Solriamfetol
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
- Solriamfetol
- Solriamfetol: From Excessive Daytime Sleepiness to Attention-Deficit/Hyperactivity Disorder (ADHD)
Solriamfetol: From Excessive Daytime Sleepiness to Attention-Deficit/Hyperactivity Disorder (ADHD)
One-Sentence Summary
Solriamfetol is a dopamine/norepinephrine reuptake inhibitor (DNRI) wake-promoting agent, known from the literature to be used for excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. The TxGNN model predicts it may be effective for Attention-Deficit/Hyperactivity Disorder (ADHD), with 2 completed clinical trials — including a confirmatory Phase 3 RCT (n=516) — and 6 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (per published literature evidence; no structured original-indication or EU license data is available in this Evidence Pack) |
| Predicted New Indication | Attention-Deficit/Hyperactivity Disorder (ADHD) |
| TxGNN Prediction Score | 99.99% |
| Evidence Level | L1 |
| EU Market Status | Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed formal mechanism-of-action documentation is not available in this Evidence Pack (DrugBank query returned a data gap). However, based on collateral evidence and known pharmacology, solriamfetol is a dopamine-norepinephrine reuptake inhibitor (DNRI) — a wake-promoting agent that increases synaptic dopamine and norepinephrine concentrations. This is the same core mechanism as established first-line ADHD stimulant therapies such as methylphenidate and amphetamine derivatives.
Its original use — managing excessive daytime sleepiness in narcolepsy or obstructive sleep apnea — and the newly predicted indication, ADHD, both involve central catecholaminergic pathways governing alertness, attention, and executive function. This shared neurobiological target is the basis for the TxGNN prediction and gives the hypothesis strong a priori mechanistic plausibility.
Critically, this is not purely a computational prediction: it is already corroborated by real clinical development. A completed Phase 2/3 pilot RCT (n=66) and a completed, confirmatory Phase 3 RCT — FOCUS (n=516) — have directly tested solriamfetol in adults with ADHD, moving this candidate well beyond mechanism-only speculation and into an evidence-backed repurposing opportunity.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04839562 | Phase 2/3 | Completed | 66 | Double-blind, placebo-controlled pilot study of solriamfetol in adults (18–65) with ADHD |
| NCT05972044 | Phase 3 | Completed | 516 | FOCUS trial: multi-center, randomized, double-blind, placebo-controlled, parallel-group confirmatory trial assessing efficacy and safety of solriamfetol in adults with ADHD |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37819836 | 2023 | RCT | J Clin Psychiatry | Remotely conducted, randomized, double-blind, placebo-controlled 6-week dose-optimization pilot trial (75/150 mg) of solriamfetol in adults with DSM-5 ADHD |
| 33870884 | 2022 | RCT/Pilot | CNS Spectrums | Early clinical report examining solriamfetol use for ADHD |
| 38771653 | 2024 | Review | Expert Opin Pharmacother | Reviews emerging non-stimulant pharmacological options for ADHD, moving beyond traditional stimulants |
| 40986064 | 2025 | Review | Expert Opin Pharmacother | Focused review of Phase 3 trials for potential new ADHD treatments |
| 41621729 | 2026 | Review | Pharmacol Ther | Broad review of pharmacological, neuromodulatory, and psychotherapeutic interventions for adult ADHD |
| 34534876 | 2021 | Review | Epilepsy & Behavior | Reviews drugs for excessive daytime sleepiness/attentional deficits in epilepsy patients (indirect relevance) |
EU Market Information
Solriamfetol currently has no registered EU marketing authorizations in this Evidence Pack (market status: Not Marketed; total licenses: 0).
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Two completed clinical trials — including a confirmatory Phase 3 RCT (n=516) — directly support the ADHD indication, and the shared DNRI mechanism with established stimulant ADHD therapies gives strong mechanistic plausibility. However, the drug is not currently authorized in the EU and key safety documentation is missing, so guardrails are needed before further action.
To proceed, the following is needed:
- TFDA/EMA label warnings, contraindications, and DDI data (currently a Blocking data gap — required before any safety pre-assessment/S1 stage)
- Formal DrugBank-sourced mechanism-of-action documentation (currently a High-severity data gap)
- Clarification of actual EU regulatory/marketing status, since published literature references EU approval for the original indication while this Evidence Pack shows “Not Marketed”
- Cardiovascular/blood pressure monitoring plan, given the DNRI mechanism’s potential noradrenergic effects, especially relevant if extending to psychiatric populations
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.