Osmotic-release Oral System Methylphenidate Research Articles

An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported more often for OROS-methylphenidate than for atomoxetine. After 24 weeks of treatment, OROS-methylphenidate and atomoxetine had comparable efficacy in reducing core ADHD symptoms in drug-naïve children and adolescents with ADHD.

Anxiety and Depressed Mood Decline Following Smoking Abstinence in Adult Smokers with Attention Deficit Hyperactivity Disorder

IntroductionA preponderance of relevant research has indicated reduction in anxiety and depressive symptoms following smoking abstinence. This secondary analysis investigated whether the phenomenon extends to smokers with attention deficit hyperactivity disorder (ADHD). MethodsThe study setting was an 11-Week double-blind placebo-controlled randomized trial of osmotic release oral system methylphenidate (OROS-MPH) as a cessation aid when added to nicotine patch and counseling. Participants were 255 adult smokers with ADHD. The study outcomes are: anxiety (Beck Anxiety Inventory (BAI)) and depressed mood (Beck Depression Inventory II (BDI)) measured one Week and six Weeks after a target quit day (TQD). The main predictor is point-prevalence abstinence measured at Weeks 1 and 6 after TQD. Covariates are treatment (OROS-MPH vs placebo), past major depression, past anxiety disorder, number of cigarettes smoked daily, demographics (age, gender, education, marital status) and baseline scores on the BAI, BDI, and the DSM-IV ADHD Rating Scale. ResultsAbstinence was significantly associated with lower anxiety ratings throughout the post-quit period (p<0.001). Depressed mood was lower for abstainers than non-abstainers at Week 1 (p<0.05), but no longer at Week 6 (p=0.83). Treatment with OROS-MPH relative to placebo showed significant reductions at Week 6 after TQD for both anxiety (p<0.05) and depressed mood (p<0.001), but not at Week 1. Differential abstinence effects of gender were observed. Anxiety and depression ratings at baseline predicted increased ratings of corresponding measures during the post-quit period. ConclusionStopping smoking yielded reductions in anxiety and depressed mood in smokers with ADHD treated with nicotine patch and counseling. Treatment with OROS-MPH yielded mood reductions in delayed manner.

Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate.

BackgroundAttention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH) formulation may improve drug response and economic efficiency.ObjectiveTo evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.MethodsA daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1) optimal response, (2) sub-optimal response, (3) discontinued treatment, and (4) natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS) and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs). Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.ResultsSwitching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.ConclusionsThis study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: Estimates based on indirect analysis using a systematic review and meta-regression analysis

BackgroundThere are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data. MethodsA systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design. ResultsTwenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses. ConclusionThis model predicts that LDX may have a large treatment effect size in European adults with ADHD.

Toward personalized smoking-cessation treatment: Using a predictive modeling approach to guide decisions regarding stimulant medication treatment of attention-deficit/hyperactivity disorder (ADHD) in smokers.

Osmotic-release oral system methylphenidate (OROS-MPH) did not show overall benefit as an adjunct smoking cessation treatment for adult smokers with ADHD in a randomized, placebo-controlled, multicenter clinical trial. A secondary analysis revealed a significant interaction between ADHD symptom severity and treatment-response to OROS-MPH, but did not account for other baseline covariates or estimate the magnitude of improvement in outcome if treatment were optimized. This present study addressed the gaps in how this relationship should inform clinical practice. Using data from the Adult Smokers with ADHD Trial (N = 255, six sites in five US States), we build predictive models to calculate the probability of achieving prolonged abstinence, verified by self-report, and expired carbon monoxide measurement. We evaluate the potential improvement in achieving prolonged abstinence with and without stratification on baseline ADHD severity. Predictive modeling demonstrates that the interaction between baseline ADHD severity and treatment group is not affected by adjusting for other baseline covariates. A clinical trial simulation shows that giving OROS-MPH to patients with baseline Adult ADHD Symptom Rating Scale (ADHD-RS) >35 and placebo to those with ADHD-RS ≤35 would significantly improve the prolonged abstinence rate (52 ± 8% vs. 42 ± 5%, p < .001). In smokers with ADHD, utilization of a simple decision rule that stratifies patients based on baseline ADHD severity can enhance overall achievement of prolonged smoking abstinence. Similar analysis methods should be considered for future clinical trials for other substance use disorders.

Dikkat Eksikliği Hiperaktivite Bozukluğu Tedavisinde Atomoksetin ve Osmotik Salınımlı Metilfenidat: Etkinlik ve Yan Etki Profilinin Değerlendirildiği Altı Aylık İzlem Çalışması

Objective: Attention deficit hyperactivity disorder (ADHD) is one of the most frequently seen neuropsychiatric disorders in childhood. The aim of this study is to compare the efficacy and the adverse effects of two FDA-approved agents, atomoxetine (ATX) and osmotic release oral system methylphenidate (OROS-MPH), in the treatment of ADHD. Material and Methods: This research was designed as a randomized, open label, prospective and follow-up study. The study was performed by 120 cases between ages 7-16 years who were diagnosed as ADHD for the first time and given prescription. The cases were divided into two by randomization. One group was given ATX (n=59) while the other was given OROS-MPH (n=61) were evaluated prospectively by clinical examination and Conner's Comprehensive Behavior Rating Scale-Teacher (CRS-T) at the 2nd, 4th, and 6th months. Efficacy of treatment was regarded as a 40% reduction in CRS-T scores when compared to baseline values, and the adverse effects were questioned in every follow up visit. Results: The efficacy was 55.7% in CRS-T hyperactivity score, 63.9% in the attention deficit score, and 55.7% in the behavior problems score in OROS-MPH group. Those values were 47.5%, 69.5% and 57.6% respectively in ATX group. Adverse effects were seen in 27.1% (n=16) of the patients in the ATX group, and in 31.1% (n=19) of the patients in the OROS-MPH group. Two groups were not found significantly different for the frequency of adverse effects as well as the efficacy of the medication, at the follow-up evaluations which were performed at 2nd, 4th and 6th months. Conclusion: In this study, ATX and OROS-MPH were compared for their efficacy and adverse effects for the treatment of ADHD, and two agents were found similar for their efficacies and adverse effect profiles. ATX and OROS-MPH have similar efficacies in the treatment of ADHD and adverse effect profiles are similar.

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 ...

Cognitive Improvement of Attention and Inhibition in the Late Afternoon in Children With Attention-Deficit Hyperactivity Disorder (ADHD) Treated With Osmotic-Release Oral System Methylphenidate.

Long-acting medications have been developed and approved for use in the treatment of attention-deficit hyperactivity disorder (ADHD). These compounds are intended to optimize and maintain symptoms control throughout the day. We tested prolonged effects of osmotic-release oral system methylphenidate on both attention and inhibition, in the late afternoon. A double-blind, randomized, placebo-controlled study was conducted in 36 boys (7-12 years) with ADHD and 40 typically developing children. The ADHD children received an individualized dose of placebo or osmotic-release oral system methylphenidate. They were tested about 8 hours after taking with 2 continuous performance tests (continuous performance test-X [CPT-X] and continuous performance test-AX [CPT-AX]) and a counting Stroop. A positive effect of osmotic-release oral system methylphenidate was present in CPT-AX with faster and less variable reaction times under osmotic-release oral system methylphenidate than under placebo, and no difference with typically developing children. In the counting Stroop, we found a decreased interference with osmotic-release oral system methylphenidate but no difference between children with ADHD under placebo and typically developing children.

Post hoc analyses of the impact of previous medication on the efficacy of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in a randomized, controlled trial.

BackgroundFollowing the approval of lisdexamfetamine dimesylate (LDX) in several European countries for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with an inadequate response to methylphenidate (MPH) treatment, the aim of the present analysis was to establish the response to LDX in subgroups of patients with different ADHD medication histories.MethodsThis was a post hoc subgroup analysis of data from a 7-week, European, double-blind, dose-optimized, Phase III study. Patients aged 6–17 years were randomized 1:1:1 to LDX, placebo, or osmotic-release oral system methylphenidate (OROS-MPH). OROS-MPH was included as a reference arm rather than as a direct comparator. Efficacy was assessed in patients categorized according to their ADHD medication history using the ADHD Rating Scale IV and Clinical Global Impressions-Improvement (CGI-I) scores.ResultsThe difference between active drug and placebo in least-squares mean change from baseline to endpoint in ADHD Rating Scale IV total score (95% confidence interval) was similar between the overall study population (n=317; LDX, −18.6 [−21.5, −15.7]; OROS-MPH, −13.0 [−15.9, −10.2]) and treatment-naïve individuals (n=147; LDX, −15.1 [−19.4, −10.9]; OROS-MPH, −12.7 [−16.8, −8.5]) or patients previously treated with any ADHD medication (n=170; LDX, −21.5 [−25.5, −17.6]; OROS-MPH, −14.2 [−18.1, −10.3]). In addition, similar proportions of patients receiving active treatment were categorized as improved based on CGI-I score (CGI-I of 1 or 2) in the overall study population and among treatment-naïve individuals or patients previously treated with any ADHD medication.ConclusionIn these post hoc analyses, the response to LDX treatment, and to the reference treatment OROS-MPH, was similar to that observed for the overall study population in subgroups of patients categorized according to whether or not they had previously received ADHD medication.

Parental quality of life and depressive mood following methylphenidate treatment of children with attention‐deficit hyperactivity disorder

This naturalistic study investigated the associations between quality of life and depressive mood in parents and symptom changes in attention-deficit hyperactivity disorder (ADHD) children. At baseline and at weeks 4 and 8, the parents evaluated their children, who were receiving treatment with osmotic-release oral system methylphenidate (mean dosage 36.3 ± 15.5 mg/day), using the Swanson, Nolan, and Pelham - Fourth Edition (SNAP-IV-18) scale. The parents evaluated themselves using the Beck Depression Inventory (BDI) and the World Health Organization Quality of Life Assessment, Brief Version (WHOQOL-BREF). A significant reduction in SNAP-IV-18 scores and improvements in parental BDI scores and parental WHOQOL-BREF scores were observed. The decrease in BDI scores from baseline to 8 weeks was significantly associated with increases in WHOQOL-BREF sub-domain scores from baseline to 8 weeks, with a greater decrease at 4 weeks and after. The decrease in the SNAP-IV-18 hyperactivity-impulsivity score was significantly associated with increases in WHOQOL social sub-domain scores from baseline to 8 weeks. For those patients who showed a 25% or greater decrease in the SNAP-IV-18 total scores from baseline to 8 weeks, the decreases in the SNAP-IV-18 total score and in the inattention and hyperactivity-impulsivity scores were significantly associated with a decrease in BDI scores from baseline to 8 weeks. Methylphenidate treatment for ADHD was associated with both symptom alleviation in children with ADHD and improvement in parental depressive mood and quality of life, suggesting that the effects of treatment could go beyond symptom improvement in ADHD.

OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: A randomized, placebo-controlled cross-over study

Attention-deficit/hyperactivity disorder (ADHD) is linked to impaired executive functioning (EF). This is the first study to objectively investigate the effects of a long-acting methylphenidate on neurocognitive test performance of adults with ADHD. Twenty-two adults with ADHD participated in a 6-weeks study examining the effect of osmotic-release oral system methylphenidate (OROS-mph) on continuous performance tests (CPTs; objective measures), and on the self-reported ADHD rating scale (subjective measure) using a randomized, double-blind, placebo-controlled cross-over design. OROS-mph significantly improved reaction time variability (RTV), commission errors (CE) and d-prime (DP) as compared to baseline (Cohen's d>.50), but did not affect hit reaction time (HRT) or omission errors (OE). Compared to placebo, OROS-mph only significantly influenced RTV on one of two CPTs (p<.050). Linear regression analyses showed predictive ability of more beneficial OROS-mph effects in ADHD patients with higher EF severity (RTV: β=.670, t=2.097, p=.042; omission errors (OE): β=−.098, t=−4.759, p<.001), and with more severe ADHD symptoms (RTV: F=6.363, p=.019; HRT: F=3.914, p=.061). Side effects rates were substantially but non-significantly greater for OROS-mph compared to placebo (77% vs. 46%, p=.063). OROS-mph effects indicated RTV as the most sensitive parameter for measuring both neuropsychological and behavioral deficits in adults with ADHD. These findings suggest RTV as an endophenotypic parameter for ADHD symptomatology, and propose CPTs as an objective method for monitoring methylphenidate titration.

EPA-1078 – The child health and illness profile as a measure of health-related quality of life in stimulant-treated children and adolescents with ADHD

Introduction The Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE:PRF) is a generic measure of child health-related quality of life (HRQoL). Scores in the five domains and 12 subdomains are standardized to T-scores (mean=50, SD=10), based on US community data. Objective Evaluate CHIP-CE:PRF results from two studies of lisdexamfetamine dimesylate (LDX) in children and adolescents with ADHD. Methods Patients’ parents or guardians completed CHIP-CE:PRF assessments at baseline, and weeks 4 and 7 of SPD489-325, a 7-week randomized, placebo-controlled trial incorporating a reference treatment (osmotic-release oral system methylphenidate; OROS-MPH). The Achievement domain was pre-specified as the primary HRQoL outcome. Statistical comparison of LDX versus OROS-MPH was not pre-specified. In SPD489-326, CHIP-CE:PRF assessments were performed in the ≥26-week open-label period and the subsequent 6-week randomized-withdrawal period. Results Pre-treatment CHIP-CE:PRF T-scores were ≥1 SD below 50 in Achievement, Risk Avoidance, Satisfaction and Resilience. In SPD489-325, LDX and OROS-MPH were both significantly more effective than placebo in these four domains, but not in Comfort. Effect sizes were largest (p Conclusions Short-term LDX or OROS-MPH treatment led to improved HRQoL scores. These benefits were maintained during long-term LDX treatment, and HRQoL scores declined following treatment withdrawal. Supported by funding from Shire

EPA-1407 – The first European studies of lisdexamfetamine dimesylate in children and adolescents with attention-deficit/hyperactivity disorder

Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for treatment of attention-deficit/hyperactivity disorder (ADHD). Review efficacy and safety data from two double-blind, randomized trials (SPD489-325 and SPD489-326) in patients with ADHD aged 6–17 years. In SPD489-325, patients received placebo or optimized doses of LDX or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH) for ≤7 weeks. The primary efficacy measure was ADHD Rating Scale IV (ADHD-RS-IV) total score. Statistical comparison of LDX versus OROS-MPH was not pre-specified. In SPD489-326, a ≥26-week open-label LDX period preceded a 6-week, placebo-controlled, randomized-withdrawal period (RWP). The primary endpoint was treatment failure (50% increase in ADHD-RS-IV total score and ≥2-point increase in Clinical Global Impressions-Severity score from RWP baseline). Efficacy was assessed in the full analysis sets. In SPD489-325 (N=317), placebo-adjusted least-squares-mean changes in ADHD-RS-IV total score from baseline to endpoint were: LDX, –18.6 (95% confidence interval [CI]: –21.5, –15.7; p<0.001; effect size 1.80) and OROS MPH, –13.0 (–15.9, –10.2; p <0.001; 1.26). In SPD489-326 (N=262, open-label period; N=153, RWP), 15.8% and 67.5% of patients receiving LDX and placebo, respectively, met treatment failure criteria at RWP endpoint (difference: –51.7%; 95% CI: –65.0%, –38.5%; p <0.001). The most common treatment-emergent adverse events in LDX-treated patients were decreased appetite, headache and decreased weight. Short-term LDX treatment improved symptoms of ADHD in children and adolescents. Continued LDX treatment was associated with maintenance of efficacy compared with placebo. The safety profile of LDX was generally consistent with that of stimulant therapy.

EPA-0993 – Health utility scores in children and adolescents with attention-deficit/hyperactivity disorder: response to stimulant treatment

The Health Utilities Index-Mark 2 (HUI2), a generic instrument for assessing health status, is an important effectiveness input for pharmacoeconomic modelling. It has not previously been used in patients with attention deficit/hyperactivity disorder (ADHD). To use HUI2 to assess health utility in patients aged 6–17 years with ADHD receiving the prodrug stimulant lisdexamfetamine dimesylate (LDX). SPD489-325 was a 7-week, randomized, double-blind, placebo-controlled trial of LDX, with osmotic-release oral system methylphenidate (OROSMPH) as a reference treatment. Patients’ parents or guardians completed HUI2 questionnaires at baseline and weeks 4 and 7. Utilities were estimated for treatment responders and non-responders, with response defined as a Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2, or a ≥25% or ≥30% reduction in ADHD Rating Scale IV (ADHD-RS-IV) total score. Of 336 patients randomized, 317 were included in the full analysis set (LDX, n=104; OROS-MPH, n=107; placebo, n=106) and 196 completed the study. At endpoint, mean HUI2 utility scores across all treatment groups were higher for responders than non-responders when response was based on CGI-I score (responders: 0.896 [SD, 0.0990]; non-responders: 0.838 [0.1421]), on a ≥25% reduction in ADHD-RS-IV score from baseline (responders, 0.899 [0.0969]; non-responders, 0.809 [0.1474]), or on a ≥30% reduction in ADHD-RS-IV score from baseline (responders, 0.902 [0.0938]; non-responders 0.814 [0.1477]). The HUI2 instrument is sensitive to treatment response in the child and adolescent ADHD patient population. Health utilities generated using HUI2 are therefore suitable for cost effectiveness evaluations of ADHD medications. Supported by funding from Shire

EPA-0994 – Assessing adhd stimulant treatment efficacy using the weiss functional impairment rating scale: strengths and weaknesses

Introduction The Weiss Functional Impairment Rating Scale–Parent Report (WFIRS-P) is an ADHD-specific instrument comprising 50 items, grouped into six domains. Parents score each item on a Likert scale (0–3 or not applicable). Objective To evaluate functional impairment using the WFIRS-P in two phase 3 studies (SPD489-325 and SPD489-326) of lisdexamfetamine dimesylate (LDX) in children and adolescents with ADHD. Methods Patients’ parents or guardians completed WFIRS-P assessments at baseline, and weeks 4 and 7 of SPD489-325, a 7-week, randomized, placebo controlled trial incorporating a reference treatment (osmotic-release oral system methylphenidate; OROS-MPH). Statistical comparison of LDX versus OROS-MPH was not pre-specified. In SPD489-326, WFIRS-P assessments were performed in the ≥26-week open-label period and the subsequent 6-week randomized-withdrawal period. Results In SPD489-325, statistically significant placebo-adjusted effects of LDX were observed in WFIRS-P total score (effect size, 0.924; p p p Conclusions Short-term treatment with LDX or OROS-MPH led to improved functional impairment scores. These benefits were maintained during long-term LDX treatment, and scores declined following treatment withdrawal. Supported by funding from Shire .

EPA-0719 – Post hoc analyses on the efficacy of lisdexamfetamine dimesylate following previous treatment with attention deficit/hyperactivity disorder medication

The prodrug lisdexamfetamine dimesylate (LDX) is licensed in several European countries for treating attention-deficit/hyperactivity disorder (ADHD) in children and adolescents with an inadequate response to methylphenidate (MPH) treatment. To evaluate post hoc the impact of ADHD medication history on the efficacy of LDX. In this 7-week, dose-optimized, double-blind, study, patients (6–17 years) were randomized 1:1:1 to LDX, placebo or osmotic-release oral system methylphenidate (OROS-MPH). Efficacy assessments included ADHD Rating Scale IV (ADHD-RS-IV) and Clinical Global Impressions-Improvement (CGI-I) scores. The full analysis set (FAS) comprised 317 patients. Baseline characteristics were similar across treatment groups and previous treatment subgroups. At endpoint, the mean change from baseline in ADHD-RS-IV total score and proportions of responders based on a CGI-I of 1 or 2 for LDX, OROS-MPH and placebo are presented below. Previous treatment sub-group LDX Placebo OROS-MPH Mean change (SD) in ADHD-RS-IV total score FAS (N=317) −24.7 (10.15) −6.3 (10.02) −18.9 (12.92) Treatment-naïve (n=147) −24.0 (10.00) −8.5 (10.34) −21.4 (13.09) Any previous ADHD medication (n=170) −25.3 (10.34) −4.2 (9.30) −16.9 (12.53) Previous MPH treatment (n=146) −25.4 (10.67) −4.7 (9.70) −17.7 (11.96) Proportion of responders (95% CI): CGI-I 1 or 2 FAS (N=317) 78.0% (69.9, 86.1) 14.4% (7.7, 21.2) 60.6% (51.2, 70.0) Treatment-naïve (n=147) 80.4% (69.0, 91.9) 19.6% (8.7, 30.5) 63.8% (50.1, 77.6) Any previous ADHD medication (n=170) 75.9% (64.5, 87.3) 9.4% (1.6, 17.3) 57.9% (45.1, 70.7) LDX and OROS-MPH were associated with clinically relevant improvements in ADHD symptoms irrespective of ADHD medication history. Study funded by Shire

Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24‐week randomized placebo‐controlled trial

AimTo test the efficacy and safety of osmotic release oral system (OROS) methylphenidate (MPH) in doses up to 180 mg/day to treat attention deficit hyperactivity disorder (ADHD) and prevent any drug relapse in individuals with a co-diagnosis of ADHD and amphetamine dependence.DesignRandomized placebo-controlled 24-week double-blind trial with parallel groups design.SettingParticipants were recruited from medium security prisons in Sweden. The medication started within 2 weeks before release from prison and continued in out-patient care with twice-weekly visits, including once-weekly cognitive behavioural therapy.ParticipantsFifty-four men with a mean age of 42 years, currently incarcerated, meeting DSM-IV criteria for ADHD and amphetamine dependence.MeasurementsChange in self-reported ADHD symptoms, relapse to any drug use (amphetamine and other drugs) measured by urine toxicology, retention to treatment, craving and time to relapse.FindingsThe MPH-treated group reduced their ADHD symptoms during the trial (P = 0.011) and had a significantly higher proportion of drug-negative urines compared with the placebo group (P = 0.047), including more amphetamine-negative urines (P = 0.019) and better retention to treatment (P = 0.032).ConclusionsMethylphenidate treatment reduces attention deficit hyperactivity disorder symptoms and the risk for relapse to substance use in criminal offenders with attention deficit hyperactivity disorder and substance dependence.

What Does Risperidone Add to Parent Training and Stimulant for Severe Aggression in Child Attention-Deficit/Hyperactivity Disorder?

Although combination pharmacotherapy is common in child and adolescent psychiatry, there has been little research evaluating it. The value of adding risperidone to concurrent psychostimulant and parent training (PT) in behavior management for children with severe aggression was tested. One hundred sixty-eight children 6 to 12 years old (mean age 8.89 ± 2.01 years) with severe physical aggression were randomized to a 9-week trial of PT, stimulant (STIM), and placebo (Basic treatment; n= 84) or PT, STIM, and risperidone (Augmented treatment; n= 84). All had diagnoses of attention-deficit/hyperactivity disorder and oppositional-defiant disorder (n= 124) or conduct disorder (n= 44). Children received psychostimulant (usually Osmotic Release Oral System methylphenidate) for 3 weeks, titrated for optimal effect, while parents received PT. If there was room for improvement at the end of week 3, placebo or risperidone was added. Assessments included parent ratings on the Nisonger Child Behavior Rating Form (Disruptive-Total subscale was the primary outcome) and Antisocial Behavior Scale; blinded clinicians rated change on the Clinical Global Impressions scale. Compared with Basic treatment (PT+ STIM [44.8 ± 14.6mg/day]+ placebo [1.88 mg/day ± 0.72]), Augmented treatment (PT+ STIM [46.1 ± 16.8 mg/day]+ risperidone [1.65 mg/day ± 0.75]) showed statistically significant improvement onthe Nisonger Child Behavior Rating Form Disruptive-Total subscale (treatment-by-time interaction, p= .0016), the Nisonger Child Behavior Rating Form Social Competence subscale (p= .0049), and Antisocial Behavior Scale Reactive Aggression subscale (p= .01). Clinical Global Impressions scores weresubstantially improved for the 2 groups but did not discriminate between treatments (Clinical Global Impressions-Improvement score≤2, 70% forBasic treatment versus 79% for Augmented treatment). Prolactin elevations and gastrointestinal upset occurred more with Augmented treatment; other adverse events differed modestly from Basic treatment; weight gain in the Augmented treatment group was minor. Risperidone provided moderate butvariable improvement in aggressive and other seriously disruptive child behaviorswhenadded to PT and optimized stimulant treatment. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study), URL: http://clinicaltrials.gov, unique identifier: NCT00796302.

Treating Nicotine Dependence by Targeting Attention-Deficit/ Hyperactivity Disorder (ADHD) With OROS Methylphenidate

To determine whether treatment of attention-deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. This is a secondary analysis of data from a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites; the original trial was sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n = 127) or matching placebo (n = 128). All participants received nicotine patches (21 mg/d) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline ADHD Rating Scale-IV (ADHD-RS) score, change in ADHD-RS score during treatment, and their interactions. Treatment interacted with both ADHD-RS score at baseline (P = .01) and change in ADHD-RS score during treatment (P = .008). Among patients with higher ADHD-RS scores (> 36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score ≥ 24), 70.0% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo (P = .02). In contrast, among patients with the lowest ADHD-RS baseline scores (≤ 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo (P = .02). OROS methylphenidate, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD and more robust response of ADHD symptoms to medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD. ClinicalTrials.gov identifier: NCT00253747.

The possible effect of methylphenidate on kleptomania in a school-age girl with attention-deficit/hyperactivity disorder

Kleptomania is an impulse-control disorder (ICD) defined as the recurrent failure to resist impulses to steal objects that are not needed for personal use or for their monetary value. Kleptomania is a relatively rare condition; therefore, few studies have been conducted, and the treatment of the disorder tends to be based on small studies or case reports [1, 4, 6, 8]. Because the frequency of attention deficit/ hyperactivity disorder (ADHD) was found to be higher in patients with ICD [2], some research has focused on the effects of ADHD drugs on the treatment of kleptomania. Two different case reports examined the effect of methylphenidate (MPH) in these patients. In the first report, the authors showed that a combination of sertraline and MPH was successful in treating a child with kleptomania and ADHD [4]. In the second report, the positive effect of MPH on kleptomania was examined on an adolescent with kleptomania and ADHD [8]. The current report presents the case of a 7-year-old girl with kleptomania and ADHD who displayed a complete remission from kleptomania during MPH therapy. The subject patient was referred to the child and adolescent psychiatry outpatient clinic with complaints of stealing behavior, oppositional behavior, and inattention. Her stealing behavior had been observed since she had attended kindergarten. She had stolen her friends’ school materials, including pencil sharpeners, pen cap, eraser dust, a puzzle piece, or Legos. The frequency of her stealing behaviors increased over time, and for last 6 months, she had been stealing these materials nearly every day. Her parents reported that although she collected the things that she had stolen, she almost never used them. They also reported that the girl did not steal the items in anger, and her stealing behavior did not show a temporal relationship with her oppositional attitudes. Although her parents were unsure whether she experienced tension prior to stealing, she typically seemed to be comfortable after the acts. Although the parents had used various punishments to reprimand her for her actions, no reduction in her stealing behaviors was observed. During her psychiatric assessment, inattentiveness, mild hyperactivity, and impulsiveness were clinically observed. There were no signs of anxiety, elevated or depressed mood, psychosis, or compulsive behaviors. Her physical examination was within normal limits, and she had no history of any physical disease. According to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), she met criteria for ADHD (inattentive type) and kleptomania. The severity of her ADHD and kleptomania were detected with using Conner’s Parent Rating Scale and Clinical Global Impression Scale (Table 1) [5, 7]. The patient’s parents were reluctant to try behavioral intervention, so it was not undertaken at this stage. An 18 mg osmotic-release oral system MPH treatment was initiated daily. It resulted in moderate improvement in the girl’s ADHD symptoms and the complete resolution of the kleptomania within the first 10 days. The parents reported improvement in her ADHD, and her coexisting disruptive behavioral disorders’ symptoms continued over time. Complete resolution of the kleptomania continued as well. At the 4-month follow-up, the girl had not exhibited any stealing behavior. According to DSM-IV-TR, when diagnosing kleptomania, a patient’s stealing behavior is not better accounted for S. Yilmaz (&) A. Bilgic Meram School of Medicine, Necmettin Erbakan University, Konya, Turkey e-mail: drsavash@gmail.com