Zopiclone - Tolerance, Dependence and Withdrawal

Tolerance, Dependence and Withdrawal

Zopiclone, a benzodiazepine-like drug was introduced and initially promoted as having less dependence and withdrawal than traditional benzodiazepine drugs. However, zopiclone may have an even greater addictive potential than benzodiazepines and has been described as a "benzodiazepine in disguise". Tolerance to the effects of zopiclone can develop after a few weeks. Long term use should be avoided. Abrupt withdrawal particularly with prolonged and high doses can in severe cases cause seizures and delirium.

Publications in the British Medical Journal do not give any evidence to the claim that zopiclone has a low dependence potential. In fact, physical dependence and recreational abuse and withdrawal syndromes similar to those seen in benzodiazepine withdrawal are frequently encountered. Withdrawal symptoms included anxiety, tachycardia, tremor, sweats, flushes, palpitations, derealisation, and further insomnia. Suspected withdrawal convulsions during detoxification from zopiclone has been reported, however the individual was a high dose zopiclone misuser.

The risk of dependency on zopiclone when used for less than 2 weeks or only used occasionally is low. However, this is disputed by one study of low dose zopiclone taken for only 7 nights. It found that discontinuation of zopiclone caused significant rebound insomnia. Furthermore when midazolam taken for 7 nights was discontinued no rebound insomnia occurred suggesting that zopiclone may have even more significant problems of tolerance and dependence than the benzodiazepines. After 3 weeks of use mild to moderate rebound withdrawal symptoms appear upon discontinuation of zopiclone. Due to the risk of tolerance and physical dependence, zopiclone is only recommended for short term (1–4 weeks max) relief of insomnia, or alternatively, long term infrequent use. Long-term zopiclone users who have become physically dependent should not discontinue their medication abruptly as severe withdrawal symptoms may occur such as delirium. If zopiclone has been taken for more than a few weeks then the medication should be gradually reduced or preferably to cross over to an equivalent dose of diazepam (Valium), which has a much longer half-life which makes withdrawal easier and then gradually taper their dosage over a period of several months in order to avoid extremely severe and unpleasant withdrawal symptoms (e.g., inner restlessness, psychomotor agitation, abdominal pain, hypertension, hallucinations, seizures, anxiety, depression, psychosis, etc.) which can last up to two years after withdraw if the withdrawal is done too abruptly. After 4 weeks of nightly use of zopiclone day time withdrawal related anxiety begin to emerge in some users. However, the day time withdrawal anxiety does not appear to be as intense as that seen with the much shorter acting triazolam which provokes even more profound day time withdrawal anxiety symptoms in long term users.

According to the World Health Organisation, zopiclone, although molecularly is not a benzodiazepine, binds unselectively with high affinity to the same benzodiazepine sites that the benzodiazepine class of drugs do. The World Health Organisation also stated that zopiclone is cross tolerant with benzodiazepines and one can substitute one for the other. In the review of zopiclone by the World Health Organisation they found that the appearance of withdrawal symptoms usually occurred either when the drug was misused in excessive doses or when use of zopiclone was prolonged. The withdrawal symptoms from zopiclone reported included anxiety, tachycardia, tremor, sweating, rebound insomnia, derealisation, convulsions, palpitations and flushes.

Zopiclone is cross tolerant with benzodiazepines. Alcohol has cross tolerance with GABA_A receptor positive modulators such as the benzodiazepines and the nonbenzodiazepine drugs. For this reason alcoholics or recovering alcoholics may be at increased risk of physical dependency on zopiclone. Also, alcoholics and drug abusers may be at increased risk of abusing and or becoming psychologically dependent on zopiclone. Zopiclone should be avoided in those with a history of Alcoholism, drug misuse (illicit or prescription misuse), or in those with history of physical dependency or psychological dependency on sedative-hypnotic drugs.

Withdrawing from Zopiclone sleeping tablets has been recommended to be done via a cross over to an equivalent dose of diazepam. This is because diazepam is available in low potency tablets, is cross-tolerant with zopiclone and is longer acting than zopiclone, which allows for a smoother withdrawal and for the body to adjust to a constant dose. While zopiclone acts on the same benzodiazepine receptors as the benzodiazepine family of drugs it is not classed as a benzodiazepine (with which it shares a number of characteristics and effects) due to its differing molecular structure. Zopiclone is classed as a cyclopyrrolone derivative.