Solriamfetol (Sunosi)
Cognitive · DNRI / wakefulness-promoting
Tier B
What this is
Originally developed by Aerial BioPharma and Jazz Pharmaceuticals; **Axsome Therapeutics acquired Sunosi from Jazz in March 2022** and now drives the development program. Distinguishing pharmacology vs modafinil: direct dopamine + norepinephrine reuptake inhibition (closer to a mild amphetamine than to modafinil); preclinical mouse data show comparable wake-promotion but less anxiety-related behavior and lower locomotor activation than modafinil at equivalent wake-promoting doses. **Major 2025 development**: FOCUS Phase 3 in adult ADHD (Axsome press release March 25 2025) met primary endpoint at 150 mg (AISRS reduction -17.7 vs placebo -14.3; statistically significant; 53.5% response rate vs 41.3% placebo). Axsome announced sNDA preparation for the ADHD indication. SUSTAIN Phase 3 in shift work disorder ongoing with topline expected 2026. **Cardiovascular caveat**: dose-related SBP/DBP increases at peak (~2 hr post-dose) are transient across 24 hr at 150 mg/day, but the indicated populations all carry elevated baseline CV risk — small chronic BP elevations are clinically meaningful for MACE risk. 2024 FAERS retrospective pharmacovigilance (Q3 2019 – Q1 2024) identified 30 disproportionality signals; AE profile consistent with label. Real-world preference: in a 62-patient retrospective, 71% of patients preferred solriamfetol over modafinil/armodafinil after switching; 29% reverted. Distinct from Pitolisant (Wakix) — the only non-scheduled wakefulness Rx — see adjacent row.
Mechanism
Selective dopamine and norepinephrine reuptake inhibitor (DNRI); mechanistically distinct from modafinil's adenosine/orexin pathway; FDA-approved 2019 for excessive daytime sleepiness in narcolepsy and OSA; March 2025 FOCUS Phase 3 also positive in adult ADHD
Dose & route
75-150 mg PO once daily (FOCUS Ph3 300 mg dose was numerically superior but NOT statistically significant on primary)
Citations
- https://pubmed.ncbi.nlm.nih.gov/30702348/
- https://pubmed.ncbi.nlm.nih.gov/31021471/
- https://www.globenewswire.com/news-release/2025/03/25/3048592/33090/en/Axsome-Therapeutics-Announces-FOCUS-Phase-3-Trial-of-Solriamfetol-in-Adults-with-Attention-Deficit-Hyperactivity-Disorder-ADHD-Achieves-Primary-Endpoint.html
- https://pmc.ncbi.nlm.nih.gov/articles/PMC12453233/
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1415918/full
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10121964/
- https://doi.org/10.3389/fmed.2026.1712097
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