Why This Matters
Most ADHD medications affect one or two brain signaling systems. Centanafadine works differently—it targets three neurotransmitters involved in attention and regulation. Its strongest effect is on norepinephrine, which plays an important role in attention and alertness. It also modestly affects dopamine and serotonin, which are involved in motivation, mood, and emotional regulation. If approved, it would represent a new class of ADHD medication.
What the Clinical Trials Showed
Two Phase 3 randomized trials tested centanafadine in adults with ADHD. Both studies found that centanafadine significantly improved ADHD symptoms compared with placebo.
A 52-week open-label follow-up study suggested that these improvements were maintained over time and that the medication was generally well tolerated. Most side effects reported in the trials were mild to moderate (common side effects were decreased appetite, nausea, insomnia dry mouth).
How It Compares With Other ADHD Medications
We only have data for indirect comparisons rather than head-to-head studies, so they should be interpreted cautiously:
vs. Vyvanse (lisdexamfetamine): somewhat smaller symptom improvement, but lower rates of side effects such as insomnia and dry mouth
vs. Concerta (methylphenidate): roughly similar effectiveness, with lower rates of insomnia and several stimulant-type side effects
vs. Strattera (atomoxetine): similar effectiveness, with lower rates of nausea, dry mouth, and fatigue
vs. Qelbree (viloxazine): similar effectiveness, with lower rates of fatigue, insomnia, and nausea
My Take
Centanafadine may represent a useful middle ground in ADHD treatment. It does not appear to match stimulants like Vyvanse for raw symptom reduction, but it may offer comparable effectiveness to several current non-stimulant options with a potentially gentler side-effect profile. For adults who have struggled with insomnia, appetite suppression, or other tolerability issues on ADHD medications, it could become a welcome additional option if approved.
Sources
Adler LA, Adams J, Madera-McDonough J, et al. 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. Journal of Clinical Psychopharmacology. 2022 Sep-Oct;42(5):429-439. doi:10.1097/JCP.0000000000001575.
Mattingly GW, Turkoglu O, Chang D, et al. 52-Week Open-Label Safety and Tolerability Study of Centanafadine Sustained Release in Adults With Attention-Deficit/Hyperactivity Disorder. Journal of Clinical Psychopharmacology. 2025. doi:10.1097/JCP.0000000000002020.
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