Yes, it would be fine to switch from Ativan to Valium so long as the equivalent dosages are observed. 1 milligram of Ativan is equivalent to 5 milligrams of Valium, therefore, the correct equivalent dosage would be 2.5 milligrams of Valium.
However, given that Valium has less binding affinity (potency) in comparison to Ativan, it would be more ideal to substitute the 0.5 milligram dose of Ativan with 5 milligrams of Valium. This would also help to cover any tolerance that may have developed as a result of Ativan.
Also, observe the half-life variations of the two drugs. The glucuronide metabolite of Ativan carries a half-life of 18 hours, while Valium has a half-life ranging from 24-100 hours. Therefore, it would be wise to gradually step the Ativan out while simultaneously stepping in the Valium. An example would look like this:
Days 1-5: Morning (Ativan 0.25 mg, Valium 2.5 mg)
Day 5: Valium, 5 mg, qd.
By gradually introducing the Valium, the potential for withdrawal is greatly reduced. Valium must accumulate to replace the Ativan in its entirety.
I would also note that while Valium carries an impressive half-life, the distribution phase of the drug in the brain is only one hour. The duration of action ranges from 6-8 hours. In that respect, it is comparable in duration of action to Ativan. You may wish to inquire about adding a second dosage of 5 mg. Dosed in this fashion (twice daily), the Valium will accumulate to a steady-state plasma concentration and prevent interdose. A single daily dose of Valium will not prevent the interdose that you are currently experiencing with Ativan. An additional strategy is to implement three 2 milligram dosages. This will provide for an even greater reduction in interdose. To implement the 2 mg, t.i.d. strategy, an example would look like this:
Days 1-5: Morning (Ativan 0.25 mg, Valium 1 mg), Afternoon (Valium 2 mg), Night (Ativan 0.25 mg, Valium 1 mg)
Days 5-10: Morning (Valium 2 mg), Afternoon (Valium 2 mg), Night (Ativan 0.25 mg, Valium 1 mg).
Day 10: Valium, 2 mg, t.i.d.
Let us know how it works out for you, and what the plan is.
Hi can you tell me what t.i.d is ? also I was under the impression I could dose once a day with the Valium since it stays in the body longer than Ativan.
t.i.d. is an abbreviation for three times daily.
While Valium does carry a longer half-life than Ativan (stays in your body longer), it only remains in the brain for a limited period of time. Valium is highly lipophilic (likes fat tissue), and the majority of the absorbed dosage is stored in fat tissue.
The half-life of a drug does not correlate with duration of action. The duration of action for Valium is 6-8 hours. A single daily dose would not be adequate. The bare minimum would be twice daily. Optimally, it should be dosed three to four times daily.
If you are looking for something that may be dosed once daily, Klonopin carries a duration of action ranging from 12-18 hours. This may be a more appropriate choice for you. Equivalent dosage is 0.25 mg for Klonopin, although 0.5 mg would be more optimal. Valium isn't particularly effective for anxiety or panic at lower dosages, but Ativan and Klonopin are. Of the Benzodiazepines, Klonopin carries the longest duration of action. It is also less likely to induce tolerance.
Your information is contrary from everything I have read in the ashton manual.
I refuse to take klonopin
Is there any particular reason(s) why you'd refuse to take Klonopin? This is the one Benzodiazepine that is the least likely to induce tolerance over the long-term. And unlike Ativan, it is relatively easy to discontinue if the need should arise.
In reference to my information on Valium being contrary to what you have read elsewhere, I would recommend that you simply request a script and try it for yourself. You will find that it is actually shorter-acting than Ativan. That isn't necessarily a problem, but it would require multiple dosing to prevent interdose or rebound anxiety.
Another one to consider if Klonopin isn't an option is Librium, which is very similar to Valium, but carries a longer duration of action. Equivalent dosage is 25 milligrams.
I just would like to know where you got the information about duration of action on these drugs.
Kaplan & Sadock's Synopsis of Psychiatry, 2007.
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:
1) Desmethyldiazepam – marketed as clorazepate (Tranxene) and
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 benzodiazepinesa 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
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 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
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.
REASONS FOR A DIAZEPAM (VALIUM) TAPER
Professor C Heather Ashton DM, FRCP
Professor Heather Ashton
School of Neurosciences
Division of Psychiatry
The Royal Victoria Infirmary
Queen Victoria Road
Newcastle upon Tyne NE1 4LP
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.
ALL BENZODIAZEPINES ARE NON-SELECTIVE
Professor C Heather Ashton, DM, FRCP
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.
If you reside in the United States, I wish you luck in finding a physician who will accept the viewpoints expressed by either of these authors. 75% of this information is incorrect. The remaining 25% are half-truths. The "information" comes off as highly biased (which it is).
The power of suggestion is very strong - stronger than any Benzodiazepine is. If you are easily suggestible and you read this type of biased material, you will be inclined to believe it, as did many others before you. I think at this stage the best option for you is to follow what you have read, and go from there. I don't think that you'll be satisfied until you try Valium.
The truth is that Valium is 98% bound to plasma proteins. It rapidly crosses the blood-brain barrier and peaks within 2 hours following administration. Following the peak, the initial distribution phase in the brain is one hour. Since Valium is highly bound to plasma proteins, the drug is rapidly redistributed to adipose (fat) tissue. It is stored there, and slowly eliminated over a period of 4 days (or one month for prolonged use). Given that it is redistributed throughout the body, the duration of action following a single dose is 6-8 hours (average 6). The actual half-life of the drug (which is actually 30-100 hours) means very little.
Additionally, the so called "active metabolites" (Oxazepam and Temazepam) are Glucuronidated during the metabolic process and are excreted rapidly via the kidneys. So, they are not "active", and they do not count as part of Valium's overall pharmacological effect. Valium's active metabolite is Desmethyldiazepam. This is what exerts an effect. The concept of several active metabolites is praised in the above articles, but what it really means is that the drug is "dirty". Librium was Sternbach's first creation, and was even dirtier. Then Valium followed. Today, we have Tranxene (pure Desmethyldiazepam), which is cleanest Diazepam variant.
By comparison, Klonopin is 86% bound to plasma proteins. Therefore, it is less lipophilic than Valium, Librium or Tranxene. It also takes longer to peak (2-4 hours). The initial distribution phase is the same as Valium, however, Klonopin is not redistributed to fat tissue like Valium. For this reason, the duration of action is prolonged to 12-18 hours. Klonopin is the longest-acting Benzodiazepine that is currently marketed. The half-life ranges from 18-50 hours (mean 34 hours). Klonopin has both a long half-life and very prolonged duration of action. It is also the drug of choice for tapering off of higher-potency Benzodiazepines, such as Ativan and Xanax. Valium has little to no affinity for alpha subunits 2 and 3 (which Ativan, Klonopin and Xanax bind to), therefore Valium is more problematic to substitute in place of them. Valium is less selective and binds to alpha subunits 1 and 5, as do all of the low-potency Benzodiazepines.
Trade Name Half-Life Duration of Action Equivalent Dosage
Ativan 12-18 8-12 Hours 1 mg
Klonopin 18-50 12-18 Hours 0.25 mg
Librium 24-48 6-8 Hours 50 mg
Serax 4-8 4-6 Hours 30 mg
Tranxene 30-100 6 Hours 7.5 mg
Valium 30-100 6-8 Hours 5 mg
Xanax 6-11 6 Hours 0.5 mg
Hi Carmen, never seen that chart before but I have seen some advice you have given to someone who wants to taper and it was bad advice. The only reason I could think of that you would have someone withdraw in 30 days from .25mg Klonopin is because they were not on the drug for very long. I also don't agree with your equivalencies of these drugs either. I will get back at you on the durations you listed.
4 months @ 0.25 mg isn't very long. The manufacturer suggests a reduction of 0.125 mg, b.i.d. every three days (which I don't agree with). Having previously been on 4 milligrams of Klonopin (and 120 of Valium before that), I found it easier to reduce the Klonopin in 0.125 mg increments every two weeks. There is no real benefit in extending the time frame beyond two weeks. 0.25 mg/month is ideal for most. It depends on the individual though.
Here is a pretty accurate Benzodiazepine comparison chart:
There are about twenty of them floating around, and no two are exactly the same. The one that I posted earlier is the one found in most medical textbooks. Numbers don't mean much in the grand scheme of things. Your response does, which is why the actual dosage should be individualized. Compare the above linked chart to Ashton's and you will see some significant variations. The above is more accurate in my view as it provides for a range, rather than some fixed arbitrary value.
Hi Carmen, thanks for that link it was very insightful. I am trying to get my hands on one of those Kaplan & Sadock's Synopsis of Psychiatry Books too.
First of all, I apologize for reviving such an old thread.
For me, it's a current issue. I have been trying to withdraw from clonazepam (2mg, once daily, muscle relaxant) for a long time (years).
I have tried both the direct method and a switch to diazepam. Diazepam is such a different drug. As night and day. Direct tapering from clonazepam is such a physical experience.
Since I didn't get any sensible support from my GP (couldn't get either a neurologist or a pdoc) I have been trying to gather more information.
However, these days there are very few websites devoted to withdrawal from benzodiazepines. ************ is one, they support the regular direct taper and the Ashton method. Nothing else. I haven't been able to find much of use over there.
I think Carmen_Sandiego made some very good points. The Ashton method, what is it based on anyway ? 300 people ? Not much of a sample size, and I'm pretty sure that clonazepam was not included.
As far as my personal situation is concerned, I have to be brief because there is a long background story. I'll add that I live in a country in Europe where doctors have very little experience with clonazepam. Unlike in the USA.
I have come across a number of obstacles when trying to taper. I can get into those in more detail, but I'll start with a question about common taper strategies for this drug. Beyond 'slowly'. It has some very odd properties and although there are unusual physical side effects, there are mental side effects as well. At the moment, mostly cognitive.
For some reason, I have difficulty tolerating more than one daily dose. I believe that is related to its serotonergic properties, hormones as well.
'By comparison, Klonopin is 86% bound to plasma proteins. Therefore, it is less lipophilic than Valium, Librium or Tranxene. It also takes longer to peak (2-4 hours). The initial distribution phase is the same as Valium, however, Klonopin is not redistributed to fat tissue like Valium. For this reason, the duration of action is prolonged to 12-18 hours.'
Long acting, indeed. I could always get by on one dose a day, with diazepam I'd need 2-3 doses and I'd still be a mess.
I've been trying to do some research on my own. At first, I was under the impression that clonazepam was not lipophilic at all. (low to medium)
Some sources claim otherwise.
I get that diazepam is distributed to fatty tissues and it just 'sits there'.
Clonazepam has a high volume of distribution, higher than diazepam.
Sources state that it distributes to various tissues, being completely non-specific.
I'm wondering why it actually has a very long duration of action ?
(how does the binding to plasma proteins enter into it being less lipophilic than diazepam ?) I'm trying to understand the drug.
Are there actually any reliable sources for this ?
And is Tranxene really that short acting ? Some people have been claiming otherwise.