Valium (Diazepam) vs. Klonopin (Clonazepam) in
by Dr. Reg Peart Victims of Tranquilizers
About 20 different drugs, including diazepam, clonazepam, barbiturates and other non-benzodiazepine
drugs have been used for treating benzodiazepine withdrawals with varying degrees of success or
failure. Diazepam is the most commonly used drug and has the highest success rate for the reasons
given below, but because of the large inter-individual variability of response to benzodiazepines,
there is no “one size fits all” solution to the withdrawal problem.
Diazepam and clonazepam, like all benzodiazepine drugs, were found to have five therapeutic actions,
i.e. anxiolytic, muscle relaxant, anticonvulsant, amnesic and hypnotic. Diazepam was marketed in the
mid 1960’s for all five therapeutic actions; while clonazepam was developed and researched in the late
1960’s and early 1970’s and marketed in the mid 1970’s primarily as an anxiolytic and anticonvulsant.
Any drug with similar therapeutic spectrum to the above will be both cross tolerate and cross dependent
with the benzodiazepines and in principle will be of some help in benzodiazepine withdrawal. As well
as the therapeutic actions, drugs with long half-lives are essential to prevent interdose withdrawals and
to produce a helpful accumulation of the parent drug.
In a few benzodiazepines the metabolites of the parent drug are also therapeutically active with the
same five therapeutic actions. Of these only diazepam and chlordiazepoxide (Librium) have long
half-lives for the parent drug and for the active metabolites. Librium is most commonly used for
alcohol withdrawal and diazepam for a range of drug withdrawal problems.
The active metabolites of diazepam are:
1) Desmethyldiazepam – marketed as clorazepate (Tranxene) and prazepam (Centrax).
2) Oxazepam – marketed as Serenid
3) Temazepam – marketed as Normison/Euhypnos
The combined half-life of diazepam and its active metabolites is over 200 hours and this produces an
accumulation of 5-7 times the therapeutic action of diazepam. It takes up to eight weeks for most of
the accumulated drugs to be eliminated from the body. This "umbrella" of the benzodiazepines is the
main reason for the success of diazepam tapering. The high accumulation levels produced by the
diazepam active metabolites also reduces the probability of tolerance problems during tapering.
There is no obvious reason why about 10% of the people have problems with
diazepam tapering, but it is sometimes due to one or more of the following:
1) Incorrect equivalent dose – the values quoted by Ashton, et. al. are those found to be effective
in benzodiazepine withdrawal and should in principle compensate for any difference in binding of
the benzodiazepines to either the same or different benzodiazepine receptors. There values are
not necessarily the same as therapeutically effective doses, but sometimes are.
2) Poorly planned or too short a period for the exchange from another benzodiazepine to diazepam.
Mild daytime sedation at the end of a 2-3 weeks exchange suggests the equivalent dose is correct.
3) Failure to maximize accumulation of diazepam used and its metabolites – it takes about four
weeks to achieve 90% accumulation, i.e. four weeks after exchange.
4) Tapering too fast. Each person should find the rate suitable to themselves. A good starting guide
is 2 ˝ % of the initial dose/week. The rate for the last 1/3 of the taper should be reduced to ˝ of
that for the first 2/3.
Clonazepam is one of the nitro-benzodiazepines series, i.e. nitrazepam, flunitrazepam, clonazepam,
and nimetazepam. It has a half-life of 20-50 hours and accumulates from 1.5 to 3 times the daily
dose level. Most of it is eliminated from the body in 5–10 days. Along with triazolam, clonazepam has
the highest incidence of side effects/adverse reactions of the benzodiazepines.
An important difference between diazepam and clonazepam is that clonazepam does not
produce active metabolites. Withdrawal symptoms increase markedly with accumulation of
clonzepam, much of which is due to action of the inactive metabolites as well as the parent drug.
This withdrawal symptom problem can be minimized at dose levels below 3 mg/day.
In most countries, diazepam is marketed in 2 mg, 5 mg, and 10mg tablets and solution yielding 0.1 mgs
or less. Clonazepam is marketed only as 0.5 mg. and 2 mg. (in the US it is produced as 0.125 mg,
0.25 mg, 0.50 mg, 1.0 mg, and 2.0 mg tablets). Hence for many, the option of using clonazepam will
not be available for practical reasons.
Very few papers have been published on the use of clonazepam in benzodiazepine withdrawals
compared with many on the use of diazepam; hence it is not possible to make an assessment of their
relative merits. Clonazepam meets three out of four of the criteria (1. The five therapeutic actions,
2. A long half-life, and 3. Accumulation) and it may well be suitable for a minority – it’s a “black art” not a science.
N.B. It has been reported that diazepam produced by generic suppliers can vary by as much as 20%
of the stated dose from batch to batch. If so, in order to avoid possible dose variations, Valium
as produced by Roche should be used in diazepam tapering – it is more expensive.
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.
Last updated 21 July 2020