Investigational ADHD drug shows benefit in adults with comorbid anxiety

Clinical takeaway: In adults with ADHD and comorbid anxiety, centanafadine improved core ADHD symptoms and showed a modest anxiety-score benefit versus placebo. If approved, it could offer clinicians a nonstimulant option for patients whose anxiety complicates ADHD treatment selection.

ADHD and anxiety commonly overlap in adults, and this combination can make treatment selection more difficult. Otsuka noted that up to 50% of adults with ADHD have comorbid anxiety disorders, which are associated with worse clinical presentation, poorer occupational outcomes, and reduced quality of life. In a phase 3b trial, centanafadine XR improved ADHD symptoms in adults with ADHD and comorbid anxiety, according to topline results announced by Otsuka.

Centanafadine is described by the company as a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor. The investigational drug is currently under FDA Priority Review for ADHD in children, adolescents, and adults, with a target action date of July 24, 2026.

The randomized, double-blind, placebo-controlled study enrolled 315 adults aged 18 to 65 years with ADHD and comorbid generalized anxiety disorder and/or social anxiety disorder. Participants received centanafadine XR 280 mg once daily or placebo for 8 weeks.

The trial met its primary endpoint. At week 8, adults receiving centanafadine had greater improvement in ADHD symptoms on the Adult Investigator Symptom Rating Scale than those receiving placebo. Symptom improvement separated from placebo as early as week 1 and was maintained through the 8-week trial.

Centanafadine also showed a statistically significant improvement versus placebo on the Hamilton Anxiety Rating Scale at week 8, the key secondary endpoint. The anxiety effect was smaller than the ADHD symptom effect, but it may be clinically relevant in a population where anxiety can influence tolerability, adherence, and treatment choice.

The most frequently observed adverse effects occurring in more than 5% of patients and more often than with placebo were nausea, decreased appetite, diarrhea, insomnia, dry mouth, and vomiting. Otsuka said the safety findings were consistent with prior centanafadine studies. Full safety data have not yet been presented.

For clinicians, centanafadine’s potential role may be in patients who need ADHD symptom control but have comorbid anxiety that makes treatment decisions more nuanced. The topline data suggest the drug may improve core ADHD symptoms while also providing a small anxiety-score benefit. However, clinicians will need full efficacy, safety, abuse-potential, and labeling details before determining how it fits relative to stimulants, atomoxetine, alpha-2 agonists, and other ADHD treatment strategies.

“Adults with ADHD and comorbid anxiety represent a substantial and particularly challenging population to treat,” said John Kraus, MD, PhD, executive vice president and chief medical officer at Otsuka. “These results provide additional insight into centanafadine’s clinical profile and expand the evidence base supporting its potential in adults with ADHD across diverse patient presentations.”

Source: Otsuka. 2026 June 25. Otsuka announces positive phase 3b results for centanafadine in adults with ADHD and comorbid anxiety