The Rest of the Story

Sepracor's new medication, Lunesta, was approved by the FDA last year.  I just heard that it is being shipped to pharmacies as of today.  I don't have a lot to add since my original post, although a couple more abstracts have appeared on Medline.  Also, I have a few comments about the potential for ancillary use of Lunesta in treatment of depression and chronic pain. 

Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia.
Zammit GK, McNabb LJ, Caron J, Amato DA, Roth T    
Curr Med Res Opin (2004 Dec) 20(12):1979-91       ISSN: 0300-7995

OBJECTIVE: Eszopiclone is a new, single-isomer, non-benzodiazepine, cyclopyrrolone agent under investigation for the treatment of insomnia.  The present study was a randomized, double-blind, multicenter, placebo-controlled trial conducted to assess the efficacy and safety of eszopiclone in adults with chronic primary insomnia.

RESEARCH DESIGN AND METHODS: Patients (n = 308) were randomized to receive placebo or eszopiclone (2 mg or 3 mg) for 44 consecutive nights, followed by 2 nights of single-blind placebo.  Efficacy was evaluated with polysomnography (Nights 1, 15 and 29) and patient-reports (Nights 1, 15, 29 and 43/44).  Next-day residual effects were evaluated using the Digit-Symbol Substitution Test (DSST).

RESULTS: Eszopiclone 3 mg had significantly less time to sleep onset (p < or = 0.0001), more total sleep time and sleep efficiency (p < or = 0.0001), better sleep maintenance (p < or = 0.01), and enhanced quality and depth of sleep (p < 0.05) across the double-blind period compared with placebo.  Eszopiclone 2 mg had significantly less time to sleep onset (p < or = 0.001), more total sleep time (p < or = 0.01) and sleep efficiency (p < or = 0.001), and enhanced quality and depth of sleep (p < 0.05) compared with placebo, but did not significantly improve sleep maintenance.  There was no evidence of tolerance or rebound insomnia after therapy discontinuation.  Median DSST scores showed no decrement in psychomotor performance relative to baseline and did not differ from placebo in either eszopiclone group.  Treatment was well tolerated; the most common adverse event related to eszopiclone was unpleasant taste.

CONCLUSIONS: Patients treated with nightly eszopiclone 3 mg had better polysomnographic (through Night 29) and patient-reported measures (through Night 44) of sleep over the 6-week trial.  There was no evidence of tolerance or rebound insomnia and no detrimental effects on next-day psychomotor performance using the DSST.

There is a blurb in Drugs in R&D about the product.  I won't copy the whole thing here, but I did find this bit interesting:

Preliminary results from a completed phase IIIB/IV trial report that eszopiclone in combination with fluoxetine significantly improved sleep parameters among patients with insomnia and co-existing major depressive disorder. Furthermore the combination of eszopiclone and fluoxetine resulted in greater improvement in HAM-D17 scores in patients than the fluoxetine-placebo group. This trial and three other phase IIIB/IV were initiated in late 2003 to evaluate the efficacy of eszopiclone in the treatment of insomnia in patients with depression, rheumatoid arthritis, chronic insomnia, and in women who experience symptoms of perimenopause.

Note that this could be taken to imply that eszopiclone has a significant role in treatment of depression.  The reference to the HAM-D17 refers to a rating scale (Hamilton, 17-item version) that is used to gauge severity of depression in the course of research studies.  The fact is, anything that helps a person sleep will result in an improvement on the HAM-D.  In order to really assess the significance of the study, we would need to see the mean changes in each item of the 17-item scale. 

From a clinical perspective, it is common practice to give a sleep aid in the acute phase of treatment of major depression.  Probably the most commonly-used drug in this context is trazodone.  Note that you can get a month's supply of trazodone for less than ten dollars.  I don't know the price of Lunesta, but I would guess that a month's supply is going to run in the $75-100 range.  Sure, if price were not a factor, I probably would rather give more patients Lunesta than trazodone -- the effect is more predictable -- but it would be hard to justify that as a routine practice. 

Most often, patients with depression and insomnia find that the insomnia resolves once the depression is controlled adequately.  For that reason, most of the prescriptions written in such a context are intended to be short-term interventions. 

What is more significant is the study with rheumatoid arthritis patients.  RA is a chronic, painful condition.  It is not desirable to use opiate pain killers to facilitate sleep in such patients, but sometimes that is the only option.  It would be good to have a nonopiate, nonaddicting, sleep aid that is suitable for long-term use in RA patients.  I would venture a guess, that Lunesta may establish a niche in the armementarium of drugs used for chronic pain patients.