Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder

Robert M Bilder; Sandra K Loo; James J McGough; Fiona Whelan; Gerhard Hellemann; Catherine Sugar; Melissa Del'Homme; Alexandra Sturm; Jennifer Cowen; Grant Hanada; James T McCracken

doi:10.1016/j.jaac.2016.05.016

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder

J Am Acad Child Adolesc Psychiatry. 2016 Aug;55(8):667-73. doi: 10.1016/j.jaac.2016.05.016. Epub 2016 Jun 7.

Authors

Affiliations

¹ David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA; UCLA College of Letters and Science. Electronic address: rbilder@mednet.ucla.edu.
² David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.
³ David Geffen School of Medicine at University of California, Los Angeles (UCLA), and the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA; UCLA School of Public Health.
⁴ Graduate School of Education and Information Sciences at UCLA.
⁵ UCLA and the Semel Institute for Neuroscience and Human Behavior at UCLA.
⁶ School of Engineering at the University of Michigan, Ann Arbor.

Abstract

Objective: Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD.

Method: Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables.

Results: The ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group.

Conclusion: Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD.

Clinical trial registration information: Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273.

Keywords: attention-deficit/hyperactivity disorder; cognition; guanfacine; stimulant; working memory.

Publication types

Randomized Controlled Trial

MeSH terms

Adolescent
Adrenergic alpha-2 Receptor Agonists / administration & dosage
Adrenergic alpha-2 Receptor Agonists / pharmacology*
Attention Deficit Disorder with Hyperactivity / complications
Attention Deficit Disorder with Hyperactivity / drug therapy*
Central Nervous System Stimulants / administration & dosage
Central Nervous System Stimulants / pharmacology*
Child
Cognitive Dysfunction / drug therapy*
Cognitive Dysfunction / etiology
Double-Blind Method
Drug Therapy, Combination
Female
Guanfacine / administration & dosage
Guanfacine / pharmacology*
Humans
Male
Methylphenidate / administration & dosage
Methylphenidate / pharmacology*
Outcome Assessment, Health Care*

Substances

Adrenergic alpha-2 Receptor Agonists
Central Nervous System Stimulants
Methylphenidate
Guanfacine

Associated data

ClinicalTrials.gov/NCT00429273

Grants and funding

P50 MH077248/MH/NIMH NIH HHS/United States