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Zeitschrift Fur Kinder- Und... May 2018Research has implicated glutamatergic projections between the various frontal subregions in the pathogenesis of compulsivity and impulsivity. Reducing striatal glutamate... (Review)
Review
OBJECTIVE
Research has implicated glutamatergic projections between the various frontal subregions in the pathogenesis of compulsivity and impulsivity. Reducing striatal glutamate release, or antagonising the action of glutamate at its receptors, may therefore represent viable treatment strategies. Several glutamatergic agents with regulatory approval for other indications are available and may be of potential benefit in the treatment of compulsivity/impulsivity in psychiatric disorders in paediatric patients.
METHOD
This review was performed according to PRISMA guidelines and evaluates available scientific literature concerning the use of glutamatergic agents in these patients, in order to determine their reported effectiveness/efficacy and tolerability/safety.
RESULTS
Out of a total of 1,426 publications, 21 trials examining six glutamatergic substances in patients with obsessive-compulsive disorder, autism spectrum disorders, and attention deficit/hyperactivity disorder were included.
CONCLUSIONS
Trial designs as well as results were heterogeneous and thus comparability was limited. Available data support the hypothesis that glutamatergic agents are of potential value in the treatment of compulsivity/impulsivity in children and adolescents. Based on the data reviewed, memantine and N-acetylcysteine suggest the best risk-benefit profile for future trials. Riluzole should primarily be further investigated in adults. Clinical research of this nature is a key element of the TACTICS Consortium project funded by the European Union (FP7).
Topics: Acetylcysteine; Adolescent; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Brain; Child; Corpus Striatum; Excitatory Amino Acid Agents; Glutamic Acid; Humans; Memantine; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Receptors, Glutamate; Risk Assessment; Treatment Outcome
PubMed: 28922069
DOI: 10.1024/1422-4917/a000546 -
The Cochrane Database of Systematic... Apr 2017Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. Appropriate interventions may bring... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. Appropriate interventions may bring considerable improvements in function and quality of life to seriously ill people and their families, reducing physical, psychological and spiritual distress.
OBJECTIVES
To conduct an overview of the evidence available on the efficacy of interventions used in the management of fatigue and/or unintentional weight loss in adults with advanced progressive illness by reviewing the evidence contained within Cochrane reviews.
METHODS
We searched the Cochrane Database of Systematic Reviews (CDSR) for all systematic reviews evaluating any interventions for the management of fatigue and/or unintentional weight loss in adults with advanced progressive illness (The Cochrane Library 2010, Issue 8). We reviewed titles of interest by abstract. Where the relevance of a review remained unclear we reached a consensus regarding the relevance of the participant group and the outcome measures to the overview. Two overview authors extracted the data independently using a data extraction form. We used the measurement tool AMSTAR (Assessment of Multiple SysTemAtic Reviews) to assess the methodological quality of each systematic review.
MAIN RESULTS
We included 27 systematic reviews (302 studies with 31,833 participants) in the overview. None of the included systematic reviews reported quantitative data on the efficacy of interventions to manage fatigue or weight loss specific to people with advanced progressive illness. All of the included reviews apart from one were deemed of high methodological quality. For the remaining review we were unable to ascertain the methodological quality of the research strategy as it was described. None of the systematic reviews adequately described whether conflict of interests were present within the included studies. Management of fatigueAmyotrophic lateral sclerosis/motor neuron disease (ALS/MND) - we identified one systematic review (two studies and 52 participants); the intervention was exercise.Cancer - we identified five systematic reviews (116 studies with 17,342 participants); the pharmacological interventions were eicosapentaenoic acid (EPA) and any drug therapy for the management of cancer-related fatigue and the non pharmacological interventions were exercise, interventions by breast care nurses and psychosocial interventions.Chronic obstructive pulmonary disease (COPD) - we identified three systematic reviews (59 studies and 4048 participants); the interventions were self management education programmes, nutritional support and pulmonary rehabilitation.Cystic fibrosis - we identified one systematic review (nine studies and 833 participants); the intervention was physical training.Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) - we identified two systematic reviews (21 studies and 748 participants); the interventions were progressive resistive exercise and aerobic exercise.Multiple sclerosis (MS) - we identified five systematic reviews (23 studies and 1502 participants); the pharmacological interventions were amantadine and carnitine. The non pharmacological interventions were diet, exercise and occupational therapy.Mixed conditions in advanced stages of illness - we identified one systematic review (five studies and 453 participants); the intervention was medically assisted hydration. Management of weight lossALS/MND - we identified one systematic review but no studies met the inclusion criteria for the systematic review; the intervention was enteral tube feeding.Cancer - we identified three systematic reviews with a fourth systematic review also containing extractable data on cancer (66 studies and 5601 participants); the pharmacological interventions were megestrol acetate and eicosapentaenoic acid (EPA) (this systematic review is also included in the cancer fatigue section above). The non pharmacological interventions were enteral tube feeding and non invasive interventions for patients with lung cancer.COPD - we identified one systematic review (59 studies and 4048 participants); the intervention was nutritional support. This systematic review is also included in the COPD fatigue section.Cystic fibrosis - we identified two systematic reviews (three studies and 131 participants); the interventions were enteral tube feeding and oral calorie supplements.HIV/AIDS - we identified four systematic reviews (42 studies and 2071 participants); the pharmacological intervention was anabolic steroids. The non pharmacological interventions were nutritional interventions, progressive resistive exercise and aerobic exercise. Both of the systematic reviews on exercise interventions were also included in the HIV/AIDS fatigue section.MS - we found no systematic reviews which considered interventions to manage unintentional weight loss for people with a clinical diagnosis of multiple sclerosis at any stage of illness.Mixed conditions in advanced stages of illness - we identified two systematic reviews (32 studies and 4826 participants); the interventions were megestrol acetate and medically assisted nutrition.
AUTHORS' CONCLUSIONS
There is a lack of robust evidence for interventions to manage fatigue and/or unintentional weight loss in the advanced stage of progressive illnesses such as advanced cancer, heart failure, lung failure, cystic fibrosis, multiple sclerosis, motor neuron disease, Parkinson's disease, dementia and AIDS. The evidence contained within this overview provides some insight into interventions which may prove of benefit within this population such as exercise, some pharmacological treatments and support for self management.Researchers could improve the methodological quality of future studies by blinding of outcome assessors. Adopting uniform reporting mechanisms for fatigue and weight loss outcome measures would also allow the opportunity for meta-analysis of small studies.Researchers could also improve the applicability of recommendations for interventions to manage fatigue and unintentional weight loss in advanced progressive illness by including subgroup analysis of this population within systematic reviews of applicable interventions.More research is required to ascertain the best interventions to manage fatigue and/or weight loss in advanced illness. There is a need for standardised reporting of these symptoms and agreement amongst researchers of the minimum duration of studies and minimum percentage change in symptom experience that proves the benefits of an intervention. There are, however, challenges in providing meaningful outcome measurements against a background of deteriorating health through disease progression. Interventions to manage these symptoms must also be mindful of the impact on quality of life and should be focused on patient-orientated rather than purely disease-orientated experiences for patients. Systematic reviews and primary intervention studies should include the impact of the interventions on standardised validated quality of life measures.
Topics: Adult; Amyotrophic Lateral Sclerosis; Cystic Fibrosis; Disease Progression; Emaciation; Fatigue; HIV Infections; Humans; Multiple Sclerosis; Neoplasms; Pulmonary Disease, Chronic Obstructive; Review Literature as Topic; Weight Loss
PubMed: 28387447
DOI: 10.1002/14651858.CD008427.pub3 -
Journal of Cachexia, Sarcopenia and... Mar 2016In palliative care patients, fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Further... (Review)
Review
BACKGROUND
In palliative care patients, fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The review aimed to evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases.
METHODS
We considered randomized controlled trials concerning adult palliative care with a focus on pharmacological treatment of fatigue compared with placebo, application of two drugs, usual care or a non-pharmacological intervention. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). We searched the CENTRAL, MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. Two review authors independently assessed trial quality and extracted the data.
RESULTS
We screened 1645 publications of which 45 met the inclusion criteria. In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials. Meta-analysis of data was possible for modafinil, pemoline, and methylphenidate.
CONCLUSIONS
Due to the limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Some drugs, which may be beneficial for the treatment of fatigue associated with palliative care such as amantadine, methylphenidate, and modafinil, should be further researched.
PubMed: 27066315
DOI: 10.1002/jcsm.12101 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD)...
BACKGROUND
Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD) includes mild cognitive impairment (MCI) due to AD and mild AD dementia.
OBJECTIVE
The aim of this study was to investigate symptomatic treatment prevalence and treatment patterns in eAD.
METHODS
Embase, MEDLINE, and EBM Reviews were searched in November 2021 for observational studies reporting symptomatic treatment patterns in eAD. The range of patients receiving treatment was collated. Risk of bias was assessed using the Joanna Briggs Institute (JBI) prevalence tool. Two independent reviewers screened the records, one performed data extraction and quality assessment while a second checked.
RESULTS
Twenty-one studies (prospective and retrospective cohorts, cross-sectional studies, and a survey) were included. Population size ranged from 23 to 2,028. Worldwide, 18 to 35% of patients diagnosed with MCI due to AD received any AChE inhibitor (three studies; n = 631), 7 to 8% memantine (two studies; n = 229), and 9% combination therapy (one study; n = 402). Patients receiving no treatment ranged from 41 to 54% (two studies; n = 733). Worldwide, in mild AD dementia patients, 13 to 89% received any AChE inhibitor (six studies; n = 3,715), 1 to 21% memantine (five studies, n = 3,527), and 0.4 to 39% combination therapy (four studies, n = 3,018). Patients receiving no treatment ranged from 9 to 26% (five studies, n = 4,073).
CONCLUSION
Limitations in reporting led to unclear risk of bias. The results reveal a pattern of use of symptomatic treatment in eAD beyond approved labels and highlights the opportunity for new consensus guidelines to inform clinical practice.
Topics: Humans; Alzheimer Disease; Memantine; Prospective Studies; Cross-Sectional Studies; Retrospective Studies; Dementia; Cognitive Dysfunction; Disease Progression
PubMed: 36404542
DOI: 10.3233/JAD-220471 -
Annals of Physical and Rehabilitation... Feb 2016The agitation crisis in the awakening phase after traumatic brain injury (TBI) is one of the most difficult behavioral disorders to alleviate. Current treatment options... (Review)
Review
UNLABELLED
The agitation crisis in the awakening phase after traumatic brain injury (TBI) is one of the most difficult behavioral disorders to alleviate. Current treatment options are heterogeneous and may involve excessive sedation. Practice guidelines are required by professionals in charge of TBI patients. Few reviews were published but those are old and based on expert opinions. The purpose of this work is to propose evidence-based guidelines to treat the agitation crisis.
METHODS
The elaboration of these guidelines followed the procedure validated by the French health authority for good practice recommendations, close to the Prisma statement. Guidelines were elaborated on the basis of a systematic and critical review of the literature.
RESULTS
Twenty-eight articles concerning 376 patients were analyzed. Recommendations are: when faced with an agitation crisis, the management strategy implies to search for an underlying factor that should be treated such as pain, acute sepsis, and drug adverse effect (expert opinion). Physical restraints should be discarded when possible (expert opinion). Neuroleptic agent with a marketing authorization can be used in order to obtain a quick sedation so as to protect the patient from himself, closed ones or the healthcare team but the duration should be as short as possible (expert opinion). The efficacy of beta-blockers and antiepileptics with mood regulation effects like carbamazepine and valproate yield the most compelling evidence and should be preferably used when a background regimen is envisioned (grade B for beta-blocker and C for antiepileptics). Neuroleptics, antidepressants, benzodiazepines, buspirone may be prescribed but are considered second-line treatments (expert opinion).
CONCLUSION
This study provides a strategy for treating the agitation crisis based on scientific data and expert opinion. The level of evidence remains low and published data are often old. New studies are essential to validate results from previous studies and test new drugs and non-pharmaceutical therapies.
Topics: Adrenergic beta-Antagonists; Aggression; Amantadine; Anti-Anxiety Agents; Anticonvulsants; Antipsychotic Agents; Benzodiazepines; Brain Injuries; Buspirone; Central Nervous System Stimulants; Dopamine Agents; Humans; Methylphenidate; Psychomotor Agitation; Restraint, Physical
PubMed: 26700025
DOI: 10.1016/j.rehab.2015.11.001 -
Annals of Physical and Rehabilitation... Feb 2016There are no handbook or recommendations for the use of pharmacological agents to treat neurobehavioral disorders after traumatic brain injury (TBI). This work proposes... (Review)
Review
OBJECTIVE
There are no handbook or recommendations for the use of pharmacological agents to treat neurobehavioral disorders after traumatic brain injury (TBI). This work proposes a systematic review of the literature and a user guide on neuroleptics, antidepressants, beta-blockers, mood stabilizers and other medications for irritability, aggressiveness, agitation, impulsivity, depression, apathy…
METHOD
Steering, working and reading groups (62 people) were formed under the control of the French High Authority for Health (HAS) in collaboration with the SOFMER scientific society (French Society of Physical and Rehabilitation Medicine). Articles were searched by HAS officers in the Medline database from 1990 to 2012, crossing TBI and pharmacological agents. The HAS method to select, read and analyze papers is close to the PRISMA statements.
RESULTS
Out of 772 references, 89 were analyzed, covering a total of 1306 people with TBI. There is insufficient evidence to standardize drug treatments for these disorders. There are however some elements to establish consensus recommendations for good clinical practice. Propranolol can improve aggression (B grade). Carbamazepine and valproate seem effective on agitation and aggression and are recommended as first line treatment (Expert Consensus [EC]). There is no evidence of efficacy for neuroleptics. Their prescription is based on emergency situation for a crisis (loxapine) but not for long-term use (EC). Antidepressants are recommended to treat depression (EC) with a higher standard of proof for Selective Serotonin Reuptake Inhibitors (SSRI, grade B). Other products are described.
CONCLUSION
The choice of treatment depends on the level of evidence, target symptoms, custom objectives, clinical experience and caution strategies.
Topics: Adrenergic beta-Antagonists; Amantadine; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Brain Injuries; Consensus; Dopamine Agents; Evidence-Based Medicine; France; Humans; Mental Disorders
PubMed: 26797170
DOI: 10.1016/j.rehab.2015.10.003 -
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 -
Frontiers in Pharmacology 2023Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still...
Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH. Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence. In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3). Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators. https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.
PubMed: 37426819
DOI: 10.3389/fphar.2023.1199794 -
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 -
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