Peptide & Experimental
Zopiclone
Z-drug (cyclopyrrolone), prescription-only for the short-term treatment of sleep disorders · Ximovan, Imovane
Zopiclone has been approved in Germany since 1990 and belongs to the Z-drugs, the successors of the benzodiazepines. It works quickly and reliably: in the largest network meta-analysis of sleeping pills, it is among the agents with a clear effect compared with placebo. However, it is approved only for a short time, at most four weeks including discontinuation, because tolerance and dependence become a risk with longer use. The morning after, driving performance in driving tests is as impaired as under 0.5 per mille of alcohol.
What zopiclone is
Zopiclone is a sleeping pill from the cyclopyrrolone group. Together with zolpidem and zaleplon it is called a Z-drug, because chemically it is not a benzodiazepine but acts on the same receptor complex. In Germany it is available on prescription as Ximovan and as a generic, approved for the short-term treatment of clinically significant sleep disorders in adults.
What is rated is the state of knowledge. After more than three decades of use, it is broad: many controlled studies on efficacy, plus driving tests, registry data on accidents and analyses of dependence. The newer alternatives are the orexin receptor antagonists; trazodone is frequently prescribed off-label. The basics of sleep are covered under Sleep & sleep hygiene.
How it works
Zopiclone binds to the GABA-A receptor complex, at a different site from the benzodiazepines, and enhances the inhibitory effect of the messenger GABA via the chloride channel. According to the summary of product characteristics, this results in sleep-inducing, anxiolytic, muscle-relaxant and anticonvulsant properties.
The effect sets in rapidly. Zopiclone shortens the time to fall asleep, lengthens sleep duration and reduces night-time and early-morning awakening. Compared with benzodiazepines, it appears to alter sleep architecture less; according to the summary of product characteristics, the REM phase in particular is less affected.
What is well supported
- Effective compared with placebo. In the network meta-analysis in the Lancet covering 154 double-blind studies with 44,089 participants, zopiclone is among the agents that were more effective than placebo in acute treatment, with high to moderate certainty of evidence.
- Stronger than melatonin. In the same analysis, zopiclone, zolpidem, eszopiclone and benzodiazepines were more effective than melatonin, ramelteon and zaleplon.
- As effective as benzodiazepines. A review of the clinical studies up to 1998 found zopiclone generally at least as effective as benzodiazepines. Short-term studies of up to four weeks showed no tolerance.
- Recommended in the guideline for short-term use. The 2023 European insomnia guideline recommends benzodiazepine receptor agonists such as zopiclone with the highest grade of recommendation for short-term treatment of up to four weeks.
What the studies show
De Crescenzo 2022: the big comparison
The network meta-analysis compared 30 sleeping pills. In acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem and zopiclone were more effective than placebo (effect sizes 0.36 to 0.83). Zopiclone, however, led to study dropouts due to side effects twice as often as placebo (OR 2.00) and more often than eszopiclone (OR 1.82), daridorexant (OR 3.45) and suvorexant (OR 3.13).
Noble 1998: review of the clinical studies
The review summarizes the studies since market launch: zopiclone was mostly at least as effective as benzodiazepines, no tolerance appeared in studies of up to four weeks, and data from longer studies were contradictory. Rebound insomnia after discontinuation occurred in short-term studies, but not often. The most common side effect was a bitter aftertaste, at 3.6 percent in the largest post-marketing surveillance study.
McElroy 2021: driving tests in the morning
The meta-analysis evaluated 14 studies with standardized on-the-road driving tests. An increase in lane weaving of 2.4 cm, equivalent to 0.5 per mille of alcohol, was considered significant. Zopiclone exceeded this threshold in healthy people in 10 of 10 studies; in 5 of 10 studies, test drives were stopped early. Lemborexant showed no such effect; the work was funded by Eisai, the manufacturer of lemborexant.
Gustavsen 2008: accidents in the registry
All Norwegians aged 18 to 69, 3.1 million people, were followed for almost three years. In the week after a prescription for zopiclone or zolpidem was dispensed, the risk of road traffic accidents was 2.3 times higher, and 4.0 times higher for flunitrazepam. It was highest among the youngest users.
Treves 2018: falls and fractures in older people
The meta-analysis of 14 observational studies found an increased risk of fractures with Z-drugs (OR 1.63) and a trend toward more falls. The studies were very heterogeneous and prone to bias.
Where the data stop
- Effect beyond a few weeks. Zopiclone is approved for at most four weeks, and that is exactly as far as the reliable data reach. Whether it remains effective with long-term use is unclear; data from longer studies were already contradictory in 1998.
- The gentler alternative to benzodiazepines. Zopiclone was initially considered almost free of dependence potential. An analysis of the world literature up to 2002 found 22 case reports of dependence on zopiclone and 36 on zolpidem, with dose escalations of 30 to 120 times in extreme cases, predominantly in people with a history of addiction or psychiatric illness. Measured against prescription figures, the rate of reported dependence was clearly below that of benzodiazepines.
- Tolerability in comparison. In the network meta-analysis, participants on zopiclone dropped out due to side effects more often than those on daridorexant or suvorexant.
Status, approval and legal
Zopiclone has been approved in Germany since March 23, 1990 (Ximovan), for the short-term treatment of clinically significant sleep disorders in adults. It is prescription-only (German Prescription Drugs Ordinance, AMVV, Annex 1). It is not listed in the German Narcotics Act (BtMG), unlike the related zolpidem, which falls under Annex III in preparations containing more than 8.5 mg per tablet.
According to the summary of product characteristics, the approved dose is 7.5 mg as a single dose immediately before going to bed; no second dose in the same night. In older or debilitated people, treatment starts at 3.75 mg. Treatment, including the gradual discontinuation phase, should not exceed four weeks; an extension requires a renewed medical assessment. Zopiclone is not approved for children and adolescents under 18.
Safety
Tolerance as well as physical and psychological dependence increase with dose and duration. On abrupt discontinuation, insomnia can return in a stronger form, accompanied by restlessness, anxiety and mood swings; in severe cases, according to the summary of product characteristics, confusion, hallucinations or seizures are possible. Treatment should therefore be ended gradually and under medical supervision.
According to the summary of product characteristics, no vehicle should be driven for at least 12 hours after taking it; the driving tests and the Norwegian accident registry show why. Memory gaps after taking it and complex sleep behaviors such as sleepwalking or driving while half asleep are also possible; if anything like this occurs, treatment must be stopped immediately. Alcohol, opioids and other sedating drugs dangerously enhance the effect.
In older people, Z-drugs are associated with more bone fractures. The most common harmless side effect is a bitter taste. Zopiclone is not recommended during pregnancy.
BK-Score Supported, with caveats
| Human evidence | 7 | |
|---|---|---|
| Mechanism | 8 | |
| Safety data | 8 | |
| Hype gap | 6 | |
| Track record of use | 9 |
Evidence 7, because the short-term effect is demonstrated in many randomized studies and zopiclone is among the agents with a clear advantage over placebo in the network meta-analysis of 154 studies (De Crescenzo 2022), but data on the effect beyond a few weeks are lacking. Mechanism 8, because the enhancement of the GABA effect at the GABA-A receptor complex is well understood (summary of product characteristics). Safety 8, because the risks have been well measured over decades – driving tests with impairment in 10 of 10 studies (McElroy 2021), a 2.3-fold increased accident risk in the registry (Gustavsen 2008), more fractures in older people (Treves 2018) and cases of dependence (Hajak 2003). Hype 6, because zopiclone was considered a gentler alternative to benzodiazepines, but tolerance, dependence and impaired driving the next morning must be taken similarly seriously. Use 9, because it has been approved in Germany since 1990 and is widely prescribed. Direction positive: the short-term effect is demonstrated; the limits lie in duration and safety.
The score rates the state of knowledge, not the substance. “Safety data 9” means well studied – not harmless. “Track record of use 9” means used long and widely – that is not proof of efficacy.
Subjective assessment by Biohacking Kompakt based on published scoring rules – not a scientific rating and not a medical recommendation. Rules and all ratings (German)
Frequently asked questions about zopiclone
How well does zopiclone work?
Reliably in the short term. In the network meta-analysis of 154 double-blind studies, zopiclone is among the sleeping pills with a clear effect compared with placebo and was more effective than melatonin. Reliable data on the effect beyond a few weeks are lacking.
How long can zopiclone be taken?
According to the summary of product characteristics, for at most four weeks including the gradual discontinuation phase. Longer treatment requires a renewed medical assessment, because the risk of misuse and dependence increases with duration.
Is zopiclone addictive?
Yes, that is possible. The risk increases with dose and duration; people with a history of addiction or psychiatric illness are particularly at risk. Abrupt discontinuation can lead to rebound insomnia and withdrawal symptoms.
Can I drive after taking zopiclone?
According to the summary of product characteristics, not for at least 12 hours after taking it. In 10 of 10 driving tests with healthy people, lane keeping the next morning was as impaired as under 0.5 per mille of alcohol, and in a Norwegian registry the accident risk was 2.3 times higher.
Is zopiclone a controlled narcotic?
No. Zopiclone is prescription-only but is not listed in the German Narcotics Act. The related zolpidem, by contrast, falls under the Narcotics Act in preparations containing more than 8.5 mg per tablet.
What side effects does zopiclone have?
A bitter taste is common. More important are drowsiness in the morning, memory gaps, sleepwalking or driving while half asleep, dependence and, in older people, an increased risk of falls and bone fractures.
Related
- Related topicOrexin receptor antagonists (daridorexant, suvorexant, lemborexant)
- Related topicTrazodone
- Related topicPhenibut
- Same sectionDapoxetine (Priligy)
- Same sectionModafinil
- Same sectionCabergoline
Sources
- De Crescenzo F et al., Lancet 2022 – network meta-analysis of sleeping pills for insomnia, 154 studies
- Noble S et al., Drugs 1998 – zopiclone, review of pharmacology, efficacy and tolerability
- Riemann D et al., J Sleep Res 2023 – European insomnia guideline 2023
- McElroy H et al., Sleep Adv 2021 – sleeping pills and next-morning driving performance, meta-analysis of 14 driving studies
- Gustavsen I et al., Sleep Med 2008 – road traffic accident risk after prescription of zopiclone, zolpidem, flunitrazepam and nitrazepam
- Treves N et al., Age Ageing 2018 – Z-drugs, falls and fractures in older people, meta-analysis
- Hajak G et al., Addiction 2003 – abuse and dependence potential of zolpidem and zopiclone
- Summary of product characteristics (Fachinformation) Ximovan 7.5 mg film-coated tablets (as of October 2022)
- German Prescription Drugs Ordinance (AMVV), Annex 1
- German Narcotics Act (BtMG), Annex III
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Information only, not medical advice and not a usage or dosage recommendation. Prescription-only and unapproved substances belong in the hands of a physician. Last updated: 2026-10-09.