Visualizing Neuropharmacological Effects of Guanfacine Extended Release in Attention Deficit Hyperactivity Disorder Using Functional Near-Infrared Spectroscopy
Open accessAbstract
Objective: In the current study, we explored the neural substrate for acute effects of guanfacine extended release (GXR) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD), using functional near-infrared spectroscopy (fNIRS). Methods: Following a GXR washout period, 12 AD HD children (6–10 years old) performed a go/no-go task before and 3 h after GXR or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design study. In the primary analysis, fNIRS was used to monitor the right prefrontal cortical hemodynamics of the participants, where our former studies showed consistent dysfunction and osmotic release oral system-methylphenidate (OROS-MPH) and atomoxetine hydrochloride (ATX) elicited recovery. We examined the inter-medication contrast, comparing the effect of GXR against the placebo. In the exploratory analysis, we explored neural responses in regions other than the right prefrontal cortex (PFC). Results: In the primary analysis, we observed no significant main effects or interactions of medication type and age in month (two-way mixed ANCOVA, Fs < 0.20, all ps > .05). However, in the post-hoc analysis, we observed significant change in the oxy-Hb signal in the right angular gyrus (AG) for inter-medication (one sample t-test, p < 0.05, uncorrected, Cohen's d = 0.71). Conclusions: These results are different from the neuropharmacological effects of OROS-MPH and ATX, which, in an upregulated manner, reduced right PFC function in ADHD children during inhibitory tasks. This analysis, while limited by its secondary nature, suggested that the improved cognitive performance was associated with activation in the right AG, which might serve as a biological marker to monitor the effect of GXR in the ADHD children.
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The study's findings extend evidence of no acute or chronic effects of guanfacine on cognitive performance in children and adults with ADHD.
“They also extend evidence of no acute or chronic effects of guanfacine on cognitive performance in children and adults with ADHD (39–42).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [42]
The Discussion (‘Behavioral Performance for go/no-go Task’; page unavailable) reports no significant behavioral differences before and after guanfacine versus placebo in children with ADHD. The study tested an acute dose after a washout, not chronic effects, and included no adults. Its nonsignificant result also does not establish that guanfacine has no effect. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe study adds to the majority of previous studies showing either no or negative effects of guanfacine on cognition in children with ADHD.
“Nevertheless, our study adds to the majority of previous studies showing either no (39–42) or negative effects (43) of guanfacine on cognition in children with ADHD, with only a single very small numbered study in 17 adults with ADHD showing cognitive improvement in interference inhibition (44).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [42]
The study's findings are in line with the majority of previous negative findings of guanfacine effects on inhibitory measures.
“While this is in line with the majority of the previous negative findings of guanfacine effects on these measures (39, 41, 42), for lisdexamfetamine, some studies of longer-term use found improvement in inhibitory measures (34, 36) while others did not (38).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [42]
Out of six studies testing effects of mostly longer-term guanfacine effects on cognition, four reported sedative symptoms or fatigue while two other studies did not record or report them.
“Out of six studies testing effects of mostly longer-term guanfacine effects on cognition, four reported sedative symptoms (39, 40, 43) or fatigue (44) while two other studies did not record or report them (39, 42).”
From Differential effects of a single dose of Lisdexamfetamine and Guanfacine on cognitive function in children with ADHD (2025) · cites this paper as [42]
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- Authors
- Ikeda, T., Inoue, A., Tanaka, D., Hashimoto, T., Sutoko, S., Tokuda, T., Kyutoku, Y., Maki, A., Yamagata, T., Dan, I., & Monden, Y.
- Affiliations
- Jichi Medical University (JP)
- Chuo University (JP)
- Hitachi (Japan) (JP)
- Corresponding author
- Monden, Yukifumi
- Venue
- Frontiers in Neuroergonomics
- Publisher
- Frontiers Media SA
- Published
- 2021-07-07
- Volume
- 2
- Pages
- 657657-657657
- ISSN
- 2673-6195 (ISSN-L)
- PMC
- PMC10790846
- OpenAlex
- W3180882087
- Cited by
- 7
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Neuroergonomics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Jichi Medical University
- Japan Society for the Promotion of Science (19K17016, 18K17330)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- guanfacine extended release, attention deficit hyperactivity disorder, inhibitory control, right prefrontal cortex, go/no-go task, school-aged children, OROS methylphenidate, atomoxetine, biomarkers
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