Cognitive and Behavioral Effects of Multilayer-Release Methylphenidate in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder

Schachar, Russell; Ickowicz, Abel; Crosbie, Jennifer; Donnelly, Graeme; Reiz, Joseph L.; Miceli, Paula C.; Harsanyi, Zoltan; Darke, Andrew C.

doi:10.1089/cap.2007.0039

Cited by 29 publications

(25 citation statements)

References 25 publications

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“…This patient-reported amelioration was supported by the significant improvement reported by knowledgeable informants; for the other secondary cognitive end point, a performance-based computerized test of neurocognitive function, the improvement seen with LDX was not statistically superior to placebo. Overall, these findings support previous evidence of the ability of dopaminergic agents to mitigate cognitive dysfunction (Killgore et al, 2008;Schachar et al, 2008). However, because there are typically only modest correlations between BRIEF-A and performance-based measures of executive function , this finding is not surprising.…”

Section: Discussionsupporting

confidence: 86%

Lisdexamfetamine Dimesylate Augmentation in Adults With Persistent Executive Dysfunction After Partial or Full Remission of Major Depressive Disorder

Madhoo

Keefe

Roth

et al. 2013

Neuropsychopharmacol

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Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy for executive dysfunction in partially or fully remitted major depressive disorder (MDD). This randomized, placebo-controlled study (NCT00985725) enrolled 143 adults (18-55 years) with mild MDD (Montgomery-Å sberg Depression Rating Scale (MADRS) score p18) and executive dysfunction (Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global Executive Composite (GEC) T score X60) on stable antidepressant monotherapy for X8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks of double-blind LDX (20-70 mg/day) or placebo augmentation, followed by 2 weeks of single-blind placebo. The primary end point was change from baseline to week 9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse events (TEAEs). Of 143 randomized participants, 119 completed double-blind treatment (placebo, n ¼ 59; LDX, n ¼ 60). Mean±standard deviation (SD) BRIEF-A GEC T scores decreased from baseline (placebo, 74.2±8.88; LDX, 76.8±9.66) to week 9/EOS (placebo, 61.4±14.61; LDX, 55.2±16.15); the LS mean (95% CI) treatment difference significantly favored LDX ( À 8.0 ( À 12.7, À 3.3); P ¼ 0.0009). The LS mean (95% CI) treatment difference for MADRS total score also significantly favored LDX ( À 1.9 ( À 3.7, 0.0); P ¼ 0.0465). TEAE rates were 73.6% with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this trial, LDX augmentation significantly improved executive dysfunction and depressive symptoms in participants with mild MDD. The safety profile of LDX was consistent with prior studies in adults with attention-deficit/hyperactivity disorder.

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Section: Discussionsupporting

confidence: 86%

Lisdexamfetamine Dimesylate Augmentation in Adults With Persistent Executive Dysfunction After Partial or Full Remission of Major Depressive Disorder

Madhoo

Keefe

Roth

et al. 2013

Neuropsychopharmacol

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“…After morning administration of MPH-MLR, a small drop in plasma MPH concentration occurs *4 hours postdosing, followed by a gradual increase in MPH concentrations, producing a second attenuated peak at *7 hours after dosing and then a gradual decline throughout the evening and nighttime hours (Adjei et al 2014a,b). Phase 2 studies of MPH-MLR in children, adolescents, and adults across a variety of settings demonstrated that once-daily administration produces significant improvements in behavioral and cognitive measures Weiss et al 2007;Schachar et al 2008). The MPH-MLR capsule is ingested orally or opened for its contents to be sprinkled on food; the two administration modes are bioequivalent (Adjei et al 2014b).…”

Section: Introductionmentioning

confidence: 99%

A Randomized Placebo-Controlled Double-Blind Study Evaluating the Time Course of Response to Methylphenidate Hydrochloride Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

Wigal¹,

Greenhill

Nordbrock³

et al. 2014

Journal of Child and Adolescent Psychopharmacology

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Objective: The purpose of this study was to assess the time of onset and time course of efficacy over 12.0 hours of extendedrelease multilayer bead formulation of methylphenidate (MPH-MLR) compared with placebo in children 6-12 years of age with attention-deficit/hyperactivity disorder (ADHD) in a laboratory school setting. Methods: This randomized double-blind placebo-controlled study included children 6-12 years of age with ADHD. Enrolled children went through four study phases: 1) Screening period ( £ 4 weeks) and a 2 day medication washout period; 2) openlabel period with dose initiation of MPH-MLR 15 mg daily and individual dose optimization treatment period (2-4 weeks); 3) double-blind crossover period in which participants were randomized to sequences (1 week each) of placebo and the optimized MPH-MLR dose given daily; and 4) follow-up safety call. Analog classroom time course evaluations were performed at the end of each double-blind week. The primary efficacy end-point was the mean of the on-treatment/postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Total scores over time points collected 1.0-12.0 hours after dosing. End-points were evaluated using a mixed-effects analysis of covariance. Results: The evaluable population included 20 participants. The least-squares mean postdose SKAMP-Total score was higher for placebo than for MPH-MLR (2.18 vs. 1.32, respectively; p = 0.0001), indicating fewer symptoms with MPH-MLR therapy than with placebo. No difference in SKAMP-Total score between participants who received sequence 1 or sequence 2 was noted. From each of hours 1.0-12.0, least-squares mean SKAMP-Total score was significantly lower for those receiving MPH-MLR than for those receiving placebo ( p £ 0.0261). Neither serious adverse events nor new or unexpected safety findings were noted during the study. Conclusions: MPH-MLR showed a significant decrease in SKAMP scores compared with placebo in children with ADHD 6-12 years of age, indicating a decrease in ADHD symptoms. The estimated onset was observed within 1.0 hour, and duration was measured to 12.0 hours postdose.

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“…Multilayer-release (MLR ® ) MPH (Biphentin ® ) is a once-daily MLR bead formulation with a rapid rise in plasma levels after oral administration and an onset of action within 1 hour (Purdue Pharma Canada 2006; Schachar et al 2007) that has previously been shown to reduce ADHD symptoms in adults (Jain et al 2007). In single-dose pharmacokinetic studies, in young, healthy adults and children with ADHD, this controlled-release MLR formulation was fully bioavailable relative to the IR formulation, with a relative area under the plasma concentrationtime curve of approximately 100% over the total 24-hour dosing interval and 70-75% over the period corresponding to the duration of a typical school day (Quinn et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Once-Daily Multilayer-Release Methylphenidate in a Double-Blind, Crossover Comparison to Immediate-Release Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder

Weiss

Hechtman²,

Turgay³

et al. 2007

Journal of Child and Adolescent Psychopharmacology

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Of the 90 enrolled patients, aged 6.4-17.5 years, 79 (88%) completed the study. Stable daily doses were 32.0 and 32.5 mg for MLR and IR-MPH, respectively. All efficacy parameters were significantly improved from baseline. A total of 73.2% and 81.0% of patients on MLR and IR-MPH were rated as "much" or "very much improved" on the CGI. A total of 77.4% and 81.1% of patients were normalized on the CPRS-R and 78.9 and 90.4% of patients were normalized on the CTRS-R for MLR and IR-MPH, respectively. The mean CASE score was not different from baseline for either treatment.

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Cognitive and Behavioral Effects of Multilayer-Release Methylphenidate in the Treatment of Children with Attention-Deficit/Hyperactivity Disorder

Cited by 29 publications

References 25 publications

Lisdexamfetamine Dimesylate Augmentation in Adults With Persistent Executive Dysfunction After Partial or Full Remission of Major Depressive Disorder

Lisdexamfetamine Dimesylate Augmentation in Adults With Persistent Executive Dysfunction After Partial or Full Remission of Major Depressive Disorder

A Randomized Placebo-Controlled Double-Blind Study Evaluating the Time Course of Response to Methylphenidate Hydrochloride Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

Once-Daily Multilayer-Release Methylphenidate in a Double-Blind, Crossover Comparison to Immediate-Release Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder

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