Eszopiclone: Review and Clinical Applications in Chronic and Comorbid Insomnia

Abstract

Eszopiclone, the active S(+)-enantiomer of zopiclone [(R,S)-zopiclone], was approved by the Food and Drug Administration (FDA) in 2004 for the treatment of insomnia in adult patients !18 years of age, and in 2005 became the first sedative hypnotic approved by the FDA for the long-term treatment of chronic insomnia. It is classified by the FDA as a Schedule IV drug under the Controlled Substances Act and is available in the United States as the brand Lunesta ® in dosages of 1, 2, and 3 mg. Eszopiclone 2 and 3 mg consistently demonstrated significant improvements of the primary variable, latency to persistent sleep, assessed subjectively or objectively, in short-and long-term clinical trials. Additionally, improvements in sleep maintenance, sleep quality, and daytime functioning have also been observed. Eszopiclone 3 mg has been shown to improve insomnia associated with comorbid conditions. Tolerance with eszopiclone was not apparent in any of the sleep parameters for up to 12 months treatment duration and rebound insomnia, where documented, tends to be transient and limited to the first night of withdrawal. Eszopiclone is generally well tolerated and the most frequent adverse event is unpleasant bitter taste. Both eszopiclone and its racemic compound, zopiclone, are nonbenzodiazepine hypnotic agents that are derivatives of the cyclopyrrolone class, with eszopiclone exhibiting greater affinity than the R(À)-enantiomer for the GABA A /benzodiazepine receptor complex; hence the sedative hypnotic effects of the racemate are primarily linked to the S(+)-enantiomer rather than the R(À)-enantiomer. The racemate zopiclone is available as 3.75, 5, and 7.5 mg tablets; the latter contains 3.75 mg of S(+)-zopiclone, which is more than the highest dose (3 mg) available in the United States. Eszopiclone is not marketed in the European Union, as it was too similar to the racemate to be considered a patentable product.