Centanafadine's Route to FDA Review: A Clinical Path of the ADHD Medication

Centanafadine, a first-in-class norepinephrine-dopamine-serotonin reuptake inhibitor (NDSRI), awaits a regulatory decision by the US Food and Drug Administration (FDA) on Friday, July 24. Ahead of the FDA action, review the path of Otsuka Pharmaceutical’s centanafadine for treatment of ADHD.

First In Class Norepinephrine, Dopamine, and Serotonin Reuptake Inhibitor for ADHD

In 2023, positive topline results were reported from 2 pivotal phase 3 trials of centanafadine in pediatric ADHD populations: adolescents aged 13-17 years and children aged 6-12 years. Both were 6-week, double-blind, placebo-controlled, fixed-dose trials with weight-based dosing, using change from baseline in ADHD-RS-5 total score at week 6 as the primary endpoint. Both trials met their primary endpoint; high-dose centanafadine produced statistically significant improvement over placebo in both trials, with benefit emerging as early as week 1. Commonly reported adverse effects included decreased appetite, nausea, rash, fatigue, upper abdominal pain, and somnolence. These results extended prior adult efficacy findings to younger populations and supported subsequent regulatory submission.

Centanafadine Pharmacological Profile Affirms Potential for Treatment of ADHD

Poster data presented at the 2026 American Professional Society of ADHD and Related Diseases meeting characterized centanafadine's mechanism using intracerebral microdialysis in rats. The compound produced dose-dependent increases in extracellular norepinephrine, dopamine, and serotonin within the prefrontal cortex and ventral striatum—regions implicated in ADHD pathophysiology—with effects plateauing near 60 minutes and sustained through 4 hours. Prefrontal cortex increases averaged 1184% for serotonin, 604% for norepinephrine, and 281% for dopamine (all P < 0.001), with serotonin effects exceeding earlier in vitro predictions. Notably, locomotor activity was unchanged relative to vehicle, suggesting low psychomotor stimulant liability. Authors linked this triple-monoamine profile to potential benefit for emotional dysregulation, executive dysfunction, and comorbid anxiety in ADHD.

New Drug Application Submitted for Centanafadine for Treatment of ADHD

A New Drug Application (NDA) was submitted to the FDA in November 2025, for centanafadine to treat children, adolescents, and adults with ADHD, based on 4 phase 3 trials. Pediatric and adolescent trials used ADHD-RS-5 change at week 6 as the primary endpoint; high-dose groups reached significance while low-dose groups did not. Two adult trials evaluated sustained-release centanafadine 200 mg and 400 mg against placebo over 6 weeks using the Adult ADHD Investigator Symptom Rating Scale, with both doses showing statistically and clinically meaningful improvement. All trials indicated low abuse and dependence potential. Centanafadine's pharmacology emphasizes norepinephrine reuptake inhibition with lesser dopaminergic and more pronounced serotonergic activity than traditional stimulants.

FDA Accepts NDA for Priority Review: Centanafadine for Treatment of ADHD

The FDA accepted the submitted NDA for priority review in January 2026. The application, originally submitted in November 2025, was supported by 4 pivotal phase 3 trials demonstrating statistically significant, clinically meaningful symptom improvement versus placebo on the ADHD-RS-5 in youth and the ADHD Investigator Symptom Rating Scale in adults. Otsuka's chief medical officer called the priority review designation an important milestone toward a novel treatment option. The FDA set a Prescription Drug User Fee Act (PDUFA) target action date of July 24, 2026, for its decision.

New Phase 3 Post Hoc Analyses of Centanafadine for the Treatment of Adults With ADHD

At the 2026 American Society of Clinical Psychopharmacology Annual Meeting, post hoc, exploratory analyses were presented from 2 identical phase 3 adult trials (n=744; centanafadine 200 mg, n=242; 400 mg, n=241; placebo, n=261). Beyond core symptom reduction, centanafadine was associated with improved executive function at week 6, measured via the Executive Functioning subscale of the Adult ADHD Self-Report Scale Expanded Version, spanning time management, planning, task initiation, and working memory. Centanafadine was also associated with improvement on the ASRS Emotional Dyscontrol subscale, including reduced emotional overactivity, affective lability, and anger outbursts, relative to placebo.

Expanding the ADHD Pharmacology Pipeline: Highlights With Ann Childress, MD

Centanafadine was highlighted this July at the 2026 Southern California Psychiatry meeting, where Ann Childress, MD, reviewed FDA-approved ADHD agents from the past 5 years, including viloxazine extended-release, extended-release amphetamine chewable tablets, serdexmethylphenidate/dexmethylphenidate, and late-stage pipeline agents like centanafadine. Childress noted the extensive work done on centanafadine to help it reach the point of an FDA decision.

Positive Phase 3 Data for Centanafadine to Treat Comorbid ADHD and Anxiety

While the upcoming FDA action will be on centanafadine for ADHD, recent data showed the drug may be beneficial in comorbid ADHD and anxiety. A phase 3b randomized, double-blind, placebo-controlled trial evaluated centanafadine 280 mg once daily over 8 weeks in 315 adults, aged 18-65, with ADHD and comorbid generalized or social anxiety disorder. The trial met its primary endpoint: least squares mean change in Adult Investigator Symptom Rating Scale score was -18.5 with centanafadine versus -12.6 with placebo (P < 0.0001), with separation apparent by week 1 and sustained through week 8. The secondary endpoint, Hamilton Anxiety Rating Scale change, also favored centanafadine (-12.5 vs -10.6; P = 0.02). Adverse events were consistent with the drug's established safety profile.