A retrospective chart review of 432 children and adolescents with attention-deficit/hyperactivity disorder (ADHD) found use of a stimulant medication in addition to atomoxetine to be associated with treatment success in patients being treated with atomoxetine. Use of a stimulant was the only one of several factors examined, including a number of demographic characteristics and presence or absence of comorbid disorders, which was found to be associated with atomoxetine efficacy.

Study results were published in the Journal of Child and Adolescent Psychopharmacology.

A research team led by Nakia Gray Scott, M.D., of Scott and White Memorial Hospital in Temple, Texas set out to study atomoxetine’s efficacy in various subgroups of youths with ADHD — seeking this information in part because of somewhat disappointing clinical results overall with use of atomoxetine in this population. Corresponding author Jane Ripperger-Suhler, M.D., told The Update that research findings showing atomoxetine’s efficacy for treating ADHD generally have not been as evident in clinical practice.

This study then was intended to determine which groups of patients might be most likely to have success with atomoxetine treatment. The retrospective study was conducted using data from the electronic medical record system of a large multispecialty group practice affiliated with a university training program.

Children ages 5 to 17 who were diagnosed with ADHD and were prescribed atomoxetine between November 2002 and April 2005 were included in the analysis. Based in large part on whether (and why) atomoxetine treatment was discontinued in each individual case by one of the authors using the content of the clinical progress note, each child was classified as either a treatment success, a treatment failure, or undetermined.

The researchers then studied the children’s medical records to determine if there was a relationship between atomoxetine efficacy and demographic characteristics, comorbid diagnoses, subtype of ADHD, and use of a stimulant medication in addition to atomoxetine.

Results

Of the 432 patients with sufficient data for study inclusion, 88 were categorized as treatment successes, having a successful response to atomoxetine based upon progress note review. A total of 197 patients were classified as treatment failures, and 147 were included in the undetermined category.

There were no significant differences in demographic characteristics between the treatment success and treatment failure groups, although there was a marginal association between non-White ethnicity and treatment success. In the treatment success and treatment failure groups combined, 73.3% of subjects were male, and 77.5% were White. The average age at initiation of atomoxetine was 10.5 years ±3.2 in the treatment success group and 10.6 years ±3.0 in the treatment failure group.

There also were no significant differences in comorbid diagnoses among members of the treatment success and treatment failure groups. The most common comorbid diagnosis in both groups was oppositional defiant disorder (ODD), affecting 36.4% of members of the treatment success group and 31% of members of the treatment failure group. There were no significant differences in comorbid depression and anxiety in the two groups.

There also was no significant difference between the two groups in the type of ADHD diagnosed. In the treatment success group, 67% of subjects were diagnosed with the combined type of ADHD and 11.4% with the inattentive type. In the treatment failure group, 58.7% of subjects were diagnosed with the combined type of ADHD and 15.3% with the inattentive type.

The researchers found that 27.3% of subjects in the treatment success group were prescribed a stimulant in addition to atomoxetine, while 15.2% of subjects in the treatment failure group were prescribed a stimulant in addition to atomoxetine. A multivariate analysis revealed a p value of 0.0319, suggesting a significant difference in the number of youths taking stimulants in the treatment success group compared with the treatment failure group.

Implications

Ripperger-Suhler, who is now an assistant professor at the University of Texas Southwestern Medical Center in Austin, said it was somewhat surprising that stimulant use was the only factor found to be associated with successful atomoxetine treatment. Researchers expected to find that children with comorbid anxiety and/or depression would fare better with atomoxetine treatment, because symptoms of both their ADHD and their comorbid disorder would be treated.

There has been some research evidence that combining atomoxetine and stimulant medication can result in additional improvement in ADHD symptoms in some children, according to the study article. With stimulants acting primarily on the dopaminergic system and atomoxetine acting primarily on the noradrenergic system, the researchers wrote that “the two medications can complement each other, addressing symptoms arising from both neurotransmitter systems.”

Ripperger-Suhler added in her comments to The Update, “For a few patients of my own who were taking both medications, this seemed to be working for them. This led me to thinking about how they might work together.”

The researchers suggest that controlled trials are needed in order to understand in greater detail the potential benefit of combining medications in this way. They bring up the possibility that in the youths who fared better while on both medications, the stimulant alone might have provided the entire benefit. They wrote, “Without objective evidence, there remains uncertainty regarding the source of the symptom resolution that may have been experienced by the clinician as well and thus both medications were continued.”

A major limitation of this study centered on the method by which the researchers classified children into the treatment success and treatment failure groups. This determination was based on a manual review of an electronic medical record system that did not guarantee consistent documentation from providers.

“That was the thing that caused us the most consternation — how to determine a benefit from treatment,” Ripperger-Suhler said. The researchers essentially determined that if a physician kept a patient on atomoxetine, it must have been having a benefit. Yet it is also possible in some cases that a patient was left on the medication even if it wasn’t working.

“It is really hard to tell from the notes,” Ripperger-Suhler said. “People don’t apparently document as well as we’d like them to.”

The researchers wrote in the article, “This issue highlights the general need for all clinicians to systematically use objective tools for measuring efficacy of treatments and for recording the resultant data in the progress notes.”

In addition, the researchers cited as a limitation the fact that one third of potential subjects were excluded from the analysis because of insufficient data in the chart. “With a larger sample size there may have been sufficient power to reveal additional findings,” they wrote.

The researchers concluded that the association between stimulant treatment and success in atomoxetine treatment may suggest a benefit in combining the two medications in the treatment of ADHD. They added that additional efforts to identify predictors of success under atomoxetine treatment need to take place.

The study authors report no potential conflicts of interest.

* * *

Scott NG, Ripperger-Suhler J, Rajab MH, et al.: Factors associated with atomoxetine efficacy for treatment of attention-deficit/hyperactivity disorder in children and adolescents. J Child Adolesc Psychopharm 2010; 20:197–203. E-mail: JARippergersuhler@seton.org.