FDA approves centanafadine for ADHD in children, adolescents, and adults

The FDA has approved centanafadine (SIMTRIYO; Otsuka), an investigational once-daily extended-release capsule and first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI), for the treatment of attention-deficit/hyperactivity disorder (ADHD) in patients 6 years and older. ^1,2

“The approval of SIMTRIYO marks an important milestone for people living with ADHD, as it introduces a novel treatment approach for this condition,” said John Kraus, MD, PhD, executive vice president and chief medical officer, Otsuka. “ADHD is a complex and highly individualized disorder that can affect people throughout childhood, adolescence, and adulthood. Today’s approval reflects our commitment to advancing innovative treatment options that address the diverse needs of patients and families managing ADHD. We are deeply grateful to the patients, caregivers, investigators, and clinical teams whose participation made this achievement possible.”

Centanafadine trial design and efficacy in children and adolescents with ADHD

The application was supported by 4 pivotal phase 3 trials spanning children, adolescents, and adults. In the pediatric trial, 480 children aged 6 to 12 years were randomized to weight-based low-dose centanafadine, high-dose centanafadine, or placebo for 6 weeks. At week 6, high-dose centanafadine produced significantly greater improvement than placebo on the ADHD Rating Scale, version 5 (ADHD-RS-5) symptoms total raw score (mean change, –16.3 vs –10.8; P < .001), with separation from placebo apparent as early as week 1. Low-dose centanafadine did not reach statistical significance on the primary endpoint.³

In the adolescent trial, 459 patients aged 13 to 17 years were randomized to centanafadine 164.4 mg, 328.8 mg, or placebo. The 328.8-mg dose met the primary endpoint, with a mean ADHD-RS-5 change of –18.5 versus –14.2 for placebo (P = .0006), while the 164.4-mg dose did not achieve statistical significance. Both trials showed concordant secondary-endpoint improvements on the Clinical Global Impression of Severity–ADHD scale and Conners 3–Parent Short inattention, hyperactivity/impulsivity, and executive functioning subscales.^3,4

ADHD disease burden and current standard of care

ADHD affects an estimated 7.6% of children globally and is a leading cause of childhood disability, with more than half of affected children continuing to have impairing symptoms into adulthood. Stimulants remain first-line therapy for most patients, but appetite suppression, insomnia, cardiovascular effects, and misuse potential limit their use in some children and adolescents. Existing nonstimulants, including atomoxetine, guanfacine, and viloxazine, act primarily through norepinephrine and are generally considered less effective than stimulants for core symptoms.^3,4

Mechanism and regulatory history of centanafadine

Centanafadine inhibits reuptake of norepinephrine, dopamine, and serotonin, with the highest affinity for the norepinephrine transporter. Earlier phase 3 trials in adults aged 18 to 55 years established statistically significant improvement on the Adult ADHD Investigator Symptom Rating Scale at doses of 200 mg and 400 mg daily. Otsuka submitted the new drug application to the FDA in November 2025, and the agency accepted it for priority review in January 2026.^2,3

Safety profile of centanafadine across age groups

Across the pediatric and adolescent trials, treatment-emergent adverse events occurred more often with centanafadine than placebo but were predominantly mild to moderate. In children, the most common events were decreased appetite (5%), rash (3%), and vomiting (3%). In adolescents, decreased appetite, nausea, headache, and rash were most frequent, and 3 severe events occurred: liver function test increase, aggression, and (in the placebo group) somnolence. Investigators noted a low likelihood of medication withdrawal or abuse based on structured withdrawal questionnaires in both trials.^3,4

“ADHD can significantly affect many aspects of daily life across school, work, and relationships,” said Dr. Lenard A. Adler, director of the adult ADHD program at NYU Langone Health. “Even when on treatment, because of the heterogenic nature of ADHD, many patients continue to experience symptoms that can interfere with daily functioning. The approval of SIMTRIYO introduces a novel mechanism of action and expands the range of options available to healthcare professionals and patients. Having more therapeutic choices is important because ADHD is a highly individualized condition and treatment decisions should reflect the unique needs of each patient.”

References

1. Otsuka. Otsuka Receives FDA Approval for First-in-Class SIMTRIYO® (centanafadine) for the Treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in Adults and Pediatric Patients Aged 6 Years and Older. Otsuka. July 27, 2026. Accessed July 27, 2026. https://www.otsuka-us.com/otsuka-shares-fda-review-update-for-centanafadine

2. Otsuka Pharmaceutical Co., Ltd. Otsuka announces FDA acceptance and priority review of new drug application for centanafadine for the treatment of ADHD in children, adolescents, and adults. Published January 27, 2026. Accessed July 24, 2026. https://www.otsuka.co.jp/en/company/newsreleases/2026/20260127_1.html

3. Ward CL, Wilens TE, Jin N, Turkoglu O, Skubiak T, Childress AC. Efficacy and safety of centanafadine for ADHD treatment in children: a randomized clinical trial. Pediatrics Open Sci. 2025;1(3):1-11. doi:10.1542/pedsos.2024-000349

4. Ward CL, Childress AC, Jin N, Turkoglu O, Skubiak T, Wilens TE. Centanafadine for attention-deficit/hyperactivity disorder in adolescents: a randomized clinical trial. J Am Acad Child Adolesc Psychiatry. 2026;65(6):805-817. doi:10.1016/j.jaac.2025.06.023