The Z Drugs

The Z drugs are a group of drugs commonly referred to as the "nonbenzodiazepines". The Z drugs are molecularly distinct from the benzodiazepines but their mechanism of action is very similar. The Z drugs work via benzodiazepine receptors in the same way as benzodiazepines work. The only difference is that some of the Z drugs are more selective in their targeting of certain benzodiazepine receptors.

In order to explain the logic behind several methods of tapering off of Z drugs and in order to help you to decide which method to use to withdraw from your nonbenzodiazepine Z drugs, it is necessary to give a brief summary of the mechanism of actions of the Z drugs.

There are 6 subtypes of benzodiazepine receptors. The subtypes (known as alpha subunits) of receptors that benzodiazepines bind to are as follows, alpha1, alpha2, alpha3 and alpha5. Benzodiazepines and Z drugs have no affinity at all for alpha4 and alpha6 GABAa-benzodiazepine receptors. The alpha1 receptor is responsible predominantly for the hypnotic action of benzodiazepines receptor agonist drugs. The alpha2 receptors are primarily muscle relaxant but also have some effect on anxiety. The alpha3 subunits are primarily anxiolytic. The alpha5 receptors are responsible for memory and produce the amnesia side effects of benzodiazepines. Alpha1, alpha2 and alpha3 subunits are responsible for the anticonvulsant properties of benzodiazepines. The GABAa receptor is made up of different subunits and the alpha subunits contain a benzodiazepine receptor. Depending on the subunit a certain property will be exerted if those subunits are activated such as sedation, antianxiety or hypnotic etc.

Zopiclone and eszopiclone, behave identically to benzodiazepines binding unselectively to all the types of benzodiazepine receptors that benzodiazepines bind to with the same affinity. Zaleplon and zolpidem have a high affinity for the alpha1 subunits and a low to moderate affinity for alpha2 and alpha3 receptors and very low affinity for the alpha5 subunits.

Withdrawing from Z drugs

Withdrawing directly from the Z drugs can be particularly problematic because the Z drugs are short acting drugs. This can lead to day time withdrawal symptoms such as anxiety, agitation, headaches, nausea, muscle spasms and a range of symptoms similar to benzodiazepine withdrawal symptoms. In order to reduce these day time withdrawal symptoms if one is experiencing them and in order to allow for stable dose levels of a benzodiazepine acting drug a switch to diazepam is the prefered method of withdrawing from Z drugs. The reasons for a diazepam taper are its long half life and availability in low potency doses. Read the article by Dr JG McConnell on the reasons for using a diazepam dose taper to come off of Z drugs.

Concerns about diazepam

Sometimes people express concern about switching from a Z-drug to an equivalent dose of diazepam. They sometimes worry that they are merely starting a new addiction. This is not the case because the Z drugs work on the same brain receptors, although in the case of zolpidem and zaleplon there is more selectivity in binding to benzodiazepine receptors as explained above. People who are worried about the differences between the binding affinities and are worried about small differences between receptor affinities may prefer to do a partial cross over to diazepam to allay any fears, so their bodies will only ever be exposed to low doses of diazepam.

Partial cross over method

So for example lets say someone was taking 20 mg of zolpidem (ambien, stilnox etc) and wanted to withdraw via a partial cross over and taper. They could switch 5 mg of zolpidem for 2.5 mg of diazepam using the 2 mg tablets (1 and a quarter 2 mg tablets). That would leave them on 15 mg of zolpidem and 2.5 mg of diazepam. They could then reduce by 0.5 mg of diazepam every few weeks to zero diazepam. Then switch another 5 mg of zolpidem for 2.5 mg of diazepam leaving them on 10 mg of zolpidem and 2.5 mg of diazepam and taper down by 0.5 mg every few weeks or so. Keep repeating these steps until you are completely withdrawn from zolpidem.

The equivalency for zaleplon is the same as for zolpidem. 20 mg of zolpidem is equivalent to 10 mg of diazepam. 20 mg of zaleplon is also equivalent to 10 mg of diazepam. So the partial cross over and taper method suggested above for zolpidem can be applied to tapering off of zaleplon.

Direct taper method

The direct taper method basically means just that. Tapering directly off of the Z drug that you are taking without switching to diazepam. This may be particularly difficult for many people largely due to the very short half life of the Z drugs. It is not what we would generally recommend. However, some people have managed to directly taper off of Z drugs directly eg by reducing by a quarter of a tablet every few weeks but most find it very difficult.