Combined Stimulant and Guanfacine Administration in Attention-Deficit/Hyperactivity Disorder: A Controlled, Comparative Study
Year: 2016
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: OBJECTIVE: Because models of attention-deficit/hyperactivity disorder (ADHD) therapeutics emphasize benefits of both enhanced dopaminergic and noradrenergic signaling, strategies to enhance D1 and α2A agonism may yield enhanced clinical and cognitive responses. This study tested the hypothesis that combined effects of a dopamine and noradrenergic agonist, d-methylphenidate extended-release (DMPH) with guanfacine (GUAN), an α2A receptor agonist, would be clinically superior to either monotherapy and would have equal tolerability. METHOD: An 8-week, double-blind, 3-arm, comparative trial randomized 7- to 14-year-olds with DSM-IV ADHD to GUAN (1-3 mg/day), DMPH (5-20 mg/day), or a combination (COMB) with fixed-flexible dosing. Outcome measures were the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Data on adverse events and safety measures were obtained. RESULTS: A total of 207 participants were randomized and received drug. Analyses showed significant treatment group main effects for ADHD-RS-IV ADHD total (p = .0001) and inattentive symptoms (p = .0001). COMB demonstrated small but consistently greater reductions in ADHD-RS-IV Inattentive subscale scores versus monotherapies (DMPH: p = .05; f(2) = .02; and GUAN: p = .02; f(2) = .02), and was associated with a greater positive response rate by CGI-I (p = .01). No serious cardiovascular events occurred. Sedation, somnolence, lethargy, and fatigue were greater in both guanfacine groups. All treatments were well tolerated. CONCLUSION: COMB showed consistent evidence of clinical benefits over monotherapies, possibly reflecting advantages of greater combined dopaminergic and α2A agonism. Adverse events were generally mild to moderate, and COMB treatment showed no differences in safety or tolerability. CLINICAL TRIAL REGISTRATION INFORMATION: Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder (Project1); http://clinicaltrials.gov/; NCT00429273.
Institution: University of California, Los Angeles
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,710
Funders: John Templeton Foundation, Purdue University, Sunovion, FORUM Pharmaceuticals, University of Oxford, H. Lundbeck A/S, University of California, Los Angeles, National Institute of Mental Health, David Geffen School of Medicine, University of California, Los Angeles, Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles
OpenAlex ID: W2416192894