Starting Dose for Centanafadine (Simtriyo)
For adults (18-55 years), start centanafadine at 200 mg once daily without titration; for adolescents (13-17 years), start at 328.8 mg once daily without titration.
Dosing by Age Group
Adults
The FDA-approved starting dose for adults is 200 mg once daily 1. This dose demonstrated statistically significant efficacy in two Phase 3 trials, with least-squares mean differences in ADHD symptom scores of -3.16 (p=0.019) and -4.01 (p=0.002) compared to placebo 1. The 400 mg dose showed similar efficacy but with increased treatment-emergent adverse events, making 200 mg the preferred starting dose for most patients.
Key point: No titration is required—patients begin at the target therapeutic dose 1.
Adolescents (13-17 years)
For adolescents, the starting dose is 328.8 mg once daily without titration 2. This higher dose (compared to the lower 164.4 mg dose tested) was the only dose that met the primary efficacy endpoint in the pivotal adolescent trial, showing significant improvement in ADHD-RS-5 scores (-18.50 vs -14.15 for placebo; p=0.0006) 2. Efficacy was demonstrated as early as Week 1 and maintained throughout the 6-week study 2, 3.
Critical distinction: The 164.4 mg dose failed to meet the primary endpoint in adolescents, so do not use this lower dose 2.
Children (6-12 years)
While Phase 3 data exist for children 3, specific dosing information for this age group is not provided in the available evidence. The adolescent dose should not be extrapolated to younger children without FDA guidance.
Administration Details
- Timing: Once daily dosing
- Food: Can be taken with or without food (based on similar extended-release formulations)
- Formulation: Extended-release tablets—do not crush, chew, or split
- No titration required: Unlike many ADHD medications, centanafadine is started at the target therapeutic dose 2, 1
Safety Considerations
Common Adverse Events
The most frequent treatment-emergent adverse events include 2, 1:
- Decreased appetite (most common)
- Nausea
- Headache
- Rash (particularly in adolescents)
Tolerability Profile
- In adults: 200 mg showed better tolerability than 400 mg, with lower discontinuation rates 1
- In adolescents: 328.8 mg was generally well tolerated, with 50.3% experiencing any adverse event vs 23.8% on placebo 2
- Most adverse events were mild to moderate in severity 2, 1
Important Caveats
Do not start with lower doses hoping to improve tolerability—the 164.4 mg dose in adolescents lacked efficacy 2, and doses below 200 mg in adults have not been adequately studied for efficacy 1, 4.
Mechanism matters: Centanafadine is a triple reuptake inhibitor (norepinephrine > dopamine > serotonin) without direct neurotransmitter release, distinguishing it from traditional stimulants 5. This may explain its different dosing paradigm compared to amphetamines or methylphenidate.