Chlordiazepoxide
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Chlordiazepoxide: From Anxiety to Insomnia
One-Sentence Summary
Chlordiazepoxide is a benzodiazepine (the first of its class), used clinically for anxiety and alcohol withdrawal. The TxGNN model predicts it may be effective for Insomnia. No clinical trials directly test this idea, and the 6 retrieved publications are mostly class-level reviews and anxiety-population studies, so evidence is indirect.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the supplied US label data (the literature places its use in anxiety and alcohol withdrawal) |
| Predicted New Indication | Insomnia |
| TxGNN Prediction Score | 99.998% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (ANDA generic approvals) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for chlordiazepoxide is not available in the source record. Based on general pharmacology, chlordiazepoxide is a benzodiazepine that enhances GABA-A receptor signalling. This produces anxiolytic, sedative and hypnotic effects.
The link between anxiety and insomnia is plausible at the class level. Benzodiazepines are used as hypnotics, and the retrieved reviews discuss them for that purpose. The sedative-hypnotic effect is therefore the most credible mechanistic bridge between the original use and the predicted one.
However, the direct evidence is thin. The sleep-related studies involve either a combination product (chlordiazepoxide-amitriptyline) or populations with anxiety or alcohol problems, not patients with primary insomnia. The literature also raises safety concerns, especially in older adults. The prediction is biologically reasonable but clinically unproven for this specific drug.
A closely related prediction, “sleep disorder, initiating and maintaining sleep” (rank 6, score 99.88%), describes essentially the same clinical concept and rests on the same rationale.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01109030 | Phase 2/3 | Completed | 50 | Pioglitazone added to citalopram in moderate to severe depression. Not relevant: it involves neither chlordiazepoxide nor insomnia |
No registered clinical trial directly tests chlordiazepoxide for insomnia. The one retrieved trial was graded as providing no evidence for this indication.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 2883822 | 1986 | Review | Acta Psychiatr Scand Suppl | Benzodiazepine hypnotics in the elderly. Older people show a 2-3 fold greater response to benzodiazepines, not explained by plasma concentrations |
| 23330992 | 2013 | Review | Expert Opin Drug Metab Toxicol | Pharmacokinetics of anxiolytic drugs, used widely for anxiety disorders. Only class-level relevance to insomnia |
| 6111745 | 1981 | Review | Med Lett Drugs Ther | Guidance on choosing among benzodiazepines. No abstract available |
| 30680986 | 2019 | Cohort (cross-sectional) | Med Glas (Zenica) | Potentially inappropriate medication use (Beers criteria) among Iranian older adults. A safety context, not efficacy evidence |
| 4628683 | 1972 | Clinical trial | Curr Ther Res Clin Exp | Molindone vs chlordiazepoxide in anxious outpatients. Anxiety, not insomnia |
| 14085195 | 1963 | Clinical study | Acta Psychiatr Scand | Treatment of anxiety neuroses with a chlordiazepoxide (Librium) metabolite. Anxiety, not insomnia |
For the related “sleep disorder” prediction, the literature includes a randomized study of chlordiazepoxide-amitriptyline (Limbitrol) vs amitriptyline (PMID 3536890, 1986). Symptoms improved faster with Limbitrol, but there was no difference in sleep-laboratory parameters. There is also a review of benzodiazepines for insomnia in community-dwelling elderly (PMID 7595266, 1995), which found no long-term effectiveness studies.
US Market Information
The record lists 20 authorizations; five main ones are shown. Approved indication text was not provided in the supplied data.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA084041 | Chlordiazepoxide Hydrochloride | Capsule | Chartwell RX, LLC |
| ANDA084769 | Chlordiazepoxide Hydrochloride | Capsule | Mylan Institutional Inc. |
| ANDA084768 | Chlordiazepoxide Hydrochloride | Capsule | Teva Pharmaceuticals USA, Inc. |
| ANDA084768 | Chlordiazepoxide Hydrochloride | Capsule | Bryant Ranch Prepack |
| ANDA085472 | Chlordiazepoxide Hydrochloride | Capsule, gelatin coated | Epic Pharma LLC |
All listed products are oral capsules.
Safety Considerations
Package insert warnings, contraindications and drug-interaction data were not available in the source record. Please refer to the package insert for safety information.
The retrieved literature points to these concerns for benzodiazepines as a class:
- Older adults: heightened sensitivity to benzodiazepine effects, and classification as potentially inappropriate medications under the Beers criteria. Reviews also describe risks of dependence and falls.
- Dependence and abuse: benzodiazepines carry recognized dependence, withdrawal and abuse liability.
Conclusion and Next Steps
Decision: Hold
Rationale: The GABA-A sedative-hypnotic rationale is plausible, but no trial tests chlordiazepoxide in insomnia and the literature is indirect (class reviews, combination products, anxiety and alcohol populations). Blocking safety data (package insert warnings and contraindications) is also missing, so the candidate cannot advance past an initial research question.
To proceed, the following is needed:
- The full package insert, to allow safety screening
- Mechanism-of-action data, for example from DrugBank
- Direct clinical evidence of chlordiazepoxide in insomnia, ideally randomized trials with sleep outcomes in primary insomnia
- A comparison against existing insomnia therapies, including benzodiazepines already approved for this use
- An assessment of dependence, falls and cognitive risk, especially for older adults
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.