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Soa--ch'ongsonyon Chongsin Uihak =... Apr 2023This study investigated the relationship between suicidal behavior and the use of methylphenidate (MPH) or atomoxetine (ATX) in patients with attention deficit... (Review)
Review
OBJECTIVES
This study investigated the relationship between suicidal behavior and the use of methylphenidate (MPH) or atomoxetine (ATX) in patients with attention deficit hyperactivity disorder (ADHD).
METHODS
The Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines were used to conduct a meta-analysis. The Physiotherapy Evidence Database scale was used to score the quality of the studies.
RESULTS
Nine studies were included in this quantitative analysis. The analysis included 602864 patients with ADHD (521125 and 81739 patients were taking methylphenidate [MPH group] and atomoxetine [ATX group], respectively) and 19230 healthy controls. The overall estimates were in the order of the control, MPH, and ATX groups; however, no statistically significant between-group difference was observed in the incidence of events (p=0.553 for control vs. MPH; p=1.000 for control vs. ATX; p=1.000 for MPH vs. ATX).
CONCLUSION
The rate of suicidal behavior was higher in the ADHD groups treated with MPH and ATX than in the control group. However, no statistically significant difference was observed between the ADHD groups treated with MPH and ATX, and the control group. Therefore, MPH and ATX did not increase suicidal behavior.
PubMed: 37035791
DOI: 10.5765/jkacap.220040 -
The Cochrane Database of Systematic... Mar 2023Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015.
OBJECTIVES
To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to March 2022. In addition, we checked reference lists and requested published and unpublished data from manufacturers of methylphenidate.
SELECTION CRITERIA
We included all randomised clinical trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. The search was not limited by publication year or language, but trial inclusion required that 75% or more of participants had a normal intellectual quotient (IQ > 70). We assessed two primary outcomes, ADHD symptoms and serious adverse events, and three secondary outcomes, adverse events considered non-serious, general behaviour, and quality of life.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted data extraction and risk of bias assessment for each trial. Six review authors including two review authors from the original publication participated in the update in 2022. We used standard Cochrane methodological procedures. Data from parallel-group trials and first-period data from cross-over trials formed the basis of our primary analyses. We undertook separate analyses using end-of-last period data from cross-over trials. We used Trial Sequential Analyses (TSA) to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the GRADE approach.
MAIN RESULTS
We included 212 trials (16,302 participants randomised); 55 parallel-group trials (8104 participants randomised), and 156 cross-over trials (8033 participants randomised) as well as one trial with a parallel phase (114 participants randomised) and a cross-over phase (165 participants randomised). The mean age of participants was 9.8 years ranging from 3 to 18 years (two trials from 3 to 21 years). The male-female ratio was 3:1. Most trials were carried out in high-income countries, and 86/212 included trials (41%) were funded or partly funded by the pharmaceutical industry. Methylphenidate treatment duration ranged from 1 to 425 days, with a mean duration of 28.8 days. Trials compared methylphenidate with placebo (200 trials) and with no intervention (12 trials). Only 165/212 trials included usable data on one or more outcomes from 14,271 participants. Of the 212 trials, we assessed 191 at high risk of bias and 21 at low risk of bias. If, however, deblinding of methylphenidate due to typical adverse events is considered, then all 212 trials were at high risk of bias.
PRIMARY OUTCOMES
methylphenidate versus placebo or no intervention may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -0.88 to -0.61; I² = 38%; 21 trials; 1728 participants; very low-certainty evidence). This corresponds to a mean difference (MD) of -10.58 (95% CI -12.58 to -8.72) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points). The minimal clinically relevant difference is considered to be a change of 6.6 points on the ADHD-RS. Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 0.91 (CI 0.31 to 2.68).
SECONDARY OUTCOMES
methylphenidate may cause more adverse events considered non-serious versus placebo or no intervention (RR 1.23, 95% CI 1.11 to 1.37; I² = 72%; 35 trials 5342 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 1.22 (CI 1.08 to 1.43). Methylphenidate may improve teacher-rated general behaviour versus placebo (SMD -0.62, 95% CI -0.91 to -0.33; I² = 68%; 7 trials 792 participants; very low-certainty evidence), but may not affect quality of life (SMD 0.40, 95% CI -0.03 to 0.83; I² = 81%; 4 trials, 608 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
The majority of our conclusions from the 2015 version of this review still apply. Our updated meta-analyses suggest that methylphenidate versus placebo or no-intervention may improve teacher-rated ADHD symptoms and general behaviour in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. Methylphenidate may be associated with an increased risk of adverse events considered non-serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilised. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognised adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomised trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes.
Topics: Male; Female; Child; Adolescent; Humans; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36971690
DOI: 10.1002/14651858.CD009885.pub3 -
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 -
Cancer Medicine May 2023Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including... (Review)
Review
BACKGROUND
Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours.
METHODS
We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021.
RESULTS
In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention.
CONCLUSION
The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.
Topics: Adult; Humans; Quality of Life; Cognitive Dysfunction; Cognition; Cognition Disorders; Brain Neoplasms
PubMed: 36880363
DOI: 10.1002/cam4.5760 -
Journal of Attention Disorders Mar 2023A new formulation of extended-release methylphenidate (PRC-063) was approved to treat ADHD. This meta-analysis was conducted to study the efficacy and safety of PRC-063... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A new formulation of extended-release methylphenidate (PRC-063) was approved to treat ADHD. This meta-analysis was conducted to study the efficacy and safety of PRC-063 for ADHD.
METHOD
We searched for published trials to October 2022 in several databases.
RESULTS
A total of 1,215 patients from 5 RCTs were included. We observed significant improvement for PRC-063 in ADHD Rating Scale (ADHD-RS; MD = -6.73, 95% CI [-10.34, -3.12]) compared with placebo. The effect of PRC-063 on the sleep problems due to ADHD was not statistically different from placebo. Six subscales of Pittsburg Sleep Quality Index (PSQI) showed no statistical significance between PRC-063 and placebo. The result showed no significant difference comparing PRC-063 with placebo in serious treatment-emergent adverse events (TEAEs) (RR = 0.80, 95% CI [0.03, 19.34]). In subgroup analysis according to age, PRC-063 was more efficacious in minors compare to adults.
CONCLUSION
PRC-063 is an efficacious and safe treatment for ADHD, especially in children and adolescents.
Topics: Child; Adult; Adolescent; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Randomized Controlled Trials as Topic; Methylphenidate; Data Management; Treatment Outcome; Double-Blind Method; Dose-Response Relationship, Drug
PubMed: 36794817
DOI: 10.1177/10870547231153941 -
Cureus Dec 2022The treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents can be challenging and involve a combination of pharmacologic and... (Review)
Review
Efficacy of Cognitive Behavioral Therapy and Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder in Children and Adolescents: A Systematic Review.
The treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents can be challenging and involve a combination of pharmacologic and non-pharmacological approaches. Using recent literature, we aim to identify the effectiveness of cognitive behavioral therapy (CBT) and methylphenidate (MPH) in reducing the symptoms and improving the quality of life. The investigators conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Investigators independently conducted a routine search on PubMed and Google Scholar for articles published within the last five years through July 30, 2022. Fourteen studies were identified as generally good quality but with some limitations. The final analysis included 2098 patients with an age range of three to eighteen. Nine studies reporting the efficacy of MPH in children, adolescents, or both had different formulations and doses. Six studies documenting the effectiveness of CBT had varying sessions, duration per therapy, modality of administration, and participants. The diagnostic assessment measures showed that the parent symptom rating was the highest and appeared in 11 studies, reflecting the burden on the family. In addition, a structured-self-rated questionnaire rating appeared in eight studies, and two diagnostic assessment measures, teacher symptom rating and investigators, appeared in six. The studies demonstrated significant reductions in the primary symptoms of ADHD at assessment, which led to improved behavioral and functional status with a reduced impact on family and society. Further trials are needed to understand the benefits of CBT and MPH when combined to reduce psychiatry co-morbidities and improve learning and overall quality of life in the long term.
PubMed: 36660538
DOI: 10.7759/cureus.32647 -
Acta Neuropsychiatrica Aug 2023Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect... (Review)
Review
OBJECTIVES
Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect treatment outcomes adversely. We aimed to review all relevant previous reports.
METHODS
We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI).
RESULTS
According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants - usually SSRIs - can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate-modafinil-olanzapine combination.
CONCLUSION
Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition.
Topics: Selective Serotonin Reuptake Inhibitors; Apathy; Olanzapine; Antidepressive Agents; Bupropion
PubMed: 36644883
DOI: 10.1017/neu.2023.6 -
Child and Adolescent Psychiatry and... Nov 2022Attention Deficit/Hyperactivity disorder (ADHD) is one of the most common disorders in school-age children. In addition to learning difficulties associated with the... (Review)
Review
Attention Deficit/Hyperactivity disorder (ADHD) is one of the most common disorders in school-age children. In addition to learning difficulties associated with the disorder's core symptoms of inattention and hyperactivity, children with ADHD display substantial social impairments. Methylphenidate (MPH) in formulations such as Ritalin or Concerta mitigates inattention and hyperactivity, but the effects of the therapy on social behavior in children with ADHD are not clear. This review aims to determine the effectiveness of short term (up to 6 months) MPH treatment on three domains of social skills in children aged 6-14 with ADHD: (i) Recognition of nonverbal emotional expressions, which are a marker of inherent (unlearned) social understanding, (ii) theory of mind (ToM) components that relate to learned cognition and social communication, and (iii) social competence in everyday environments. 15 relevant studies were identified based on inclusion/exclusion criteria. The results show mixed effects: the overall social performance as evaluated by parents, teachers or peers, and some components of ToM, were found to improve following a weeks-long course of MPH treatment. However, the effects of the medication are less clear when evaluating momentary/nonverbal social responses such as reactions to emotional facial expressions. While the findings of this review indicate that an MPH medication regime of order weeks to months could improve, to a degree, social impairment in children with ADHD, more studies are required to identify the medications' mechanism and confirm such a conclusion.
PubMed: 36443766
DOI: 10.1186/s13034-022-00526-2 -
The Cochrane Database of Systematic... Nov 2022Cognitive 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... (Review)
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. This is an updated version of the original Cochrane Review published in Issue 12, 2014.
OBJECTIVES
To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation.
SEARCH METHODS
For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022.
SELECTION CRITERIA
We included randomised controlled (RCTs) trials 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 (MK, JD) 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
Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated "prevention" of cognitive problems (during radiotherapy and follow-up) and four studies investigated "amelioration" (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible. Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the "early radiotherapy treatment phase" were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the "early radiotherapy treatment phase" included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme. In the memantine 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 d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results. The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups. Studies in delayed radiation or late effect phase (four studies) The "amelioration" pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had "stable" brain cancer. The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another study comparing two different doses of modafinil 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 Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed. There were a number of limitations across studies and few were without high risks of bias.
AUTHORS' CONCLUSIONS
In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, 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, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.
Topics: Adult; Humans; Modafinil; Donepezil; Memantine; Quality of Life; Cognitive Dysfunction; Cranial Irradiation; Cognition; Methylphenidate; Brain Neoplasms; Fatigue; Dementia
PubMed: 36427235
DOI: 10.1002/14651858.CD011335.pub3 -
Journal of Clinical Medicine Oct 2022Approximately 10−20% of patients who have sustained a mild Traumatic Brain Injury (mTBI) show persistent post-concussion symptoms (PCS). This review aims to summarize... (Review)
Review
Approximately 10−20% of patients who have sustained a mild Traumatic Brain Injury (mTBI) show persistent post-concussion symptoms (PCS). This review aims to summarize the level of evidence concerning interventions for PCS. Following the PRISMA guidelines, we conducted a systematic review regarding interventions for PCS post-mTBI until August 2021 using the Medline, Cochrane, and Embase databases. Inclusion criteria were the following: (1) intervention focusing on PCS after mTBI, (2) presence of a control group, and (3) adult patients (≥18 y.o). Quality assessment was determined using the Incog recommendation level, and the risk of bias was assessed using the revised Cochrane risk-of-bias tool. We first selected 104 full-text articles. Finally, 55 studies were retained, including 35 that obtained the highest level of evidence. The risk of bias was high in 22 out of 55 studies. Cognitive training, psycho-education, cognitive behavioral therapy, and graded return to physical activity demonstrated some effectiveness on persistent PCS. However, there is limited evidence of the beneficial effect of Methylphenidate. Oculomotor rehabilitation, light therapy, and headache management using repetitive transcranial magnetic stimulation seem effective regarding somatic complaints and sleep disorders. The preventive effect of early (<3 months) interventions remains up for debate. Despite its limitations, the results of the present review should encourage clinicians to propose a tailored treatment to patients according to the type and severity of PCS and could encourage further research with larger groups.
PubMed: 36294545
DOI: 10.3390/jcm11206224