Z-drugOverview: Z-drugs for sleep

Z-drugs are a group of non-benzodiazepine drugs with effects similar to benzodiazepines. They are used in the treatment of insomnia, and their names usually start with the letter “Z”. Some Z drugs may have advantages over benzodiazepines. Benzodiazepines actually worsen sleep architecture whereas the Z-drug (such as Zaleplon) may have less or no disruption of sleep architecture.

The first three non-benzodiazepine drugs to enter the market were the “Z-drugs”: zopiclone, zolpidem and zaleplon. These three drugs are all sedatives used exclusively for the treatment of mild insomnia. They are safer than the older barbiturates especially due to the risk of overdosing and they may, when compared to the benzodiazepines, have less of a tendency to induce physical dependence and addiction, although these issues can still become a problem. This has led to the Z-drugs becoming widely prescribed for the treatment of insomnia particularly in elderly patients.

Z-drugs (zaleplon, zolpidem, zopiclone and eszopiclone) are strictly speaking not benzodiazepines. They don’t have the same chemical structure as a benzodiazepine, but act on the same area in the brain and have a similar effect on the brain cells as benzodiazepines.

Non-benzodiazepines/Z-drugs are thought to have fewer side effects, and less risk of dependency, but are still considered controlled substances. Generally, Z-drugs have fewer drawbacks than benzodiazepines, but that doesn’t make them suitable for everyone. Some may find this type of sleep medication ineffective at helping them sleep, while the long-term effects remain largely unknown.

There is some limited evidence that suggests that tolerance to nonbenzodiazepines is slower to develop than with benzodiazepines. However, data are limited so no conclusions can be drawn. Data are also limited into the long term effects of Z-drugs and nonbenzodiazepines. Further research into the safety of Z-drugs and long term effectiveness of them has been recommended in a review of the literature.

Using Z-drugs for sleep

Taking one of the new sleeping tablets can help you get to sleep more easily. You may also sleep a bit longer (30-40 minutes) and wake less at night.

Z-drugs can usually be taken as tablets or capsules. You should only take Z-drugs in the doses prescribed for you. Don’t take more than your GP has recommended, as an overdose of Z-drugs can be fatal.

Don’t mix Z-drugs with alcohol as they could interact and potentially be dangerous. Always ask your GP for advice and read the patient information leaflet that comes with your medicine.

You shouldn’t take one of the newer sleeping tablets for more than four weeks, because you could become dependent on them. This means you get unpleasant effects when you stop taking the medicine. For example, you may feel anxious and have panic attacks if you don’t take your medicine every night. You may also find it hard to sleep without the medicine.

If you are a woman and you are pregnant, you shouldn’t take Z-drugs regularly as your baby may be at risk of getting withdrawal symptoms. You also shouldn’t take them if you are breastfeeding.

Z-drugs have a relatively high potential to be abused. Often this use involves a different delivery method to induce effects faster. The mind and judgment altering effects of Zaleplon are similar to those of many other benzodiazepines but the fast-acting nature and short half-life of the chemical mean that high dosages come on much more quickly and last for short periods of time (usually from 45 to 60 minutes). Insufflating the drug causes effects to happen even more quickly, and last for even shorter periods of time, with some loss of yield as Zaleplon is not entirely water soluble.

Side-effects of Z-drugs

The Z-drugs are not without disadvantages. Latest studies have revealed the following (most common) side effects: headaches, pain, drowsiness, a blocked nose and dizziness. This said, it’s commonly agreed that further studies are required.

More rarely these drugs can produce a fugue state where the patient sleepwalks and may perform relatively complex actions, including cooking meals or driving cars, while effectively unconscious and with no recollection of the events upon awakening. While this effect is rare (and has also been reported to occur with some of the older sedative drugs such as temazepam and secobarbital) it can be potentially hazardous and so further development of this class of drugs has continued in an effort to find new compounds with further improved profiles.

Daytime withdrawal related anxiety can also occur from chronic nightly non-benzodiazepine usage such as with zopiclone.

Side effects can differ within the drug class due to differences in metabolism and pharmacology. For example long acting benzodiazepines have problems of drug accumulation especially in the elderly or those with liver disease and shorter acting benzodiazepines have a higher risk of more severe withdrawal symptoms. In the case of the non-benzodiazepines, zaleplon may be the safest in terms of next day sedation and, unlike zolpidem and zopiclone, zaleplon has been found to have no association with increased motor vehicle accidents even when taken for middle of the night insomnia due to its ultra short elimination half life.

Non-benzodiazepines and Z-drugs should not be discontinued abruptly if taken for more than a few weeks due to the risk of rebound withdrawal effects and acute withdrawal reactions which may resemble those seen during benzodiazepine withdrawal. Treatment usually entails gradually reducing the dosage over a period of weeks or several months depending on the individual, dosage and length of time the drug has been taken. If this approach fails a cross over to a benzodiazepine equivalent dose of a long acting benzodiazepine such as chlordiazepoxide or preferably diazepam can be tried followed by a gradual reduction in dosage. In extreme cases and particularly where severe addiction and or abuse has manifested, an inpatient detoxification may be required with flumazenil as a possible detoxification tool.

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