Armodafinil
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Armodafinil: From Sleep-Wake Disorders to Insomnia (Adjunctive Use)
One-Sentence Summary
Armodafinil is a wake-promoting drug used for excessive sleepiness in sleep-wake disorders such as narcolepsy and shift work disorder. The TxGNN model predicts it may help with insomnia, but the score most likely reflects the drug’s closeness to sleep disorders in the knowledge graph, not proof that it treats insomnia. Currently 12 clinical trials and 20 publications are linked to this prediction, but few are directly about insomnia and no trial results are provided.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the US license records. The pack’s rationale describes use in narcolepsy and shift work disorder. |
| Predicted New Indication | Insomnia |
| TxGNN Prediction Score | 99.89% |
| Evidence Level | L2 (rests on Phase 2 RCTs whose results are not provided, so efficacy is unconfirmed) |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 licenses (NDAs and ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Armodafinil is a wake-promoting agent, and the pack’s rationale points to dopamine transporter inhibition. It is used where excessive daytime sleepiness is the problem, as in narcolepsy and shift work disorder.
The high TxGNN score most likely comes from the drug’s proximity to these sleep-wake disorders in the knowledge graph. A direct benefit for insomnia is mechanistically counterintuitive, because a wake-promoting drug would be expected to worsen sleep, and insomnia is a labeled adverse effect.
The only plausible role is adjunctive. Armodafinil might treat residual daytime sleepiness or fatigue in people whose insomnia comes with sleep-disordered breathing or cancer-related fatigue, alongside cognitive behavioral therapy for insomnia (CBT-I). The trials below test this idea, but no results are provided, so it remains a research question.
Clinical Trial Evidence
Only the first four trials directly study insomnia. The remaining trials study armodafinil in other conditions and are listed as context. No trial results are provided, so the findings below describe study design only.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02552303 | N/A | Completed | 39 | Armodafinil, CBT-I, or both for insomnia with sleep-disordered breathing; measures sleep continuity and adherence to CBT-I and CPAP. No results provided. |
| NCT01091974 | Phase 2 | Completed | 138 | Four-arm RCT of CBT-I with or without armodafinil for insomnia after chemotherapy in breast cancer patients (226 planned). Armodafinil targets fatigue; no results provided. |
| NCT01019187 | Phase 2 | Completed | 226 | Randomized phase II of CBT with or without armodafinil for insomnia and fatigue in cancer survivors. May be a related or extended cohort of NCT01091974. No results provided. |
| NCT01011218 | Phase 2 | Completed | 70 | Pilot study of brief behavioral therapy or CBT-I, with or without armodafinil 150 mg/day, for insomnia in breast cancer patients. No results provided. |
| NCT01080807 | Phase 4 | Completed | 385 | Placebo-controlled study of armodafinil 150 mg for excessive sleepiness in shift work disorder. Not an insomnia trial. |
| NCT00678691 | Phase 4 | Completed | 55 | Eight-week double-blind study of armodafinil augmentation for fibromyalgia fatigue. Not an insomnia trial. |
| NCT01072630 | Phase 3 | Completed | 492 | Placebo-controlled adjunctive armodafinil (150 and 200 mg/day) for bipolar I depression. Not an insomnia trial. |
| NCT01072929 | Phase 3 | Completed | 433 | Placebo-controlled adjunctive armodafinil (150 and 200 mg/day) for bipolar I depression. Not an insomnia trial. |
| NCT01305408 | Phase 3 | Completed | 399 | Placebo-controlled armodafinil 150 mg/day as adjunctive therapy for bipolar I depression. Not an insomnia trial. |
| NCT00772005 | Phase 2 | Completed | 287 | 24-week placebo-controlled adjunctive armodafinil for negative symptoms of schizophrenia. Not an insomnia trial. |
Literature Evidence
None of the retrieved publications is an armodafinil RCT in insomnia. Key findings below are limited to what each abstract states about its scope.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 24312590 | 2013 | Systematic review / meta-analysis | PLoS One | Assesses safety and effects of modafinil (armodafinil’s parent compound) on fatigue and daytime sleepiness in neurological disorders. Existing trials gave inconsistent results. |
| 27010071 | 2016 | Systematic review / meta-analysis | Parkinsonism & Related Disorders | Reviews drug treatments for daytime sleepiness and sleep disorders in Parkinson’s disease. Few clinical trials have been done. |
| 22021174 | 2011 | Evidence-based review | Movement Disorders | Movement Disorder Society review of treatments for non-motor symptoms of Parkinson’s disease. |
| 18729534 | 2008 | Evidence-based review | Drugs | Reviews randomized placebo-controlled trials of modafinil in excessive sleepiness, fatigue and impaired cognition. |
| 21904092 | 2011 | Review | Postgraduate Medicine | Describes shift work disorder (excessive sleepiness and/or insomnia tied to work schedule) and its emerging therapies. |
| 17181377 | 2006 | Review | Drugs | Burden of illness and management approaches in shift work sleep disorder. |
| 24138359 | 2013 | Review | Medical Journal of Australia | Health burden of shift work, including insomnia and shift work disorder, and how to manage it. |
| 39535843 | 2024 | Review | Expert Opinion on Pharmacotherapy | Drug and non-drug management of sleep disturbances in Parkinson’s disease. |
| 24272458 | 2014 | Review | Neurotherapeutics | Treatment of sleep disorders in Parkinson’s disease. Best treatments for insomnia there are undetermined; early evidence favors CBT and light therapy. |
| 17060310 | 2006 | Case series | American Journal of Hospice & Palliative Care | Modafinil for fatigue in Charcot-Marie-Tooth disease type 1A. Not about insomnia. |
US Market Information
The license records do not list approved indication text.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA021875 | Nuvigil (Golden State Medical Supply, Inc.) | Tablet | Not listed in the license record |
| NDA021875 | Nuvigil (Apotex Corp.) | Tablet | Not listed in the license record |
| ANDA206069 | Armodafinil (Direct_Rx) | Tablet | Not listed in the license record |
| ANDA202768 | Armodafinil (Natco Pharma USA LLC) | Tablet | Not listed in the license record |
| ANDA206069 | Armodafinil (Aurobindo Pharma Limited) | Tablet | Not listed in the license record |
Safety Considerations
Please refer to the package insert for safety information.
- Insomnia as an adverse effect: The pack’s rationale notes that insomnia is a labeled adverse effect of armodafinil, which works against its use for insomnia.
- Drug Interactions: The interaction query returned no results.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score most likely reflects closeness to sleep-wake disorders in the knowledge graph, not evidence of benefit in insomnia. Armodafinil is a wake-promoting drug and insomnia is a labeled adverse effect. The L2 rating rests on Phase 2 RCTs whose results are not provided. The most that can be supported is an adjunctive role for daytime sleepiness or fatigue in comorbid insomnia. This is a research question, and the missing package insert data blocks safety screening.
To proceed, the following is needed:
- Package insert warnings and contraindications, from the FDA website (the blocking gap)
- Mechanism of action data, from DrugBank
- Published results of NCT01091974, NCT01019187, NCT01011218 and NCT02552303, to see whether insomnia outcomes improved
- Approved indication text for the US licenses
- A safety review of insomnia and sleep worsening in patients with insomnia
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.