A Double-Blind Comparative Study of Zolpidem versus Zopiclone in the Treatment of Chronic Primary Insomnia

Abstract

Zolpidem (10 mg/day) and zopiclone (7.5 mg/day), administered at night, were compared in a 14-day, double-blind, equivalence trial on 479 chronic primary insomniacs (zolpidem, 231; zopiclone, 248) throughout Japan, with a 1-week follow-up to assess rebound. The primary endpoint was the investigators' rating of global improvement of sleep disorders. A total of 32 patients in the zolpidem group (13.9%) and 45 patients in the zopiclone group (18.1%) withdrew from the study before the end of the treatment. In the zolpidem group, 67.9% (142/209) of patients were rated at least ‘moderately improved’ versus 61.6% (135/219) with zopiclone, zolpidem being at least as effective as zopiclone (90% confidence interval: −1.7, 14.3). With zolpidem, sleep onset latency improved in significantly more patients (85.8% versus 77.5%) and significantly fewer patients showed aggravated sleep onset latency relative to baseline at follow-up (4.5% versus 15.4%). Significantly fewer patients receiving zolpidem experienced drug-related adverse events (31.3% versus 45.3%), with bitter taste representing 5.8% (six of 104) of such complaints with zolpidem compared with 39.9% (69/173) with zopiclone. In conclusion, zolpidem was at least as effective as zopiclone, showed significantly less rebound on discontinuation and was better tolerated

Comparative efficacy of newer hypnotic drugs for the short‐term management of insomnia: a systematic review and meta‐analysis

“…One study (Pull et al, 1983) did not state the diagnostic criteria used and three (Wheatley, 1985;Allain et al, 2003;Tsutsui, 2001) reported only that participants experienced sleep difficulties. Eight studies (Leppik et al, 1997;Ngen and Hassan, 1990;Van der Kleijn, 1989;Wheatley, 1985;Elie et al, 1999;Fry et al, 2000;Ancoli-Israel et al, 1999;Tsutsui, 2001) acknowledged funding or other support from a pharmaceutical company for the trial.…”

“…Only one study by Tsutsui (2001) compared zolpidem with zopiclone. Sleep latency improved from baseline at the end of treatment and Daytime alertness, global impression of treatment.…”

“…These included 17 studies (Leppik et al, 1997;Ansoms et al, 1991;Agnoli et al, 1989;Anderson, 1987;Kazamatsuri et al, 1993;Klimm et al, 1987;Kudo et al, 1993;Kerkhof et al, 1996;Jovanovic and Dreyfus, 1983;Ohtomo, 1985a, Ohtomo, 1985b, Pull et al, 1983Tamminen and Hansen, 1987;Ngen and Hassan, 1990;Stip et al, 1999;Van der Kleijn, 1989;Wheatley, 1985) comparing a Z-drug with a benzodiazepine and seven (reported in six publications) (Allain et al, 2003;Elie et al, 1999;Fry et al, 2000;Ancoli-Israel et al, 1999;Zammit, 2000;Tsutsui, 2001) comparing a Z-drug with another Z-drug. Of these 19 were parallel group designs and five were crossover studies (Agnoli et al, 1989;Pull et al, 1983;Van der Kleijn, 1989;Wheatley, 1985;Allain et al, 2003).…”

Sleep Maintenance Insomnia: Strengths and Weaknesses of Current Pharmacologic Therapies

“…Zolpidem's short half-life (1.5 to 2.4 hours) (43) likely contributes to its relatively low incidence of residual effects as compared with benzodiazepines (44), and may also limit its ability to maintain sleep (45). In general, randomized, controlled clinical trials have shown that zolpidem improves sleep latency and sleep duration (35,37,38,(46)(47)(48)(49). However, in the 10 of the 10 studies found, WASO and/or NAW were either not assessed or not improved/sustained compared with placebo (35,38,(46)(47)(48)50,51).…”

“…In general, randomized, controlled clinical trials have shown that zolpidem improves sleep latency and sleep duration (35,37,38,(46)(47)(48)(49). However, in the 10 of the 10 studies found, WASO and/or NAW were either not assessed or not improved/sustained compared with placebo (35,38,(46)(47)(48)50,51). In a 2-week study there were statistically significant improvements compared with placebo in NAW and WASO during week 1 that were not sustained in week 2 (36).…”