Centanafadine Gains FDA Approval for ADHD Across Age Groups

The US Food and Drug Administration has approved centanafadine (Simtriyo; Otsuka), a once-daily extended-release capsule, for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients aged 6 years and older who weigh at least 20 kg, according to a company announcement.

Simtriyo is the first approved norepinephrine, dopamine, serotonin reuptake inhibitor (NDSRI) for ADHD, Otsuka stated. The medication is also classified as a central nervous system stimulant and is expected to become commercially available later this year after scheduling by the US Drug Enforcement Administration.

The approval was supported by 4 randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating centanafadine in children, adolescents, and adults with ADHD. In these trials, Simtriyo demonstrated statistically significant and clinically meaningful improvements in ADHD symptoms compared with placebo, as measured by the ADHD Rating Scale-5 in children and adolescents and the Adult ADHD Investigator Symptom Rating Scale in adults.

“ADHD is a complex and highly individualized disorder that can affect people throughout childhood, adolescence, and adulthood,” John Kraus, MD, PhD, executive vice president and chief medical officer at Otsuka, said in the announcement. “Today’s approval reflects our commitment to advancing innovative treatment options that address the diverse needs of patients and families managing ADHD.”

What data supported FDA approval?

In the 2 pivotal adult studies, NCT03605680 and NCT03605836, both centanafadine dose groups demonstrated statistically significant improvements in Adult ADHD Investigator Symptom Rating Scale total scores compared with placebo. Improvements were observed as early as week 1 and were maintained through the 6-week treatment period.

In the pivotal pediatric and adolescent studies, NCT05428033 and NCT05257265, high-dose centanafadine demonstrated statistically significant improvements in ADHD Rating Scale-5 total scores compared with placebo. Improvements also were observed as early as week 1.

Across the phase 3 clinical development program, Otsuka reported that centanafadine was generally well tolerated and had a well-characterized safety profile. The most common adverse reactions were rash and decreased appetite in children aged 6 to 12 years; decreased appetite, nausea, rash, headache, and abdominal pain in adolescents aged 13 to 17 years; and headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea in adults.

Otsuka also stated that a recently completed phase 3b study in adults with ADHD and comorbid anxiety found statistically significant improvements in ADHD symptoms with centanafadine compared with placebo. Full results from that study are expected to be presented at an upcoming scientific meeting.

What should clinicians know about safety?

Simtriyo carries boxed warnings for suicidal ideation and behaviors in pediatric patients aged 6 years and older and for abuse, misuse, and addiction. The prescribing information states that higher rates of suicidal ideation and behaviors occurred in Simtriyo-treated patients aged 6 to 12 years with ADHD than in placebo-treated patients, and all pediatric patients should be closely monitored.

Because Simtriyo is a CNS stimulant, clinicians should assess each patient’s risk for abuse, misuse, and addiction before prescribing and monitor for signs and symptoms throughout treatment.

Simtriyo is contraindicated in patients with known hypersensitivity to centanafadine or any excipients, patients taking a monoamine oxidase inhibitor or within 14 days of stopping one, and patients with pheochromocytoma or a history of pheochromocytoma. The drug should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

The safety information also advises clinicians to monitor blood pressure and heart rate, assess for new psychotic or manic symptoms, discontinue treatment in the event of clinically significant hypersensitivity, monitor growth in pediatric patients, assess for peripheral vasculopathy including Raynaud phenomenon, monitor for serotonin syndrome when used with other serotonergic drugs, and monitor for motor or verbal tics or worsening Tourette syndrome.

Why is this relevant to primary care?

ADHD affects approximately 22.5 million children, adolescents, and adults in the US, including approximately 7 million children and 15.5 million adults, according to the release. Although often diagnosed in childhood, symptoms frequently persist into adolescence and adulthood and can affect school, work, relationships, and daily functioning.

For primary care clinicians, the approval adds another pharmacologic option for ADHD management across a broad age range, including pediatric patients aged 6 years and older and adults. The boxed warnings and monitoring requirements also underscore the importance of careful patient selection, cardiovascular and psychiatric assessment, growth monitoring in children, and ongoing follow-up after initiation or dose changes.

“The approval of Simtriyo introduces a novel mechanism of action and expands the range of options available to healthcare professionals and patients,” Lenard A. Adler, MD, director of the adult ADHD program at NYU Langone Health, said in the announcement. “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 Pharmaceutical Development & Commercialization, Inc.; Otsuka Pharmaceutical Co., Ltd. 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. Published July 24, 2026.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, text rev. American Psychiatric Association; 2022.
3. Staley BS, et al. Attention-deficit/hyperactivity disorder diagnosis, treatment, and telehealth use in adults — National Center for Health Statistics Rapid Surveys System, United States, October-November 2023. Centers for Disease Control and Prevention.
4. Centers for Disease Control and Prevention. Data and statistics on ADHD. Updated November 19, 2024.