Guanfacine extended-release effective, safe for adult ADHD

Guanfacine extended-release was associated with significant improvement in adult ADHD symptoms without any major safety concerns, according to results of a randomized, double-blind, placebo-controlled trial conducted in Japan and published in Journal of Clinical Psychiatry.

“Guanfacine extended-release (GXR), a nonstimulant selective [alpha 2A]-adrenergic receptor agonist, enhances noradrenergic activity in the dorsolateral-prefrontal cortex and has been demonstrated to improve ADHD symptoms in Japanese and non-Japanese children with ADHD,” Akira Iwanami, MD, PhD, of the department of psychiatry at Showa University School of Medicine in Tokyo, and colleagues wrote. “Although GXR monotherapy is approved for the treatment of pediatric ADHD, its efficacy and safety have not been investigated in adult ADHD. Therefore, it would be beneficial to study the effect of GXR in this patient population.”

To determine the drug’s efficacy and safety among adults with ADHD, the researchers randomly assigned 201 patients to GXR (n = 101) or placebo (n = 100), titrated from 2 mg per day to 4 mg to 6 mg per day with dose optimization of 5 weeks. This initial dose was followed by 4 to 6 mg per day with dose maintenance of 5 weeks, then tapered doses to 2 mg per day for 2 weeks. Change from baseline in total score on the Japanese version of the ADHD-Rating Scale IV with adult prompts (ADHD-RS-IV) at week 10 served as the primary endpoint. The investigators also measured ADHD-RS-IV subscales, Clinical Global Impression-Improvement (CGI-I) and Patient Global Impression-Improvement (PGI-I) scales, incidence of treatment-emergent adverse events (TEAEs), and TEAEs leading to discontinuation.

Results showed significantly greater improvement in ADHD-RS-IV total score reduction with GXR compared with placebo (P = .0005), as well as significantly greater improvements with GXR in ADHD-RS-IV inattention (P = .0032) and hyperactivity-impulsivity (P = .0021) subscale scores, CGI-I scores (48.1% vs. 22.6%; P = .0007) and PGI-I scores (25.3% vs. 11.8%; P = .0283). Patients in the GXR vs. placebo group were more likely to report TEAEs (81.2% vs. 62%) and discontinuation due to TEAEs (19.8% vs. 3%). In the GXR group, the most common TEAEs were somnolence, thirst, blood pressure decrease, nasopharyngitis, postural dizziness and constipation; however, most were mild to moderate in severity.

“[Among] Japanese adults with ADHD, 10 weeks of monotherapy with GXR improved core symptoms, physician- and patient-rated clinical impression, and some aspects of executive function and quality of life and reflected the known safety profile of GXR,” the researchers wrote. “Additional investigation of GXR in adults with ADHD may be needed to further support the benefits observed in this study.” – by Joe Gramigna

Disclosures: Iwanami reports honoraria and other payments from Eisai, Eli Lilly Japan, Janssen, Kyowa, Meiji Seika, Mitsubishi Tanabe, Merck Sharp & Dohme, Otsuka, Pfizer Seiyaku, Sumitomo Dainippon and Yoshitomiyakuhin. Please see the study for all other authors’ relevant financial disclosures.