATA COLLECTION AND ANALYSIS
Data were extracted from the published reports of the one relevant study identified.
MAIN RESULTS
The one study included in this review is a small (n=30) randomised controlled trial lasting 24 weeks. It was followed-up by an open label study with a crossover design.No significant differences were found on any four validated outcomes including global functioning and three measures of cognitive abilities and behavioural problems. 6 out of 16 carers (37%) of participants on donepezil and 2 out of 15 (13%) on placebo reported improvement. No data were available for day to day skills, institutionalisation, reduction in carers' stress or economic outcomes. Half the intervention group and 20% of the placebo group reported adverse events; two participants left because of adverse events.
AUTHORS' CONCLUSIONS
To date there is only one small randomised controlled study on the effect of donepezil. This shows, at best, a modest, non statistically significant trend in favour of people with Down syndrome and Alzheimer's dementia who are able to tolerate donepezil (this drug is currently only dispensed in relatively large doses and is contraindicated for those with cardiac and respiratory problems).This study does not provide good evidence on which to base practice. Findings in an open-label follow up to this study suggest possible benefit in some individuals. Further, larger randomised controlled studies with longer-term follow up are required.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Down Syndrome; Humans; Indans; Piperidines; Randomized Controlled Trials as Topic
PubMed: 19160328
DOI: 10.1002/14651858.CD007178.pub2 -
The British Journal of Psychiatry : the... Sep 2013More people are presenting with mild cognitive impairment (MCI), frequently a precursor to dementia, but we do not know how to reduce deterioration. (Review)
Review
BACKGROUND
More people are presenting with mild cognitive impairment (MCI), frequently a precursor to dementia, but we do not know how to reduce deterioration.
AIMS
To systematically review randomised controlled trials (RCTs) evaluating the effects of any intervention for MCI on cognitive, neuropsychiatric, functional, global outcomes, life quality or incident dementia.
METHOD
We reviewed 41 studies fitting predetermined criteria, assessed validity using a checklist, calculated standardised outcomes and prioritised primary outcome findings in placebo-controlled studies.
RESULTS
The strongest evidence was that cholinesterase inhibitors did not reduce incident dementia. Cognition improved in single trials of: a heterogeneous psychological group intervention over 6 months; piribedil, a dopamine agonist over 3 months; and donepezil over 48 weeks. Nicotine improved attention over 6 months. There was equivocal evidence that Huannao Yicong improved cognition and social functioning.
CONCLUSIONS
There was no replicated evidence that any intervention was effective. Cholinesterase inhibitors and rofecoxib are ineffective in preventing dementia. Further good-quality RCTs are needed and preliminary evidence suggests these should include trials of psychological group interventions and piribedil.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cholinesterase Inhibitors; Cognitive Behavioral Therapy; Cognitive Dysfunction; Dopamine Agonists; Drugs, Chinese Herbal; Exercise Therapy; Fatty Acids, Omega-3; Ginkgo biloba; Humans; Nicotine; Nicotinic Agonists; Phytotherapy; Piribedil; Psychotherapy, Group; Quality of Life; Randomized Controlled Trials as Topic; Therapy, Computer-Assisted; Treatment Outcome; Vitamins
PubMed: 24085737
DOI: 10.1192/bjp.bp.113.127811