A New Mechanism for ADHD: Raman Baweja, MD, on Centanafadine's FDA Approval

The US Food and Drug Administration approved Simtriyo (centanafadine) on July 24, 2026, for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and pediatric patients aged 6 years and older weighing at least 20 kg, making it the first approved norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) for this indication.¹ Unlike existing stimulant and nonstimulant options, which primarily target dopamine and norepinephrine pathways, centanafadine's triple reuptake mechanism incorporates serotonin, a departure supported by a comprehensive phase 3 program spanning children, adolescents, and adults.² Post hoc analyses from this program have suggested benefit beyond core inattentive and hyperactive-impulsive symptoms, including improvements in executive functioning and emotional dysregulation. Raman Baweja, MD, discussed the clinical significance of centanafadine's novel mechanism, how it compares with existing ADHD treatments, and the patient profiles most likely to benefit from its use.

Psychiatric Times: What was your initial reaction to the FDA approval of Simtriyo (centanafadine)?

Raman Baweja, MD: For me, it was actually expected because I was following this at different levels, as well as publications and research. The publication of the ADHD adult trial some time ago, and the recent trial published on adolescents. So I was not surprised, and actually was more exciting to see, especially it has a novel mechanism which we do not have with the other medications we have so far with ADHD.

So traditionally we have CNS stimulants for a long period of time, we have the methylphenidate or amphetamine group medication, and then we have the non-stimulant medication. Stimulants work for the dopamine and norepinephrine mechanism, and the non-stimulants, the other one we have, work more with the norepinephrine, and this novel mechanism of this drug is that it is also bringing in the serotonin and the ADHD, and that was the novel thing. This is the novel one, it is triple reuptake inhibitor, it is a norepinephrine, dopamine, as well as serotonin reuptake inhibitor. So that broad approach is the novelty of this medication.

PT: How is centanafadine different from other available ADHD medications?

Baweja: So we have CNS stimulants that have the more effect size. Effect size means they are more effective with the ADHD core symptoms, but ADHD is beyond that inattention problem, hyperactivity, and impulsivity. It also has other comorbid associated symptoms. It is associated with executive functioning problems, day-to-day functioning problems, emotional dysregulation, and many sleep problems. So having this novel molecule, the serotonin and reuptake inhibitor, the studies published on this drug have shown, in addition to the core symptoms, especially the recent publication reported that it was the post hoc analysis, it shows that it is helping the executive functioning, as well as the learning problem, as well as the daily functioning, in children and adolescents. As well as the recent, I believe the poster was there, it also helped in the improvement in the emotional dysregulation, which is very commonly associated with adults with ADHD.

PT: With the novel mechanism, how might this new option fulfill unmet needs in ADHD?

Baweja: So ADHD is a very heterogeneous condition, as I mentioned, beyond inattention, hyperactivity, and impulsivity. The effect size of centanafadine is more like the other non-stimulants and is comparatively lesser than with the CNS stimulants, but it also has a broader coverage, symptom improvement appears to be that emotional dysregulation as well. It has a less abuse potential, which is the problem with the CNS stimulants. And again, as I mentioned, it is a very heterogeneous presentation we can have with ADHD, so depending upon the patient presentation, either they have the executive functioning problem, or they are not able to tolerate the other medication, so here the centanafadine has the role where we are having the cluster of symptoms where this individual product can be helpful.

PT: What should clinicians keep in mind when deciding if centanafadine is right for their patients?

Baweja: So I think it is across the spectrum, I would say. Depending upon, if I am treating a seven or eight year old child who has executive functioning as one of the major challenges, or rather is not able to tolerate the other medication, for example the CNS stimulant, then I would go with this medication. And in the adult literature, in the adult world of ADHD, adults with ADHD who have emotional dysregulation that is very prominent, that can also be considered. Or the other area is that abuse potential or misuse potential is less with this molecule, with this drug, in those with concern about substance use disorder in adults with ADHD, that this molecule can be an option.

PT: What is important to know about switching ADHD medications generally?

Baweja: In medicine, if someone is having a good symptom response, we do not change the meds, right, if the patient is doing very well with the medication. But at the same time, if their symptoms are not fully controlled with the medication the patient is currently on, or they have other associated symptoms like emotional dysregulation or executive functioning, learning problem, there can be the potential to switch onto this new medication, sentenine, as well as if there is a concern about abuse or misuse of the CNS stimulants, and likely that this new drug can be helpful in those.

Dr Baweja is professor of psychiatry and public health sciences at Penn State College of Medicine, specializing in ADHD.

References

1. Otsuka receives FDA approval for first-in-class SIMTRIYO® (centanafadine) for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults and pediatric patients aged 6 years and older. Press release. July 27, 2026. Accessed July 31, 2026. https://www.otsuka-us.com/otsuka-shares-fda-review-update-for-centanafadine

2. 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. Press release. May 28, 2026. Accessed July 31, 2026. https://www.otsuka-us.com/news/otsuka-presents-new-phase-3-post-hoc-analyses-centanafadine-highlighting-improvement-executive