Benzodiazepines (Valium, Sobril, Xanax, Xanor, Mogadon, Rohypnol, etc.) Half Life (Duration of effect)

Written by: Prof. Heather Ashton, DM, FRCP Emeritus Professor of Psychopharmacology School of Neurosciences, Division of Psychiatry, The Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, England, UK

First version: 22 Jul 2008. Latest revision: 18 Jan 2016.

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Potency

A large number of benzodiazepines are available. There are major differences in potency between different benzodiazepines, so that equivalent doses vary as much as 20-fold. For example, 0.5 milligrams (mg) of alprazolam (Xanax) is approximately equivalent to 10mg of diazepam (Valium). Thus a person on 6mg of alprazolam daily, a dose not uncommonly prescribed in the US, is taking the equivalent of about 120mg of diazepam, a very high dose. These differences in strength have not always been fully appreciated by doctors, and some would not agree with the equivalents given here. Nevertheless, people on potent benzodiazepines such as alprazolam, lorazepam (Ativan) or clonazepam (Klonopin) tend to be using relatively large doses. This difference in potency is important when switching from one benzodiazepine to another, for example changing to diazepam during withdrawal, as described in the next chapter.

Speed of elimination

Benzodiazepines also differ markedly in the speed at which they are metabolised (in the liver) and eliminated from the body (in the urine). For example, the "half-life" (time taken for the blood concentration to fall to half its initial value after a single dose) for triazolam (Halcion) is only 2-5 hours, while the half-life of diazepam is 20-100 hours, and that of an active metabolite of diazepam (desmethyldiazepam) is 36-200 hours. By a metabolite is meant a drug, which the original drug is converted to when the body disposes of the original drug. By an active metabolie is meant a metabolite which still has the same effect as the original drug. This means that half the active products of diazepam are still in the bloodstream up to 200 hours after a single dose. Clearly, with repeated daily dosing accumulation occurs and high concentrations can build up in the body (mainly in fatty tissues). There is a considerable variation between individuals in the rate at which they metabolise benzodiazepines.

Note that traces of these drugs can be detected in the hair for as long time as the hair has been growing.

Table 1. BENZODIAZEPINES AND SIMILAR DRUGS ⁵

1. Half-life: time taken for blood concentration to fall to half its peak value after a single dose. Half-life of active metabolite shown in square brackets. This time may vary considerably between individuals.
2. Market aim: although all benzodiazepines have similar actions, they are usually marketed as anxiolytics (a, tranquilizers), hypnotics (h, sleeping pills) or anticonvulsants (e, reducing epileptic seizures or convulsions).
3. A higher value in this column means that a larger dose is needed to get equivalent effect of durgs with a lower value in this column. These equivalents do not agree with those used by some authors. They are firmly based on clinical experience but may vary between individuals.
4. These drugs are chemically different from benzodiazepines but have the same effects on the body and act by the same mechanisms.
5. All these drugs are recommended for short-term use only (2-4 weeks maximum).

Duration of effects

The speed of elimination of a benzodiazepine is obviously important in determinisizeng the duration of its effects. However, the duration of apparent action is usually considerably less than the half-life. With most benzodiazepines, noticeable effects usually wear off within a few hours. Nevertheless the drugs, as long as they are present, continue to exert subtle effects within the body. These effects may become apparent during continued use or may appear as withdrawal symptoms when dosage is reduced or the drug is stopped.

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