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Professor C Heather Ashton DM, FRCP
April 2001

School of Neurosciences
Division of Psychiatry
The Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne NE1 4LP

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  1. Diazepam [Valium] is one of the most slowly eliminated benzodiazepines. It has a half-life of up to 200 hours, which means that the blood level for each dose falls by only one half in about 8.3 days. The only other benzodiazepines with similar half lives are chlordiazepoxide [Librium], flunitrazepam [Rohypnol] and flurazepam [Dalmane] all of which are converted to a diazepam metabolite in the body. The slow elimination of diazepam allows a smooth, gradual fall in blood level, allowing your body to adjust slowly to a decreasing concentration of the benzodiazepine. With more rapidly eliminated benzodiazepine e.g. lorazepam, (Ativan) (which has a half-life of 10-20 hours) the blood concentration drops rapidly and withdrawal symptoms can occur between doses, because your body has little time to adjust to low concentrations.

  2. Diazepam comes in the smallest dosage levels of all benzodiazepines – 2mg tablets which can be halved to give 1mg doses. This means you can reduce in stages of 1mg every 1-4 weeks or more. It is difficult to obtain such low doses of other benzodiazepines. For example the lowest dose of lorazepam in the UK is 1mg, equivalent to 10mg of diazepam. (In the US 0.5mg lorazepam are available, but these are equivalent to 5mg diazepam).

  3. Many other benzodiazepines are more potent than diazepam. For example lorazepam (Ativan) is 10 times stronger and it is difficult to reduce from this gradually. Temazepam [Restoril], though less potent than diazepam, has a shorter half-life and the smallest tablet is 10 mg (equivalent to 5mg diazepam).

  4. Because of the slow elimination and small available dosage strengths of diazepam, it is often advisable to switch to diazepam when withdrawing from other stronger or more rapidly eliminated benzodiazepines. This switch allows you to tail off your benzodiazepine dosage smoothly and gradually and minimises withdrawal symptoms.

  5. When making the switch it is important to do it gradually, replacing one dose at a time and at approximately weekly intervals and making allowance for the difference in potency. For example, if you are taking lorazepam 1mg three times daily, first change the night dose to 10mg diazepam. (This can be done in two stages if necessary e.g. lorazepam 0.5mg (half a 1mg tablet) plus diazepam 5mg; then drop the lorazepam and go on to diazepam 10mg). A week or two later change one of the day-time doses, and two weeks later change the other day-time dose.

    Suggested schedules and information on relative potencies and elimination half-life are available in the Manual: "Benzodiazepines: How they work and how to withdraw".


Professor C Heather Ashton, DM, FRCP
April 2001

It is often suggested that the chemical makeup of diazepam [Valium] does not address many of the receptor sites the newer medications (eg alprazolam [Xanax], clonazepam [Klonopin]) have an effect on.

All the benzodiazepines are non-selective and act on all types of GABA/benzodiazepine receptors. Valium acts on exactly the same receptors as Klonopin etc.

The GABA-A receptor subtype alpha2 is responsible for anti-anxiety effects and amnesia, GABA-A alpha1 subtype for sedation, and both alpha1 and alpha2 as well as alpha5 subtypes for the anticonvulsant effects. All the benzodiazepines act on all of these. Zopiclone and zolpidem are meant to be more selective, acting mainly on alpha1 subtype, though this is only relative.

Therefore there is no reason for not substituting Valium in Klonopin, Xanax and Ativan withdrawal. I have done it successfully in many patients. The only reasons for people getting "a type of withdrawal" while still on medication are if the correct equivalent dose has not been given, or if the substitution has been carried out abruptly instead of stepwise.

Klonopin, Ativan and Xanax are all much more potent than Valium (equivalents given in Manual). Xanax and Ativan are relatively rapidly eliminated. Klonopin has a half life of 18 to 50 hours compared to Valium's 200 hours, so Klonopin cannot be called long-acting. The suggestion that "Klonopin is the only long-acting benzo that is able to cover Klonopin receptors" is nonsense. There are no such things as just Klonopin receptors, as explained above.

"The classical benzodiazepines act indiscriminately on all diazepam-sensitive GABA-A receptors", according to Rudolph, Crestani & Möhler in an article entitled "GABA receptor subtypes: dissecting their pharmacological functions", Trends in Pharmacological Sciences, 22: 188-193, 2001. References 28-32 in this article support this point. Hans Möhler is a highly respected biochemist who first described the benzodiazepine receptor.

The main reason that benzodiazepines have somewhat different structures is not so much that they act on different receptors (they don't) but so that the drug companies can call them different drugs. They remain chemically benzodiazepines (a chemical name). Although they may differ in binding affinity for the receptors, potency, elimination time, etc., they all act on all subclasses of benzodiazepine receptors.

Further Note on Klonopin vs Valium: April 15, 2002. It is well known that Klonopin is a good anticonvulsant. In fact its only indication for use in the UK is for epilepsy. The fact that it has a higher affinity for GABA-A receptor sites than diazepam simply means that it is more potent, but potency is mainly a matter of equivalent dosages. Binding of clonazepam to receptors that do not bind to other benzodiazepines and action on sodium channel conductors are relevant to anticonvulsant effects, not tranquillising effects. The fact that clonazepam has sedative and anxiolytic actions and typical adverse effects of benzodiazepines including ataxia, irritability, depression and tolerance shows that there is little overall difference.

Since clonazepam has a relatively short half life, from 18 to 50 hours, I don't think it would be any easier to come off it using 1/64th mg capsules. I think you still need a long-acting benzodiazepine such as diazepam. I would also reiterate that I have known people make the clonazepam to diazepam substitution and final withdrawal without difficulty.

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