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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 Feb 2019Academic improvement is amongst the most common treatment targets when prescribing stimulants to children with ADHD. Previous reviews on stimulant-related academic... (Meta-Analysis)
Meta-Analysis
Academic improvement is amongst the most common treatment targets when prescribing stimulants to children with ADHD. Previous reviews on stimulant-related academic improvements are inconclusive and focus on task engagement. Recent literature suggests outcome-domain-specific medication effects that are larger for productivity than for accuracy. The aims of this study are quantifying methylphenidate effects on academic productivity and accuracy for math, reading, spelling; exploring the mediating or moderating effects of symptom improvements, demographic-, design- and disorder-related variables. PubMed, EMBASE, ERIC and PsycINFO were searched for articles reporting methylphenidate effects on academic productivity and accuracy. Thirty-four studies met entry criteria. Methylphenidate improved math productivity (7.8% increase, p < .001); math accuracy (3.0% increase, p = .001); increased reading speed (SMD .47, p < .001) but not reading accuracy. None of the mediators or moderators tested affected methylphenidate efficacy. Academic improvements were small compared to symptom improvements; qualitative changes limited to math. Clinicians should take this discrepancy into account when prescribing medication for ADHD.
Topics: Academic Performance; Achievement; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Educational Measurement; Female; Humans; Mathematics; Methylphenidate; Outcome Assessment, Health Care; Reading; Task Performance and Analysis
PubMed: 29353323
DOI: 10.1007/s00787-018-1106-3 -
Bipolar Disorders May 2024Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder... (Review)
Review
Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.
BACKGROUND
Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD.
METHODS
We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials.
RESULTS
Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias.
CONCLUSIONS
Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Cognitive Dysfunction; Central Nervous System Stimulants; Off-Label Use; Methylphenidate
PubMed: 38433530
DOI: 10.1111/bdi.13414 -
Scandinavian Journal of Child and... 2018There is little evidence in the literature on the association between methylphenidate treatment and psychotic symptoms in children and adolescents with... (Review)
Review
Hallucinations and other psychotic symptoms in response to methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder: a Cochrane systematic review with meta-analysis and trial sequential analysis.
BACKGROUND
There is little evidence in the literature on the association between methylphenidate treatment and psychotic symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).
OBJECTIVE
We examine the occurrence of psychotic symptoms during methylphenidate treatment of children and adolescents with ADHD. The data arise from our two Cochrane systematic reviews on methylphenidate, reported elsewhere.
METHODS
Electronic databases were searched up to January 2016 (for observational studies) and March 2017 (for randomized trials). We summarized data as risk ratios and pooled prevalences. Trial Sequential Analysis was used to control for random errors. We assessed the risk of bias and the quality of evidence according to Cochrane guidelines.
RESULTS
Ten randomized trials (1103 participants), 17 non-randomized studies (76,237 participants) and 12 patient reports or series (18 patients) were identified. In the randomized trials, there was no significant difference in the risk of developing psychotic symptoms [10 of 654 (pooled prevalence, 2.5%) methylphenidate versus 1 of 508 (pooled prevalence, 1.7%) placebo patients; risk ratio, 2.07; 95% confidence interval, 0.58 to 7.35]. Nine of 10 trials had a high risk of bias, and according to the Trial Sequential Analysis, the required information size was not achieved, that is, the meta-analysis was considerably underpowered. There were 873 instances of psychotic symptoms in the non-randomized studies among 55,603 participants (pooled prevalence, 1.2%; 95% confidence interval, 0.7 to 2.4). In the comparative cohort study, methylphenidate significantly increased the risk for any psychotic disorder by 36% (risk ratio, 1.36; 95% confidence interval, 1.17 to 1.57). The overall risk of bias was rated as critical for this study.
CONCLUSIONS
Because of sparse data and low quality of evidence, we cannot confirm or refute whether methylphenidate increases the risk of psychotic symptoms in children and adolescents with ADHD. This possible adverse event may affect 1.1% to 2.5%, and physicians, patients and caregivers should be aware of this to ensure proper treatment in case of occurrence during methylphenidate treatment.
PubMed: 33520751
DOI: 10.21307/sjcapp-2018-003 -
JCPP Advances Sep 2023Robust synthesis of evidence to support treatment recommendations for preschoolers with attention-deficit/hyperactivity disorder (ADHD) is lacking. The aim of this...
BACKGROUND
Robust synthesis of evidence to support treatment recommendations for preschoolers with attention-deficit/hyperactivity disorder (ADHD) is lacking. The aim of this systematic review and meta-analysis was to review currently available evidence to evaluate the efficacy and acceptability of stimulants for preschool children with ADHD.
METHODS
We searched electronic databases (CENTRAL, Embase, PubMed) from the database inception to March, 2022; and clinical trial registries through WHO ICTRP from the database inception to July, 2022, and selected double-blinded randomized controlled trials (RCTs) that compared stimulants against placebo for the treatment of preschoolers (age ≤ 7 years) with ADHD. Change in ADHD symptom severity was the primary outcome (efficacy) and all-cause dropout rates (acceptability) was the secondary outcome. Data were pooled with random-effects models weighted by the inverse of the variance. Risk of bias of individual studies were assessed with the Cochrane Risk of Bias tool version 2. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence. This study is registered with PROSPERO (CRD42022348597).
RESULTS
Five RCTs (three methylphenidate immediate-release, one methylphenidate extended-release, and one lisdexamfetamine) were included. The analysis of efficacy was based on 489 participants. Meta-analysis of change in ADHD symptom severity demonstrated a significant effect in favor of stimulants over placebo (standardized mean difference = -0.59; 95% CI -0.77, -0.41; < 0.0001). There was no evidence of heterogeneity but some concerns about publication bias. Regardless, the confidence of evidence was considered moderate. For acceptability, stimulants did not lead to an increased rate of all-cause discontinuation rates in comparison to placebo (OR = 0.59; 95% CI 0.15, 2.37; = 0.45) but the confidence of estimate was very low.
CONCLUSIONS
Our findings demonstrated that stimulants are efficacious in reducing ADHD symptoms among preschool children. Clinicians should consider the use of stimulants when making treatment recommendations for preschoolers with ADHD.
PubMed: 37720577
DOI: 10.1002/jcv2.12146 -
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 -
Trends in Psychiatry and Psychotherapy 2015Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric pathology that has an important prevalence among young people and is difficult to diagnose. It is... (Review)
Review
INTRODUCTION
Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric pathology that has an important prevalence among young people and is difficult to diagnose. It is usually treated with methylphenidate, a psychostimulant with a mechanism of action similar to that of cocaine. Previous studies show that repeated use of psychostimulants during childhood or adolescence may sensitize subjects, making them more prone to later abuse of psychostimulant drugs such as cocaine and methamphetamine.
OBJECTIVE
To review experimental studies in non-human models (rodents and monkeys) treated with methylphenidate during infancy or adolescence and tested for reinforcing effects on psychostimulant drugs in adulthood.
METHOD
Systematic collection of data was performed on four databases (Web of Knowledge, PsycARTICLE, PubMed and SciELO). The initial search identified 202 articles published from 2009 to 2014, which were screened for eligibility. Seven articles met the inclusion criteria and were reviewed in this study.
RESULTS
The findings indicate that early exposure to methylphenidate has an effect on an ADHD animal model, specifically, on spontaneously hypertensive strain rats, especially those tested using the self-administration paradigm.
CONCLUSION
Future studies should prioritize the spontaneously hypertensive rat strain - an animal model of ADHD. Experimental designs comparing different behavioral paradigms and modes of administration using this strain could lead to improved understanding of the effects of exposure to methylphenidate during childhood and adolescence.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Disease Models, Animal; Female; Methylphenidate; Pregnancy; Substance-Related Disorders
PubMed: 26630401
DOI: 10.1590/2237-6089-2014-0060 -
European Psychiatry : the Journal of... Jul 2017Emotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of pharmacological treatments for ADHD on EL symptoms is unknown. We conducted a systematic review and meta-analysis to examine the effects of stimulants and atomoxetine on symptoms of EL and compare these with the effects on core ADHD symptoms.
METHODS
A systematic search was conducted on the databases Embase, PsychInfo, and Ovid Medline and the clinicaltrials.gov website. We included randomised, double-blind, placebo-controlled trials of stimulants and atomoxetine in adults aged 18-60 years, with any mental health diagnosis characterised by emotional or mood instability, with at least one outcome measure of EL. All identified trials were on adults with ADHD. A random-effects meta-analysis with standardised mean difference and 95% confidence intervals was used to investigate the effect size on EL and compare this to the effect on core ADHD symptoms.
RESULTS
Of the 3,864 publications identified, nine trials met the inclusion criteria for the meta-analysis. Stimulants and atomoxetine led to large mean weighted effect-sizes for on ADHD symptoms (n=9, SMD=-0.8, 95% CI:-1.07 to -0.53). EL outcomes showed more moderate but definite effects (n=9, SMD=-0.41, 95% CI:-0.57 to -0.25).
CONCLUSIONS
In this meta-analysis, stimulants and atomoxetine were moderately effective for EL symptoms, while effect size on core ADHD symptoms was twice as large. Methodological issues may partially explain the difference in effect size. Reduced average effect size could also reflect heterogeneity of EL with ADHD pharmacotherapy responsive and non-responsive sub-types. Our findings indicate that EL may be less responsive than ADHD symptoms overall, perhaps indicating the need for adjunctive psychotherapy in some cases. To clarify these questions, our findings need replication in studies selecting subjects for high EL and targeting EL as the primary outcome.
Topics: Adult; Affective Symptoms; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Emotions; Female; Humans; Methylphenidate; Middle Aged; Mood Disorders; Young Adult
PubMed: 28646732
DOI: 10.1016/j.eurpsy.2017.05.021 -
Biological Psychiatry Oct 2014Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of neuropsychological impairments. The relationship between these neuropsychological... (Meta-Analysis)
Meta-Analysis Review
Effects of methylphenidate on cognitive functions in children and adolescents with attention-deficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis.
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of neuropsychological impairments. The relationship between these neuropsychological deficits and the defining symptoms of ADHD seems more complex than originally thought. Methylphenidate (MPH) is an effective treatment for ADHD symptoms, but its impact on cognition is less clearly understood.
METHODS
With a common systematic search strategy and a rigorous coding and data extraction strategy across domains, we searched electronic databases to identify published placebo controlled trials that compared MPH and placebo on executive and nonexecutive memory, reaction time, reaction time variability and response inhibition in children and adolescents (5-18 years) with a formal diagnosis of ADHD.
RESULTS
Sixty studies were included in the review, of which 36 contained sufficient data for meta-analysis. Methylphenidate was superior to placebo in all five meta-analyses: executive memory, standardized mean difference (SMD) .26, 95% confidence interval (CI): -.39 to -.13; non-executive memory, SMD .60, 95% CI: -.79 to -.41; reaction time, SMD .24, 95% CI: -.33 to -.15; reaction time variability, SMD .62, 95% CI: -.90 to -.34; response inhibition, SMD .41, 95% CI: -.55 to -.27.
CONCLUSIONS
These data support the potentially important effects of MPH on various aspects of cognition known to be associated with ADHD. Consideration should be given to adding cognitive outcomes to the assessment of treatment outcome in ADHD, considering the complexity of the relationship between ADHD symptoms and cognition.
Topics: Age Factors; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cognition Disorders; Methylphenidate; Neuropsychological Tests
PubMed: 24231201
DOI: 10.1016/j.biopsych.2013.10.005 -
PloS One 2017To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity... (Meta-Analysis)
Meta-Analysis Review
Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.
OBJECTIVES
To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.
METHODS AND FINDINGS
We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.
CONCLUSION
Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Dose-Response Relationship, Drug; Female; Gastrointestinal Diseases; Humans; Male; Methylphenidate; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 28617801
DOI: 10.1371/journal.pone.0178187