Diazepam
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Diazepam: Insomnia (disease)
One-Sentence Summary
Diazepam is a benzodiazepine that enhances GABA-A receptor activity and is marketed in Canada. The TxGNN model predicts it may be effective for insomnia. Support is limited: no registered clinical trials and 16 publications, only one of which is a clinical efficacy trial in insomnia patients (a 1981 double-blind comparison with lormetazepam).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Insomnia (disease) |
| TxGNN Prediction Score | 1.0000 |
| Evidence Level | L2 |
| Canada Market Status | Marketed (marketed DINs: 8 of 8) |
| Number of DINs | 8 (marketed: 8) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Diazepam is known to be a positive allosteric modulator of GABA-A receptors. This produces sedative, anxiolytic and hypnotic effects, which makes a role in sleep disorders biologically plausible.
Benzodiazepines as a class are already used for short-term insomnia. The 1981 double-blind study (PMID 6113175) tested diazepam 5 mg directly in outpatients with sleep disorders. However, the other retrieved literature is general (benzodiazepine pharmacology reviews, GABA-A modulator reviews, herbal insomnia studies). The very high TxGNN score is a model prediction, not clinical evidence.
Long-term risks limit enthusiasm. These include dependence, disruption of sleep architecture, and a reported association between long-term benzodiazepine and Z-drug use and breast cancer progression.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6113175 | 1981 | Double-blind trial | J Int Med Res | 7-day comparison of lormetazepam 1 mg vs diazepam 5 mg in 100 outpatients with sleep disorders. Lormetazepam was significantly better at shortening time to fall asleep. |
| 39581171 | 2024 | Review | Bioorg Chem | GABA-A modulators, including diazepam, are used in epilepsy, anxiety and insomnia. Sedation and other side effects are noted. |
| 36692463 | 2023 | Meta-analysis | Acta Pharm | Tranquilizers in elderly patients with chronic diseases, assessed by dose, outcomes and adverse effects. |
| 40583063 | 2025 | Cohort | Cell Mol Biol Lett | Long-term benzodiazepine and Z-drug use, including diazepam, was linked to exacerbation of breast cancer. |
| 23330992 | 2013 | Review | Expert Opin Drug Metab Toxicol | Pharmacokinetics of anxiolytic drugs. |
| 35196378 | 2022 | Non-randomized intervention | Fam Pract | Safe discontinuation of chronic benzodiazepine use in primary care. |
| 37984023 | 2024 | Predictive model | Value Health Reg Issues | Long-term benzodiazepine use is associated with memory loss, dependence, falls and accident risk. |
| 32623439 | 2020 | Animal study | Med Sci Monit | Berberine in insomnia rats, with diazepam used as a comparator treatment. |
Canada Market Information
Eight valid single-ingredient licences are on record. The approved indication text is not recorded in the local data.
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 00362158 | DIAZEPAM | Not recorded | Not recorded |
| 00405329 | DIAZEPAM | Not recorded | Not recorded |
| 02519089 | DIASTAT | Not recorded | Not recorded |
| 00405337 | DIAZEPAM | Not recorded | Not recorded |
| 00399728 | DIAZEPAM INJECTION USP | Not recorded | Not recorded |
Safety Considerations
- Drug Interactions: 100 interactions are on record. Examples:
- Major: morphine.
- Moderate: bupropion, aprepitant, omeprazole, esomeprazole, cimetidine, clarithromycin, cisapride, clotrimazole, miconazole, dronabinol, metoclopramide.
- Minor: dexamethasone, betamethasone and several antacids (magnesium oxide, aluminum hydroxide, calcium carbonate).
- Literature-reported concerns: dependence and withdrawal, cognitive decline, falls in older adults, and a possible association with breast cancer progression with long-term use.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence is limited to one small, older double-blind comparison trial in insomnia patients, which supports an L2 level. No placebo-controlled trials of diazepam for insomnia were found. Long-term safety concerns and the lack of label safety data weigh against proceeding.
To proceed, the following is needed:
- Package insert warnings and contraindications from Health Canada
- Detailed mechanism of action data
- Placebo-controlled or modern comparative trial data for diazepam in insomnia
- A benefit-risk assessment for short-term use, with a dependence and falls mitigation plan 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.