Zopiclone
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Zopiclone: From Insomnia to Sleep Disorder (Initiating and Maintaining Sleep)
One-Sentence Summary
Zopiclone is a Z-drug hypnotic originally used to treat insomnia. The TxGNN model predicts it may be effective for sleep disorder, initiating and maintaining sleep, but this is essentially the same condition as the original indication, so it is not a true repurposing candidate. Currently there are 0 registered clinical trials and 20 publications (mostly reviews, network meta-analyses and guidelines) for this prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Insomnia (the Singapore licence records contain no approved indication text; the original indication comes from the TxGNN knowledge graph) |
| Predicted New Indication | Sleep disorder, initiating and maintaining sleep |
| TxGNN Prediction Score | 98.83% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from the data compiled for this report. Based on known information, zopiclone is a Z-drug that acts as a positive allosteric modulator of the GABA-A receptor. This is the same general mechanism as benzodiazepines, although it is structurally unrelated to them.
The predicted indication, difficulty initiating and maintaining sleep, is essentially the same as the original indication of insomnia. The high score therefore reflects the model recovering a known use rather than discovering a new one. The literature supports zopiclone's role in insomnia, but it does not point to a new therapeutic area.
Other predictions in the list (for example agoraphobia, restless legs syndrome, absence epilepsy, and several conditions with no plausible mechanistic link) rest only on computational scores. Most have no trials or literature. Restless legs syndrome is the only one with any retrieved publications, and those are indirect.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The publications below are listed by study type (network meta-analyses and systematic reviews first, then guidelines and reviews). Relevance has not yet been confirmed for these records.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35843245 | 2022 | Network meta-analysis | Lancet | Compares pharmacological treatments for acute and long-term management of adult insomnia disorder |
| 36947394 | 2023 | Systematic review / NMA (153 RCTs) | Drugs | Compares effectiveness, safety and tolerability of insomnia drugs across classes |
| 34023645 | 2021 | Systematic review | Eur Neuropsychopharmacol | Efficacy and safety of zopiclone for insomnia in older adults versus other hypnotics, placebo or non-drug treatment |
| 34121443 | 2021 | Network meta-analysis | J Manag Care Spec Pharm | Compares lemborexant with other insomnia treatments (zopiclone is among the comparators) |
| 38401406 | 2024 | Systematic review / NMA of RCTs | Eur Neuropsychopharmacol | Residual effects of sleep medications on driving performance |
| 39923608 | 2025 | Clinical practice guideline | Sleep Med | European expert consensus on switching or deprescribing hypnotics for chronic insomnia; lists zopiclone among recommended options |
| 41187937 | 2025 | Clinical guideline | Arq Neuropsiquiatr | Z-drug abuse and dependence; use is recommended for no longer than four weeks |
| 29487083 | 2018 | Review | Pharmacol Rev | Reviews insomnia drugs beyond benzodiazepines; notes Z-drug side effects such as cognitive impairment, tolerance, rebound insomnia and dependence |
| 38551874 | 2024 | Review | Rev Prat | Z-drugs (zolpidem, zopiclone) taken at the right time and dose promote sleep initiation, with fewer harmful effects than long-acting benzodiazepines |
| 1523276 | 1992 | Review | Psychopharmacology | Rebound insomnia after stopping hypnotics, including newer agents |
Several other retrieved records concern lemborexant or eszopiclone rather than zopiclone, so they were not included.
For restless legs syndrome (rank 8), the retrieved literature is indirect. One is a 1997 double-blind insomnia study comparing zopiclone with propiomazine (9327191), and the other is a 2025 survey of symptom management in chronic kidney disease (40269733). Neither is specific to restless legs syndrome.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN05047P | IMOVANE TABLET 7.5 mg (Opella Healthcare International SAS) | Film-coated tablet | Not stated in the available records |
| SIN09355P | APO-ZOPICLONE TABLET 7.5 mg (Apotex Inc) | Film-coated tablet | Not stated in the available records |
| SIN11416P | ZOPICLONE TABLET 7.5 mg (Dragenopharm Apotheker Püschl GmbH & Co KG) | Tablet | Not stated in the available records |
All three licences are valid single-ingredient oral products.
Safety Considerations
- Contraindications recorded in the knowledge graph (not taken from package insert text): liver failure, anxiety disorder, neurotic disorder, dysthymic disorder.
- Class-related risks from the literature: cognitive impairment, tolerance, rebound insomnia on discontinuation, falls, car accidents, abuse and dependence. Residual next-day effects on driving are also described. Use is generally recommended for no longer than four weeks.
- Drug interactions: The interaction query returned 100 records, but none has a severity grade (all are "Unknown"). Examples include morphine, metformin, omeprazole, pantoprazole, prednisone and epinephrine. Interaction severity cannot be judged from this data. Morphine is the one example that deserves attention given likely additive central nervous system depression, but this is general pharmacological reasoning rather than a graded finding.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top prediction is simply zopiclone's existing indication, so it offers no new repurposing opportunity. The other nine predictions are model outputs only. Almost none has trials or literature, and several are mechanistically implausible or potentially unsafe, for example in infants, in anxiety disorders given dependence risk, and in absence epilepsy. Restless legs syndrome is the only one marked as a possible research question, but its evidence is indirect.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Singapore regulator (HSA), as well as approved indication text for the three licences
- Mechanism of action data from DrugBank
- Graded drug interaction severity, especially for other central nervous system depressants
- For restless legs syndrome, a targeted literature search and review of trials specific to that condition before any further evaluation
- A reframing of the evaluation toward genuinely new indications, since the top-ranked prediction duplicates the current one
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.