An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder

Yi Zheng, Jian-Min Liang, Hong-Yun Gao, Zhi-Wei Yang, Fu-Jun Jia, Yue-Zhu Liang, Fang Fang, Rong Li, Sheng-Nan Xie, Jian-Min Zhuo, Yi Zheng, Jian-Min Liang, Hong-Yun Gao, Zhi-Wei Yang, Fu-Jun Jia, Yue-Zhu Liang, Fang Fang, Rong Li, Sheng-Nan Xie, Jian-Min Zhuo

Abstract

Background: Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.

Methods: This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.

Results: A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study.

Conclusions: The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks.

Trial registration: ClinicalTrials.gov, NCT01933880; https://ichgcp.net/clinical-trials-registry/NCT01933880?term=CONCERTAATT4099&rank=1.

Figures

Figure 1
Figure 1
Patient disposition: Cognitive assessments include Digit Span Test, Stroop Color-word Test, Wisconsin Card Sorting Test, Coding Test. CGI: Clinical Global Impression; FAS: Full analysis set; IOWA Conners: Inattention/Overactivity with Aggression Conners Behavior Rating Scale; OROS-MPH: Osmotic-Release Oral System Methylphenidate; PPS: Per protocol set; SS: Safety set.
Figure 2
Figure 2
Remission rate and parent-rated IOWA Conners scale of Chinese children. (a) Remission rate and I/O subscale of IOWA Conners; (b) O/D subscale of IOWA Conners. Remission rate and I/O subscale of IOWA Conners recorded in 6 visits (weeks 0, 1, 2, 3, 7, and 12). Mean scores of week 0–12 are significantly reduced (*P < 0.0001), compared with that of baseline. I/O: Inattention/Overactivity; O/D: Opposition/defiant; IOWA Conners: Inattention/Overactivity with Aggression Conners Behavior Rating Scale.
Figure 3
Figure 3
Incidence of adverse events in Chinese children with attention-deficit hyperactivity disorder. The percentage of treated children who reported AEs was plotted. The trend of three common AEs (poor sleep, tic, and poor appetite) at each visit (week 0, week 1, week 2, week 3, week 7, and week 12) is depicted.

References

    1. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: A systematic review and metaregression analysis. Am J Psychiatry. 2007;164:942–8.
    1. Scahill L, Schwab-Stone M. Epidemiology of ADHD in school-age children. Child Adolesc Psychiatr Clin N Am. 2000;9:541–55. vii.
    1. Effective Health Care Review. Comparative Effectiveness Review Number 44. Attention Deficit Hyperactivity Disorder: Effectiveness of Treatment in At-Risk Preschoolers; Long-Term Effectiveness in All Ages; and Variability in Prevalence, Diagnosis and Treatment. U.S. Department of Health and Human Services. 2011. [Last cited on 2015 Jan 12]. Available from: .
    1. Li SC, Lewandowsky S. Forward and backward recall: Different retrieval processes. J Exp Psychol Learn Mem Cogn. 1995;21:837–47.
    1. Hong HJ, Lee JB, Kim JS, Seo WS, Koo BH, Bai DS, et al. Impairment of concept formation ability in children with ADHD: Comparisons between lower grades and higher grades. Psychiatry Investig. 2010;7:177–88.
    1. Loe IM, Feldman HM. Academic and educational outcomes of children with ADHD. J Pediatr Psychol. 2007;32:643–54.
    1. Das D, Cherbuin N, Butterworth P, Anstey KJ, Easteal S. A population-based study of attention deficit/hyperactivity disorder symptoms and associated impairment in middle-aged adults. PLoS One. 2012;7:e31500.
    1. Mattos P, Louzã MR, Palmini AL, de Oliveira IR, Rocha FL. A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) study. J Atten Disord. 2013;17:444–8.
    1. 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:e50–62.
    1. Venkatraman VK, Aizenstein HJ, Newman AB, Yaffe K, Harris T, Kritchevsky S, et al. Lower digit symbol substitution score in the oldest old is related to magnetization transfer and diffusion tensor imaging of the white matter. Front Aging Neurosci. 2011;3:11.
    1. Wigal SB, Wigal T, Schuck S, Brams M, Williamson D, Armstrong RB, et al. Academic, behavioral, and cognitive effects of OROS® methylphenidate on older children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2011;21:121–31.
    1. Zoëga H, Rothman KJ, Huybrechts KF, Ólafsson Ö, Baldursson G, Almarsdóttir AB, et al. A population-based study of stimulant drug treatment of ADHD and academic progress in children. Pediatrics. 2012;130:e53–62.
    1. Lv XZ, Shu Z, Zhang YW, Wu SS, Zhan SY. Effectiveness and safety of methylphenidate and atomoxetine for attention deficit hyperactivity disorder: A systematic review (in Chinese) Chin J Contemp Pediatr. 2011;13:365–9.
    1. Wietecha L, Williams D, Shaywitz S, Shaywitz B, Hooper SR, Wigal SB, et al. Atomoxetine improved attention in children and adolescents with attention-deficit/hyperactivity disorder and dyslexia in a 16 week, acute, randomized, double-blind trial. J Child Adolesc Psychopharmacol. 2013;23:605–13.
    1. Rapport MD, Orban SA, Kofler MJ, Friedman LM. Do programs designed to train working memory, other executive functions, and attention benefit children with ADHD? A meta-analytic review of cognitive, academic, and behavioral outcomes. Clin Psychol Rev. 2013;33:1237–52.
    1. Yang P, Chung LC, Chen CS, Chen CC. Rapid improvement in academic grades following methylphenidate treatment in attention-deficit hyperactivity disorder. Psychiatry Clin Neurosci. 2004;58:37–41.
    1. Balthazor MJ, Wagner RK, Pelham WE. The specificity of the effects of stimulant medication on classroom learning-related measures of cognitive processing for attention deficit disorder children. J Abnorm Child Psychol. 1991;19:35–52.
    1. Waschbusch DA, Willoughby MT. Parent and teacher ratings on the IOWA conners rating scale. J Psychopathol Behav Assess. 2008;30:180–92.
    1. Wechsler D. Administration and Scoring Manual. 4th ed. San Antonio, TX: Harcourt Assessment, Inc; 2003. Wechsler intelligence scale for children.
    1. Shelton JT, Elliott EM, Hill BD, Calamia MR, Gouvier WD. A comparison of laboratory and clinical working memory tests and their prediction of fluid intelligence. Intelligence. 2009;37:283.
    1. Tchanturia K, Davies H, Roberts M, Harrison A, Nakazato M, Schmidt U, et al. Poor cognitive flexibility in eating disorders: Examining the evidence using the Wisconsin Card Sorting Task. PLoS One. 2012;7:e28331.
    1. Weiss G, Hechtman L, Milroy T, Perlman T. Psychiatric status of hyperactives as adults: A controlled prospective 15-year follow-up of 63 hyperactive children. J Am Acad Child Psychiatry. 1985;24:211–20.
    1. Barkley RA, Fischer M, Edelbrock CS, Smallish L. The adolescent outcome of hyperactive children diagnosed by research criteria: I. An 8-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry. 1990;29:546–57.
    1. Zhou KY, Gao MH, Yang CH, Zhang JN, Chen YZ, Song JZ, et al. An epidemiological survey of attention deficit hyperactivity disorder in school-age children in Shenzhen (in Chinese) Chin J Contemp Pediatr. 2012;14:689–92.
    1. Zheng Y, Wang YF, Qin J, Wang LW, Zou LP, Jin XM, et al. Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder. Chin Med J. 2011;124:3269–74.
    1. Chou WJ, Chen SJ, Chen YS, Liang HY, Lin CC, Tang CS, et al. Remission in children and adolescents diagnosed with attention-deficit/hyperactivity disorder via an effective and tolerable titration scheme for osmotic release oral system methylphenidate. J Child Adolesc Psychopharmacol. 2012;22:215–25.
    1. Brault MC, Lacourse É. Prevalence of prescribed attention-deficit hyperactivity disorder medications and diagnosis among Canadian preschoolers and school-age children: 1994-2007. Can J Psychiatry. 2012;57:93–101.
    1. Tzang RF, Wang YC, Yeh CB, Hsu CD, Liang HY, Yang PC, et al. Naturalistic exploration of the effect of osmotic release oral system-methylphenidate on remission rate and functional improvement in Taiwanese children with attention-deficit-hyperactivity disorder. Psychiatry Clin Neurosci. 2012;66:53–63.
    1. Tsai CS, Huang YS, Wu CL, Hwang FM, Young KB, Tsai MH, et al. Long-term effects of stimulants on neurocognitive performance of Taiwanese children with attention-deficit/hyperactivity disorder. BMC Psychiatry. 2013;13:330.
    1. Yang L, Cao Q, Shuai L, Li H, Chan RC, Wang Y. Comparative study of OROS-MPH and atomoxetine on executive function improvement in ADHD: A randomized controlled trial. Int J Neuropsychopharmacol. 2012;15:15–26.
    1. Murdock BB. Developing TODAM: Three models for serial-order information. Mem Cognit. 1995;23:631–45.
    1. Thomas JG, Milner HR, Haberlandt KF. Forward and backward recall: Different response time patterns, same retrieval order. Psychol Sci. 2003;14:169–74.
    1. Vilkki J, Holst P. Mental programming after frontal lobe lesions: Results on digit symbol performance with self-selected goals. Cortex. 1991;27:203–11.
    1. Parkin AJ, Java RI. Deterioration of frontal lobe function in normal aging: Influences of fluid intelligence versus perceptual speed. Neuropsychology. 1999;13:539–45.
    1. Yamanouchi N, Okada S, Kodama K, Sakamoto T, Sekine H, Hirai S, et al. Effects of MRI abnormalities on WAIS-R performance in solvent abusers. Acta Neurol Scand. 1997;96:34–9.
    1. Demakis GJ, Sawyer TP, Fritz D, Sweet JJ. Incidental recall on WAIS-R digit symbol discriminates Alzheimer's and Parkinson's diseases. J Clin Psychol. 2001;57:387–94.
    1. Ratti MT, Bo P, Giardini A, Soragna D. Chronic alcoholism and the frontal lobe: Which executive functions are imparied? Acta Neurol Scand. 2002;105:276–81.
    1. Blekher TM, Yee RD, Kirkwood SC, Hake AM, Stout JC, Weaver MR, et al. Oculomotor control in asymptomatic and recently diagnosed individuals with the genetic marker for Huntington's disease. Vision Res. 2004;44:2729–36.
    1. Nakahachi T, Iwase M, Takahashi H, Honaga E, Sekiyama R, Ukai S, et al. Discrepancy of performance among working memory-related tasks in autism spectrum disorders was caused by task characteristics, apart from working memory, which could interfere with task execution. Psychiatry Clin Neurosci. 2006;60:312–8.
    1. Bakar EE, Bakar B, Taner YI, Akalan N. Evaluation of the intellectual skill problems of hydrocephalic children: A clinical study. Turk Neurosurg. 2009;19:29–35.
    1. Burlison JD, Dwyer WO. Risk screening for ADHD in a college population: Is there a relationship with academic performance? J Atten Disord. 2013;17:58–63.
    1. Williamson D, Murray DW, Damaraju CV, Ascher S, Starr HL. Methylphenidate in children with ADHD with or without learning disability. J Atten Disord. 2014;18:95–104.

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