Nitrazepam

證據等級: L5

預測適應症: 6 個

Nitrazepam: From Unregistered Original Indication to Sleep Disorder, Initiating and Maintaining Sleep (Insomnia)

One-Sentence Summary

Nitrazepam’s own approved indication is not on record in this Evidence Pack (original_indications is a data gap), but it is a long-marketed benzodiazepine hypnotic (Mogadon). The TxGNN model predicts it is effective for Sleep Disorder, Initiating and Maintaining Sleep (insomnia) with a 99.89% prediction score, supported by 20 publications (including 1 RCT) and no registered clinical trials. Note: this predicted indication overlaps with nitrazepam’s well-known historical use, so the finding should be read as a confirmation of known pharmacology rather than a novel repurposing signal.

Quick Overview

Item	Content
Original Indication	Not on record (data gap — no `original_indications` entries; drug is not currently marketed in Denmark)
Predicted New Indication	Sleep Disorder, Initiating and Maintaining Sleep (Insomnia)
TxGNN Prediction Score	99.89%
Evidence Level	L2
Denmark Market Status	Not Marketed
Number of Marketing Authorisations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

The original_moa field is a data gap, but the model’s own repurposing rationale supplies the mechanism: nitrazepam is a classic benzodiazepine that binds the benzodiazepine site on the GABA-A receptor’s α subunit, positively modulating GABA-gated chloride influx and enhancing central inhibitory neurotransmission. This produces sedative, hypnotic, anxiolytic, anticonvulsant and muscle-relaxant effects.

Importantly, the “predicted new indication” here — sleep-onset and sleep-maintenance insomnia — is not actually a new therapeutic hypothesis. Nitrazepam has been marketed for decades under the brand name Mogadon specifically as a hypnotic for insomnia. The literature evidence below (pharmacokinetics reviews, a head-to-head RCT against triazolam, safety reviews) reflects this established use rather than an unproven extrapolation. The apparent “prediction” arises because the original_indications field in this Evidence Pack is empty (data gap), so the model/report pipeline is unable to recognize that this is already the drug’s core indication.

Mechanistically the link is therefore direct and well-established, not inferred: GABA-A receptor potentiation reduces sleep latency and increases total sleep time, consistent with nitrazepam’s known clinical pharmacology.

Clinical Trial Evidence

Currently no related clinical trials registered

Literature Evidence

PMID	Year	Type	Journal	Key Findings
6135296	1983	RCT	Acta Psychiatrica Scandinavica	Double-blind cross-over in 26 geriatric inpatients: nitrazepam 5mg vs triazolam 0.25mg — comparable sleep quantity/quality and psychomotor performance
7037262	1981	Review	Clinical Pharmacokinetics	Review of nitrazepam’s clinical pharmacokinetics
4892037	1969	Review	British Medical Journal	27 patients with acute nitrazepam overdose (up to 80 tablets) showed only drowsiness; double-blind trial found nitrazepam as effective as butobarbitone as a hypnotic
1125532	1975	Case Report	British Journal of Psychiatry	Case report of nitrazepam (Mogadon) dependence
4712500	1973	Case Report	British Medical Journal	Case report on nitrazepam’s effects on dreaming/subconscious content
238826	1975	Review	Drugs	Review of sleep physiology and hypnotic drug efficacy assessment
19450355	2007	Review	BMJ Clinical Evidence	Up to 40% of adults have insomnia; prevalence rises with age; risk factors include psychological stress and hyperarousal
7725291	1995	Review	Tidsskrift for den Norske Laegeforening	Review of insomnia classification, diagnosis and treatment developments
15089115	2004	Review	CNS Drugs	Review of residual “hangover” effects of hypnotics (daytime sleepiness, psychomotor/cognitive impairment) and accident risk
39231170	2024	—	PLoS ONE	Study of inappropriate benzodiazepine prescribing patterns in primary care, including dependence and cognitive-decline risk in older adults

Denmark Market Information

Nitrazepam has 0 marketing authorisations on file and is currently not marketed in Denmark. No Laegemiddelstyrelsen or EMA centralised authorisation records are available in this Evidence Pack.

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information. No key warnings, contraindications, or drug-drug interaction data are currently on file (DDI query status: not found).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Literature evidence (including a direct RCT of nitrazepam as a hypnotic) supports plausibility for insomnia, but this largely reconfirms nitrazepam’s known, decades-old clinical use rather than establishing a genuinely new indication. Critical data gaps — no Danish SmPC/warnings/contraindications (Blocking, DG001), no formal MOA record (High, DG002), and no confirmed original indication — block any registration-level decision, and the drug is not currently marketed in Denmark.

To proceed, the following is needed:

Danish/EU SmPC warnings, contraindications and DDI data (resolve DG001, blocking)
Formal MOA documentation via DrugBank (resolve DG002)
Confirmation of nitrazepam’s actual approved indication(s) in source markets, to clarify whether this is a genuine new-use signal or a data-registration gap
Marketing-authorisation pathway assessment given current “Not Marketed” status in Denmark

Note: The model also flagged two lower-confidence candidates — acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and Wernicke-Korsakoff syndrome — both at Evidence Level L5 with no supporting literature or trials; both are recommended Hold.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.