Frequently Asked Questions

Yes. In this randomized, double-blind, placebo-controlled trial in Japanese adults with ADHD, guanfacine extended-release produced a greater reduction in ADHD-RS-IV total score at week 10 than placebo (-11.55 ± 1.10 vs -7.27 ± 1.07; LS mean difference -4.28; 95% CI, -6.67 to -1.88; P = .0005), with an effect size of 0.52. The study concluded that guanfacine extended-release improved ADHD symptoms without major safety concerns in this population.

Guanfacine extended-release improved both symptom domains. At week 10, the ADHD-RS-IV inattention subscale changed by -7.39 ± 0.79 with guanfacine extended-release versus -4.89 ± 0.76 with placebo (P = .0032), and the hyperactivity-impulsivity subscale changed by -3.84 ± 0.54 versus -2.10 ± 0.52 (P = .0021). The study reported that these benefits were sustained from week 4 for inattention and from week 5 for hyperactivity-impulsivity through week 10.

The treatment difference emerged during the first month of therapy. The greater decrease in ADHD-RS-IV total score with guanfacine extended-release was seen from weeks 4 through 10 of treatment (P < .005), and the improvements in inattention and hyperactivity-impulsivity were sustained from week 4 and week 5, respectively, through week 10.

Yes. At week 10, the proportion rated very much improved or much improved was higher with guanfacine extended-release than placebo on both the clinician-rated CGI-I (48.1% vs 22.6%; P = .0007) and the patient-rated PGI-I (25.3% vs 11.8%; P = .0283). However, illness severity rated as normal or borderline mentally ill on the CGI-S was similar between groups at week 10 (3.8% vs 4.3%; P = 1.0000).

The study found improvement in some, but not all, patient-reported functional outcomes. Compared with placebo, guanfacine extended-release increased the Adult ADHD Quality of Life Questionnaire total score and all subscale scores at week 10, but the between-group difference was statistically significant for the life productivity subscale only (P = .0072). On the BRIEF-A, guanfacine extended-release improved all subscale T-scores at week 10, with significant differences for Inhibit, Initiate, Plan/Organize, and the Global Executive Composite Index (P < .05).

The most common treatment-emergent adverse events with guanfacine extended-release were somnolence, thirst, blood pressure decrease, nasopharyngitis, postural dizziness, and constipation. Most adverse events were mild to moderate in severity, and except for nasopharyngitis, most of these common events were considered related to the study drug.

Adverse-event-related discontinuation was more common with guanfacine extended-release than placebo. TEAEs leading to discontinuation occurred in 19.8% of patients receiving guanfacine extended-release versus 3.0% receiving placebo. The main adverse events leading to discontinuation in the guanfacine extended-release group were blood pressure decrease and somnolence, and all of these occurred during the dose-optimization period.

Compared with placebo, guanfacine extended-release was associated at week 10 with decreases in pulse or heart rate, blood pressure, and QTc corrected by the Bazett formula, while QT and RR intervals increased. These changes mostly returned toward baseline by week 12. At last observation, 2 patients in the guanfacine extended-release group had abnormal ECG findings reported as treatment-emergent adverse events: sinus bradycardia and QT prolongation.

Patients started at 2 mg/day and were titrated during a 5-week dose-optimization period to 4-6 mg/day, followed by a 5-week maintenance period at 4-6 mg/day and then a 2-week taper to 2 mg/day. The mean maintenance dose was 5.07 mg. During maintenance, 27 patients received 4 mg, 23 received 5 mg, and 33 received 6 mg.

The trial enrolled Japanese adults aged 18 years or older with DSM-5 ADHD, an ADHD-RS-IV total score of at least 24, and a CGI-S score of at least 4. Patients were excluded if they had schizophrenia, bipolar disorder, personality disorder, mental retardation, a moderate or severe psychiatric disorder requiring treatment, documented anxiety or depression, a history of substance use disorder or seizures, a serious tic disorder, suicide risk, or cardiovascular abnormalities such as prolonged QTc, orthostatic hypotension, continuous bradycardia, or abnormal ECG findings.

The main limitations were the short treatment duration, exclusion of patients with psychiatric or cardiovascular comorbidities, imbalance in age distribution between groups, relatively large proportion of men, and possible lack of generalizability to non-Japanese populations. The authors stated that long-term prospective studies in real-life clinical settings and in different races are needed to confirm the efficacy and safety profile in adult ADHD.