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What To Know About Simtriyo, A New FDA-Approved ADHD Medication

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Simtriyo is being promoted as a new kind of ADHD drug that may help with emotional dysregulation. But the strongest evidence so far is for core ADHD symptoms, and questions remain about how it compares to existing treatments

Kristel Tjandra, Ph.D.

September 11, 2026

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Photo: Peter Hemmel

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Highlights

Simtriyo (centanafadine) is a new once-daily ADHD medication approved for adults and children ages 6 and older.
It acts on norepinephrine, dopamine, and serotonin, distinguishing it from many existing ADHD treatments.
Clinical trials found that Simtriyo improved core ADHD symptoms, but it hasn’t been directly compared with other ADHD medications.
Simtriyo has been touted for potentially improving emotional dysregulation and executive function, but those benefits have not yet been proven in prospective clinical trials.

A newly approved medication for attention-deficit/hyperactivity disorder (ADHD) is being promoted as a novel option for people living with the condition: A drug that may go beyond treating core symptoms like inattention and impulsivity to help with co-occurring emotional dysregulation.

But whether it can deliver that additional benefit remains to be seen.

ADHD is a common developmental disorder characterized by persistent symptoms of inattention, hyperactivity, and impulsivity. Symptoms begin in childhood and can persist into adulthood, where they may interfere with work, relationships, and everyday life. People with ADHD may also experience emotional dysregulation, including difficulty managing frustration, irritability, and intense or rapidly changing emotions.

A variety of medications are used to treat ADHD, including stimulants, non-stimulants approved for ADHD, and certain antidepressants that are prescribed off-label. On July 24, 2026, the Food and Drug Administration (FDA) approved Simtriyo (centanafadine), a new once-daily extended-release capsule for adults and children ages 6 and older with ADHD. Simtriyo is classified by the FDA as a central nervous system stimulant, but it works differently from traditional ADHD stimulants such as amphetamine and methylphenidate.

Simtriyo acts on three neurotransmitters: dopamine and norepinephrine — which play central roles in attention, motivation, and executive function — as well as serotonin. Traditional stimulants, such as Adderall (amphetamine/dextroamphetamine) and Ritalin (methylphenidate), primarily affect dopamine and norepinephrine. Serotonin, meanwhile, is involved in mood and emotional processing.

In a press release from Simtriyo’s manufacturer, Otsuka, Lenard A. Adler, M.D., director of the Adult ADHD Program at NYU Langone Health and a principal investigator on the centanafadine clinical trials, said the drug may help emotional symptoms of ADHD that are “not always adequately addressed by current treatments.”

“Emotional dysregulation in ADHD shows up as a low frustration threshold and a reaction that’s disproportionate to the trigger,” says Ritu Goel, M.D., an integrative psychiatrist and a member of MedShadow’s Health and Medical Advisory Panel.

“A minor setback produces anger, tears, or shutdown far beyond what the situation warrants. Patients often describe going from zero to sixty with little warning, then feeling shame once they’ve calmed down.”

Centanafadine is not yet commercially available, and is still awaiting controlled substance scheduling by the U.S. Drug Enforcement Administration (DEA), which will determine how tightly the drug is regulated based in part on its potential for abuse and dependence. Placement in a lower schedule would generally mean fewer prescribing and refill requirements.

Dr. Adler and colleagues described centanafadine as “a stimulant with nonstimulant characteristics” in a 2022 paper. But Kevin Williams, M.D., a psychiatrist at the telehealth platform ADHD Advisor who specializes in treating adults with ADHD, says that if the DEA places centanafadine in the same highly restricted schedule as other commonly prescribed ADHD stimulants, it would suggest the drug is “more of a stimulant than I would think Otsuka would like to admit.”

Does Simtriyo Really Help With Emotional Dysregulation?

In a May 2026 press release, Otsuka reported that centanafadine improved executive function and emotional dysregulation in adults, including emotional overactivity, mood instability, and anger outbursts.

But those findings did not come from the primary analyses used to establish Simtriyo’s effectiveness for ADHD. Instead, they came from an unpublished, exploratory post hoc analysis of data from the drug’s two Phase 3 adult trials. Post hoc analyses examine existing trial data after a study has been designed and can be useful for identifying potential effects worth investigating further, but they also carry a greater risk of false-positive or overinterpreted findings.

While centanafadine clearly works on core ADHD symptoms (the primary outcomes of its clinical trials), notes Dr. Goel, its executive-function and emotional-regulation benefits are so far “promising secondary signals that the company is emphasizing, not an established primary finding.”

Simtriyo Side Effects, And How It May Compare With Other ADHD Medications

Because no head-to-head trials have compared centanafadine with existing ADHD medications, differences in effectiveness can only be estimated indirectly, using a statistical method known as matching-adjusted indirect comparison (MAIC).

Based on a MAIC analysis of trial results, centanafadine appears to have similar efficacy compared with the non-stimulant ADHD medications atomoxetine and viloxazine, but less effective than the stimulant lisdexamfetamine. In terms of onset, centanafadine appears to work faster than non-stimulants, demonstrating benefits more in line with the timeframe of stimulants.

While the drug “won’t displace stimulants on raw efficacy,” notes Dr. Goel, it could fill a gap for people who can’t take existing stimulant medications.

As in the case with other ADHD medications, clinicians will need to consider a patient’s medical and psychiatric history before prescribing centanafadine. Jeffrey Ditzell, D.O., a psychiatrist specializing in adults with ADHD with a private practice in New York, says that some conditions may rule out the medication altogether, while others warrant additional caution or monitoring.

“There are some conditions, [including] people with cardiac issues or serious arrhythmias, we want to be real careful about; anybody who has severe hepatic impairment; if they have a personal history of high blood pressure, if they have a history of bipolar disorder or mania, tics and Tourette — you probably wouldn’t offer the med in these cases,” he says.

Not all of these conditions are formal contraindications to Simtriyo. The drug is contraindicated in people with certain hypersensitivity reactions, those taking monoamine oxidase inhibitors (MAOIs) or who stopped taking one within the previous 14 days, and people with pheochromocytoma (a rare tumor of the adrenal gland) or a history of the condition. Its prescribing information separately recommends avoiding the drug in people with serious cardiac disease and monitoring for increases in blood pressure and heart rate, psychiatric symptoms, and new or worsening tics.

The most common side effects for centanafadine are rash and decreased appetite in children ages 6 to 12, decreased appetite, nausea, rash, headache, and abdominal pain in adolescents ages 13 to 17, and headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea in adults.

Centanafadine’s side-effect profile overlaps with existing ADHD medications. Commonly reported side effects of existing non-stimulants include nausea, decreased appetite, insomnia, increased blood pressure and heart rate, and reduced libido. Common side effects of stimulant medications include insomnia, decreased appetite, weight loss, nausea, headache, abdominal pain, increased blood pressure, and mood changes.

Serious adverse reactions reported with stimulant medications — including sudden unexplained death and increased heart rate — were not observed in the centanafadine trials. However, the medication has not yet been studied in routine clinical practice, and its long-term safety profile is still being established.

Vera Prisacari, M.D., a psychiatrist specializing in treating adults with ADHD with a private practice in Minnesota, says that centanafadine may ultimately make the most difference for individuals taking multiple drugs to ease their symptoms.

“Not infrequently, I’ll see somebody who’s on [different] medications for anxiety, depression, sleep, and ADHD, and I don’t like that because they have interactions; they have side effects,” she says. “A much better approach would be if a medication targeted more mechanisms and had a cleaner side-effect profile. Bottom line: [it’s] easier to remember to take just one medication once a day.”

In children older than six, stimulants remain the first-line treatment for ADHD, and are often used alongside non-drug approaches such as behavioral interventions, classroom accommodations, and physical activity. However, their side effects — particularly decreased appetite and insomnia — can raise concerns about growth and development.

In the pediatric trial for centanafadine, decreased appetite was reported in 4% to 8% of children taking centanafadine, compared with roughly 30% of children taking Ritalin (methylphenidate) in previous studies.

Centanafadine’s Boxed Warnings

Centanafadine carries two boxed warnings.

The first warns about suicidal thoughts and behaviors in children. In a six-week clinical trial of children ages 6 to 12, suicidal thoughts and behaviors were reported more frequently among those taking centanafadine than those receiving placebo. Although investigators did not consider the serious adverse events reported during the trial to be related to centanafadine, the FDA determined that the overall safety findings warranted a boxed warning and recommends monitoring children and adolescents taking the drug for suicidal thoughts or behaviors and changes in psychiatric symptoms.

Centanafadine is not the only ADHD medication to carry such a warning: Strattera (atomoxetine), a non-stimulant, has a boxed warning about increased suicidal ideation in children and adolescents.

Antidepressants, including SSRIs, carry a similar warning about suicidal thoughts and behaviors in children, adolescents, and young adults.

Centanafadine’s second boxed warning is for the potential for abuse, misuse, and addiction, language more commonly associated with stimulant medications. “These [warnings] are not something you classically see with a non-stimulant,” says Dr. Williams.

A Closer Look at the Clinical Trials Behind Simtriyo’s Approval

The FDA based its approval of Simtriyo on four phase 3 clinical trials comparing centanafadine with a placebo in adults, adolescents, and children as young as 6.

“These are solid, well-run studies,” notes Dr. Goel, who has overseen psychiatric clinical trials, including work focused on participant safety and adverse event review. She adds that the trials included an independent data monitoring committee that reviewed participant safety and study conduct independently of the sponsoring pharmaceutical company.

Adult Phase 3 Clinical Trials 1 and 2

The first two phase 3 clinical trials of centanafadine — Study 1 and Study 2 — enrolled adults aged 18 to 55. The trials included 446 and 430 participants, respectively, who were randomly assigned to receive centanafadine at a total daily dose of either 200 mg or 400 mg, or a matching placebo, for six weeks.

Across both studies, about half of the participants were male. Most were White (approximately 80%), followed by Black participants (13%), with an average age of 35. Most had been diagnosed with ADHD either in childhood or at least one year before enrolling. Participants already taking ADHD medication completed a washout period before treatment began. The trials were conducted at 91 clinical sites between January 2019 and May 2020.

The trials excluded certain groups, including females who were breastfeeding and people with certain coexisting psychiatric conditions such as generalized anxiety disorder, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), or a current major depressive episode.

Both studies measured whether centanafadine improved ADHD symptoms using the Adult ADHD Investigator Symptom Rating Scale, or AISRS, a validated, clinician-administered questionnaire used in adults with ADHD. The scale includes 18 items: nine assessing inattentive symptoms and nine assessing hyperactive-impulsive symptoms. During semi-structured interviews, participants answered questions about common ADHD behaviors, such as making careless mistakes when bored, fidgeting while seated, or having difficulty waiting their turn. At the start of the studies, participants’ scores suggested moderate to severe ADHD symptoms.

In both trials, participants who received either the 200 mg or 400 mg daily dose of centanafadine had statistically significant improvements in AISRS scores compared with those who received placebo. These improvements emerged as early as seven days in Study 2 and 28 days in Study 1.

Centanafadine was generally well tolerated in this adult cohort, according to a report summarizing the results. The most common side effects included gastrointestinal problems, diarrhea, nausea, decreased appetite, and dry mouth. About 10% to 12% of participants taking centanafadine also experienced side effects classified under the broad category of “psychiatric disorders,” which included insomnia, irritability, anxiety, depressed mood, and abnormal dreams. Twelve participants discontinued treatment because of side effects in this category.

After completing the two placebo-controlled trials, participants were invited to enroll in a 52-week open-label extension study, in which all received 400 mg of centanafadine daily. Researchers continued to evaluate the drug’s long-term safety and effectiveness in 653 participants, including both rollover participants and newly enrolled patients. Overall, the findings suggested that centanafadine remained generally safe and effective over one year, with no new safety concerns identified. The most commonly reported adverse effects in this longer study were insomnia (8%), nausea (7.7%), diarrhea, and headache (7% each).

Because anxiety commonly co-occurs with ADHD, Otsuka also conducted a separate Phase 3b trial in adults with both conditions. According to preliminary results released by the company, centanafadine improved ADHD symptoms compared with placebo and also reduced anxiety symptoms on the Hamilton Anxiety Rating Scale. Otsuka told MedShadow that the full study will be presented at an upcoming scientific meeting.

Phase 3 Clinical Trial on Adolescents Ages 13 to 17

The adolescent clinical trial for centanafadine consisted of 451 participants aged 13 to 17 years who had a primary diagnosis of ADHD. More than two-thirds of the participants were White, 59% were male, and all were diagnosed with at least a moderate level of ADHD based on the Clinical Global Impression of Severity scale. Those on existing medication underwent a washout period before starting treatment. The study took place at 48 clinical sites: 47 in the U.S. and one in Canada.

The trial excluded adolescents with a comorbid diagnosis of Tourette syndrome, panic disorder, psychosis, posttraumatic stress disorder, bipolar disorder, autism spectrum disorder, anxiety disorder, and obsessive-compulsive disorder.

The primary endpoint was the change from baseline in the ADHD Rating Scale-5 (ADHD-RS-5), a validated caregiver-completed questionnaire that measures the severity of ADHD symptoms in children.

During the trial, participants were given either a high (328.8 mg) or low (164.4 mg) dose of centanafadine, or a matching placebo, for 6 weeks. Relative to those in the placebo group, adolescents who received 164.4 mg of centanafadine showed significant improvement in their overall ADHD-RS-5 score starting from week 4, but the effect did not continue into week 6. The reason for this loss of efficacy was unclear. Meanwhile, those who received the higher dose (328.8) showed improvement starting in week 1 and sustained through week 6.

As with the adult studies, the investigators deemed centanafadine as generally safe and well-tolerated in this study population. The most common adverse effects reported by the adolescents were decreased appetite, nausea, rash, drowsiness, and abdominal pain (a more detailed breakdown of these side effects can be found in the graph below).

Phase 3 Clinical Trial on Children Ages 6 to 12

The pediatric phase 3 trial of centanafadine enrolled 480 children aged 6 to 12 years who had a primary diagnosis of ADHD. Participants were randomly assigned to receive either once-daily centanafadine or a matching placebo for six weeks. Children already taking ADHD medication underwent a washout period prior to the start of the trial.

In the pediatric trial, 58% of participants were male, and 42% were female. Most participants were White (71%), while 27% were Black. The trial was conducted at 58 clinical sites — 57 in the U.S., 1 in Canada — between July 2022 and August 2023.

The trial included a list of exclusion criteria, including children with Tourette syndrome, panic disorder, bipolar disorder, autism spectrum disorder, major depressive disorder, and posttraumatic stress disorder.

Centanafadine doses were based on each child’s weight, with capsules containing 41.1 mg, 82.2 mg, or 164.4 mg. Within each weight group, participants were randomly assigned to either a low- or high-dose regimen, with the high-dose group receiving twice the daily dose of the low-dose group.

As with the adolescent trial, the primary endpoint of the pediatric groups was assessed based on changes in their ADHD-RS-5 score.

The group of children who received the highest doses of centafanadine showed the greatest improvement in ADHD-RS-5 score compared to placebo, an effect observed as early as the first week. Meanwhile, those in the low-dose group did not appear to improve compared with placebo.

Centanafadine was generally well tolerated at both the low and high doses. The most commonly reported adverse events were rash, decreased appetite, and upper abdominal pain. (See the graph below for a more detailed breakdown of these side effects.) Three serious adverse events occurred in the low-dose group — a suicide attempt, a panic attack, and appendicitis — and one suicide attempt occurred in the high-dose group. Investigators did not consider any of the serious events to be related to the study drug.

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