Centanafadine Phase 3 Analyses Report Executive Function Gains in Adult ADHD

Otsuka reported new exploratory post hoc findings from 2 phase 3 trials of centanafadine in adults with attention-deficit/hyperactivity disorder (ADHD), adding patient-reported data on executive function and emotional dysregulation as the investigational agent remains under FDA Priority Review for adult ADHD.¹

“Executive function deficits and emotional dysregulation are challenging aspects of ADHD for many adults and are not always adequately addressed by current treatments,” Lenard A. Adler, MD, director of the adult ADHD program at NYU Langone Health and an investigator in the studies, said in the company announcement.¹ The FDA target action date under the Prescription Drug User Fee Act is July 24, 2026, according to Otsuka.¹

The analyses were presented at the 2026 American Society of Clinical Psychopharmacology Annual Meeting and were derived from 2 identical randomized, double-blind, placebo-controlled phase 3 trials, NCT03605680 and NCT03605836. The trials evaluated centanafadine sustained-release tablets in adults aged 18 to 55 years with ADHD over 6 weeks. Participants were assigned to centanafadine 200 mg, centanafadine 400 mg, or placebo.¹

The post hoc population included 744 adults: 242 assigned to centanafadine 200 mg, 241 assigned to centanafadine 400 mg, and 261 assigned to placebo. The company reported that centanafadine was associated with greater improvement than placebo on the Executive Functioning subscale of the Adult ADHD Self-Report Scale Expanded Version at week 6. Reported domains included time management, planning and prioritization, task initiation and completion, and working memory.¹

Otsuka also reported improvement vs placebo on the Adult ADHD Self-Report Scale Emotional Dyscontrol subscale at week 6, including reductions in emotional overactivity, affective lability, and anger outbursts.¹ The press release did not provide numerical treatment differences, confidence intervals, or multiplicity-adjusted P values for these post hoc endpoints, limiting independent assessment of the magnitude and robustness of the findings.

In the pivotal adult trials, the primary endpoint was change from baseline to week 6 in Adult ADHD Investigator Symptom Rating Scale total score. According to Otsuka, both dose groups demonstrated statistically significant and clinically meaningful improvements vs placebo on this primary measure.¹ The company also described the safety and tolerability profile as favorable, with decreased appetite and headache listed among the most common adverse events.¹

ADHD is a chronic neurodevelopmental disorder characterized by impairing patterns of inattention and/or hyperactivity-impulsivity.² Although often diagnosed in childhood, ADHD frequently persists into adulthood, where symptoms may affect occupational functioning, relationships, adherence to daily responsibilities, and comorbid psychiatric burden. CDC survey data cited by Otsuka estimate approximately 15.5 million adults in the US have ADHD.³

Current ADHD pharmacotherapy includes stimulant and nonstimulant options, with treatment decisions shaped by symptom profile, adverse effects, comorbidities, patient preference, and misuse or diversion concerns.⁴ Nonstimulant approaches remain clinically relevant for adults who do not tolerate stimulants, have inadequate response, or have contraindications or substance use concerns. However, comparative efficacy, onset of benefit, persistence of effect, and functional outcomes remain important considerations when evaluating new agents.

Centanafadine is described by Otsuka as an investigational norepinephrine, dopamine, and serotonin reuptake inhibitor. If approved, it would add a mechanistically distinct nonstimulant option for adult ADHD, though its clinical positioning will depend on the full FDA review package, labeling, dosing requirements, contraindications, and postapproval data.¹

The new analyses may be clinically relevant because executive dysfunction and emotional dysregulation are common sources of impairment in adult ADHD but are not always captured fully by core symptom scales. Still, the findings should be interpreted cautiously because they are exploratory and post hoc. Patient-reported improvements can help characterize treatment effects, but without prespecified statistical hierarchy and detailed effect sizes, they are best viewed as hypothesis-generating supportive data rather than definitive evidence of benefit on functional outcomes.

Next steps include the FDA decision expected in July 2026 and publication or presentation of full phase 3 datasets with detailed efficacy, safety, discontinuation, cardiovascular, psychiatric, and abuse-liability findings. Longer-term data will also be important for clinicians, given that ADHD treatment in adults often extends well beyond 6 weeks.

References

1. Otsuka Pharmaceutical Co, Ltd. Otsuka presents new phase 3 post hoc analyses of centanafadine highlighting improvement in executive function and emotional dysregulation in adults with ADHD at the 2026 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting. Business Wire. Published May 28, 2026. https://www.businesswire.com/news/home/20260528411791/en/Otsuka-Presents-New-Phase-3-Post-Hoc-Analyses-of-Centanafadine-Highlighting-Improvement-in-Executive-Function-and-Emotional-Dysregulation-in-Adults-with-ADHD-at-the-2026-American-Society-of-Clinical-Psychopharmacology-ASCP-Annual-Meeting
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed, text rev. American Psychiatric Association Publishing; 2022.
3. Staley BS, et al. Attention-deficit/hyperactivity disorder diagnosis, treatment, and telehealth use in adults—National Center for Health Statistics Rapid Surveys System, United States, October-November 2023. Centers for Disease Control and Prevention. Published 2024.
4. Cortese S. Pharmacologic treatment of attention deficit-hyperactivity disorder. N Engl J Med. 2020;383(11):1050-1056.