Methylphenidate For Attention Deficit Hyperactivity Disorder Research Articles

Brief report: effects of methylphenidate on the light adapted electroretinogram.

To explore changes in the electroretinogram (ERG) following methylphenidate use in attention-deficit/hyperactivity disorder (ADHD). Light adapted ERGs were recorded in five individuals (3 male and 2 female, age range 13.6-21.8years) with a diagnosis of ADHD. Six flash strengths ranging from 71 to 446Td.s were qualitatively evaluated following a minimum of 24h without any medication and from 2 to 6h following the individuals' standard slow-release (XL) methylphenidate dose that ranged from 18 to 60mg. Of the six flash strengths, the 178Td.s strength revealed changes in four of the five participants with a median 27.4% increase in b-wave amplitude. For three individuals there was an increase in the a-wave amplitude and for two of the same individuals there was also a noticeable pronouncement of the oscillatory potentials. The a-wave amplitude showed a greatest median increase at the 446Td.s flash strength of 25.8%. One individual - on the highest dose (60mg) exhibited no morphologically distinct changes in the ERG. No differences in the time to peaks of the a- and b-wave were observed for any individual. The a- and b-wave amplitudes of the light adapted ERG could provide insights into the effect of methylphenidate in ADHD.

Phasic dopamine signals are reduced in the spontaneously hypertensive rat and increased by methylphenidate.

The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention-deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast-scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward-predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low-dose methylphenidate in ADHD.

Conflict of interest and risk of bias in systematic reviews on methylphenidate for attention-deficit hyperactivity disorder: a cross-sectional study

BackgroundSystematic reviews (SRs) are pivotal to evidence-based medicine, yet there is limited research on conflicts of interest in SRs. Our aim was to investigate financial conflicts of interest and risk of bias (RoB) in SRs of a well-defined clinical topic.MethodsA librarian searched Medline, Cochrane Library, Embase, and PsycINFO for SRs investigating the effect of methylphenidate on ADHD in December 2020. The selection process adhered to the PRISMA guidelines. Two blinded reviewers independently searched open websites, including other publications, for information on financial conflicts of interest of all authors of the included SRs. A time limit of 3 years before or after the index SR was adopted. Declarations on conflict of interest were extracted from the included SRs for comparison. ROBIS was used for RoB assessment.ResultsOut of 44 SRs included, 15 (34%) declared conflict of interest, 27 (61%) did not, and a declaration of conflict of interest was missing for 2 (5%). On open websites, conflict of interest was found for at least one author of 23 (52%) SRs: disclosed in 15 (34%) and not disclosed in 8 (18%) SRs.Seven (16%) SRs had low, 36 (82%) had high, and 1 (2%) had unclear RoB. Among SRs with financial conflict of interest found in open sources, 6/22 (27%) had low RoB compared to 1/21 (5%) if no such conflict of interest was identified. Among SRs with financial conflict of interest identified, 1/6 (17%) at low RoB did not disclose their conflict of interest, whereas the corresponding proportion among SRs at high RoB was 7/16 (44%).Eight (18%) SRs presented conflict of interest disclosed in the included primary studies. Four of them (50%) had low RoB, compared to 3/36 (8%) for SRs not reporting on this aspect.ConclusionFinancial conflict of interest was underreported in 18% of the SRs using our reference standard, and overall it was present for every second SR. This group embraced both SRs at low RoB disclosing conflict of interest and SRs at high RoB not disclosing their conflict of interest. Further studies to explore this heterogeneity are warranted.

Attention-Deficit/Hyperactivity Disorder Animal Model Presents Retinal Alterations and Methylphenidate Has a Differential Effect in ADHD versus Control Conditions.

Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders. Interestingly, children with ADHD seem to experience more ophthalmologic abnormalities, and the impact of methylphenidate (MPH) use on retinal physiology remains unclear. Thus, we aimed to unravel the retina's structural, functional, and cellular alterations and the impact of MPH in ADHD versus the control conditions. For that, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were used as animal models of ADHD and the controls, respectively. Animals were divided into four experimental groups as follows: WKY vehicle (Veh; tap water), WKY MPH (1.5 mg/kg/day), SHR Veh, SHR MPH. Individual administration was performed by gavage between P28-P55. Retinal physiology and structure were evaluated at P56 followed by tissue collection and analysis. The ADHD animal model presents the retinal structural, functional, and neuronal deficits, as well as the microglial reactivity, astrogliosis, blood-retinal barrier (BRB) hyperpermeability and a pro-inflammatory status. In this model, MPH had a beneficial effect on reducing microgliosis, BRB dysfunction, and inflammatory response, but did not correct the neuronal and functional alterations in the retina. Curiously, in the control animals, MPH showed an opposite effect since it impaired the retinal function, neuronal cells, and BRB integrity, and also promoted both microglia reactivity and upregulation of pro-inflammatory mediators. This study unveils the retinal alterations in ADHD and the opposite effects induced by MPH in the retina of ADHD and the control animal models.

Association Between Tic Aggravation and Methylphenidate in Youth With Attention-Deficit/Hyperactivity Disorder.

ObjectiveThis study aimed to determine the tic aggravation event rate and cumulative incidence rate in the use of methylphenidate (MPH) treatment in attention-deficit/hyperactivity disorder (ADHD) and the factors that influence tic aggravation. MethodsWe conducted a retrospective chart review of children and adolescents aged between 6 to 15 years, who were diagnosed with ADHD from January 2017 to December 2019. A total of 121 subjects were included. The MPH dosage, psychiatric family history, comorbidity and past history of tics were assessed through chart review and the psychological examinations data were included. Collected data were analyzed using Cox regression and Kaplan-Meier survival analysis. ResultsTic aggravation event rates without a past history of tics were 2.9% with MPH treatment in ADHD. Past history of tics, total MPH dosage and age were the factors associated with tic aggravation ([HR 21.46, p<0.001], [HR 0.94, p=0.023], [HR 0.79, p=0.021] for each). Cumulative incidence of tic aggravation was different between groups with or without past tic history. When treated with MPH, all tic aggravation appeared within approximately eight months but for subjects with a past history of tic, aggravation showed within approximately six months (p<0.001). ConclusionTic aggravation event rate was significantly low especially in the group without a past history of tics with the use of MPH in ADHD. However, a thorough assessment of past history of tics, and close monitoring during the first six-eight months of treatment with MPH is needed to avert a potential worsening of tics.

Methylphenidate for attention-deficit/hyperactivity disorder in patients with Smith\u2013Magenis syndrome: protocol for a series of N-of-1 trials

BackgroundSmith–Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Often, patients with SMS are diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the effectiveness of methylphenidate (MPH), the first-line pharmacological treatment for ADHD, in patients with SMS is unclear. Our objective is to examine the effectiveness of MPH for ADHD symptoms in individuals with SMS, proposing an alternative trial design as traditional randomized controlled trials are complex in these rare and heterogeneous patient populations.Methods and analysisWe will initiate an N-of-1 series of double-blind randomized and placebo-controlled multiple crossover trials in six patients aged ≥ 6 years with a genetically confirmed SMS diagnosis and a multidisciplinary established ADHD diagnosis, according to a power analysis based on a summary measures analysis of the treatment effect. Each N-of-1 trial consists of a baseline period, dose titration phase, three cycles each including randomized intervention, placebo and washout periods, and follow-up. The intervention includes twice daily MPH (doses based on age and body weight). The primary outcome measure will be the subscale hyperactivity/inattention of the Strengths and Difficulties Questionnaire (SDQ), rated daily. Secondary outcome measures are the shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index, Goal Attainment Scaling (GAS), and the personal questionnaire (PQ). Statistical analysis will include a mixed model analysis. All subjects will receive an assessment of their individual treatment effect and data will be aggregated to investigate the effectiveness of MPH for ADHD in SMS at a population level.ConclusionsThis study will provide information on the effectiveness of MPH for ADHD in SMS, incorporating personalized outcome measures. This protocol presents the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder, providing a much-needed bridge between science and practice to optimize evidence-based and personalized care.Trial registration This study is registered in the Netherlands Trial Register (NTR9125).

Does Methylphenidate Work in Children and Adolescents with Attention Deficit Hyperactivity Disorder?

Objective: Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder diagnosed in increasing proportions of children and adolescents. The psychostimulant methylphenidate has been considered the first-line pharmacological treatment for children and adolescents with ADHD for more than 60 years. Considering recent publications on methylphenidate for ADHD, we here give an overview of its effects in children and adolescents with ADHD, elicited by a well-disputed Cochrane review and narratively synthesise the evidence in the field. Method: We searched for systematic reviews and meta-analyses that investigated methylphenidate as an intervention for children and adolescence with ADHD compared with placebo or no treatment. We assessed the quality of the evidence using AMSTAR II. Results: We found 24 eligible systematic reviews and meta-analyses of which 11 were rated as high- quality evidence according to AMSTAR II. The evidence claiming that methylphenidate is beneficial in treating children and adolescents with ADHD was of very low certainty. The underreporting of adverse events in randomised clinical trials may impede an adequate depiction of the balance between benefits and harms. Conclusions: It appears that there is uncertain evidence on group-level to support the claim that methylphenidate is beneficial in treating children and adolescents with ADHD. Future randomised clinical trials and systematic reviews should include individual participant data, which would allow us to assess intervention effects across modifiers, like age, sex, ADHD subtypes, comorbidities, and dose.

Cognitive mechanisms of methylphenidate in ADHD: Do improvements in sustained attention mediate behavioral improvements in the natural environment?

ABSTRACT The relation between sustained attention in the laboratory and behaviors exhibited in naturalistic settings among children with Attention Deficit/Hyperactivity Disorder (ADHD) remains unclear. Additionally, research on stimulant medication effects in these areas and their association with one another remains scarce. Twenty-one children with ADHD and 21 children without ADHD completed a novel continuous performance test (CPT) involving high cognitive demands (e.g., visual search). Participants with ADHD also attended a Summer Treatment Program and received three doses of stimulant medication (placebo, low, and high). Their behavior in classroom and peer settings was observed and recorded, and they completed the CPT in each medication condition. The CPT measures of bias and sensitivity were used in analyses. Results indicated that children with ADHD had impaired overall performance and worse bias during the second half of the task compared to controls. Methylphenidate improved both naturalistic behavior and overall CPT performance but did not specifically improve the sustained attention deficit. Despite improvements in overall CPT performance, medication-related improvement in CPT performance did not mediate medication-related improvement in observed behavior in classroom or recreational settings. As such, our findings suggest that although children with ADHD do demonstrate a sustained attention deficit, salutary psychostimulant effects on CPT performance are not indicative of, or causally linked to, psychostimulant effects on presenting problems in naturalistic settings.

The interactive effects of test-retest and methylphenidate administration on cognitive performance in youth with ADHD: A double-blind placebo-controlled crossover study

Studies have shown that Methylphenidate (MPH) affects cognitive performance on the neuropsychological tests and clinical symptoms of individuals diagnosed with attention deficit/hyperactivity disorder (ADHD). This study investigated the acute effects of MPH on neuropsychological tests to explore the interaction between MPH and test-retest effects. Twenty youths with ADHD were tested before and after MPH intake in a double-blind placebo-controlled crossover design and compared to twenty matched controls. Participants were tested on a range of standardized tasks including sustained attention to response, N-Back, and Word/Color Stroop. Identical tasks were administered twice each testing day, before and 1 hour after MPH/Placebo administration. Healthy controls were tested similarly with no intervention. Decreases in response time (RT) variability across tasks and in commission errors were found in ADHD after MPH. Conversely, a significant increase in RT variability and increase in omission errors were observed after the placebo. In the control group, RT variability and omission errors increased whereas commission errors decreased, suggesting fatigue and practice effects, respectively. Test-retest reliability was higher in controls than ADHD. It is suggested that cognitive tests are sensitive objective measures for the assessment of responses to MPH in ADHD but are also affected by repetition and fatigue.

Effects of medications on ventricular repolarization in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a multifactorial neurodevelopmental disorder that manifests during childhood. Methylphenidate (MPH), which is a psychostimulant drug, has been often prescribed for the treatment of ADHD in patients. It may increase the risk of fatal arrhythmias by impairing ventricular repolarization. Indicators of ventricular repolarization in ECG are intervals of QT, corrected QT (QTc), QT dispersion (QTd), T-peak to T-end (Tp-e), and Tp-Te/QTc ratio. We aimed to determine ventricular repolarization findings before and after MPH drug therapy in children with ADHD. The study retrospectively examined the medical records of 33 children aged 6-15 years who received MPH for ADHD and who had a control ECG one month after medication. The ECG parameters, heart rate, intervals of QRS, QT, QTc, QTd, Tp-Te, and Tp-Te/QTc ratio, were compared for each patient before and after drug therapy. No significant change was observed in heart rate, QRS, QT, QTc, and QTd interval in ECGs of patients after treatment but pre and posttreatment mean Tp-Te interval was 73.4 ± 9.72 ms and 79.7 ± 10.48 ms, and mean Tp-Te/QTc ratio was 0.17 ± 0.024 and 0.18 ± 0.023, respectively (P = 0.015, P = 0.028). Tp-Te intervals and Tp-Te/QTc ratios remained within normal values after treatment with MPH, but values were higher than baseline.

Diagnosis and Treatment Options for Preschoolers with Attention-Deficit/Hyperactivity Disorder.

Objective: The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), classifies attention-deficit/hyperactivity disorder (ADHD) as a neurodevelopmental disorder, with symptoms becoming apparent as early as the preschool years. Early recognition can lead to interventions such as parent/teacher-administered behavior therapy, the recommended first-line treatment for preschool patients. There are few data, however, to inform the use of second-line, pharmacotherapy options in this population. In this review, we identified recent literature on the diagnosis and treatment of ADHD in preschool children. Methods: A PubMed and clinicaltrials.gov search was conducted for trials assessing efficacy or safety of ADHD medications in children aged <6 years. Diagnostic methods and criteria focusing on recognition of ADHD in preschool children were also surveyed. Results: The DSM-5 describes different manifestations of ADHD in preschool versus school-aged children, but does not list separate criteria by age group. Importantly, behaviors indicative of ADHD in older children may be developmentally appropriate in preschool children. Several behavioral rating scales have been validated in children younger than 6 years of age for assessing ADHD. The Preschool ADHD Treatment Study (PATS) has provided the most extensive efficacy and safety data on methylphenidate (MPH) for ADHD in preschoolers to date, with significant improvement in ADHD symptoms observed with MPH compared with placebo, although adverse event-related discontinuation was higher in PATS compared with studies of MPH for ADHD in school-aged children. Since PATS was conducted, few studies designed to assess ADHD medication effectiveness in preschool children have been published. One article reported significant improvement in ADHD symptoms with MPH (immediate release) versus placebo, two studies showed no difference between MPH and risperidone or MPH plus risperidone in relief of ADHD symptoms, and one study demonstrated the efficacy of atomoxetine versus placebo for ADHD symptoms in preschoolers. Conclusions: Further research is needed on pharmacotherapy for preschool children with ADHD.

Long‐term use of methylphenidate continues to confer benefits

Patients continue to receive benefits from treatment for attention‐deficit/hyperactivity disorder (ADHD) with methylphenidate after long‐term use, researchers have found. Some patients may be withdrawn from the medication, however. Therefore, all patients should be assessed periodically to determine whether they continue to need the medication. The study, published in the American Journal of Psychiatry, was conducted because, while long‐term use of methylphenidate for children with ADHD is frequent clinical practice, its benefits are unclear. They looked at whether the medication remains beneficial after 2 years. Methylphenidate, a stimulant, has been controversial in some quarters because it is a controlled substance, However, the first‐line treatment for ADHD is psychostimulant medication, such as methylphenidate. How long children should take is is a question, but 60% of children receive stimulant treatment for ADHD for more than 2 years, and this is increasingly common, extending even into adolescence and adulthood. This is partly due to the awareness that ADHD is not a pediatric‐only condition. The study, “Continued benefits of methylphenidate in ADHD after 2 years in clinical practice: A randomized placebo‐controlled discontinuation study,” was published online May 21 by the American Journal of Psychiatry.

Effects of methylphenidate on the ERP amplitude in youth with ADHD: A double-blind placebo-controlled cross-over EEG study.

Methylphenidate (MPH) is a first line drug for attention-deficit/hyperactivity disorder (ADHD), yet the neuronal mechanisms underlying the condition and the treatment are still not fully understood. Previous EEG studies on the effect of MPH in ADHD found changes in evoked response potential (ERP) components that were inconsistent between studies. These inconsistencies highlight the need for a well-designed study which includes multiple baseline sessions and controls for possible fatigue, learning effects and between-days variability. To this end, we employ a double-blind placebo-controlled cross-over study and explore the effect of MPH on the ERP response of subjects with ADHD during a Go/No-Go cognitive task. Our ERP analysis revealed significant differences in ADHD subjects between the placebo and MPH conditions in the frontal-parietal region at 250ms-400ms post stimulus (P3). Additionally, a decrease in the late 650ms-800ms ERP component (LC) is observed in frontal electrodes of ADHD subjects compared to controls. The standard deviation of response time of ADHD subjects was significantly smaller in the MPH condition compared to placebo and correlated with the increased P3 ERP response in the frontoparietal electrodes. We suggest that mental fatigue plays a role in the decrease of the P3 response in the placebo condition compared to pre-placebo, a phenomenon that is significant in ADHD subjects but not in controls, and which is interestingly rectified by MPH.

Continued Benefits of Methylphenidate in ADHD After 2 Years in Clinical Practice: A Randomized Placebo-Controlled Discontinuation Study.

The benefits of long-term use of methylphenidate treatment in children and adolescents with attention deficit hyperactivity disorder (ADHD), as frequently prescribed in clinical practice, are unclear. The authors investigated whether methylphenidate remains beneficial after 2 years of use. Ninety-four children and adolescents (ages 8-18 years) who had been treated in regular care with methylphenidate for more than 2 years were randomly assigned to double-blind continuation of treatment for 7 weeks (36 or 54 mg/day of extended-release methylphenidate) or gradual withdrawal over 3 weeks, to 4 weeks of placebo. The primary outcome measure was the investigator-rated ADHD Rating Scale (ADHD-RS); secondary outcome measures were the investigator-rated Clinical Global Impressions improvement scale (CGI-I) and the Conners' Teacher Rating Scale-Revised: Short Form (CTRS-R:S). Continuous ratings were analyzed with mixed model for repeated measures analyses, and the CGI-I with a chi-square test. The mean ADHD-RS scores at baseline for the continuation and discontinuation groups, respectively, were 21.4 (SD=9.7) and 19.6 (SD=8.9); after 7 weeks, the mean scores were 21.9 (SD=10.8) and 24.7 (SD=11.4), with a significant between-group difference in change over time of -4.6 (95% CI=-8.7, -0.56) in favor of the group that continued methylphenidate treatment. The ADHD-RS inattention subscale and the CTRS-R:S ADHD index and hyperactivity subscale also deteriorated significantly more in the discontinuation group. The CGI-I indicated worsening in 40.4% of the discontinuation group, compared with 15.9% of the continuation group. Continued treatment with methylphenidate remains effective after long-term use. Some individual patients may, however, be withdrawn from methylphenidate without deterioration. This finding supports guideline recommendations that patients be assessed periodically to determine whether there is a continued need for methylphenidate treatment.

Preventive effect of cyproheptadine on sleep and appetite disorders induced by methylphenidate: an exploratory randomised, double-blinded, placebo-controlled clinical trial

Objectives: Insomnia and loss of appetite are the most common side effects of methylphenidate in patients with attention deficit/hyperactivity disorder (ADHD). The adverse effects may limit optimal dosing and patients’ compliance with treatment leading to the discontinuation of treatment. This research evaluates the preventive effects of cyproheptadine on sleeping and appetite disorders induced by methylphenidate in ADHD children.Methods: During this exploratory, randomised, double-blinded, placebo-controlled clinical trial, forty patients with ADHD diagnosis who had received methylphenidate randomly were assigned to participate in the cyproheptadine or the placebo group. Patients’ weight and Pittsburgh Sleep Quality Index (PSQI) score were recorded at baseline, after four, six and eight weeks of treatment. The ADHD Parent Rating Scale-V score was also defined at the beginning and the end of study for each patient.Results: There was no significant difference between the cyproheptadine and the placebo groups regarding their weight, rate of growth and PSQI score in the monthly assessment. In addition, there was no significant difference in response to the therapy between the two groups.Conclusions: Based on our findings, cyproheptadine does not have any considerable preventive effect on sleeping and appetite disorders induced by methylphenidate in ADHD children.Trial registration: Iranian Registry of Clinical Trials identifier: IRCT2015070623099N1.

The Jury Is Still Out on the Benefits and Harms of Methylphenidate for Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.

Much remains unclear about the benefits and harms of methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Between 2012 and 2018, we conducted two Cochrane systematic reviews on methylphenidate for ADHD. This article explores the main findings in relation to evidence-based practice and our current understanding of ADHD.

Are psychiatric comorbidities and associated cognitive functions related to treatment response to methylphenidate in boys with attention-deficit/hyperactivity disorder?

BackgroundMethylphenidate (MPH) has been found to be an effective medication for attention-deficit/hyperactivity disorder (ADHD). However, there are neither consistent nor sufficient findings on whether psychiatric comorbidities and associated cognitive functions of ADHD are related to treatment response to MPH in ADHD children.ObjectivesThis study investigated whether psychiatric comorbidities, IQ, and neurocognitive deficits are related to treatment response to MPH in ADHD children. In some ways, it is preferable to have a drug that the effectiveness of which to a disorder is not affected by its associated cognitive functions and psychiatric comorbidities. On the other hand, it is likely that the baseline symptom severity of ADHD is associated with the effectiveness of MPH treatment on the symptoms post treatment.MethodsA total of 149 Chinese boys (aged 6–12 years) with ADHD, combined type, and normal IQ participated in this study. Assessment of ADHD symptom severity was conducted pre and post MPH treatment, while assessment of psychiatric comorbidities, IQ, and neurocognitive deficits was performed in a non-medicated condition. Treatment response was defined as the ADHD symptom severity post MPH treatment.ResultsResults indicated that MPH treatment was effective, significantly improving the ADHD condition. Yet, comorbid disorders, IQ, and neurocognitive deficits were not related to MPH treatment response on ADHD symptoms. These findings indicated that the effectiveness of MPH was not affected by psychiatric comorbidities and associated cognitive functions of ADHD. Instead, as expected, it was the baseline symptom severity that was mainly related to the treatment response, ie, the milder the baseline condition, the better the treatment response.ConclusionThe current findings positively endorse the widespread clinical use of MPH for treating ADHD. It improves the behavioral symptoms of ADHD regardless of varying psychiatric comorbidities, IQ, and neurocognitive deficits.

Methylphenidate for ADHD in children and adolescents: throwing the baby out with the bathwater

A recent Cochrane review assessed the efficacy of methylphenidate for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Notwithstanding the moderate-to-large effect sizes for ADHD symptom reduction found in the meta-analysis,...

Effects of Maternal Symptom Ratings and Other Clinical Features on Short-Term Treatment Response to OROS Methylphenidate in Children and Adolescents with ADHD in a Naturalistic Clinical Setting

To investigate the effect of Attention Deficit Hyperactivity Disorder (ADHD), antisocial behavior and anxiety/depression ratings of mothers, and child and adolescents' age, gender, ADHD subtype, and comorbidity on one-month drug treatment response to OROS methylphenidate in ADHD in a naturalistic setting. The analyses included 223 subjects (191 boys, 32 girls; age 6-15 years, mean: 9.4) treated with OROS methylphenidate (18-72 mg/day, mean: 31 mg/d; 0.4-1.4 mg/kg/d) for one-month. Treatment response was defined as larger than 25% or more decrease in pre-treatment the Conners Parent Rating Scale (CPRS) or the Conners Teacher Rating Scale (CTRS) total scores and the Clinical Global Impression improvement with drug treatment 3 (minimally improved) or higher. Maternal ADHD, antisocial behavior and anxiety/depression ratings were obtained by the Adult Self Rating (ASR). Logistic regression analyses were computed in order to calculate the effects of gender; age; ADHD subtype; comorbid anxiety disorder, learning disorder, oppositional defiant/conduct disorder; maternal ASR Anxiety/Depression, ADHD and Antisocial scores. 35.2% of subjects had statistically significant 25% or more decrease in pretreatment CPRS total scores and 38.6% of subjects had statistically significant 25% or more decrease in pretreatment CTRS total scores. The subjects with comorbid anxiety disorder had the poorest drug response. Maternal self-reported antisocial and anxiety/depressive symptomatology were statistically significantly associated with worse response to treatment in terms of CPRS (respectively, OR=0.83, 95% CI: 0.75-0.92, p<0.01; OR=0.95, 95% CI: 0.9-0.99, p<0.05) and CTRS total scores (OR=0.9, 95% CI: 0.82-0.99, OR=0.95, 95% CI: 0.91-1, p<0.05). Baseline rating scores were also important predictors of drug treatment response. Effects of age, gender and maternal ADHD were not statistically significant. ADHD children and adolescents with comorbid anxiety disorders and those whose mothers have more self-reports of antisocial and depressive symptoms showed less favorable short-term response to OROS-MPH. These subjects may require further attention and additional interventions to augment treatment with OROS methylphenidate.

N-of-1 trials can be aggregated to generate group mean treatment effects: a systematic review and meta-analysis

ObjectivesTo evaluate how data from n-of-1 trials may be used in systematic reviews and meta-analyses by examining the effects of amphetamine and methylphenidate for attention-deficit hyperactivity disorder (ADHD). Study Design and SettingElectronic search of MEDLINE, EMBASE, and PsychINFO for English language articles published from 1950 to 2013. N-of-1 trials of pediatric participants with ADHD that assessed either amphetamine or methylphenidate vs. placebo were included. The primary outcome was improvement of core symptoms of ADHD, which was assessed by multiple rating scales. Studies with obtainable individual participant data were included in the meta-analysis. Weighted mean differences were computed using a random-effects model. ResultsNine studies were included in the amphetamine-placebo comparison and 10 in the methylphenidate-placebo comparison. Meta-analyses were consistently in favor of amphetamine in 10 of 11 ADHD symptom domains and methylphenidate in 7 of 12 symptom domains. A high degree of heterogeneity across participant treatment response was observed. ConclusionsMeta-analysis of n-of-1 trials suggests that amphetamine and methylphenidate are effective treatments for pediatric ADHD. Synthesizing n-of-1 trials enables assessment of individual responses to treatment as well as aggregate summaries across individuals and studies. It offers a promising general approach with applications across diverse treatments and disorders.