A 14-month randomized clinical trial in 579 children, aged 7 to 9.9 years, with ADHD Combined type, compared the effects of four different treatment programs (Multimodal Treatment Study). This cooperative study was performed by 6 independent research teams in collaboration with the National Institutes of Mental Health, and the Office of Special Education, Washington, DC. Treatment assignments were medication alone, psychosocial behavior therapy, combined medication and behavior therapy, and community care. Assessments analysed were ADHD symptoms, oppositional/aggressive symptoms, social skills, internalizing symptoms (anxiety and depression), parent-child relations, and academic achievement in reading, math, and spelling. Behavioral treatment included parent and child training, and school-based intervention. Medication management was methylphenidate (MPH), 28-day, double-blind, daily-switch titration, using 5 repeats of placebo, 5, 10, and 15 or 20 mg t.i.d. The optimal dose of MPH for each subject (average, 38 mg/d) was used in subsequent treatment of 73% of 289, and an alternative drug (dextroamphetamine (10%), pemoline (1%) etc) was prescribed in the remaining patients who failed to respond to MPH.
All 4 groups showed reductions in symptoms of variable degrees during the course of the study. Medication and combined treatment were significantly superior to behavioral treatment and community care in controlling ADHD symptoms. Combined behavioral and stimulant treatment was not superior to medication alone for core ADHD symptoms, but had modest benefits in treating non-ADHD symptoms (ODD etc). Short-term benefits from MPH therapy persist during treatment while continued up to 14 months. Total daily doses of MPH in the combined treatment group were lower (31 mg/d) than in the medication alone group. 
COMMENT. For the treatment of ADHD, carefully monitored methylphenidate is superior to behavioral therapy and to routine community care, that includes medication. Combined behavioral and stimulant therapies yield no greater benefits than medication alone for core ADHD symptom control, but may provide modest advantages for non-ADHD symptoms, including oppositional behavior and anxiety. One possible advantage of combining behavioral therapy with medication is the reduction in dose of MPH required and the consequent lessening of adverse effects. However, in practice the additional benefits of combined therapy are small and may not warrant the inconvenience and expense to the parents, except in patients who respond only partially to medication. The key to successful medical therapy is frequent monitoring and adjustment of dosage, not always achieved in clinical practice situations.
For a comment on the results of this study from an expert in the UK . In the UK, the recognition and treatment of ADHD with medication is not as readily accepted as in the US. Many UK parents will opt for no therapy or behavioral therapy, despite the obvious benefits of MPH demonstrated in this MTA study.
ADHD Genetics. Association of the dopamine transporter gene (DAT1) with poor methylphenidate response is reported from Brookdale University Hospital, Brooklyn, NY . Homozygosity of the 10-repeat allele was found to characterize nonresponse to methylphenidate therapy.