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Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder

ZHENG, Yi; WANG, Yu-feng; QIN, Jiong; WANG, Li-wen; ZOU, Li-ping; JIN, Xing-ming; XU, Tong; WANG, Yi; QI, Yuan-li; GONG, Mei-en; YIN, Qing-yun; MAI, Jian-ning; JING, Jin; LUO, Xiang-yang; MA, Hong-wei; LI, Hai-bo; XIE, Ling; LI, Yan; Kuang, Gui-fang; YI, Ming-ji; WANG, Feng; ZHU, Xiao-hua; YAO, Yan-bin

doi: 10.3760/cma.j.issn.0366-6999.2011.20.011
Original article
Free
SDC

Background Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, characterized by the core symptoms of hyperactivity, impulsivity and inattention and puts great burden on children themselves, their families and the society. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH). It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles. The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.

Methods This 6-week, multi-center, prospective, open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg, 36 mg or 54 mg) treatment. The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales, physician-rated CGI-I and parent-rated global efficacy assessment scale. Blood pressure, pulse rate measurement, adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.

Results A total of 1447 children with ADHD (mean age (9.52±2.36) years) were enrolled in this trial. Totally 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study. The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P <0.001) improvement with OROS-MPH (mean: 6.95±2.71) versus the score at baseline (10.45±2.72). The change in the parent IOWA Conners O/D subscale, CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). No serious adverse events were reported during the study.

Conclusion This open-label, naturalistic study provides further evidence of effectiveness and safety of OROS-MPH in school-aged children under routine practice.

Department of Pediatrics, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China (Zheng Y); Department of Pediatrics, Institute of Mental Health, Peking University, Beijing 100191, China (Wang YF); Department of Pediatric Neurology, Women's and Children's Department, Peking University First Hospital, Beijing 100034, China (Qin J); Department of Pediatric Neurology, Capital Institute of Pediatrics, Beijing 100020, China (Wang LW); Department of Pediatric Medicine, Beijing Children's Hospital of Capital Medical University, Beijing 100045, China (Zou LP); Department of Pediatrics, Shanghai Children's Medical Center of Shanghai Jiaotong University, Shanghai 200127, China (Jin XM); Department of Pediatrics, Shanghai Changzheng Hospital of Second Military Medical University, Shanghai 200003, China (Xu T); Department of Pediatrics, Pediatric Hospital of Fudan University, Shanghai 200032, China (Wang Y); Department of Psychiatry, Institute of Mental Health, Guangzhou, Guangdong 510080, China (Qi YL); Department of Psychology, Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510150, China (Gong ME); Department of Psychiatry, Guangzhou Brain Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510510, China (Yin QY); Department of Neural Rehabilitation, Guangzhou Children's Hospital, Guangzhou, Guangdong 510120, China (Mai JN); Department of Pediatrics, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China (Jing J); Department of Pediatric Medicine, Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510130, China (Luo XY); Department of Child Health, Second Hospital of China Medical University, Shenyang, Liaoning 110022, China (Ma HW); Department of Pediatrics, First Hospital of Jilin University, Changchun, Jilin 130021, China (Li HB); Department of Child Health, Nanjing Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, China (Xie L); Department of Neurology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, China (Li Y); Department of Pediatric Mental Health, Qingdao Women and Children Health Care Centers, Qingdao, Shandong 266011, China (Kuang GF); Department of Child Health, Affiliated Hospital of Qingdao University Medical School, Qingdao, Shandong 266003, China (Yi MJ); Department of Neurology, Hubei Material and Child Health Hospital, Wuhan, Hubei 430070, China (Wang F); Department of Psychiatry, Seventh People's Hospital of Hangzhou, Hangzhou, Zhejiang 310013, China (Zhu XH); Department of Child Health, Tianjin Women's and Children's Health Center, Tianjin 300270, China (Yao YB)

Correspondence to: Dr. ZHENG Yi, Department of Pediatrics, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China (Tel: 86-10-58303181. Email: doctorzy@yahoo.com)

This study is funded by Xi'an Jassen Pharmmaceutical Ltd, China.

(Received November 3, 2010)

Edited by CHEN Li-min

Attention deficit hyperactivity disorder (ADHD), a highly prevalent and clinically heterogeneous behavioral disorder, is estimated to affect up to approximately 3%-5% of children and adolescents world wild,1,2 and often persists into adulthood.3 ADHD is associated with a broad range of negative outcomes for affected subjects4 and puts a serious burden on families and societies.5 As a result, early identification and treatment of symptoms of ADHD is essential to effective management of this disorder.

Stimulant agents are well-established as first-line pharmacotherapy for both school-aged children and adults.6 Immediate-release methylphenidate (IR-MPH) is the most commonly prescribed and best-studied stimulant medication and has been shown to be highly efficacious for treating ADHD.7,8 However, its short duration of action usually results in a requirement to administer multiple times daily in order to achieve optimal clinical benefit. The need for multiple dosing produces problems with medication administration during school and after-school hours and therefore leads to poor compliance. Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with IR-MPH9 and has demonstrated efficacy and safety in reducing the core symptoms of ADHD in well-designed, multicenter, placebo-controlled, double-blind trials.10-12

OROS-MPH has been marketed in China since 2005 and it still lacks data from large-sample clinical trials on efficacy and safety profiles. Therefore, the urgent need is to conduct an observational study, collecting the effectiveness and safety data under the naturalistic clinical setting and then provide more supportive evidence for the use of OROS-MPH in the real clinic background.

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METHODS

Study population

Twenty-three research centers across China recruited physically healthy, male and female outpatients, aged 6-16 years inclusive, with a documented Diagnostic Statistical Manual-Fourth Edition (DSM-IV) diagnosis of attention-deficit/hyperactivity disorder.1 Subjects were patients willing to take OROS-MPH as the only medicine for ADHD and the written informed content forms must be obtained from their parents/guardians.

Exclusion criteria included: (1) Subjects with anxiety disorder, mood disorder, general development disorder, serious depression, schizophrenia; (2) Known to be allergic to methylphenidate or other ingredients of the study drug; (3) Subjects with glaucoma; (4) Subjects with family history or diagnosed as Tourette syndrome; (5) Taking or having taken monoamine oxidase inhibitor in the past 14 days, taking the following drugs such as clonidine, other α-2 adrenergic receptor agonist, tricyclic antidepressants, theocine, bishydroxycoumarin and so on; (6) Participating in clinical trials of other drugs; (7) Cardiovascular diseases including moderate to severe hypertension, hyperthyroidism; (8) History of drug dependence or alcohol dependence; (9) Subjects with serious gastrointestinal stenosis, dysphagia and other serious somatic diseases.

During the 6-week treatment period, the subjects will be excluded from our observation if the conditions as below occurred: (1) Subjects are unwilling to keep receiving OROS-MPH therapy due to poor therapeutic effect, intolerance of adverse events, etc; (2) Serious adverse events related to OROS-MPH; (3) Violating the study protocol by taking ADHD drugs which are not allowed; (4) Other serious somatic diseases judged by investigators occur (The condition that the child is in danger based on the BP measurement at any time was also included); (5) Tic symptoms increase or new serious tic symptoms appear; (6) Pregnancy.

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Study design

This study was a prospective, naturalistic, open-label, pilot study of OROS-MPH conducted in an outpatient setting. Potentially eligible school-aged children were screened for categorical diagnosis and willingness of medication to determine eligibility. Subjects were prescribed OROS-MPH (18, 36 or 54 mg once daily) at the discretion of investigators. However, the recommended dosing strategy is: (1) For subjects who have not received methylphenidate treatment before, the initial dosage was 18 mg. (2) For subjects who were receiving methylphenidate treatment, subjects receiving 5 mg IR-MPH 2 or 3 times a day were assigned to OROS-MPH 18 mg q.d.; subjects receiving 10 mg IR-MPH 2 or 3 times a day or receiving a total daily dose of 40 mg IR-MPH were assigned to OROS-MPH 36 mg q.d.; and subjects receiving 15 mg IR-MPH 2 or 3 times a day or a total daily dose of >45-60 mg were assigned to OROS-MPH 54 mg q.d. Doses of OROS-MPH could be adjusted between a total daily dose range of 18 and 54 mg after 14 days of treatment by the investigator on the basis of safety and efficacy.

There were four protocol-specified visits: screening/ baseline, week 2, week 4 and week 6. The visits were scheduled based on the frequency of naturalistic clinical interview which was derived from the consensus of the principle investigators involved in this observational study.

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Measures

The primary effectiveness measure was the Inattention/ Overactivity with Aggression (IOWA) Conners Rating Scale.13 The IOWA Conners Rating Scale consists of 10 items divided into 2 subsets, I/O and Oppositional/ Defiance (O/D). Items were scored on a 4-point scale (from 0=not at all to 3=very much) and the subsets were analyzed separately. Parents completed both subsets of the IOWA Conners Rating Scale at each visit to evaluate inattention and behavior of children at home. The IOWA Conners Rating Scale has been used in treatment studies and has shown adequate discriminant validity.14

Secondary effectiveness measures included: (1) Physician-rated Clinical Global Impression-Improvement (CGI-I), rated on 7-point scale (1-7, 1=Very much improved, to 7=Very much worse). The rating was based on a review of parents' ratings and a parent interview. The CGI-I has been shown to be sensitive to medication effects in a trial with children and adolescents.15 (2) Global assessment of efficacy rated by parents.10 Parents completed a global assessment of efficacy at baseline, weeks 2, 4 and 6 rating the patient's behavior and attention on a 4-point scale (1=poor; 2=fair; 3=good; 4=excellent) in response to the following question: What is your opinion of the effectiveness of treatment this 2 weeks?

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Safety assessment

Each subject had a general physical examination and baseline blood work-up (if necessary) before initiating OROS-MPH. Blood pressure, pulse rate measurement, AE review, and concomitant medications and treatment review were conducted by the investigator at baseline and at each subsequent monitoring visit. Additionally, parents rated the subject's sleep quality on days 0, 14, 28 and 42. Sleep quality was rated as good, fair or poor. Parents were also questioned on days 0, 14, 28 and 42 about the presence of motor and/or verbal tics.

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Statistical analysis

Primary analysis was based on the Full Analysis Set (FAS) that was comprised of those children who received at least one dose of OROS-MPH and had Connners scale score evaluated at baseline and had at least one of data above at visit 2 as well. Per-protocol set was defined as a set of all children who reasonably followed the protocol procedures and had good compliance to the treatment drug and had Connners scale score at visits 1-4. Safety analysis was performed in safety set (SS) population that was comprised of those who received at least one dose of the investigational drug and had safety data at visits 2-4.

The demographic descriptive statistics was performed in FAS population. Efficacy analysis was performed in FAS population. Safety analysis was performed in SS population. The t test was performed to compare the difference in mean values between baseline and endpoint of study. Qualitative data were analyzed using the χ2 test and a P value of less than 0.05 was considered as having a significant difference. Number, type, relevance and severity of adverse events were also summarized and the numbers and reasons of withdrawal caused by adverse events were given. The descriptive method was used to summarize vital signs, laboratory tests and other safety data. The statistical software SAS V8.1 was used.

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RESULTS

Baseline characteristics

During the period from April 1, 2006 to February 15, 2007, 1447 ADHD patients were enrolled in the observational study and received OROS-MPH treatment. The 1447 subjects were included in the safety analysis. The ITT effectiveness analysis consisted of 1398 subjects based on the criteria of FAS defined in this protocol. Among them, 1154 subjects (79.8%) completed the 6-week trial. The 889 subjects conformed to the PP criteria defined in this protocol and were included in PP set. During the study, 293 subjects (20.2%) dropped out the study, including 34 cases dropped out from baseline to week 2, 182 at week 3-4 and 77 at week 5-6. The reasons of patients discontinued prematurely included: lost to follow-up (n=133, 45.4%); Parent not interested (n=40, 13.7%); AEs (n=34, 11.6%); Economic factors (30, 10.2%); Lack of efficacy (n=27, 9.2%); Concern for side-effects (n=8, 2.7%) and no reason stated (21, 7.2%). The baseline characteristics is shown in Table 1.

Table 1

Table 1

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Medications

At baseline, 99.8% children were treated with an OROS-MPH modal dose of 18 mg and 0.2% with 36 mg at baseline. In contrast, 96.8% children received an OROS-MPH modal dose of 18 mg, 3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study.

Good compliance was defined as more than 80% adherence to the prescribed regimen of OROS-MPH. The 1300 (93.4%) patients meet the criteria at days 1-14, while 1131 (93.5%) at days 14-28, 1045 (93.9%) at days 28-42, and 1301(93.5%) at days 1-42. The results on the compliance suggested that OROS-MPH has a good tolerability in treating ADHD.

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Primary effectiveness outcomes

Table 2 shows the baseline, weeks 2, 4 and 6 results for the parent IOWA Conners I/O and O/D subscales. The parent IOWA Conners I/O scores at the end of week 2 showed statistically significant (P <0.001) improvement with OROS-MPH (mean: 6.95±2.71) versus the scores at baseline (10.45±2.72). The trend of improvement was seen in the parent ratings on the IOWA Conners I/O scores over time with OROS-MPH and the I/O score decreased to 4.30±2.52 at the end of this trial. The results of parent IOWA Conners O/D scores also supported the superior efficacy for OROS-MPH treatment.

Table 2

Table 2

When analyzed based on the age group (≤12 or >12 years old) and the types of ADHD, the data also suggested that OROS-MPH could improve the core symptoms significantly (P <0.001).

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Secondary effectiveness outcomes

Results of the secondary effectiveness analyses are reported in Table 3. The CGI-I scores at the end of weeks 4 and 6 showed statistically significant (P <0.001) improvement with OROS-MPH (mean: 3.34±0.92 and 3.31±0.98, respectively) versus the scores at week 2 (3.44±0.97). On the CGI-I, 1230 (90.1%) subjects were rated as “Very much improved” or “Much improved” at week 6.

Table 3

Table 3

The results of the global assessment of efficacy, completed by parent at each visit, also showed significant benefits (P <0.001) for OROS-MPH treatment. At the end of trial, ratings of “Good” or “Excellent” were obtained by 79.4% of patients who were taking OROS-MPH.

Among the subgroup based on the different age (≤ 12 or > 12 years old) and the types of ADHD, the global assessment of efficacy by parent and CGI-I also supported the superior efficacy for OROS-MPH treatment (P <0.001).

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Safety assessment

AEs

In this trial, patients who received at least one dose of OROS-MPH and had Connners scale score evaluated at baseline and had at least one of data above at visit 2 as well were included in the analysis of safety (n=1447). No serious adverse events were reported during the study. Fewer than half of 1447 patients (511(35.3%)) reported AEs, and the majority of the events reported were mild (68.2%). The AE incidence of 18 mg OROS-MPH group was 28.6%, while the incidence of 36 mg OROS-MPH group was 31.8%. A total of 34 patients discontinued the study early due to the following AEs: loss of appetite (n=13), rash (n=1), insomnia (n=1) and other (n=19). The most commonly reported AEs were loss of appetite (47.9%), insomnia (12.6%), headache (12.4%) and stomach ache (12.1%).

In this study, most subjects (89.2%) were not greater than 12 years old. The incidence of AEs was lower in 6-12 years group (34.55%) than that of 13-16 years group (40.79%). When analyzed based on the types of ADHD, the data showed that the incidence of AEs occurred in patients of hyperactive/impulsive type (23.02%) was lower than that of combined type (37.35%) or inattention type (36.38%).

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Sleep quality and Tic

Sleep quality was rated as good, fair or poor. At baseline, most patients (59.2%) were assessed as have good sleep quality. As rated on days 14, 28 and 42, the majority of patients (>59%) continued to have good sleep quality (Table 4). During this study, the number of patients who were reported to have Tic at each visit is shown in Table 4. With prolongation of the treatment time, the incidence of tic symptom decreased gradually.

Table 4

Table 4

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BP and pulse rate

There was no significant difference in blood pressure at weeks 2, 4 after administering versus the value at baseline. Blood pressure at week 6 increased significantly. However, it had no clinical significance since the value still varied within the normal range. After 6-week treatment, the pulse changed (0.28±4.77) beats/min compared with that of the baseline. Pulse was stable and was not affected after OROS-MPH treatment.

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DISCUSSION

To the best of our knowledge, this is the first systematic assessment of the effectiveness and safety of OROS-MPH in a sample of 6- to 16-year old patients with ADHD under naturalistic settings. OROS-MPH improved parent-rated hyperactive, inattentive, oppositional and defiant behaviors of school-aged children diagnosed with ADHD. A significant improvement (mean reduction of score: 6.29±3.12) at the end of study (week 6) was observed over baseline on the parent-rated IOWA Conners I/O subscale, and a similar improvement was also seen on the parent-rated IOWA Conners O/D subscale, physician-rated CGI-I, and global assessment scale of efficacy rated by parents. Improvement in the ADHD symptoms experienced by the school-aged children with OROS-MPH in the current trial is comparable to the previous studies.16,17 In addition to children, OROS-MPH also showed good efficacy and safety in adult ADHD patients.18-20 Since OROS-MPH was approved to use in treating ADHD by FDA in May of 2000 OROS-MPH can extend treatment continuity of patients significantly and improve the compliance of the treatment.10,21-23 It was further demonstrated in our study that a high percentage of patients were in compliance to the dose prescribed by physician throughout the 6-week treatment. Only 34 patients discontinued prematurely due to adverse events and the results suggested that OROS-MPH had good tolerability for the school-aged children.

The incidence of adverse events was 35.3%, which was approximate to 37.8% reported in South Korea24 and 41.2% reported in USA,13 but it was much lower than 72.4% reported in Europe.25 In this study, the AE incidence of 36 mg OROS-MPH group was a little higher than that of 18 mg OROS-MPH group ( 31.8% vs. 28.6%). However, there was only 44 patients taking 36 mg OROS-MPH, needing further evidence in future study. No serious adverse events were reported. Besides, the majority of adverse events reported were mild. This may be attributable, in part, to the fact that the doses prescribed in this trial were lower compared with the other trial.17 However, this is still controversy since several studies indicated that the efficacy of 36 mg and 54 mg dose groups was significantly better than that of 18 mg dose group and the incidence of adverse events was not affected.24-27 A high percentage of patients (96.9%) were treated with an OROS-MPH modal dose of 18 mg at the endpoint of this trial while only 42 patients took 36 mg and one patient took 54 mg. The most common adverse event was loss of appetite (47.9%), but only 13 patients dropped out the study due to significant loss of appetite. Since the patients in this study only received 6-week OROS-MPH treatment, the long-term adverse events such as influence on growth and weight can not be observed. This is a limitation of this study because ADHD patients need long-term treatment.

There was no significantly negative effect on sleep quality in our study. On the contrary, the sleep quality in 6-12 years group was improved after OROS-MPH treatment. It further enforced the available evidence28 that OROS-MPH treatment was not a possible cause of sleep problems in the treated children although this stimulant as well as immediate-release methylphenidate has long been suspected to adversely affect sleep qualities of treated patients, especially children. In a 6-week, prospective, open-label, flexible-dose trial with OROS-MPH monotherapy, the treatment does not seem to impair sleep and may even improve some aspects of sleep demonstrated by both a parental sleep questionnaire and polysomnography.29 Similarly, the data from our study suggested that OROS-MPH therapy did not significantly induce or exacerbate tics in children with ADHD.

The development of OROS-MPH satisfied the need of administering once daily and maintaining an effective dosage. Many multi-center, double-blind, randomized clinical trials showed the efficacy of OROS-MPH was stable and durable home and abroad. Comparing with IR-MPH, it can avoid the fluctuation of plasma concentration, make efficacy more stable, have a good tolerability and safety and increase the compliance significantly.17,25,30,31 Since OROS-MPH came into the market shortly, this multi-center, prospective, open-lable observation filled up information of clinical efficacy and safety in a large sample of treating ADHD with OROS-MPH, had a guiding significance for medication more reasonably in the future and further proved OROS-MPH safe and effective in treating ADHD. In conclusion, OROS-MPH is an effective and safe drug in treating ADHD.

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REFERENCES

1. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet 2005; 366: 237-248.
2. Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2003; 2: 104-113.
3. Searight HR, Burke JM, Rottnek F. Adult ADHD: evaluation and treatment in family medicine. Am Fam Phychiatry 2000; 62: 2077-2086.
4. Swanson JM, Sergeant JA, Taylor E, Sonuga-Barke EJ, Jensen PS, Cantwell DP. Attention-deficit hyperactivity disorder and hyperkinetic disorder. Lancet 1998; 351: 429-433.
5. National Institutes of Health Consensus Development Conference. National Institutes of Health Consensus Development Conference Statement: diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD). J Am Acad Child Adolesc Psychiatry 2000; 39: 182-193.
6. Greenhill LL, Pliszka S, Dulcan MK, Bernet W, Arnold V, Beitchman J, et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2002; 41 (2 Suppl): 26S-49S.
7. Rapport MD, Denney C, DuPaul GJ, Gardner MJ. Attention deficit disorder and methylphenidate: normalization rates, clinical effectiveness, and response prediction in 76 children. J Am Acad Child Adolesc Psychiatry 1994; 33: 882-893.
8. Van der Oord S, Prins PJ, Oosterlaan J, Emmelkamp PM. Efficacy of methylphenidate, psychosocial treatments and their combination in school-aged children with ADHD: a meta-analysis. Clin Psychol Rev 2008; 28: 783-800.
9. Adesman AR. New medications for treatment of children with attention-deficit/hyperactivity disorder: review and commentary. Pediatr Ann 2002; 31: 514-522.
10. Wolraich ML, Greenhill LL, Pelham W, Swanson J, Wilens T, Palumbo D, et al. Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder. Pediatrics 2001; 108: 883-892.
11. Gau SS, Shen HY, Soong WT, Gau CS. An open-label, randomized, active-controlled equivalent trial of osmotic release oral system methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Child Adolesc Psychopharmacol 2006; 16: 441-455.
12. Pan XX, Ma HW, Wan B, Dai XM. Effectiveness of oral osmotic-methylphenidate in treatment of attention deficit hyperactivity disorder in children. Chin J Contemp Pediatr (Chin) 2008; 10: 471-474.
13. Kim Y, Shin MS, Kim JW, Yoo HJ, Cho SC, Kim BN. Neurocognitive effects of switching from methylphenidate-IR to OROS-methylphenidate in children with ADHD. Hum Psychopharmacol 2009; 24: 95-102.
14. Atkins MS, Pelham WE, Licht MH. The differential validity of teacher ratings of inattention/overactivity and aggression. J Abnorm Child Psychol 1989; 17: 423-435.
15. Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry 1997; 54: 1031-1037.
16. Kemner JE, Starr HL, Ciccone PE, Hooper-Wood CG, Crockett RS. Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter, randomized prospective study. Adv Ther 2005; 22: 498-512.
17. Steele M, Weiss M, Swanson J, Wang J, Prinzo RS, Binder CE. A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder. Can J Clin Pharmacol 2006; 13: e50-e62.
18. Ramos-Quiroga JA, Corominas M, Castells X, Bosch R, Casas M. OROS methylphenidate for the treatment of adults with attention-deficit/hyperactivity disorder. Expert Rev Neurother 2009; 9: 1121-1131.
19. Marchant BK, Reimherr FW, Halls C, Williams ED, Strong RE. OROS methylphenidate in the treatment of adults with ADHD: a 6-month, open-label, follow-up study. Ann Clin Psychiatry 2010; 22: 196-204.
20. Biederman J, Mick E, Surman C, Doyle R, Hammerness P, Kotarski M, et al. A randomized, 3-phase, 34-week, double-blind, long-term efficacy study of osmotic-release oral system-methylphenidate in adults with attention-deficit/ hyperactivity disorder. J Clin Psychopharmacol 2010; 30: 549-553.
21. Pelham WE, Gnagy EM, Burrows-Maclean L, Williams A, Fabiano GA, Morrisey SM, et al. Once-a day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics 2001; 107: E105.
22. Marcus SC, Wan GJ, Kemner JE, Olfson M. Continuity of methylphenidate treatment for attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 2005; 159: 572-578.
23. Lage M, Hwang P. Effect of methylphenidate formulation for attention deficit hyperactivity disorder on patterns and outcomes of treatment. J Child Adolesc Psychopharmacol 2004; 14: 575-581.
24. Lee SI, Hong SD, Kim SY, Kim EJ, Kim JH, Kim JH, et al. Efficacy and tolerability of OROS methylphenidate in Korean children with Attention-Deficit/Hyperactivity Disorder. Prog Neuropsychopharmacol Biol Psych 2007; 31: 210-216.
25. Wilens T, Pelham W, Stein M, Conners CK, Abikoff H, Atkins M, et al. ADHD treatment with once-daily OROS methylphenidate: interim 12-month results from a long-term open label study. J Am Acad Child Adolesc Psychiatry 2003; 42: 424-433.
26. Hoare P, Remschmidt H, Medori R, Ettrich C, Rothenberger A, Santosh P, et al. 12-month efficacy and safety of OROS MPH in children and adolescents with attention-deficit/ hyperactivity disorder switched from MPH. Eur Child Adolesc Psychiatry 2005; 14: 305-309.
27. Newcorn JH, Stein MA, Cooper KM. Dose-response characteristics in adolescents with attention-deficit/ hyperactivity disorder treated with OROS methylphenidate in a 4-week, open-label, dose-titration study. J Child Adolesc Psychopharmacol 2010; 20: 187-196.
28. Faraone SV, Glatt SJ, Bukstein OG, Lopez FA, Arnold LE, Findling RL. Effects of once-daily oral and transdermal methylphenidate on sleep behavior of children with ADHD. J Atten Disord 2009; 12: 308-315.
29. Kim HW, Yoon IY, Cho SC, Kim BN, Chung S, Lee H, et al. The effect of OROS methylphenidate on the sleep of children with attention-deficit/hyperactivity disorder. Int Clin Psychopharmacol 2010; 25: 107-115.
30. Ramos-Quiroga JA, Bosch R, Castells X, Valero S, Nogueira M, Gómez N, et al. Effect of switching drug formulations from immediate-release to extended-release OROS methylphenidate: a chart review of Spanish adults with attention-deficit hyperactivity disorder. CNS Drugs 2008; 22: 603-611.
31. Chou WJ, Chou MC, Tzang RF, Hsu YC, Gau SS, Chen SJ, et al. Better efficacy for the osmotic release oral system methylphenidate among poor adherents to immediate-release methylphenidate in the three ADHD subtypes. Psychiatry Clin Neurosci 2009; 63: 167-175.
Keywords:

attention deficit hyperactivity disorder; methylphenidate; pharmacotherapy

© 2011 Chinese Medical Association