New ADHD Drug Adds a Key Piece of Evidence in Patients With Comorbid Anxiety

For attention-deficit/hyperactivity disorder (ADHD) drugs, the real test often is not only whether they can improve core symptoms in cleanly diagnosed, tightly controlled trial participants, but whether they can move into more complex patients closer to everyday outpatient practice. Otsuka’s announcement that centanafadine met the primary endpoint in a Phase 3b trial of adults with ADHD and comorbid anxiety is meaningful for that reason: it tested a new drug approaching a U.S. regulatory decision in a clinically common setting that is carefully excluded or restricted in many trials.

The trial is registered as NCT06973577. Otsuka said in a press release that the study was randomized, double-blind and placebo-controlled, enrolling 315 adults ages 18 to 65 who had both ADHD and generalized anxiety disorder or social anxiety disorder. The treatment group received centanafadine XR 280 mg once daily, with changes compared against placebo after 8 weeks.

The primary endpoint was change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. Topline data disclosed by Otsuka showed that the centanafadine group fell by 18.5 points at week 8, while the placebo group fell by 12.6 points, a between-group difference of 5.87 points that reached statistical significance. The company also said a separation signal appeared from week 1 and was maintained through the end of the trial. These numbers show the drug had a measurable effect on core ADHD symptoms, but full details on participant disposition, subgroup analyses and discontinuation rates have not yet been seen.

Anxiety symptoms were the key secondary aspect of the study. Measured by the Hamilton Anxiety Rating Scale (HAM-A), the centanafadine group fell by 12.5 points at week 8, while the placebo group fell by 10.6 points, a placebo-adjusted difference of 1.92 points that also reached statistical significance. This means that, in adults with ADHD and comorbid anxiety, the drug was at least not shown by topline data to worsen anxiety scores. However, the real clinical feel and durability of a 1.92-point difference still require full data and follow-up research to interpret.

Centanafadine is described by Otsuka as a first-in-class norepinephrine, dopamine and serotonin reuptake inhibitor. It differs from traditional central nervous system stimulants, but similarly targets neurotransmission pathways related to attention, impulse control and emotional regulation. Otsuka had previously accumulated pediatric, adolescent and adult data in its Phase 3 ADHD program. What this Phase 3b study adds is a piece of the puzzle for patients with comorbid anxiety, a group that is not rare in the real world but has relatively limited trial evidence.

On safety, the company said the most common adverse events that occurred more often than with placebo included nausea, decreased appetite, diarrhea, insomnia, dry mouth and vomiting, and that the overall safety profile was consistent with existing centanafadine data and the ADHD-with-comorbid-anxiety population. Because the data remain company-disclosed topline results, it is not yet possible to examine the full picture of adverse event severity, reasons for discontinuation, or cardiovascular or psychiatric-symptom-related safety signals.

The regulatory timeline gives these data more practical weight. Centanafadine is currently under U.S. FDA priority review, with the proposed indication covering ADHD in children, adolescents and adults, and a PDUFA target date of July 24, 2026. If approved, it will enter an ADHD treatment market that has long been competitive but still needs options with different mechanisms and tolerability profiles. If regulators require more data, this comorbid-anxiety trial could still become an important basis for later label discussions, physician confidence in use and clinical positioning.