Long-term zopiclone

The cyclopyrrolone zopiclone was one of the first compounds other than the benzodiazepines to be shown to bind at the benzodiazepine receptor. More potent compounds have also been developed (e.g., suriclone and pagoclone). The cyclopyrrolones may actually bind to a different domain on the a subunit from the benzodiazepines (Canton and Doble 1992), and this may underlie the pharmacological differences seen in vivo, that is, lack of some side effects and lack of tolerance after long-term dosing. 

Pecknold J, Wilson R, Le Morvan P (1990) Long-term efficacy and withdrawal of zopiclone a sleep laboratory study. Int Clin Psychopharmacol 5 57-67... 

An evaluation has been made of the utility of zopiclone substitution in facilitating the withdrawal of flunitrazepam [31]. Twenty-four volunteers with insomnia and a history of long-term benzodiazepine hypnotic use were assessed with both subjective and objective measures during a 5-week substitution with zopiclone and subsequent withdrawal or continuation on flunitrazepam. Withdrawal from flunitrazepam was accompanied a worsening of sleep quality, both subjectively and objectively. No such deterioration was seen in the zopiclone-substituted groups. 

Chiffoleau A, Baudot S, Larousse C et al (1991) Zopiclone what does happen after discontinuation of long-term treatment Proceedings of Heme Joumees Francoises de Pharmacovigilance. Oct 28-29, Nice... 

Diazepam is better indicated if insomnia is associated with daytime anxiety. Other benzodiazepines prescribed for insomnia include nitrazepam, flur-azepam, loprazolam, lormetazepam and temazepam. The non-benzodiazepine hypnotics zaleplon, zolpidem and zopiclone are not licensed for long-term use. The sedative antipsychotic promethazine hydrochloride is sometimes used to facilitate sleep, with a 25-50 mg recommended dose. Melatonin has proved effective for some clients, mostly in regulating the sleep/waking cycle. Although evidence of efficacy is limited, some clients use herbs such as valerian and chamomile. If Mr AB will finally be diagnosed with depression, a trial with an antidepressant will be indicated. 

Long-term adaptations of zopiclone, a mixture of an active S enantiomer and an inactive R enantiomer, have not been well studied, but chronic studies of the active isomer eszopiclone suggest lack of notable tolerance or dependence developing over time... 

Long-term effects of zopiclone in children/adolescents are unknown... 

The use of benzodiazepines with carbamazepine is common, although some evidence suggests that the effects of the benzodiazepines are sometimes reduced. Levels of alprazolam were reduced by almost 50% and levels of midazolam were markedly reduced and its effects almost abolished by carbamazepine. Single-dose studies have shown that the sedative effects of zopiclone and carbamazepine are additive, however it has been predicted that when taken long-term carbamazepine will reduce the effects of zopiclone. 

The evidence for an interaction between zopiclone and carbamazepine is slim, and the effects of long-term use unclear. However, it would seem prudent to be alert for the need to increase the zopiclone dosage in patients taking carbamazepine. More study of this potential interaction is needed. 

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