Centanafadine: First Triple Reuptake Inhibitor for ADHD Nears FDA Approval
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by persistent patterns of inattention, hyperactivity, and impulsivity. Traditional pharmacological treatments primarily include stimulant medications and selective norepinephrine reuptake inhibitors. Centanafadine, an investigational compound, offers a novel approach as a triple reuptake inhibitor targeting norepinephrine, dopamine, and serotonin.
Mechanism of Action
Centanafadine functions as a norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI). By inhibiting the reuptake of these neurotransmitters, centanafadine increases their synaptic availability, potentially enhancing attention and reducing hyperactivity and impulsivity in individuals with ADHD. This multimodal mechanism distinguishes it from existing treatments that typically target a single neurotransmitter system.
Clinical Trials
The efficacy and safety of centanafadine have been evaluated in four pivotal Phase 3 clinical trials encompassing children, adolescents, and adults with ADHD. These studies demonstrated statistically significant and clinically meaningful improvements in ADHD symptoms compared with placebo, as measured by standardized rating scales. Centanafadine was generally well tolerated across these trials.
Adverse Effects and Safety Considerations
The most common adverse events associated with centanafadine include decreased appetite, nausea, rash, fatigue, abdominal pain, and somnolence in pediatric populations, and decreased appetite and headache in adults. Most adverse events were mild to moderate in severity. Notably, centanafadine exhibited a low potential for abuse and dependence, addressing a significant concern associated with stimulant medications.
FDA Developments
On January 27, 2026, the U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for centanafadine and granted it priority review status. The Prescription Drug User Fee Act (PDUFA) target action date is set for July 24, 2026. If approved, centanafadine would be the first-in-class NDSRI for ADHD treatment, offering a novel therapeutic option for patients across all age groups.
Comparison with Existing ADHD Therapies
Current ADHD treatments primarily consist of stimulant medications, such as amphetamines and methylphenidate, and non-stimulant options like atomoxetine. While effective, stimulants carry risks of abuse and dependence. Centanafadine's triple reuptake inhibition mechanism offers a distinct pharmacological profile, potentially providing comprehensive symptom management with a lower abuse potential. This differentiation may make centanafadine a valuable alternative for patients who are unsuitable for or do not respond to existing therapies.
Takeaways
Centanafadine represents a promising advancement in ADHD management, offering a novel mechanism of action through triple reuptake inhibition. Its favorable safety profile and low abuse potential address critical limitations of current treatments. Healthcare professionals should monitor forthcoming FDA decisions and consider centanafadine's potential role in personalized ADHD treatment strategies upon approval.
Source
- Otsuka Pharmaceutical Development & Commercialization, Inc., & Otsuka Pharmaceutical Co., Ltd. (2026, January 27). Otsuka announces FDA acceptance and priority review of New Drug Application for centanafadine for the treatment of ADHD in children, adolescents, and adults. Otsuka US. Retrieved from https://www.otsuka-us.com/news/otsuka-announces-fda-acceptance-and-priority-review-new-drug-application-centanafadine
