Drug compliance research in ADHD children and Efficacy and safety evaluation of OROS MPH compared with IR MPH in NTUH ADHD children
Date Issued
2004
Date
2004
Author(s)
Shen, Hsin-Yi
DOI
zh-TW
Abstract
Background:
Immediate-released methylphenidate (IR MPH), the only CNS stimulant available for attention-deficit/hyperactivity disorder (ADHD) in Taiwan, has a short half-life, which needs 3 times a day dosing to maintain the effect throughout daytime. The first generation sustained-release formulation of MPH has an only 8 hours effect and has been be less effective when compared with IR MPH due to acute tolerance. A new generation Once-daily Osmotic Release Oral System (OROS) MPH provides a 12-hour effect with ascending profile of pharmacokinetics, which has been proved to have similar efficacy to IR MPH thrice daily and has been approved by FDA in 2000. No study has been done to investigate the patterns and impact of the compliance of IR MPH and efficacy of OROS in Taiwanese or other Asian populations. The objectives of this study are to identify the determinants of IR MPH compliance among children with ADHD, to examine the association of IR MPH compliance on family interaction, parent-child relationship, and parental mental status, and to evaluate the efficacy and safety of once-daily OROS MPH as compared with thrice daily IR MPH among ADHD children.
Methods:
This study consisted of two parts: Part I: compliance survey, and part II: OROS MPH clinical trial.
Part I: This study was a cross-sectional questionnaire survey on compliance to IR MPH. The sample consisted of 375 ADHD children (329 boys, 46 girls), who were recruited from National Taiwan University Hospital (n = 218), Chung-Gung hospital (n = 56), and ADHD Educational Foundation (n=101 ) from November 2003 to March 2004. Parents reported on the measures of demographics, children’s compliance to IR MPH, the Chinese version of Parental Bonding Instrument (PBI-C), the Family APGAR, the Home Behaviors subscale of the Chinese version of Social Adjustment for Children and Adolescent (SAICA-C), and the Chinese Health Questionnaire (CHQ).
Part II: The second part was a randomized clinical trial comparing the efficacy and safety of OROS MPH (n = 32) with trice daily dosing IR MPH (n = 32) among 64 ADHD children aged 6-15 yeas, who were recruited from February 2004 to April 2004. The study period was 28 days. The outcome measures covered the domains of ADHD symptoms at home and school settings, social functioning, and side effects. On study days 1, 6, 13, 20, 27, the ADHD symptoms in the previous week were evaluated by the school teacher and parent using the Conner’s Teacher and Parent Rating Scale-Revised: Short Form (CTRS-R:S and CPRS-R:S). The SKAMP Rating Scale scores were also evaluated by school teachers on study days 1, 13 and 27. The Home Situation Questionnaire was answered by parents on study days 1 and 27. The SAICA-C and Peer Interaction Items were rated by parents and school teachers on study days 1 and 27. Global assessments of treatment effects were determined by parents and the investigator at the end of the treatment. The side effects were evaluated globally at baseline, and after 2 and 4 weeks of treatment by the parents using the Barkley’s Side Effect Rating Scale. Mixed model and generalized linear model were used to conduct analysis of variance.
Results:
Part I: Among 375 ADHD children, 307 were taking IR MPH during study period, 82.8% of their parents thought their child always or often took IR-MPH according to instruction. The main reason for not regularly taking IR-MPH was forget to take medication (72.7%). Poor compliance was most prevalent at noon time (63.4%). Increased age and thrice daily dosing of IR MPH were the major determinants for poor compliance. Compared to their counterparts, parents of children with poor compliance appeared to have less affection and warmth toward their children, and their children were less likely to have interactions with mothers and more severe problems with parents.
Part II: There were no difference between the two treatment groups in demographics and baseline severity in ADHD. Both groups demonstrated significantly reductions in the ADHD core symptoms and inappropriate behaviors after the treatment. Compared to the IR MPH group, the OROS MPH group had greater improvement of symptoms over time in terms of all dimensions related to the ADHD symptoms. Regarding the four domains of social functioning, the OROS MPH group had a significant improvement in school relationships, peer relationships, and sibling relationships, and a decline in problems with parents, while these were not observed in the IR MPH group. The rates of adverse effects showed no significant difference between the two groups, except that the OROS MPH group had a less impact on appetite over time. The majority of the OROS MPH group (68.8%) were more satisfied with OROS MPH than IR MPH, which was used before this clinical trial.
Conclusions:
Findings from this study indicate that multi-dosing regimen decreases the drug compliance in ADHD children, and poor compliance is associate with adverse parent-child relationship. Similar efficacy and safety profile of once-daily OROS MPH to thrice daily IR MPH implies that OROS MPH is effective and acceptable to Taiwanese population. Accordingly, once-daily dosing regimen may improve treatment efficacy and enhance parent-child relationship among families with ADHD children, which is particularly important for ADHD children who are older and with more severe symptoms, due to a strong relation of good drug compliance to improvement in clinical outcomes.
Subjects
口服滲透壓釋放劑型MPH
服藥順從性
注意力缺陷過動症
drug compliance
Attention deficit hyperactivity disorder
OROS methylphenidate
Type
text
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