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Centanafadine (brand name Simtriyo) is a new once-daily ADHD medication from Otsuka. The FDA approved it on July 24, 2026 for adults and for children 6 and older who weigh at least 20 kg, and the DEA placed it in Schedule III effective October 30, 2026. It blocks the reuptake of norepinephrine, dopamine, and serotonin (an "NDSRI"), its label calls it a central nervous system stimulant, and it carries two boxed warnings: suicidal thoughts and behaviors in children and teens, and abuse, misuse, and addiction. As of November 1, 2026, launch timing, price, and insurance coverage had not been confirmed.
What is centanafadine (Simtriyo)?
Centanafadine is the active ingredient in Simtriyo, an extended-release capsule taken once a day in the morning. It is the first ADHD medication in a new pharmacological class: a norepinephrine, dopamine, and serotonin reuptake inhibitor, often shortened to NDSRI or "triple reuptake inhibitor." The FDA label describes it as both an NDSRI and a central nervous system (CNS) stimulant.
The FDA signed the approval letter for new drug application 218145 on July 24, 2026. The approved population is ADHD in adults and pediatric patients 6 years of age and older who weigh at least 20 kg (about 44 lb). The label specifically says it is not recommended for children younger than 6, because that group had a higher incidence of weight loss in studies, or for children under 20 kg.
How does centanafadine work?
Most ADHD medications act on two neurotransmitters. Stimulants such as amphetamine and methylphenidate increase dopamine and norepinephrine signaling. Atomoxetine (Strattera) mainly blocks norepinephrine reuptake. Centanafadine inhibits the reuptake transporters for norepinephrine, dopamine, and serotonin.
The label is careful here: it states that the mechanism of action in ADHD "is unclear," and that efficacy "could be mediated" through this triple reuptake activity. In other words, we know what the molecule binds to, not exactly why that improves ADHD symptoms. That is true of several ADHD medications, but it is worth knowing when you read marketing that sounds more certain.
The serotonin activity has a practical consequence. The label warns that combining centanafadine with other serotonergic drugs (for example, many antidepressants) may cause serotonin syndrome, and it is contraindicated with, or within 14 days of stopping, an MAO inhibitor. If you take an antidepressant, this is a conversation to have before starting.
Is centanafadine a stimulant or a non-stimulant?
It does not fit neatly into either box. The FDA label calls it a CNS stimulant and includes an abuse, misuse, and addiction boxed warning similar to the one on stimulant labels. But the DEA placed it in Schedule III, not Schedule II where amphetamine, lisdexamfetamine, and methylphenidate sit. In its scheduling rule, the DEA concluded that centanafadine has "an abuse potential lower than those of schedule II stimulants" while still having a real potential for abuse.
| Classic stimulants | Centanafadine (Simtriyo) | Non-stimulants (e.g., atomoxetine, guanfacine ER) | |
|---|---|---|---|
| Main targets | Dopamine and norepinephrine | Norepinephrine, dopamine, and serotonin reuptake | Norepinephrine reuptake (atomoxetine) or alpha-2A receptors (guanfacine) |
| Federal controlled-substance status | Schedule II | Schedule III (interim final rule, effective Oct 30, 2026) | Not controlled |
| Abuse/misuse boxed warning | Yes | Yes | No |
| Suicidal-thinking boxed warning | No | Yes (pediatric patients) | Yes for atomoxetine; no for guanfacine ER |
| Approved ages | Varies by product | 6+ years and at least 20 kg | Varies by product |
For a refresher on the two established categories, see our guide to stimulant vs. non-stimulant ADHD medication.
What are the boxed warnings on Simtriyo?
A boxed warning is the FDA's most prominent safety warning. Simtriyo has two:
- Suicidal ideation and behaviors in pediatric patients aged 6 years and older. In a 6-week study of children 6 to 12, higher rates of suicidal ideation and behaviors were reported with centanafadine than with placebo. Suicide attempt was reported in 0.7% (2 of 304) of centanafadine-treated children in that study versus 0 of 153 on placebo. The label tells prescribers to monitor all pediatric patients closely, especially in the first months, and to consider stopping the drug if suicidal thinking emerges.
- Abuse, misuse, and addiction. The label states that Simtriyo has a potential for abuse and misuse, and that misuse of CNS stimulants can lead to overdose and death. Prescribers are told to assess each patient's risk before prescribing and to keep reassessing during treatment.
If you or your child has new or worsening thoughts of self-harm, unusual mood changes, agitation, or aggression on any ADHD medication, contact the prescriber promptly. If someone is in immediate danger, call 911. You can also call or text 988 (Suicide & Crisis Lifeline) in the US.
What did the clinical trials show?
The approval rests on four 6-week, randomized, double-blind, placebo-controlled trials. All numbers below come from the FDA label (section 14) unless noted.
| Study | Population | Result on primary symptom scale |
|---|---|---|
| Study 1 | Children 6–12 (480 randomized in this cohort) | Weight-based dose equivalent to 280 mg: symptom score fell 16.3 points vs. 10.8 on placebo (difference −5.6 on ADHD-RS-5). The lower 140 mg-equivalent dose did not separate from placebo. |
| Study 2 | Adolescents 13–17 (459 randomized) | 280 mg: −18.5 vs. −14.2 on placebo (difference −4.4 on ADHD-RS-5). 140 mg did not separate from placebo. |
| Studies 3 and 4 | Adults 18–55 (906 randomized in total) | Both doses beat placebo in both studies, with differences of −2.7 to −4.4 points on the AISRS (baseline scores around 38–40). |
Two details matter for interpreting these results:
- Only the higher dose is approved for children and teens. Because the lower dose failed in both pediatric trials, the label approves only the 280 mg dose (or its weight-based equivalent) for ages 6 to 17. The 210 mg dose was not studied in pediatric patients.
- The adult trials used a different formulation. Adult efficacy is based on studies of an earlier sustained-release tablet. The label states no differences in effectiveness are expected between those doses and Simtriyo 210 mg and 280 mg. The published adult trials (Adler et al., 2022) reported effect sizes versus placebo of 0.24 to 0.40, which are in the small-to-moderate range.
None of these trials compared centanafadine head-to-head with a stimulant or another non-stimulant, so the label cannot tell you whether it works better or worse than medications you may already know. Anyone claiming it is "better than Adderall" or "as good as Vyvanse" is going beyond the evidence that supported approval.
What are the common side effects?
Rates of the most common adverse reactions (at least 5% and more than placebo) in the 6-week trials, from the FDA label:
| Group (dose) | Most common side effects, centanafadine vs. placebo |
|---|---|
| Adults (higher dose) | Headache 8% vs. 7%; decreased appetite 7% vs. 2%; insomnia 7% vs. 4%; nausea 7% vs. 2%; dry mouth 6% vs. 0%; diarrhea 5% vs. 1% |
| Children 6–12 (280 mg equivalent) | Rash 9% vs. 0%; decreased appetite 8% vs. 3% |
| Adolescents 13–17 (280 mg) | Decreased appetite 15% vs. 2%; nausea 10% vs. 3%; rash 8% vs. 1%; headache 7% vs. 6%; abdominal pain 5% vs. 0% |
Rash stands out compared with older ADHD medications and was the most common reason people stopped the drug in the trials. The label also warns about serious hypersensitivity reactions, including anaphylaxis and angioedema. Swelling of the face, lips, or throat, or trouble breathing, is an emergency: call 911.
Other label warnings include increases in blood pressure and heart rate, risks in people with serious heart disease, new psychotic or manic symptoms, long-term growth suppression in children, Raynaud's phenomenon, and new or worsening tics. Your prescriber is expected to check heart rate, blood pressure, and cardiac history before starting. Our general guide to ADHD medication side effects covers how to track and report these.
How is Simtriyo dosed?
- Adults: start at 210 mg once daily; may increase to a maximum of 280 mg once daily.
- Adolescents 13–17: 280 mg once daily.
- Children 6–12: dose by weight: 140 mg (20 to under 35 kg), 210 mg (35 to 50 kg), or 280 mg (over 50 kg).
- Take in the morning, with or without food. Swallow whole, or open the capsule and sprinkle the entire contents on applesauce, yogurt, or orange juice. Do not cut, crush, or chew.
Alcohol is a specific concern. The label says to avoid drinking at the same time as, and for at least two hours after, taking Simtriyo. In laboratory testing, 40% alcohol released essentially all of the drug within 1.5 hours, compared with 23% released without alcohol, which could raise side effects early in the day and reduce coverage later. See ADHD and alcohol for the broader picture.
Is Simtriyo available yet?
Here is what is known and unknown as of November 1, 2026:
- Known: The FDA's approval letter said Simtriyo could be marketed only after the DEA published an interim final scheduling rule in the Federal Register. The DEA published that rule on October 30, 2026, placing centanafadine in Schedule III effective the same day, with public comments open until November 30, 2026.
- Known: The approval letter also requires Otsuka to update the label to reflect the schedule. The label available at approval still read "controlled substance schedule pending."
- Not yet confirmed: the exact date it reaches pharmacies, its price, whether your insurance plan will cover it, and whether prior authorization or "step therapy" (trying other drugs first) will be required. Expect coverage to be uneven for a newly launched brand-name drug, and there is no generic.
We will update this page as launch and coverage details are confirmed.
Who might ask a prescriber about centanafadine?
There is no official guideline yet on where centanafadine fits. Reasonable reasons to raise it with your prescriber include:
- You did not respond well to, or could not tolerate, one or more stimulants or non-stimulants.
- You are curious about a once-daily option with a different mechanism and are comfortable with a newer drug that has less real-world experience behind it.
Reasons to be more cautious, or to discuss carefully first:
- You take an antidepressant or other serotonergic medication, or an MAO inhibitor (contraindicated).
- Your child has a history of depression, self-harm, or suicidal thoughts, given the pediatric boxed warning.
- You have serious heart disease, uncontrolled high blood pressure, a history of mania or psychosis, a tic disorder, severe liver impairment (not recommended), or a history of substance misuse.
- You drink alcohol regularly in the morning or early in the day.
Newer is not automatically better. Established stimulants and non-stimulants have decades of real-world safety data; centanafadine has its clinical trial program. That trade-off is worth discussing openly with your prescriber. If you are still building a picture of your options, start with our ADHD medication overview and non-stimulant medication guide.
Frequently asked questions
When was Simtriyo approved?
The FDA signed the approval letter for Simtriyo (centanafadine) on July 24, 2026. Under federal law the approval took effect once the DEA published its scheduling rule, which happened on October 30, 2026.
Is centanafadine a controlled substance?
Yes. The DEA placed centanafadine in Schedule III through an interim final rule effective October 30, 2026. That is a lower schedule than amphetamine, lisdexamfetamine, and methylphenidate, which are Schedule II.
Is centanafadine a stimulant?
Its FDA label describes it as a norepinephrine-dopamine-serotonin reuptake inhibitor and a central nervous system stimulant, and it carries an abuse and misuse boxed warning. It is not an amphetamine or methylphenidate product.
Who can take Simtriyo?
It is approved for ADHD in adults and in children 6 years and older who weigh at least 20 kg. It is not recommended for children younger than 6 or under 20 kg, and it must not be combined with MAO inhibitors.
Is centanafadine better than Adderall or Vyvanse?
Nobody knows yet. The approval trials compared centanafadine only with placebo, not with stimulants, so there is no head-to-head evidence on which works better.
Can I drink alcohol on Simtriyo?
The label says to avoid alcohol at the same time as, and for at least two hours after, taking a dose, because alcohol can make the capsule release the drug too quickly.
References
- Otsuka / US FDA (2026). SIMTRIYO (centanafadine) extended-release capsules, Prescribing Information, revised 7/2026. NDA 218145.
- US FDA (2026). NDA 218145 approval letter, July 24, 2026.
- Drug Enforcement Administration (2026). Schedules of Controlled Substances: Placement of Centanafadine in Schedule III. Interim final rule, Federal Register, October 30, 2026 (Docket DEA-1743).
- Adler LA et al. (2022). Efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with ADHD: two phase 3 trials. J Clin Psychopharmacol, 42(5):429-439.
- Ward CL et al. (2026). Centanafadine for ADHD in adolescents: a randomized clinical trial. J Am Acad Child Adolesc Psychiatry, 65(6):805-817.