Dual Drug Therapy May Help Kids With ADHD and Aggression

Megan Brooks

September 09, 2014

Children with attention-deficit/hyperactive disorder (ADHD) and severe aggression may benefit from having an antipsychotic added to a psychostimulant medication as well as behavioral parent training, new research suggests.

Dr. Kenneth Gadow

New data from the Treatment of Severe Childhood Aggression (TOSCA) study confirms that such combination therapy is efficacious.

"A large percentage of children who receive medication for ADHD and disruptive behavior problems often take 2 or more medications. However, there is very little research indicating whether or not this treatment strategy is truly effective," Kenneth Gadow, PhD, professor of psychiatry at Stony Brook University School of Medicine, in New York, told Medscape Medical News.

"I think what we learned from this study is that a combination of 2 medications, in this case, a stimulant and risperidone [Risperdal, Janssen Pharmaceuticals, Inc], may be helpful for some children, but the amount of additional benefit appears to be moderate. I think that's the important take-home message," Dr. Gadow said.

The study is published in the September issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

Challenging Group

Children with ADHD may have co-occurring oppositional defiant disorder (ODD) or conduct disorder (CD) and exhibit severe physical aggression, which can have significant consequences for family, school, and community.

There is evidence that psychostimulants for ADHD can suppress ODD symptoms, particularly when combined with parent training in child behavior management. However, some children remain impaired.

The TOSCA study found that augmenting stimulant and parent training with the antipsychotic risperidone had therapeutic benefit.

The TOSCA team enrolled 168 children between the ages of 6 and 12 years (76.8% boys) with severe physical aggression, ADHD, and co-occurring ODD/CD in an open trial of parent training and psychostimulant medication for 3 weeks.

Children failing to respond adequately were randomly assigned to continue with stimulant medication/parent training (basic therapy) or to have risperidone added to their regimen (augmented therapy) for an additional 6 weeks.

Compared with children receiving basic therapy, those receiving augmented therapy experienced greater reduction in parent-rated ODD severity (P = .002, Cohen's d = 0.27) and peer aggression (P = .02, Cohen's d = 0.32) but not ADHD or CD symptoms.

At week 9, fewer children receiving augmented (16%) than basic (40%) therapy were rated by their parents as being impaired by ODD symptoms (P = .008).

Teacher ratings indicated greater reduction in ADHD severity (P =.02, Cohen's d = 0.61) with augmented therapy, but not for ODD or CD symptoms or peer aggression.

"Although the breadth of clinical improvement was encouraging, effect sizes were generally small for the added benefits of Augmented therapy, probably because of large improvement already attained by the Basic multimodal treatment," the authors say.

Their findings build on earlier results from the TOSCA trial, reported earlier this year by Medscape Medical News.

In the next few months, the researchers hope to report on intermediate (3-month) and long-term (12-month) outcomes, Dr. Gadow told Medscape Medical News.

Dr. Gadow noted that it is important to note that although basic and augmented therapies were associated with marked symptom reduction, a "relatively large percentage" of children were still rated as impaired for at least 1 targeted disorder by parents (basic, 47%; augmented, 27%) and teachers (basic, 48%; augmented, 38%).

"Even though we should be pleased that we have highly effective interventions for these children, many of them still have unmet service needs," Dr. Gadow said. "Some of these families may need more intense behavioral intervention, and we all know unfortunately that our healthcare system may not be able to provide those services for these families."

"In the real world, it is very difficult for low-income families to get this kind of support because traditionally, they have not been able to afford it, and insurance plans may not cover this kind of intervention. They also might not have access to a therapist," Dr. Gadow said.

New Questions

In an accompanying editorial, Peter S. Jensen, MD, from the REACH Institute in New York City, notes that the study raises new questions that "we must now struggle to answer." Among them, why more improvements in children's oppositional and aggressive behavior are seen at home than at school.

"When such discrepancies exist clinically, how do we determine whether the nature of 'the problem' lies in some characteristics of the child, features of his or her environment, or in an interaction between children and their differing environments?

"Understandably, Gadow et al anticipated and skirted this question, but only somewhat, by providing a proven pharmacologic intervention for the child and behavioral management and skills training for the parents. As clinicians, we cannot dodge quite so easily," Dr. Jensen writes.

Given the discrepancies in children's behavior and outcomes across settings, it is also unclear how interventions for children should differ if the aggression is seen only within 1 setting vs multiple settings, Dr. Jensen notes.

"Should we intervene with the child, such as using medication, or should we intervene with the environment, such as more intensive coaching or training of parents or teachers? If we always assume that we should first 'fix' the child, it is likely that a good number of children will receive medication when other interventions might be more appropriate, such as teacher support and training, a change of the child's classroom, assistance to parents in developing their skills in working with a hard-to-manage child, or even anger control psychotherapy," he writes.

Dr. Jensen says it is also unclear how much initial "pretreatment" should be provided before an antipsychotic is added.

The study was supported by the National Institute of Mental Health and the National Institutes of Health General Clinical Research Center. Several TOSCA study investigators have made disclosures, a complete list of which is with the original article.

J Am Acad Child Adolesc Psychiatry. 2014;53:948-959. Abstract, Editorial


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