Medication Adherence in the MTA: Saliva Methylphenidate Samples Versus Parent Report and Mediating Effect of Concomitant Behavioral Treatment
The NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) was a National Institute of Mental Health (NIMH) cooperative agreement randomized clinical trial involving six clinical sites. Collaborators from the National Institute of Mental Health: Peter S. Jensen, M.D. (currently at Columbia University), L. Eugene Arnold, M.D., M.Ed. (currently at Ohio State University), Joanne B. Severe, M.S. (Clinical Trials Operations and Biostatistics Unit, Division of Services and Intervention Research), Benedetto Vitiello, M.D. (Child and Adolescent Treatment and Preventive Interventions Research Branch), Kimberly Hoagwood, Ph.D. (currently at Columbia); previous contributors from NIMH to the early phase: John Richters, Ph.D. (currently at National Institute of Nursing Research); Donald Vereen, M.D. (currently at National Institute on Drug Abuse). Principal investigators and coinvestigators from the clinical sites are as follows: University of California, Berkeley/San Francisco: Stephen P. Hinshaw, Ph.D. (Berkeley), Glen R. Elliott, Ph.D., M.D. (San Francisco); Duke University: C. Keith Conners, Ph.D., Karen C. Wells, Ph.D., John March, M.D., M.P.H., Jeffery Epstein, Ph.D.; University of California, Irvine/Los Angeles: James Swanson, Ph.D. (Irvine), Dennis P. Cantwell, M.D., (deceased, Los Angeles), Timothy Wigal, Ph.D. (Irvine); Long Island Jewish Medical Center/Montreal Children's Hospital: Howard B. Abikoff, Ph.D. (currently at New York University School of Medicine), Lily Hechtman, M.D. (McGill University); New York State Psychiatric Institute/Columbia University/Mount Sinai Medical Center: Laurence L. Greenhill, M.D. (Columbia), Jeffrey H. Newcorn, M.D. (Mount Sinai School of Medicine); University of Pittsburgh: William E. Pelham, Ph.D. (currently at State University of New York, Buffalo), Betsy Hoza, Ph.D. (currently at University of Vermont), Brooke Molina, Ph.D. Original statistical and trial design consultant: Helena C. Kraemer, Ph.D. (Stanford University). Follow-up phase statistical collaborators: Robert D. Gibbons, Ph.D. (University of Illinois, Chicago), Sue Marcus, Ph.D (Mt. Sinai College of Medicine), Kwan Hur, Ph.D. (University of Illinois, Chicago). Collaborator from the Office of Special Education Programs/U.S. Department of Education: Thomas Hanley, Ed.D. Collaborator from Office of Juvenile Justice and Delinquency Prevention/Department of Justice: Karen Stern, Ph.D. Other authors include: Columbia University: Elizabeth Pappadopulos, Ph.D. (currently at Pfizer), Alanna R. Chait, B.A. (currently a New York Medical College student). Nathan Kline Institute: Thomas Cooper, M.S
Accepted 18 December 2008.
Disclosure: Dr. Pappadopulos has been an employee of Pfizer. Dr. Jensen has received training and/or research funds from the Lowenstein Foundation, the Klingenstein Third Generation Foundation, the Annie E. Casey Foundation, Casey Family Programs, Novartis, Magellan, and Value Options. He participates in the speakers' bureaus of CMED, UCB Pharma, CME Outfitters, the Neuroscience Education Institute, Janssen-Ortho, and McNeil. He serves as a consultant to Best Practice, McNeil, Novartis, Janssen-Ortho, Otsuka, and Shire. Dr. Arnold has received research funding from the National Institute of Mental Health, Autism Speaks, Shire, Neuropharm, and CureMark. He has received consulting honoraria from Shire, Organon, Neuropharm, and Targacept. He has received speakers' honoraria from Shire. Dr. Swanson has received support for speaking at and travel to meetings from Janssen, UCB, and Novartis. Dr. Greenhill is the recipient of the 2007 Elaine Schlosser Lewis Award for Greenhill L, Kollins S, Abikoff H, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry. 2006; 45:1284–1293. He has received research funding from Otsuka Pharmaceuticals, Bristol-Myers Squibb, the National Institute of Mental Health, and Johnson & Johnson, and has served as the chair for Pfizer's ziprasidone pediatric studies. Dr. Hechtman has received research funding from the National Institute of Mental Health, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Purdue Pharma, and Shire; has been on the speakers' bureaus of the National Institute of Mental Health, Eli Lilly, Purdue Pharma, Janssen-Ortho, and Shire; and has been on the advisory boards of Eli Lilly, Janssen-Ortho, Purdue Pharma, and Shire. Dr. Wells receives workshop training fees from the REACH Institute and from the state of New York. Dr. Pelham has spoken at a conference for McNeil. Dr. Newcorn has received grants for research support from Eli Lilly and Ortho-McNeil-Janssen. He has been a consultant and/or advisor to Abbott, BioBehavioral Diagnostics, Eli Lilly, Novartis, Ortho-McNeil-Janssen, Psychogenics, Sanofi-Aventis, and Shire, and a speaker for Ortho-McNeil-Janssen. The other authors report no conflicts of interest.
Abstract
Objectives
Although research supports the use of appropriately administered stimulant medication to treat children with ADHD, poor adherence and early termination undermine the efficacy of this treatment in real-world settings. Moreover, adherence measures often rely on parent report of medication use, and their validity and reliability are unknown.
Method
Drawing on data from 254 participants in the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder, we examine the discrepancy between parents' verbal reports of medication adherence and physiological adherence measures determined via methylphenidate saliva assays collected at four time points during the 14-month treatment period. In addition, we examine the impact of physiologically documented medication adherence on parent- and teacher-reported outcomes through 14 months.
Results
Overall, nearly one fourth (24.5%) of the saliva samples indicated nonadherence. Among subjects, 63 (24.8%) of the 254 participants were nonadherent on 50% or more of their repeated saliva assays. Only 136 (53.5%) of the subjects were adherent at every time point at which saliva assays were taken, indicating that some degree of nonadherence characterized nearly half of all other NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder-treated children. Findings also indicated that nonadherence produced greater deleterious effects in children in the medication-only condition compared with those receiving both medication and behavioral treatment.
Conclusions
Same-day saliva methylphenidate assays suggest that nearly half of the parents are inaccurate informants of their child's ADHD medication adherence and that parents may overestimate actual (physiological) adherence. This finding suggests the need for interventions to improve accuracy of parental report. Clinicians need to focus on adherence enhancement strategies to improve outcomes of children being treated with medication, particularly when benefits are suboptimal.
Key Words:
medication
,
pharmacotherapy
,
methylphenidate
,
saliva levels
The work reported was supported by cooperative agreement grants and contracts from the National Institute of Mental Health to the following: University of California, Berkeley: U01 MH50461 and N01MH12009; Duke University: U01 MH50477 and N01MH12012; University of California, Irvine: U01 MH50440 and N01MH 12011; Research Foundation for Mental Hygiene (New York State Psychiatric Institute/Columbia University): U01 MH50467 and N01 MH12007; Long Island-Jewish Medical Center U01 MH50453; New York University: N01MH 12004; University of Pittsburgh: U01 MH50467 and N01 MH 12010; and McGill University N01MH12008. The Office of Special Education Programs of the U.S. Department of Education and the Office of Juvenile Justice and Delinquency Prevention of the Justice Department also participated in funding.The opinions and assertions contained in this article are the private views of the authors and are not to be construed as official or as reflecting the views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Health and Human Services.This article is the subject of an editorial by Dr. Philip L. Hazell in this issue.Clinical trial registration information—The NIMH MTA Study. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000388.
PII: S0890-8567(09)60067-8
doi:10.1097/CHI.0b013e31819c23ed
© 2009 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
