Clinical Summary
Clinical Summary: Efficacy and Safety of Guanfacine Extended-Release in the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults: Results of a Randomized, Double-Blind, Placebo-Controlled Study
Adult attention-deficit/hyperactivity disorder is often underdiagnosed, functionally impairing, and difficult to treat when current options are limited. This trial tests whether guanfacine extended-release, a nonstimulant already used in pediatric ADHD, improves core symptoms in adults without introducing major safety problems.
Design
This phase 3, randomized, double-blind, placebo-controlled, dose-optimized trial
N
201 were randomized to the treatment period
Population
Japanese patients aged ≥ 18 years with ADHD (DSM-5)
Duration
screening (1-4 weeks), treatment (optimization [5 weeks], maintenance [5 weeks]), tapering (2 weeks), and follow-up (1 week)
Key Findings
- At week 10, ADHD-RS-IV total score improved more with guanfacine extended-release than placebo: least squares mean ± SE, -11.55 ± 1.10 vs -7.27 ± 1.07; LS mean difference -4.28; 95% CI, -6.67 to -1.88; P = .0005; effect size 0.52.
- Guanfacine extended-release improved both ADHD-RS-IV symptom domains at week 10: inattention -7.39 ± 0.79 vs -4.89 ± 0.76; P = .0032, and hyperactivity-impulsivity -3.84 ± 0.54 vs -2.10 ± 0.52; P = .0021.
- Clinician- and patient-rated improvement rates were higher with guanfacine extended-release at week 10: CGI-I 48.1% vs 22.6%; P = .0007, and PGI-I 25.3% vs 11.8%; P = .0283.
- Tolerability favored placebo: TEAEs occurred in 81.2% with guanfacine extended-release vs 62.0% with placebo, and TEAEs leading to discontinuation occurred in 19.8% vs 3.0%.
- Illness severity by CGI-S did not differ at week 10 despite symptom improvement: 3.8% with guanfacine extended-release vs 4.3% with placebo; P = 1.0000.
Clinical Bottom Line
Dose-optimized guanfacine extended-release 4-6 mg/d reduced core adult attention-deficit/hyperactivity disorder symptoms and improved global improvement ratings versus placebo over 10 weeks. The tradeoff was a higher rate of mostly mild to moderate adverse events and more discontinuations during dose optimization.
Practice Implications
- Consider guanfacine extended-release as a nonstimulant option for adults with ADHD when improvement is needed in both inattentive and hyperactive-impulsive symptoms, with separation from placebo evident by weeks 4-10.
- Monitor closely during initiation and titration, because many somnolence events occurred within the first week and the main TEAEs leading to discontinuation were blood pressure decrease and somnolence during the dose-optimization period.
- Check blood pressure, pulse or heart rate, and ECG-related tolerability during treatment, as pulse/heart rate, blood pressure, and QTc corrected by the Bazett formula were decreased with guanfacine extended-release at week 10 and mostly returned to baseline levels by week 12.
- Apply these results mainly to relatively uncomplicated adult ADHD, since the trial excluded patients with schizophrenia, bipolar disorder, personality disorder, documented anxiety/depression necessitating treatment, substance use disorder history, seizures, serious tic disorder, suicide risk, or cardiovascular disease.
