Midazolam
| Evidence Level: L3 | Predicted Indications: 1 |
Table of Contents
Midazolam: From Procedural Sedation to Insomnia
One-Sentence Summary
Midazolam is a short-acting benzodiazepine, marketed in the US mainly as injectable products. The supplied data does not list its approved indications, so sedation is inferred from general pharmacology. The TxGNN model predicts it may be effective for Insomnia. Support is limited to 11 publications (including 1980s oral-midazolam sleep studies) and 30 retrieved trials, none of which tests midazolam for insomnia directly.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the supplied data (all US license records have empty indication text) |
| Predicted New Indication | Insomnia |
| TxGNN Prediction Score | 99.74% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the Evidence Pack. Based on general pharmacology, midazolam is a short-acting benzodiazepine that enhances GABA-A receptor signalling as a positive allosteric modulator. This is the same mechanism that produces sedation and hypnosis, so it plausibly applies to difficulty falling or staying asleep. This link rests on general knowledge, not on the supplied data.
Because the original indications are not recorded, the relationship between the old and new use cannot be checked against the pack. Sedation and insomnia both involve dampening central nervous system arousal, and the high TxGNN score (0.997) is consistent with that.
Older human studies support the idea. Double-blind and dose-finding studies from 1981 to 1990 tested oral midazolam in sleep disorders, including a head-to-head comparison with flurazepam in chronic insomniacs. No modern trial has tested this, and none of the registered trials evaluates midazolam for insomnia.
Clinical Trial Evidence
No registered trial tests midazolam as a treatment for insomnia. The trials below are the closest matches, mostly sleep-quality studies in which midazolam is a comparator or perioperative drug. No results are reported in the pack.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT06407518 | N/A | Recruiting | 280 | Preoperative oral midazolam vs placebo for postoperative pain in colorectal cancer patients with sleep disturbance or anxiety |
| NCT02142595 | Phase 4 | Completed | 111 | Dexmedetomidine vs midazolam sedation: postoperative sleep quality after transurethral prostate resection |
| NCT01966315 | N/A | Terminated | 5 | Dexmedetomidine vs midazolam: sleep quality and quantity (24-hour polysomnography) in ventilated ICU patients |
| NCT00826553 | Phase 1 | Terminated | 6 | Polysomnography of sleep stages in ventilated patients sedated with α2 agonists vs GABA agonists |
| NCT00744380 | N/A | Completed | 23 | Dexmedetomidine vs midazolam for facilitating extubation in ICU patients (sleep not an endpoint) |
| NCT07336095 | Phase 3 | Not yet recruiting | 195 | Oral melatonin vs oral midazolam as premedication in children undergoing tonsillectomy |
| NCT04082767 | Phase 3 | Unknown | 120 | Dexmedetomidine vs midazolam sedation in ventilated critically ill children |
| NCT06480500 | Phase 2 | Recruiting | 110 | Internet-based CBT plus ketamine for suicidality in depression, with midazolam as the active control |
| NCT04149626 | Phase 2 | Unknown | 60 | Dexmedetomidine vs midazolam vs remifentanil sedation in orthopedic surgery under regional anesthesia |
| NCT05466279 | N/A | Completed | 131 | Remimazolam vs propofol plus midazolam for general anesthesia |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6138072 | 1983 | Double-blind clinical study | Br J Clin Pharmacol | Midazolam 15 mg vs Vesparax in 30 patients with insomnia secondary to neuromuscular disease. Both were effective hypnotics; midazolam was better tolerated and caused no hangover. |
| 2121802 | 1990 | Randomized double-blind multicenter study | J Clin Psychopharmacol | Design of a 14-day comparison of flurazepam and midazolam on sleep, performance and mood in chronic insomniacs |
| 2229461 | 1990 | Multicenter clinical study | J Clin Psychopharmacol | Executive summary of the same flurazepam vs midazolam study. No abstract is available in the pack. |
| 6120704 | 1981 | Dose-finding study | Arzneimittel-Forschung | Oral midazolam 10-30 mg in 75 hospitalized patients with mild to moderate secondary insomnia, used to establish the optimal dose range |
| 2883820 | 1986 | Review | Acta Psychiatr Scand Suppl | Clinical use of hypnotics; benzodiazepines with different pharmacokinetic profiles are clinically effective for insomnia |
| 17988972 | 2007 | Review | Orvosi Hetilap | Background review of insomnia and cerebral hypoperfusion (not about midazolam) |
| 36615100 | 2022 | Clinical study (different drug) | J Clin Med | Lemborexant for insomnia and delirium risk after endoscopy under sedation; a benzodiazepine alternative, not midazolam |
US Market Information
The pack lists 20 US licenses; 5 are shown below. Dosage forms across all licenses also include syrup. Indication text is empty in every record.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA075243 | Midazolam (Hikma Pharmaceuticals USA Inc.) | Injection | Not listed in the supplied data |
| NDA216359 | Product name not listed (Rafa Laboratories, Ltd.) | Injection, solution | Not listed in the supplied data |
| ANDA090850 | Midazolam Hydrochloride (Belcher Pharmaceuticals, LLC) | Injection, solution | Not listed in the supplied data |
| ANDA090850 | Midazolam Hydrochloride (Gland Pharma Limited) | Injection, solution | Not listed in the supplied data |
| ANDA203460 | Midazolam (Fresenius Kabi USA, LLC) | Injection, solution | Not listed in the supplied data |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanism is plausible and the TxGNN score is very high, but the only direct evidence is a set of small studies from 1981 to 1990. No registered trial tests midazolam for insomnia. Package-insert safety information is also missing, so safety screening cannot start.
To proceed, the following is needed:
- Package-insert warnings and contraindications, obtained from the FDA label
- Confirmed mechanism-of-action data from DrugBank, and the approved indications for the original use
- A check of route compatibility: the 1980s sleep studies used oral midazolam, while the listed US products are mostly injectable
- A review of the 1980s insomnia studies against current standards, including full text for PMID 2229461
- A modern, controlled trial of midazolam in insomnia, or a documented rationale for preferring it over current hypnotics
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.