Otsuka’s centanafadine Phase 3b study showed significant improvements in ADHD, anxiety, executive function and emotional dysregulation.
Written By: Anamika Koshti, PharmD
Reviewed By: Pharmacally Editorial Team
Otsuka has reported expanded Phase 3b results showing that centanafadine improved core ADHD symptoms, anxiety, executive function and emotional dysregulation in adults with ADHD and comorbid anxiety disorders. The findings broaden the clinical evidence for SIMTRIYO (centanafadine) following its FDA approval for ADHD in adults and pediatric patients aged 6 years and older weighing at least 20 kg.
Centanafadine Improves ADHD and Anxiety Symptoms
The new data come from the randomized, double-blind, placebo-controlled Phase 3b study (NCT06973577), which enrolled 315 adults aged 18 to 65 years with ADHD and comorbid generalized anxiety disorder (GAD) and/or social anxiety disorder (SAD). Participants received centanafadine extended-release 280 mg once daily or placebo for eight weeks.
At Week 8, centanafadine produced a significantly greater improvement in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score than placebo. Least-squares mean change from baseline was -18.48 with centanafadine versus -12.62 with placebo, giving a treatment difference of -5.87 points (p<0.0001). Separation from placebo was observed as early as Week 1.
The treatment also significantly improved anxiety symptoms. The Hamilton Anxiety Rating Scale (HAM-A) total score changed by -12.55 with centanafadine versus -10.63 with placebo at Week 8, corresponding to a treatment difference of -1.92 points (p=0.0244).
Expanded Analyses Show Effects Beyond Core ADHD Symptoms
The expanded dataset included three pre-specified analyses examining ADHD-associated features and global treatment response.
On the 31-item expanded Adult ADHD Self-Report Scale (ASRS-31), centanafadine produced greater improvement than placebo in the ASRS-18 Total score, with least-squares mean changes of -23.10 versus -15.80 and a treatment difference of -7.26 points (p=0.0002).
The treatment also improved the Hyperactivity/Impulsivity and Inattention subscales, with treatment differences of -3.42 (p=0.0009) and -3.8 (p=0.0002), respectively. Improvements extended to Executive Function and Emotional Dyscontrol, with treatment differences of -2.89 (p<0.0048) and -0.95 (p<0.0484).
Centanafadine also improved executive function on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). The Global Executive Composite showed a least-squares mean change of -17.73 versus -13.46 with placebo, producing a treatment difference of -4.3 points (p=0.0126). The Behavioral Regulation Index showed a treatment difference of -4.1 points (p=0.0086).
Clinician- and patient-rated global assessments also favored centanafadine across ADHD and anxiety severity measures, indicating consistent changes across investigator and patient-reported outcomes.
Safety Findings and FDA Warnings
The Phase 3b safety profile was generally consistent with the known profile of centanafadine. The most common treatment-emergent adverse events occurring in at least 5% of patients and more frequently than placebo were nausea (17.2% vs 5.7%), decreased appetite (13.4% vs 3.2%) and diarrhea (10.2% vs 3.2%).
The FDA-approved prescribing information carries boxed warnings for suicidal ideation and behaviors in pediatric patients aged 6 years and older, and for abuse, misuse and addiction. The label states that higher rates of suicidal ideation and behaviors occurred in SIMTRIYO-treated children aged 6 to 12 years than in placebo-treated patients. It also identifies the abuse and misuse potential associated with CNS stimulants and requires assessment and ongoing monitoring for abuse, misuse and addiction.
Clinical Context and Mechanism
Centanafadine is a norepinephrine, dopamine and serotonin reuptake inhibitor (NDSRI) and CNS stimulant. Its pharmacologic activity increases the availability of these neurotransmitters in pathways involved in attention and behavioral regulation.
ADHD frequently occurs alongside anxiety disorders, creating overlapping difficulties involving attention, organization, emotional regulation and anxiety symptoms. The Phase 3b dataset therefore provides information across several clinically relevant domains rather than focusing solely on core ADHD symptoms.
SIMTRIYO’s Regulatory Status
The FDA approved SIMTRIYO on July 24, 2026, for the treatment of ADHD in adults and pediatric patients aged 6 years and older weighing at least 20 kg. It is an extended-release, once-daily formulation and is the first FDA-approved NDSRI for ADHD.
The FDA prescribing information currently lists the controlled-substance schedule as pending. Otsuka has said SIMTRIYO is expected to become available following scheduling by the U.S. Drug Enforcement Administration (DEA).
The Phase 3b findings add evidence for centanafadine in adults with ADHD and comorbid anxiety disorders, particularly across executive function, emotional dysregulation and patient- and clinician-reported outcomes. Otsuka also presented additional centanafadine research and data from its broader psychiatric neuroscience portfolio at Psych Congress 2026.
Reference
Otsuka Presents New Phase 3b Results for SIMTRIYO® (centanafadine) Highlighting Consistent Improvements Across ADHD Symptoms, Anxiety, and Associated Features in Adults with ADHD and Comorbid Anxiety Disorders at Psych Congress 2026, Otsuka, 18 September 2026
P3b Short-term Study of CTN in Patients with ADHD and Comorbid Anxiety, ClinicalTrials.gov ID NCT06973577
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.