Nitrazepam
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Nitrazepam: Wernicke-Korsakoff syndrome
One-Sentence Summary
Nitrazepam is a benzodiazepine originally used to treat insomnia and early myoclonic encephalopathy. The TxGNN model (deep learning) predicts it may be effective for Wernicke-Korsakoff syndrome. Currently there are 0 registered clinical trials and 20 publications (mostly reviews and older clinical reports) linked to this prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Wernicke-Korsakoff syndrome |
| TxGNN Prediction Score | 0.9931 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the compiled data. Based on established class pharmacology, nitrazepam is a benzodiazepine that enhances inhibitory neurotransmission by positively modulating GABA-A receptors, producing sedative-hypnotic effects.
The TxGNN model (deep learning) predicted Wernicke-Korsakoff syndrome with a score of 0.9931. This is supported by computational prediction only, with no trials or literature. Benzodiazepines are used for alcohol withdrawal that can accompany the condition. They do not address the underlying disease, and sedation, respiratory depression, cognitive impairment and misuse risk are concerns in this population.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 4892037 | 1969 | Clinical report (double-blind trial) | Br Med J | Nitrazepam was as effective as butobarbitone as a hypnotic; no untoward effects beyond drowsiness in 27 acute overdose patients |
| 1743245 | 1991 | Double-blind crossover | Eur J Clin Pharmacol | Nitrazepam 5 mg and oxazepam 25 mg were both effective in inducing sleep and improving sleep quality in 28 insomnia patients |
| 15252823 | 2004 | Systematic review / meta-analysis | Hum Psychopharmacol | Compared Z-drugs with benzodiazepines (including nitrazepam) for short-term insomnia management |
| 10804040 | 2000 | Review | Drugs | Zolpidem efficacy was generally comparable to benzodiazepines including nitrazepam |
| 3281819 | 1988 | Review | Drugs | Brotizolam improved sleep similarly to nitrazepam 2.5 and 5 mg |
| 15089115 | 2004 | Review | CNS Drugs | Residual “hangover” effects of hypnotics: daytime sleepiness, psychomotor and cognitive impairment |
| 20171127 | 2010 | Review | Sleep Med Rev | Hypnotics impair body balance, with falls and hip fractures reported |
| 7037262 | 1981 | Review | Clin Pharmacokinet | Clinical pharmacokinetics of nitrazepam |
| 1125532 | 1975 | Clinical report | Br J Psychiatry | Nitrazepam (Mogadon) dependence |
| 19450355 | 2007 | Review | BMJ Clin Evid | Overview of insomnia in the elderly |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 00511536 | MOGADON | Not specified | Not specified |
| 00511528 | MOGADON | Not specified | Not specified |
Safety Considerations
- Drug Interactions: 55 potential interactions were identified, but none has a severity level recorded. Examples include morphine, metformin, metronidazole, bupropion, omeprazole, pantoprazole, lansoprazole, dexamethasone and hydrocortisone. Concomitant opioids warrant particular caution given additive central nervous system depression.
- Class-related concerns from the literature: Residual daytime sedation, impaired balance and falls, and dependence with long-term use.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction largely restates nitrazepam’s existing insomnia indication, so it offers little new repurposing value. The other two predictions have no clinical trials or literature behind them, and the evidence level is L4 at best.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications, which are currently missing and block safety screening
- Mechanism of action data from DrugBank
- Approved indication text and dosage forms for the two Canadian DINs
- Severity grading for the identified drug interactions
- If pursuing the encephalopathy or Wernicke-Korsakoff predictions, any supporting clinical or preclinical studies, along with a risk assessment of sedation and respiratory depression in those populations
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.