Methylphenidate Group Research Articles

Combined Methylphenidate and Selective Serotonin Reuptake Inhibitors in Adults With Attention-Deficit/Hyperactivity Disorder.

Depression is a common comorbidity of adult attention-deficit/hyperactivity disorder (ADHD), and the combination of methylphenidate and selective serotonin reuptake inhibitors (SSRIs) is a frequently prescribed treatment. However, there is limited clinical evidence on the safety of this medication combination in adults with ADHD. To evaluate the safety of administering a combination of SSRI and methylphenidate in adults with ADHD and comorbid depression. This cohort study obtained data from a nationwide claims database in South Korea from January 2016 to February 2021. Participants were adults aged 18 years or older with a diagnosis of ADHD and depressive disorder who were prescribed methylphenidate. Comparisons of 4 groups who received prescriptions were conducted: (1) SSRI plus methylphenidate (hereafter, SSRI) group vs methylphenidate-only group and (2) methylphenidate plus fluoxetine (hereafter, fluoxetine) group vs methylphenidate plus escitalopram (hereafter, escitalopram) group (compared to find a preferable treatment option). Data analysis was conducted between July and December 2023. New users of the methylphenidate and SSRI combination among adults with both ADHD and depressive disorder. A total of 17 primary and secondary outcomes, including neuropsychiatric and other events, were assessed, with respiratory tract infection used as a control outcome. Groups were matched at a 1:1 ratio using a propensity score to balance confounders. A Cox proportional hazards regression model was used to calculate hazard ratio (HRs) and 95% CIs. Subgroup analysis by sex and sensitivity analyses in varying epidemiologic settings were conducted. The study included 17 234 adults with ADHD (mean [SD] age at study entry, 29.4 [10.8] years; 9079 females [52.7%]). There was no difference in the risk of outcomes between the methylphenidate-only and SSRI groups, except for a lower risk of headache in the SSRI group (HR, 0.50; 95% CI, 0.24-0.99). In sensitivity analyses of fluoxetine vs escitalopram, the risk of hypertension (HR: 1:n matching, 0.26; 95% CI, 0.08-0.67) and hyperlipidemia (HR: 1:n matching, 0.23; 95% CI, 0.04-0.81) was lower in the fluoxetine group than in the escitalopram group. Results of this study revealed no significant increase in adverse event risk associated with use of SSRI plus methylphenidate vs methylphenidate alone in adults with ADHD and comorbid depression. Instead, the combination was associated with a lower risk of headache.

Comparison of the effectiveness of modafinil and methylphenidate in treatment of excessive daytime sleepiness in patients with Parkinson's disease.

Background: A large percentage of patients with Parkinson's disease (PD) suffer from excessive daytime sleepiness (EDS). This study aims to compare the effectiveness of modafinil and methylphenidate on EDS and side effects. Methods: Fifty nine patients with PD and EDS [Epworth Sleepiness Scale (ESS) more than 9] were recruited in a double-blind placebo controlled trial. Twenty-two patients received modafinil 200 mg daily, twenty-six patients received methylphenidate 10 mg daily, and 11 patients received placebo for 6 weeks. Pittsburgh Sleep Quality Index (PSQI) and ESS were filled out at baseline and 6 weeks later. Results: There was no significant difference in demographics, PSQI, and ESS variables at baseline. The mean of ESS scores decreased significantly in modafinil (17.36 ± 5.05 vs. 10.55 ± 4.62, P < 0.001) and methylphenidate (16.27 ± 5.40 vs. 12.23 ± 6.28, P < 0.001) groups after 6-week trial, compared with control group (14.27 ± 4.49 vs. 14.09 ± 4.46, P = 0.710). The effectiveness of modafinil and methylphenidate on improving daytime sleepiness and night sleep of patients was not significantly different. Conclusion: Both modafinil and methylphenidate were effective drugs in improving EDS and quality of sleep without significant difference in efficiency and side effects.

QOL-08. THE LONG-TERM UTILITY OF METHYLPHENIDATE FOR THE PRESERVATION OF INTELLECTUAL DEVELOPMENT IN CHILDHOOD SURVIVORS OF BRAIN TUMOUR

Abstract BACKGROUND Enduring neurocognitive late effects are a common consequence of childhood brain tumour survivorship. Conceptual modelling of intelligence suggests initial deficits to processing speed and attention lead to the subsequent plateauing of intellectual and academic development. The utility of methylphenidate in improving attentional and processing speed deficits within the early phase of recovery has been previously reported. The longer-term contribution of methylphenidate in preserving intellectual ability through ameliorating these early deficits is yet to be evaluated. METHODS Twenty-nine childhood survivors were matched retrospectively with a no-treatment synthetic control. Intellectual assessments were conducted prior to starting methylphenidate and a minimum of 12 months thereafter. For the no-treatment control group, intellectual data were collected retrospectively from archival records, employing a similar assessment period. Linear Mixed Models were used to assess the influence of methylphenidate on intellectual trajectories between groups and fatigue scores over time. RESULTS Methylphenidate was associated with raw score improvements across all intellectual indices compared to no-treatment controls. Linear Mixed Modelling reported a borderline significant improvement in Processing Speed (t = 1.98, p =.05) for the methylphenidate group. In comparison, a borderline significant (p =.05) within-group decrease in Working Memory scores was reported for the no-treatment group. There was a significant within-group decrease in pooled PedsQL MFS scores between assessments for the treatment group (t = -4.01, p &amp;lt;.01), with the most notable decrease observed in Sleep/Rest Fatigue (t = -10.17, p &amp;lt;.01). CONCLUSIONS Methylphenidate may pose a valuable long-term rehabilitative strategy in preserving Processing Speed in childhood survivors of brain tumour. Whilst our sample size is small, there is tentative evidence for the utility of methylphenidate in alleviating fatigue experienced by childhood survivors.

Adverse effects of methylphenidate for apathy in patients with Alzheimer's disease (ADMET2 trial).

To examine clinically important adverse events (AEs) associated with methylphenidate (MPH) treatment of apathy in Alzheimer's Disease (AD) versus placebo, including weight loss, vital signs, falls, and insomnia. The Apathy in Dementia Methylphenidate Trial 2 (ADMET2) trial was a multicenter randomized, placebo-controlled trial of MPH to treat apathy in individuals with apathy and AD. Participants in ADMET2 had vital signs and weight measured at monthly visits through 6months. AEs, including insomnia, falls, and cardiovascular events, were reported at every visit by participants and families using a symptom checklist. The study included 98 participants in the MPH group and 101 in the placebo group. Participants in the MPH group experienced greater weight loss on average than the placebo through the 6-month follow-up, with a difference in change between MPH and placebo of 2.8lb (95% confidence interval, CI: 0.7, 4.9lb). No treatment group differences in change during the trial were found in systolic and diastolic blood pressure. More participants in the MPH group reported falls during the follow-up, 10 versus 6 in MPH and placebo groups, respectively. No differences in post-baseline insomnia were observed between the treatment groups. No participants reported instances of myocardial infarction, congestive heart failure, arrhythmia, stroke, or cardiomyopathy throughout the study period. MPH use in AD patients for treating apathy is relatively safe, particularly notable given the many medical comorbidities in this population. There was a statistically significant but modest weight loss associated with MPH use, and clinicians are thus advised to monitor weight during MPH treatment.

Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial.

To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer. This is a randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients had advanced incurable cancer and fatigue >3/10. Principal exclusions were hypertension; psychiatric, cardiovascular, cerebrovascular, renal, liver, or blood disorders; substance dependency; and epilepsy. Patients were randomly assigned 1:1 methylphenidate or placebo starting at 5 mg twice daily. Dose of methylphenidate/placebo was titrated once per week, over 6 weeks, up to a maximum of 20 mg three times daily. Trial ended at 10 weeks. Primary outcome was the difference in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores between groups at 6 ± 2 weeks. Secondary outcomes included adverse effects, quality of life, and mood. One hundred sixty-two patients (73 men; mean, 65.8; standard deviation [SD], 10.3 years) were randomly assigned, and three were excluded from analysis. Seventy-seven were allocated placebo (baseline FACIT-F = 22 [SD, 10]); 82 were allocated methylphenidate (FACIT-F = 20 [SD, 9]). After 6 ± 2 weeks, FACIT-F scores were 1.97 points (95% CI, -0.95 to 4.90; P = .186) higher (better) on methylphenidate than placebo. Across 10 weeks of the study, FACIT-F was nominally higher in the methylphenidate group versus placebo (Diff, 2.20 [95% CI, 0.39 to 4.01]), but this did not reach the minimally clinically important difference (5-points). At 6 weeks, there were no differences between groups in quality-of-life or symptom domains except for depression scores (nominally reduced in the methylphenidate group: Diff, -1.35 [95% CI, -2.41 to -0.30]). There were no differences in mortality or serious adverse events. After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well-tolerated.

The Impact of Methylphenidate on Pubertal Maturation and Bone Age in ADHD Children and Adolescents: Results from the ADHD Drugs Use Chronic Effects (ADDUCE) Project

Objective: The short-term safety of methylphenidate (MPH) has been widely demonstrated; however the long-term safety is less clear. The aim of this study was to investigate the safety of MPH in relation to pubertal maturation and to explore the monitoring of bone age. Method: Participants from ADDUCE, a two-year observational longitudinal study with three parallel cohorts (MPH group, no-MPH group, and a non-ADHD control group), were compared with respect to Tanner staging. An Italian subsample of medicated-ADHD was further assessed by the monitoring of bone age. Results: The medicated and unmedicated ADHD groups did not differ in Tanner stages indicating no higher risk of sexual maturational delay in the MPH-treated patients. The medicated subsample monitored for bone age showed a slight acceleration of the bone maturation after 24 months, however their predicted adult height remained stable. Conclusion: Our results do not suggest safety concerns on long-term treatment with MPH in relation to pubertal maturation and growth.

Cardiovascular Safety of Amphetamine/Dextroamphetamine versus Methylphenidate in Older Adults

Background: Recent epidemiological data has shown a sharp increase in stimulant use among older adults, which is notable as older adults may be especially vulnerable to their cardiovascular effects. Results of recent studies have shown an increase in cardiovascular events among older adults using stimulants; however, little data exists comparing cardiovascular safety of these agents head-to-head. Objective: To determine if the incidence of serious cardiovascular events, including myocardial infarction (MI), stroke/transient ischemic attack (TIA), or arrhythmia, are different in patients taking amphetamine/dextroamphetamine compared with patients taking methylphenidate. Methods: Retrospective chart review of veterans 50 years and older at the Veterans Affairs North Texas Health Care System (VANTHCS) who were first prescribed a stimulant between 2015 and 2021. The primary outcome was the difference in composite cardiovascular events between amphetamine/dextroamphetamine and methylphenidate. Secondary outcomes were the composite cardiovascular endpoints compared individually (MI, stroke/TIA, or arrhythmia). Hazard ratios were calculated based off of a time-to-event analysis displayed using a Kaplan-Meier curve for primary and secondary outcomes. Results: 466 veterans were screened for inclusion, 30 were excluded, and 436 were included. There was no difference found in composite cardiovascular events between the 241 veterans in the amphetamine/dextroamphetamine group and the 195 veterans in the methylphenidate group with 12 (5%) vs 8 (4.1%) events respectively (P = .6635). There was also no difference in time-to-event analysis (P = .4966). Conclusion: In elderly veterans, there was no difference found in incidence of major cardiovascular events with the use of amphetamine/dextroamphetamine compared with methylphenidate.

Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial

Introduction: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. Objective: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. Method: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. Results: Participants rated psychotherapy as moderately effective, attended 78.40–94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. Discussion: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

Blood‐based biomarkers for predicting treatment response in the Apathy in Dementia Methylphenidate Trial 2 randomized clinical trial

AbstractBackgroundThe Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate (MPH) was modestly efficacious is treating apathy in Alzheimer’s disease (AD) with 66% response (&gt; = 4 point decrease on Neuropsychiatric Inventory – apathy (NPI‐A). Here, we evaluated if blood‐based biomarkers potentially associated with treatment‐limiting neuronal damage predicted the probability of treatment response.MethodADMET 2 participants with baseline and endpoint (6 month) NPI‐A and baseline concentrations of (i) neuronal damage: neurofilament light (NFL) and S‐100B, (ii) inflammation: interleukin (IL)‐6, IL‐10, Tumor Necrosis Factor‐alpha (TNFα), and (iii) oxidative stress: lipid hydroperoxide (LPH), 4‐hydroxynonenal (4‐HNE), 8‐isoprostane (8‐ISO) were included. Biomarkers were normalized by log transformation and pareto scaling. Univariate models examined whether each biomarker interacted with the treatment condition to predict a change of at least 2 points on the NPI‐A. Next, biomarkers with significant associations were included in a multivariate logistical regression model that was used to predict treatment response to MPH and placebo. The index score (difference between response probabilities for MPH and placebo) of each participant indicated their favourability for MPH treatment. Participants were grouped into quartiles by their index score with confidence intervals estimated using non‐parametric bootstrapping.ResultForty‐nine participants (placebo = 26, MPH = 23, age = 75.4 years (standard deviation [SD] = 7.6), 57% males, Mini Mental State Examination = 19.7 [SD = 4.6]) were included. MPH was more efficacious than placebo in those with higher baseline NFL (‐5.8, t = ‐3.1, p = 0.003), and less efficacious in those with higher LPH (2.0, t = 1.48, p = 0.15). Apathy worsened in participants with high TNFα (2.71, t = 1.94, p = 0.06) in both MPH and placebo groups. Participants in the top quartile of the biomarker index score (66.7% on MPH) were more likely to respond to MPH than placebo (index score = 0.58, 95%CI: 0.48, 0.69).ConclusionIndividuals with greater neuronal injury were more likely to respond to MPH, suggesting that MPH supplementation provides more benefit when neuronal injury is more severe. Combining blood biomarkers yielded a prediction score where participants with high NFL and low LPH levels were more likely to respond to MPH. This approach utilizes biomarkers to address heterogeneity in treatment response to MPH.

The effect of methylphenidate on pain perception thresholds in children with attention deficit hyperactivity disorder

BackgroundPain perception is important in children with attention deficit hyperactivity disorder (ADHD) since they are more likely to experience painful events due to increased accident rates. The aim of this study is to contribute to the literature concerning the relationship between ADHD diagnosis, methylphenidate (MPH) therapy, and pain thresholds, since findings regarding the change in pain perception in children with ADHD are scarce and inconsistent.MethodsChildren aged 8–13 years constituted both the ADHD group (n = 82) and the healthy controls (n = 41). The ADHD group was divided into two subgroups, ADHD without MPH (not treated pharmacologically) and ADHD with MPH (treated pharmacologically for at least three-months). The Conners’ Parent Rating Scale–Revised: Short Form was employed to assess ADHD, a visual analog scale was applied to evaluate chronic pain severity, and a manual pressure algometer was used to assess pain thresholds.ResultChildren with ADHD had lower pain thresholds than the healthy controls (P < 0.05). However, lower regional pain thresholds were observed in the ADHD group without MPH compared to both the healthy control and ADHD with MPH groups. Although pain thresholds in the ADHD with MPH group were regionally lower than in the healthy controls, low pain thresholds were found in fewer regions compared to the ADHD without MPH group.ConclusionsChildren with ADHD are more sensitive to pain sensation, and MPH may help normalize these individuals’ pain experiences by raising pain thresholds. Families and clinicians must be aware of situations that may cause pain in children with ADHD. In addition, these children’s low threshold for pain may lead them to experience it more intensely.

Ketogenic diet ameliorates attention deficit hyperactivity disorder in rats via regulating gut microbiota.

Attention deficit hyperactivity disorder (ADHD) is a common mental behavioral disorder in children. Alterations in gut microbiota composition are associated with neurological disorders. We aimed to investigate whether a ketogenic diet (KD) can be an alternative therapy for ADHD by altering the gut microbiota. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomly allocated to the normal diet (ND), methylphenidate (MPH), and KD groups. SHR in groups KD and MPH exhibited a significant increase in behavioral characteristics of ADHD, such as distance moved and immobility time. KD and MPH treatment led to a significant elevation in concentrations of 5-HT, AC, cAMP, and NE of brain tissue and the expression of DRD1, DAT, PKA, DARPP32, and cAMP at the protein level in WKY rats and SHR. KD and MPH significantly increased the richness and diversity of gut microbiota in SHR. The abundance of Ruminococcus_gauvreauii_group, Bacteroides, Bifidobacterium, and Blautia significantly increased, whereas that of Lactobacillus, Romboutsia, Facklamia, and Turicibacter significantly declined in the KD group compared with the ND group. The gut microbiota in the KD group of SHR mainly participated in amino acid metabolism- and sugar metabolism-related pathways. KD might alleviate behavioral disorders in ADHD by regulating gut microbiota. This study provides novel insights for the use of KD in treating ADHD.

L-Arginine/nitric oxide pathway and oxidative stress in adults with ADHD: Effects of methylphenidate treatment

IntroductionAttention deficit hyperactivity disorder (ADHD) is a mental disorder that was once thought to occur only in children. Meanwhile, it is known that adults can also be affected. The first-line drug in children and adults to treat symptoms of inattention, impulsivity, lack of self-regulation, and hyperactivity is methylphenidate (MPH). Known adverse effects of MPH include cardiovascular problems, such as elevated blood pressure and heart rate. Therefore, biomarkers to monitor potential cardiovascular side effects of MPH are needed. The l-Arginine/Nitric oxide (Arg/NO) pathway is involved in noradrenaline and dopamine release as well as in normal cardiovascular functioning and is therefore a prime candidate for the search of biomarkers. The aim of the present study was to investigate the Arg/NO pathway as well as oxidative stress in adult ADHD patients in plasma and urine and the potential influence of MPH medication. MethodsIn plasma and urine samples of 29 adults with ADHD (39.2 ± 10.9 years) and 32 healthy adults serving as controls (CO) (38.0 ± 11.6 years) the major NO metabolites nitrite and nitrate, Arg, the NO synthesis inhibitor asymmetric dimethylarginine (ADMA) and its major urinary metabolite dimethylamine (DMA) as well as malondialdehyde (MDA) were measured by gas chromatography–mass spectrometry. ResultsOf the 29 patients with ADHD 14 were currently without MPH treatment (-MPH) and 15 were treated with MPH (+MPH). Plasma nitrate concentrations were significantly higher in patients not treated with MPH vs. CO (-MPH 60.3 μM [46.2–76.0] vs. CO 44.4 μM [35.0–52.7]; p = 0.002), while plasma nitrite tended to be higher in -MPH patients (2.77 μM [2.26–3.27]) vs. CO (2.13 μM [1.50–2.93]; p = 0.053). Additionally, plasma creatinine concentrations were significantly different, with -MPH showing significantly higher concentrations than the other two groups (-MPH 141 μM [128–159]; +MPH 96.2 μM [70.2–140]; Co 75.9 μM [62.0–94.7]; p < 0.001). Urinary creatinine excretion tended to be lowest in -MPH group vs. +MPH and CO (-MPH 11.4 ± 8.88 mM; +MPH 20.7 ± 9.82 mM; 16.6 ± 7.82 mM; p = 0.076). None of the other metabolites, including MDA, a marker of oxidative stress, showed a difference between the groups. ConclusionAdult patients with ADHD, who are not treated with MPH (-MPH), showed varied Arg/NO pathway, but Arg bioavailability seemed to be consistent over the groups. Our findings imply that urinary reabsorption may be increase and/or excretion of nitrite and nitrate may be decreased in ADHD, resulting in an increase in the plasma concentration of nitrite. MPH seems to partially reverse these effects by not yet known mechanisms, and does not affect oxidative stress.

METHYLPHENIDATE EXPOSURE DURING PERIPUBERTAL PHASE AFFECTS LEARNING AND MEMORY OF ADULT RATS

Methylphenidate (MPH) is the active ingredient in Ritalin, although effective in treating ofthe attention deficit hyperactivity disorder (ADHD), its neurostimulation action is attractiveamong students in order to increase the focus or improving student performance. In context ofthe Developmental Origins of Health and Disease (DOHaD) concept, states that insults incritical phases of development, as the peripubertal period, may program the organism todysfunctions in adulthood. The aim of this work was to investigate the impact of peripubertalMPH exposure on learning and retrograde memory in adult rats. Male Wistar rats wereexposed to MPH (5 mg/kg) from post-natal day (PN) 30 until PN60 (MPH). Control animalsreceived 0.9% saline (Sal). At PN60, learning was evaluated true 10 days in an eight-armelevated maze and at PN120 retrograde memory. At PN60, MPH group showed a delay of61% in the latency, an increase of 100% in the number of errors and 200% in the number ofrepetition errors when compared to the Sal group, until the day 5 of learning period (p=0.004).After the washout period, at PN120, the MPH group showed an increase of 37% in thelatency, 49% in the number of errors of reference and 600% in the number of repetition errorscompared with the Sal group (p=0.001, p=0.004 and p=0.01). Exposure to MPH duringperipubertal phase decreases learning and memory in adult male Wistar rats.

Systematic Review of Suicidal Behaviors Related to Methylphenidate and Atomoxetine in Patients With Attention Deficit Hyperactivity Disorder.

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). 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. 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). 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.

Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study

Methylphenidate is the most frequently prescribed medication for the treatment of ADHD in children and adolescents in many countries. Although many randomised controlled trials support short-term efficacy, tolerability, and safety, data on long-term safety and tolerability are scarce. The aim of this study was to investigate the safety of methylphenidate over a 2-year period in relation to growth and development, psychiatric health, neurological health, and cardiovascular function in children and adolescents. We conducted a naturalistic, longitudinal, controlled study as part of the ADDUCE research programme in 27 European child and adolescent mental health centres in the UK, Germany, Switzerland, Italy, and Hungary. Participants aged 6-17 years were recruited into three cohorts: medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medication (no-methylphenidate group), and a control group without ADHD. Children with ADHD diagnosed by a qualified clinician according to the DSM-IV criteria and, in the control group, children who scored less than 1·5 on average on the Swanson, Nolan, and Pelham IV rating scale for ADHD items, and whose hyperactivity score on the parent-rated Strengths and Difficulties Questionnaire was within the normal range (<6) were eligible for inclusion. Participants were excluded if they had previously taken any ADHD medications but remained eligible if they had previously taken or were currently taking other psychotropic drugs. The primary outcome was height velocity (height velocity SD score; estimated from at least two consecutive height measurements, and normalised with reference to the mean and SD of a population of the same age and sex). Between Feb 01, 2012, and Jan 31, 2016, 1410 participants were enrolled (756 in methylphenidate group, 391 in no-methylphenidate group, and 263 in control group). 1070 (76·3%) participants were male, 332 (23·7%) were female, and for eight gender was unknown. The average age for the cohort was 9·28 years (SD 2·78; IQR 7-11). 1312 (93·0%) of 1410 participants were White. The methylphenidate and no-methylphenidate groups differed in ADHD symptom severity and other characteristics. After controlling for the effects of these variables using propensity scores, there was little evidence of an effect on growth (24 months height velocity SD score difference -0·07 (95% CI -0·18 to 0·04; p=0·20) or increased risk of psychiatric or neurological adverse events in the methylphenidate group compared with the no-methylphenidate group. Pulse rate and systolic and diastolic blood pressure were higher in the methylphenidate group compared with the no-methylphenidate group after 24 months of treatment. No serious adverse events were reported during the study. Our results suggest that long-term treatment with methylphenidate for 2 years is safe. There was no evidence to support the hypothesis that methylphenidate treatment leads to reductions in growth. Methylphenidate-related pulse and blood pressure changes, although relatively small, require regular monitoring. EU Seventh Framework Programme.

Pharmacological Treatment of Children and Adolescents Diagnosed with Attention-deficit/hyperactivity Disorder at Mental Health Services in Qatar: A Retrospective Study

Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common mental disorders affecting children. The consequences of ADHD could seriously impact the patient’s life, and thus parental training, behavioral therapies, and pharmacological interventions are the main therapeutic options applied. This study was conducted to explore the trends of prescribing pharmacological medications used in ADHD and identify the reasons for discontinuation of such medications. Methodology: A retrospective chart review for patients diagnosed with ADHD at Child and Adolescent Mental Health Services (CAMHS) in Qatar from January 2019 to December 2019 was carried out. Patients less than 18 years old, diagnosed with ADHD as per the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and were on pharmacological treatment for ADHD were suitable to be included. Patients who were not on anti-ADHD medications were excluded from the study. Results: Ninety-two patients were eligible to be included in the study. Autism Spectrum Disorder (ASD) was found to be the most coexisting condition in addition to ADHD in 16.3%. Methylphenidate was the most prescribed medication (68.5%), followed by atomoxetine (30.4%). None of the participants were found on modafinil, guanfacine, bupropion, or benzodiazepines, and none exceeded the maximum licensed dose of either methylphenidate or atomoxetine. Half (50%) of the sample on atomoxetine discontinued treatment compared to 14.2% in the methylphenidate group. Conclusion: The clinical practice of prescribing pharmacological options for ADHD was thoroughly in alignment with international guidelines. The effects of long-term use of these psychotropics in this particular group of patients on their neurobiological, behavioral, and physical health should be studied further.

Efficacy and safety of methylphenidate and behavioural parent training for children aged 3–5 years with attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled, and sham behavioural parent training-controlled trial

There is insufficient evidence to support treatment recommendations for preschool children aged 3-5 years with attention-deficit hyperactivity disorder (ADHD). We aimed to investigate the efficacy and safety of methylphenidate and behavioural parent training in reducing the frequency and severity of symptoms and improving global functioning in preschool children with ADHD. We did an 8-week, randomised, double-blind, placebo-controlled and sham behavioural parent training-controlled clinical trial (the MAPPA Study) in children aged 3-5 years with moderate-to-severe ADHD. The trial was conducted at the Institute of Psychiatry, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. Participants were randomly assigned (1:1:1) to receive immediate-release methylphenidate plus educational intervention (sham behavioural parent training), placebo medication plus behavioural parent training, or placebo medication plus educational intervention. Randomisation was done by an independent research manager by use of a permuted block randomisation procedure. Parents, teachers, study staff, and evaluators remained masked to group allocation. Methylphenidate and placebo were titrated to a maximum dose of 1·25 mg/kg per day administered orally twice daily, and behavioural parent training and the educational intervention were delivered weekly through 90 min sessions with both the child and parent, conducted by two psychologists or learning therapists. The primary outcomes were parents' and teachers' composite scores of the Swanson, Nolan, and Pelham-IV scale (SNAP-IV-P/T), the Clinical Global Impressions Severity (CGI-S) scale, and the Children's Global Assessment Scale (CGAS). This trial is registered with ClinicalTrials.gov, NCT02807870, and is now complete. All participants were invited to participate in an open observational follow-up, which is ongoing. Between Aug 21, 2016, and Oct 21, 2019, 153 children were randomly assigned to receive methylphenidate plus the educational intervention (n=51), placebo plus behavioural parent training (n=51), or placebo plus the educational intervention (n=51). Nine (6%) children discontinued treatment. All participants were included in the intention-to-treat analysis. Children in the methylphenidate plus educational intervention group showed greater reductions in the SNAP-IV-P/T (endpoint mean difference -3·93 [95% CI -7·14 to -0·73], p=0·049; effect size -0·55 [95% CI -0·99 to -0·10]) and CGI-S scores (endpoint mean difference -0·49 [-0·82 to -0·17], p=0·0088; effect size -0·70 [-1·16 to -0·24]) and a greater increase in CGAS scores (endpoint mean difference 5·25 [95% CI 2·09 to 8·40], p=0·0036; effect size 0·80 [95% CI 0·32 to 1·28]) than children in the placebo plus educational intervention group. Children in the placebo plus behavioural parent training group did not have significantly different SNAP-IV-P/T scores (endpoint mean difference -3·18 [95% CI -6·38 to 0·02], p=0·077; effect size -0·44 [95% CI -0·89 to 0·003]) or CGI-S scores (endpoint mean difference -0·35 [-0·68 to -0·03], p=0·052; effect size -0·50 [-0·96 to -0·04]) compared to children in the placebo plus educational intervention group, but they had a greater increase in CGAS scores compared to the placebo plus educational intervention group (endpoint mean difference 3·69 [0·53 to 6·85], p=0·033; effect size 0·56 [0·08 to 1·04]). Children in the methylphenidate plus educational intervention versus placebo plus behavioural parent training group did not have statistically or clinically significant differences in primary outcomes. Children in the methylphenidate plus educational intervention group had more mild adverse events than the other two groups, and there were no between-group differences for moderate or severe adverse events. Methylphenidate was effective in reducing ADHD symptoms and improving functionality, and behavioural parent training was effective in improving functionality for preschool children with ADHD after 8 weeks of treatment. São Paulo Research Foundation and Brazilian National Council for Scientific and Technological Development.

Effect of Rehmanniae Radix Praeparata on energy metabolism in prefrontal cortex of rats with attention deficit hyperactivity disorder based on "static Yin and dynamic Yang" theory

The present study investigated the effect of Rehmanniae Radix Praeparata(RRP) on the energy metabolism of prefrontal cortex(PFC) of spontaneously hypertensive rats with attention deficit hyperactivity disorder(ADHD) based on the &quot;static Yin and dynamic Yang&quot; theory.Thirty spontaneously hypertensive male rats aged 3 weeks were randomly divided into a model group, a methylphenidate(MPH) group(2 mg·kg~(-1)), and an RRP group(2.4 g·kg~(-1)).Wistar-Kyoto(WKY) male rats of the same age were assigned to the normal group.Rats were treated with corresponding drugs twice per day, and those in the model group and the normal group received the same volume of 0.9% sodium carboxymethyl cellulose(CMC-Na) solution by gavage.The open-field test was performed to evaluate the spontaneous and impulsive behaviors of rats before treatment and on the 4~(th) week after treatment.Four weeks after treatment, PFC was isolated and mitochondria were prepared.The content of adenosine triphosphate(ATP), adenosine diphosphate(ADP), and adenosine monophosphate(AMP) in the PFC was determined by high-performance liquid chromatography(HPLC), and energy charge(EC) was calculated.The parameters related to mitochondrial respiratory function were measured by the Clark oxygen electrode, specifically, state 3 respiration(ST3), state 4 respiration(ST4), and respiratory control rate(RCR).Enzymatic activities of succinate dehydrogenase(SDH), cytochrome C oxidase(COX), Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase were measured by chemical colorimetry.Mitochondrial permeability transition pore(mPTP) opening was measured by spectrophotometry.Protein expression of glucose transporter 1(GLUT1) and GLUT3 in PFC was tested by Western blot.Compared with the results in the model group, RRP could significantly reduce the total distance of movement, vertical times, and distance in the central area in the open field test(P&lt;0.05 or P&lt;0.01), increase the content of ATP and EC, decrease the content of AMP(P&lt;0.05), elevate ST3 and RCR(P&lt;0.05), potentiate activities of SDH, COX, Na~+-K~+-ATPase, and Ca~(2+)-Mg~(2+)-ATPase(P&lt;0.05 or P&lt;0.01), inhibit the opening of mPTP, and increase the expression levels of GLUT1 and GLUT3 proteins(P&lt;0.05).It was inferred that RRP could inhibit hyperacti-vity and impulsivity by improving the energy metabolism disorder in PFC of ADHD rats, and its mechanism may be related to the improvement of mitochondrial respiratory function, potentiation of Na~+-K~+-ATPase, Ca~(2+)-Mg~(2+)-ATPase, and mitochondrial respiratory enzymes, inhibition of the opening of mPTP, and up-regulation of the expression of glucose transporter proteins.This study initially reveals the biological connotation of the &quot;static Yin and dynamic Yang&quot; theory in ADHD.

Abstinence following intermittent methylphenidate exposure dose-dependently modifies brain glucose metabolism in the rat brain.

Methylphenidate (MP) is a psychostimulant chronically prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). Additionally, MP users may take breaks from using the medication during "drug holidays," which may include short-term or long-term breaks from medication. The present study utilized fluorodeoxyglucose (FDG) positron emission tomography (PET) to analyze the effects of chronic oral MP use and abstinence on brain glucose metabolism (BGluM) in rats at two different doses: high dose (HD) and low dose (LD). The schedule of treatment was 3weeks on-treatment and 1week off-treatment for a period of 13weeks, followed by an abstinence period of 4 total weeks. Results showed that chronic MP treatment using this schedule did not lead to significant changes in BGluM when comparing the control to HD MP groups. However, significant activation in BGluM was observed after periods of abstinence between control and HD MP rats in the following brain regions: the trigeminal nucleus, reticular nucleus, inferior olive, lemniscus, mesencephalic reticular formation, inferior colliculus, and several areas of the cerebellum. These brain regions and functional brain circuit play a role in facial sensory function, the auditory pathway, organizing connections between the thalamus and cortex, motor learning, auditory function, control over eye movement, auditory information integration, and both motor and cognitive functions. These results, when considered with previous studies, indicate that MP schedule of use may have differing effects on BGluM. BGluM following long-term MP use was dependent on MP dose and schedule of use in rats. This study was conducted in non-ADHD model rats with the aim to establish an understanding of the effects of MP itself, especially given the growing chronic off-label and prescribed use of MP. Further studies are needed for analysis of the drug's effects on an ADHD model.

Efficacy of Risperidone and Methylphenidate for Problem Behaviors and Core Symptoms in Autism Spectrum Disorder: A Randomized Trial

Background: Risperidone and methylphenidate are commonly used drugs to manage problem behaviors in individuals with autism spectrum disorder (ASD). Studies report that these 2 drugs may be helpful in improving core symptoms of ASD as well. Aim: To assess and compare the efficacy and safety profile of risperidone and methylphenidate for problem behaviors and core symptoms in children and adolescents with ASD. Setting and Design: An 8-week, prospective, interventional, randomized, and open-label trial carried out in a tertiary care hospital of northern India. Materials and Methods: Forty subjects with a diagnosis of ASD according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition were randomized to risperidone and methylphenidate groups. Childhood Autism Rating Scale, Second Edition, Indian Scale for Assessment of Autism, and Nisonger Child Behavior Rating Form were used for assessments. Adverse effects, physical, and laboratory parameters were monitored regularly. Statistical Analysis: Tests applied include chi-square test, repeated measures Analysis of Variance, and Student t test, and nonparametric tests for skewed data. Data was analyzed using SPSS Version 22.0. Level of significance was set at 0.05. Results: Both drugs improved inattention, hyperactivity, and stereotypies. Methylphenidate reduced self-isolation, and risperidone improved emotional dysregulation, aggression, and self-injury. Adverse effects were seen in 55% of methylphenidate group (commonly decreased appetite and irritability) and 40% of risperidone group (commonly sedation and increased appetite). Improvement in stereotypy with both drugs and self-isolated behavior with methylphenidate indicates a possible role in improving core symptoms of ASD. Conclusion: Both drugs were beneficial in the management of behaviors associated with ASD. Further research to establish their role in reducing core symptoms and long-term safety is warranted.