Immediate-release Methylphenidate Research Articles

The efficacy of atomoxetine for the treatment of children and adolescents with attention-deficit/hyperactivity disorder: a comprehensive review of over a decade of clinical research.

Atomoxetine was first licensed to treat attention-deficit/hyperactivity disorder (ADHD) in children and adolescents in the US in 2002. The aim of this paper is to comprehensively review subsequent publications addressing the efficacy of atomoxetine in 6- to 18-year-olds with ADHD. We identified 125 eligible papers using a predefined search strategy. Overall, these papers demonstrate that atomoxetine is an effective treatment for the core ADHD symptoms (effect sizes 0.6-1.3, vs. placebo, at 6-18 weeks), and improves functional outcomes and quality of life, in various pediatric populations with ADHD (i.e., males/females, patients with co-morbidities, children/adolescents, and with/without prior exposure to other ADHD medications). Initial responses to atomoxetine may be apparent within 1 week of treatment, but can take longer (median 23 days in a 6-week study; n=72). Responses often build gradually over time, and may not be robust until after 3 months. A pooled analysis of six randomized placebo-controlled trials (n=618) indicated that responses at 4 weeks may predict response at 6-9 weeks, although another pooled analysis of open-label data (n=338) suggests that the probability of a robust response to atomoxetine [≥40% decrease in ADHD-Rating Scale (ADHD-RS) scores] may continue to increase beyond 6-9 weeks. Atomoxetine may demonstrate similar efficacy to methylphenidate, particularly immediate-release methylphenidate, although randomized controlled trials are generally limited by short durations (3-12 weeks). In conclusion, notwithstanding these positive findings, before initiating treatment with atomoxetine, it is important that the clinician sets appropriate expectations for the patient and their family with regard to the likelihood of a gradual response, which often builds over time.

Osmotic Release Oral System Methylphenidate is More Effective Than Immediate Release Methylphenidate: A Retrospective Chart Review in Turkish Children with Attention Deficit Hyperactivity Disorder

ABSTRACTObjective: The aim of this study was to evaluate the efficacy and safety of osmotic release oral system methylphenidate (OROS-MPH) compared with immediate release methylphenidate (IR-MPH) in Turkish children with attention deficit hyperactivity disorder (ADHD).Method: The medical records of primary school-aged children, who were first-time referrals to the outpatient clinic, were reviewed; 67 children receiving OROS-MPH and 47 children receiving IR-MPH were recruited for the study. A total of 114 children receiving treatment for ADHD were evaluated over 8 weeks.Results: The total Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale scores from both the parent and teacher forms decreased significantly in both groups over 8 weeks (p<0.001). OROS-MPH was found to be superior to IR-MPH when comparing baseline-to-8th-week- mean inattention score changes on both the teacher (p=0.007) and parent (p=0.015) forms. OROS-MPH and IR-MPH were both well tolerated, with similar ...

Steady-state bioavailability of extended-release methylphenidate (MPH-MLR) capsule vs. immediate-release methylphenidate tablets in healthy adult volunteers.

The objective of the study was to determine the relative bioavailability of an extended-release multilayer bead formulation of methylphenidate hydrochloride (MPH-MLR) 80mg vs. methylphenidate immediate-release (IR; Ritalin(®)) tablets as single and multiple doses in the fed state. A single-center, multiple-dose, randomized, open-label, two-period crossover study conducted in 26 healthy adults assigned to 4days of once-daily MPH-MLR 80mg or IR methylphenidate 25mg three times daily. MPH-MLR 80mg produced reproducible biphasic profiles of plasma methylphenidate concentrations characterized by a rapid initial peak, followed by a moderate decline reaching a plateau ~5 h post dose, then a gradual increase culminating in an attenuated second peak ~7h post dose. Maximum concentration was lower for MPH-MLR 80mg than IR methylphenidate 25mg three times daily on day 1 (23.70 vs. 31.47ng/mL); exposure was similar. The geometric mean ratios (MPH-MLR/IR methylphenidate [90% CI]) of log-transformed area under the plasma drug concentration-time curve to the last measurable observation (day 1: 0.88 [84.75-91.80]; day 4: 0.84 [81.16-86.94]), and area under the plasma drug concentration extrapolated to infinity (day 1: 0.93 [88.57-97.28]; day 4: 0.88 [84.48-91.17]) were within the 80-125% bioequivalence range. The mean±SD MPH-MLR 80-mg capsule day 4 area under the plasma drug concentration vs. time curve from 0 to 4h (74.5±15.2ng·h/mL) was greater than IR methylphenidate 25mg three times daily (66.0±17.4ng·h/mL), confirming steady-state levels during the study period. All treatment regimens were safe and well tolerated. MPH-MLR 80-mg capsule once daily or IR methylphenidate 25mg three times daily provides comparable maximum methylphenidate concentrations and systemic exposure in the fed state.

Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

Symptoms of attention deficit hyperactivity disorder (ADHD), diagnosed mainly in children, often persist into adulthood. Adults in this group have a high rate of other psychiatric problems and functional difficulties in a number of key areas such as academic achievement, interpersonal relationships, and employment. Although the usefulness of immediate-release methylphenidate in children has been extensively studied, studies in adults, which are few, demonstrate varying results. To evaluate the efficacy and tolerability of immediate-release methylphenidate versus placebo in the treatment of adults with ADHD. We searched the following databases in November 2013: CENTRAL, Ovid MEDLINE, EMBASE, PsycINFO, Database of Abstracts of Reviews of Effects (DARE), and two trials registers. Biosis was searched in December 2013. We inspected references of all relevant papers to identify more studies and contacted authors of recently published trials. We included all randomized trials comparing immediate-release methylphenidate versus placebo in participants aged 18 years or older with ADHD. We excluded trials conducted on subpopulations of adults with ADHD such as adults with both ADHD and substance dependence. Two review authors independently selected trials, extracted data, and assessed trial risk of bias. We contacted authors of trials to ask for additional and missing data. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs. Results from the 11 randomized controlled trials (474 participants, counting participants from cross-over studies as a single arm, and counting both arms from parallel studies) included in the review demonstrated improvement in core clinical ADHD symptoms of hyperactivity, impulsivity, and inattentiveness, and overall improvement. We were able to pool results from 10 studies, which included 466 participants.Most included studies were judged to have unclear risk of bias for most categories. However, as all studies were randomized, double-blind, and placebo-controlled and, in general, did not contain factors that significantly decreased the quality of the body of evidence, the quality of evidence was assessed as "high" for most outcomes according to the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. For one outcome-inattentiveness-most information came from studies at unclear risk of bias, and so the quality of evidence for this outcome was judged as "moderate."Results are given as SMD for each of the core clinical symptoms of ADHD. In all cases, participant numbers were calculated by counting participants in a single arm from cross-over studies and in both arms from parallel studies. The SMD for the outcome of hyperactivity was -0.60 (95% CI -1.11 to -0.09, 6 studies, number of participants (n) = 245, high-quality evidence) in favor of immediate-release methylphenidate; the SMD for impulsivity was -0.62 (95% CI -1.08 to -0.17, 5 studies, n = 207, high-quality evidence) in favor of immediate-release methylphenidate; and the SMD for inattentiveness was -0.66 (95% CI -1.02 to -0.30, 7 studies, n = 391, moderate-quality evidence) in favor of immediate-release methylphenidate. Moderate to extreme statistical heterogeneity was detected for all outcomes. Subgroup analysis comparing high versus low doses did not indicate that higher doses of immediate-release methylphenidate were associated with greater efficacy.For overall change, the SMD was -0.72 (95% CI -1.12 to -0.32, 9 studies, n = 455, high-quality evidence) in favor of immediate-release methylphenidate.The effects of immediate-release methylphenidate on anxiety and depression as parameters of general changes in mental state were equivocal. Some trials reported reduction in depression and anxiety, others detailed no change, and still others described an increase in depressive and anxious symptoms.The most common adverse effect was loss of appetite, in some cases with weight loss. Although no study reported either of these effects as problematic or severe, the included studies were of short duration; thus clinical significance could not be properly assessed. Five studies reported changes in systolic or diastolic blood pressure, and three reported increases in heart rate. None of these results were judged to present cause for concern. No study reported clinically significant adverse effects-cardiovascular or other. Three studies did not mention adverse effects. We were unable to determine whether adverse effects were not discussed by study authors because none occurred, or because no data on adverse effects were collected. Data from randomized controlled trials suggest that immediate-release methylphenidate is efficacious for treating adults with ADHD with symptoms of hyperactivity, impulsivity, and inattentiveness, and for improving their overall clinical condition. Trial data suggest that adverse effects from immediate-release methylphenidate for adults with ADHD are not of serious clinical significance, although this conclusion may be limited, certainly in the case of weight loss, by the short duration of published studies.

Methylphenidate and dexmethylphenidate formulations for children with attention-deficit/hyperactivity disorder.

Current literature on the safety and efficacy of various intermediate- and long-acting preparations of methylphenidate and dexmethylphenidate for pediatric attention-deficit/hyperactivity disorder (ADHD) is reviewed. The efficacy of methylphenidate in controlling ADHD symptoms is firmly established. Given the drug's relatively short half-life in pediatric patients (about 2.5 hours), a number of intermediate- and long-acting products have been developed; these extended-release methylphenidate products provide the same efficacy as immediate-release (IR) formulations, with the convenience of less frequent dosing. Intermediate-acting methylphenidate preparations have effects lasting as long as 8 hours, but peak concentrations are not attained for up to 5 hours, and many patients may require twice-daily dosing. Long-acting methylphenidate products developed to address these challenges include a controlled-release tablet and bimodal-delivery capsules containing mixtures of IR and extended-release beads (durations of effect, 8-12 hours). Options for patients with difficulty swallowing tablets or capsules include a once-daily transdermal delivery system and a once-daily liquid formulation. Dexmethylphenidate (the more pharmacologically active d-isomer of racemic methylphenidate) can provide efficacy comparable to that of IR methylphenidate at half the dose; an extended-release form of dexmethylphenidate can provide less fluctuation in peak and trough concentrations than the IR form. Methylphenidate and dexmethylphenidate products in capsule form can be opened and sprinkled on applesauce. The various formulations of IR and intermediate- and extended-release methylphenidate and dexmethylphenidate can be useful options in satisfying patients' individual needs in the management of ADHD. All are equally efficacious in controlling ADHD symptoms.

Severity But Not Comorbidities Predicts Response to Methylphenidate in Adults With Attention-Deficit/Hyperactivity Disorder

Although the identification of reliable predictors of methylphenidate response in adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide treatment decisions, very few data exist on this issue. Here, we assessed the predictors of clinical response to immediate-release methylphenidate hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of demographic factors, severity, and a wide range of comorbid psychiatric disorders. Two hundred fifty adult patients with ADHD were evaluated and completed a short-term treatment with IR-MPH. Mental health diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria through the use of standard structured interviews. The Swanson, Nolan, and Pelham Rating Scale, version 4, adapted to adults was used to assess the severity of ADHD. In the linear regression model, only higher severity of ADHD was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of comorbidities in a subsample (n = 62) did not modify this pattern. Our findings suggest that in clinical settings, patients with more severe ADHD symptoms have a good response to treatment independently from the presence of mild or stabilized comorbidities and their treatments. For adults with ADHD, differently from other common psychiatric disorders such as depression and anxiety, higher severity is associated with better treatment response.

A head-to-head randomized clinical trial of methylphenidate and atomoxetine treatment for executive function in adults with attention-deficit hyperactivity disorder

Results regarding the effects of methylphenidate and atomoxetine on executive functions were inconsistent and no study has directly compared the efficacy of these two medications in improving executive functions in adults with attention-deficit hyperactivity disorder (ADHD). We conducted an 8-10 wk, open-label, head-to-head, randomized clinical trial involving adults with a clinical diagnosis of ADHD confirmed by psychiatric interview. The two treatment arms were immediate-release methylphenidate (IR-methylphenidate) (n = 31) and atomoxetine once daily (n = 32). Executive functions were assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB), including spatial working memory, spatial span, intra-extra dimensional set shifts, rapid visual information processing and Stockings of Cambridge (SOC). In addition to the symptom assessments at baseline (week 0), visit 2 (week 4-5) and visit 3 (week 8–10), they received CANTAB assessments at baseline and visit 3 (60.4 ± 6.3 d). Compared to baseline, adults treated with atomoxetine showed significant improvement in spatial working memory, spatial short-term memory, sustained attention and spatial planning at visit 3; adults treated with IR-methylphenidate showed significant improvement in spatial working memory at visit 3. Comparing the magnitude of improvement in executive functions between these two medications, the effect was generally similar for the two groups, although atomoxetine might have significantly greater efficacy than IR-methylphenidate in terms of improving spatial planning (SOC). Our results provide evidence to support that both IR-methylphenidate and atomoxetine improved various executive functions in adults with ADHD with greater improvement in atomoxetine than IR-methylphenidate in spatial planning.

Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies

BackgroundThe stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed.The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection.MethodsA systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included.ResultsOf 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study.ConclusionsEmerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation. No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment. For patients achieving suboptimal symptom control, switching long-acting MPH formulations may be beneficial. When switching formulations, it is usually appropriate to titrate the immediate-release component of the formulation; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components. Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response.

Effects of Extended Release Methylphenidate Treatment on Ratings of Attention-Deficit/Hyperactivity Disorder (ADHD) and Associated Behavior in Children with Autism Spectrum Disorders and ADHD Symptoms

The purpose of this study was to examine the behavioral effects of four doses of psychostimulant medication, combining extended-release methylphenidate (MPH) in the morning with immediate-release MPH in the afternoon. The sample comprised 24 children (19 boys; 5 girls) who met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age=8.8 years, SD=1.7; mean intelligence quotient [IQ]=85; SD=16.8). Effects of four dose levels of MPH on parent and teacher behavioral ratings were investigated using a within-subject, crossover, placebo-controlled design. MPH treatment was associated with significant declines in hyperactive and impulsive behavior at both home and school. Parents noted significant declines in inattentive and oppositional behavior, and improvements in social skills. No exacerbation of stereotypies was noted, and side effects were similar to those seen in typically developing children with ADHD. Dose response was primarily linear in the dose range studied. The results of this study suggest that MPH formulations are efficacious and well-tolerated for children with ASD and significant ADHD symptoms.

PMH40 - Once-a-day extended-release versus two-times-daily immediate-release methylphenidate for the treatment of adhd - A cost minimization study

PMH40 - Once-a-day extended-release versus two-times-daily immediate-release methylphenidate for the treatment of adhd - A cost minimization study

A review of medications used in the treatment of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is one of the most common developmental disorders in children and adolescents with core symptoms of hyperactivity, impulsivity andinattention. Atomoxetine, immediate-release methylphenidate and extended release methylphenidate are approved for use in patients with ADHD in Slovenia. In addition, ADHD is also treated off-label with bupropion, tricyclic antidepressants and some other drugs. According to the recently adopted American and European guidelines, pharmacotherapy includes the initial, maintenance and terminal phase. Consideration of pharmacokinetic parameters of the selected drugs and potential drug-drug interactions, if the patient is taking other medications, helps to reduce symptoms of ADHD, and improves the selection of drug and appropriate dosing regimen. Clinical outcomes should be measured by standardised questionnaires. The drug of choice is methylphenidate. Guidelines for the treatment of ADHD should also include recommendations on psychosocial treatments and destigmatization of patients with this disorder. In this paper, pharmacotherapy guidelines for patients with ADHD are highlighted.

Response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study

Background:The purpose of this multicenter Spanish study was to evaluate the response to immediate-release methylphenidate by children and adults diagnosed with attention-deficit/hyperactivity disorder (ADHD), as well as to obtain information on current therapy patterns and safety characteristics.Methods:This multicenter, observational, retrospective, noninterventional study included 730 patients aged 4–65 years with a diagnosis of ADHD. Information was obtained based on a review of medical records for the years 2002–2006 in sequential order.Results:The ADHD predominantly inattentive subtype affected 29.7% of patients, ADHD predominantly hyperactive-impulsive was found in 5.2%, and the combined subtype in 65.1%. Overall, a significant lower Clinical Global Impression (CGI) score and mean number of DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision) symptoms by subtype were found after one year of treatment with immediate-release methylphenidate; CGI decreased from 4.51 to 1.69, symptoms of inattention from 7.90 to 4.34, symptoms of hyperactivity from 6.73 to 3.39, and combined subtype symptoms from 14.62 to 7.7. Satisfaction with immediate-release methylphenidate after one year was evaluated as “very satisfied” or “satisfied” by 86.90% of the sample; 25.75% of all patients reported at least one adverse effect. At the end of the study, 41.47% of all the patients treated with immediate-release methylphenidate were still receiving it, with a mean time of 3.80 years on therapy.Conclusion:Good efficacy and safety results were found for immediate-release methylphenidate in patients with ADHD.

Effect of Ferritin on Short-Term Treatment Response in Attention Deficit Hyperactivity Disorder.

Several studies have shown that iron deficiency and ferritin levels are associated with parent and teacher Attention Deficit Hyperactivity Disorder (ADHD) ratings. Although there are conflicting results, it has also been reported that iron supplementation may help to decrease ADHD symptoms. When all these previous studies are taken into account, it is clear that a large study investigating the effects of iron deficiency and ferritin levels on routine pharmacological treatment of ADHD with stimulants would be helpful to elucidate this treatment from a clinical point of view. A total of 345 subjects with combined or predominantly hyperactive-impulsive (PHI) subtypes of ADHD were included. All diagnoses were based on the DSM-IV criteria and ascertained by direct interviews conducted by the authors, who are experienced child psychiatrists certified in the use of the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL) semi-structured interview. The two treatment response criteria were: 1) 25% or more decrease in pre-treatment Conners Parent Rating Scale (CPRS) and Conners Teacher Rating Scale (CTRS) Hyperactivity (HA) and Total Problems scores; 2) CPRS and CTRS HA scores lower than the cut-off point ("very improved"). A total of 255 (73.9%) patients were on OROS-methylphenidate (OROS-MPH) and 90 (26.1%) were on immediate release methylphenidate (IR-MPH). The mean±sd of OROS-MPH and IR-MPH doses were 28.8±8.1 and 20.9±7.1 mg, respectively. More than half (52.5%) of the subjects were previously drug-naive at treatment inception. Two hundred and seventy eight (80.6%) subjects had combined subtype ADHD and the remainder had predominantly hyperactive-impulsive subtype. Only 60 (17.4%) of the subjects had no comorbid disorders, while 38.3% had one comorbid disorder, 32.8% had two comorbid disorders, and 11.6% had three or more comorbid disorders. The most frequent comorbidity was Oppositional Defiant Disorder/Conduct Disorder (ODD/CD, 51.6%), followed by Learning Disabilities (LD, 35.4%) and Anxiety Disorders (AD, 15.9%). Logistic regression analysis showed that subjects with comorbid ODD/CD and LD were less likely to respond to treatment. Ferritin levels and iron deficiency were not associated significantly with outcomes. In a large sample of subjects with combined or predominantly hyperactive-impulsive subtypes of ADHD, after controlling for several factors, we found that neither iron deficiency (ferritin <12 ng/ml) nor ferritin levels were associated with less favorable short-term treatment outcomes with stimulants. Subjects with comorbid ODD/CD and LD were less likely to have a 25% or more decrease in CTRS Total score. The presence of ODD/CD was also a negative predictor of treatment response in terms of CPRS Total and HA scores. The lack of a negative treatment response in ADHD subjects with iron deficiency and lack of a negative association with ferritin levels suggest that the relationship between iron metabolism and ADHD, a highly heterogeneous disorder, may be more complicated than previously believed.

Pharmacologic Intervention for Attention-Deficit Hyperactivity Disorder in Preschoolers

Pharmacologic intervention for attention-deficit hyperactivity disorder (ADHD) in preschool children is a controversial issue. Non-pharmacologic interventions (psychosocial and restricted dietary interventions) have been shown to benefit oppositional, non-compliant, aggressive and disruptive, as well as hyperactive and inattentive behaviors in preschoolers with ADHD and other disruptive behavior disorders. However, not all families have access to non-pharmacologic interventions or prefer them. The Preschool ADHD Treatment Study recently provided evidence of benefit with immediate-release methylphenidate; however, effect sizes were small to moderate and preschoolers had a high rate of adverse effects and a unique adverse effect profile. Furthermore, no information is available about long-term safety and effects of psychopharmacologic agents on the rapidly developing brains of preschoolers. Based on current evidence and guidelines, a careful trial with psychopharmacologic agents is indicated to treat ADHD in preschoolers if there is no improvement with behavior therapy and the preschoolers continue to exhibit significantly impaired hyperactive and inattentive symptoms. Preschoolers should be monitored closely for adverse effects and tried off medications after 6 months to assess the need for ongoing psychopharmacologic intervention. Further research is needed to identify predictors and moderators of response to guide individualized/optimal treatment options for ADHD in preschoolers.

P.7.d.002 The relationship between sleep duration and inflammatory markers in Korean adolescents

This study aims to investigate the short-term efficacy and tolerability of immediate-release methylphenidate (IR-MPH) in children with a history of traumatic brain injury (TBI).Twenty children with TBI (mean age: 12.7 ± 3.1 years) who had clinically significant attention deficit and/or hyperactivity-impulsivity symptoms and twenty children with primary Attention Deficit Hyperactivity Disorder (ADHD) (mean age: 12.3 ± 3.05 years) were included. Study measures, which included the Turgay DSM-IV based ADHD rating Scale (T-DSM-IV-S), Conners’ Parent Rating Scale (CPRS), Conners’ Teacher Rating Scale (CTRS-R) and Clinical Global Impression-Improvement Scale (CGI-I), were completed at the baseline for both of the groups. For the TBI group, study measures and an adverse effect scale developed by the authors were completed 8 weeks after IR-MPH treatment (10 mg dose t.i.d).No significant difference was found regarding the baseline scale scores between the study groups. Among children with TBI, most of the scores on T-DSM-IV-S, CPRS and CTRS-R were found to improve significantly after MPH treatment, (p < 0.05). 70% (N = 14) of the sample were much improved at the endpoint. MPH was generally well-tolerated (95% had either no adverse effect or mild adverse effects).In this preliminary open-label study, IR-MPH was found as a safe and effective treatment option for ADHD symptoms after TBI. However, future controlled studies are needed to confirm our findings.

The family impact in children and adolescent with ADHD after the switch of treatment from immediate-release MPH to OROS-MPH

The family impact in children and adolescent with ADHD after the switch of treatment from immediate-release MPH to OROS-MPH

Remission in Children and Adolescents Diagnosed with Attention-Deficit/Hyperactivity Disorder via an Effective and Tolerable Titration Scheme for Osmotic Release Oral System Methylphenidate

The purpose of this study was to identify the optimal dose of osmotic release oral system methylphenidate (OROS-MPH) using a dosage forced-titration scheme to achieve symptomatic remission in children with attention- deficit/hyperactivity disorder (ADHD). We also evaluated the efficacy and safety of, and patient and parent satisfaction with, the change in therapy from immediate-release methylphenidate (IR-MPH) to OROS-MPH over 10 weeks. We recruited 521 children and adolescents aged 6-18 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of ADHD, who had received IR-MPH treatments (<70 mg/day) for at least 1 month. The treatment, switched from IR-MPH to OROS-MPH according to a conversion scheme, started with a 6-week forced-titration phase of OROS-MPH to achieve symptomatic remission (defined as a score of 0 or 1 for each of the first 18 ADHD items in the Chinese version of the Swanson, Nolan, and Pelham, Version IV [SNAP-IV]), followed by a 4-week maintenance phase. The global ADHD severity and drug side effects of the participants were evaluated. Parents completed the ratings scales for the ADHD-related symptoms. Patient and parent satisfaction for the OROS-MPH treatment was also assessed. Among the 439 participants with ADHD who completed the trial, 290 participants (66.1%) achieved symptomatic remission. The mean dose of OROS-MPH among participants in remission was 36.7 mg (1.08 mg/kg) per day. Increased efficacy, superior satisfaction, and safety equivalent to that of IR-MPH were demonstrated in intra-individual comparisons from the baseline to the end of study. Determinants for remission included less severe ADHD symptoms (SNAP-IV score < 40), no family history of ADHD, and an appropriate dosage of medication according to the patient's weight. The findings suggest remission as a treatment goal for ADHD therapy by providing an optimal dosage of medication for children and adolescents with ADHD through using an effective and tolerable forced-titration scheme.

Modulation of Attention-Deficit/Hyperactivity Disorder Symptoms by Short- and Long-Acting Methylphenidate over the Course of a Day

The purpose of this study was to investigate whether a long-acting methylphenidate formulation (MPH-ret) is as effective as two doses of immediate-release methylphenidate (MPH-IR) in reducing attention-deficit/hyperactivity disorder (ADHD) symptoms including inattention, impulsivity, and hyperactivity during the course of the day. Two groups of children (n=18 each) with ADHD aged between 8 and 12 years completed a continuous performance test in combination with a motion-tracking system four times a day within 8 hours. Inattention (standard deviation of reaction time), impulsivity (commission error rate), and hyperactivity (path length of the headband) were simultaneously measured. We included a control group (n=20) to rule out circadian fluctuations of attentional performance and motor activity. We observed a postlunch dip in attentional performance and an increasing trend of motor activity throughout the day whereas impulsivity remained stable in controls. The MPH-ret and MPH-IR groups had comparable treatment effects on measures of hyperactivity and inattention and normalized participant performance to control levels. In contrast, MPH-IR seems to have an advantage over MPH-ret in impulsivity treatments. Thus, our data suggest that it is crucial to assess the different domains of ADHD symptoms precisely over the course of a day to determine the optimal titration and stimulant formulation for a person with ADHD.

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

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). 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. 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. 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.

Exploring the Impact of Once-Daily OROS® Methylphenidate (MPH) on Symptoms and Quality of Life in Children and Adolescents with ADHD Transitioning from Immediate-Release MPH

Objectives: To explore the clinical and health-related quality of life (HRQoL) outcomes in children/adolescents with attention-deficit/hyperactivity disorder (ADHD) who required a therapy switch from immediate-release (IR) methylphenidate (MPH) and were initiated on Osmotic Release Oral System (OROS®) MPH. Methods: Prospective, noninterventional study including patients (aged 6–18 years) with a confirmed diagnosis of ADHD who transitioned from IR MPH to OROS® MPH based on medical needs. Patients were transitioned to OROS® MPH and were followed for 12 weeks. Attention-deficit/hyperactivity disorder symptoms, functional outcomes, HRQoL, and tolerability were assessed throughout the study. Results: 598 patients entered the intention-to-treat analysis. The mean OROS® MPH starting dose was 29.5 ± 12.0 mg/day, increasing slightly to 33.5 ± 13.2 mg/day at final visit. Compared with baseline, there were significant (all P < 0.0001) symptomatic, functional, and HRQoL improvements after transitioning from IR MPH to OROS® MPH as assessed by the Conners' Parent Rating Scale (from 29.0 ± 10.5 to 19.5 ± 11.1), Children's Global Assessment Scale (by 11.0 ± 13.3), and Inventory for Assessing Quality of Life (ILC) LQ0–28 scores (parents' rating from 17.2 ± 3.9 to 19.4 ± 4.0; patients' rating from 18.7 ± 4.0 to 20.5 ± 3.9). Overall, no significant changes in quality of sleep or appetite were observed. More than 70% of parents and physicians rated the effectiveness of OROS® MPH as at least “good” and were at least “satisfied” with OROS® MPH. The most common treatment-emergent adverse events were insomnia and anorexia. No clinically relevant changes in body weight or vital signs were observed. Conclusions: In this naturalistic setting, transitioning from IR MPH to OROS® MPH, in patients who showed previously insufficient response and/or poor tolerability, was successful. Patients' and parents' HRQoL as well as burden of disease showed a clinically relevant improvement. OROS® MPH was generally safe and well tolerated.