The Food and Drug Administration has approved oral centanafadine, marketed as Simtriyo, as a first-in-class triple reuptake inhibitor for attention deficit-hyperactivity disorder in patients ages 6 years and older weighing at least 20 kg, according to an announcement from drugmaker Otsuka. The once-daily extended-release capsule functions as a central nervous system stimulant by targeting norepinephrine, dopamine, and serotonin.
Understanding the Mechanism of Action of Simtriyo
Simtriyo works by inhibiting the reuptake of three key neurotransmitters simultaneously. According to Otsuka, this action increases the availability of norepinephrine, dopamine, and serotonin in the specific neural pathways responsible for attention and behavioral regulation. Lenard A. Adler, MD, of NYU Langone Health in New York City, stated in a company press release that the approval introduces a novel mechanism of action that expands available options for healthcare professionals and patients.
Clinical Trial Results and Efficacy in Adults and Children
Regulatory approval was backed by data from four randomized, double-blind, placebo-controlled phase III trials. These included two studies focusing on adults and two examining pediatric and adolescent populations, according to Otsuka. Across these trials, centanafadine demonstrated statistically significant and clinically meaningful improvements in ADHD symptoms. Symptom reduction was measured using the ADHD Rating Scale-5 for children and adolescents and the Adult ADHD Investigator Symptom Rating Scale for adults, with improvements noted as early as week 1.
Pro Tip: Healthcare providers evaluating treatment options should note that centanafadine recently showed success in a phase IIIb clinical study involving adults managing ADHD alongside comorbid anxiety, according to company reports.
Side Effects, Safety Warnings, and Contraindications
Clinical data showed that adverse reactions varied by age group. The most common side effects included rash and decreased appetite in children ages 6 to 12. Teens ages 13 to 17 experienced decreased appetite, nausea, rash, headache, and abdominal pain. Adults reported headache, decreased appetite, insomnia, nausea, dry mouth, and diarrhea, according to study findings.
The drug label carries boxed warnings outlining a risk of suicidal ideation and behaviors in pediatric patients, alongside potential risks for abuse, misuse, and addiction. Additional warnings cover serious cardiac disease, increased blood pressure and heart rate, adverse psychiatric reactions, hypersensitivity reactions, long-term growth suppression in children, peripheral vasculopathy, serotonin syndrome, and tics. Centanafadine is not recommended for children under 6 due to weight loss incidence, and it is contraindicated in patients with known hypersensitivity, those taking or recently taking monoamine oxidase inhibitors within 14 days, and individuals with a history of pheochromocytoma.
The Broader Impact on ADHD Treatment Landscape
An estimated 7 million children and 15.5 million adults live with ADHD in the U.S., according to data from the Centers for Disease Control and Prevention. Dr. Adler noted that ADHD significantly impacts daily life across school, work, and relationships. Even during treatment, the heterogeneous nature of the condition means many patients continue experiencing symptoms that disrupt daily functioning. Otsuka announced that the medication will become available later this year following drug scheduling determinations.
Did You Know? Centanafadine functions as a norepinephrine, dopamine, and serotonin reuptake inhibitor.
Frequently Asked Questions
What is Simtriyo?
Simtriyo (centanafadine) is a once-daily extended-release capsule approved by the FDA as a first-in-class triple reuptake inhibitor for ADHD in patients 6 years and older weighing at least 20 kg, according to Otsuka.
When will centanafadine be available to patients?
Otsuka stated that the medication will launch later this year, pending final drug scheduling.
What are the primary safety warnings for Simtriyo?
The drug label includes boxed warnings for suicidal ideation and behaviors in pediatric patients, as well as risks for abuse, misuse, and addiction, alongside cardiovascular and psychiatric warnings.
How was the medication tested prior to approval?
Approval was supported by four randomized, double-blind, placebo-controlled phase III trials covering adult, pediatric, and adolescent populations, according to company disclosures.
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