April 29, 2024
Guanfacine is a non-stimulant medication for ADHD. It is an Alpha-2 agonist that targets and excites receptors in the prefrontal cortex of the brain, the region that governs executive functions such as judgment, decision making, planning, and response suppression. These functions tend to be sub-optimal in ADHD.
Most treatment guidelines recommend stimulants as the preferred treatment for ADHD, because they respond faster, and studies show they have higher efficacy in reducing symptoms. But for individuals for whom treatment with stimulants is subpar, guidelines recommend non-stimulants as second-line treatment.
Previous meta-analyses have focused on efficacy among children and adolescents with ADHD. This meta-analysis, by a Chinese study team, expanded its reach to not only update the former, but also include studies of adults.
The team’s systematic search of the medical literature for double-blind randomized controlled trials (RCTs) identified eleven that could be combined for meta-analysis. With only a single study of efficacy for adults, however, no meta-analysis could be performed specific to persons 18 and older.
Meta-analysis of all eleven studies with a combined total of 2,623 participants found guanfacine to be roughly 75% more effective than placebo for reducing ADHD symptoms. Variation between studies (heterogeneity) was low. There was no sign of publication bias.
Breaking that down by length of time on guanfacine found no evidence of a dose-response effect, however. In fact, participants with less than ten weeks of treatment (seven RCTs, 1,771 participants) outperformed those with longer periods of treatment (four RCTs, 852 participants) with a narrow overlap in the 95% confidence limits.
The outcomes were also sensitive to the ADHD symptom scale used. Meta-analysis of RCTs using the Clinical Global Impression of Improvement treatment response score (four studies, 850 participants) reported no significant improvement, while RCTs relying on ADHD-Rating-Scale-IV (six studies, 1,128 participants) reported a significant improvement, but without providing a standardized effect size.
Finally, a meta-analysis of ten RCTs with a combined total of 2,273 persons found a 23% increase in treatment-emergent adverse events for guanfacine relative to placebo. The three most common such events in the guanfacine group were somnolence (38.6%), headache (20.5%), and fatigue (15.2%).
Sijie Yu, Sihao Shen, and Ming Tao, “Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis,” Journal of Child and Adolescent Psychopharmacology (2023), https://doi.org/10.1089/cap.2022.0038.