This article is more than 5 years old. Information may no longer be current.

Combination therapy showed significant benefit in children with ADHD

Wilens TE. J Am Acad Child Adolesc Psychiatry. 2012;51:74-85.

Combined treatment with guanfacine extended-release and a psychostimulant appears to be effective in children with attention-deficit/hyperactivity disorder who have had a suboptimal response to psychostimulant monotherapy.

This is the first randomized, placebo-controlled trial designed to assess efficacy and safety of guanfacine extended-release (GXR) as an adjunct to psychostimulants in children and adolescents aged 6 to 17 years diagnosed with ADHD who had a suboptimal response to a psychostimulant alone.

Timothy E. Wilens, MD, and colleagues conducted a 9-week multicenter, double blind, placebo-controlled, dose-optimization study, with patients in 59 study sites who continued their stable dose of psychostimulant given in the morning and were randomly assigned to receive GXR in the morning, GXR in the evening or placebo, according to the study findings.

Patients who received 4 mg/day or less of GXR plus a psychostimulant showed significantly greater improvement from baseline to endpoint, as measured by the ADHD-Rating Scale IV total score, compared with those receiving placebo plus a psychostimulant. The results did not differ depending on the time of day GXR was given.

“Although this study was not designed to compare morning with evening dosing of GXR, upon visual inspection, similar responses were seen in the GXR a.m. plus psychostimulant and GXR p.m. plus psychostimulant groups, suggesting that both dosing regimens are efficacious, safe and tolerable,� the researchers wrote.

Wilens and colleagues said the inattention subscale rating and the hyperactivity/impulsivity subscales of the ADHD-RS-IV showed significantly greater improvements from baseline in those receiving GXR with a psychostimulant compared with patients who received placebo plus psychostimulant.

At endpoint, small mean decreases in pulse, systolic and diastolic blood pressure were observed in GXR treatment groups vs. placebo plus psychostimulant, but no new safety signals emerged, according to the investigators.

Disclosure: This study was supported by Shire Development Inc. Dr. Wilens has received grant support from Abbott, Eli Lilly, McNeil, Merck, the National Institutes of Health and Shire. He has served as a speaker for Eli Lilly, McNeil, Novartis and Shire. He has served as a consultant for Abbott, AstraZeneca, Eli Lilly, Euthymics, McNeil, Merck, NextWave, NIH, NIDA, Novartis and Shire. Dr. Wilens receives royalties from Guilford Press.

The study by Tim Wilens and colleagues shows efficacy of the long-acting preparation of guanficine in treating ADHD in youngsters who were on one of several psychostimulants without complete control of their symptoms. This industry-sponsored, double blinded, placebo-controlled study of 9 weeks using 461 subjects in several centers showed that this drug was a useful treatment adjunct without showing any serious sid effects. This is not surprising, as guanficine has been around a very long time and has been used effectively in ADHD treatment. However, the older, short-acting form had to be given two or even three times daily, which was difficult to manage with children in school. The long-acting form was long awaited by many of us. This drug builds effectiveness over time and missed doses may result in reactive hypertension, as cautioned by manufacturers, although I have never seen this myself. Mild decreases in pulse and blood pressure were observed in this study but did not require discontinuance of this alpha-agonist. I have seen serious bradycardia and hypotension with accidental overdoses.

My experience suggests that guanficine is particularly helpful in children who are highly impulsive and aggressive, although this study did not look at subgroup profiles of responsiveness. Interestingly, in this report, both the AM and PM administrations of the drug were equally efficacious, perhaps taking advantage of the mild sedation seen with all forms of guanficine to get youngsters to sleep, a side-effect most parents appreciate. In spite of its benefits, adding a second drug is more than twice as complex as prescribing one, requires even closer monitoring, and is best used in families that are highly compliant, faithful in follow-up and have good access to care, should any concerns arise.

Suzanne D. Dixon, MD, MPH
Infectious Diseases in Children Editorial Board member

Disclosure: Dr. Dixon is the editor of the Journal of Developmental and Behavioral Pediatrics.

Follow the PediatricSuperSite.com on Twitter.