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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 -
Psychiatrike = Psychiatriki 2016Bipolar disorder (BD) has a complex and variable clinical picture which is characterized by many different phacets and phases and as a result its therapeutical options... (Review)
Review
Bipolar disorder (BD) has a complex and variable clinical picture which is characterized by many different phacets and phases and as a result its therapeutical options are also complex and often unsatisfactory. Typically the so-called "mood stabilizers" are used in the treatment of BD and in this class lithium and specific antiepileptics are included. The present study aimed to systematically review the literature concerning the presence of randomized double blind clinical trials of 'non conventional' pharmaceutical treatment options. The present systematic review utilized the PRISMA method and searched the MEDLINE through January 1st 2015 with the use of appropriate key words. In order to identify randomized controlled trials- RCTs a combination of the words "bipolar", "manic", "mania", "manic depression" and "manic depressive" with "randomized" was used. Webpages with lists of trials were also searched including http://clinicaltrials.gov and http://www.clinicalstudyresults.org as well as the official webpages of all pharma companies with products marketed in the treatment of BD. The reference lists of various review papers were also searched. The MEDLINE was searched with the combination of the words "guidelines" or "algorithms" with "mania", "manic", "bipolar", "manicdepressive" or "manic depression" in order to identify articles with treatment guidelines. The reference list of these articles were also scanned. From 3,284 papers which were initially traced, only 47 papers were included in the present study. From those agents studied in acute mania, tamoxifen is efficacious as monotherapy and as combination therapy with lithium and other mood stabilizers, however its safety profile is relatively poor. Allopurinol manifests efficacy in combination with lithium but not with other agents and its safety profile is satisfactory. Methoxyprogesterone is efficacious in combination with mood stabilizers and its safety profile is very good. In acute bipolar depression the combinations of FEWP with carbamazepine and ketamine, modafinil, pramipexole, pregnenolone and maybe armodafinil with mood stabilizers are efficacious. The safety profile of these combinations is medium. The use of celecoxib, lisdexamfetamine and memantine have negative data. Concerning the maintenance treatment, the data are negative for memantine and for Nacetylcysteine. Although most of the data concerning the usefulness of "non-conventional" pharmacotherapeutic agents in the treatment of bipolar disorder are negative, it is encouraging that those agents who have been proven efficacious probably exert their therapeutic effect through pathways which differ from usual and probably different from those classically considered in most biological models of bipolar illness. In this way there constitute new paradigms and open new horizons in the understanding of the disease.
Topics: Antimanic Agents; Bipolar Disorder; Drug Therapy, Combination; Humans; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 28114089
DOI: 10.22365/jpsych.2016.274.253 -
Journal of Substance Abuse Treatment Jan 2022Sequalae of opioid misuse constitute a public health emergency in the United States. A robust evidence base informs the use of medication for opioid use disorders (MOUD)...
BACKGROUND
Sequalae of opioid misuse constitute a public health emergency in the United States. A robust evidence base informs the use of medication for opioid use disorders (MOUD) in adults, with far less research in transition-age youth. This systematic review evaluates the effectiveness of MOUD for transition-age youth (age 16 to 25).
METHODS
This synthesis was part of a larger systematic review focused on adolescent substance use interventions. The study team conducted literature searches in MEDLINE, the Cochrane CENTRAL Registry of Controlled Trials, EMBASE, PsycINFO, and CINAHL through October 31, 2019. We screened studies, extracted data, and assessed risk of bias using standard methods. The primary and secondary outcomes were the effect of MOUD on opioid abstinence and treatment retention, respectively.
RESULTS
The study team screened a total of 33,272 records and examined 1831 full-text articles. Four randomized trials met criteria for inclusion in the current analysis. All four trials assessed a combination of buprenorphine plus cognitive behavioral therapy versus a comparison condition. Some trials included additional behavioral interventions, and the specific duration/dosage of buprenorphine varied. Risk of bias was moderate for all studies. Studies found that buprenorphine was more effective than clonidine, effectively augmented by memantine, and that longer medication taper durations were more effective than shorter tapers in promoting both abstinence and retention. Notably, we did not identify any studies of methadone or naltrexone, adjunctive behavioral interventions were sparingly described, and treatment durations were far shorter than recommended guidelines in adults.
DISCUSSION
The literature guiding youth MOUD is limited, and more research should evaluate the effectiveness of options other than buprenorphine, optimal treatment duration, and the benefit of adjunctive behavioral interventions. Subgroup analyses of extant randomized clinical trials could help to extend knowledge of MOUD effectiveness in this age cohort.
Topics: Adolescent; Adult; Analgesics, Opioid; Buprenorphine; Humans; Methadone; Naltrexone; Opioid-Related Disorders; United States; Young Adult
PubMed: 34098208
DOI: 10.1016/j.jsat.2021.108494 -
The Cochrane Database of Systematic... Dec 2014Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear.
OBJECTIVES
To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adult patients treated with cranial irradiation.
SEARCH METHODS
In August 2014. we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO and checked the reference lists of included studies. We also searched for ongoing trials via ClinicalTrials.gov, the Physicians Data Query and the Meta Register of Controlled Trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors (JD, KZ) independently extracted data from selected studies and carried out a 'Risk of bias' assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled.
MAIN RESULTS
Sixteen studies were identified for possible inclusion in the review, six of which were included. Three studies investigated prevention and three studies investigated amelioration. Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Two studies investigated a pharmacological intervention for the prevention of cognitive deficits; memantine compared with placebo, and d-threo-methylphenidate HCL compared with placebo. In the first study the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The second study found no statistically significant difference between arms, with few adverse events. The third study investigated a rehabilitation program for the prevention of cognitive deficits but did not carry out a statistical comparison of cognitive performance between groups.Three studies investigated the use of a pharmacological intervention for the treatment of cognitive deficits; methylphenidate compared with modafinil, two different doses of modafinil, and donepezil compared with placebo. The first study found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. The second study combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The third study did not find an improvement in the primary cognitive outcome of overall performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. No non-pharmacological studies for the amelioration of cognitive deficits were eligible. There were a number of limitations across studies but few without high risks of bias.
AUTHORS' CONCLUSIONS
There is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil may have a role in treating cognitive deficits in adults with primary or metastatic brain tumours who have been treated with cranial irradiation. Patient withdrawal affected the statistical power of both studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher quality of evidence.There is no strong evidence to support any non-pharmacological interventions (medical or cognitive/behavioural) in the prevention or amelioration of cognitive deficits. Non-randomised studies appear promising but are as yet to be conclusive via translation into high quality evidence. Further research is required.
Topics: Adult; Benzhydryl Compounds; Cognition Disorders; Cranial Irradiation; Donepezil; Humans; Indans; Memantine; Methylphenidate; Modafinil; Nootropic Agents; Piperidines; Randomized Controlled Trials as Topic
PubMed: 25519950
DOI: 10.1002/14651858.CD011335.pub2 -
Neurological Sciences : Official... Oct 2020Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer's disease... (Review)
Review
INTRODUCTION
Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer's disease (AD) or mild cognitive impairment (MCI). The aim of this systematic review is to investigate the cognitive effects of oral saffron intake, in patients with MCI/AD and/or in non-demented individuals, by following the PRISMA guidelines.
METHODS
We performed a literature search on MedLine, Cochrane library, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) investigating the effects of oral saffron administration in patients with MCI/AD and/or in non-demented individuals.
RESULTS
Five studies (enrolling 325 individuals) met our inclusion criteria. Four studies included patients with MCI/AD, and one study included cognitively normal individuals. Saffron was well-tolerated in all groups. Regarding cognitively impaired patients, scores on Alzheimer's Disease Assessment Scale-cognitive subscale or Mini mental state examination were significantly better when saffron was compared with placebo and did not differ significantly when saffron was compared with donepezil or memantine. Saffron effects on functional status were similar with its effects on cognition.
CONCLUSIONS
Saffron was shown to be equally effective to common symptomatic drugs for MCI/AD and resulted in no difference in the incidence of side effects, when compared with placebo or drugs. The promising results should be seen cautiously, since the evidence was derived from studies with potentially high risk of bias (ROB). RCTs with larger sample sizes and low ROB are required to definitively assess the potential role of saffron as an MCI/AD treatment.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Crocus; Donepezil; Humans
PubMed: 32445136
DOI: 10.1007/s10072-020-04427-0 -
Frontiers in Pharmacology 2023Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the...
Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies.
Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].
PubMed: 37214454
DOI: 10.3389/fphar.2023.1185277 -
Journal of Geriatric Psychiatry and... Jul 2022Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy...
IMPORTANCE
Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most prevalent cause of dementia. In spite of the urgent need for more effective AD drug therapy strategies, evidence of the efficacy of combination therapy with existing drugs remains unclear.
OBJECTIVE
To assess the efficacy of combined drug therapy on cognition and progress in patients with AD in comparison to single agent drug therapy.
METHODS
The electronic databases MEDLINE and EMBASE were systematically searched to identify relevant publications. Only randomized controlled clinical trials were included, but no limits were applied to language or time published. Data were extracted from May 27th until December 29th, 2020.
RESULTS
Three trials found that a combination of ChEI with additional memantine provides a slight benefit for patients with moderate to severe AD over ChEI monotherapy and placebo. However, a further 4 trials could not replicate this effect. One trial reported benefits of add-on in donepezil-treated patients with moderate AD (using a formula containing Gingko and other antioxidants) compared to donepezil with placebo. A further trial found no significant effect of combining EGb 761® and donepezil in patients with probable AD over donepezil with placebo. Approaches with idalopirdine, atorvastatin or vitamin supplementation in combination with ChEI have not proven effective and have not been retried since. Fluoxetine and ST101 have shown partial benefits in combination with ChEI over ChEI monotherapy and placebo. However, these effects must be replicated by further research.
CONCLUSION
Additional memantine in combination with ChEI might be of slight benefit in patients with moderate to severe AD, but evidence is ambiguous. Longer trials are needed. No major cognitive benefit is missed, if solely appropriate ChEI monotherapy is initiated.
Topics: Alzheimer Disease; Cholinesterase Inhibitors; Donepezil; Drug Therapy, Combination; Humans; Indans; Memantine; Piperidines
PubMed: 34476990
DOI: 10.1177/08919887211044746 -
Clinical Interventions in Aging 2018The increasing prevalence of Alzheimer's disease (AD) demands more effective drugs, which are still unclear. The aim of this study is to compare the effectiveness of six...
PURPOSE
The increasing prevalence of Alzheimer's disease (AD) demands more effective drugs, which are still unclear. The aim of this study is to compare the effectiveness of six drugs, such as donepezil, rivastigmine, galantamine, memantine, huperzine-A, and tacrine, in senior AD patients and identify the most effective one to improve patients' cognitive function.
METHODS
A system of search strategies was used to identify relevant studies including randomized controlled trials and clinical controlled trials evaluating the efficacy of six drugs in patients with AD. We updated relevant studies that were published before March 2018 as full-text articles. Using Bayesian network meta-analysis (NMA), we ranked cognitive ability objectively based on Mini-Mental State Examination (MMSE). Pairwise and NMAs were sequentially performed for the efficacy of drugs compared to each drug or control group through the trials included.
RESULTS
Among the 35 trials included, no obvious heterogeneity ( =0.0%, =0.583) was revealed according to the pooled data for cognition in NMA and the mean difference (MD) of memantine (MD=1.7, 95% CI: 0.73, 2.8) showed that the memantine was significantly efficacious in the treatment group in terms of MMSE. Followed by galantamine, huperzine-A, rivastigmine, tacrine, and donepezil.
CONCLUSION
As the first NMA comparing the major drugs in market for AD, our study suggests that memantine might have a more significant benefit on cognition than other five drugs available.
Topics: Alzheimer Disease; Antiparkinson Agents; Bayes Theorem; Cholinesterase Inhibitors; Cognition; Donepezil; Galantamine; Humans; Memantine; Neuroprotective Agents; Nootropic Agents; Rivastigmine
PubMed: 30425461
DOI: 10.2147/CIA.S184968 -
BMC Pharmacology & Toxicology Nov 2021Obsessive-compulsive disorder (OCD) is among the most disabling neuropsychiatric conditions characterized by the presence of repetitive intrusive thoughts, impulses, or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Obsessive-compulsive disorder (OCD) is among the most disabling neuropsychiatric conditions characterized by the presence of repetitive intrusive thoughts, impulses, or images (obsessions) and/or ritualized mental or physical acts (compulsions). Serotonergic medications, particularly Selective Serotonin Reuptake Inhibitors (SSRIs), are the first-line treatments for patients with OCD. Recently, dysregulation of glutamatergic system has been proposed to be involved in the etiology of OCD. We designed this systematic review and meta-analysis to evaluate clinical efficacy of glutamatergic medications in patients with OCD, according to the guidelines of Cochrane collaboration.
METHOD
We searched Medline, Scopus, and Cochrane library without applying any language filter. Two of the authors independently reviewed search results for irrelevant and duplicate studies and extracted data and assessed methodological quality of the studies. We transformed data into a common rubric and calculated a weighted treatment effect across studies using Review Manager.
RESULTS
We found 476 references in 3 databases, and after exclusion of irrelevant and duplicate studies, 17 studies with total number of 759 patients with OCD were included. In the present review we found evidence for several drugs such as memantine, N-acetylcysteine (NAC), Minocycline, L-carnosine and riluzole. Glutamaterigic drug plus SSRIs were superior to SSRI+ Placebo with regard to Y-BOCS scale [standardized mean difference (SMD = - 3.81 95% CI = - 4.4, - 3.23).
CONCLUSION
Augmentation of glutamatergic medications with SSRIs are beneficial in obsessive-compulsive patients, no harmful significant differences in any safety outcome were found between the groups.
Topics: Adult; Drug Therapy, Combination; Excitatory Amino Acid Agents; Humans; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors
PubMed: 34736541
DOI: 10.1186/s40360-021-00534-6 -
Frontiers in Pharmacology 2020Pharmacological treatments play a significant role in treating mild to moderate Alzheimer's disease (AD), but the optimal doses of various drugs used for these...
BACKGROUND
Pharmacological treatments play a significant role in treating mild to moderate Alzheimer's disease (AD), but the optimal doses of various drugs used for these treatments are unknown. Our study compared the efficacy, acceptability, and safety of different doses of pharmacological treatments for mild to moderate AD.
METHODS
Randomized controlled trials (RCTs) were identified by searching the PubMed, EMBASE, and Cochrane Library databases (all RCTs published from the date of inception of the databases until September 19, 2019). Trials comparing the efficacy, acceptability, and safety of pharmacological interventions involving donepezil, galantamine, rivastigmine, memantine, huperzine A, and extract EGb761, alone or in combination, were identified. The primary outcomes were efficacy, acceptability, and safety.
RESULTS
Our meta-analysis included 37 studies involving 14,705 participants. In terms of improving cognitive function, galantamine 32 mg, galantamine 24 mg, donepezil 5 mg, and donepezil 10 mg were more effective than other interventions, with the surface under the cumulative ranking curve (SUCRA) values of 93.2, 75.5, 73.3, and 65.6%, respectively. According to the SUCRA values, EGb761 240 mg was considered to be the optimal intervention in terms of both acceptability and safety. With regard to clinical global impression, rivastigmine 12 mg had the highest probability of being ranked first (83.7%). The rivastigmine 15 cm patch (SUCRA = 93.7%) may be the best choice for daily living. However, there were no interventions that could significantly improve neuropsychiatric symptoms, compared with the placebo.
CONCLUSIONS
Different doses of the tested pharmacological interventions yielded benefits with regard to cognition, acceptability, safety, function, and clinical global impressions, but not effective behaviors.
PubMed: 32528296
DOI: 10.3389/fphar.2020.00778