FDA Approves First-in-Class Centanafadine for ADHD in Adults and Pediatric Patients

The FDA has approved centanafadine extended-release capsules (Simtriyo; Otsuka Pharmaceutical) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients 6 years and older who weigh at least 20 kg. Centanafadine is a once-daily central nervous system (CNS) stimulant and the first approved norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) for ADHD.¹˒²

Through inhibiting the reuptake of norepinephrine, dopamine, and serotonin, centanafadine increases the availability of these neurotransmitters in pathways involved in attention and behavioral regulation. The novel mechanism expands the range of pharmacologic options available for ADHD, a chronic neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and impulsivity that can affect academic, occupational, and social functioning.¹

Approximately 7 million children aged 3 to 17 years in the United States have received an ADHD diagnosis, according to CDC data. An estimated 15.5 million US adults had a current ADHD diagnosis in 2023.¹

Phase 3 Data Support Approval

The approval was supported by 4 randomized, double-blind, placebo-controlled phase 3 studies evaluating centanafadine in children, adolescents, and adults with ADHD. Across the studies, treatment produced statistically significant reductions in ADHD symptoms compared with placebo, with improvements observed as early as the first week.¹˒²

In a 6-week pediatric trial (NCT05428033), patients aged 6 to 12 years received a weight-based centanafadine dose equivalent to the adult 280-mg dose, a lower weight-based dose, or placebo. At week 6, the least-squares mean reduction from baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale Version 5 (ADHD-RS-5) total score was 16.3 points with the higher centanafadine dose and 10.8 points with placebo, corresponding to a placebo-adjusted difference of –5.6 points (95% CI, –8.78 to –2.33). The lower-dose regimen did not produce a statistically significant benefit and is not an approved regimen.²

A separate 6-week trial (NCT05257265) enrolled 459 adolescents aged 13 to 17 years. The least-squares mean reduction in ADHD-RS-5 total score was 18.5 points with centanafadine 280 mg once daily compared with 14.2 points with placebo. The placebo-adjusted difference was –4.4 points (95% CI, –6.83 to –1.87).²

Efficacy in adults was established through 2 six-week studies, NCT03605680 and NCT03605836, involving a combined 906 patients aged 18 to 55 years. The trials evaluated another centanafadine formulation at exposures corresponding to the approved 210- and 280-mg extended-release doses. Both dose groups produced statistically significant improvements from baseline in Adult ADHD Investigator Symptom Rating Scale total scores compared with placebo. Statistically significant improvements were also reported for the key secondary end point of the Clinical Global Impression-Severity of Illness score.²

Dosing and Administration

For children aged 6 to 12 years, the recommended once-daily dosage is based on body weight:²

• 140 mg for patients weighing 20 kg to less than 35 kg
• 210 mg for patients weighing 35 kg to 50 kg
• 280 mg for patients weighing more than 50 kg

For adolescents aged 13 to 17 years who weigh at least 20 kg, the recommended dosage is 280 mg once daily. Adults should begin treatment at 210 mg once daily, which may be increased to the maximum recommended dosage of 280 mg based on clinical response and tolerability.²

Centanafadine should be administered in the morning at approximately the same time each day, with or without food. Capsules may be swallowed whole or opened and sprinkled over applesauce or yogurt or mixed into orange juice. The granules should not be chewed, crushed, or saved for later use.²

The medication is not recommended for children younger than 6 years because this group experienced a higher incidence of weight loss, or for pediatric patients weighing less than 20 kg because of insufficient data and the risk of weight loss.²

Safety and Pharmacist Considerations

The prescribing information includes boxed warnings for suicidal ideation and behaviors in pediatric patients and for abuse, misuse, and addiction. Higher rates of suicidal ideation and behaviors occurred among centanafadine-treated patients aged 6 to 12 years compared with placebo-treated patients. All pediatric patients should be monitored closely for suicidal ideation, behavioral changes, or clinical worsening, particularly during the initial months of therapy. Treatment modification or discontinuation should be considered if suicidal ideation or behavior emerges.²

Because centanafadine is a CNS stimulant, pharmacists should reinforce safe storage and disposal practices and counsel patients and caregivers not to share the medication. Before and throughout treatment, clinicians should assess the patient’s risk of abuse, misuse, and addiction. The product’s controlled-substance schedule will be determined following review by the Drug Enforcement Administration. Commercial availability is expected later in 2026 after scheduling is completed.¹˒²

Centanafadine is contraindicated in patients with hypersensitivity to centanafadine or its excipients, those taking a monoamine oxidase inhibitor or who discontinued one within the preceding 14 days, and patients with pheochromocytoma or a history of the condition. Heart rate and blood pressure should be assessed before treatment, following dosage increases, and periodically during therapy.²

Additional warnings and precautions address serious cardiac disease, psychiatric adverse reactions, hypersensitivity, suppression of growth in pediatric patients, peripheral vasculopathy, serotonin syndrome, and the emergence or worsening of motor or verbal tics and Tourette syndrome. Pharmacists should review concomitant medications for serotonergic agents and other CNS stimulants and monitor pediatric patients’ weight, body mass index, and linear growth.²

The most common adverse reactions occurring in at least 5% of patients and more frequently than with placebo were rash and decreased appetite in children aged 6 to 12 years; decreased appetite, nausea, rash, headache, and abdominal pain in adolescents; and headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea in adults.²

REFERENCES

1. 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. News release. Otsuka Pharmaceutical Development & Commercialization, Inc; July 24, 2026. Accessed August 3, 2026. https://www.otsuka-us.com/otsuka-shares-fda-review-update-for-centanafadine

2. Simtriyo (centanafadine) extended-release capsules. Prescribing information. Otsuka America Pharmaceutical, Inc; 2026. Accessed August 3, 2026. https://otsuka-us.com/media/static/Simtriyo-PI.pdf

3. Novel drug approvals for 2026. FDA. Updated July 2026. Accessed August 3, 2026. https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026