Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder: the Multimodal Treatment Study of children with Attention-deficit/hyperactivity disorder

Arch Gen Psychiatry. 1999 Dec;56(12):1088-96. doi: 10.1001/archpsyc.56.12.1088.


Background: Intent-to-treat analyses of the study revealed that medication management, alone or combined with intensive behavioral treatment, was superior to behavioral treatment and community care in reducing attention-deficit/hyperactivity disorder (ADHD) symptoms; but only combined treatment showed consistently greater benefit than community care across other outcome domains (disruptive and internalizing symptoms, achievement, parent-child relations, and social skills). We examine response patterns in subgroups defined by baseline variables (moderators) or variables related to treatment implementation (mediators).

Methods: We reconducted random-effects regression (RR) analyses, adding factors defined by moderators (sex, prior medication use, comorbid disruptive or anxiety disorder, and public assistance) and a mediator (treatment acceptance/attendance).

Results: Study outcomes (N = 579) were upheld in most moderator subgroups (boys and girls, children with and without prior medication, children with and without comorbid disruptive disorders). Comorbid anxiety disorder did moderate outcome; in participants without anxiety, results paralleled intent-to-treat findings. For those with anxiety disorders, however, behavioral treatment yielded significantly better outcomes than community care (and was no longer statistically different from medication management and combined treatment) regarding ADHD-related and internalizing symptoms. In families receiving public assistance, medication management yielded decreased closeness in parent-child interactions, and combined treatment yielded relatively greater benefits for teacher-reported social skills. In families with high treatment acceptance/attendance, intent-to-treat results were upheld. Acceptance/attendance was particularly important for medication treatments. Finally, two thirds of children given community care received stimulants. Behavioral treatment did not significantly differ from, but medication management was superior to, this subgroup.

Conclusions: Exploratory analyses revealed that our study (the Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder [MTA]) results were confirmed across most baseline variables and treatment acceptance/attendance. In children with ADHD plus anxiety, behavioral treatment surpassed community care and approached medication-based treatments regarding parent-reported ADHD symptoms.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Attention Deficit Disorder with Hyperactivity / therapy*
  • Behavior Therapy* / methods
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / therapeutic use*
  • Child
  • Combined Modality Therapy
  • Community Mental Health Services
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Methylphenidate / administration & dosage
  • Methylphenidate / therapeutic use*
  • Treatment Outcome


  • Central Nervous System Stimulants
  • Methylphenidate