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Centanafadine A once-daily reuptake inhibitor of norepinephrine, dopamine and serotonin, approved July 2026 for ADHD in adults and children aged 6 and older.
- Once daily, with or without food
- Markedly less appetite loss than stimulants
- Less insomnia and dry mouth than lisdexamfetamine
- Matches atomoxetine and viloxazine on symptom control
- Approved down to age 6
- Rash, and it is the leading cause of stopping
- Decreased appetite
- Nausea
- Headache
- Insomnia
- Dry mouth
- Slowed growth in children on long-term use
- The FDA approved SIMTRIYO on 24 July 2026 for ADHD in adults and in children aged 6 and older weighing at least 20 kg, making it the first norepinephrine, dopamine and serotonin reuptake inhibitor approved for the condition [1].
- The label calls centanafadine a central nervous system stimulant and carries a boxed warning for abuse, misuse and addiction; the coverage describing it as a non-stimulant alternative is wrong on the point that matters most to somebody choosing between it and an amphetamine.
- In the two pivotal adult trials the placebo-subtracted reduction in symptom score at day 42 ran from 2.7 to 4.4 points, with effect sizes of 0.24 to 0.40 [1].
- In children aged 6 to 12 the placebo-subtracted reduction was 5.6 points and in adolescents 4.4 points; the lower dose failed in both age groups [2].
- Human PET imaging tells a different story from the test tube: transporter occupancy was 47 percent at dopamine and 44 percent at serotonin, a ratio of 1.1, so in a living brain the drug does not distinguish between the two [5].
- Indirect comparison places it 6.6 symptom points below lisdexamfetamine while showing appetite loss 23 percentage points lower, dry mouth 19 points lower and insomnia 15 points lower [10].
- Rash is the distinctive adverse effect and the leading cause of stopping in every age group, taking 6 percent of children, 8 percent of adolescents and 6 percent of adults off the drug.
Mechanism
Blocks the , and transporters, most potently at norepinephrine; it raises monoamines by preventing reuptake rather than by forcing release, which is the mechanistic difference from amphetamine.
receptor fingerprint
transporter (NET, SLC6A2)Reuptake inhibition
(, SLC6A3)Reuptake inhibition
transporter occupancy in living human brainMeasured by PET at the dose used in trials
transporter (SERT, SLC6A4)Reuptake inhibition
and transporter occupancy in living human brainMeasured by PET
Safetyrisks and cautions, not medical advice
Two boxed warnings: suicidal ideation and behaviour in children aged 6 to 12, and abuse, misuse and addiction. Rash is the leading reason people stop it in every age group, and long-term use slowed growth in younger children.
Resources
No suppliers are provided for compounds like this. This entry is here for reference.
Research
- 2012first citedPharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020:…
- 2025most active year5 papers
- 2026most recentEfficacy and Safety of Centanafadine in Attention-Deficit/Hyperactivity Disorder: A Systematic…
- 1.Efficacy, Safety, and Tolerability of Centanafadine Sustained-Release Tablets in Adults With Attention-Deficit/Hyperactivity Disorder: Results of 2 Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Trials
- 2.Centanafadine for Attention-Deficit/Hyperactivity Disorder in Adolescents: A Randomized Clinical Trial
- 3.Efficacy of Centanafadine for Executive Functioning and Learning Problems in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder
- 4.Safety and Efficacy of Centanafadine Sustained-Release in Adults With Attention-Deficit Hyperactivity Disorder: Results of Phase 2 Studies
- 5.Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults
- 6.52-Week Open-Label Safety and Tolerability Study of Centanafadine Sustained Release in Adults With Attention-Deficit/Hyperactivity Disorder
- 7.A Randomized Thorough QT Trial Using Concentration-QT Analysis to Evaluate the Effects of Centanafadine on Cardiac Repolarization
- 8.Efficacy and Safety of Centanafadine in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
- 9.Efficacy and safety of monoamine reuptake inhibitors in attention deficit hyperactivity disorder: A Bayesian network meta-analysis
- 10.Assessment of centanafadine in adults with attention-deficit/hyperactivity disorder: A matching-adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine hydrochloride, and viloxazine extended-release
- 11.A Matching-Adjusted Indirect Comparison (MAIC) of Centanafadine versus Methylphenidate Hydrochloride in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD): Short-Term Safety and Efficacy Outcomes
- 12.Pharmacological characterization of the norepinephrine and dopamine reuptake inhibitor EB-1020: implications for treatment of attention-deficit hyperactivity disorder
13 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is centanafadine a stimulant or a non-stimulant?
The label calls it a central nervous system stimulant, which surprises people who expected a non-stimulant alternative. It does not force dopamine release the way amphetamine does; it blocks reuptake instead. It is a controlled substance, so it does not escape the prescribing and refill rules that apply to stimulants.
How does it compare with Adderall or Vyvanse?
In an indirect comparison it reduced adult symptoms about 6.6 points less than lisdexamfetamine, so it is meaningfully less powerful. It was easier to tolerate on appetite, dry mouth, insomnia and jitteriness. The trade is fewer side effects for a smaller effect.
How does it compare with atomoxetine or viloxazine?
Indirect comparison found no significant difference in symptom reduction against either. It showed lower rates of nausea, dry mouth, fatigue and erectile dysfunction than atomoxetine, and lower fatigue, insomnia, nausea and constipation than viloxazine. Against those two it looks like a genuine tolerability gain at similar efficacy.
Why is there a suicide warning for children?
In the six-week trial in children aged 6 to 12, suicide attempt was reported in 0.7 percent of treated children and in none on placebo; that is two children out of 304. The monitoring requirement applies to everyone aged 6 and older even though the signal appeared only in the younger group.
Does it affect growth in children?
Long-term treatment slowed linear growth, concentrated in the 6 to 12 group. By week 88 of open-label treatment 15.6 percent of those children had dropped at least one height band, against 1.5 percent of adolescents. Height, weight and BMI need monitoring, and the label suggests interrupting treatment in a child who is not growing as expected.
When can it actually be prescribed?
Approval and availability are different things. The DEA had not assigned a schedule at approval and the label shipped with the schedule field blank, so pharmacies could not stock it until that finished.
Limitations of the evidence
- About 6.6 symptom points weaker than lisdexamfetamine
- A 2024 network meta-analysis found it no better than placebo
- DEA schedule was still unassigned at approval
- The serotonin component has never been isolated in a trial
- No head-to-head trial against any stimulant exists
Adverse effects
- Rash, and it is the leading cause of stopping
- Decreased appetite
- Nausea
- Headache
- Insomnia
- Dry mouth
- Slowed growth in children on long-term use
Notes and cautions
- Two boxed warnings: suicidal ideation and behaviour in children aged 6 to 12, where suicide attempt was reported in 0.7 percent against none on placebo, and abuse, misuse and addiction.
- Anyone starting it, and the family of any child on it, should be told what to watch for in the first months.
- Long-term treatment slowed linear growth in the 6 to 12 group specifically; by week 88 of open-label treatment 15.6 percent of those children had dropped at least one height percentile band, against 1.5 percent of adolescents. Height and weight need monitoring.
- Human abuse-potential testing was not reassuring: drug liking at 400 mg and 800 mg was not significantly lower than amphetamine 40 mg or lisdexamfetamine 150 mg, although abrupt discontinuation after chronic dosing produced no withdrawal beyond placebo.
- Alcohol strips the extended-release control and releases the full dose at once; it must be avoided at dosing and for two hours afterwards.