Centanafadine (Simtriyo): What Prescribers Should Know

Centanafadine (brand name Simtriyo) is a new ADHD medication that the FDA approved on July 24, 2026, for patients ages 6 and older, including adults [1][2]. It is not yet available to prescribe: as of this writing, the DEA has not finalized the controlled-substance schedule it will be assigned, and Otsuka’s own approval announcement states the product will be “commercially available later this year following scheduling by the U.S. Drug Enforcement Administration” [1]. This post summarizes what’s confirmed about centanafadine’s mechanism, efficacy, and safety profile, and what remains genuinely open — the scheduling decision that will shape how easily you can prescribe it.

Photo by Melany on Unsplash

What is centanafadine, and how does it work?

Centanafadine is described as the first-in-class norepinephrine-dopamine-serotonin reuptake inhibitor (NDSRI) approved for ADHD, meaning it blocks reuptake of all three of those neurotransmitters rather than the two (norepinephrine and dopamine) that stimulants and atomoxetine primarily target [1][3]. Despite that novel mechanism, the FDA classifies it as a central nervous system stimulant, which is why it requires DEA scheduling before it can be dispensed [1][2]. Approval was based on four Phase 3 trials in children, adolescents, and adults, which the sponsor reports showed statistically significant improvements in ADHD symptoms compared with placebo, with some improvement observed as early as week one of treatment [1].

How does its efficacy compare with stimulants and other non-stimulants?

Reported effect sizes for centanafadine fall in a similar range to existing non-stimulants rather than stimulants. Clinical summaries describe standardized effect sizes of roughly 0.3–0.4 across the pediatric and adult trials, compared with roughly 0.8–1.0 typically reported for stimulants and approximately 0.45 for atomoxetine [3]. In practical terms, that places centanafadine’s expected symptom benefit closer to atomoxetine or bupropion than to a stimulant. If a patient needs the largest achievable symptom reduction and tolerates stimulants well, centanafadine is not positioned as a replacement for that; if a patient can’t tolerate stimulants, or needs an option distinct from the current shortage-affected drug classes, it may be a reasonable addition to the choices available. For context on that broader non-stimulant landscape, see our guide to ADHD documentation for stimulant prescribing, which covers the pre-prescribing risk assessment that current stimulant labeling requires and that a similar risk discussion for centanafadine will likely echo.

What do the boxed warnings say?

Centanafadine’s label carries two boxed warnings, an unusual combination for a single product [3]:

• Suicidal ideation and behavior in children ages 6–12. Trials in this age group showed a higher rate of suicidal ideation than placebo.
• Abuse, misuse, and addiction. Human abuse-potential studies reportedly found the drug’s “liking” scores were not statistically significantly lower than a comparator dose of amphetamine, which is the basis for the boxed warning language and for its stimulant classification [3].

That second warning is the direct link to the DEA scheduling question below: a drug with measurable abuse liability similar to a stimulant is a strong candidate for placement in a more restrictive schedule, regardless of its distinct chemical mechanism.

What are the most commonly reported side effects?

Reported adverse events vary somewhat by age group in the trials. In children ages 6–12, decreased appetite and rash were among the more common effects, with rash cited as a leading reason for discontinuation in that group [3]. In adolescents, decreased appetite, nausea, and rash were reported. In adults, headache, decreased appetite, insomnia, and nausea were each reported by a minority of patients at the higher trial dose [3]. As with any new medication, these figures come from clinical trial data before broader post-marketing experience, so expect the safety picture to be refined as more patients are treated.

What is the current DEA scheduling status?

Pending, as of this writing. Multiple sources confirm that centanafadine’s DEA scheduling had not been finalized as of late September 2026, several weeks after its July 24, 2026 FDA approval [1][2][3]. A few points worth understanding about what’s at stake in that decision:

• Schedule II would place centanafadine under the same restrictions as methylphenidate and amphetamine products: no refills on a single prescription, quantity limits, and the prescription monitoring and DEA registration requirements that already apply to your stimulant prescribing.
• A less restrictive schedule (for example, Schedule IV, the category assigned to serdexmethylphenidate and modafinil) would allow refillable prescriptions and less administrative friction, which would matter for telehealth prescribing given the DEA’s ongoing telemedicine flexibilities for controlled substances [4].
• Before approval, centanafadine had been discussed in some clinician-facing coverage as a likely unscheduled or low-schedule option, given its distinct mechanism from amphetamine and methylphenidate [1]. The abuse-potential trial data disclosed at approval — and the resulting boxed warning — makes that outcome less certain than earlier expectations suggested.

We could not confirm a final DEA scheduling order as of this writing. Do not treat any schedule assumption in this post, or anywhere else, as final — check the DEA’s own scheduling actions and the product’s current label before prescribing.

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How to verify the current status before you prescribe

Because scheduling and availability can change quickly once DEA acts, check directly rather than relying on any single article, including this one:

1. Drugs@FDA, for the current approved label, including the finalized boxed warning language and any REMS requirement.
2. The DEA’s Diversion Control Division scheduling actions page and the Federal Register, for the scheduling order once it’s published.
3. The manufacturer’s own product site, which is likely to announce availability once scheduling clears.
4. Your state’s controlled-substance rules, since some states schedule substances independently of, or more restrictively than, the federal schedule.

Where might centanafadine fit once it’s available?

Based on its reported effect size and abuse-liability data, clinician-facing analyses have suggested a few plausible use cases, none of which are established recommendations yet given the drug’s newness [3]:

• Adults or adolescents with moderate ADHD symptoms where a stimulant-level effect size isn’t necessary
• Patients who can’t tolerate stimulants’ cardiovascular or appetite effects, but who haven’t had success with atomoxetine or viloxazine
• Patients affected by the ongoing stimulant shortage who need a bridge option, keeping in mind centanafadine’s own supply will depend on how quickly manufacturing scales after scheduling — see our companion piece on switching stimulants during the shortage
• Patients with a history of stimulant misuse, where the abuse-warning language nonetheless requires the same careful risk discussion as any Schedule II option, pending its actual schedule assignment

None of this is a recommendation to prescribe centanafadine for any specific patient before you’ve reviewed the finalized label yourself.

How this looks in practice

A psychiatrist or PMHNP evaluating a new medication option once centanafadine reaches pharmacies might work through it like this:

1. Check the current label and schedule before considering it for any patient — this article is a snapshot, not a live reference.
2. Continue the same pre-prescribing risk assessment you already use for stimulants: substance-use history, cardiac history, and a documented discussion of abuse-potential risk, given the boxed warning.
3. Set expectations with the patient about the effect size — closer to a non-stimulant’s typical benefit than a stimulant’s — so a switch or trial isn’t judged against the wrong benchmark.
4. Use an objective measure to track the response, the same way you would with any medication change. With objective ADHD testing with AxonCPT, a patient completes a standardized attention test from home in about 16 minutes, giving you a dated, norm-referenced data point to compare against baseline regardless of which medication class you’re evaluating. Our guide to when to retest around stimulant dosing covers timing considerations that apply to any medication trial, not just stimulants.

You can see what the report looks like before deciding whether it fits your monitoring workflow.

Frequently asked questions

Is centanafadine available to prescribe right now? Not as of this writing. FDA approved it July 24, 2026, but the DEA has not finalized its controlled-substance schedule, and the manufacturer states it will be commercially available only after that scheduling is complete [1][2].

Is centanafadine a stimulant? The FDA classifies it as a central nervous system stimulant for regulatory purposes, even though its triple-reuptake-inhibitor mechanism differs from amphetamine and methylphenidate [1][3]. That classification is also why it requires DEA scheduling before dispensing.

How does centanafadine compare to atomoxetine or viloxazine? Reported effect sizes are in a similar range to those non-stimulants, roughly 0.3–0.4 standardized effect size compared with about 0.45 for atomoxetine [3]. Unlike atomoxetine and viloxazine, centanafadine carries an abuse/misuse boxed warning and will be a scheduled substance, while atomoxetine and viloxazine are not controlled substances.

Does centanafadine have the same cardiac warnings as stimulants? This post doesn’t make a claim either way — check the finalized label for the specific cardiovascular warning language once it’s available, the same way you would for any stimulant-class product.

Can a CPT help decide if centanafadine is working? A continuous performance test doesn’t diagnose ADHD or select a medication, but it can serve as one objective data point during a medication trial, alongside rating scales and clinical observation, the same way it’s used during stimulant titration.

Start testing your patients with AxonCPT

Whatever medication a patient ends up on, tracking response with more than a symptom checklist strengthens the record. AxonCPT adds a standardized, norm-referenced attention measure with 2 free tests every month and no card required. Create your free AxonCPT account or learn more at axoncpt.com.

References

1. Otsuka Pharmaceutical. Otsuka Receives FDA Approval for First-in-Class SIMTRIYO (centanafadine). July 24, 2026.
2. Understood.org. FDA approves Simtriyo (centanafadine), a “first of its kind” ADHD medication. Accessed September 28, 2026.
3. Sultan R. Centanafadine (Simtriyo): What the Label Says. Accessed September 28, 2026.
4. Drug Enforcement Administration & Department of Health and Human Services. Fourth Temporary Extension of COVID-19 Telemedicine Flexibilities for Prescription of Controlled Medications. Federal Register, December 31, 2025.