Armodafinil
| Evidence Level: L2 | Predicted Indications: 1 |
Table of Contents
Armodafinil: From Narcolepsy to Insomnia
One-Sentence Summary
Armodafinil is a wake-promoting agent (the R-enantiomer of modafinil), originally used to treat narcolepsy and related excessive sleepiness. The TxGNN model predicts it may be effective for insomnia, with 3 clinical trials and 2 publications listed directly under this prediction. The evidence suggests armodafinil is more useful for the daytime sleepiness that accompanies insomnia treatment than for insomnia itself.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Narcolepsy (excessive sleepiness); the approved indication text for the Australian entry is not available |
| Predicted New Indication | Insomnia (disease) |
| TxGNN Prediction Score | 0.9989 |
| Evidence Level | L2 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold (research question) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Armodafinil is a wake-promoting agent that is understood to act mainly through dopamine transporter inhibition. Its efficacy in excessive sleepiness from narcolepsy has been established.
The link to insomnia is indirect. Armodafinil does not treat the disturbance of sleep initiation or maintenance itself. In the trials, it was used to counter the daytime sleepiness and fatigue that accompany insomnia and sleep restriction therapy, usually together with cognitive behavioural therapy for insomnia (CBT-I). The prediction is therefore best read as symptom relief for daytime consequences, not a direct treatment of insomnia.
The largest trial’s associated literature reports that CBT-I, not armodafinil, improved fatigue in cancer survivors with insomnia. The armodafinil-specific benefit is therefore weak or unproven.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01091974 | Phase 2 | Completed | 138 | Four-arm randomised trial of CBT-I with or without armodafinil for insomnia and fatigue after chemotherapy in breast cancer patients. Associated literature suggests CBT-I, not armodafinil, improved fatigue. |
| NCT01011218 | Phase 2 | Completed | 70 | Pilot study of brief behavioural therapy for insomnia (BBT-I) or CBT-I, with or without armodafinil 150 mg/day, in breast cancer patients. Preliminary, specific population. |
| NCT02552303 | Not applicable | Completed | 39 | Armodafinil and/or CBT-I for insomnia comorbid with sleep disordered breathing (obstructive sleep apnoea). Small sample. |
Literature Evidence
Publications listed under the insomnia prediction:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25452447 | 2015 | RCT | J Clin Oncol | Placebo-controlled trial of CBT-I and armodafinil for insomnia in cancer survivors. |
| 27318221 | 2016 | RCT | Sleep Med | Effects of armodafinil and CBT-I on sleep continuity, daytime sleepiness and CBT-I adherence in cancer survivors. |
| 26542272 | 2016 | RCT (secondary analysis) | Support Care Cancer | CBT-I, but not armodafinil, improved fatigue in cancer survivors with insomnia. |
| 28105576 | 2017 | RCT (secondary analysis) | J Cancer Surviv | Effects of CBT-I with and without armodafinil on quality of life in cancer survivors. |
| 36003019 | 2023 | Open-label pilot | J Sleep Res | Armodafinil 150 mg/day added to sleep restriction therapy to reduce daytime sleepiness, compared with historical controls (33 patients). |
| 20957846 | 2010 | Open-label extension | J Clin Sleep Med | Long-term (12 months or more) tolerability and efficacy of armodafinil in sleepiness associated with sleep apnoea, shift work disorder or narcolepsy. |
| 17181377 | 2006 | Review | Drugs | Burden of illness and management of shift work sleep disorder. |
| 21904092 | 2011 | Review | Postgrad Med | Emerging theories and therapies for shift work disorder. |
| 29734973 | 2018 | Case report (safety) | J Clin Sleep Med | Stevens-Johnson syndrome after armodafinil use in a 21-year-old woman. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 10912H | Nuvigil | Tablet 150 mg (oral) | Not available in the data compiled for this report |
Safety Considerations
- Contraindications suggested by the knowledge graph (not label text): hypertension and hypertensive disorders, liver failure, anxiety and neurotic disorders, dysthymic disorder, psychotic disorders (including schizophreniform and schizoaffective disorders), mental disorder, mitral valve prolapse (including familial and congenital forms), and postural orthostatic tachycardia syndrome. These should be verified against the TGA-approved Product Information.
- Serious skin reactions: A published case report describes Stevens-Johnson syndrome after armodafinil use, and this reaction is listed on the drug’s label.
- Seizure risk: Psychostimulants carry a small seizure risk, and guidance on armodafinil in patients at risk of seizures is limited.
- Drug interactions: The interaction screen returned 100 interactions. Those listed include moderate interactions with rabeprazole, esomeprazole, cisapride, dexamethasone, eliglustat and linagliptin. Minor interactions include hydrocortisone, pioglitazone, aprepitant, cimetidine and clarithromycin, among others.
Warnings and contraindications from the approved label were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for full safety information.
Conclusion and Next Steps
Decision: Hold (research question)
Rationale: Phase 2 trials exist, but the armodafinil-specific benefit for insomnia is weak or negative, and the mechanism targets daytime sleepiness rather than the sleep disturbance itself. Evidence supports at most a narrow adjunct role alongside CBT-I or sleep restriction therapy.
To proceed, the following is needed:
- Mechanism of action data, which is currently missing
- Approved indication text and label warnings and contraindications from the TGA Product Information, which are required for safety screening
- A trial focused on armodafinil as an adjunct to sleep restriction therapy, in a broader population than cancer survivors, with a clear primary outcome such as daytime sleepiness
- A risk assessment for the knowledge-graph contraindications (cardiovascular, psychiatric and hepatic conditions) and for serious skin reactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.