Modafinil
| 證據等級: L5 | 預測適應症: 1 個 |
目錄
Modafinil: From Excessive Daytime Sleepiness Disorders to Insomnia
One-Sentence Summary
Modafinil is a wake-promoting agent whose established uses (per the underlying mechanistic evidence in this pack) center on narcolepsy, OSA-related excessive daytime sleepiness, and shift work sleep disorder. The TxGNN model predicts it may be effective for Insomnia (disease), a prediction currently supported by 29 clinical trials and 19 publications — though most of that evidence addresses fatigue/excessive sleepiness comorbid with insomnia rather than insomnia itself, and the drug’s stimulant mechanism runs counter to conventional insomnia treatment.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not licensed in Taiwan (0 records); known approved uses are narcolepsy, OSA-related excessive daytime sleepiness, and shift work sleep disorder |
| Predicted New Indication | Insomnia (disease) |
| TxGNN Prediction Score | 99.85% |
| Evidence Level | L3 |
| US Market Status | Not marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed original mechanism-of-action data is marked as a data gap in this pack, so the analysis below relies on the pharmacology summarized in the repurposing rationale rather than a verified DrugBank MOA record. Modafinil (and its isomer armodafinil) is a wake-promoting agent that increases dopaminergic, noradrenergic, and histaminergic signaling to promote alertness. Its established clinical uses — narcolepsy, OSA-related excessive daytime sleepiness, and shift work sleep disorder — are all conditions of excessive sleepiness, not difficulty sleeping.
This creates a mechanistic tension with the predicted indication: a stimulant that promotes wakefulness is, in principle, more likely to worsen than treat insomnia (difficulty initiating or maintaining sleep). The clinical trial evidence largely reflects this — most studies use modafinil/armodafinil to treat fatigue or residual daytime sleepiness that co-occurs with insomnia (e.g., post-chemotherapy fatigue, post-TBI fatigue, insomnia comorbid with sleep-disordered breathing), typically as an adjunct to cognitive behavioral therapy for insomnia (CBT-I), rather than treating insomnia’s core symptoms directly.
Given this, the high TxGNN score (99.85%) most plausibly reflects a strong graph-level association between modafinil and the “insomnia” disease node driven by these comorbid-fatigue trials, rather than a validated therapeutic effect on insomnia itself. This disease-label ambiguity — whether “insomnia” here truly means primary insomnia or the sleep/fatigue cluster studied in these trials — needs manual clarification before further evaluation.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00124384 | Phase 4 | Completed | 40 | Modafinil alone or with CBT-I evaluated for daytime functioning and symptom severity in primary insomnia — the most directly on-target trial in this evidence set |
| NCT02552303 | N/A | Completed | 39 | Armodafinil ± CBT-I in insomnia comorbid with OSA; assessed sleep continuity and CPAP/CBT-I adherence |
| NCT01091974 | Phase 2 | Completed | 138 | CBT-I ± armodafinil for insomnia and fatigue following chemotherapy in breast cancer patients |
| NCT01019187 | Phase 2 | Completed | 226 | Larger cohort of the same CBT-I ± armodafinil design for post-chemotherapy insomnia/fatigue |
| NCT01011218 | Phase 2 | Completed | 70 | Pilot of behavioral therapy (BBT-I/CBT-I) ± armodafinil for insomnia in breast cancer patients |
| NCT07295834 | Phase 2 | Not yet recruiting | 70 | Planned modafinil vs. placebo feasibility RCT for severe fatigue in inflammatory bowel disease; not insomnia-specific |
| NCT00233090 | Phase 2 | Terminated | 21 | Modafinil vs. placebo for post-TBI fatigue; terminated early, small sample |
| NCT01072630 | Phase 3 | Completed | 492 | Armodafinil as adjunctive therapy for major depression in bipolar I disorder — large completed Phase 3 RCT, but not insomnia-focused |
| NCT00481195 | Phase 2 | Completed | 257 | 8-week fixed-dose armodafinil adjunct RCT for bipolar I depression |
| NCT06404086 | Phase 2 | Completed | 830 | RECOVER-SLEEP platform trial for post-COVID sleep disturbances; modafinil is one arm among multiple interventions |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15824337 | 2005 | RCT | Neurology | Randomized, placebo-controlled, double-blind trial of modafinil for fatigue in multiple sclerosis |
| 18219235 | 2008 | RCT | J Head Trauma Rehabil | Randomized trial of modafinil for fatigue and excessive daytime sleepiness in chronic TBI |
| 24312590 | 2013 | Systematic Review/Meta-analysis | PLoS One | Modafinil’s efficacy on fatigue and EDS across neurological disorders; safety also assessed |
| 27010071 | 2016 | Systematic Review/Meta-analysis | Parkinsonism Relat Disord | Pharmacological interventions for daytime sleepiness and sleep disorders in Parkinson’s disease |
| 39535843 | 2024 | Review | Expert Opin Pharmacother | Pharmacological and non-pharmacological management of sleep disturbances in Parkinson’s disease |
| 18729534 | 2008 | Review | Drugs | Evidence-based review of approved and investigational uses of modafinil |
| 22021174 | 2011 | Review | Mov Disord | MDS evidence-based medicine review of treatments for non-motor symptoms of Parkinson’s disease |
| 20166851 | 2010 | Review | Expert Opin Emerg Drugs | Emerging treatments for narcolepsy and related disorders |
| 17181377 | 2006 | Review | Drugs | Shift work sleep disorder: burden of illness and management approaches |
| 17060310 | 2006 | Case Series | Am J Hosp Palliat Care | Modafinil reduces fatigue in Charcot-Marie-Tooth disease type 1A |
US Market Information
Modafinil currently has no license records in this dataset (0 NDAs; market status: not marketed).
Safety Considerations
Please refer to the package insert for safety information. (Key warnings, contraindications, and drug interaction data are currently unavailable — TFDA label data is flagged as a blocking data gap in this evidence pack.)
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence base is at L3 (observational/review-level) and consists mostly of trials treating fatigue or comorbid excessive sleepiness rather than insomnia itself, while modafinil’s wake-promoting mechanism is mechanistically counter-intuitive for an insomnia indication. Combined with the absence of TFDA label/safety data (a blocking gap) and no current market presence, the evidence does not yet support proceeding.
To proceed, the following is needed:
- TFDA/label warnings and contraindications (currently blocking — DG001)
- Verified original mechanism-of-action data from DrugBank (DG002)
- Manual clarification of what “insomnia” denotes in the TxGNN disease label (primary insomnia vs. comorbid fatigue/EDS)
- Trials or evidence directly targeting sleep-onset/maintenance outcomes in primary insomnia, ideally with modafinil (not only armodafinil)
- A safety monitoring plan given the stimulant mechanism’s potential to exacerbate insomnia symptoms
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.