Centanafadine Granted FDA Priority Review for the Treatment of ADHD Across Pediatric and Adult Populations

The US Food and Drug Administration (FDA) has accepted for priority review a New Drug Application (NDA) for centanafadine, an investigational once-daily extended-release agent being developed for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. The decision sets a Prescription Drug User Fee Act (PDUFA) target action date of July 24, 2026, and positions centanafadine as a potential new entrant into a therapeutic landscape that remains dominated by stimulant medications and a smaller group of nonstimulant options, according to a January 27, 2026, press release from Otsuka Pharmaceuticals.

The priority review designation shortens the FDA’s standard review timeline and signals that the agency considers the application to address an unmet medical need. If approved, centanafadine would be the first agent in a proposed class of norepinephrine, dopamine, and serotonin reuptake inhibitors (NDSRIs) for ADHD, expanding beyond existing stimulant and selective nonstimulant mechanisms. For clinicians, the regulatory milestone raises questions about where a triple–monoamine reuptake inhibitor might fit within current ADHD treatment algorithms, particularly for patients who do not tolerate or respond adequately to available therapies.

Regulatory and Trial Overview

The NDA is supported by four pivotal phase 3 randomized, placebo-controlled trials evaluating centanafadine in pediatric, adolescent, and adult populations with ADHD. According to the sponsor, these studies demonstrated statistically significant improvements in core ADHD symptoms compared with placebo, measured by age-appropriate, validated rating scales. In children and adolescents, efficacy was assessed using the ADHD Rating Scale–5 (ADHD-RS-5), while adult trials used the ADHD Investigator Symptom Rating Scale (AISRS).^1-3

Across the trials, centanafadine was reported to be generally well tolerated. The most commonly reported adverse events in pediatric and adolescent participants included decreased appetite, nausea, rash, fatigue, abdominal pain, and somnolence. In adults, decreased appetite and headache were the most frequently observed adverse events.^1-3 No detailed comparative safety data versus active treatments were included in the press release, and head-to-head trials against standard stimulant or nonstimulant agents have not been reported.

Clinical Context: ADHD Burden and Current Care

ADHD is a chronic neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and impulsivity that interfere with functioning or development. Diagnostic criteria are defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR).⁴ Although often identified in childhood, longitudinal data indicate that symptoms frequently persist into adolescence and adulthood, contributing to academic, occupational, and psychosocial impairment.

In the US, ADHD affects an estimated 7 million children and approximately 15.5 million adults, according to data from the US CDC.^5,6 Stimulant medications, including amphetamine and methylphenidate formulations, remain first-line pharmacologic therapy for many patients due to their robust efficacy. However, tolerability concerns, contraindications, misuse potential, and patient or caregiver preferences often necessitate nonstimulant alternatives such as atomoxetine, extended-release guanfacine, or clonidine.

Drug and Drug-Class Background

Centanafadine is described as a first-in-class NDSRI, inhibiting the reuptake of norepinephrine, dopamine, and serotonin. This pharmacologic profile distinguishes it from currently approved nonstimulants, which typically target a single neurotransmitter system or specific receptor pathways. Theoretical advantages of broader monoaminergic modulation include potential efficacy across multiple symptom domains, although such benefits require confirmation in comparative clinical studies.

Adult efficacy and safety data for centanafadine have previously been published, including a 2022 randomized trial demonstrating symptom improvement compared with placebo.³ More recent pediatric and adolescent data, published in 2025, extend these findings to younger populations.^1,2 To date, centanafadine has not received regulatory approval for any indication.

Interpretation and Clinical Implications

From a clinical perspective, the FDA’s acceptance of the NDA does not establish centanafadine’s place in therapy but underscores continued interest in diversifying ADHD treatment options. While the reported phase 3 results suggest efficacy across age groups, clinicians will need to weigh the magnitude of benefit, safety profile, and real-world considerations (eg, adherence, tolerability, and abuse potential) against established therapies.

Notably, claims of low abuse potential cited in sponsor materials are based on clinical and preclinical assessments rather than postmarketing data, which are unavailable for investigational agents. In addition, the absence of direct comparisons with stimulants or existing nonstimulants limits conclusions about relative effectiveness.

Limitations and Next Steps

The available evidence is derived primarily from placebo-controlled trials, and longer-term safety data remain limited. Important unanswered questions include durability of response, effects on comorbid conditions, and comparative effectiveness in routine clinical practice. The FDA review process will further evaluate the totality of evidence, including safety, labeling, and risk management considerations.

References:

1. Ward CL, et al. Efficacy and safety of centanafadine for ADHD treatment in children: a randomized clinical trial. Pediatrics Open Science. 2025;1(3):1-11. doi:10.1542/pedsos.2024-000349
2. Ward CL, Childress AC, et al. Centanafadine for attention-deficit/hyperactivity disorder in adolescents: a randomized clinical trial. J Am Acad Child Adolesc Psychiatry. 2025. doi:10.1016/j.jaac.2025.06.023
3. Adler LA, et al. Efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with attention-deficit/hyperactivity disorder. J Clin Psychopharmacol. 2022;42(5):429-439. doi:10.1097/JCP.0000000000001575
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, text rev. Washington, DC: APA; 2022.
5. Centers for Disease Control and Prevention. Data and statistics on ADHD. https://www.cdc.gov/adhd/data/index.html. Accessed January 2026.
6. Centers for Disease Control and Prevention. Facts about ADHD in adults. https://www.cdc.gov/adhd/php/adults/. Accessed January 2026.