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Frontiers in Pharmacology 2023Alzheimer's disease (AD) is a progressive neurodegenerative disorder, that is, characterized by cognitive decline. To date, there are no effective treatments for AD....
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, that is, characterized by cognitive decline. To date, there are no effective treatments for AD. Therefore, the objective of this study was to map new perspectives on the effects of pharmacological treatment on cognitive function and the overall psychological state in patients with AD. Two independent researchers searched for randomized clinical trials (RCTs) exploring new pharmacological approaches related to cognition in Alzheimer's disease in adults from 2018 to 2023 in PubMed, Web of Science, Scopus, and Cochrane Library databases. A total of 17 RCTs were included in this review. The results show that in recent years, new drugs have been tested in patients with Alzheimer's disease, including masitinib, methylphenidate, levetiracetam, Jiannao Yizhi, and Huannao Yicong formulas. Most studies have been conducted in populations with mild to moderate Alzheimer's disease. Although some of the drugs found suggested improvement in cognitive function, the scarcity of available studies highlights the need for further research in this area. [www.crd.york.ac.uk/prospero], identifier [CRD42023409986].
PubMed: 37332343
DOI: 10.3389/fphar.2023.1190604 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887 -
Frontiers in Cellular Neuroscience 2023It is now well-accepted that psychostimulants act on glial cells causing neuroinflammation and adding to the neurotoxic effects of such substances. Neuroinflammation can...
It is now well-accepted that psychostimulants act on glial cells causing neuroinflammation and adding to the neurotoxic effects of such substances. Neuroinflammation can be described as an inflammatory response, within the CNS, mediated through several cytokines, reactive oxygen species, chemokines and other inflammatory markers. These inflammatory players, in particular cytokines, play important roles. Several studies have demonstrated that psychostimulants impact on cytokine production and release, both centrally and at the peripheral level. Nevertheless, the available data is often contradictory. Because understanding how cytokines are modulated by psychoactive substances seems crucial to perspective successful therapeutic interventions, here, we conducted a scoping review of the available literature. We have focused on how different psychostimulants impact on the cytokine profile. Publications were grouped according to the substance addressed (methamphetamine, cocaine, methylphenidate, MDMA or other amphetamines), the type of exposure and period of evaluation (acute, short- or long-term exposure, withdrawal, and reinstatement). Studies were further divided in those addressing central cytokines, circulating (peripheral) levels, or both. Our analysis showed that the classical pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were those more investigated. The majority of studies have reported increased levels of these cytokines in the central nervous system after acute or repeated drug. However, studies investigating cytokine levels during withdrawal or reinstatement have shown higher variability in their findings. Although we have identified fewer studies addressing circulating cytokines in humans, the available data suggest that the results may be more robust in animal models than in patients with problematic drug use. As a major conclusion, an extensive use of arrays for relevant cytokines should be considered to better determine which cytokines, upon the classical ones, may be involved in the progression from episodic use to the development of addiction. A concerted effort is still necessary to address the link between peripheral and central immune players, including from a longitudinal perspective. Until there, the identification of new biomarkers and therapeutic targets to envision personalized immune-based therapeutics will continue to be unlikely.
PubMed: 37305435
DOI: 10.3389/fncel.2023.1109611 -
Expert Opinion on Pharmacotherapy 2023The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though... (Review)
Review
INTRODUCTION
The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though drugs for ADHD and BD are largely accepted, there is relatively little research on the management of comorbidity in children and adolescents, particularly in terms of safety. We provide a synthesis of these findings because one hasn't been made yet.
AREAS COVERED
As a primary outcome, we wanted to determine whether stimulant or non-stimulant treatment of children and adolescents with ADHD and comorbid BD was effective. As a secondary outcome, we wanted to determine tolerability, especially the risk of mood switch.
EXPERT OPINION
The findings of this systematic review suggest that methylphenidate, when used with a mood stabilizer, may be safe and not significantly increase the risk of a manic switch or psychotic symptoms when used to treat ADHD that co-occurs with a BD. In situations where stimulants are ineffective or have low tolerance, atomoxetine also seems to be a good alternative, and also in cases of co-morbid anxiety, oppositional defiant disorder, conduct disorders, ICT disorders, and substance use disorders. Additional research with a higher level of evidence is necessary to corroborate these preliminary findings.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Atomoxetine Hydrochloride; Methylphenidate; Central Nervous System Stimulants
PubMed: 37300473
DOI: 10.1080/14656566.2023.2224920 -
Revista Paulista de Pediatria : Orgao... 2023The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD).
OBJECTIVE
The aim of this study was to analyze the effect of the pharmacological treatment on the sleep patterns of children with attention deficit hyperactivity disorder (ADHD).
DATA SOURCE
A high-sensitivity electronic search was performed in the following databases: Cochrane Library, MEDLINE via PubMed, LILACS via the Regional Health Portal (BVS), Embase, Scopus, CINAHL, and Web of Science, as recommended by the Cochrane Handbook, and which has undergone peer review according to the PRESS Guide.
DATA SYNTHESIS
The studies contemplated the use of the drugs atomoxetine, guanfacine, methylphenidate, dasotraline, L-theanine, and lisdexamfetamine. They showed efficiency in reducing the symptoms of ADHD, although all, except atomoxetine, affected sleep quality, such as by reducing total rapid eye movement (REM), non-REM phase, slow-wave sleep time, and longer sleep-onset latency.
CONCLUSIONS
The drugs used in the treatment of ADHD seem to have negative repercussions on the sleep quality of children, with the drug atomoxetine showing lesser effects on this variable.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Central Nervous System Stimulants; Methylphenidate; Sleep
PubMed: 37255110
DOI: 10.1590/1984-0462/2023/41/2022065 -
Journal of Attention Disorders Oct 2023To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD. (Review)
Review
OBJECTIVE
To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD.
METHODS
Studies reporting potentials predictors of response to MPH were searched in Medline and Embase from January 1998 to March 2022. Narrative synthesis was performed.
RESULTS
Fifty-seven reports of 46 studies totaling 6,656 ADHD patients were included. No association appears between response to MPH and age, gender, MPH dosage, ADHD subtype, comorbidities nor socioeconomic status when considering a specific patient. No conclusion could be drawn about body weight, ADHD severity, intelligence quotient, and parental symptoms of depression or ADHD.
CONCLUSIONS
None of these potential predictors have proven their usefulness to predict response to MPH on an individual basis in clinical practice. In research, potential predictors should be measured, their association with response to MPH assessed, in order to control for confounding variables when modeling response to MPH.
Topics: Humans; Child; Adolescent; Methylphenidate; Central Nervous System Stimulants; Attention Deficit Disorder with Hyperactivity; Intelligence Tests; Parents; Treatment Outcome
PubMed: 37243373
DOI: 10.1177/10870547231177234 -
Lakartidningen May 2023A well-conducted systematic review requires a scrupulous assessment of the design of included studies. This may unveil major issues in how studies were planned,...
A well-conducted systematic review requires a scrupulous assessment of the design of included studies. This may unveil major issues in how studies were planned, conducted and reported. This section presents a few examples. 1) A Cochrane review on pain and sedation management in the newborn identified a study described as a randomized trial, which later, following communication with authors and the editor-in-chief, turned out to be observational. 2) Poor evaluation of heterogeneity and active placebo when pooling studies on inhalation of saline solution for bronchiolitis led to clinical implementation of treatments later shown not to be effective. 3) A Cochrane review on methylphenidate for attention deficit hyperactivity disorder in adults did not identify problems with blinding and a »wash-out« period, resulting in erroneous conclusions. The review was therefore retracted. Although as important as benefits, harms of interventions are often given less attention in trials and systematic reviews.
Topics: Adult; Humans; Infant, Newborn; Attention Deficit Disorder with Hyperactivity; Biomedical Research; Methylphenidate; Pain
PubMed: 37191391
DOI: No ID Found -
European Neuropsychopharmacology : the... Jul 2023Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal... (Meta-Analysis)
Meta-Analysis
Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.
Topics: Humans; Selegiline; Depressive Disorder, Major; Monoamine Oxidase Inhibitors; Attention Deficit Disorder with Hyperactivity; Methylphenidate
PubMed: 37087864
DOI: 10.1016/j.euroneuro.2023.03.012 -
The Cochrane Database of Systematic... Apr 2023Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity,... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity, and impulsivity, and is associated with long-term social, academic, and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Research has shown that children and adolescents with ADHD have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. This review is an update of a previously published Cochrane Review. Overall, there was little evidence that PUFA supplementation improved symptoms of ADHD in children and adolescents.
OBJECTIVES
To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents.
SEARCH METHODS
We searched 13 databases and two trials registers up to October 2021. We also checked the reference lists of relevant studies and reviews for additional references.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials that compared PUFA with placebo or PUFA plus alternative therapy (medication, behavioural therapy, or psychotherapy) with the same alternative therapy alone in children and adolescents (aged 18 years and under) diagnosed with ADHD.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was severity or improvement of ADHD symptoms. Our secondary outcomes were severity or incidence of behavioural problems; quality of life; severity or incidence of depressive symptoms; severity or incidence of anxiety symptoms; side effects; loss to follow-up; and cost. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 37 trials with more than 2374 participants, of which 24 trials were new to this update. Five trials (seven reports) used a cross-over design, while the remaining 32 trials (52 reports) used a parallel design. Seven trials were conducted in Iran, four each in the USA and Israel, and two each in Australia, Canada, New Zealand, Sweden, and the UK. Single studies were conducted in Brazil, France, Germany, India, Italy, Japan, Mexico, the Netherlands, Singapore, Spain, Sri Lanka, and Taiwan. Of the 36 trials that compared a PUFA to placebo, 19 used an omega-3 PUFA, six used a combined omega-3/omega-6 supplement, and two used an omega-6 PUFA. The nine remaining trials were included in the comparison of PUFA to placebo, but also had the same co-intervention in the PUFA and placebo groups. Of these, four trials compared a combination of omega-3 PUFA plus methylphenidate to methylphenidate. One trial each compared omega-3 PUFA plus atomoxetine to atomoxetine; omega-3 PUFA plus physical training to physical training; and an omega-3 or omega-6 supplement plus methylphenidate to methylphenidate; and two trials compared omega-3 PUFA plus dietary supplement to dietary supplement. Supplements were given for a period of between two weeks and six months. Although we found low-certainty evidence that PUFA compared to placebo may improve ADHD symptoms in the medium term (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.47 to 2.60; 3 studies, 191 participants), there was high-certainty evidence that PUFA had no effect on parent-rated total ADHD symptoms compared to placebo in the medium term (standardised mean difference (SMD) -0.08, 95% CI -0.24 to 0.07; 16 studies, 1166 participants). There was also high-certainty evidence that parent-rated inattention (medium-term: SMD -0.01, 95% CI -0.20 to 0.17; 12 studies, 960 participants) and hyperactivity/impulsivity (medium-term: SMD 0.09, 95% CI -0.04 to 0.23; 10 studies, 869 participants) scores were no different compared to placebo. There was moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups (RR 1.02, 95% CI 0.69 to 1.52; 8 studies, 591 participants). There was also moderate-certainty evidence that medium-term loss to follow-up was likely similar between groups (RR 1.03, 95% CI 0.77 to 1.37; 13 studies, 1121 participants).
AUTHORS' CONCLUSIONS
Although we found low-certainty evidence that children and adolescents receiving PUFA may be more likely to improve compared to those receiving placebo, there was high-certainty evidence that PUFA had no effect on total parent-rated ADHD symptoms. There was also high-certainty evidence that inattention and hyperactivity/impulsivity did not differ between PUFA and placebo groups. We found moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups. There was also moderate-certainty evidence that follow-up was similar between groups. It is important that future research addresses the current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, and short follow-up times.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Quality of Life; Fatty Acids, Unsaturated; Methylphenidate; Fatty Acids, Omega-3; Amphetamine
PubMed: 37058600
DOI: 10.1002/14651858.CD007986.pub3 -
Progress in Neuro-psychopharmacology &... Jul 2023Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with cognitive, social, and academic impairment. Neurotrophins, particularly... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with cognitive, social, and academic impairment. Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), have been implicated in the pathophysiology of ADHD and response to stimulant treatment. This review aims to investigate the relationship between BDNF levels in ADHD before and after treatment with stimulants in childhood.
METHODS
This systematic review followed PRISMA-P guidelines and included 19 studies from PubMed, EMBASE, Cochrane, Capes Periodic, and Lilacs databases. The studies were evaluated for risk of bias and level of evidence.
RESULTS
There was no significant difference in peripheral BDNF levels in ADHD children before or after methylphenidate treatment. Additionally, there was no statistically significant difference in BDNF levels between children with ADHD and controls.
DISCUSSION
Understanding the role of BDNF in ADHD may provide insight into the disorder's pathophysiology and facilitate the development of biological markers for clinical use.
CONCLUSION
Our findings suggest that BDNF levels are not significantly affected by methylphenidate treatment in ADHD children and do not differ from controls.
SYSTEMATIC REVIEW REGISTRATION
"Brain-derived neurotrophic factor (BDNF) levels in children and adolescents before and after stimulant use: a systematic review". Number CRD42021261519.
Topics: Adolescent; Child; Humans; Attention Deficit Disorder with Hyperactivity; Brain-Derived Neurotrophic Factor; Central Nervous System Stimulants; Methylphenidate
PubMed: 37044279
DOI: 10.1016/j.pnpbp.2023.110761