Centanafadine: Non-Stimulant Option for ADHD That Works in Just One Week?
📌 Background
Finding safe and effective non-stimulant options for adolescents with ADHD remains a priority, especially for patients with concerns around stimulant side effects, misuse, or tolerability. A new randomized clinical trial evaluated the efficacy and safety of centanafadine, a novel norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI), in adolescents aged 13–17 years with ADHD.
🧪 Study Summary:
This 6-week, double-blind, placebo-controlled trial enrolled 459 adolescents across 48 sites in North America.
Dosing:
- Participants were randomized to receive once-daily centanafadine at either 164.4 mg, 328.8 mg, or placebo.
- Dosing was fixed (no titration).
Primary outcome:
- Change from baseline in ADHD Rating Scale-5 (ADHD-RS-5) total symptom score at week 6.
Key results:
- Centanafadine 328.8 mg led to significantly greater symptom improvement than placebo (–18.5 vs –14.2; p = 0.0006).
- Clinical improvement was evident as early as Week 1 and sustained through Week 6.
- The lower 164.4 mg dose did not reach statistical significance.
- The higher dose also improved inattention, hyperactivity/impulsivity, and executive functioning scores on Conners 3–Parent Short scale.
Adverse events:
- Most common TEAEs at 328.8 mg: decreased appetite (15%), nausea (10%), headache (6%), and rash (6%).
- Most side effects were mild to moderate.
- No serious adverse events were reported for 328.8 mg.
- A small number (7.9%) discontinued due to side effects at the higher dose.
📊 Key Clinical Implications
Effective Non-Stimulant Option: Centanafadine 328.8 mg provides statistically and clinically meaningful symptom relief, with onset in the first week.
Multimodal Mechanism: By targeting norepinephrine, dopamine, and serotonin transporters, centanafadine may address broader ADHD symptoms including executive dysfunction.
Tolerability Profile: While side effects were more common at the higher dose, they were mostly mild, and no major safety signals emerged.
✅ Expert Commentary
This study reinforces centanafadine’s role as a viable non-stimulant candidate for adolescent ADHD, especially for patients with poor tolerance or contraindications to stimulants. Its efficacy, approaching effect sizes seen with other non-stimulants, is clinically relevant, and its broad neurotransmitter profile may be beneficial in real-world populations with emotional dysregulation or comorbid anxiety.
One limitation is the short duration—longer-term safety and effectiveness data are needed, especially regarding weight, growth, and emotional regulation. Still, these results are encouraging and add an important tool to the ADHD treatment landscape.
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