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The Z Drugs

Here is what Prof. Heather Ashton said about the Z Drugs and Lunesta (eszopiclone) in her speech at the Maine Benzodiazepine Conference in Bangor Maine on October 12, 2005. NB that Lunesta is eszopiclone, a cousin of the three Z drugs: zolpidem (Ambien), zopiclone (Zimovane) and zaleplon (Sonata), and it is being marketed as safe for long-term use.  

"These are not chemically benzodiazepines but they bind to GABAreceptor complexes which are close to or actually coupled with benzodiazepine receptors.  They are said to be more selective, bindingmainly to the a1 GABA receptor subtype which mediates the hypnotic effects of benzodiazepines.  In practice they are not all that selective and have much the same actions as benzodiazepines.  In the UK, the National Institute for Clinical Excellence (NICE), which advises the Health Service on optimum drug use, recommended that Z drugs should be used for short-term treatment only (2-4 weeks) and then only as second line treatments after benzodiazepines.  They concluded that the Z drugs produced the same therapeutic and adverse effects as benzodiazepine hypnotics, including tolerance, dependence and abuse, and were also more expensive. 

"As a clinical example, a psychiatrist recently asked my advice about the nursing sister he was helping to withdraw from lorazepam (Ativan). She developed quite severe withdrawal symptoms as the dosage was lowered and had trouble sleeping.  To help her, the psychiatrist prescribed zopiclone (Zimovane) to take at night.  She found that this drug completely relieved her withdrawal symptoms.  In fact, it was so successful that she started taking zopiclone in the daytime as well. She ended up taking zopiclone six times a day as well as at night, ending up with a total dose of over 40mg/day (the recommended dose is 7.5mg at night).  The psychiatrist was chagrined to find that he had merely replaced one form of addiction with another. 

"There are a number of cases in the literature of such escalation of dosage with zopiclone, followed by dependence and withdrawal symptoms on stopping.  There are also an increasing number of cases reported of misuse and abuse of high doses of zolpidem (Ambien).  This can result in hallucinations and psychosis and is reminiscent of the adverse effects of triazolam (Halcion), the short-acting benzodiazepine hypnotic now banned in the UK.  

"Now eszopiclone [Lunesta] is being promoted for long-term use and the manufacturers report trials lasting two weeks to six months of its hypnotic effects.  They report little tolerance or loss of efficacy over these periods and a low incidence of rebound insomnia or anxiety (3.7%) on stopping.  Euphoria was noted in high doses, suggesting an abuse potential.  I remain sceptical of these results which involved relatively small numbers of subjects with various types of insomnia. I am not convinced that eszopiclone is all that different from zopiclone, apart from its potency, and I think it would be prudent to limit it to short-term use until proved otherwise."  

"There is a basic pharmacological principle that any drug which acts on intrinsic body receptors will cause adaptive changes in these receptors if used chronically.  This is because the body is programmed to restore homeostasis if its internal environment is disturbed.  For every drug action in the body there is an equal (as far as possible) reaction which tends to restore the status quo.  This mechanism underlies the development of drug tolerance and dependence and also of withdrawal reactions if the drug is stopped.  It applies not only to benzodiazepines but also to non-psychotropic drugs like b blockers. For example, B blockers such as propranolol are used to slow the heart and lower the blood pressure.  If these are suddenly stopped there is a rebound of increased heart rate and raised blood pressure.  We accept that tolerance and withdrawal reactions occur with benzodiazepines, barbiturates and all the hypnotic and sedative drugs that have gone before.  We even understand much about the molecular mechanisms involved - which I won't go into here.  There seems no reason to believe that these reactions will not apply to Z-drugs.  

"I suspect that the Z-drugs will undergo the fate of many newly introduced drugs - a fate that is becoming all too familiar."  

Other Quotes from Dr. Heather Ashton:  

Hypnotics and sedatives. Most other hypnotics and sedatives act in a similar way to benzodiazepines, including barbiturates, chloral derivatives (Noctec), ethchlorvynol (Placidyl), zopiclone (Zimovane, Imovane), zolpidem (Ambien), zaleplon (Sonata) and, incidentally, alcohol. None of these drugs should be used as alternative sleeping pills or sleeping draughts during benzodiazepine withdrawal. All can cause a similar type of dependence and some are more toxic than benzodiazepines.  

"It should go without saying that you cannot take a different benzodiazepine for sleep. That might be effective in inducing sleep, but it is the equivalent of increasing your dose and reversing your recovery process. The same holds true to varying degrees for barbiturates, alcohol, opiates and narcotics.  

You should also avoid the sedative drugs Ambien (zolpidem) and Imovane (zopiclone) which are chemically different from benzodiazepines but have the same effects on the body and act by the same mechanisms."  

"Avoid compensating for benzodiazepines by increasing your intake of alcohol, cannabis or non-prescription drugs. Occasionally your doctor may suggest other drugs for particular symptoms (see Chapter III http://www.benzo.org.uk/manual/bzcha03.htm, Withdrawal Symptoms), but do not take the sleeping tablets zolpidem (Ambien), zopiclone (Zimovane, Imovane) or zaleplon (Sonata) as they have the same actions as benzodiazepines."  

Quote from http://www.benzo.org.uk/ashbristol.htm  

"Not to be outdone, the drug companies rapidly produced a series of drugs that were not chemically benzodiazepines but produced the same effects. These were the Z-drugs zopiclone, zolpidem, zaleplon and now eszopiclone (Lunesta). They were marketed as sleeping pills but in fact have similar properties to benzodiazepines. They act on GABA receptors, cause dependence and, like benzodiazepines, cause a withdrawal syndrome."

 

Quote from this site: http://www.drug-rehabs.org/drugs/ambien.php

What are the effects of Ambien?  

Daytime drowsiness

Dizziness

Lightheadedness

Difficulty with coordination

Tolerance

Dependence

Changing in thinking and/or behavior

 

Ambien may cause special type of memory loss known as amnesia. When this occurs, a person may not remember what has happened for several hours after taking the medicine. In addition, addiction, or dependence, can be caused by Ambien, especially when used regularly for longer than a few weeks or at high doses. People who have been dependent on alcohol or other drugs in the past may have a greater chance of becoming addicted to Ambien. Some people using Ambien have experienced unusual changes in their thinking and/or behavior. 

From the Lunesta website:  

http://www.lunesta.com/lunestaOverview/lunestaPPI.html  

Dependence

Sleep medicines can cause dependence in some people, especially when these medicines are used regularly for longer than a few weeks or at high doses.  

Dependence is the need to continue taking a medicine because stopping it is unpleasant.

When people develop dependence, stopping the medicine suddenly may cause unpleasant symptoms (see Withdrawal below). They may find they have to keep taking the medicine either at the prescribed dose or at increasing doses just to avoid withdrawal symptoms. 

All people taking sleep medicines have some risk of becoming dependent on the medicine. However, people who have been dependent on alcohol or other drugs in the past may have a higher chance of becoming addicted to sleep medicines. This possibility must be considered before using these medicines for more than a few weeks. If you have been addicted to alcohol or drugs in the past, it is important to tell your doctor before starting LUNESTA or any sleep medicine.  

Withdrawal  

Withdrawal symptoms may occur when sleep medicines are stopped suddenly after being used daily for a long time. In some cases, these symptoms can occur even if the medicine has been used for only a week or two. In mild cases, withdrawal symptoms may include unpleasant feelings. In more severe cases, abdominal and muscle cramps, vomiting, sweating, shakiness, and, rarely, seizures may occur. These more severe withdrawal symptoms are very uncommon. Although withdrawal symptoms have not been observed in the relatively limited controlled trials experience with LUNESTA, there is, nevertheless, the risk of such events in association with the use of any sleep medicine.  

 

"Lunesta is a hypnotic.  ALL hypnotics can cause addiction/dependency problems and are little different from benzos in that aspect."  Dr. Peart, head of VOT (Victim of Tranquilizers) in the UK

Here are some quotes from Ashton about Ambien (also a hypnotic as you know), some drug inserts, and also some websites that show that Lunesta is not a new drug at all! 

"..... is that there is no medication which will substitute for a benzodiazepine, unless it is another benzodiazepine, or a drug with benzodiazepine-like properties (such as barbiturates or zolpidem [Ambien]).  All such drugs should be avoided as they only substitute one type of dependence for another."  

"Hypnotics and sedatives. Most other hypnotics and sedatives act in a similar way to benzodiazepines, including barbiturates, chloral derivatives (Noctec), ethchlorvynol (Placidyl), zopiclone (Zimovane, Imovane), zolpidem (Ambien), zaleplon (Sonata) and, incidentally, alcohol. None of these drugs should be used as alternative sleeping pills or sleeping draughts during benzodiazepine withdrawal. All can cause a similar type of dependence and some are more toxic than benzodiazepines." 

This (below) is from the drug insert and of course by now, you most likely know there is a lot of under-reporting here and they like to infer that if you should have a problem, you are an 'addictive' personality.  They also say that this 'problem' will only last 3 days or so and feel like a mild flu.  We are of course, not finding this to be true and in fact, have many on the benzo groups who are dependent/addicted to non-benzos. 

"Abuse and dependence: Studies of abuse potential in former drug abusers found that the effects of single doses of Ambien (zolpidem tartrate) 40 mg were similar, but not identical, to diazepam 20 mg, while zolpidem tartrate 10 mg was difficult to distinguish from placebo. 

Sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. These reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. The U.S. clinical trial experience from zolpidem does not reveal any clear evidence for withdrawal syndrome.  

Nevertheless, the following adverse events included in DSM-III-R criteria for uncomplicated sedative/hypnotic withdrawal were reported during U.S. clinical trials following placebo substitution occurring within 48 hours following last zolpidem treatment: fatigue, nausea, flushing, lightheadedness, uncontrolled crying, emesis, stomach cramps, panic attack, nervousness, and abdominal discomfort. These reported adverse events occurred at an incidence of 1% or less. However, available data cannot provide a reliable estimate of the incidence, if any, of dependence during treatment at recommended doses. Rare post-marketing reports of abuse, dependence and withdrawal have been received.  

Because persons with a history of addiction to, or abuse of, drugs or alcohol are at increased risk of habituation and dependence, they should be under careful surveillance when receiving zolpidem or any other hypnotic."  

Here is another site on Lunesta:  

http://www.erowid.org/pharms/zopiclone/zopiclone_health1.shtml   

 

Disclaimer:  The information contained in this website was not compiled by a doctor or anyone with medical training. The advice contained herein should not be substituted for the advice of a physician who is well-informed in the subject matter discussed. Before making any decisions about your health or treatment you should always confer with your physician and it is always assumed that you will do so.

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Last updated 22 July 2015