While zopiclone is a commonly used hypnotic medication for insomnia in many parts of the world, it is not available in the United States. Instead, the U.S. market offers eszopiclone, a related but chemically distinct medication. This distinction is rooted in the molecular structure of the drug. Zopiclone is a racemic mixture, meaning it contains two mirror-image isomers: an active S-isomer and a less active R-isomer. Eszopiclone, on the other hand, is composed solely of the active S-isomer. This article explores the important differences and similarities between these two hypnotic agents.
The US Equivalent: Eszopiclone (Lunesta)
Eszopiclone, sold under the brand name Lunesta and also available as a generic, is a nonbenzodiazepine sedative-hypnotic agent used to treat insomnia. It is the S-stereoisomer of zopiclone and is responsible for most of the hypnotic effect of the racemic mixture. The US Food and Drug Administration (FDA) approved eszopiclone in December 2004, and it is widely available by prescription. Its purpose is to help individuals fall asleep faster and stay asleep longer by enhancing the activity of the brain's calming neurotransmitter, GABA.
The Z-Drug Family
Eszopiclone belongs to a class of medications called Z-drugs, which were developed as alternatives to benzodiazepines with fewer reported side effects. Other popular Z-drugs available in the US include zolpidem (Ambien) and zaleplon (Sonata). While all three work on GABA receptors, they differ in their duration of action and specific side effect profiles.
Zopiclone vs. Eszopiclone: A Closer Look
The primary difference between zopiclone and eszopiclone lies in their chemical composition. Since eszopiclone contains only the active S-isomer, a specific dose is needed to achieve a therapeutic effect compared to the racemic zopiclone which contains both isomers. This difference means patients and prescribers must be aware of the specific medication being used to avoid errors.
Pharmacology and Mechanism of Action
Both drugs act as positive allosteric modulators on GABA-A receptors, enhancing the inhibitory effects of GABA in the central nervous system. This increases the frequency of chloride channel opening, which slows down brain activity and induces a sleep state. This shared mechanism is why eszopiclone is considered the functional equivalent of zopiclone.
FDA Approval and Controlled Substance Status
The reason for zopiclone's absence from the U.S. market is a matter of regulatory pathway and approval. Eszopiclone, the single-isomer drug, was approved by the FDA for marketing in 2004. Following this, the Drug Enforcement Administration (DEA) placed zopiclone and its isomers, including eszopiclone, into Schedule IV of the Controlled Substances Act in 2005. This classification reflects their potential for abuse and dependence, similar to benzodiazepines.
Clinical Uses and Considerations
Eszopiclone is prescribed for both short-term and long-term treatment of insomnia in adults. It is important to note that the FDA has issued warnings regarding the next-day impairment associated with eszopiclone, especially at certain dose levels. Patients taking the medication must ensure they have at least 7 to 8 hours for a full night's sleep to minimize next-day grogginess. Discontinuing the medication should be done gradually under medical supervision to avoid withdrawal symptoms, which can include rebound insomnia, anxiety, and tremors.
Comparison of Zopiclone and Eszopiclone
| Feature | Zopiclone | Eszopiclone (Lunesta) |
|---|---|---|
| Availability | Not sold in the US; available in Canada, UK, and other countries. | Widely available in the US by prescription. |
| Chemical Composition | Racemic mixture (contains both active S-isomer and less active R-isomer). | S-stereoisomer only (active component). |
| Dosage | Varies by country, a common adult dose is 7.5 mg. | Dosage varies. |
| FDA Status | Not approved by the FDA. | FDA-approved since December 2004. |
| Controlled Substance | Schedule IV in the US (not marketed). | Schedule IV in the US. |
| Unique Side Effects | No specific unique side effects noted in searches. | Often causes a metallic or bitter taste. |
| Next-Day Impairment | Possible with higher doses. | Risk increases with dose. |
Potential Side Effects and Safety Concerns
While effective for insomnia, eszopiclone carries potential risks. Common side effects include an unpleasant metallic or bitter taste, headache, and daytime drowsiness. More serious risks can include:
- Complex sleep behaviors: Actions performed while not fully awake, such as sleepwalking, sleep-driving, making phone calls, or eating.
- Dependence and Addiction: Long-term use can lead to physical and psychological dependence.
- Withdrawal Symptoms: Abruptly stopping the medication can cause withdrawal symptoms like rebound insomnia, anxiety, and tremors.
- Next-Day Impairment: Drowsiness and decreased alertness can persist the following day, affecting driving and other activities.
Alternatives to Consider
For managing insomnia, several non-pharmacological and pharmacological alternatives exist in the US.
Non-Pharmacological Options:
- Cognitive Behavioral Therapy for Insomnia (CBT-I): This therapy is a highly effective, long-term solution that addresses the underlying thoughts and behaviors contributing to sleep problems.
- Sleep Hygiene Practices: Simple lifestyle changes, such as maintaining a regular sleep schedule, creating a relaxing bedtime routine, and optimizing the sleep environment.
Other Pharmacological Options:
- Other Z-drugs: Zolpidem (Ambien) and zaleplon (Sonata) are also FDA-approved for insomnia.
- Benzodiazepines: Medications like temazepam (Restoril) are sometimes used for insomnia, though often reserved for short-term use due to dependence risk.
- Melatonin and Melatonin Receptor Agonists: Drugs like ramelteon (Rozerem) target melatonin receptors to promote sleep.
- Antidepressants: Some antidepressants with sedative properties, such as doxepin (Silenor), are prescribed for insomnia.
Conclusion
For individuals in the US, eszopiclone (Lunesta) is the available and approved equivalent of zopiclone. While they share a similar mechanism as Z-drugs, eszopiclone is a single-isomer formulation, leading to differences in administration and a distinct side effect profile, notably the metallic taste. Both are Schedule IV controlled substances, emphasizing the importance of responsible, short-term use under a doctor's supervision. Given the potential for side effects, dependence, and next-day impairment, a comprehensive treatment plan, including non-pharmacological approaches, is often the safest and most effective strategy for managing insomnia. Always consult a healthcare professional for a proper diagnosis and treatment plan, as self-treating insomnia can be dangerous.
