The Klonopin-Valium Crossover explained

Note: not everyone finds crossing-over helpful. For those who determine it’s a good idea here is some information. 

More info on benzo use and benzo withdrawal here: Benzo Info

Valium (Diazepam) vs. Klonopin (Clonazepam) in Benzodiazepine Withdrawal
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:

Desmethyldiazepam – marketed as clorazepate (Tranxene) and prazepam (Centrax).

Oxazepam – marketed as Serenid

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:

  • 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.
  • 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.
  • 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.
  • Tapering too fast. Each person should find the rate suitable to themselves. A good starting guide is 2 ½ % of the initial dose/week. The rate for the last 1/3 of the taper should be reduced to ½ 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.

More info on benzo use and benzo withdrawal here: Benzo Info

5 thoughts on “The Klonopin-Valium Crossover explained

Add yours

  1. My Mom who’s 83 now – a couple years ago a dr. – internal med – had her change from Valium to Clonsipam in one fell swoop – it didn’t go well as my mom had TONS of paranoia and after about 2 weeks of TRYING to manage her moods etc. we went HAPPILY back to Valium. She’s been on it since and she required a HIGHER dose which I have since gotten her down to 5mg a day – 2.5 morning and night.
    Dumb doctor!


  2. a doc told me my lamictal withdrawal set up a hostile environment to take the K at all…so yeah, I’ve heard the same thing too that they somehow mess with one another…

    I’ve also been told and had experience with people in benzo groups that taking K or another benzo intermittently can cause addiction and more problems with ongoing sleeping…

    you might want to do some research on amino acids to help you sleep and ditch the K…it’s really playing with fire…

    I understand the desire to sleep…it’s a powerful one and a necessary one as well but it’s also why so many people get hooked on this crap…if they don’t look for natural safer ways to help sleep.

    I have reached total benzo tolerance which means it was doing nothing to help me sleep…I got to the point where I was only sleeping 0 – 3 hours a night for months on end until I found an amino acid combo that works real well…

    but aminos are tricky and I would talk to a naturopath or integrative doc to help you out…

    I will tell you the product that seems to work best for me (I emphasize ME—as we’re all different) is Travacor by Neuroscience.

    but taurine, theanine and tryptophan are all possibilities too…and in fact Travacor is a combination of some of those.


  3. Interesting… I didn’t know all that… Klonopin is one of the drugs I’m on, I take 1 mg once or twice a week. According to a school psychologist Dave spoke to, taking klonopin and lamictal at the same time (as I’m doing) can make both drugs more addictive. I’m sure that my psychiatrist would say that’s hogwash, but to me, it’s worth looking into.

    I actually don’t think Klonopin is that bad, and plan on keeping it on store for times when I really can’t sleep, since, like all of us with this label (BP) I really go weird if I can’t sleep. But it is addictive and it is a chemical, so… oh I don’t know… this stuff is all confusing.



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