Titrating Optimal Dose of Osmotic-Controlled Release Oral Delivery (OROS)-Methylphenidate and Its Efficacy and Safety in Korean Children with ADHD: A Multisite Open Labeled Study

OBJECTIVE: This study was aimed to determine effectiveness and tolerability of Osmotic-controlled Release Oral delivery (OROS) methylphenidate (MPH) and its optimal dose administered openly over a period of up to 12 weeks in drug naive Korean children with ADHD. METHODS: Subjects (n=143), ages 6 to 18-years, with a clinical diagnosis of any subtype of ADHD were recruited from 7 medical centers in Korea. An individualized dose of OROS-MPH was determined for each subject depending on the response criteria. The subjects were assessed with several symptom rating scales in week 1, 3, 6, 9 and 12. RESULTS: 77 of 116 subjects (66.4%) achieved the criteria for response and the average of optimal daily dose for response was to 30.05+/-12.52 mg per day (0.90+/-0.31 mg/kg/d) at the end of the study. Optimal dose was not significantly different between ADHD subtypes, whereas, significant higher dose was needed in older aged groups than younger groups. The average of optimal daily dose for response for the subjects aged above 12 years old was 46.38+/-15.52 per day (0.81+/-0.28 mg/kg/d) compared to younger groups (p<0.01). No serious adverse effects were reported and the dose did not have a significant effect on adverse effects. CONCLUSION: Optimal mean dose of OROS-MPH was significantly different by age groups. Higher dose was needed in older aged groups than younger groups. Effectiveness and tolerability of OROS-MPH in symptoms of ADHD is sustained for up to 12 weeks.

Effect of Methylphenidate on Sleep Parameters in Children with ADHD

OBJECTIVE: The primary aim of this study was to investigate the acute impact of methylphenidate (MPH) on sleep parameters in attention-deficit/hyperactivity disorder (ADHD) children. The second aim was to investigate the different effects of intermediate- and longacting MPH on sleep parameters. The third aim was to test the different effects of dose and age on sleep parameters. METHODS: Ninety-three ADHD children were enrolled and randomized to two different MPH preparations. Baseline and daily sleep diaries were evaluated for four weeks after taking medication. Weekday and weekend bedtimes, wake-up times, sleep latencies and total sleep times were compared by weeks. RESULTS: After taking MPH, there was a significant delay in bedtimes and a significant reduction of total sleep time (TST) both on weekdays and at weekends. There was also a significant delay in wake-up time on weekdays. However, the difference was applied to younger age group children only. There was no difference in changes of TST between metadate-CD and OROS-MPH. There also was no difference in changes of TST with different doses of MPH. CONCLUSION: MPH had negative impacts on sleep among young ADHD children, but different preparations and doses did not affect the result.

Switching from Methylphenidate-Immediate Release (MPH-IR) to Methylphenidate-OROS (OROS-MPH): A Multi-center, Open-label Study in Korea

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of methylphenidate HCL OROS extended-release (OROS-MPH) among children with attention deficit hyperactivity disorder (ADHD) who had been previously treated with methylphenidate HCL immediate-release (MPH-IR). METHODS: The sample included 102 children aged 6-12 (9.4+/-2.6) years who had been diagnosed with ADHD according the criteria of the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV; American Psychiatric Association, 1994) and who were attending seven centers in Korea. All participants had been medicated with a stable dose of MPH (10-60 mg/day) for at least 3 weeks before entry into the study. Doses of OROS-MPH were comparable to daily doses of MPH. Efficacy was assessed at baseline (day 0) and at day 28 with the Inattentive-Overactive with Aggression (IOWA) Conners Rating Scale, which was completed by parents/caregivers and teachers, the Peer Interaction Rating Items, which were completed by teachers, and the Clinical Global Impression (CGI) scale, which was completed by child psychiatrists. Paired t-tests were used, and P-values were set at the 0.05 level. RESULTS: Of the subjects, 92.2% were boys and 79.4% were students in the first to fourth grades of elementary school. 72% were diagnosed with the combined type of ADHD, 23% were diagnosed with the inattentive type, and 5% were diagnosed with the hyperactive-impulsive type. The results of the parents' responses to the Inattention/Hyperactivity (I/H) and Oppositional/Defiant (O/D) subscales of the IOWA Conners scale indicated statistically significant improvement in childrens behavior after 4 weeks of treatment with OROS-MPH (t=6.28, p<.001, t=4.12, p<.001). However, the teachers' responses to the Conners I/H and O/D subscales indicated no significant improvement at 4 weeks. The teachers also reported no significant improvements under the OROS-MPH compared with the MPH-IR condition with respect to peer interactions. Scores on the CGI scale showed that 46.1% of children with ADHD were rated by psychiatrists as "minimally improved", 27.5% as "much improved," 1.0% as "very much improved," 3.9% as "minimally worse," and 16.7% as showing "no change". Children exhibited significantly fewer tics with OROS-MPH treatment than with MPH-IR treatment (19.6% vs. 27.7%). We found no differences between in sleep and appetite problems according to medication. CONCLUSION: The results of this study indicated that an MPH-IR regimen can be successfully changed to a once-daily OROS-MPH regimen without any serious adverse effects. The changes in parent/caregiver IOWA Conners ratings suggested that OROS-MPH improved the control of symptoms after school, a finding that is consistent with the 12-h duration of action of this medication. Because the therapeutic effect of OROS-MPH is sufficiently longer than that of a b.i.d. dose of MPH-IR, OROS-MPH had significant positive effects on oppositional/defiant behavior in addition to its effects on the core symptoms of ADHD.

The Side Effects and Correlates of OROS-Methylphenidate in the Treatment of Children and Adolescents with ADHD

OBJECTIVES: The aim of this study was to investigate the effect of the clinical and demographic variables such as body weight, dosage, family history of attention-deficit hyperactivity disorder (ADHD), and psychiatric co-morbidity on the side-effects of OROS-Methylphenidate (OROS-MPH), and to evaluate the relationship between drug response and side effect severity. METHODS: A total of 144 children (ages 6-18) with diagnosed ADHD were treated with OROS-MPH. Children were examined at baseline and after 1, 3, 6, 9, and 12 weeks of each treatment condition. The stimulant drug side effect rating scale (SERS), pulse rate, systolic blood pressure, diastolic blood pressure, and electrocardiogram (ECG) were evaluated to assess side effect profiles. Changes in these parameters from baseline were examined and analyzed. RESULTS: Anorexia (30.95%) and insomnia (13.10%) were the most commonly reported side effects during this study. Insomnia and loss of appetite score increased at one week follow-up, but was sustained or decreased as treatment progressed. Small but significant increases in pulse rate and diastolic blood pressure were observed during treatment; however, no clinically meaningful changes in ECG parameters were noted during the study. Low body weight, high dosage of OROS-MPH, and family history of ADHD were associated with cardiovascular side effect. In contrast, there was no significant relationship between OROS-MPH treatment response and the severity of side effect and no difference resulted between the responder and non-responder groups with respect to OROS-MPH dosage in the 12 weeks of follow-up. CONCLUSION: To the best of our knowledge, this study is the first Korean study to investigate comprehensive side effect profiles and their correlates in OROS-MPH treatment for ADHD children. OROS-MPH was well tolerated with no clinically significant side effects during the treatment period. In conclusion, low body weight, high dosage of OROS-MPH, and family history of ADHD could be used as predictive factors in increasing pulse rate and blood pressure.

Prescription Status and Efficacy of OROS-MPH and Parent Perception in Children with Attention Deficit Hyperactivity Disorder : Multi-Center, Observational Study during 4 Weeks / 대한정신약물학회지

OBJECTIVE: This study was performed to evaluate the current prescription status by clinicians, the efficacy of once-daily OROS-methylphenidate (MPH) in the treatment of children with attention deficit hyperactivity disorder (ADHD) and parent anticipation, concern and satisfaction about treatment. METHODS: The subjects with ADHD between 6 and 18 years were prescribed 18, 36, 54 mg OROS-MPH, depending on clinician's judgment. ADHD symptoms and improvement were assessed by clinicians using the Clinical Global Impression-Severity (CGI-S) and the Clinical Global Impression-Improvement (CGI-I). Parents were also measured the Conners Abbreviated Parent Rating Scale (CAPRS) and by the questionnaires inquiring about parental anticipation, concern, satisfaction about treatment at baseline and the 4th week after OROS-MPH trial. RESULTS: A total of 704 subjects were enrolled in the observational study and 645 completed the trial. There was an 18% increase in mean daily dose and 14% increase in mean daily dose per kg during 4 weeks. About 56% of subjects were scored 2 or less by the CGI-I. CAPRS scores were significantly decreased from 14.8 to 8.81. Before treatment, parents anticipated the symptom improvement firstly, followed by education material, parental education and non-pharmacological treatment. Parent concerned about side effect, growth, dependency and abuse. In general, 95% of parent were satisfied with OROS-MPH . CONCLUSION: According to this study, there was an increase in mean daily dose over the study period. OROS-MPH appears to be efficacious for decreasing the symptoms of ADHD and was satisfactory to parents of children with ADHD.