Zopiclone and Eszopiclone (Lunesta): Complete Guide to Z-Drug Sleep Medicines
- Dr. Ryan Heals, Pharm.D.
- 5 days ago
- 9 min read
Zopiclone is one of the most widely prescribed sleep medicines in the world — used across the UK, Europe, Canada, Australia, and many other countries for the short-term treatment of insomnia. In the United States, its active stereoisomer eszopiclone — marketed as Lunesta — is the FDA-approved equivalent and has been available since 2004. Together, zopiclone and eszopiclone represent the same core compound in slightly different molecular forms, working through identical mechanisms to promote sleep.
Both belong to the "Z-drug" class of sleep medicines — non-benzodiazepine hypnotics that include zolpidem (Ambien) and zaleplon (Sonata). Despite not being chemically related to benzodiazepines, Z-drugs act on the same GABA receptor system and produce similar clinical effects — and carry similar risks of tolerance, dependence, and withdrawal when used beyond recommended durations.
Understanding the difference between zopiclone, eszopiclone, and the broader Z-drug class is essential for anyone managing insomnia in 2026. This complete guide covers the GABA mechanism, correct use and dosage, the full side effect profile, the critical dependence and withdrawal risks, the metallic taste side effect almost no one warns patients about, and the important comparison with CBT-I — the gold-standard non-pharmacological treatment.
MedlinePlus provides comprehensive patient information on eszopiclone (the US-approved equivalent of zopiclone) at: https://medlineplus.gov/druginfo/meds/a605009.html
Zopiclone vs Eszopiclone — The Key Distinction
Before covering mechanism and uses, this relationship needs to be clearly understood:
Zopiclone is a racemic mixture — meaning it contains two molecular forms (enantiomers) that are mirror images of each other:
S-zopiclone (eszopiclone) — the pharmacologically active enantiomer; responsible for most of the sleep-promoting effect
R-zopiclone — largely inactive; contributes little to therapeutic effect but may contribute to side effects
Eszopiclone (Lunesta) is the purified S-enantiomer — the active half of zopiclone. Because it contains only the active form:
Lower doses are needed (maximum 3mg eszopiclone vs 7.5mg zopiclone)
Potentially fewer side effects from the inactive R-enantiomer
The same fundamental mechanism and clinical profile
In clinical practice, zopiclone 7.5mg and eszopiclone 3mg produce essentially equivalent sleep outcomes. The metallic or bitter taste — zopiclone's most recognisable side effect — occurs with both, as it is caused by the active S-enantiomer.
How Zopiclone Works — The GABA Mechanism
Zopiclone and eszopiclone work by enhancing the activity of GABA (gamma-aminobutyric acid) — the brain's primary inhibitory neurotransmitter — through binding to the GABA-A receptor complex:
The mechanism:
1. GABA-A receptors are ligand-gated chloride ion channels — when GABA binds, the channel opens and chloride ions flow into the neuron
2. This influx of negatively charged chloride ions hyperpolarises the neuron — making it less likely to fire
3. Zopiclone binds to a specific modulatory site on the GABA-A receptor (the benzodiazepine binding site, but at a different subunit configuration)
4. This binding increases the frequency of chloride channel opening in response to GABA
5. The net result: widespread reduction in neuronal excitability — producing sedation, hypnosis (sleep induction), muscle relaxation, and anxiolysis
Why Z-drugs differ from benzodiazepines:
Although both bind to the GABA-A receptor, Z-drugs show greater selectivity for the alpha-1 subunit — the subunit most associated with sedation and hypnosis. Benzodiazepines bind more broadly across alpha subunits (alpha-1, -2, -3, -5), producing stronger anxiolytic, muscle-relaxant, and anticonvulsant effects alongside sedation. This relative selectivity is why Z-drugs were developed as supposedly "cleaner" sleep medicines — though clinical differences in abuse potential and dependence risk versus benzodiazepines are smaller than originally claimed.
Onset and duration:
Onset of sleep-promoting effects: approximately 30–60 minutes after oral ingestion
Duration of hypnotic effect: 6–8 hours (aligned with a typical sleep period)
Half-life: zopiclone approximately 5 hours; eszopiclone 6 hours
Both should be taken immediately before going to bed — not earlier
What Zopiclone and Eszopiclone Treat
Zopiclone and eszopiclone are indicated for the short-term treatment of insomnia in adults, specifically:
Sleep onset insomnia:
Difficulty falling asleep — lying in bed for extended periods before sleep begins. Both medicines significantly reduce sleep onset latency (the time taken to fall asleep).
Sleep maintenance insomnia:
Frequent awakenings during the night or early morning waking. Both medicines reduce nocturnal awakenings and increase total sleep time.
Transient and short-term insomnia:
Insomnia related to specific stressors — bereavement, acute illness, hospitalisation, travel, jet lag, temporary work stress — where short-course pharmacological support is appropriate.
Short-term duration recommendations:
Standard recommended duration: 2 to 4 weeks maximum
Optimal course for most acute insomnia: 7 to 14 days
Eszopiclone (Lunesta) — notably, it is one of the few sleep medicines with FDA approval that does not specifically restrict duration of use, and has clinical trial evidence supporting efficacy up to 6–12 months; however, dependence risk considerations still apply with long-term use
Both zopiclone and eszopiclone help with:
Falling asleep faster (reduced sleep latency)
Fewer night-time awakenings
Improved sleep quality and total sleep duration
Reduced early morning waking
Dosage — Zopiclone and Eszopiclone
Medicine | Standard Adult Dose | Elderly / Sensitive Patients | Maximum Dose | Timing |
Zopiclone | 7.5mg at bedtime | 3.75mg — start low | 7.5mg | Immediately before bed |
Zopiclone 10mg | Higher strength formulation | Not for elderly | 10mg | Immediately before bed |
Zopiclone 20mg | High strength | Specialist use | 20mg | Immediately before bed |
Eszopiclone (Lunesta) | 1–2mg (sleep onset); 2–3mg (sleep maintenance) | 1mg — start low | 3mg | Immediately before bed |
Important dosage notes:
Always take immediately before going to bed — not in advance of sleep
Ensure at least 7–8 hours of sleep time available after taking the dose — do not take if you need to be awake in less than 7–8 hours
Do NOT take with or immediately after a heavy meal — food slows absorption and delays onset
Do NOT take with alcohol — dangerous CNS depression; see drug interactions
Elderly patients are at higher risk of falls, confusion, and cognitive impairment — lower starting doses are essential
Zopiclone 10mg and 20mg tablet strengths are available at TheMedicineKart:
Side Effects of Zopiclone and Eszopiclone
Common side effects:
Bitter or metallic taste in the mouth — the most distinctive and frequently reported side effect of zopiclone and eszopiclone; affects up to 1 in 10 users; caused by the active S-enantiomer being excreted in saliva; typically most noticeable in the morning; does not indicate harm and often diminishes after the first few nights
Drowsiness and sedation — particularly the following morning (next-day residual sedation); more prominent with higher doses; do NOT drive or operate machinery if experiencing morning grogginess
Dizziness and coordination problems
Dry mouth
Headache
Nausea — less common than with zopiclone's predecessor drugs
Next-day impairment — the most clinically important practical concern:
Zopiclone's half-life of approximately 5 hours means that residual drug is still active the next morning, particularly in elderly patients and those taking higher doses. This residual sedation impairs driving ability — multiple studies and regulatory agencies have identified next-day driving impairment as a significant safety concern with Z-drugs. The FDA specifically warns about next-day impairment with eszopiclone. Do not drive after taking zopiclone or eszopiclone unless you are certain you are fully alert.
Complex sleep behaviours (parasomnias):
A class of rare but important side effects — including sleepwalking, sleep-driving, sleep-eating, and sleep-sex — have been reported with all Z-drugs. The FDA issued a boxed warning for all non-benzodiazepine sleep medicines about complex sleep behaviours in 2019. These behaviours can occur without the patient being aware. Stop the medicine and contact a doctor if complex sleep behaviours occur.
Memory effects:
Anterograde amnesia — difficulty forming new memories after taking the medicine — can occur, particularly at higher doses or when combined with alcohol. The person may perform actions they have no memory of.
Serious drug interactions:
Alcohol — dangerous combination; both alcohol and zopiclone depress the CNS; combined use significantly increases risk of respiratory depression, coma, and death; avoid completely
Opioids — combined use dramatically increases risk of respiratory depression and death; Drugs.com explicitly warns of this interaction
Other CNS depressants — benzodiazepines, antipsychotics, antihistamines, antidepressants — additive sedation
Dependence, Tolerance and Withdrawal — The Critical Warning
Zopiclone and eszopiclone carry real and significant risks of tolerance, physical dependence, and withdrawal — particularly with use beyond the recommended 2–4 week window:
Tolerance:
With regular use, the brain adapts — downregulating GABA-A receptor sensitivity to compensate for the enhanced GABA activity produced by zopiclone. This means the same dose produces progressively less effect, driving dose escalation.
Physical dependence:
Regular use for more than 2–4 weeks typically produces physical dependence — the brain's GABA system has adapted to the presence of the drug. Stopping abruptly causes withdrawal.
Withdrawal symptoms:
Rebound insomnia — often more severe than the original insomnia; a powerful driver of continued use
Anxiety, agitation, and irritability
Sweating, tremor
Muscle cramps
In severe cases (particularly with high doses or prolonged use): seizures — a medical emergency
Safe discontinuation:
Zopiclone and eszopiclone must be tapered gradually when stopping after regular use — not stopped abruptly. Discuss a tapering schedule with your prescribing doctor. Substituting a long-acting benzodiazepine (diazepam) for the taper is sometimes used in severe dependence.
Z-Drug Comparison — Zopiclone vs Zolpidem vs Zaleplon vs Eszopiclone
Feature | Zopiclone | Eszopiclone (Lunesta) | Zolpidem (Ambien) | Zaleplon (Sonata) |
Available in USA | No (not FDA-approved) | Yes — FDA approved 2004 | Yes — most prescribed US sleep Rx | Yes — FDA approved |
Half-life | ~5 hours | ~6 hours | 1.5–2.4 hours (IR); longer XR | ~1 hour |
Duration of effect | 6–8 hours | 6–8 hours | 6–8 hours | 4 hours |
Best for | Sleep onset + maintenance | Sleep onset + maintenance | Sleep onset + maintenance | Sleep onset only / middle of night waking |
Long-term approval | No (2–4 weeks) | Yes (clinical evidence to 12 months) | No (short-term) | No (short-term) |
Metallic/bitter taste | Yes — characteristic | Yes — same compound | No | No |
Complex sleep behaviours | Yes — FDA warning | Yes — FDA warning | Yes — FDA warning (higher reports) | Yes — FDA warning |
Next-day impairment | Yes | Yes | Yes — especially with higher doses | Less (shorter half-life) |
Dependence risk | Yes | Yes | Yes | Yes |
For our complete guide on evidence-based insomnia treatment without sleep medicines — CBT-I and the 15-tip approach: [How to Sleep Better: 15 Proven Tips for Insomnia]
For our comparison guide on zopiclone versus zolpidem — the two most commonly compared Z-drugs: [Zopiclone vs Zolpidem: Which Sleep Medicine is Better?]
For our guide on anxiety disorders — frequently coexisting with and contributing to insomnia: [Anxiety Disorders: Types, Symptoms, Causes and Treatment]
Drugs.com provides comprehensive clinical information on zopiclone including all interactions at: https://www.drugs.com/zopiclone.html
The Mayo Clinic provides comprehensive patient information on eszopiclone, last updated August 1, 2026 at: https://www.mayoclinic.org/drugs-supplements/eszopiclone-oral-route/description/drg-20063743
Frequently Asked Questions
What is the metallic taste from zopiclone and does it go away?
The bitter or metallic taste in the mouth is one of zopiclone's and eszopiclone's most frequently reported and distinctive side effects — affecting up to 1 in 10 users. It is caused by the active S-enantiomer being excreted in saliva. It is most noticeable in the morning and can persist throughout the day. For most patients, the taste diminishes after the first few nights as the body adjusts. It does not indicate harm. Drinking water, brushing teeth in the morning, or eating breakfast helps reduce its impact. If the metallic taste is severe or persistent, discuss an alternative medicine with your doctor.
How quickly does zopiclone work and how long does it last?
Zopiclone typically begins working within 30 to 60 minutes of taking the tablet — which is why it should be taken immediately before going to bed, not in advance. The sleep-promoting effect lasts approximately 6 to 8 hours, corresponding to a typical night's sleep. The half-life of approximately 5 hours means the drug is still partially active the next morning, which is why next-day drowsiness and driving impairment can occur, particularly with higher doses in elderly patients.
Is zopiclone the same as Lunesta?
They are very closely related — eszopiclone (Lunesta) is the purified active stereoisomer of zopiclone. Zopiclone is a racemic mixture containing both the active S-enantiomer and the largely inactive R-enantiomer. Eszopiclone contains only the S-enantiomer — meaning a lower dose (maximum 3mg) achieves equivalent effects to the higher dose of zopiclone (maximum 7.5mg). Both produce the same mechanism of action, the same characteristic metallic taste, and essentially the same clinical outcomes for insomnia.
Can zopiclone be taken long-term?
Standard clinical guidelines recommend zopiclone for short-term use only — 2 to 4 weeks maximum — due to the risks of tolerance, dependence, and withdrawal. Eszopiclone is an exception: it has clinical trial evidence supporting efficacy and safety up to 12 months and does not carry the same specific short-term restriction in its FDA label, though dependence risk exists with any extended hypnotic use. For chronic insomnia, Cognitive Behavioural Therapy for Insomnia (CBT-I) is the gold-standard first-line treatment — more effective than sleep medicines long-term with no dependence risk.
What happens if I stop zopiclone suddenly after taking it regularly?
Stopping zopiclone abruptly after regular use — particularly beyond 2 to 4 weeks — can cause withdrawal symptoms: rebound insomnia (often worse than original sleep problems), anxiety, agitation, sweating, tremor, and in severe cases seizures. Never stop zopiclone suddenly after regular use without medical guidance. A gradual dose tapering schedule, supervised by your prescribing doctor, is the safe approach. In some cases, substitution with a long-acting benzodiazepine (diazepam) for a structured taper is appropriate.
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