Methylphenidate Transdermal System Research Articles

Single- and Multiple-Dose Pharmacokinetics of Methylphenidate Administered as Methylphenidate Transdermal System or Osmotic-Release Oral System Methylphenidate to Children and Adolescents With Attention Deficit Hyperactivity Disorder

This was a 1-month, multicenter, open-label, randomized study to determine single- and multiple-dose pharmacokinetics of d,l-methylphenidate (MPH) after MPH transdermal system (MTS) and osmotic-release oral system MPH (OROS MPH) dosing in children (6-12 years) and adolescents (13-17 years) who had a diagnosis of attention deficit hyperactivity disorder. The pharmacokinetic population consisted of 33 children and 31 adolescents. Accumulation of d-MPH was 34% in children and 57% in adolescents after multiple fixed doses of MTS for 7 days and 76% and 94%, respectively, after 28 days of dosing. After 7 days of OROS MPH dosing, accumulation was 16% in children and 19% in adolescents; fixed doses of OROS MPH were not studied beyond 7 days. After escalating the doses to 30 mg per 9 hours for MTS, accumulation was 73% in children and 83% in adolescents after allowing for dose escalation. Corresponding values for OROS MPH after dose escalation to 54 mg were 33% in both age groups. Plasma l-MPH concentrations were approximately half those of d-MPH for MTS and negligible for OROS MPH. Overall, MTS accumulation was above that expected for single-dose pharmacokinetics of MTS and OROS MPH in both age groups. As a result of accumulation, systemic exposure to d-MPH in children after multiple escalating doses was 1.4- to 1.6-fold higher for MTS compared with OROS MPH, but similar in adolescents for both formulations. After all dosing, systemic exposure was greater in children compared with adolescents, consistent with lower body weight in children. Adverse events were mild to moderate for both formulations, and MTS dermal responses were mild.

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Back to table of contents Previous article Next article Med CheckFull AccessMed CheckMark MoranMark MoranSearch for more papers by this authorPublished Online:1 Oct 2010https://doi.org/10.1176/pn.45.19.psychnews_45_19_028Regulatory Briefs•. The Food and Drug Administration's (FDA) Anesthetic and Life-Support Drugs Advisory Committee voted in August to expand indications for the antidepressant medication Cymbalta (duloxetine) to include treatment of chronic pain. By a vote of 8 to 5, with one abstention, the committee voted “yes” in answer to the following question: “Does the data from the clinical trials provide adequate evidence of efficacy for the management of chronic low back pain?” But by a vote of 9 to 4, with one abstention, the committee voted “no” in answer to the question: “Does the data from the clinical trials provide adequate evidence of efficacy for the treatment of chronic pain due to osteoarthritis?”•. The FDA approved supplemental new drug applications for Saprhis (asenapine) sublingual tablets to expand the product's indications for the treatment of schizophrenia in adults as monotherapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder. It also approved the tablets as adjunctive therapy with either lithium or valproate for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.Saphris was initially approved in the United States in August 2009 for the acute treatment of schizophrenia in adults and as monotherapy for the acute treatment of manic or mixed episodes associated with bipolar I disorder with or without psychotic features in adults.Industry Briefs•. Silenor (doxepin) is now available in the United States for treatment of insomnia characterized by difficulty with sleep maintenance. The FDA approved the drug for that indication in March. The drug is manufactured by Somaxon Pharmaceuticals in San Diego. The company signed an agreement in August with Procter and Gamble's health care division to co-promote Silenor in the United States.•. Shire announced in August the divestiture of Daytrana (methylphenidate transdermal system) to Noven Pharmaceuticals. Daytrana, which is approved and marketed in the United States for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, will continue to be available for patients through Noven. The FDA approved Daytrana as a treatment for ADHD in children in April 2006 and adolescents this past June.•. Roche and reMYND announced an agreement to develop novel therapeutics to slow neurodegeneration in Parkinson's and Alzheimer's patients by inhibiting alpha-synuclein and tau toxicity. The collaboration will focus on two of reMYND's preclinical, small-molecule programs targeting alpha-synuclein and tau-related pathologies. Roche will be responsible for preclinical and clinical development and for worldwide commercialization, while reMYND will continue to conduct nonclinical pharmacology studies to elucidate underlying molecular mechanisms. ReMYND's compounds are believed to inhibit alpha-synuclein neurotoxicity in Parkinson's disease and tau neurotoxicity in Alzheimer's disease. As such they are considered to be disease modifying, as opposed to merely symptom treatments.Research Briefs•. Eli Lilly and Co. announced in August that it plans to halt the development of semagacestat, a potential treatment for Alzheimer's disease. Two phase 3 trials showed that the treatment did not slow the progression of the disease and had an adverse effect on cognition and ability to perform daily activities. The studies also showed that semagacestat was associated with an increased risk of skin cancer.•. Rexahn Pharmaceuticals Inc. announced in September that it has submitted a phase 2b protocol to the FDA for the clinical study of Serdaxin for treatment of major depressive disorder. The phase 2b study will assess Serdaxin's efficacy as a treatment for major depressive disorder in approximately 300 subjects. The planned double-blind, randomized, placebo-controlled trial will be conducted at multiple sites in the United States and will measure the change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) as the primary efficacy endpoint. ISSUES NewArchived

A Randomized, Double-Blind, Multicenter, Parallel-Group, Placebo-Controlled, Dose-Optimization Study of the Methylphenidate Transdermal System for the Treatment of ADHD in Adolescents

The current report evaluates the efficacy and safety of methylphenidate transdermal system (MTS) compared with placebo transdermal system (PTS) in adolescents with attention-deficit/hyperactivity disorder (ADHD). A total of 217 subjects participated in a 7-week, randomized, double-blind, multicenter, parallel-group, placebo-controlled, dose-optimization study of MTS (10-, 15-, 20- or 30-mg/9 hours). Subjects were randomized into a 2:1 MTS to PTS ratio and titrated to an optimal dose during an initial 5-week period. Subjects maintained their optimal dose through a subsequent 2-week period. The primary outcome measure was the ADHD-Rating Scale-IV (ADHD-RS-IV). Safety of MTS was assessed throughout the study by analyzing adverse events, results of physical examinations, laboratory evaluations, vital sign data, electrocardiograms, and dermal evaluations. Treatment with MTS demonstrated greater reductions from baseline in ADHD-RS-IV total score compared to PTS at endpoint (P%lt;.0001). The majority of the adverse events (98.5%) were mild or moderate in intensity, the most common of which were decreased appetite, headache, irritability, and upper respiratory tract infection. Three subjects in the MTS group discontinued because of an application site reaction. MTS therapy was generally well-tolerated and resulted in significantly greater improvements in ADHD symptoms in adolescents when compared to PTS.

Methylphenidate Transdermal System in Adults With Past Stimulant Misuse

Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the Clinical Global Impression (CGI) ratings and substance abuse as quantified by urine drug screens and self-reported use. Results: Significant improvements from baseline were found on both the WRAADS and CGI measurements. No abuse of the study medication was observed. Conclusion: The findings suggested that MTS may improve ADHD symptoms in adults with a history of stimulant misuse; however, there were limitations. The study data showed the need for subsequent randomized studies that further explore findings made in this study.

A Controlled Trial of the Methylphenidate Transdermal System on Before-School Functioning in Children With Attention-Deficit/Hyperactivity Disorder

Children with attention-deficit/hyperactivity disorder (ADHD) frequently manifest behavioral difficulties in the morning prior to school. Our aim was to examine the effects of the methylphenidate transdermal system (MTS) on before-school ADHD symptoms and functioning in children with ADHD. In this randomized crossover study, conducted from May 2007 until December 2008, 6- to 12-year-old subjects with DSM-IV-defined ADHD received either MTS or a placebo transdermal system (PTS) at 10 mg for 1 week and then 20 mg for 1 week. Subjects were then crossed over directly to the other treatment for the remaining 2 weeks. The primary efficacy measure was the ADHD Rating Scale. All analyses were intent to treat, with the last observation carried forward. Thirty subjects completed at least 1 week of treatment, and 26 subjects completed the entire protocol. The sample was primarily male, with a mean +/- SD age of 9.17 +/- 1.84 years. Compared to PTS, there were significant reductions with MTS in the ADHD Rating Scale score (P < .001). Adverse effects of MTS during the active (versus PTS) phase were similar to those seen in other controlled trials of MTS. These results show that MTS is effective not only for morning ADHD symptoms, but also in improving associated activities and functioning that occur before school in children with ADHD. clinicaltrials.gov Identifier: NCT00586157.

Attention-Deficit Hyperactivity Disorder

Throughout this decade, there has been significant research into pharmacotherapies for attention-deficit hyperactivity disorder (ADHD). This article considers the efficacy and safety of five of the more novel long-acting pharmacological treatments recently approved by the FDA for marketing in the US for paediatric ADHD, along with an alpha(2)-adrenoceptor agonist in preparation. Reviewed treatments include the non-stimulant atomoxetine, three novel extended-release (XR) stimulant preparations: dexmethylphenidate, lisdexamfetamine dimesylate and the methylphenidate transdermal system (TDS), and the recently approved XR alpha(2)-adrenoceptor agonist, guanfacine. Dexmethylphenidate XR is a stimulant treatment in a single isomer form, and has an efficacy and tolerability similar to two doses of immediate-release (IR) dexmethylphenidate when taken 4 hours apart, but is dosed at half of the usual d,l-methylphenidate dose. Dexmethylphenidate XR utilizes a beaded bimodal release, with 50% initially released and another 50% released 4 hours later to provide benefit lasting up to 10-12 hours. Lisdexamfetamine was the first stimulant treatment approved as a prodrug, whereby the single isomer d-amfetamine remains pharmacologically inactive until activated by cleaving the lysine. Its efficacy and tolerability are generally consistent with that of XR mixed amfetamine salts, with this activation method and more consistent absorption generally resulting in up to an 11- to 13-hour benefit. The methylphenidate TDS patch utilizes skin absorption to provide predictable and uniform delivery of methylphenidate when worn for 9 hours/day. The efficacy and tolerability of the methylphenidate TDS patch is generally consistent with that of osmotic-controlled release oral system (OROS) methylphenidate, providing benefit for about 11-12 hours. Because of their formulation, lisdexamfetamine and methylphenidate each have an onset of effect at about 2 hours after administration. An adjustable wear time for the methylphenidate TDS patch accommodates related adverse effects, but its disadvantages are frequent skin irritation and the need to remember to take the patch off. Atomoxetine is the first non-stimulant treatment approved by the FDA and employs weight-based dosing up to 1.4 mg/kg/day. Benefit is generally observed within 2-8 weeks of initiation and is considered to have a lesser therapeutic effect than that of stimulants. A recent parallel-group controlled study found that atomoxetine (up to 1.8 mg/kg/day) and OROS methylphenidate both improved ADHD symptoms, although subjects receiving OROS methylphenidate had a significantly better response. Interestingly, treatment-naive children had a similar beneficial response to atomoxetine as those receiving OROS methylphenidate. Subsequent crossover treatment revealed a subgroup of youths who did not respond well to OROS methylphenidate but did respond to atomoxetine. Also identified was a larger than expected subgroup who did not respond well to either active treatment, confirming the need to continue the pursuit of novel treatments. As of September of 2009, guanfacine in XR form is the first alpha(2)-adrenoceptor agonist to gain approval to treat ADHD, approved for the treatment of 6- to 17-year olds. A second alpha(2)-adrenoceptor agonist, clonidine, is in development as a potential XR treatment for paediatric ADHD. IR clonidine has a fast onset and short half-life, with its use historically limited by somnolence. Although early formulations did not improve inattention well, recent evidence suggests that clonidine XR may have potential use as monotherapy or in extending benefit when taken with a stimulant. Guanfacine has a more specific neuronal action and a longer action than that of clonidine. The approved dosing of guanfacine XR 1 to 4 mg daily generally provides symptom benefit lasting 8-14 hours, and up to 24 hours in some children and adolescents receiving a higher dose. Such recent developments and ongoing study of additional potential pharmacological interventions may lead to additional future treatment options for children with ADHD.

Does switching from oral extended-release methylphenidate to the methylphenidate transdermal system affect health-related quality-of-life and medication satisfaction for children with attention-deficit/hyperactivity disorder?

BackgroundTo evaluate health-related quality of life (HRQL) and medication satisfaction after switching from a stable dose of oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD).MethodsIn a 4-week, multisite, open-label study, 171 children (164 in the intent-to-treat [ITT] population) aged 6-12 years diagnosed with ADHD abruptly switched from a stable dose of oral ER-MPH to MTS nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. Subjects remained on the scheduled dose for the first week, after which the dose was then titrated to an optimal effect. The ADHD Impact Module-Children (AIM-C), a disease-specific validated HRQL survey instrument measuring child and family impact, was used to assess the impact of ADHD symptoms on the lives of children and their families at baseline and study endpoint. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS) at study endpoint. Both the AIM-C and MSS were completed by a caregiver (parent/legally authorized representative). Tolerability was monitored by spontaneous adverse event (AE) reporting.ResultsAIM-C child and family HRQL mean scores were above the median possible score at baseline and were further improved at endpoint across all MTS doses. Similar improvements were noted for behavior, missed doses, worry, and economic impact AIM-C item scores. Overall, 93.8% of caregivers indicated a high level of satisfaction with their child's use of the study medication. The majority of treatment-emergent AEs (> 98%) were mild to moderate in intensity, and the most commonly reported AEs included headache, decreased appetite, insomnia, and abdominal pain. Seven subjects discontinued the study due to intolerable AEs (n = 3) and application site reactions (n = 4).ConclusionThis study demonstrates that MTS, when carefully titrated to optimal dose, may further improve child and family HRQL, as well as behavioral, medication worry, and economic impact item scores, as measured by the AIM-C in subjects switching to MTS from a stable dose of routinely prescribed oral ER-MPH after a short treatment period. Furthermore, following the abrupt conversion from oral ER-MPH to MTS, the majority of caregivers reported being highly satisfied with MTS as a treatment option for their children with ADHD.Trial RegistrationNCT00151983

Switching from oral extended-release methylphenidate to the methylphenidate transdermal system: continued attention-deficit/hyperactivity disorder symptom control and tolerability after abrupt conversion

Objective:To evaluate symptom control and tolerability after abrupt conversion from oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD).Methods:In a 4-week, prospective, multisite, open-label study, 171 children (164 intent-to-treat) with diagnosed ADHD aged 6–12 years abruptly switched from a stable dose of oral ER-MPH to MTS in nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. After the first week on the scheduled dose, the dose was titrated to optimal effect. The primary effectiveness outcome was the change from baseline (while taking ER-MPH) to week 4 in ADHD-Rating Scale-IV (ADHD-RS-IV) total scores. Adverse events (AEs) were assessed throughout the study.Results:Most subjects (58%) remained on the initial MTS dose defined by the dose-transition schedule; 38% increased and 4% decreased their MTS dose for optimization. MTS dose optimization resulted in significantly better ADHD-RS-IV total (mean ± SD) scores at week 4 than at baseline (9.9 ± 7.47 vs. 14.1 ± 7.48; p < 0.0001). The most commonly reported AEs included headache, decreased appetite, insomnia, and upper abdominal pain. Four subjects (2.3%) discontinued because of application site reactions and three discontinued because of other AEs.Conclusions:Abrupt conversion from a stable dose of oral ER-MPH to MTS was accomplished using a predefined dose-transition schedule without loss of symptom control; however, careful titration to optimal dose is recommended. Most AEs were mild to moderate and, with the exception of application site reactions, were similar to AEs typically observed with oral MPH. Limitations of this study included its open-label sequential design without placebo, which could result in spurious attribution of improvement to the study treatment and precluded superiority determinations of MTS over baseline ER-MPH treatment. The apparent superiority of MTS was likely due to more careful titration and clinical monitoring rather than the product itself.Trial registration: ClinicalTrials.gov identifier: NCT00151983.

HRQL and medication satisfaction in children with ADHD treated with the methylphenidate transdermal system

Objective:To evaluate the impact of methylphenidate transdermal system (MTS) on health-related quality of life (HRQL) and medication satisfaction in children with attention-deficit/hyperactivity disorder (ADHD) as well as to identify potential moderators of HRQL and medication satisfaction.Research design and methods:Children aged 6–12 years diagnosed with ADHD were enrolled (N = 128) and 115 children completed the study. MTS dose was optimized over 5 weeks using 10-, 15-, 20-, or 30-mg patches worn for 9 hours. The efficacy of 4- and 6-hour wear times was then assessed in an analog classroom setting in a randomized, placebo-controlled, double-blind, three-way crossover design study.Main outcome measures:The ADHD Impact Module-Children (AIM-C), a validated HRQL instrument, was used to assess the impact of ADHD symptoms on children and their families. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS). A parent or legally appointed representative (LAR) completed the measures. Tolerability was monitored by spontaneous adverse event reporting.Results:Mean scores on AIM-C child and family HRQL scales improved from baseline to endpoint across all MTS doses and the magnitude of improvement increased with time from baseline. Improvement was noted for behavior, missed doses, worry, and economic impact AIM-C scores. Overall, parents/LARs indicated a high level of satisfaction with their child's use of MTS (Visit 7 [92.1%]; Visit 10 [89.1%]). Most treatment-emergent adverse events (TEAEs) were mild to moderate. The most frequent TEAEs included decreased appetite (28%), headache (21%), insomnia (20%), and abdominal pain (12%).Conclusions:At study endpoint, MTS treatment of ADHD was associated with robust improvement in child and family HRQL, key economic impact items, and overall medication satisfaction with the effectiveness and ease of use of MTS as an ADHD treatment. Also, the majority of MTS TEAEs were mild to moderate in severity. Limitations of this study included the potential for a significant halo effect when measuring HRQL and medication satisfaction as well as the uncertainty regarding whether the improvements seen over this relatively short study duration would be sustainable long term.Clinical trial registration:#NCT00151970.

Methylphenidate Patch-Test Protocol and Irritancy Threshold Determination in Healthy Adult Subjects

The methylphenidate transdermal system (MTS) (Daytrana [Shire Pharmaceuticals Ireland Ltd., Wayne, PA]) has been shown to be well tolerated and effective; however, skin reactions, typically redness and itching, have also been noted with MTS use. The purpose of this study was to determine the irritancy threshold of methylphenidate (MPH), the active ingredient in the MTS, in healthy adults for use in subsequent patch testing. This was an open-label single-site pilot study. Eligible subjects had MPH (six different concentrations in two vehicles) patch tests applied to the paraspinous region of the upper back. Subjects returned after 48 hours and 96 hours for investigator assessments of each reaction. All enrolled subjects (n = 20) completed the study. There were no definite positive reactions in any subject at any test concentration. Overall, doubtful (macular erythema) reactions were noted on 12 sites at the 48-hour reading and on 6 sites at the 96-hour reading. With both aqueous and petrolatum vehicles, more doubtful reactions were noted at the lower MPH test concentrations. When performing patch testing to confirm possible allergic contact dermatitis from topical MPH, several test concentrations in the low-to-middle range (such as 0.1%, 1%, and 10%) prepared in petrolatum are advisable.

Long-term tolerability of the methylphenidate transdermal system in pediatric attention-deficit/hyperactivity disorder: A multicenter, prospective, 12-month, open-label, uncontrolled, phase III extension of four clinical trials

Background: Short-term treatment with the meth-ylphenidate transdermal system (MTS) has been well tolerated in several clinical trials in children with attention-deficit/hyperactivity disorder (ADHD). However, the effects of long-term use have not been systematically evaluated. Objectives: The primary objective of this study was to assess the 12-month tolerability of MTS in children with ADHD. Effectiveness was a secondary objective. Methods: This Phase III study was a multicenter, 12-month, open-label, flexible-dose extension of 4 previous trials. In those studies, children aged 6 to 12 years with a diagnosis of ADHD ( Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria) received MTS, osmotic-release oral system methylphenidate, or placebo. At entry into the present study, the children either continued to receive their optimal dose of MTS (10, 15, 20, or 30 mg per 9-hour patch wear time) or underwent dose titration over 4 weeks to an optimal MTS dose, which was continued for the remainder of the study. Tolerability was evaluated based on adverse events (AEs), physical examinations, vital signs, electrocardiograms, laboratory tests, the Children's Sleep Habits Questionnaire, and the occurrence of application-site reactions. Results: Of 327 enrolled subjects, 326 received treatment and 157 completed the study. The majority of enrolled subjects were male (64.8%) and white (73.7%), with a mean (SD) age of 9.2 (1.9) years. Two hundred sixty-five (81.3%) of the 326 subjects who received MTS reported AEs. AEs led to study discontinuation in 29 subjects (8.9%). The majority (98.3%) of treatment-emergent AEs were of mild or moderate severity. The most common AEs were decreased appetite (24.8%), headache (16.6%), upper respiratory tract infection (12.3%), cough (11.7%), pyrexia (10.1%), and decreased weight (10.1%). Of the 1118 AEs, 40.8% were considered possibly or probably related to study treatment. Three serious AEs (facial contusion, ankle fracture, and syncope) occurred and were considered unrelated to study treatment. Based on data collected across all study visits, application-site reactions generally consisted of mild erythema associated with mild discomfort at the patch site. Application-site reactions accounted for 22 (6.7%) study discontinuations. Conclusions: Slightly less than half (48.0%) of subjects completed this 12-month, open-label extension study of MTS. Most AEs were mild to moderate in severity and, with the exception of application-site reactions, were typical of those previously observed with methylphenidate.

Effects of Application to Two Different Skin Sites on the Pharmacokinetics of Transdermal Methylphenidate in Pediatric Patients with Attention-Deficit/Hyperactivity Disorder

This study was conducted to quantify the rate and extent of methylphenidate (MPH) absorption from a transdermal system when applied to two different skin sites in pediatric subjects with attention-deficit/hyperactivity disorder (ADHD). In an open-label, single-dose, randomized, two-way crossover study, children (6-12 years) with ADHD were randomized to wear one MPH transdermal system (MTS) on the hip area or on the scapular area for 16 hours. The following week, subjects were crossed over to the opposite application site. Serial blood samples were collected after each MTS application and pharmacokinetic (PK) parameters for d,l-MPH were calculated. Worn MTS units were assayed to calculate the Apparent Dose absorbed from MTS. PK analyses included 23 subjects. Hip and scapular application resulted in quantifiable levels of d,l-MPH, with approximately 31% higher bioavailability upon hip application. Logarithm transformed mean ratios for area under the curve (AUC) and C(max) indicated a lack of equivalence between the two sites. MTS applied to both hip and scapular areas resulted in quantifiable plasma levels of d,l-MPH. Bioavailability of MPH from the same transdermal delivery system appears to differ substantially when applied to two different skin surfaces in young children but with similar overall skin effects assessments.

Transdermal methylphenidate system: old wine in a new bottle

Background: The methylphenidate transdermal system (MTS) is a novel formulation of methylphenidate, a psychostimulant, in an adhesive-based matrix transdermal system (patch) that is applied to intact skin. This is deliverable in a transdermal patch for the treatment of attention-deficit/hyperactivity disorders. Objective: This paper seeks to review the supporting data for the use of the MTS patch, including its efficacy, safety and other considerations in its use. Methods: Clinical studies using MTS are reviewed. Results/conclusion: The MTS patch shows similar levels of efficacy and safety as other methylphenidate formulations and stimulants, although the time to onset of effects may be longer. The patch delivery system allows for flexibility in the duration of effect and reduced reliance on oral administration.

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Genome‐wide association study of response to methylphenidate in 187 children with attention‐deficit/hyperactivity disorder

We conducted a genome-wide association study of symptom response in an open-label study of a methylphenidate transdermal system (MTS). All DNA extraction and genotyping was conducted at SUNY Upstate Medical University using the Affymetrix Genome-Wide Human SNP Array 6.0. All quality control and association analyses were conducted using the software package PLINK. After data cleaning and quality control, there were 187 subjects (72% (N = 135) male) with mean age 9.2 +/- 2.0 years and 319,722 SNPs available for analysis. The most statistically significant association (rs9627183 and rs11134178; P = 3 x 10(-6)) fell short of the threshold for a genome-wide significant association. The most intriguing association among suggestive findings (rs3792452; P = 2.6 x 10(-5)) was with the metabotropic glutamate receptor 7 gene (GRM7) as it is expressed in brain structures also previously associated with ADHD. Among the 102 available SNPs covering previously studied candidate genes, two SNPs within the norepinephrine transporter gene (NET, SLC6A2) were significant at P < or = 1 x 10(-2). These results should be considered preliminary until replicated in larger adequately powered, controlled samples but do suggest that noradrenergic and possibly glutaminergic genes may be involved with response to methylphenidate.

Pharmacokinetics of Methylphenidate Transdermal System (MTS): Results from a Laboratory Classroom Study

To evaluate the pharmacokinetic properties of the methylphenidate transdermal system (MTS) in pediatric patients diagnosed with ADHD (attention-deficit/hyperactivity disorder) in a laboratory school setting. A phase II, randomized, double-blind, placebo-controlled, laboratory classroom study was conducted with prior dose optimization. Children (aged 6-12 years) with ADHD were titrated over 5 weeks to an optimal clinical MTS dose (10, 15, 20, or 30 mg/9 h). Participants were randomized to 1 week of either MTS or corresponding placebo, followed by crossover to the alternate treatment. Laboratory school evaluations, including pharmacokinetic blood sampling, occurred at the end of each treatment. MTS delivered d- and l-MPH (methylphenidate) into the systemic circulation throughout the 9-hour wear time, and plasma concentrations declined rapidly after patch removal. Over the time-course of clinical effectiveness (2-12 h), mean plasma concentrations of d-MPH at the most frequently titrated doses (15 and 20 mg/9 h) ranged from 4.97 to 28.3 ng/mL. Systemic exposure increased approximately dose proportionately. Plasma concentrations of the l-MPH were approximately one-half to two-thirds those for d-MPH. Plasma concentrations of the much less active l-MPH were consistently lower than those of d-MPH. The clinical relevance of the MTS pharmacokinetic profile is discussed.

P.7.c.002 Quality of life and parent satisfaction with the methylphenidate transdermal system

P.7.c.002 Quality of life and parent satisfaction with the methylphenidate transdermal system

P.7.c.003 12-month safety and efficacy of methylphenidate transdermal system in attention-deficit/hyperactivity disorder

P.7.c.003 12-month safety and efficacy of methylphenidate transdermal system in attention-deficit/hyperactivity disorder

Varying the Wear Time of the Methylphenidate Transdermal System in Children With Attention-Deficit/Hyperactivity Disorder

Children with attention-deficit/hyperactivity disorder often have varying needs for coverage of their symptoms throughout the day. The objectives of this study were to determine the efficacy, duration of action, and safety of methylphenidate transdermal system worn for variable times by children (ages 6-12) diagnosed with ADHD. Methylphenidate dose was optimized over 5 weeks using 10-, 15-, 20-, or 30-mg patches worn for 9 hours. The efficacy of 4- and 6-hour wear times was then assessed in an Analog Classroom setting during a randomized, placebo-controlled, double-blind, three-way crossover phase. The main efficacy measures were the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and the Permanent Product Measure of Performance math test. All of the efficacy measures indicated that 4- and 6-hour wear times improved ADHD symptoms and that medication effects on the Swanson, Kotkin, Agler, M-Flynn, and Pelham Rating Scale deportment scale and Permanent Product Measure of Performance math test decreased between 2 and 4 hours after patch removal. The majority of adverse events were transient and mild to moderate in severity. These findings suggest that the duration of medication effect is related to the wear time of the patch and may be tailored to accommodate the schedules of patients.

Practical management of cutaneous reactions to the methylphenidate transdermal system: Recommendations from a dermatology expert panel consensus meeting

Background: Psychostimulants remain the most-used medications for attention-deficit/hyperactivity disorder (ADHD). The methylphenidate transdermal system (MTS) is the first stimulant patch dosage formulation to be approved by the US Food and Drug Administration for the treatment of the symptoms of ADHD in children aged 6 to 12 years. The MTS patch is approved to be applied once daily to the hip and worn for 9 hours. While cutaneous reactions may occur with any formulation of medication, they are more likely with transdermal administration.Objective: The purpose of this commentary was to describe the types of cutaneous reactions that have been reported with transdermal systems in general, review the cutaneous adverse events seen in clinical trials with the MTS specifically, and provide practical management suggestions for prevention and treatment of these potential cutaneous reactions.Methods: In September 2007, a group of child psychiatrists, pediatricians, developmental pediatricians, and pediatric neurologists who treat ADHD and have had experience in their practices with MTS convened to discuss cutaneous reactions in relation to its use. Information collected from this meeting and from the clinical trials database of the sponsor was reviewed by a panel of 3 dermatologic clinical experts in contact dermatitis and 1 pediatric dermatologist. The panel's recommendations form the basis for this report.Conclusions: Mild to moderate erythema is a common cutaneous effect with MTS use, and is generally not a cause for discontinuation if seen in isolation. Irritant contact dermatitis is relatively common and can be reduced and treated by alternating patch application sites, moisturizing, gentle skin care, and application of topical corticosteroids at the previous patch sites if needed. Allergic contact dermatitis (ACD) and allergic contact urticaria are rare when MTS is worn as directed in the prescribing information. MTS should be discontinued if ACD is suspected.