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European Journal of Neurology Dec 2023The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European... (Review)
Review
BACKGROUND
The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management.
METHODS
A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO.
RESULTS
Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low.
CONCLUSIONS
The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.
Topics: Humans; Chorea; Tetrabenazine; Levodopa; Carbidopa; Clonazepam; Methylphenidate
PubMed: 37694681
DOI: 10.1111/ene.16038 -
European Child & Adolescent Psychiatry Jun 2024Methylphenidate (MPH), a first-line treatment for attention-deficit hyperactivity disorder (ADHD) management, has been the focus of debate for decades regarding its... (Meta-Analysis)
Meta-Analysis
Methylphenidate (MPH), a first-line treatment for attention-deficit hyperactivity disorder (ADHD) management, has been the focus of debate for decades regarding its effect on growth. The aim of this PRISMA meta-analysis was to determine the effect of MPH on height in children/adolescents with ADHD and its predictive factors based on literature reports. Available full-text articles were systematically reviewed to identify clinical studies of pediatric ADHD patients with height Z-score (HZS) data for monotherapy MPH-treated and non-treated groups. We estimated standardized mean differences (SMDs) of HZS or its changes from baseline (ΔHZS) between groups, then identified associated factors through subgroup analyses and meta-regression. For before-after treatment studies, the paired standard errors of ΔHZS were re-estimated to demonstrate in the forest plot. Risk of bias was analyzed using the Newcastle-Ottawa Scale. Among the 29 eligible studies, 26 reported ΔHZS with self-control groups, and ΔHZS or absolute HZS were compared to other external controls in 11 studies. A significant reduction was observed between post-MHP and pre-MPH use, with high heterogeneity (SMD = - 0.40; 95% confidence interval = [ - 0.54, - 0.27]; I = 91%). The study region, ADHD subtype, and stimulant-naïve status of patients at baseline may modify the effect on HZS. Because of the high clinical heterogeneity in observational studies, clinicians should consider the negative effect of MPH on height in ADHD patients by determining whether patients fulfill appropriate high-risk criteria. Further well-designed longitudinal studies are required to better quantify this effect, especially with prolonged treatment.
Topics: Humans; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Body Height; Adolescent
PubMed: 37589730
DOI: 10.1007/s00787-023-02273-x -
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 -
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 -
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 -
Molecular Psychiatry Jun 2023Psychotic disorders are severe mental disorders with poorly understood etiology. Biomarkers in the cerebrospinal fluid (CSF) could provide etiological clues and... (Meta-Analysis)
Meta-Analysis
Psychotic disorders are severe mental disorders with poorly understood etiology. Biomarkers in the cerebrospinal fluid (CSF) could provide etiological clues and diagnostic tools for psychosis; however, an unbiased overview of CSF alterations in individuals with psychotic disorders is lacking. The objective of this study was to summarize all quantifiable findings in CSF from individuals with psychotic disorders compared to healthy controls (HC). Studies published before January 25th, 2023 were identified searching PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO. Screening, full-text review, data extraction, and risk of bias assessments were performed by two independent reviewers following PRISMA guidelines. Findings in patients and healthy controls were compared and summarized using random-effects analyses and assessment of publication bias, subgroup and sensitivity analyses were performed. 145 studies, covering 197 biomarkers, were included, of which 163 biomarkers have not previously been investigated in meta-analyses. All studies showed some degree of bias. 55 biomarkers measured in CSF were associated with psychosis and of these were 15 biomarkers measured in ≥2 studies. Patients showed increased levels of noradrenaline (standardized mean difference/SMD, 0.53; 95% confidence interval/CI, 0.16 to 0.90) and its metabolite 3-methoxy-4-hydroxyphenylglycol (SMD, 0.30; 95% CI: 0.05 to 0.55), the serotonin metabolite 5-hydroxyindoleacetic acid (SMD, 0.11; 95% CI: 0.01 to 0.21), the pro-inflammatory neurotransmitter kynurenic acid (SMD, 1.58; 95% CI: 0.34 to 2.81), its precursor kynurenine (SMD,0.99; 95% CI: 0.60 to 1.38), the cytokines interleukin-6 (SMD, 0.58; 95% CI: 0.39 to 0.77) and interleukin-8 (SMD, 0.43; 95% CI: 0.24 to 0.62), the endocannabinoid anandamide (SMD, 0.78; 95% CI: 0.53 to 1.02), albumin ratio (SMD, 0.40; 95% CI: 0.08 to 0.72), total protein (SMD, 0.29; 95% CI: 0.16 to 0.43), immunoglobulin ratio (SMD, 0.45; 95% CI: 0.06 to 0.85) and glucose (SMD, 0.48; 95% CI: 0.01 to 0.94). Neurotensin (SMD, -0.67; 95% CI: -0.89 to -0.46) and γ-aminobutyric acid (SMD, -0.29; 95% CI: -0.50 to -0.09) were decreased. Most biomarkers showed no significant differences, including the dopamine metabolites homovanillic acid and 3,4-dihydroxyphenylacetic acid. These findings suggest that dysregulation of the immune and adrenergic system as well as blood-brain barrier dysfunction are implicated in the pathophysiology of psychotic disorders.
Topics: Humans; Psychotic Disorders; Biomarkers; Norepinephrine; Dopamine; Homovanillic Acid
PubMed: 37169812
DOI: 10.1038/s41380-023-02059-2 -
CNS Drugs May 2023For some adults with Attention-Deficit/Hyperactivity Disorder (ADHD), nonstimulants need to be considered either as a monotherapy or as an adjunct to stimulants. (Meta-Analysis)
Meta-Analysis
BACKGROUND
For some adults with Attention-Deficit/Hyperactivity Disorder (ADHD), nonstimulants need to be considered either as a monotherapy or as an adjunct to stimulants.
OBJECTIVES
The objectives of this systematic review and meta-analysis were to assess the efficacy, acceptability, and tolerability of nonstimulants in adults with ADHD.
METHODS
Data sources, searches, and study selection were based on a previously published network meta-analysis of randomized clinical trials (RCTs) by Cortese at al. (Lancet Psychiatry 5(9):727-738, 2018), which we updated in March 2022. Specifically, we searched PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, OpenGrey, Web of Science Core Collection, ProQuest Dissertations and Theses (UK and Ireland), ProQuest Dissertations and Theses (abstracts and international), and the WHO International Trials Registry Platform, including ClinicalTrials.gov for double-blind RCTs with a placebo arm, lasting at least one week, including adults with a diagnosis of ADHD based on DSM-III, DSM-III-R, DSM-IV(TR), DSM-5 or ICD-9- or 10, and reporting data on efficacy, tolerability (drop-out due to side effects) and acceptability (drop-out due to any cause) of guanfacine, clonidine, or atomoxetine. Additionally, we searched for RCTs of viloxazine extended release (ER), approved for ADHD in 2021. Random-effects meta-analyses were conducted, and the risk of bias for individual RCTs was assessed using the Cochrane Risk of Bias tool.
RESULTS
We included 18 studies in the meta-analyses (4308 participants) plus one additional study in the narrative synthesis (374 participants). The meta-analysis showed that atomoxetine (15 RCTs) (Hedge's g = - 0.48, 95% CI [- 0.64; - 0.33]), guanfacine (two RCTs) (Hedge's g = - 0.66, 95% CI [- 0.94; - 0.38]) and viloxazine ER (one RCT) were significantly more efficacious than placebo. Atomoxetine was less well tolerated than placebo, while tolerability of guanfacine and viloxazine ER could not be meta-analysed, since only one study, for each medication, reported on it.
CONCLUSIONS
All investigated nonstimulants were more efficacious in the treatment of ADHD in adults, than placebo, while the placebo had better acceptability and tolerability.
PROTOCOL
https://osf.io/5vnmt/?view_only=2bf87ed12ba94645babedceeee4c0120 .
Topics: Adult; Humans; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Guanfacine; Viloxazine; Central Nervous System Stimulants; Randomized Controlled Trials as Topic
PubMed: 37166701
DOI: 10.1007/s40263-023-01005-8