Guanfacine Adjunct for ADHD Improves Executive Function

The addition of guanfacine to a psychostimulant improved executive function in children with ADHD.

Judy van Stralen, MD

The addition of guanfacine to treat children with attention-deficit/hyperactivity disorder (ADHD) symptoms not adequately improved by psychostimulant medication resulted in an increase in executive function, including goal-directed behavior and self-regulation.

Judy van Stralen, MD, reported on the study from the Center for Pediatric Excellence, Ottawa, Ontario, Canada.

"Despite their effectiveness, treatment with stimulants sometimes results in inadequate response in symptom control," she wrote. "Such lingering ADHD symptoms clinically results in patients having ongoing functional impairment including executive function deficits."

van Stralen elaborated on the rationale for the study in comments to MD Magazine, "if there are residual ADHD symptoms, including those seen at the ends of the day, morning and evening, when psychostimulants are not working particularly well, it is reasonable to consider adjunctive therapy."

The investigators randomized 50 children aged 6 to 12 years to the placebo-controlled, crossover study to compare the effects of adding guanfacine extended release (GXR) (Intuniv, Shire, others) or placebo to an ongoing psychostimulant regimen. The children were deemed to have had inadequate response to not less than 30 days of psychostimulant medication, from clinical assessment and ADHD Rating Scale IV (ADHD-RS IV) measures, as well as suboptimal executive function reflected in a parent-administered Behavioral Rating Inventory of Executive Function (BRIEF-P) t score of >65.

Thirty-nine patients completed both the GXR and placebo 8-week adjunct treatment arms and a 3-week "wash out" period between crossover. Clinical assessments of therapeutic and adverse response were conducted weekly. The dose of GXR was adjusted between the second and sixth assessment visits from a starting dose of 1 mg/day, with weekly increments to a maximum of 4 mg/day and a 1-time 1 mg/day reduction if required. Psychostimulant medication was maintained throughout the study, including throughout the "wash-out" period.

The primary efficacy measure was assessment of executive function in the home with the BRIEF-P global executive composite (GEC) score, with secondary assessments drawn from clinician measures with the ADHD-RS IV and the Clinical Global Impressions of Severity of Illness (CGI-S) and improvement (CGI-I) scales.

The investigators found significantly greater improvement with GXR than with placebo addition to psychostimulant medication on the BRIEF-P GEC measure and a correlation with improvement in ADHD-RS IV. The BRIEF-P GEC score was significantly improved for patients experiencing 30% improvement on ADHD-RS IV while on GXR, and twice as many patients on GXR experienced a 30% improvement on ADHD-RS-IV than those on placebo.

"The population of patients that had the most robust effect on their executive function were those who had a response to GXR based on improvement in ADHD-RS IV," van Stalen reported.

"Although some people may question the addition of a second dosage, adjunctive therapy medication is not unusual to treat medical conditions," van Stralen said discussing the place of adjunctive medication in treating children with ADHD with MD Magazine. "If ADHD symptoms are better controlled, it can lead to a reduction in the functional impairment, which is the ultimate goal of treatment."

The controlled trial of guanfacine as an adjunct to psychostimulant medication for executive function in children with ADHD was published online January 9 in the Journal of Attention Disorders.

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