Otsuka Pharmaceutical Development & Commercialization Presents New Phase 3 Centanafadine Analyses Highlighting Broader ADHD Symptom Improvements
Otsuka Pharmaceutical Co., Ltd. and Otsuka Pharmaceutical Development & Commercialization unveiled new post hoc exploratory analyses from two pivotal Phase 3 clinical studies evaluating centanafadine, an investigational therapy for attention-deficit hyperactivity disorder (ADHD), during the 2026 annual meeting of the American Society for Clinical Psychopharmacology. The newly presented findings suggest that centanafadine may provide benefits extending beyond the treatment of core ADHD symptoms by improving executive function and emotional dysregulation in adults living with the condition.
The analyses further strengthen the growing body of clinical evidence supporting centanafadine, which is currently under regulatory review in the United States as a potential treatment option for adult ADHD. The investigational therapy has already received Priority Review designation from the U.S. Food and Drug Administration, with a Prescription Drug User Fee Act (PDUFA) target action date scheduled for July 24, 2026.
Centanafadine is being developed as a first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). Unlike conventional stimulant therapies commonly prescribed for ADHD, centanafadine is designed to simultaneously modulate three neurotransmitter systems implicated in attention, cognition, emotional regulation, and behavioral control. Researchers believe this multimodal mechanism may offer a broader therapeutic effect across the diverse symptom spectrum experienced by adults with ADHD.
ADHD is increasingly recognized as a complex neurodevelopmental disorder that extends far beyond attention deficits and hyperactivity. While diagnostic criteria primarily focus on core symptoms such as inattention, impulsivity, and hyperactivity, many adults with ADHD also experience substantial impairment related to executive dysfunction and emotional dysregulation. These associated features can significantly affect workplace performance, interpersonal relationships, organization, emotional stability, and overall quality of life.
Despite their clinical importance, executive function deficits and emotional regulation challenges are often insufficiently addressed by currently available therapies, creating an ongoing unmet need within ADHD care.
The new analyses presented at the ASCP meeting evaluated data from a combined population of 744 adults enrolled in two identical Phase 3 studies. Participants included 242 individuals treated with centanafadine 200 mg, 241 treated with centanafadine 400 mg, and 261 participants receiving placebo.
The post hoc analyses focused specifically on patient-reported measures related to executive functioning and emotional dysregulation using expanded subscales of the Adult ADHD Self-Report Scale (ASRS). According to investigators, centanafadine demonstrated meaningful improvements across multiple dimensions of executive functioning compared with placebo after six weeks of treatment.
Patients treated with centanafadine reported reductions in the frequency and severity of executive functioning difficulties. Improvements were observed in several important daily functioning domains, including time management, organization, planning and prioritization, working memory, task initiation, and the ability to complete responsibilities effectively.
These findings are considered particularly relevant because executive dysfunction is one of the most disabling and persistent aspects of adult ADHD. Difficulties with planning, organization, and sustained task completion can impair educational achievement, workplace productivity, and independent living, even among individuals whose core inattentive symptoms appear partially controlled.
In addition to executive functioning improvements, centanafadine was also associated with positive effects on emotional dysregulation. Investigators reported improvements across measures of emotional overactivity, affective instability, irritability, and anger outbursts compared with placebo-treated participants.
The emotional dysregulation findings were measured using the Emotional Dyscontrol subscale of the ASRS at Week 6. Researchers observed reductions in mood volatility and emotionally reactive behaviors, symptoms that are increasingly recognized as central contributors to psychosocial impairment in adults with ADHD.
Experts at the conference noted that emotional dysregulation remains one of the most underappreciated aspects of ADHD in adults. Patients frequently struggle with frustration intolerance, mood instability, impulsive emotional reactions, and difficulty managing stress, all of which can negatively impact social and occupational functioning.
Dr. Lenard A. Adler, director of the adult ADHD program at NYU Langone Health and an investigator involved in the studies, emphasized the importance of targeting these broader symptom domains during ADHD treatment.
According to Adler, executive function deficits and emotional dysregulation can represent some of the most challenging aspects of ADHD for adults and are not consistently addressed with existing therapeutic options. He explained that the findings demonstrate the importance of evaluating treatment benefits across the full spectrum of patient experiences rather than focusing solely on traditional symptom measurements.
Adler also noted that adults with ADHD often present with highly variable symptom profiles, reinforcing the need for therapies capable of addressing multiple manifestations of the disorder simultaneously.
Otsuka executives framed the findings as an important step toward redefining treatment expectations in ADHD care. John Kraus, M.D., Ph.D., executive vice president and chief medical officer at Otsuka, stated that the new adult data complement prior pediatric and adolescent research involving centanafadine and contribute to a more comprehensive understanding of the therapy’s clinical profile.
Kraus explained that the observed improvements in executive function and emotional dysregulation reinforce centanafadine’s potential to address ADHD in a more holistic manner. He added that the findings reflect Otsuka’s broader commitment to advancing therapies capable of treating the broader clinical burden experienced by adults living with ADHD.
The pivotal Phase 3 studies supporting these analyses were identified as NCT03605680 and NCT03605836. Both studies were randomized, double-blind, placebo-controlled trials designed to evaluate the efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults between the ages of 18 and 55 diagnosed with ADHD.
Participants in the studies received either centanafadine or placebo over a six-week treatment period. The Otsuka primary efficacy endpoint in both trials measured change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score at Week 6.
Previously reported data from the studies demonstrated statistically significant and clinically meaningful improvements in core ADHD symptoms for both centanafadine dose groups compared with placebo. The latest post hoc analyses expand upon those findings by exploring additional patient-reported outcomes related to cognitive and emotional functioning.
Investigators also reported that centanafadine maintained a favorable safety and tolerability profile across both Phase 3 studies. The most commonly observed adverse events included decreased appetite and headache, which are frequently reported with ADHD therapies. Importantly, researchers noted that centanafadine demonstrated a low potential for abuse and dependence, a factor that could distinguish it from some currently available stimulant medications used in ADHD management.
The potential for reduced abuse liability is considered clinically meaningful, particularly given ongoing concerns surrounding misuse and diversion of stimulant-based ADHD treatments. If approved, centanafadine could provide physicians with an alternative option for adults seeking non-stimulant therapies that still offer robust symptom control.
The broader ADHD treatment landscape has evolved significantly in recent years as clinicians and researchers increasingly recognize the disorder’s complexity in adulthood. Beyond difficulties with concentration and hyperactivity, adults with ADHD frequently experience impairments in executive functioning, emotional self-regulation, decision-making, motivation, and stress tolerance.
These symptoms can contribute to academic underachievement, employment instability, strained personal relationships, increased risk of substance use disorders, anxiety, depression, and diminished quality of life. Consequently, there is growing interest in therapies capable of targeting the broader neurobiological and behavioral dimensions of ADHD.
Centanafadine’s triple reuptake inhibition mechanism has attracted attention because of its potential to influence multiple neurotransmitter systems simultaneously. By affecting norepinephrine, dopamine, and serotonin signaling, the therapy may help regulate attention, reward processing, mood, emotional responsiveness, and cognitive control through a more integrated pharmacological approach.
As Otsuka awaits the FDA’s regulatory decision later this year, the new ASCP data may help strengthen the therapy’s positioning within the increasingly competitive ADHD treatment market. The additional evidence supporting improvements in executive functioning and emotional dysregulation could prove particularly meaningful for clinicians seeking therapies that address the broader day-to-day challenges faced by adults living with ADHD.
The presentations at the 2026 ASCP Annual Meeting further highlighted the growing focus within neuropsychiatric drug development on patient-centered outcomes and functional improvements that extend beyond traditional symptom rating scales. Otsuka For many experts in the field, the findings represent another step toward more comprehensive and individualized treatment strategies for ADHD and related neurodevelopmental disorders.
About Attention-Deficit Hyperactivity Disorder (ADHD)
ADHD is a chronic neurodevelopmental disorder characterized primarily by impairments in attention, hyperactivity, and impulsivity2. It affects approximately 7 million children in the U.S. and an estimated 15.5 million adults, according to the Centers for Disease Control and Prevention (CDC)3,4.
About Centanafadine
Centanafadine is an investigational, first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). Clinical studies have shown that centanafadine significantly reduced core symptoms of ADHD in children, adolescents, and adults. Additional clinical analyses have further characterized centanafadine’s potential impact on ADHD-associated features, including executive function and emotional dysregulation. Clinical data suggest centanafadine has demonstrated a favorable safety and tolerability profile and low potential for abuse, with the most common adverse events including decreased appetite and headache.
About Otsuka
Otsuka Pharmaceutical Co., Ltd. is a total healthcare company that focuses on each individual’s potential to enhance their well-being. Our medical-related business provides treatments and diagnostics for both physical and mental health. Our nutraceutical business supports daily health maintenance and improvement. Otsuka’s unique products and services are based on scientific evidence, under the guidance of our corporate philosophy: Otsuka-people creating new products for better health worldwide.
Otsuka America Pharmaceutical, Inc. and Otsuka Pharmaceutical Development & Commercialization, Inc. are the US-based indirect subsidiaries of the global healthcare company Otsuka Pharmaceutical Co. Ltd. Otsuka’s US companies share a deep commitment to the development and commercialization of innovative products in the spaces of neuroscience, nephrology, and immunology. At our core is perseverance—a fierce determination to overcome any obstacle, regardless of setbacks, on behalf of patients, caregivers, and their loved ones.
