Withdrawal from hypnotics can produce a variety of problems, especially sleep difficulties, some of which may arise from the multiple actions of most hypnotics, thus producing a range of rebound effects. This study examined whether switching patients to a hypnotic with a narrower range of action and of a different class would reduce these problems. One hundred and thirty-four patients participated; they were randomly allocated to one of three methods of switching from “previous hypnotic” to zopiclone (a cyclopyrrolone). The methods were gap (an interval between taking the two drugs); abuttal (taking zopiclone immediately on stopping previous drug); and overlap (gradually reducing previous drug after starting zopiclone). The main findings were that zopiclone was associated with better sleep and increased alertness; the abuttal method was the best method of switching; and no serious side effects from zopiclone were reported. It was concluded that zopiclone has a useful role in benzodiazepine withdrawal, and that immediate substitution is the best method.

Differences in daytime sleepiness, lifestyle disruptions, and emotional distress were compared across nine groups taking sleep-promoting substances. Groups included individuals taking zopiclone (n = 274), amitriptyline (n = 107), lorazepam (n = 258), oxazepam (n= 141), diphenhydramine HCl (n = 99), triazolam(n = 137), long acting benzodiazepines (n = 120), temazepam (n = 176), and miscellaneous other medications (n = 286). Data were gathered by self-report, using standardized instruments in a mail-back questionnaire procedure. Respondents included the first 1,598 participants enrolled in a Canadian multicentre project, including six sites attached to academic psychiatric units. Results indicated that quality of life effects differed across groups in both daytime sleepiness and lifestyle disruptions (illness intrusiveness), but not in depressive symptoms. Daytime sleepiness was significantly higher among people taking diphenhydramine HCl as compared to temazepam, zopiclone, lorazepam, and oxazepam. Illness intrusiveness was significantly higher among patients taking amitriptyline as compared to those taking triazolam, oxazepam, long-acting benzodiazepines, and zopiclone. It may be useful to inform patients of differences in psychosocial outcomes when prescribing hypnotic medications.

Two distinct double-blind randomized multicentre studies were undertaken at the same time using the same design. Patients treated for insomnia with zopiclone 7.5 mg or zolpidem 10 mg for at least three months were allocated to two groups: gradual withdrawal or control. In each study the two groups were compared but there was no comparison between zopiclone and zolpidem. The main criteria was the number of patients in each group with “withdrawal syndrome” defined as: the occurrence of an adverse event, or premature discontinuation of treatment or a total score increase of at least 3 points on the Tyrer questionnaire. In both studies the incidence of “withdrawal syndrome” as defined above was significantly higher in the “withdrawal” groups than in the “control” groups 38% vs 20% for zopiclone p = 0.008 and 38% vs 24% for zolpidem P = 0.049. In most cases, the notified symptoms were sleep complaints.

During the early treatment of a major depressive episode with amitryptiline, insomnia was treated in 81 patients in a double-blind comparative trial comparing zopiclone and flunitrazepam. The study showed no major differences in the efficacy profile and showed better tolerability for zopiclone than for flunitrazepam.

The effect of treatment (28 days) with zopiclone, triazolam, flunitrazepam and placebo on sleep quality and daytime well-being was proven in a randomised, double-blind, parallel group, multicentre study in private practice. Results of an exploratory statistic of treatment efficacy in a subgroup of 1,291 patients suffering from insomnia are presented. Patients met the following criteria: insomnia lasting at least four weeks and the presence of at least two of the following: 1) sleep latency ≥ 45 minutes, 2) total sleep time ≤ 6 hours, and 3) nocturnal awakening ≥3 times. Treatment efficacy was assessed according to the following factors: either a shortening of sleep latency by at least 15 minutes, or prolongation of total sleep time by at least 20%, or reduction of the number of nocturnal awakenings to three or less and a refreshed feeling in the morning as well as no impairment in daytime well-being due to tiredness or anxiety. The total response rate was markedly higher with zopiclone (42.3%; p = 0.0003) than with placebo (29.0%). Triazolam (36.6%; p = 0.0905) and flunitrazepam (33.1%; p = 0.3401) were also more effective than the placebo, but they both tended to have a lower response rate than with zopiclone (p = 0.1199 and 0.0151, respectively). Total response was found to be essentially a reflection of the response of the socially important parameter of daytime well-being. These results suggest that zopiclone is more effective in the treatment of insomnia than either triazolam or flunitrazepam. Since the response of daytime well-being to therapy was generally poor, this parameter embodies the next main therapeutic challenge in the treatment of patients with insomnia.