National Institute of Mental Health Collaborative Multimodal Treatment Study of Children With ADHD (the MTA): Design Challenges and Choices
Abstract
The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first child multisite cooperative agreement treatment study of children conducted by the National Institute of Mental Health, Rockville, Md. It examines the long-term effectiveness of medication vs behavioral treatment vs both for treatment of ADHD and compares state-of-the-art treatment with routine community care. In a parallel-groups design, 576 children (age, 7-9 years) with ADHD (96 at each site) are thoroughly assessed and randomized to 4 conditions: (1) medication alone, (2) psychosocial treatment alone, (3) the combination of both, (4) or community comparison. The first 3 groups are treated for 14 months and all are reassessed periodically for 24 months. Designers met the following challenges: framing clinically relevant primary questions; defining the target population; choice, intensity, and integration and combination of treatments for fair comparisons; combining scientific controls and standardization with clinical flexibility; and implementing a controlled clinical trial in a nonclinical setting (school) controlled by others. Innovative solutions included extensive decision algorithms and manualized adaptations of treatments to specific needs.
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The MTA implemented state-of-the-art treatment in the early 1990s.
“The MTA implemented state-of-the-art treatment in the early 1990s”
From Effects of Stimulant Medication on Growth Rates Across 3 Years in the MTA Follow-up (2007) · cites this paper as Arnold et al., 1997
In the early 1990s, Ritalin was prescribed for most cases when stimulant medication was used to treat children with ADHD.
“which then was prescribed for most cases when stimulant medication was used to treat children with ADHD”
From Effects of Stimulant Medication on Growth Rates Across 3 Years in the MTA Follow-up (2007) · cites this paper as Arnold et al., 1997
The MTA used an immediate-release formulation of methylphenidate (Ritalin).
“used an immediate-release formulation of methylphenidate (Ritalin”
From Effects of Stimulant Medication on Growth Rates Across 3 Years in the MTA Follow-up (2007) · cites this paper as Arnold et al., 1997
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“The National Institute of Mental Health has conducted a multi-site cooperative agreement study of 576 children with ADHD (aged from 7 to 9 years) in parallel groups randomised according to 4 conditions: (i) pharmacotherapy alone; (ii) psychosocial treatment alone; (iii) a treatment combination; and (iv) community comp…”
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“However, at three time points, the MTA (for a description, see Arnold et al., 1997) collected sociometrics on a subgroup of their sample.”
BackgroundWhich treatment for whom for ADHD? Moderators of treatment response in the MTA.
Owens, E. B., Hinshaw, S. P., KRAEMER, H. C., Arnold, L. E., Abikoff, H., Cantwell, D. P., Conners, C. K., Elliott, G. R., Greenhill, L. L., Hechtman, L. T., et al. (2003) · Journal of Consulting and Clinical Psychology · doi:10.1037/0022-006x.71.3.540 · Cited by 275 · see citing works
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“The MTA recruitment strategy, procedures for diagnosing ADHD, treatment specifics, and sample demographics have been described elsewhere (Arnold et al., 1997; Greenhill et al., 1996, 2001; Hinshaw et al., 1997; The MTA Cooperative Group, 1999a,b, 2004a,b; Wells et al., 2000).”
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“Based on parent/adult informant report using the Services Use in Children and Adolescents–Parent Interview (Arnold et al., 1997), three variables were created: (1) pharmacotherapy, (2) residential treatment (psychiatric hospitalization, residential drug and alcohol treatment, detention or…”
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“Finally, site differences typically emerge in multisite trials due to varied regional patterns (e.g., Arnold et al., 1997; Kraemer, 2000) such as distinct health plans and formal care services that are often used as recruitment sources.”
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“This study will compare the effects of purely medical management, specific psychotherapy, and the combination of both, comparable with the Multimodal Treatment Study of Children with ADHD (Arnold et al., 1997).”
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“Finally, site differences typically emerge in multisite trials due to varied regional patterns (e.g., Arnold et al., 1997; Kraemer, 2000) such as dissimilar migration patterns, and distinct health plans and formal care services that are often used as recruitment sources.”
BackgroundResultEfficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy
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“This multi-site, study represented the largest controlled trial to of treatment for ADHD to date (Arnold et al., 1997), and enrolled 579 children with ADHD, ages 7–9, who were randomized to one of four treatment strategies: medication alone, psychosocial treatment alone, combined (medication +…”
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“…screening, diagnostic instruments, outcome measures, randomization, methods, informed consent, institutional board review at the performance sites, and the basic characteristics of the full MTA sample have been described previously (Arnold et al. 1997a, 1997b, MTA Cooperative Group 1999a).”
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BackgroundAssessing medication effects in the MTA study using neuropsychological outcomes
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Pelham, W. E. (1999) · The Canadian Journal of Psychiatry · doi:10.1177/070674379904401004 · Cited by 129 · see citing works
Psychiatric Comorbidities in Children with Attention Deficit Hyperactivity Disorder
Pliszka, S. R. (2003) · Pediatric Drugs · doi:10.2165/00148581-200305110-00003 · Cited by 129 · see citing works
Miller, L. J., Nielsen, D. M., & Schoen, S. A. (2012) · Research in Developmental Disabilities · doi:10.1016/j.ridd.2011.12.005 · Cited by 125 · see citing works
Usala, T., Clavenna, A., Zuddas, A., & Bonati, M. R. (2007) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2007.06.001 · Cited by 119 · see citing works
de la Cruz, L. F., Simonoff, E., McGough, J. J., Halperin, J. M., Arnold, L. E., & Stringaris, A. (2015) · Journal of the American Academy of Child and Adolescent Psychiatry · doi:10.1016/j.jaac.2014.10.006 · Cited by 123 · see citing works
“Additional details about the sampling and the procedures in the MTA have been widely described elsewhere.(2,26,27)”
MethodRevisiting the latent structure of ADHD: is there a ‘g’ factor?
Martel, M. M., von Eye, A., & Nigg, J. T. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02232.x · Cited by 117 · see citing works
“Recruitment and identification—A broad community-based recruitment strategy was used, with mass mailings to parents in local school districts, public advertisements, as well as flyers at local clinics, to mimic the recruitment strategy of the MTA study (Arnold et al., 1997), while including all ADHD subtypes and addin…”
MethodMaternal Depressive Symptomatology and Parenting Behavior: Exploration of Possible Mediators
Gerdes, A. C., Hoza, B., Arnold, L. E., Pelham, W. E., Swanson, J. M., Wigal, T. L., & Jensen, P. S. (2007) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-007-9134-3 · Cited by 115 · see citing works
Hough, R. L., Hazen, A. L., Soriano, F. I., Wood, P., McCabe, K. M., & Yeh, M. (2002) · Psychiatric Services · doi:10.1176/appi.ps.53.12.1556 · Cited by 114 · see citing works
Shelton, T. L., Barkley, R. A., Crosswait, C., Moorehouse, M., Fletcher, K. E., Barrett, S., Jenkins, L., & Metevia, L. (2000) · Research on Child and Adolescent Psychopathology · doi:10.1023/a:1005144304071 · Cited by 110 · see citing works
“These programs typically focus on peer relations, classroom conduct, and school achievement (Arnold et al., 1997; Bierman, Miller, & Stabb, 1987; Cunningham & Cunningham, 1998; Pfiffner & Barkley, 1998).”
BackgroundConsidering Usual Medical Care in Clinical Trial Design
Dawson, L., Zarin, D. A., Emanuel, E. J., Friedman, L. M., Chaudhari, B., & Goodman, S. N. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000111 · Cited by 93 · see citing works
ASSESSMENT AND INTERVENTION FOR ATTENTION-DEFICIT/HYPERACTIVITY DISORDER IN THE SCHOOLS
Swanson, J. M., Lerner, M., March, J. S., & Gresham, F. M. (1999) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(05)70168-1 · Cited by 106 · see citing works
Blood Pressure and Heart Rate Over 10 Years in the Multimodal Treatment Study of Children With ADHD
Vitiello, B., Elliott, G. R., Swanson, J. M., Arnold, L. E., Hechtman, L. T., Abikoff, H., Molina, B. S. G., Wells, K., Wigal, T. L., Jensen, P. S., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10111705 · Cited by 106 · see citing works
Pliszka, S. R., GREENHILL, L. L., Crismon, M. L., Sedillo, A., Carlson, C. L., Conners, C. K., McCracken, J. T., Swanson, J. M., Hughes, C. W., LLANA, M. E., et al. (2000) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-200007000-00022 · Cited by 104 · see citing works
Swanson, J. M., Arnold, L. E., KRAEMER, H. C., Hechtman, L. T., Molina, B. S. G., Hinshaw, S. P., Vitiello, B., Jensen, P. S., Steinhoff, K., Lerner, M., et al. (2008) · Journal of Attention Disorders · doi:10.1177/1087054708319525 · Cited by 97 · see citing works
“…in the initial publications by the MTA Cooperative Group in the late 1990s about the medication algorithm (Greenhill et al., 1996), the design (Arnold et al., 1997a, 1997b), and the assessment battery (Hinshaw et al., 1997), and later about the psychosocial treatments (Wells et al., 2000a,…”
BackgroundInfluentialAttention Deficit Hyperactivity Disorder in Preschool Children
Greenhill, L. L., Posner, K., Vaughan, B. S., & Kratochvil, C. J. (2008) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2007.11.004 · Cited by 126 · see citing works
Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)
Storebø, O. J., Storm, M. R. O., Ribeiro, J. P., Skoog, M., Groth, C., Edemann-Callesen, H., Schaug, J. P., Rasmussen, P. D., Huus, C.-M. L., Zwi, M., et al. (2023) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009885.pub3 · Cited by 99 · see citing works
Arnold, L. E., Abikoff, H., Cantwell, D. P., Conners, C. K., Elliott, G. R., Greenhill, L. L., Hechtman, L. T., Hinshaw, S. P., Hoza, B., Jensen, P. S., et al. (1997) · Journal of Attention Disorders · doi:10.1177/108705479700200301 · Cited by 84 · see citing works
Martel, M. M., Goth-Owens, T. L., Martinez‐Torteya, C., & Nigg, J. T. (2010) · Journal of Abnormal Psychology · doi:10.1037/a0017511 · Cited by 81 · see citing works
“A broad community-based recruitment strategy was used, with mass mailings to parents in local school districts, public advertisements, and fliers at local clinics, in an effort to mimic the recruitment strategy of the MTA study (Arnold et al., 1997).”
MethodGarland, E. J. (1998) · Journal of Psychopharmacology · doi:10.1177/026988119801200410 · Cited by 77 · see citing works
PREDICTORS OF LONG-TERM OUTCOME IN CHILDREN WITH ATTENTION-DEFICIT/HYPERACTIVITY DISORDER
Hechtman, L. T. (1999) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(05)70171-1 · Cited by 76 · see citing works
Vitiello, B. (2001) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/104454601750143384 · Cited by 76 · see citing works
“In this study, 579 children 7–9 years of age were randomly assigned to receive one of four treatment strategies (medication treatment, behavioral therapy, combined medication plus behavioral therapy, and treatment as usual in the community) for 14 months (Arnold et al. 1997).”
Santosh, P. J., & Taylor, E. (2000) · European Child & Adolescent Psychiatry · doi:10.1007/s007870070017 · Cited by 94 · see citing works
Early Onset Bipolar Disorder: Clinical and Research Considerations
Carlson, G. A. (2005) · Journal of Clinical Child & Adolescent Psychology · doi:10.1207/s15374424jccp3402_13 · Cited by 74 · see citing works
“For instance, using the sample from the Multimodal Treatment Study of Children with ADHD (Arnold et al., 1997), a large population of well-diagnosed children with ADHD, Galanter et al.”
BackgroundMethodInfluentialNature, Nurture, and Attention Deficit Hyperactivity Disorder
Faraone, S., & Biederman, J. (2000) · Developmental Review · doi:10.1006/drev.2000.0515 · Cited by 78 · see citing works
Reliability of the Services for Children and Adolescents–Parent Interview
Hoagwood, K., Jensen, P. S., Arnold, L. E., Roper, M., Severe, J. B., Odbert, C., & Molina, B. S. G. (2004) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000139558.54948.1f · Cited by 73 · see citing works
Strack, S., & Guevara, L. F. (1999) · Journal of Clinical Psychology · doi:10.1002/(sici)1097-4679(199907)55:7 · Cited by 4 · see citing works
Greenhill, L. L., Swanson, J. M., Hechtman, L. T., Waxmonsky, J. G., Arnold, L. E., Molina, B. S. G., Hinshaw, S. P., Jensen, P. S., Abikoff, H., Wigal, T. L., et al. (2019) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2019.06.019 · Cited by 69 · see citing works
Self-Perception in Children with Attention Deficit/Hyperactivity Disorder
Barber, S., Grubbs, L. M., & Cottrell, B. H. (2005) · Journal of Pediatric Nursing · doi:10.1016/j.pedn.2005.02.012 · Cited by 68 · see citing works
Probabilistic epigenesis of psychopathology
Gottlieb, G., & Willoughby, M. T. (2015) · doi:10.1002/9780470939383.ch17 · Cited by 9 · see citing works
Interventions in ADHD: A comparative review of stimulant medications and behavioral therapies
Rajeh, A., Amanullah, S., Shivakumar, K., & Cole, J. (2016) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2016.09.005 · Cited by 64 · see citing works
Bulimia nervosa symptoms in the Multimodal Treatment Study of Children with ADHD
Mikami, A. Y., Hinshaw, S. P., Arnold, L. E., Hoza, B., Hechtman, L. T., Newcorn, J. H., & Abikoff, H. (2009) · International Journal of Eating Disorders · doi:10.1002/eat.20692 · Cited by 62 · see citing works
Noninvasive Brain Stimulation in Pediatric Attention-Deficit Hyperactivity Disorder (ADHD)
Rubio, B., Boes, A. D., Laganiere, S. E., Rotenberg, A., Jeurissen, D., & Pascual‐Leone, Á. (2015) · Journal of Child Neurology · doi:10.1177/0883073815615672 · Cited by 64 · see citing works
Taerk, E., Grizenko, N., Amor, L. B., Lageix, P., Mbékou, V., Deguzman, R., Torkamanzehi, A., Ter-Stepanian, M., Baron, C., & Joober, R. (2004) · BMC Medical Genetics · doi:10.1186/1471-2350-5-30 · Cited by 59 · see citing works
“Theories of dysregulated dopamine (DA) pathways in ADHD have been supported by the efficacy of dopamine agonists in reducing the core symptoms of the disorder [12].”
Puri, B. K., & Martins, J. G. (2014) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2014.01.004 · Cited by 56 · see citing works
Frick, P. J., & Silverthorn, P. (2002) · Springer eBooks · doi:10.1007/0-306-47377-1_31 · Cited by 57 · see citing works
Algorta, G. P., Kragh, C. A., Arnold, L. E., Molina, B. S. G., Hinshaw, S. P., Swanson, J. M., Hechtman, L. T., Copley, L. M., Lowe, M., & Jensen, P. S. (2014) · Journal of Attention Disorders · doi:10.1177/1087054714561290 · Cited by 56 · see citing works
“We utilized data from the MTA (Arnold et al., 1997; MTA Cooperative Group, 1999, 2004), including the auxiliary LNCG.”
MethodInfluentialMarch, J. S., Conners, C. K., Arnold, G., Epstein, J. N., Parker, J. D. A., Hinshaw, S., Abikoff, H., Molina, B. S. G., Wells, K. C., Newcorn, J. H., et al. (1999) · Journal of Attention Disorders · doi:10.1177/108705479900300202 · Cited by 54 · see citing works
“The rationale and design of the MTA have been reported elsewhere (Arnold et al., 1997; Hinshaw et al., 1997).”
BackgroundInfluentialWhat Does the MTA Study Tell Us About Effective Psychosocial Treatment for ADHD?
Greene, R. W., & Ablon, J. S. (2001) · Journal of Clinical Child & Adolescent Psychology · doi:10.1207/s15374424jccp3001_13 · Cited by 53 · see citing works
“In discussing early findings from the MTA study, it is very important to be explicit about the research questions the study was designed to answer (see Arnold et al., 1997a): (a) How do excellent long-term medication and psychosocial treatments compare with one another?”
BackgroundInfluentialHoward, A. L., Strickland, N. J., Murray, D. W., Tamm, L., Swanson, J. M., Hinshaw, S. P., Arnold, L. E., & Molina, B. S. G. (2016) · Journal of Abnormal Psychology · doi:10.1037/abn0000100 · Cited by 51 · see citing works
“Recruitment strategy, detailed exclusion criteria, diagnostic procedures, treatment, and sample demographic characteristics appear in other reports (Arnold et al., 1997; MTA Cooperative Group, 1999; 2004).”
Karpenko, V., Owens, J. S., Evangelista, N. M., & Dodds, C. M. (2008) · Journal of Clinical Psychology · doi:10.1002/jclp.20549 · Cited by 50 · see citing works
Arnold, L. E., Chuang, S. Z., Davies, M., Abikoff, H., Conners, C. K., Elliott, G. R., Greenhill, L. L., Hechtman, L. T., Hinshaw, S. P., Hoza, B., et al. (2003) · Research on Child and Adolescent Psychopathology · doi:10.1023/b:jacp.0000007579.61289.31 · Cited by 49 · see citing works
“The NIMH Cooperative Multimodal Treatment Study of Children with ADHD (the MTA) was a landmark comparison of the these two treatment strategies and their combination (Arnold et al., 1997a, 1997b; MTA Cooperative Group, 1999a, 1999b).”
MethodRelation Between Outcomes on a Continuous Performance Test and ADHD Symptoms Over Time
Vaughn, A. J., Epstein, J. N., Rausch, J., Altaye, M., Langberg, J. M., Newcorn, J. H., Hinshaw, S. P., Hechtman, L., Arnold, L. E., Swanson, J. M., et al. (2011) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-011-9501-y · Cited by 57 · see citing works
“Greater detail regarding the rationale, design, and results of the MTA study may be found elsewhere (Arnold et al., 1997; MTA Cooperative Group, 1999).”
BackgroundRutter, M. L. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830210021002 · Cited by 48 · see citing works
The Structure of Childhood Disruptive Behaviors
Martel, M. M., Gremillion, M. L., Roberts, B. A., von Eye, A., & Nigg, J. (2010) · Psychological Assessment · doi:10.1037/a0020975 · Cited by 53 · see citing works
“Recruitment and identification—A broad community-based recruitment strategy was used, with mass mailings to parents in local school districts, public advertisements, and fliers at local clinics, in an effort to mimic the recruitment strategy of the MTA study (Arnold et al., 1997).”
MethodHinshaw, S. P. (2007) · Ambulatory Pediatrics · doi:10.1016/j.ambp.2006.04.012 · Cited by 44 · see citing works
- Authors
- Arnold, L. E.
- Affiliations
- National Institute of Mental Health (US)
- Corresponding author
- Arnold, L. Eugene
- ORCID
- Arnold, L. Eugene
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1997-09-01
- Volume
- 54
- Issue
- 9
- Pages
- 865
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2157719972
- Cited by
- 240
- References
- 20
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 10 · 2014: 7 · 2013: 3 · 2012: 3
- FWCI
- 14.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (UO1 MH50461, UO1 MH50440, U01MH050447, U01MH050440, UO1 MH50447, U01MH050461)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- attention deficit hyperactivity disorder, children, multimodal therapy, stimulant medication, behavior therapy, psychosocial interventions, combination therapy, community-based care, long-term treatment effectiveness, decision-making algorithm, target population definition
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Behavior Therapy, Child, Clinical Protocols, Combined Modality Therapy, Decision Making, Dextroamphetamine, Female, Health Policy, Health Services Research, Humans, Imipramine, Male, Methylphenidate, National Institute of Mental Health (U.S.), Pemoline, Research Design, United States, Patient Selection
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