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Molecules (Basel, Switzerland) May 2022Down Syndrome (DS) is considered the most frequent form of Intellectual Disability, with important expressions of cognitive decline and early dementia. Studies on... (Review)
Review
Down Syndrome (DS) is considered the most frequent form of Intellectual Disability, with important expressions of cognitive decline and early dementia. Studies on potential treatments for dementia in this population are still scarce. Thus, the current review aims to synthesize the different pharmacological approaches that already exist in the literature, which focus on improving the set of symptoms related to dementia in people with DS. A total of six studies were included, evaluating the application of supplemental antioxidant therapies, such as alpha-tocopherol; the use of acetylcholinesterase inhibitor drugs, such as donepezil; N-methyl-d-aspartate (NMDA) receptor antagonists, such as memantine; and the use of vitamin E and a fast-acting intranasal insulin. Two studies observed important positive changes related to some general functions in people with DS (referring to donepezil). In the majority of studies, the use of pharmacological therapies did not lead to improvement in the set of symptoms related to dementia, such as memory and general functionality, in the population with DS.
Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Dementia; Donepezil; Down Syndrome; Humans; Memantine; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 35630721
DOI: 10.3390/molecules27103244 -
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 -
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 -
Journal of Parkinson's Disease 2022Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term levodopa administration for treating Parkinson's disease (PD) may shorten the duration of effect and cause dyskinesias, inducing the need for catechol-O-methyltransferase (COMT) inhibitors as adjuvant therapy.
OBJECTIVE
We provide pooled scientific evidence highlighting the efficacy and safety of opicapone, a newly approved COMT inhibitor, as an adjuvant to levodopa.
METHODS
We searched Ovid Medline, Embase, and Cochrane databases for relevant reports. Efficacy and safety were evaluated as off-time reduction and risk ratio (RR) of dyskinesia, respectively. Data were independently extracted using predefined criteria. Selected placebo-controlled trials were divided into double-blind and open-label periods. Using a random-effects model, the mean difference (MD) of the off-time reduction (efficacy), RR for the occurrence of dyskinesia, and on-time without/with troublesome dyskinesia (TD; safety assessment) were compared between opicapone and placebo groups.
RESULTS
Five studies from three randomized controlled trials were included, and a meta-analysis was performed with 407 patients receiving opicapone 50 mg and 402 patients receiving placebo. Compared with the placebo, opicapone (50 mg) reduced off-time by 49.91 min during the double-blind period (95% confidence intervals [CIs] = -71.39, -28.43; I2 = 0%). The RR of dyskinesia was 3.43 times greater in the opicapone 50 mg group than in the placebo group (95% CI = 2.14, 5.51; I = 0%). Compared with the placebo, opicapone increased the on-time without TD by 44.62 min (95% CI = 22.60, 66.64; I2 = 0%); the on-time increase with TD did not differ between treatments.
CONCLUSION
Opicapone can play a positive role as an adjuvant to levodopa in patients with PD by reducing off-time and prolonging on-time without PD.
Topics: Antiparkinson Agents; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Dyskinesias; Humans; Levodopa; Oxadiazoles; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 35180134
DOI: 10.3233/JPD-213057 -
Frontiers in Endocrinology 2022Previous studies have described the effects of different drugs in preventing ovarian hyperstimulation syndrome (OHSS). However, the efficacies of those drugs in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have described the effects of different drugs in preventing ovarian hyperstimulation syndrome (OHSS). However, the efficacies of those drugs in preventing OHSS remain inconclusive.
METHODS
We searched the PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. A network meta-analysis of randomized controlled trials (RCTs) was performed up to August 2021. We investigated the following drugs in our study: aspirin, albumin, metformin, calcium, cabergoline, quinagolide, letrozole, hydroxyethyl starch (HES), and glucocorticoids. The primary outcome was the incidence rate of moderate-to-severe OHSS, with the results presented as risk ratios (RRs) with 95% confidence intervals (CIs).
RESULTS
The incidence of moderate-to-severe OHSS was significantly reduced by calcium administration (risk ratios [RR] 0.14, 95% confidence interval [CI]: 0.04, 0.46) (grade: high), HES (RR 0.25, 95% CI 0.07, 0.73) (grade: high), and cabergoline (RR 0.43, 95% CI 0.24, 0.71) (grade: moderate). The surface under the cumulative ranking curve (SUCRA) indicated that calcium (SUCRA, 92.4%) was the most effective intervention for preventing moderate-to-severe OHSS. These drugs were safe and did not affect clinical pregnancy, miscarriage, or live birth rates.
CONCLUSION
Calcium, HES, and cabergoline could effectively and safely prevent moderate-to-severe OHSS, with calcium as the most effective intervention.
Topics: Cabergoline; Female; Humans; Network Meta-Analysis; Ovarian Hyperstimulation Syndrome; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic
PubMed: 35154015
DOI: 10.3389/fendo.2022.808517 -
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 -
International Journal of Environmental... Dec 2021Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia.... (Review)
Review
Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016-2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg ( = 0.0138) and 100 mg ( = 0.0006) have improved the Unified Parkinson's Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression-Change (CGI-C), Clinical Global Impression-Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson's Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.
Topics: Antiparkinson Agents; Humans; Levodopa; Parkinson Disease; Pharmaceutical Preparations; Psychotic Disorders; United States
PubMed: 35010624
DOI: 10.3390/ijerph19010364 -
Journal of Geriatric Psychiatry and... Sep 2022Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Orthostatic hypotension (OH) is multifactorial in Parkinson's disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue.
METHODS
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available.
RESULTS
Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81-6.46]), (OR 1.39 [95% CI:0.97-1.98]).
CONCLUSIONS
Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.
Topics: Antiparkinson Agents; Dopamine Agonists; Humans; Hypotension, Orthostatic; Levodopa; Monoamine Oxidase; Parkinson Disease
PubMed: 34964392
DOI: 10.1177/08919887211060017 -
Medicine Nov 2021Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis.
BACKGROUND
Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice.
METHODS
Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events.
RESULTS
Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD -1.31, 95% CI -1.57 to -1.04, P < .00001) for motor UPDRS score, (16 trials; SMD -1.26, 95% CI -1.49 to -1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD -1.02, 95% CI -1.27 to -0.77, P < .00001) for mental UPDRS score, (10 trials; SMD -1.54, 95% CI -1.93 to -1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD -1.56, 95% CI -1.90 to -1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001).
CONCLUSIONS
P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.
Topics: Antiparkinson Agents; Combined Modality Therapy; Humans; Levodopa; Multicenter Studies as Topic; Parkinson Disease; Pramipexole; Treatment Outcome
PubMed: 34871213
DOI: 10.1097/MD.0000000000027511 -
Medicine Nov 2021It is necessary to conduct a meta-analysis of the clinical randomized controlled trials (RCTs) on ropinirole in the treatment of Parkinson disease (PD), to explore the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is necessary to conduct a meta-analysis of the clinical randomized controlled trials (RCTs) on ropinirole in the treatment of Parkinson disease (PD), to explore the effects and safety of ropinirole, and to provide a theoretical basis for clinically safe and rational drug use.
METHODS
RCTs on the effectiveness and safety of ropinirole in the treatment of PD were searched. We searched Dutch medical literature database, Pubmed, Cochrane Library, China National Knowledge Infrastructure, Wanfang Knowledge Service Platform up to December 15, 2020. The Cochrane risk bias assessment tool was used to evaluate the quality of the included literature, and the RevMan5.3 software was used for meta-analysis.
RESULTS
A total of 12 RCTs with 3341 patients were included. The changes of Parkinson Disease Rating Scale Part II score (mean difference = -2.23, 95% confidence interval [CI] -2.82 to -1.64) and Parkinson Disease Rating Scale Part III scores (mean difference = -4.93, 95%CI -5.25 to -4.61) in the ropinirole group was significantly lower than that in the control group. The incidence of dizziness (odd risk [OR] = 1.85, 95%CI 1.50-2.28), nausea (OR = 2.17, 95%CI 1.81-2.59), vomiting (OR = 2.73, 95%CI 1.47-5.09), and lethargy (OR = 2.19, 95%CI 1.39-3.44) in the ropinirole group was significantly higher than that in the control group (all P < .05), and there were no significant differences in the incidence of headache (OR = 1.14, 95%CI 0.79-1.65) and insomnia (OR = 1.06, 95%CI 0.72-1.55) were found between 2 groups (all P > .05).
CONCLUSIONS
Ropinirole can help improve the ability of daily living and exercise function of PD patients, but it will increase the incidence of related adverse reactions, which needs to be further confirmed by subsequent large-scale, high-quality RCTs.
Topics: Antiparkinson Agents; Headache; Humans; Indoles; Nausea; Parkinson Disease; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders
PubMed: 34797288
DOI: 10.1097/MD.0000000000027653