The FDA has approved Otsuka’s SIMTRIYO (centanafadine), the first NDSRI for ADHD, for adults and children aged 6 years and older following positive Phase 3 trials.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration (FDA) has approved Otsuka’s SIMTRIYO® (centanafadine) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients aged 6 years and older weighing at least 20 kg. The once-daily extended-release capsule is the first FDA-approved norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) for ADHD. Commercial availability is expected later this year after the U.S. Drug Enforcement Administration (DEA) completes controlled substance scheduling.
Scientific and Clinical Context
ADHD is a chronic neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity that can impair academic performance, workplace productivity, and social functioning. The condition affects an estimated 22.5 million people in the United States, including approximately 7 million children and 15.5 million adults, with symptoms frequently persisting into adulthood.
Unlike conventional ADHD therapies that primarily modulate one or two monoamine neurotransmitter systems, centanafadine inhibits the reuptake of norepinephrine, dopamine, and serotonin. By increasing the availability of all three neurotransmitters in brain pathways involved in attention and behavioural regulation, the drug offers a distinct pharmacologic option for patients and clinicians managing this heterogeneous disorder. Officially, SIMTRIYO is classified as a central nervous system (CNS) stimulant NDSRI.
Trial and Development Details
FDA approval was supported by four randomized, double-blind, placebo-controlled Phase 3 clinical trials evaluating centanafadine in adults, adolescents, and children with ADHD.
The two pivotal adult studies (NCT03605680 and NCT03605836) Showed statistically significand clinically meaningful improvements in Adult ADHD Investigator Symptom Rating Scale (AISRS) total scores compared with placebo. Symptom improvement was observed as early as Week 1 and was maintained throughout the six-week treatment period.
In the pediatric and adolescent studies (NCT05428033 and NCT05257265), high-dose centanafadine significantly improved ADHD Rating Scale-5 (ADHD-RS-5) total scores versus placebo, with treatment benefits also emerging during the first week of therapy.
Across the Phase 3 development program, centanafadine demonstrated a consistent safety profile. The most common adverse reactions included 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.
Clinical Perspective on Expanding ADHD Treatment Options
John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka, said the approval introduces a new treatment option for patients living with ADHD and reflects the company’s continued commitment to expanding therapeutic choices for a condition that often requires individualized management.
Lenard A. Adler, M.D., director of the Adult ADHD Program at NYU Langone Health, noted that many patients continue to experience symptoms despite available treatments because of the heterogeneous nature of ADHD. He said the addition of a therapy with a novel mechanism of action provides clinicians with another option to better tailor treatment decisions to individual patient needs.
Commercial Launch and Ongoing Clinical Development
SIMTRIYO will become commercially available in the United States after the DEA completes scheduling of the product. Otsuka is also expanding the clinical evidence base for centanafadine. A recently completed Phase 3b study in adults with ADHD and comorbid anxiety met its primary objective, showing statistically significant improvements in ADHD symptoms compared with placebo. Full results from the study are expected to be presented at an upcoming scientific meeting.
Reference
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.