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National Survey of Adherence, Efficacy, and Side Effects of Methylphenidate in Children With Attention-Deficit/Hyperactivity Disorder in Taiwan

Susan Shur-Fen Gau, M.D., Ph.D.; Shin-Jaw Chen, M.D.; Wen-Jiun Chou, M.D.; Helen Cheng, M.D.; Ching-Shu Tang, M.D.; Hsueh-Ling Chang, M.D.; Ruu-Fen Tzang, M.D.; Yu-Yu Wu, M.D.; Ya-Fen Huang, M.D.; Miao-Chun Chou, M.D.; Hsin-Yi Liang, M.D.; Ya-Chen Hsu, M.D.; Hui-Hua Lu, M.D.; and Yu-Shu Huang, M.D.

Objectives: To identify the determinants of adherence to immediate-release (IR) methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder (ADHD); to examine the impact of adherence on ADHD-related symptoms; and to compare the efficacy, adherence, and side effects of IR methylphenidate and osmotic release oral system (OROS) methylphenidate.

Method: This national survey, involving 12 hospitals, consisted of 2 phases of assessment. Treatment adherence in 240 (39.5%) of the 607 children aged 5 to 16 years with a clinical diagnosis of DSM-IV ADHD enrolled in the study was poor (defined as missing >= 1 dose of ADHD medication a day and on 2 days or more during school days). Children with poor adherence at phase 1 were able to switch to OROS methylphenidate, while adherents remained on the IR variant. We reassessed 124 poor adherents who switched to OROS methylphenidate. The global ADHD severity, parent-child interaction, classroom behavior, academic performance, and side effects of the child subjects were evaluated by investigators. Parents completed the rating scales about the ADHD-related symptoms. The study began in April 2005 and was completed in February 2006.

Results: Determinants for poor adherence included older age, later onset of ADHD, family history of ADHD, higher paternal education level, and multi-dose administration. Mental retardation and treatment at medical centers were inversely related to poor adherence. Overall, poor adherence was associated with more severe ADHD-related symptoms by comparison to good adherence. Similar side effect profile, superior adherence, and improved efficacy were demonstrated in intra-individual comparison of the OROS and IR methylphenidate forms.

Conclusion: Given that poor adherence to medication may be an important reason for suboptimal outcome in ADHD treatment, physicians should ensure adherence with therapy before adjusting dosage or switching medication.

Trial Registration: Identifier NCT00460720.

(J Clin Psychiatry 2008;69:131-140)

Received Feb. 26, 2007; accepted Aug. 7, 2007. From the Department of Psychiatry, National Taiwan University Hospital and College of Medicine, National Taiwan University (Dr. Gau); the Department of Child Psychiatry, Chang Gung Memorial Hospital-Linkou Branch (Drs. Chang, Wu, Y.-F. Huang, Liang, and Y.-S. Huang); the Department of Psychiatry, Mackay Memorial Hospital (Dr. Tzang); and the Department of Psychiatry, Cathay General Hospital (Dr. Lu), Taipei, Taiwan; the Department of Psychiatry, National Cheng-Kung University Hospital, Tainan, Taiwan (Dr. Chen); the Department of Child Psychiatry, Chang Gung Memorial Hospital-Kaohsiung Branch, Kaohsiung, Taiwan (Drs. W.-J. Chou, Tang, and M.-C. Chou); the Department of Psychiatry, Changhua Christian Hospital, Changhua, Taiwan (Dr. Cheng); and the Department of Psychiatry, Lin Shin Hospital, Taichung, Taiwan (Dr. Hsu).

This work was supported by Janssen-Cilag, Taipei, Taiwan (Protocol ID: CCT-TWN-MA3). The preparation of this manuscript was supported by a grant from the National Health Research Institute (NHRI-EX95-9407PC), Taipei, Taiwan.

The authors would like to acknowledge the contributions from Daniel Sung, M.D.; Kai-Chi Fang, M.D.; Huei-Wen Lee, M.D.; Yuh-Ming Hou, M.D.; Shih-Kai Liu, M.D.; and Mei-Chu Chen, M.D. None of the acknowledged individuals have any pertinent financial or other disclosures relative to the subject of this article.

Dr. Gau was responsible for data analysis and writing. No medical writer was involved in the preparation of this article.

The authors report no additional financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: Susan Shur-Fen Gau, M.D., Ph.D., Department of Psychiatry, National Taiwan University Hospital & College of Medicine, No. 7, Chung-Shan South Rd., Taipei, Taiwan 10002, R.O.C. (e-mail: