James M Swanson1, L Eugene Arnold2, Brooke S G Molina3, Margaret H Sibley4, Lily T Hechtman5, Stephen P Hinshaw6, Howard B Abikoff7, Annamarie Stehli1, Elizabeth B Owens8, John T Mitchell9, Quyen Nichols10, Andrea Howard11, Laurence L Greenhill12, Betsy Hoza10, Jeffrey H Newcorn13, Peter S Jensen14, Benedetto Vitiello15, Timothy Wigal16, Jeffery N Epstein17, Leanne Tamm17, Kimberly D Lakes1, James Waxmonsky18, Marc Lerner1, Joy Etcovitch19, Desiree W Murray20, Maximilian Muenke21, Maria T Acosta21, Mauricio Arcos-Burgos22, William E Pelham23, Helena C Kraemer24. 1. Department of Pediatrics, School of Medicine, University of California, Irvine, CA, USA. 2. Department of Psychiatry, Nisonger Center, Ohio State University, Columbus, OH, USA. 3. Departments of Psychiatry and Psychology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. 4. Department of Psychiatry, Florida International University, Miami, FL, USA. 5. Division of Child Psychiatry, McGill University, Montreal Children's Hospital, Montreal, QC, Canada. 6. Department of Psychology, University of California, Berkeley, CA, USA. 7. Child Study Center at New York University Langone Medical Center, New York, NY, USA. 8. Institute of Human Development, University of California, Berkeley, CA, USA. 9. Department of Psychiatry & Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. 10. Department of Psychological Science, University of Vermont, Burlington, VT, USA. 11. Department of Psychology, Carleton University, Ottawa, ON, Canada. 12. Department of Psychiatry, Columbia University, New York, NY, USA. 13. Department of Psychiatry, Mount Sinai Medical School, New York, NY, USA. 14. Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 15. National Institute of Mental Health, Bethesda, MD, USA. 16. Avida, Inc., Newport Beach, CA, USA. 17. Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. 18. Penn State University, College of Medicine, Hershey, PA, USA. 19. Montreal Children's Hospital, Montreal, QC, Canada. 20. Frank Porter Graham Child Development Institute, University of North Carolina, Chapel Hill, NC, USA. 21. National Human Genome Research Institute, Bethesda, MD, USA. 22. Institute of Translational Medicine, Universidad del Rosario, Bogata, Colombia. 23. Department of Psychology, Florida International University, Miami, FL, USA. 24. Department of Psychiatry, Stanford University, Stanford, CA, USA.
Abstract
BACKGROUND: The Multimodal Treatment Study (MTA) began as a 14-month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7-10 years of age) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type. It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as alocal normative comparison group (LNCG), with assessments 2-16 years after baseline. METHODS:Primary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow-up, hypothesis-generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication. RESULTS: For ratings of symptom severity, the ADHD-LNCG comparison was statistically significant for the parent/self-report average (0.51 ± 0.04, p < .0001, d = 1.11), documenting symptom persistence, and for the parent/self-report difference (0.21 ± 0.04, p < .0001, d = .60), documenting source discrepancy, but the comparisons of naturalistic subgroups reflecting medication effects were not significant. For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38). CONCLUSIONS: In the MTA follow-up into adulthood, the ADHD group showed symptom persistence compared to local norms from the LNCG. Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.
RCT Entities:
BACKGROUND: The Multimodal Treatment Study (MTA) began as a 14-month randomized clinical trial of behavioral and pharmacological treatments of 579 children (7-10 years of age) diagnosed with attention-deficit/hyperactivity disorder (ADHD)-combined type. It transitioned into an observational long-term follow-up of 515 cases consented for continuation and 289 classmates (258 without ADHD) added as a local normative comparison group (LNCG), with assessments 2-16 years after baseline. METHODS: Primary (symptom severity) and secondary (adult height) outcomes in adulthood were specified. Treatment was monitored to age 18, and naturalistic subgroups were formed based on three patterns of long-term use of stimulant medication (Consistent, Inconsistent, and Negligible). For the follow-up, hypothesis-generating analyses were performed on outcomes in early adulthood (at 25 years of age). Planned comparisons were used to estimate ADHD-LNCG differences reflecting persistence of symptoms and naturalistic subgroup differences reflecting benefit (symptom reduction) and cost (height suppression) associated with extended use of medication. RESULTS: For ratings of symptom severity, the ADHD-LNCG comparison was statistically significant for the parent/self-report average (0.51 ± 0.04, p < .0001, d = 1.11), documenting symptom persistence, and for the parent/self-report difference (0.21 ± 0.04, p < .0001, d = .60), documenting source discrepancy, but the comparisons of naturalistic subgroups reflecting medication effects were not significant. For adult height, the ADHD group was 1.29 ± 0.55 cm shorter than the LNCG (p < .01, d = .21), and the comparisons of the naturalistic subgroups were significant: the treated group with the Consistent or Inconsistent pattern was 2.55 ± 0.73 cm shorter than the subgroup with the Negligible pattern (p < .0005, d = .42), and within the treated group, the subgroup with the Consistent pattern was 2.36 ± 1.13 cm shorter than the subgroup with the Inconsistent pattern (p < .04, d = .38). CONCLUSIONS: In the MTA follow-up into adulthood, the ADHD group showed symptom persistence compared to local norms from the LNCG. Within naturalistic subgroups of ADHD cases, extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.
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