Adverse response to methylphenidate in combination with valproic acid

The use of methylphenidate (MPH) in combination with antiepileptic drugs is gaining acceptance for children with epilepsy who have the symptoms of attention-deficit hyperactivity disorder (ADHD). We report two cases of an adverse effect of dyskinesia and bruxism when MPH was given to children maintained on valproic acid. These adverse effects were rapid and severe. Because of the potential for serious and persistent side effects from this combination of medications, caution is warranted in the treatment of ADHD with MPH for children taking valproic acid. Further prospective studies of the use of valproic acid and MPH in combination are required.     

High-dose methylphenidate treatment of attention deficit hyperactivity disorder in a preschooler

Although attention deficit hyperactivity disorder is thought to be present in preschoolers, there are no clear guidelines for dosing stimulant medications in this population. This is a case of a 4-year-old boy who was given 108 mg/day extended-release methylphenidate (OROS) MPH) (6.1 mg/kg/day) by his caregiver with notable behavioral improvement. However, weight loss incurred due to the anorexic side effect of the medication led the clinician to decrease his dose to 72 mg/day OROS MPH (3.7 mg/kg/day). The case highlights that some young children with attention deficit hyperactivity disorder treated with MPH may require higher doses than would be predicted by weight-based dosing. An increased frequency of side effects associated with high doses of MPH necessitates that the clinician balance the positive behavioral response of the medication with adverse side effects in determining ideal dose.     

Methylphenidate and behavior modification in children with ADHD and comorbid ODD or CD: main and incremental effects across settings

OBJECTIVE: Although the combination of methylphenidate (MPH) and behavior modification (BMOD) has been advocated to enhance clinical outcome for children with attention-deficit hyperactivity disorder (ADHD) and comorbid disruptive disorders, few group studies have been conducted. This study evaluates the separate and incremental effects of these modalities on rating scale and observational measures in multiple settings. METHOD: Sixteen of 22 children with ADHD and comorbid disruptive disorder completed a randomized, placebo-controlled study examining the separate and incremental effects of 2 doses of MPH and BMOD during a partial hospitalization program. Of the 6 who did not complete the study, 2 children developed significant side effects. For the 16 who did complete the study, effects were examined on measures of symptom ratings, behavioral frequencies, and stimulant side effects across program activities. RESULTS: Based on alpha-adjusted analyses of variance, there were several main effects of MPH and BMOD on ADHD symptoms, oppositional behavior, and positive social behavior, with certain effects unique to each intervention and setting. One incremental effect each was found for MPH (positive mood/behavior) and BMOD (negative behavior). MPH and BMOD were associated with few side effects. Effect sizes for each intervention showed considerable variability in clinical response. CONCLUSIONS: That MPH and BMOD had certain unique main and incremental effects extends findings supporting their combination and suggests that integrated studies evaluate multiple dimensions of functioning and in novel settings (e.g., home, school). The incorporation of other intervention components in combined treatments may be warranted to enhance clinical efficacy.     

Effects of osmotic-release methylphenidate in attention-deficit/hyperactivity disorder as measured by event-related potentials

Aim: Attention‐deficit/hyperactivity disorder (ADHD) is a relatively common central nervous system disorder in school‐age children, which may involve a specific disorder in cognition and/or information processing. Event‐related potentials (ERP) are commonly used as physiological measures of cognitive function as they are easily measured and non‐invasive. Thus, in the present study, we examined the effects of osmotic‐release methylphenidate (MPH) (Concerta), a common treatment for childhood attention‐deficit/hyperactivity disorder (ADHD), in ADHD children as measured by ERP. Methods: Ten ADHD children participated after giving consent. Based on the guidelines for evoked potential measurement, mismatch negativity (MMN) and P300 were obtained by auditory odd‐ball tasks. We measured both MMN and P300 in the drug‐naive condition and after intake of osmotic‐release MPH. Results: The MMN amplitudes after intake of osmotic‐release MPH were significantly greater than those in the drug‐naive situation at Pz and C4. The P300 amplitudes after intake of osmotic‐release MPH were significantly greater than those in the drug‐naive situation at Cz and Pz. Conclusion: MMN and P300 are sensitive tools for measuring the pharmacological effects of osmotic‐release MPH in ADHD children.     

Drug and placebo side effects in methylphenidate-placebo trial for attention deficit hyperactivity disorder

In a double-blind methylphenidate placebo trial for children with Attention Deficit Hyperactivity Disorder (ADHD), side effects were reported on both placebo and methylphenidate (MPH), and many side effects were similar to the symptoms of ADHD. We suggest that parents and teachers may mistake the symptoms of ADHD for side effects of MPH, and this misconstrual may contribute to the poor acceptance of and compliance with taking MPH. This research was supported by a grant from CIBA-Geigy Canada.     

Dose-Response Effects of Long-Acting Liquid Methylphenidate in Children with Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD): A Pilot Study

Attention deficit/hyperactivity disorder (ADHD) symptoms are common in youth with autism spectrum disorders (ASD) and are frequently treated with stimulant medications. Twenty-seven children were randomized to different dose titration schedules, and ADHD symptoms, tolerability, and aberrant behaviors were assessed weekly during a 6-week trial with long-acting liquid methylphenidate (MPH). MPH at low to moderate doses was effective in reducing ADHD symptoms and was well tolerated in young children with ASD and ADHD. Future studies are needed to assess generalization and maintenance of efficacy.     

The Effects of Methylphenidate on Neural Substrates Associated with Interference Suppression in Children with ADHD: A Preliminary Study Using Event Related fMRI

Objective

The core deficit of attention deficit hyperactivity disorder (ADHD) is associated with frontal cortex and related circuitry. Children with ADHD and a medication history have shown atypical brain activation in prefrontal and striatal brain regions during cognitive challenge. We investigated two cognitive control operations such as interference suppression (IS) and response inhibition (RI) in children with ADHD. We also assessed the brain functions affected by the methylphenidate (MPH) effect by comparing the blood-oxygen level dependent (BOLD) signals in ADHD children on and off medication.

Methods

Eight children (9-11 years of age) with combined-type ADHD underwent rapid event-related functional magnetic resonance imaging (fMRI) during performance of a modified flanker task. Two fMRI (3.0 T) scans were conducted with a one week interval-one with MPH treatment and the other without. Functional maps were generated through group averaging and performance-based correlational analyses.

Results

Performances of the two cognitive control operations did not differ significantly between on-MPH and off-MPH status other than the reaction time to incongruent stimuli in ADHD children. In those affected by MPH treatment, an increased activation in the right prefrontal cortex during incongruent task was observed relative to a neutral trial in children with ADHD.

Conclusion

On the treatment of MPH, the ADHD children exhibited increased activation of the right frontal cortex during interference suppression. This finding suggested that MPH affected the right frontal cortex in ADHD compensating for a reduced level of interference suppression. Future studies will be required to ascertain the MPH effect of cognitive brain regions among large number of children with ADHD.     

Acute effects of methylphenidate on performance during the Test of Variables of Attention in children with attention deficit/hyperactivity disorder

This study attempted to determine the acute effects of methylphenidate (MPH) on cognitive performance using the Test of Variables of Attention (TOVA) in children with attention deficit/hyperactivity disorder (ADHD). The study subjects comprised 57 children diagnosed with ADHD aged 6-13 years. Diagnoses of ADHD and other comorbid psychiatric disorders were based on Diagnostic and Statistical Manual of Mental Disorders-fourth edition criteria following a standard interview with the Schedule for Affective Disorder and Schizophrenia for School-Age Children, epidemiologic version. The subjects' performance on the TOVA was compared before and 1 h after administration of MPH. After administration of MPH, commission scores, response time and ADHD scores improved significantly, however, there were no significant changes in omission scores, response time variability or response sensitivity. The authors concluded that administration of one dose of MPH (0.5-1.0 mg/kg) produced more effects on impulsivity than on attention deficiency in children with ADHD, and that the second half section of the TOVA could be more sensitive than the first half in determining the acute effects of MPH therapy in children with ADHD. However, the effects of different MPH doses on the TOVA results need further investigation.     

Attention deficit hyperactivity disorder: anxiety phenomena in children treated with psychostimulant medication for 6 months or more.

OBJECTIVE: The intermediate- to long-term use of psychostimulant medication has unclear benefits on the core symptoms of attention deficit hyperactivity disorder (ADHD) and delayed onset affective symptom side effects which can mimic these core ADHD symptoms. 'ADHD and anxiety' has also been associated with a poor response to short-term psychostimulant medication treatment. In addition, it is unclear whether 'ADHD and anxiety' should be defined from the child's and/or the parent's perspective. We propose that anxiety will be increased in children with ADHD who are treated with psychostimulant medication in the intermediate- to long-term who are identified by clinicians as poor responders. METHOD: Twenty children with ADHD who were medicated for 6 months or more and who had ongoing core symptoms of ADHD were compared to 20 age- and IQ-matched children with ADHD who were medication-na?ve. Chi-squared tests were performed on the categorical dependent variables and independent t-tests on the dependent continuous variables. RESULTS: Anxiety is significantly increased in children with ADHD treated with psychostimulant medication in the intermediate- to long-term who are noted by clinicians to have ongoing core symptoms of ADHD. This statistically significant finding is evident with both categorical and dimensional measures of anxiety from the child's perspective. CONCLUSIONS: The recognition of anxiety and its management in children with ADHD is generally poorly understood. In this particular group of children with ADHD, anxiety may be a side effect of intermediate- to long-term psychostimulant medication and/or a potential marker for a poor response to intermediate- to long-term psychostimulant medication treatment.     

Response to methylphenidate in children with ADHD and comorbid anxiety

OBJECTIVE: To determine whether comorbid anxiety alters response to methylphenidate (MPH) in children with attention-deficit hyperactivity disorder (ADHD). METHOD: Ninety-one children with ADHD were assessed for anxiety. Children were randomly assigned to receive MPH or placebo, titrated to a dose of 0.7 mg/kg, while side effects were minimized. Measures of side effects and behavioral response were obtained from parents and teachers before treatment, after titration to optimal dose, and after 4 months of treatment. These measures, dose of drug, and rate of adherence to assigned medication assignment were compared for nonanxious (ADHD- ANX) and anxious ADHD children (ADHD+ ANX). RESULTS: Rates of adherence to original medication assignment did not differ between the groups. ADHD+ ANX on both MPH and placebo titrated to a lower dose at the end of titration, although the dose of drug did not differ among the groups after 4 months of treatment. No differential response to MPH between ADHD+ ANX and ADHD- ANX was noted at end-titration or at 4 months on any side effect or behavioral measures. CONCLUSIONS: Comorbid anxiety does not appear to influence development of side effects or behavioral response to MPH when dose is titrated as in standard clinical practice.     

Efficacy of methylphenidate among preschool children with developmental disabilities and ADHD.

OBJECTIVE: This was a double-blind, placebo-controlled, crossover design study of the safety and efficacy of methylphenidate (MPH) in 11 preschool children (aged 4.0-5.11 years) with developmental disabilities and attention-deficit hyperactivity disorder (ADHD). METHOD: MPH doses of 0.3 and 0.6 mg/kg per dose and a placebo were given. Drug response was evaluated via teacher-completed behavior checklists and clinic-based observations of activity level, attention, and compliance to adult requests. A side effects checklist was also completed by teachers and parents. RESULTS: Significant improvement on teacher ratings of hyperactivity and inattention as well as clinic-based observations of activity level and compliance were associated with MPH. Eight of 11 preschool children were medication responders (based on a minimum 40% decrease between placebo and one drug condition on either the teacher-rated Conners Hyperactivity Index or the Hyperactive-Distractible subscale of the Preschool Behavior Questionnaire). Five children exhibited significant adverse drug side effects such as severe social withdrawal, increased crying, and irritability, especially at the higher dose (0.6 mg/kg). CONCLUSIONS: Results suggest that preschool children with developmental disabilities and ADHD respond to MPH at rates similar to those of school-age children with mental retardation and ADHD. However, this population appears to be especially susceptible to adverse drug side effects.     

An open-label, randomized, active-controlled equivalent trial of osmotic release oral system methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan

This study examined the efficacy and safety of osmotic release oral system methylphenidate (OROS MPH) as compared with immediate-release MPH (IR MPH) in children with attention-deficit/hyperactivity disorder (ADHD) in Taiwan. Sixty-four children with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD, ages 6-15 years, were randomized to OROS MPH once daily (n = 32) and IR MPH three times daily (n = 32) in an open, randomized, active-controlled equivalent 28-day trial. The main outcome measures included the Conner's Teacher Rating Scale -Revised: Short Form and Conner's Parent Rating Scale-Revised: Short Form, and other measures of social adjustment and side effects. Results showed significant reductions in the core ADHD symptoms, which did not differ between the two treatment groups. Compared to the IR MPH group, the OROS MPH group showed a significantly greater slope of reductions in ADHD symptoms and decline in the severity of problems at school, and with peers and parents over time. There was no difference in rates of side effect profile between the two groups. Our findings suggest that OROS MPH is superior over IR MPH in the greater magnitude of improvement over study period without increased side effects in the Chinese population.     

Attention-deficit/hyperactivity disorder with obstructive sleep apnea: a treatment outcome study

BACKGROUND: Children diagnosed with attention-deficit/hyperactivity disorder (ADHD), based on Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM-IV) criteria, may also have obstructive sleep apnea (OSA), but it is unclear whether treating OSA has similar results as methylphenidate (MPH), a commonly used treatment for ADHD. METHODS: This study enrolled 66 school-age children, referred for and diagnosed with ADHD, and 20 healthy controls. Polysomnography (PSG) performed after ADHD diagnosis showed the presence of mild OSA. After otolaryngological evaluation, parents and referring physicians of the children could select treatment of ADHD with MPH, treatment of OSA with adenotonsillectomy or no treatment. Systematic follow-up was performed six months after initiation of treatment, or diagnosis if no treatment. All children had pre- and post-clinical interviews; pediatric, neurologic, psychiatric and neurocognitive evaluation; PSG; ADHD rating scale, child behavior checklist (CBCL) filled out by parents and teacher; test of variables of attention (TOVA); and the quality of life in children with obstructive sleep disorder questionnaire (OSA-18). RESULTS: ADHD children had an apnea-hypopnea index (AHI)>1<5 event/hour; 27 were treated with MPH, 25 had adenotonsillectomy, and 14 had no treatment. The surgical and MPH groups improved more than the non-treatment group. When comparing MPH to post-surgery, the PSG and questionnaire sleep variables, some daytime symptoms (including attention span) and TOVA subscales (impulse control, response time and total ADHD score) improved more in the surgical group than the MPH group. The surgical group had an ADHD total score of 21.16+/-7.13 on the ADHD rating scale (ADHD-RS) post-surgery compared to 31.52+/-7.01 pre-surgery (p=0.0001), and the inattention and hyperactivity subscales were also significantly lower (p=0.0001). Finally, the results were significantly different between surgically and MPH-treated groups (ADHD-RS p=0.007). The surgical group also had a TOVA ADHD score lower than -1.8 and close to those obtained in normal controls. CONCLUSION: A low AHI score of >1 considered abnormal is detrimental to children with ADHD. Recognition and surgical treatment of underlying mild sleep-disordered breathing (SDB) in children with ADHD may prevent unnecessary long-term MPH usage and the potential side effects associated with drug intake.     

Differential effects of methylphenidate and atomoxetine on attentional processes in children with ADHD: An event-related potential study using the Attention Network Test

Methylphenidate (MPH) and atomoxetine (ATX) are effective medications in the treatment of attention deficit/hyperactivity disorder (ADHD). The aim of this study was to investigate differential effects of MPH and ATX on attentional functions at the performance and the neuronal level in children with ADHD. Using the Attention Network Test (ANT), differential effects of both medications on the noradrenergic alerting network and the dopaminergic executive attention network were considered. Nineteen children with ADHD performed the ANT three times while event-related potentials (ERPs) were recorded. The baseline testing was conducted without medication. In two medication blocks of 8 weeks each, medication was individually titrated for each child (cross-over design, balanced order). At the end of the medication blocks the testing was repeated. While both medications comparably reduced ADHD symptomatology, MPH had some advantages over ATX with regard to performance measures on the ANT and the underlying neuronal mechanisms. Compared with ATX, MPH led to a larger reduction in reaction time variability, which was accompanied by an MPH-related increase in the contingent negative variation (CNV) compared to the baseline testing. Contrary to our expectations, specific alerting network effects were not observed with ATX. Due to the chosen study design, it remains unresolved to what extent e.g. shortened reaction times and smaller conflict scores that were observed with both medications reflect practice or medication effects. The differential pattern of MPH vs. ATX effects on attentional functions in children with ADHD may be explained by the dopaminergic effects of MPH within the cortico-striato-thalamo-cortical circuit.     

A preliminary study on the effect of methylphenidate on motor performance in children with comorbid DCD and ADHD

Attention Deficit Hyperactive Disorder (ADHD) and Developmental Coordination Disorder (DCD) are two developmental disorders with considerable comorbidity. The impact of Methylphenidate (MPH) on ADHD symptoms is well documented. However, the effects of MPH on motor coordination are less studied. We assessed the influence of MPH on motor performance of children with comorbid DCD and ADHD. Participants were 18 children (13 boys, mean age 8.3 years) diagnosed with comorbid DCD and ADHD. A structured clinical interview (K-SADS-PL) was used to determine psychopathology and the Movement Assessment Battery for Children–Checklist were used to determine criterion for motor deficits. The Movement Assessment Battery for Children (M-ABC) was administrated to all participants once under the influence of MPH and once under a placebo pill condition. The motor tests were administered on two separate days in a double-blinded design. Participants’ motor performance with MPH was significantly superior to their performance in the placebo condition. Significant improvement was observed in all the M-ABC sub-tasks except for static balance performance. The findings suggest that MPH improves motor coordination in children with comorbid DCD and ADHD but clinically significant improvement was found in only 33% of the children.     

Effect of methylphenidate on Stroop Color-Word task performance in children with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome common in the pediatric population. It is associated with multiple nonspecific deficits on neuropsychological tests of executive function, and a beneficial response to pharmacotherapy with methylphenidate (MPH) and other psychostimulants. The Stroop Color-Word task is used empirically as an aid in diagnosis and treatment monitoring of ADHD; however, data on the sensitivity of the Stroop interference score to the effects of MPH are limited. To address this issue, we studied Stroop performance in a cohort of 18 MPH-treated prepubescent boys with ADHD and six healthy controls on and off MPH treatment conditions. MPH significantly improved performance in both groups, with the ADHD participants consistently displaying worse scores than those of controls both on and off MPH. These results suggest that though the diagnostic value of the Stroop task in ADHD remains controversial, it has heuristic value for monitoring clinical responses to MPH treatment. More research is needed to ascertain the clinical significance of our findings and to replicate this relatively small effect in a larger cohort, to determine whether MPH effects on Stroop performance are specific to ADHD symptoms or they generalize to other forms of symptomatology.     

Methylphenidate differentially regulates c-fos and fosB expression in the developing rat striatum

Methylphenidate (MPH, Ritalin) is a psychostimulant drug used in very young children with attention deficit hyperactivity disorder (ADHD). To explore the central effects of MPH, we compared repeated MPH treatments on c-fos and fosB expression in the striatum of immature and adult rats. Prepubertal (PD25-38) or adult (PD53-66) male rats were treated once daily for: (a) 14 days with either saline or MPH (2 or 10 mg/kg) or (b) 13 days with saline followed by a single dose of MPH (2 or 10 mg/kg) on day 14. To determine long-term effects of MPH, another group of prepubertal rats was allowed a drug-free period of 4 weeks following the initial 14 days of treatment, and received a challenge dose of MPH at adulthood. All rats were sacrificed 2 h post-injection on the final day. Expression of c-fos and fosB was quantified by densitometric analysis of cFOS and FOSB-immunoreactivity (-ir). We demonstrated that FOSB-ir was increased by a single dose of MPH in the prepubertal and adult striatum, and this effect was further elevated by chronic MPH in prepubertal rats, in contrast to the inhibitory effect of MPH (2 and 10 mg/kg) on cFOS-ir. In adult rats, repeated MPH down-regulated cFOS-ir only at the higher dose (10 mg/kg), while fosB expression remained at levels comparable to acute MPH. The reduction in cFOS-ir observed in prepubertal rats given repeated MPH (10 mg/kg) persisted in the adult striatum following MPH challenge at adulthood. Our results suggest that (1) repeated MPH treatment differentially regulates c-fos and fosB expression in the immature and adult brain; (2) MPH-induced changes in gene expression may be enduring, and (3) the immature brain is more sensitive to the stimulant effects of MPH than the adult. Thus, our findings have implications for the long-term use of MPH in ADHD.     

Attention deficit disorder: multidisciplinary observational study over 1 year

Introduction

In France, attention deficit disorder (ADHD) has traditionally met with two opposing approaches (biological and psychoanalytic). This conflict led us to conduct a multidisciplinary observational study, on a group of 36 children over a period of 1 year.

Methods

Thirty-six children with ADHD diagnostic (DSM IV), not treated by MPH were included. Initial “multi-field” evaluation (T0) consisted of: neuro-paediatric consultation (Conners questionnaire, Child Behaviour Checklist, reading and writing scores by French tests); semi-structured child psychiatric interview (DSM-IV axis I), structural hypothesis (CFTMEA), existence of narcissistic fragility, parents/child interactions; neuropsychological standardized evaluation (attention and executive functions); psychodynamic interview and projective tests (Rorscharch, CAT or TAT). A therapeutic project is proposed combining MPH and psychotherapy according to the results. A new evaluation 1 year later (T1) included a consultation and a neuropsychological evaluation.

Results T0

All parental questionnaires appreciating attention deficit and hyperactivity/impulsivity were significantly pathological. The neuropsychological evaluation showed usual characteristics of ADHD with individual differences. The psychiatric evaluation revealed the frequency of comorbidity in axis I (23% of children with more than two diagnoses, 57% with anxiety disorder, 23 and 3% with oppositional and conduct disorder).

Follow up (T1)

Thirty-one children were re-examined (20 treated by MPH and 11 not treated because of parental refusal or particular psychopathological situations). Psychoanalytical psychotherapy, proposed to 28 children, was undertaken with only 19. An improvement in scores for attention and executive tests was registered only in the treated group.

Discussion

The tests confirm deficits of attention and executive functions without correlation with the scores of questionnaires, underlining the need for a neuropsychological evaluation to objectify attention disorders. Projective tests refine and enrich psychiatric evaluation and showed that half of the children had borderline organization. However, structural hypotheses were heterogeneous, suggesting the need for specific therapeutic projects to be devised according to each child. The treated children were the only ones to improve attention deficit. On the other hand, the scores of anxiety are not improved by MPH, emphasizing the indications of psychotherapy if comorbidity is present. Psychotherapeutic care was carried out only among part of the population, because of parental reservations, exacerbated by differences of opinion among professionals and lack of access.

Conclusion

This study is innovative, providing precise data on ADHD from a multidisciplinary perspective. Psychopathological comorbidity is high in this population, so the concept of ADHD cannot be limited to a cognitive point of view. These elements and doubts regarding the efficacy of behavioural therapies suggest the need for a rigorous evaluation of analytical psychotherapies independent of MPH to treat attention deficit.     

Naturalistic exploration of the effect of osmotic release oral system-methylphenidate on remission rate and functional improvement in Taiwanese children with attention-deficit-hyperactivity disorder

Aim: To determine the differences in the remission rate, recovery rate, functional improvement, and treatment adherence related to treatment with short‐acting immediate‐release methylphenidate (IR‐MPH) and long‐acting osmotic‐release oral system‐methylphenidate (OROS‐MPH) in a naturalistic setting among Taiwanese children with attention‐deficit–hyperactivity disorder (ADHD). Methods: A total of 757 children with ADHD, aged 6–18 years, was evaluated using the following in order determine functional improvement and treatment adherence: the Chinese version of the Swanson, Nolan, and Pelham, version IV scale (SNAP‐IV‐C), Clinical Global Impression‐ADHD‐Severity (CGI‐S) to measure remission and recovery rates, the Chinese version of the Social Adjustment Inventory for Children and Adolescents (CSAICA), and caregiver's satisfaction rate, treatment adherence, and frequency of adverse effects. Results: According to the SNAP‐IV‐C scores, the remission rate was 30.72%, and the recovery rate was 16.38%. Compared to short‐acting IR‐MPH, OROS‐MPH was associated with greater functional improvement and treatment adherence among children with ADHD. Conclusion: OROS‐MPH treatment at the adequate dosage can achieve higher remission and recovery rates, produce greater functional improvement, and result in better treatment adherence than IR‐MPH treatment.