Zopiclone drug withdrawal

Zopiclone (7.5 mg) was compared to temazepam (30 mg) and placebo in a double-blind 3-week study in insomniac patients. The patients were assessed before and at the end of each of the 3 weeks active treatment phase and 1 week and 3 weeks posttreatment. The results indicated that zopiclone and temazepam possess a clinically significant hypnotic activity with no rebound insomnia or anxiety occurring during the week of drug withdrawal... 

Related hypnotics that also act at benzodiazepine receptors are the newer agents zolpidem, a imida-zopyridine, zaleplon a pyrazolopyrimidine and the cyclopyrrolone zopiclone. Zopiclone might have a role for the treatment of benzodiazepine addiction. In patients in whom zopiclone was substituted for a benzodiazepine for 1 month and then itself abmptly terminated, improved sleep was reported during the zopiclone treatment, and withdrawal effects were absent on discontinuation of zopiclone. A series of non-sedating anxiolytic drugs derived from the same structural families as the above mentioned nonbenzodiazepines, have been developed, such as alpi-dem and pagoclone. 

As well as unwanted effects related to direct drug effects, hypnotics, like many other medications, are associated with offset effects, namely withdrawal reactions after discontinuation, abrupt or gradual [4], Numerous terms are used in this context, and include those relating to non-medical use, i.e., abuse and addiction. The purpose of this chapter is to review briefly the clinical problems that can be encountered when discontinuing hypnotic dmgs within the normal therapeutic context. For a review on the abuse and dependence potential of the non-benzodiazepine hypnotics, zolpidem and zopiclone, reference should be made to the paper by Hajak et al. [5],... 

The substantial fall in plasma zopiclone concentration after withdrawal of nefazodone probably reflected a drug interaction due to inhibition of CYP3A4 by nefazodone (38). Despite the normally short half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction had clinical significance. 

Zolpidem 10 mg/day and zopiclone 7.5 mg/day, given at night, have been compared in a 14-day, double-blind study in 479 chronic primary insomniacs (17). With zolpidem 68% of the patients were rated at least moderately improved, versus 62% with zopiclone. However, with zolpidem sleep-onset latency improved in significantly more patients (86 versus 78%). In addition, significantly fewer patients who took zolpidem had drug-related adverse events (31 versus 45%) bitter taste accounted for 5.8% of such complaints with zolpidem compared with 40% with zopiclone. In conclusion, zolpidem was at least as effective as zopiclone but showed significantly less rebound on withdrawal overall it was better tolerated. 

Zopiclone is a cyclopyrrolone in structure. It has a fairly fast (about 1 hour) onset of action which lasts for 6-8 hours, making it an effective drug both for initial and maintenance insomnia. It may cause fewer problems on withdrawal than benzodiazepines. Its duration of action is prolonged in the elderly and in hepatic insufficiency. About 40% of patients experience a metallic aftertaste. Care should be taken with concomitant medication that affects its metabolic pathway (see Table 19.2a). The dose is 3.75-7.5 mg p.o. 

The substantial fall in plasma zopiclone concentration after withdrawal of nefazodone probably reflected a drug interaction due to inhibition of CYP3A4 by... 

---