Los Angeles—While drug therapy for attention-deficit/hyperactivity disorder (ADHD) appears to significantly reduce symptoms, individual medications generally have not been shown to improve long-term academic, social, and clinical outcomes, according to a new study.

The researchers report, however, that combining two standard medications could lead to greater clinical improvements for children with ADHD than either of the drugs by themselves. Results were published recently in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP).

Noting that most clinical studies have not objectively measured the effect of ADHD treatments on brain function, researchers from the UCLA Semel Institute recruited a sample of children and adolescents aged 7 to 14 years with and without ADHD to perform three studies examining the effects of combining standard medications on clinical, cognitive, and brain activity measures.

Their hypothesis was that combined treatment would be superior to d-methylphenidate and guanfacine alone, on both clinical and cognitive outcomes, and that a distinct profile of effects on brain wave activity (EEG) could be identified. To that end, participants with ADHD were randomly assigned to eight weeks of double-blinded treatment with either d-methylphenidate, guanfacine, or a combination of the two.

Results indicate that the combined therapy was more beneficial than the two single treatments, especially for symptoms of inattention, and more global response indices. The rate of good clinical response went up from 62% to 63% in the single-drug therapy to 75% in the combined therapy, according to the study.

Cognitive functioning showed a slightly different pattern, study authors report. Working memory improved similarly with both combination and stimulant treatments, but no change in working memory function was noted with guanfacine, despite improvement in ADHD symptomatology.

The EEG study, meanwhile, showed that only the combination therapy resulted in improved brain activity patterns that were associated with reduced ADHD symptoms and improved cognitive functions.

Overall, the results from the three studies indicated that combination therapy resulted in the best outcomes in areas such as ADHD symptom change, working memory performance, and brain activity patterns.

“ADHD is the most commonly diagnosed neuropsychiatric disorder in children, and we know full well the risks it poses for children's future success in every area of functioning. Our current treatments clearly benefit most children in the short-term, but we've yet to find ways to protect those with ADHD from suffering many of the long-term risks,” explained co-author James McCracken, MD. “While we are encouraged by some of the advantages we observed of the combined treatment, we have a long way to go still in improving interventions for ADHD, as seen by the more limited cognitive effects.”

Lead author Sandra Loo, PhD, suggested, “The use of objective biological measures in diagnosis and treatment can also help to reduce stigma, increase acceptance of the disorder, and more accurately track treatment response to yield better outcomes.”

Study authors conclude that combining stimulants with medications such as guanfacine should get more consideration, even in pediatric patients benefiting from monotherapy. The study also found combination treatment with appropriate monitoring to be well-tolerated and safe.

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