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Child: Care, Health and Development Jan 2024The efficacy of structured physical exercise (SPE) has been examined in empirical studies to treat attention deficit hyperactivity disorder (ADHD). This review aimed (i)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy of structured physical exercise (SPE) has been examined in empirical studies to treat attention deficit hyperactivity disorder (ADHD). This review aimed (i) to systematically review and quantify the effects of SPE on ADHD symptomology and executive function (primary outcomes) and on physical health, physical fitness and mental health issues (secondary outcomes) in children/adolescents with ADHD; (ii) to evaluate the study quality and explore moderation of the effects of SPE; and (iii) to summarize the design of SPE interventions.
METHODS
An extensive literature search in the databases of PubMed, Web of Science and EBSCOhost was conducted to identify eligible intervention studies for meta-analysis. A descriptive account of the features of the studies is provided, including assessment of risk/quality (ROB-2/ROBINS-I). Standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated with random effects models to compare post-intervention effects.
RESULTS
A total of 18 studies were included in the review. The majority of the studies examined the effects of SPE lasting for 3-12 weeks. Assessment of bias/quality indicated half of the included studies as high quality. The meta-analysis (pooled n = 627) revealed that SPE had a positive effect on primary and secondary outcomes, that is, inattention (SMD = -1.79), executive function (SMD = 2.19), physical fitness (SMD = 1.39) and mental health issues (SMD = -0.89). Subgroup analysis showed that long-term practice of SPE, featured/tailored SPE, non-Chinese participants, taking methylphenidate and study with low quality had larger effects.
CONCLUSIONS
There is emerging evidence that SPE is a promising option to enhance symptom management and physical/mental health in children/adolescents with ADHD.
Topics: Child; Adolescent; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Exercise; Exercise Therapy
PubMed: 37433667
DOI: 10.1111/cch.13150 -
BMJ Supportive & Palliative Care Sep 2023Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.
METHODS
Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.
RESULTS
This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil.
CONCLUSION
Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.
Topics: Humans; Modafinil; Central Nervous System Stimulants; Paroxetine; Network Meta-Analysis; Methylphenidate; Fatigue; Neoplasms
PubMed: 34593386
DOI: 10.1136/bmjspcare-2021-003244 -
Neuroscience and Biobehavioral Reviews Jul 2024Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant... (Meta-Analysis)
Meta-Analysis Review
Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with executive function deficits that are improved with medications. However, meta-analyses of stimulant effects on cognition have mostly tested single-dose effects, and there is no meta-analysis of non-stimulant effects. This systematic review and meta-analysis tested the clinically more relevant longer-term effects of Methylphenidate (20 studies; minimum 1 week) and Atomoxetine (8 studies; minimum 3 weeks) on reaction time, attention, inhibition, and working memory, searching papers on PubMed, Embase, Ovid MEDLINE, and PsycINFO. The meta-analysis of 18 studies in 1667 subjects showed that methylphenidate was superior to placebo in all cognitive domains with small to medium effect sizes (Hedges g of 0.34-0.59). The meta-analysis of atomoxetine included 7 studies in 829 subjects and showed no effects in working memory, but superior effects in the other domains with medium to large effect sizes (Hedge's g of 0.36-0.64). Meta-regression analysis showed no drug differences on cognitive effects. The meta-analyses show for the first time that chronic Methylphenidate and Atomoxetine have comparable effects of improving executive functions in people with ADHD.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Executive Function; Central Nervous System Stimulants; Methylphenidate; Atomoxetine Hydrochloride; Memory, Short-Term
PubMed: 38718988
DOI: 10.1016/j.neubiorev.2024.105703 -
Minerva Anestesiologica Oct 2023Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering.
EVIDENCE ACQUSITION
Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery.
EVIDENCE SYNTHESIS
Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks.
CONCLUSIONS
Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.
Topics: Humans; Adult; Shivering; Nefopam; Clonidine; Tramadol; Network Meta-Analysis; Doxapram; Meperidine; Methylphenidate
PubMed: 37458681
DOI: 10.23736/S0375-9393.23.17410-4 -
British Journal of Clinical Pharmacology Aug 2023Animal studies suggest that methylphenidate treatment for around 3 months may lead to less mineralized and weaker appendicular bones. A systematic review was conducted...
AIMS
Animal studies suggest that methylphenidate treatment for around 3 months may lead to less mineralized and weaker appendicular bones. A systematic review was conducted to summarize the evidence from observational studies, and a self-controlled case series study was used to compare the risk before and after treatment initiation.
METHODS
Literature search was conducted using PubMed, Embase and the Cochrane Library to identify observational studies on methylphenidate and fractures. We also conducted a self-controlled case series study with individuals aged 5-24 years who received methylphenidate treatment and experienced fractures from 2001 to 2020 in Hong Kong. Incidence rate ratios and 95% confidence intervals were calculated by comparing the incidence rate in the methylphenidate-exposed period compared with nonexposed period.
RESULTS
Six cohort studies and 2 case-control studies were included in the systematic review. For all-cause fractures, studies found a 39-74% lower risk in treated-attention deficit hyperactivity disorder (ADHD) group compared with untreated ADHD but no difference between stimulants and nonstimulants. Differences between sexes and treatment duration were also found-significant results were shown in males and those with longer treatment duration. Among 43 841 individuals with ADHD medication before the year 2020, 2023 were included in the self-controlled case series analysis. The risks of fractures were lower by 32-41% in different treatment periods when compared with 6 months before treatment initiation.
CONCLUSION
Methylphenidate treatment may lower the risk of all-cause fractures from both study designs; however, further evidence is needed about the treatment duration and sex effect. Conclusions on stress fractures are not yet established, and further research is required.
Topics: Male; Humans; Methylphenidate; Central Nervous System Stimulants; Attention Deficit Disorder with Hyperactivity; Cohort Studies; Research Design
PubMed: 36918367
DOI: 10.1111/bcp.15714 -
Clinical NeuropharmacologyFatigue is a chronic and debilitating symptom of many long-term neurological conditions (LTNCs). Although methylphenidate provides some promise in alleviating fatigue in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Fatigue is a chronic and debilitating symptom of many long-term neurological conditions (LTNCs). Although methylphenidate provides some promise in alleviating fatigue in other clinical groups, little work has explored its potential utility within LTNCs. The current systematic review and meta-analysis evaluates the utility of methylphenidate for symptoms of fatigue in LTNCs.
METHODS
Five databases (PsycINFO, MEDLINE, Embase, Scopus, and Cochrane Library) were searched for relevant articles from their inception to February 2022. A purpose-developed evaluation tool was used to assess each study's research quality (QuEST:F).
RESULTS
Of the 1698 articles identified, 11 articles were included within this review (n = 370). Meta-analytical findings reported an overall significant benefit of methylphenidate for symptoms of fatigue across a mixed neurological sample ( g = -0.44; 95% confidence interval, -0.77 to -0.11). Subgroup analyses identified a significantly greater benefit ( P < 0.001) of methylphenidate for fatigue in LTNCs with static pathogenic trajectories (eg, traumatic brain injury) (number needed to treat = 2.5) compared with progressive conditions (eg, multiple sclerosis) (number needed to treat = 40.2).
CONCLUSIONS
Methylphenidate may pose an effective intervention for the treatment of fatigue in a number of LTNCs. Nonetheless, given the quality of the current evidence base, there exists a clear need for further robust assessment of the utility of methylphenidate-with a focus on subgroup-specific variability.
Topics: Humans; Methylphenidate; Neoplasms; Fatigue; Multiple Sclerosis; Central Nervous System Stimulants
PubMed: 37962311
DOI: 10.1097/WNF.0000000000000572 -
European Journal of Drug Metabolism and... Mar 2024BACKGROUND AND OBJECTIVE: Attention deficit hyperactivity disorder is one of the most common neuropsychiatric conditions in children, and methylphenidate (MPH) is one...
UNLABELLED
BACKGROUND AND OBJECTIVE: Attention deficit hyperactivity disorder is one of the most common neuropsychiatric conditions in children, and methylphenidate (MPH) is one of the first-line therapies. MPH is available in a variety of extended-release (ER) formulations worldwide, and most formulations are not considered bioequivalent due to differences in pharmacokinetics. It is hypothesized that the current bioequivalence guidelines from the different regulatory bodies may generate inconsistent findings or recommendations when assessing the bioequivalence of ER MPH formulations. This manuscript aims to conduct a comprehensive and narrative critical literature review to analyze pharmacokinetic data pertaining to ER formulations of MPH in order to assess bioequivalence, differences in regulatory guidelines, and additional pharmacokinetic-pharmacodynamic parameters that may help define interchangeability.
METHODS
A literature search was conducted in EMBASE, Medline, and Cochrane Library with no time limits. Study characteristics, non-compartmental pharmacokinetic parameters, and bioequivalence data were extracted for analysis.
RESULTS
Thirty-three studies were identified with primary pharmacokinetic data after the administration of ER MPH, of which 10 were direct comparative studies (i.e., at least 2 formulations tested within a single setting) and 23 were indirect comparisons (i.e., different experimental settings). Two formulations were consistently reported as bioequivalent across the regulatory bodies using criteria from their guidance documents, although inconsistencies have been observed. However, when additional kinetic criteria (discussed in this manuscript) were imposed, only one study met the more stringent definition of bioequivalence. Various clinical factors also had inconsistent effects on the pharmacokinetics and interchangeability of the different formulations, which were associated with a lack of standardization for assessing covariates across the regulatory agencies.
CONCLUSION
Additional pharmacokinetic parameters and consistency in guidelines across the regulatory bodies may improve bioequivalence assessments. Based on our findings, more research is also required to understand whether bioequivalence is an appropriate measure for determining MPH interchangeability. This critical review is suitable for formulation scientists, clinical pharmacologists, and clinicians.
Topics: Child; Humans; Methylphenidate; Central Nervous System Stimulants; Therapeutic Equivalency; Attention Deficit Disorder with Hyperactivity; Delayed-Action Preparations; Cross-Over Studies
PubMed: 38127227
DOI: 10.1007/s13318-023-00873-1 -
Addiction (Abingdon, England) Feb 2024There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo-controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD.
METHODS
Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random-effect meta-analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random-effect meta-analysis of continuous variables.
RESULTS
Ten RCTs (n = 561 participants) were included in the meta-analysis. Trials studied methylphenidate (n = 7), with daily doses of 54-180 mg, and dextroamphetamine (n = 3), with daily doses of 60-110 mg, for 2-24 weeks. PPs significantly decreased end-point craving [SMD -0.29; 95% confidence interval (CI) = -0.55, -0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85-1.01). No effect was observed for self-reported ATS use, retention in treatment, dropout following adverse events, early-stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79-0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention.
CONCLUSIONS
Among individuals with amphetamine-type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications.
Topics: Humans; Central Nervous System Stimulants; Methylphenidate; Substance-Related Disorders; Amphetamines; Prescriptions; Randomized Controlled Trials as Topic
PubMed: 37880829
DOI: 10.1111/add.16347 -
Journal of the American Academy of... May 2024We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to...
OBJECTIVE
We conducted a systematic review and meta-analysis to quantify the effect of attention-deficit/hyperactivity disorder (ADHD) medication on quality of life (QoL), and to understand whether this effect differs between stimulants and non-stimulants.
METHOD
From the dataset of a published network meta-analysis (Cortese et al., 2018), updated on 27 February 2023 (https://med-adhd.org/), we identified randomized controlled trials (RCTs) of ADHD medications for individuals aged 6 years or more with a diagnosis of ADHD based on the DSM (from third to fifth editions) or the International Classification of Diseases (ICD; ninth or tenth revision), reporting data on QoL (measured with a validated scale). The risk of bias for each RCTs was assessed using the Cochrane Risk of Bias tool 2. Multi-level meta-analytic models were conducted with R 4.3.1.
RESULTS
We included 17 RCTs (5,388 participants in total; 56% randomized to active medication) in the meta-analyses. We found that amphetamines (Hedges g = 0.51, 95% CI = 0.08, 0.94), methylphenidate (0.38; 0.23, 0.54), and atomoxetine (0.30; 0.19, 0.40) were significantly more efficacious than placebo in improving QoL in people with ADHD, with moderate effect size. For atomoxetine, these effects were not moderated by the length of intervention, and did not differ between children/adolescents and adults.
CONCLUSION
In addition to being efficacious in reducing ADHD core symptom severity, both stimulant and non-stimulant medications are efficacious in improving QoL in people with ADHD, albeit with lower effect sizes. Future research should explore whether, and to what degree, combining pharmacological and non-pharmacological interventions is likely to further improve QoL in people with ADHD.
STUDY PREREGISTRATION INFORMATION
Effects of pharmacological treatment for ADHD on quality of life: a systematic review and meta-analysis; https://osf.io/;qvgps.
PubMed: 38823477
DOI: 10.1016/j.jaac.2024.05.023 -
Cureus Mar 2024Limb fractures are a common cause of pediatric hospital admissions and surgeries, with a significant prevalence in the United Kingdom across all injury categories. Among... (Review)
Review
Limb fractures are a common cause of pediatric hospital admissions and surgeries, with a significant prevalence in the United Kingdom across all injury categories. Among psychiatric conditions in children, attention deficit hyperactivity disorder (ADHD) stands out as frequently associated with fractures, particularly those involving extremities. ADHD, with diagnoses prevalent among a significant proportion of school-age children and adolescents, has witnessed a growing global incidence. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist for our systematic literature search, using various databases and specific search terms related to ADHD and fractures. We considered articles from 2018 to 2023, focusing on English language papers with free full-text access. Our selection process used the PRISMA flowchart. We began with 1,890 articles and, after deduplication, title screening, abstract assessment, and quality evaluation included nine research papers in our review. Our primary focus was on examining fracture-related outcomes in individuals with ADHD compared to those without, considering medication status. These studies encompassed various designs, with a focus on the ADHD-fracture relationship and methylphenidate's (MPH) impact. Our study confirms that ADHD increases fracture risk and suggests that MPH may help mitigate this risk. Early ADHD detection is vital for nonpharmacological interventions. Orthopedic surgeons should proactively identify ADHD, while healthcare professionals should offer injury prevention guidance, particularly for at-risk groups.
PubMed: 38654766
DOI: 10.7759/cureus.56833