Simtriyo

Simtriyo (centanafadine) is a new prescription medicine used to treat ADHD in adults and children 6 years of age and older who weigh at least 20 kg (about 44 pounds). It is a once-daily extended-release capsule taken by mouth in the morning.

Simtriyo is the first medicine in a class called norepinephrine, dopamine, serotonin reuptake inhibitors (NDSRIs). It works by blocking the reuptake of three brain messengers (neurotransmitters), norepinephrine, dopamine, and serotonin, which increases their availability in pathways involved in attention and behavior. Simtriyo is also a central nervous system (CNS) stimulant. The exact way Simtriyo improves ADHD symptoms is not fully understood.

Simtriyo FDA approval was granted on July 24, 2026, based on four Phase 3 clinical trials in children, adolescents, and adults, which demonstrated centanafadine produced statistically significant improvements in ADHD symptoms compared with placebo. Improvements were seen as early as week 1.

Because centanafadine is a CNS stimulant, Simtriyo will be a federally controlled substance. Its exact controlled substance schedule is still being determined by the U.S. Drug Enforcement Administration (DEA), and the medicine is expected to become available later in 2026 once scheduling is complete.

Simtriyo works by increasing the activity of three chemical messengers involved in focus and self-control. It blocks the reuptake of norepinephrine, dopamine, and serotonin at nerve endings, which leaves more of these neurotransmitters available in the brain. Unlike amphetamine-based ADHD medicines, Simtriyo is a first-in-class NDSRI, so it acts on all three of these chemical messengers at once. It is still a CNS stimulant, and the precise mechanism behind its effect on ADHD is not fully known.

In clinical trials, Simtriyo significantly reduced ADHD symptoms compared with placebo (an inactive treatment), and improvement was seen as early as week 1. The FDA approval was based on four Phase 3 studies in children, adolescents, and adults that measured symptoms using standard ADHD rating scales.

In the pediatric studies, symptoms were measured with the ADHD Rating Scale-5 (ADHD-RS-5), where a larger drop in score means greater improvement. After 6 weeks of treatment:

• Children 6 to 12 years taking the approved weight-based dose had about a 5.6-point greater reduction in symptom scores than those taking placebo.
• Adolescents 13 to 17 years taking 280 mg had about a 4.4-point greater reduction than those taking placebo.

In the adult studies, symptoms were measured with the Adult ADHD Investigator Symptom Rating Scale (AISRS). Adults treated with centanafadine had a significantly greater reduction in ADHD symptoms than those taking placebo, and also improved on a measure of overall symptom severity (the Clinical Global Impression-Severity scale).

Not every dose worked in the studies. The lower 140 mg dose did not separate from placebo in the pediatric trials, which is why it is not an approved standalone dose. Simtriyo has not been compared directly with other ADHD medicines in head-to-head trials, so how it compares with stimulants such as amphetamine or methylphenidate products is not known. Individual results vary, and a healthcare provider can advise whether Simtriyo is an appropriate option.

Take Simtriyo exactly as prescribed. Follow these instructions:

• Take Simtriyo once a day in the morning, at about the same time each day.
• It can be taken with or without food.
• Swallow the capsules whole. Do not cut, crush, or chew them.
• If the capsule cannot be swallowed whole, it may be opened and the entire contents sprinkled over one tablespoon (15 mL) of applesauce or yogurt, or stirred into one tablespoon (15 mL) of orange juice. Swallow the mixture right away, then drink water. Do not chew the granules and do not save the mixture for later.
• Do not drink alcohol at the same time as, or within 2 hours after, taking Simtriyo.

Simtriyo has a Boxed Warning, the FDA's most prominent safety warning, for the risk of suicidal thoughts and behaviors in children and for the risk of abuse, misuse, and addiction.

Suicidal thoughts and behaviors in children 6 years and older

In a short-term (6-week) study, higher rates of suicidal thoughts and behaviors were reported in children aged 6 to 12 years treated with Simtriyo than in children given placebo. All children 6 years and older taking it should be watched closely for suicidal thoughts and behaviors, worsening symptoms, or unusual changes in behavior, especially during the first few months of treatment and after dose changes. Tell the prescriber right away about any new, sudden, or worsening changes in mood, behavior, or thoughts.

Abuse, misuse, and addiction

Simtriyo is a CNS stimulant and has a potential for abuse and misuse, which can lead to a substance use disorder, including addiction. Misuse and abuse of stimulants can result in overdose and death. This risk is higher with larger doses or with unapproved ways of taking the medicine, such as snorting or injecting it. Store it in a safe place, preferably locked, and do not give it to anyone else.

Other serious warnings

Simtriyo may also cause other serious effects that need monitoring:

• Serious heart problems: Sudden death has been reported with stimulants in people who have structural heart problems or other serious heart disease. It should be avoided in people with these conditions.
• Increased blood pressure and heart rate: Simtriyo can raise blood pressure and heart rate. These should be checked before starting, after dose increases, and regularly during treatment.
• Mental (psychiatric) symptoms: Simtriyo may cause new or worsening psychotic or manic symptoms, such as hallucinations, delusional thinking, or mania, even in people with no prior history.
• Serious allergic reactions: Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported.
• Slowing of growth in children: Long-term stimulant use can slow weight gain and height growth in children. Height and weight should be monitored.
• Circulation problems (peripheral vasculopathy, including Raynaud's phenomenon): Fingers or toes may feel numb, cool, or painful, or change color. Rarely, sores can develop.
• Serotonin syndrome: Taking Simtriyo with other medicines that raise serotonin can cause this potentially life-threatening reaction.
• Tics and Tourette's syndrome: Stimulants can bring on or worsen motor and verbal tics.

Do not take Simtriyo if you or your child:

• Are allergic to centanafadine or any of the ingredients in Simtriyo
• Are taking, or have stopped within the past 14 days, a type of medicine called a monoamine oxidase inhibitor (MAOI). Taking Simtriyo with an MAOI can cause a dangerous rise in blood pressure and serotonin syndrome.
• Have a condition called pheochromocytoma, a rare tumor of the adrenal glands

Before starting Simtriyo, tell the healthcare provider about all medical conditions, including if you or your child:

• Have heart problems, heart defects, high blood pressure, or a family history of sudden death
• Have mental health conditions such as psychosis, mania, bipolar disorder, or depression, or a family history of suicide, bipolar disorder, or depression
• Have circulation problems in the fingers or toes
• Have or had tics or Tourette's syndrome, or a family history of these
• Have an allergy or sensitivity to FD&C Yellow No. 5 (tartrazine), which is present in the 210 mg capsule
• Have liver problems
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed

Also tell the provider about all medicines being taken, including prescription and over-the-counter medicines, vitamins, and herbal supplements, since it can interact with several of them.

The most common side effects of Simtriyo include decreased appetite, nausea, headache, rash, insomnia, dry mouth, and diarrhea. Which effects are most common depends on age group.

• Children 6 to 12 years: rash and decreased appetite
• Adolescents 13 to 17 years: decreased appetite, nausea, rash, headache, and abdominal (stomach area) pain
• Adults: headache, decreased appetite, insomnia (trouble sleeping), nausea, dry mouth, and diarrhea

Serious side effects can include suicidal thoughts and behaviors in children, abuse and misuse, heart-related effects, increased blood pressure and heart rate, psychiatric symptoms, serious allergic reactions, slowed growth in children, circulation problems in the fingers and toes, serotonin syndrome, and new or worsening tics. See the warnings section above for details. Get medical help right away for chest pain, fainting, trouble breathing, swelling of the face or throat, or signs of serotonin syndrome such as agitation, confusion, fast heartbeat, high fever, or muscle stiffness.

These are not all the possible side effects. Report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Simtriyo comes as extended-release capsules in three strengths: 140 mg, 210 mg, and 280 mg. The dose depends on age and, for younger children, body weight.

Dose for children 6 to 12 years of age

In children 6 to 12 years of age weighing at least 20 kg, the dose is based on body weight:

Dose for adolescents 13 to 17 years of age

In adolescents 13 to 17 years of age weighing at least 20 kg, the recommended dose is 280 mg once daily.

Dose for adults

In adults, the recommended starting dose is 210 mg once daily. The dose may be increased to a maximum of 280 mg once daily based on how well the medicine works and how well it is tolerated.

Simtriyo is not recommended for children younger than 6 years of age, because this age group had more weight loss than older children, or for children weighing less than 20 kg, because of a lack of data and the risk of weight loss. It is also not recommended for people with severe liver problems.

If a dose is missed, take it as soon as you remember, but no later than 4 hours after the normal dosing time. If more than 4 hours have passed, skip the missed dose and take the next dose at the regular time. Do not take more than one dose of Simtriyo in the same day.

In case of an overdose, call the Poison Help Line at 1-800-222-1222. If someone has collapsed, had a seizure, has trouble breathing, or cannot be woken up, call 911 right away. Overdose symptoms can include vomiting, fast breathing, fast heartbeat, and raised blood pressure.

Simtriyo can interact with several medicines. Tell the healthcare provider about all medicines being taken. Important interactions include:

• MAOIs: Do not take Simtriyo with an MAOI or within 14 days of stopping one. This includes linezolid and intravenous methylene blue. The combination can cause a dangerous rise in blood pressure and serotonin syndrome.
• Alcohol: Avoid alcohol at the same time as, and for at least 2 hours after, taking Simtriyo. Alcohol can cause the medicine to be released too quickly, which may increase side effects and reduce how well it works later in the day.
• Other CNS stimulants: Taking Simtriyo with other stimulants can add to the effect on blood pressure and heart rate.
• Serotonergic medicines: Medicines that raise serotonin, such as certain antidepressants (SSRIs and SNRIs), triptans for migraine, certain opioids, tryptophan, and St. John's Wort, can raise the risk of serotonin syndrome.
• CYP1A2 substrates: Centanafadine is a moderate CYP1A2 inhibitor and can increase the levels of medicines processed by this liver enzyme. For example, it roughly doubled caffeine exposure in a study. A dose reduction of the affected medicine may be needed.

This is not a complete list. Do not start any new medicine while taking Simtriyo without first checking with the healthcare provider or pharmacist.

There is not enough information to know whether Simtriyo is safe to use during pregnancy. Anyone who is pregnant or planning to become pregnant should discuss the risks and benefits with their healthcare provider. A pregnancy exposure registry monitors outcomes in people who take ADHD medicines, including Simtriyo, during pregnancy. To enroll, call the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visit womensmentalhealth.org.

It is not known whether centanafadine passes into breast milk or how it might affect a breastfed infant. Talk to the healthcare provider about the best way to feed your baby while taking it.

Store Simtriyo at room temperature, between 68°F and 77°F (20°C to 25°C). Keep it in a safe place, such as a locked cabinet, and out of the reach of children and pets. Dispose of any unused medicine through a DEA-authorized take-back program. Visit www.fda.gov/drugdisposal for more information.

Active ingredient: centanafadine

Inactive ingredients (capsule beads): colloidal silicon dioxide, ethyl acrylate and methyl methacrylate copolymer, hypromellose, mannitol, microcrystalline cellulose, plasacryl, poly (methyl acrylate-CO-methyl methacrylate-CO-methacrylic acid), polysorbate 80, and talc. The capsule shells contain hypromellose, titanium dioxide, and coloring agents: FD&C Blue No. 1 (280 mg capsule), FD&C Yellow No. 5 (210 mg capsule), and FD&C Yellow No. 6 (140 mg capsule). The capsules are imprinted with edible black ink.