DEA places centanafadine, the active ingredient in Otsuka's ADHD drug Simtriyo, in Schedule III

A new ADHD medicine has just become a controlled substance. On October 30, 2026, the Drug Enforcement Administration published an interim final rule placing centanafadine, the active ingredient in Otsuka's Simtriyo, in Schedule III of the Controlled Substances Act. The classification matters for anyone who prescribes or receives ADHD care online, because it decides which federal and state controlled-substance rules apply to a prescription the day a clinician writes it.

What the DEA rule does

The DEA, part of the Department of Justice, added centanafadine, including its salts and isomers, to Schedule III of the Controlled Substances Act (CSA). The action is an interim final rule published at 91 FR 68470 under Docket No. DEA-1743, effective October 30, 2026. The DEA used the expedited scheduling path in 21 U.S.C. 811(j), added by the Improving Regulatory Transparency for New Medical Therapies Act of 2015, which requires the agency to issue an interim final rule within 90 days when HHS reports that the FDA has approved a drug with a stimulant, depressant, or hallucinogenic effect and an apparent abuse potential, and recommends control in Schedule II through V.

HHS sent the DEA a scientific and medical evaluation and a Schedule III recommendation on July 18, 2026. The DEA completed its own eight-factor review and agreed that centanafadine meets the criteria for Schedule III under 21 U.S.C. 812(b)(3).

What centanafadine and Simtriyo are

The FDA approved Simtriyo (centanafadine) extended-release capsules on July 24, 2026, under NDA 218145, for the treatment of attention-deficit/hyperactivity disorder in adults and in pediatric patients aged 6 years and older who weigh at least 20 kg. The sponsor is Otsuka, which submitted the application on November 24, 2025. The product is a once-daily oral capsule supplied in 140 mg, 210 mg, and 280 mg free-base strengths.

The DEA describes centanafadine as a new molecular entity that acts as a novel triple reuptake inhibitor, blocking the reuptake of norepinephrine, dopamine, and serotonin, and classifies it as a central nervous system stimulant. The agency notes that its mechanism shares similarities with Schedule II stimulants such as cocaine and methylphenidate.

Why Schedule III and not Schedule II

The eight-factor analysis found signals of abuse potential alongside evidence that it is lower than for Schedule II stimulants. In an animal drug-discrimination study, oral centanafadine fully generalized to an amphetamine cue, and a self-administration study showed the drug sustained self-administration above saline levels in rats. Two human abuse-potential studies found that centanafadine produced rewarding, stimulant-type subjective responses, though those effects came with dose-dependent negative subjective responses and adverse effects such as nausea.

Across 37 clinical trials, HHS reported zero overdoses. In one 52-week trial of 662 adults taking centanafadine at 400 mg per day, three participants were removed for medication-handling irregularities involving suspected abuse or diversion. The DEA's National Forensic Laboratory Information System showed no law-enforcement encounters with the drug. HHS also concluded that abrupt discontinuation after chronic use did not produce a withdrawal syndrome, indicating no physical dependence, while the drug can still produce psychological dependence to a lesser degree than Schedule II stimulants. On those findings, the DEA placed it in Schedule III rather than the stricter Schedule II tier that holds amphetamine and methylphenidate products.

What the controls require

Schedule III status brings a set of CSA handling requirements. Manufacturers, distributors, pharmacies, researchers, and other handlers must register with the DEA and follow security, labeling, inventory, and recordkeeping rules. Prescriptions for centanafadine must comply with 21 U.S.C. 829 and 21 CFR parts 1306 and 1311, subpart C. The rule states that these registration, security, and inventory requirements do not apply to patients who possess the drug under a lawful prescription.

What this means for telehealth

For online ADHD care, the practical effect is that centanafadine is now a controlled substance and is prescribed under DEA telemedicine rules rather than the looser rules for non-controlled drugs. Under a DEA and HHS joint rule, the pandemic-era flexibilities that let clinicians prescribe controlled substances by telemedicine without a prior in-person evaluation run through December 31, 2026. If those flexibilities are not extended again, the Ryan Haight Act's default requirement of at least one in-person medical evaluation would return for controlled-substance telehealth prescribing.

Schedule III placement is also less restrictive than the Schedule II tier that governs most prescription stimulants used for ADHD, which affects refills and other prescribing mechanics under the CSA. The DEA's proposed framework for a permanent telemedicine special registration remains unfinished, a status TeleRanked tracks in its coverage of the DEA telemedicine special registration rule under OMB review. State controlled-substance and telehealth laws apply on top of the federal rules and can be stricter.

What comes next

The interim final rule is effective now, but it is not the last word. The DEA is accepting written comments and requests for a hearing through November 30, 2026, and must issue a final rule after that process under the scheduling criteria of the CSA. A hearing, if the Administrator grants one, would examine whether centanafadine meets the statutory criteria for Schedule III. Until a final rule issues, the Schedule III controls remain in effect.

General information, not medical or legal advice

This article explains a regulatory action and its sourcing. It is general information, not medical or legal advice. Patients with questions about centanafadine or ADHD treatment should talk with a licensed clinician, and anyone with questions about controlled-substance prescribing rules should consult the primary sources below or qualified counsel.