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Aim: To determine the differences in the remission rate, recovery rate, functional improvement, and treatment adherence related to treatment with short-acting immediate-release methylphenidate (IR-MPH) and long-acting osmotic-release oral system-methylphenidate (OROS-MPH) in a naturalistic setting among Taiwanese children with attention-deficit–hyperactivity disorder (ADHD).
Methods: A total of 757 children with ADHD, aged 6–18 years, was evaluated using the following in order determine functional improvement and treatment adherence: the Chinese version of the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV-C), Clinical Global Impression-ADHD-Severity (CGI-S) to measure remission and recovery rates, the Chinese version of the Social Adjustment Inventory for Children and Adolescents (CSAICA), and caregiver's satisfaction rate, treatment adherence, and frequency of adverse effects.
Results: According to the SNAP-IV-C scores, the remission rate was 30.72%, and the recovery rate was 16.38%. Compared to short-acting IR-MPH, OROS-MPH was associated with greater functional improvement and treatment adherence among children with ADHD.
Conclusion: OROS-MPH treatment at the adequate dosage can achieve higher remission and recovery rates, produce greater functional improvement, and result in better treatment adherence than IR-MPH treatment.
ATTENTION-DEFICIT–HYPERACTIVITY DISORDER (ADHD) is a common pediatric mental disorder that often manifests as chronic learning difficulty and emotional disturbance during childhood.1 Although ADHD is common, the causes of ADHD remain unclear; most authors agree, however, that around 80% of cases are due to hereditary factors.2 Many child mental health-care experts are in agreement that children with ADHD receive delayed or ineffective treatment due to a variety of biopsychosocial obstacles.3,4 Therefore, ADHD may be allowed to progress unchecked, and recovery from ADHD via longitudinal follow up or through general developmental strategies may be difficult.5,6
Although immediate-release methylphenidate (IR-MPH; short-acting treatment) was introduced in 1953, ADHD was considered to be a treatable disease only after the publication of DSM-III-R in 1987.7 Moreover, after the Multimodal Treatment Study on ADHD (MTA study) in the USA, main effective ADHD treatment was considered to be a combination therapy including pharmacotherapy and behavior modification.8 Many researchers had already compared treatment response rate for IR-MPH with that of the osmotic-release oral system (OROS-MPH; long-acting treatment), introduced in 1983.9,10 Among them, the newly introduced OROS-MPH treatment was more effective11,12 and had better patient adherence than IR-MPH treatment.13,14
Effective treatment for children with ADHD should result in functional improvement in addition to symptomatic improvement. In other words, the most effective ADHD treatment should minimize or even completely eliminate ADHD symptoms and optimize functioning in various areas such as academic performance,15 social interaction,16,17 and family functioning.18 Moreover, some authors, following the concept of remission originally established by studying depressed patients treated with antidepressants,19,20 indicated that remission can be achievable under specific OROS-MPH.19,21
Most of these studies on the remission rate and response rate of ADHD patients, comparing two frequently used types of MPH preparation (OROS-MPH vs IR-MPH), had been conducted in Canada by Steel et al.21 Little information regarding the aforementioned parameters is available for ADHD patients in Asian countries.22 Using the hypothesis that OROS-MPH is superior in effectiveness to its IR form, as per Western research, the aim of the present study was to determine the remission rate, recovery rate, and functional improvement for two types of MPH treatment, namely, OROS-MPH and IR-MPH, among the Taiwanese population using a naturalistic observation design.
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The aim of the present study was to confirm whether the superiority of OROS-MPH treatment over IR-MPH treatment, in terms of higher rates of remission and recovery, and greater improvement in social functioning, that has been reported in the Western literature is maintained in the Taiwanese population. We found that once-daily treatment with long-acting OROS-MPH was associated with higher remission and recovery rates, greater improvement in social functioning, better adherence, and higher drug dosage than usual IR-MPH-based treatments (OROS, 30.16 ± 10.75 mg vs IR, 19.40 ± 11.40 mg). Also, because only few concomitant psychosocial interventions were provided by the clinician (not shown), this naturalistic study is important because it focuses only on the drug treatment effect of the two different kinds of MPH. This naturalistic observational study plays a useful role in clarifying general trends in MPH utilization and comparing remission and recovery rates between two differently acting MPH delivery systems in the Asian population.
Analysis of the four study groups showed that treatment effectiveness increased in the following order: no treatment group, IR-MPH only, OROS-MPH only, IR-MPH+OROS-MPH. The remission and recovery rates for the children with ADHD treated with short-acting MPH was 0.15–0.45-fold higher than those untreated. Supporting the MTA study recommendation, this finding demonstrates that pharmacotherapy is not only helpful for children with ADHD but also important for reaching remission or achieving recovery from ADHD.8,26 Regarding the actual remission or recovery rate of pharmacotherapy for children with ADHD, in the present study, 30.72% of children with ADHD attained remission on OROS-MPH; further, this remission rate was 1.61-fold greater than that obtained on short-acting IR-MPH. A total of 16.38% of children with ADHD achieved recovery on OROS-MPH according to SNAP-IV-C scores, and this recovery rate was 1.96-fold greater than that on IR-MPH. Therefore, the present naturalistic observational study of Taiwanese ADHD children highlights higher remission rates compatible with those of recently published western studies,19,21 and shows that higher recovery rates are achievable when using long-acting OROS-MPH compared to short-acting IR-MPH.
Once-daily OROS-MPH improves treatment adherence among patients with ADHD according to a study conducted in Taiwan.27 The present results are compatible with that study; another study also found higher adherence with OROS-MPH (67.24%) than IR-MPH (36.23%).28 With regard to risks that influence treatment adherence, severity of ADHD symptoms, presence of oppositional defiant disorder/conduct disorder, learning difficulties, anxiety, age, family dysfunction, socioeconomic adversity, response to treatment at school and parent satisfaction are usually regarded as factors that exacerbate poor treatment adherence.29–31 Compatible with results of two local studies,4,13 the present results indicate that long-acting OROS-MPH treatment actually reduced poor treatment adherence and raised caregiver satisfaction rate compared to IR-MPH treatment.
Regarding the difference in adverse effects among the three groups, the present results are similar to other studies:4,9 there were no significant differences related to adverse effects between the two different MPH delivery systems or the combination of the two different MPH delivery systems. This finding is against general thinking that children with ADHD experience less adverse effects when using OROS-MPH than IR-MPH. A possible explanation is that the dosage of OROS-MPH during the short study period was higher than that of IR-MPH; therefore, a similar percentage of patients experienced loss of appetite in both the OROS-MPH and IR-MPH groups. But although the frequency of adverse effects was similar between the long- and short-acting MPH, the parents were more satisfied with OROS-MPH than with IR-MPH, and hence, adherence to the former treatment was greater than that to the latter.
Steele et al. have emphasized that an adequate dose of MPH (36 mg/day) is required to attain remission in ADHD.19 In the present study, a mean dose of 30.16 ± 10.75 mg/day OROS-MPH was sufficient to induce remission, which is near that required in the Steele et al. study in Canada. But the mean dose to achieve remission in the Taiwanese IR-MPH group was 19.40 ± 11.40 mg/day, which is 50% lower than that used for the Canadian subjects in the Steele et al. study. A study in Korea also found that children with ADHD experienced more adverse effects, specifically loss of appetite, and usually required a lower mean dose than that reported in Western literature.16 A possible explanation for lower IR-MPH doses is that Asian parents are very anxious about the side-effects of short-acting stimulant drugs. This may explain why Taiwanese or Asian subjects usually use lower doses than Western subjects.
Functional improvement, as determined using the parents' and investigators' global scores, was better in the OROS-MPH-based treatment groups than in the IR-MPH-only group for all the parameters studied, except for relationship with peers. In particular, OROS-MPH was found to significantly improve the parameter ‘problems in interaction with mother’, as determined using the investigators' scores. The possible reason for the absence of significant improvement in relationship with peers may be that investigators and parents find it more difficult to evaluate this parameter than teachers. Or that the stimulant effect produces better results in study performance than interpersonal relationships, because it improves attention. Previous authors, however, have assessed only academic or emotional improvement after OROS-MPH treatment.16,17 Our present study demonstrates effectiveness in social interpersonal functioning improvement among children with ADHD32,33 when using OROS-MPH rather than IR-MPH.
This study had the following limitations. First, although the study involved nine hospitals, four phases of assessment, and 1 year of follow up, the results cannot be generalized to all children with ADHD in Taiwan. Second, the actual MPH-utilization patterns in the present study were divided into four groups according to natural observation. Although we divided the OROS-MPH-based treatment groups into the OROS-MPH only group and the OROS-MPH+IR-MPH group, the significant effectiveness of pure OROS-MPH treatment might not have been fully estimated; also, there are no details on significant group differences in dose change of MPH. Third, in the OROS-MPH+IR-MPH group, we did not specify whether IR-MPH was used as the physician recommended (at 17.00 hours) or as a twice- or thrice-daily treatment to strengthen the effect of OROS-MPH or lower the cost of OROS-MPH therapy (national insurance in Taiwan limits the use of OROS-MPH because of economic reasons). Fourth, the reference for the Chinese version of SNAP-IV is not an international journal easily accessible by international readers. Fifth, teacher ratings were not used to assess symptom severity and social function. And sixth, symptom improvement cannot be explained only by MPH treatment. Other treatment factors should be explored.
In conclusion, remission; recovery, functional improvement, and good adherence can be achieved using an adequate dose of OROS-MPH.