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Frontiers in Neuroscience 2023Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment... (Review)
Review
OBJECTIVE
Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment (MCI). In light of this, our study aims to examine the efficacy and safety of this treatment approach for patients with MCI.
METHODS
We conducted a comprehensive search of various databases, including Medline ( PubMed), Cochrane, Embase, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wanfang Database from their inception to November 16, 2022. The selection of studies, risk of bias assessment, and data extraction were carried out independently by two authors. The statistical analysis was performed using STATA.
RESULTS
Our meta-analysis included a total of 35 studies with 2,833 patients, published between 2008 and 2022, with intervention durations ranging from 4 weeks to 12 months. However, most of the studies had a high risk of detection bias. Our findings indicated that the combination of donepezil and TCM significantly improved the Montreal Cognitive Assessment (MoCA) score (weighted mean difference [WMD] = 2.79, 95% confidence interval [CI]: 1.82 to 3.75) and the Barthel Index score (WMD = 9.20, 95% CI: 5.39 to 13.00) compared to donepezil alone. However, subgroup analyses showed that the MoCA score did not increase significantly in patients with MCI resulting from cerebrovascular disease (WMD = 1.47, 95% CI: -0.02 to 2.96).
CONCLUSION
The combination of donepezil and TCM may have a more positive effect on cognitive function and activities of daily living in patients with MCI compared to the use of donepezil alone. However, due to the limited quality of the studies included in our analysis, these findings should be interpreted with caution.
PubMed: 37476835
DOI: 10.3389/fnins.2023.1206491 -
Medicine Oct 2022Gunao-Yizhi decoction has the effects of supplementing intelligence, strengthening marrow, resolving phlegm, and reducing turbidity. It is clinically used for the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gunao-Yizhi decoction has the effects of supplementing intelligence, strengthening marrow, resolving phlegm, and reducing turbidity. It is clinically used for the treatment of vascular dementia (VaD). However, there is still a lack of systematic evaluation of its efficacy and safety. This review conducted a systematic review of the current evidence on the efficacy and safety of Gunao-Yizhi decoction combined with donepezil for VaD.
METHODS
China National Knowledge Infrastructure (CNKI), Wanfang database (Wanfang), Chinese Science and Technology Periodical Database (VIP), China Biology Medicine disc (CBM), MEDLINE, EMBASE, and Cochrane Library were searched for randomized controlled trials on Gunao-Yizhi decoction combined with donepezil for VaD. RevMan 5.3 software was used for data analysis.
RESULTS
Twelve studies were obtained, including 1036 patients. Compared with donepezil alone, meta-analysis showed that Gunao-Yizhi decoction combined with donepezil could improve clinical efficacy, mini-mental state examination (MMSE) score, Hasegawa dementia scale (HDS), increase the level of superoxide dismutase (SOD) in serum, and reduce the level of malonaldehyde dismutas (MDA) in serum. The GRADE system was adopted to evaluate the outcome index. Clinical efficiency and the MMSE score were evaluated as very-low-quality evidence. HDS score, serum SOD level, and serum MDA level were evaluated as low-quality evidence.
CONCLUSION
Gunao-Yizhi decoction combined with donepezil has a significant prevalence in the treatment of vascular dementia, with no increase in adverse events. Gunao-Yizhi decoction can be recommended for routine use in the treatment of VaD.
Topics: Dementia, Vascular; Donepezil; Drugs, Chinese Herbal; Humans; Malondialdehyde; Superoxide Dismutase
PubMed: 36221397
DOI: 10.1097/MD.0000000000030971 -
Clinics (Sao Paulo, Brazil) 2024Summarize the evidence on drug therapies for obstructive sleep apnea. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Summarize the evidence on drug therapies for obstructive sleep apnea.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched on February 17th, 2023. A search strategy retrieved randomized clinical trials comparing the Apnea-Hypopnea Index (AHI) in pharmacotherapies. Studies were selected and data was extracted by two authors independently. The risk of bias was assessed using the Cochrane Risk of Bias tool. RevMan 5.4. was used for data synthesis.
RESULTS
4930 articles were obtained, 68 met inclusion criteria, and 29 studies (involving 11 drugs) were combined in a meta-analysis. Atomoxetine plus oxybutynin vs placebo in AHI mean difference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86, p = 0.004]. Trazodone vs placebo in AHI mean difference of -12.75 (-21.30, -4.19) [Fixed, 95 % CI, I2 = 0 %, overall effect: Z = 2.92, p = 0.003].
CONCLUSION
The combination of noradrenergic and antimuscarinic drugs shows promising results. Identifying endotypes may be the key to future drug therapies for obstructive sleep apnea. Moreover, studies with longer follow-up assessing the safety and sustained effects of these treatments are needed.
PROSPERO REGISTRATION NUMBER
CRD42022362639.
Topics: Humans; Sleep Apnea, Obstructive; Atomoxetine Hydrochloride; Donepezil; Norepinephrine
PubMed: 38341903
DOI: 10.1016/j.clinsp.2024.100330 -
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 -
Archives of Gerontology and Geriatrics 2021We investigated the efficacy and acceptability of pharmacotherapy for dementia with Lewy bodies (DLB) while simultaneously considering the neuropsychiatric symptoms... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
We investigated the efficacy and acceptability of pharmacotherapy for dementia with Lewy bodies (DLB) while simultaneously considering the neuropsychiatric symptoms (NPS), cognitive function, motor symptoms, and acceptability.
METHODS
Electronic databases were searched from inception through June 5, 2019, for randomized controlled trials (RCTs) and open-label trials (OLTs) in patients with DLB. We performed a pairwise conventional meta-analysis (PWMA) and network meta-analysis (NMA) within a frequentist framework. The main outcomes were mean change scores in NPS, general cognition, motor symptoms and acceptability. The effect sizes and odds ratios with 95% confidence intervals (CIs) were calculated. This study was registered with PROSPERO (CRD42018096996).
RESULTS
In total, we included 29 studies (9 RCTs and 20 OLTs). In the NMA with 9 RCTs, both high- (mean difference [MD] 2.00, 95% CIs, 0.69 to 3.31) and low-dose (1.86, 0.58 to 3.15) donepezil were associated with a greater cognitive improvement than placebo. High-dose zonisamide was associated with greater motor symptom improvement ( -4.10, -7.03 to -1.17]). No medications reached statistical significance regarding improving neuropsychiatric symptoms or developing intolerable adverse effects as compared to placebo. In the second NMA, with 29 studies as an exploratory analysis, aripiprazole and yokukansan may be effective for neuropsychiatric symptoms, while levodopa may be associated with cognitive impairment.
CONCLUSIONS
We report the most comprehensive evidence for the selection of pharmacotherapy for treating different clusters of DLB-related symptoms. Due to the limited availability of RCTs on DLB, more well-conducted RCTs are needed for MMA to warrant clinical efficacy in the future.
Topics: Cognition; Humans; Lewy Body Disease; Network Meta-Analysis; Treatment Outcome
PubMed: 34256210
DOI: 10.1016/j.archger.2021.104474 -
Pharmaceuticals (Basel, Switzerland) Jan 2022Alzheimer's disease (AD) is a leading progressive neurodegenerative disease worldwide, and its treatment is a challenging clinical problem. This review was conducted to... (Review)
Review
Alzheimer's disease (AD) is a leading progressive neurodegenerative disease worldwide, and its treatment is a challenging clinical problem. This review was conducted to evaluate the efficacy and safety of herbal medicine for AD treatment. The PubMed, CENTRAL, EMBASE, CNKI, OASIS, KTKP, and CiNii databases were searched until June 2020 for randomized controlled trials (RCTs) on herbal medicine for AD, and a meta-analysis of 57 RCTs was conducted. For cognitive function, herbal medicine significantly improved the Mini-Mental State Examination (MMSE) and AD Assessment Scale-Cognitive Subscale (ADAS-cog) scores compared with conventional medicine. The MMSE scores showed no significant difference between the groups treated with herbal medicine and donepezil; however, herbal medicine significantly lowered the ADAS-cog score. Acori Graminei Rhizoma-containing and Cnidii Rhizoma-containing herbal medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine showed a positive, but not statistically significant, tendency toward improving the MMSE score compared with conventional medicine. Herbal medicine with conventional medicine significantly improved the MMSE, ADAS-cog, and Montreal Cognitive Assessment (MoCA) scores compared with conventional medicine, and herbal medicine with donepezil also significantly improved these scores compared with donepezil. Acori Graminei Rhizoma or Cnidii Rhizoma-containing herbal medicine with conventional medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine + conventional medicine significantly improved the MMSE score, but not the ADAS-cog score, compared with conventional medicine. For behavioral and psychological symptoms of dementia, the Neuropsychiatry Inventory (NPI) score was not significantly different between herbal and conventional medicines. Herbal medicine with conventional medicine significantly improved the NPI and Behavioral Pathology in Alzheimer's Disease Rating Scale scores compared with conventional medicine. The NPI score showed no significant difference between the groups treated with herbal medicine and placebo. Furthermore, herbal medicine with conventional medicine significantly lowered plasma amyloid beta levels compared with conventional medicine alone. Herbal medicine, whether used alone or as an adjuvant, may have beneficial effects on AD treatment. However, owing to the methodological limitations and high heterogeneity of the included studies, concrete conclusions cannot be made.
PubMed: 35215287
DOI: 10.3390/ph15020174 -
Interactive Journal of Medical Research Aug 2022Bacopa monnieri, a herb that has been used for many centuries in India, has shown neuroprotective effects in animal and in vitro studies; human studies on patients with... (Review)
Review
BACKGROUND
Bacopa monnieri, a herb that has been used for many centuries in India, has shown neuroprotective effects in animal and in vitro studies; human studies on patients with Alzheimer disease have been inconclusive.
OBJECTIVE
The primary objective of this review was to determine the clinical efficacy and safety of B. monnieri in persons with mild, moderate, or severe dementia, or mild cognitive impairment, due to Alzheimer disease.
METHODS
We searched PubMed, Embase, Cochrane Library, clinical trial registries (World Health Organization, Australia-New Zealand, United States, and South Africa), the metaRegister of Controlled Trials, and CINAHL. We intended to include all randomized and quasi-randomized controlled trials that compared B. monnieri, its extract or active ingredients (at any dosage), with a placebo or a cholinesterase inhibitor among adults with dementia due to Alzheimer disease and in those with mild cognitive impairment due to Alzheimer disease.
RESULTS
Our comprehensive search yielded 5 eligible studies. A total of 3 studies used B. monnieri in combination with herbal extracts while the remaining 2 used B. monnieri extracts only. Two studies compared B. monnieri with donepezil while the others used a placebo as the control. There was considerable variation in the B. monnieri dose used (ranging between 125 mg to 500 mg twice daily) and heterogeneity in treatment duration, follow-up, and outcomes. The major outcomes were Mini-Mental State Examination scores reported in 3 trials, Cognitive subscale scores of the Alzheimer's Disease Assessment Scale in 1 study, and a battery of cognitive tests in 2 studies. Using the Cochrane risk-of-bias tool, overall, we judged all 5 studies to be at high risk of bias. While all studies reported a statistically significant difference between B. monnieri and the comparator in at least one outcome, we rated the overall quality of evidence for the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Postgraduate Institute Memory Scale, Mini-Mental State Examination, and Wechsler Memory Scale to be very low due to downgrading by 2 levels for high risk of bias and 1 more level for impreciseness due to small sample sizes and wide CIs.
CONCLUSIONS
There was no difference between B. monnieri and the placebo or donepezil in the treatment of Alzheimer disease based on very low certainty evidence. No major safety issues were reported in the included trials. Future randomized controlled trials should aim to recruit more participants and report clinically meaningful outcomes.
TRIAL REGISTRATION
PROSPERO CRD42020169421; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=169421.
PubMed: 35612544
DOI: 10.2196/38542 -
Medicine Aug 2022Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular dementia (VaD) is a comprehensive syndrome related to the damage of cognitive function and various cerebral vascular illnesses. VaD is also generally recognized as the second most common type of dementia after Alzheimer disease, contributing to 30% of the dementia population in Asia and developing countries. The ability of donepezil hydrochloride and nimodipine had been respectively proven in improving cognitive function in vascular dementia. However, whether the combined application of both drugs contribute to better efficacy remains as a research hotspot. Studies had shown definite satisfactory result with such combination, however evidence-based evaluation of the efficacy is still lacking. Therefore, meta-analysis is employed in this study to evaluate the efficacy and safety of using donepezil hydrochloride combined with nimodipine in treating VaD to provide references for clinical treatments. The efficacy of donepezil hydrochloride combined with nimodipine on treating vascular dementia is systematically reviewed to provide evidence-based references for clinical applications.
METHODS
Both Chinese and English databases were searched from the start till August, 2020 for any RCT regarding the combined use of the 2 drugs in treating vascular dementia. Two investigators would later evaluate and screened out research and data based on an improved Jaded scale. Software Rev Man 5.3.0 was employed to carry out meta-analysis on clinical effificacy, mini-mental state examination (MMSE) ratings, activity of daily living (ADL) ratings, and clinical dementia scale (CDR) ratings.
RESULTS
Donepezil hydrochloride combined with nimodipine had demonstrated satisfactory efficacy on the treatment of vascular dementia. Improvements were namely spotted on MMSE scale, ADL scale, and CDR scale, with the utmost efficacy by 12 weeks after intervention.
CONCLUSIONS
Donepezil hydrochloride combined with nimodipine had good efficacy in the treatment of patients with vascular dementia, mainly in terms of improving the Simple MMSE scores, the ability to use daily living scale (ADL) scores and the CDR, and the best results were obtained after 12 weeks of intervention. Such conclusion should be cautiously evaluated.
Topics: Alzheimer Disease; Dementia, Vascular; Donepezil; Humans; Mental Status and Dementia Tests; Nimodipine
PubMed: 35945739
DOI: 10.1097/MD.0000000000029307 -
Ageing Research Reviews Dec 2022Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the disease, evidence on the clinical effectiveness of treatments for people with severe dementia remains limited.
AIMS
To systematically review the effectiveness of pharmacological and non-pharmacological treatments for people living with severe dementia and assess the quality of the evidence.
METHOD
We searched MEDLINE, EMBASE, PsycINFO, CINAHL and online clinical trial registers up to January 2022, for Randomised Controlled Trials (RCT) in people living with severe dementia. Quality and risk of bias were assessed independently by two authors.
RESULTS
A total of 30 trials met our inclusion criteria of which 14 evaluated the effectiveness of pharmacological treatments, and 16 evaluated a non-pharmacological intervention. Pharmacological treatments: Meta-analyses indicated that pharmacological treatments (donepezil: 10 mg, 5 mg; galantamine: 24 mg; memantine: 10 mg) are associated with better outcomes compared to placebo for: severity of symptoms (standardized mean difference (SMD) 0.37, 95% CI 0.26-0.48; 4 studies; moderate-certainty evidence), activities of daily living (SMD 0.15, 95% CI 0.04-0.26; 5 studies; moderate-certainty evidence), and clinical impression of change (Relative Risk (RR) 1.34, 95% CI 1.14-1.57; 4 studies; low-certainty evidence). Pharmacological treatments were also more likely to reduce mortality compared to placebo (RR 0.60, 95% CI 0.40-0.89; 6 studies; low-certainty evidence). Non-pharmacological treatments: Five trials were included in the meta-analyses of non-pharmacological interventions (multi-sensory stimulation, needs assessment, and activities-based interventions); results showed that non-pharmacological interventions may reduce neuropsychiatric symptoms of dementia compared to usual care (SMD -0.33, 95% CI -0.59 to -0.06; low certainty evidence).
CONCLUSIONS
There is moderate-certainty evidence that pharmacological treatments may decrease disease severity and improve function for people with severe dementia. Non-pharmacological treatments are probably effective in reducing neuropsychiatric symptoms but the quality of evidence remains low. There is an urgent need for high-quality evidence for other outcomes and for developing service-user informed interventions for this under-served group.
Topics: Humans; Dementia; Activities of Daily Living; Memantine; Treatment Outcome
PubMed: 36243355
DOI: 10.1016/j.arr.2022.101758 -
Health Science Reports Nov 2022Dementia is becoming a major global public health menace in the aging population affecting 47 million people globally. Dementia has no cure and effective interventions....
BACKGROUND AND AIMS
Dementia is becoming a major global public health menace in the aging population affecting 47 million people globally. Dementia has no cure and effective interventions. Treatment of dementia is a big problem. The most common symptomatic medications for cognition, behavior, and global functioning among patients with dementia currently are cholinesterase inhibitors and memantine. However, Information on the effectiveness of cholinesterase inhibitors for dementia is conflicting and controversial. Thus, this makes it difficult for decision-makers, healthcare providers, patients, and caregivers to decide on the most effective intervention. The current meta-analysis sought to investigate the efficacy of pharmacologic interventions to improve cognitive and behavioral symptoms in people with living dementia.
METHODS
This current systematic review and meta-analysis used the preferred reporting items for systematic reviews and meta-analyses to ensure accuracy and comprehensiveness. The Cochrane MEDLINE, Database of Systematic Reviews, and other databases were thoroughly searched for relevant studies. We selected Studies such as randomized controlled trials published in English with a sample size of at least 20 subjects. We selected and applied the random-effects meta-analysis as the most preferred model because of the heterogeneity across studies. The computation of the weighted effect size was based on the result from the test of heterogeneity.
RESULTS
Twenty-two studies were finally used in the meta-analysis. The study subjects who received donepezil 5 mg/day, donepezil 10 mg/day, and galantamine 24 mg/day had improved cognition symptoms (ADAS-cog) score of -1.46 (95% CI = -2.24, -0.68, = 3.67, < 0.001), -2.31 (95% CI = -3.30, -1.31, = 5.45, < 0.001) and -3.04 (95% CI = -4.16, -1.92, = 5.31, < 0.001) respectively.
CONCLUSION
The current meta-analysis suggests significant benefits of cholinesterase inhibitors such as donepezil (5 and 10 mg/day) and galantamine on cognitive symptoms.
PubMed: 36381407
DOI: 10.1002/hsr2.913