Web site: July 1998
Prescriber Update No.16:20-22
Medsafe Editorial Team
Dependence and withdrawal effects with zopiclone do occur, although rarely. These effects can occur in people without prior substance dependence and who are taking the recommended dose. The duration of treatment with zopiclone should be limited to ≤ 4 weeks. Dose tapering on withdrawal may be necessary if treatment is continued for a longer period.
Zopiclone reduces day time anxiety; has
low frequency of rebound insomnia
Withdrawal effects & dependence may occur & are being under-reported
CARM has received reports of dependence
Dependence may occur without previous substance abuse
Dosage may need to be tapered in withdrawal for use > 4 weeks
Zopiclone (Imovane) is indicated for the short-term treatment of insomnia and appears to be associated with a very low risk of dependence, rebound insomnia, and withdrawal problems.1,2 Nevertheless some individuals do become dependent on zopiclone, and many of these have not experienced substance dependence or abuse previously. The approved data sheet for Imovane advises no more than 4 weeks continuous treatment, and a maximum dose of 7.5mg (1 tablet) a day.
Indicators of the propensity for dependence with a hypno-sedative such as zopiclone are day time anxiety and rebound insomnia. A study3 comparing 4 weeks’ treatment with zopiclone 7.5mg, triazolam 0.5mg and placebo in patients with generalised anxiety disorder found significantly (p < 0.05) lower mean scores for anxiety, on the Hamilton Anxiety Rating Scale, for patients taking zopiclone (n=30) than for those given triazolam (n=30). The scores were 18.2 with zopiclone and 22.4 with triazolam. In the withdrawal phase of the study,4 zopiclone was associated with a lower frequency and lesser intensity of rebound insomnia following abrupt discontinuation than triazolam.
At June 1997, the WHO database held 46 reports of dependence and 42 of withdrawal syndrome with zopiclone. From March 1994 to June 1997, Rhône-Poulenc Rorer received 17 spontaneous reports of dependence and 13 of withdrawal syndrome or symptoms with zopiclone.5
These figures suggest a very low rate of occurrence of these problems. However, during a 2.5 year period, Tranx Services, Auckland (an organisation that assists people to withdraw from addiction to minor tranquillisers) saw 24 clients seeking help for dependence who were taking zopiclone.6 As only a small proportion of dependent people seek assistance from addiction services, extrapolating this figure would suggest that there is significant under-reporting worldwide.
The New Zealand Centre for Adverse Reactions Monitoring (CARM) has received 3 reports of dependence or withdrawal problems with zopiclone. One patient had been taking zopiclone 15mg daily for 2.5 years. On missing one dose the patient became depressed and irritable and claimed to have a "fuzzy head". Another patient had taken zopiclone 7.5mg every night for 6 months. With abrupt withdrawal the patient felt "strange in the head" for 2-3 days, but experienced no physical effects. The third person, who was also on lithium carbonate and thyroxine, was taking 11 tablets per day of zopiclone (82.5mg) and experienced withdrawal phenomena (not described) with discontinuation.
Eight people contacted Tranx, Christchurch in a two-week period seeking help for zopiclone dependence.7 Daily doses of zopiclone for these individuals ranged from half a 7.5mg tablet daily or one tablet alternate days, to 4 tablets daily. One client had previously taken 8 tablets each night for a year. Two were on other medication (benzodiazepines and antidepressants), one had a previous history of drug dependence (opioids), and one had previously used benzodiazepines and antidepressants but had been drug-free for 6 months before commencing zopiclone. All except one were women. Ages ranged from 20s (not specified) to 72 years. Three had been taking zopiclone for only 2 months, but most had been using it from 18 months to 2 years. The withdrawal symptoms described included anxiety, sleeping difficulties, tremor and diarrhoea.
Physical dependence can occur with zopiclone, although much less frequently than with benzodiazepines. The risk of dependence is increased with a history of substance abuse or dependence, but individuals who have no previous history of substance dependence or abuse may become dependent even in as short a time as 2 months.
It is important, therefore, to follow the advice in the data sheet for zopiclone, and to limit the treatment duration to no more than 4 weeks. If a longer duration is required, it may be necessary to taper the dose in withdrawal or even gain the assistance of those who have experience in assisting withdrawal from minor tranquillisers to minimise the disruption to the life of the patient.