Because eszopiclone is metabolized via CYP3A4 and CYP2E1, caution is recommended when a potent CYP3A4 inhibitor (e.g., ketoconazole, itracon-azole, clarithromycin, troleandomycin, nefazodone, ritonavir, nelfinavir) is co-administered. A lower dose, such as 1 mg, should be prescribed when es-zopiclone is used with any of these drugs.
Krystal et al./Roth et al.
The first part of this two-part study was a six-month double-blind, placebo-controlled trial, the second part being a six-month open-label extension, which was available to all patients who completed the double-blind portion of the study. The patients received either eszopiclone 3 mg or placebo. buy tadacip
To be eligible for enrollment in the study, patients had to:
- be between the ages of 21 and 65 years of age.
- have a diagnosis of primary insomnia, as described in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition.
- report a usual total sleep time of less than 6.5 hours per night and/or a usual sleep latency of more than 30 minutes each night for at least one month prior to screening. (Sleep latency was defined as the time it took a patient to fall asleep.)
Patients were excluded from the study if they:
- met criteria for another DSM-IV Axis I diagnosis or Axis II personality disorder.
- had a history of substance abuse or substance dependence.
- consumed more than two alcoholic beverages per day or more than 14 per week.
- used any psychotropic, hypnotic, or other medication known to affect sleep.
- used over-the-counter products containing caffeine or herbal supplements, including melatonin and St. John’s Wort.
Of the 1,194 patients screened for the trial, 788 were randomly assigned to receive either eszopiclone 3 mg (n = 593) or placebo (n = 195). Baseline demographics were similar in both treatment arms, but the eszopiclone patients had a statistically significant higher mean body mass index and weight (mean, 29.5 kg/m2) than the placebo patients (mean, 27.8 kg/m2). Discontinuation rates were similar in the eszopiclone treatment arm (39.5%) and in the placebo arm (43.4%).
The primary endpoint was originally defined as the average sleep latency over the last three months of the double-blind portion of the study, and the key secondary endpoint was the average total sleep time during the same period. The patients called in to an interactive voice response system once weekly to report their sleeping patterns. At the end of the six-month study, the investigators decided it would be best to publish the information for seven different time points (at the first week and at months one to six) rather than for only the three original time points.
Baseline characteristics for sleep latency were higher with placebo than with eszopiclone. The median sleep latency was 60 minutes with eszopiclone and 75 minutes with placebo. However, the investigators reported that this difference was not statically significant (P = .6317). By the first week, the median sleep latency had decreased to 30 minutes with eszopiclone and to 60 minutes with placebo (P < .0001). The median sleep latency for the eszopiclone treatment arm remained at or close to 30 minutes for the remainder of the six-month study.
For the placebo treatment arm, the median sleep time decreased to 45 minutes by the third month and remained at that level for the remainder of the study. By the sixth month, the difference in median sleep latency times was 15 minutes between placebo and eszopiclone. This 15-minute difference was found to be statistically significant (P< .0001).
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For the key secondary endpoint of sleep duration, both treatment groups had a baseline median total sleep time of 300 minutes. By the first week, the median total sleep time was 330 minutes for the placebo patients and 375 minutes for the eszopiclone patients. By the sixth month, the median total sleep time was 339.3 minutes with placebo and 382.5 minutes with eszopiclone (P< .0001).
The most commonly reported ADEs in the patients receiving eszopiclone, in contrast to those receiving placebo, were dizziness, dry mouth, infection, nausea, pain, and pharyngitis. Notable differences in effects were the reports of an unpleasant taste (5.6% with placebo vs. 26.1% with eszopiclone) and infection (6.7% with placebo vs. 15.9% with eszopiclone).
Following discontinuation of the drug, no significant withdrawal effects were observed; there was only one report of anxiety after eszopiclone was stopped. There were no reports of seizures, hallucinations, or perceptual-disturbance events. The authors did not mention the method of discontinuation used in the study.
The investigators concluded that the nightly use of eszopiclone 3 mg resulted in improved sleep onset, sleep maintenance, sleep quality, and next-day functioning, compared with placebo (P < .0001). This study also showed no tolerance effect upon discontinuation.
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The same results were seen in the six-month open-label extension phase of this trial. Patients previously treated with placebo reported rapid and significant improvements in sleep and daytime functioning (P < .05). Patients who took eszopiclone for 12 months showed no evidence of tolerance.