Is one benzo more dangerous than the others?

In discussing benzos, I find that many feel as if their benzo is the worse of the bunch, so I thought I'd ask, is there one particular benzodiazepine which is harsher or more difficult to taper off of than the others, or are they all equal when you take them at their equivalent dose?

 

I ask because someone was being transitioned from Ati to Klonopin and my knee jerk reaction to that person is to not cross over to klonopin because of all of the horrors my wife has gone through tapering off of it... But with that being said, I don't have an appreciation for how difficult Ativan is to taper off of.

I don't really know cause you could argue the shorter acting ones are difficult as they cause interdose withdrawal but clonazepam also does affect serotonin and binds to the receptors more tightly so it really seems one of the toughest ones.

TheSunAlsoRises:  My take is the worst benzo to taper is whatever benzo you are tapering.

 

Cocodot: I know you have devoted much time and effort to research.  I wonder if you have up-to-date references from credible sources you could share with us to support the claims that: (1) Clonazepam affects serotonin to a greater degree than other benzodiazepines and (2) Clonazepam binds more tightly to receptors than other benzodiazepines.

 

I’ve read posts from other members claiming both of the above but it would be interesting to read/review the actual scientific/research literature. Thank you in advance for helping us all learn more about this topic!

 

I'm not sure there's any scientific evidence that one benzo is worse than the others - but then of course, there's very little scientific research about benzo withdrawal in general, because no one wants to fund such research. However, in this

, both Heather Ashton and Malcolm Lader expressed the opinion that, based on their clinical experience, lorazepam (Ativan) was particularly difficult to withdraw from.

 

 

I've cued this video to the time when Ashton and Lader talk about the difficulty of withdrawing from lorazepam. But the entire program is definitely worth watching.

What an amazing video, redevan!  Thank you so much for bringing it to our attention.

 

I share your sense there is a dearth of scientific literature on this topic.

Very interesting, Redevan, I wonder how clonazepam comes into play because to my knowledge, Ashton didn't have that much patients on clonazepam? It makes me sad every time seeing this research was even from before I was born.

 

I don't remember the sources but I'll try to find them again later. I did call with an Indian neuroscientist about my benzodiazepine situation extensively and he said the same thing. He's the one scientist/doctor/pharmacologist I spoke to so far that is extremely knowledgeable and legit compared to the others. He is interested in med injured patients and research as he's in regenerative medicine and working on a cure for MS. He doesn't like big pharma.

 

It might start to slowly come now that the US seems more knowledgeable on this?

I'm not sure about the UK, but in the US clonazepam was approved for use in 1975 - and actually, it had already been under patent since 1960. So by the time the above-cited BBC documentary was made in 1987, clonazepam could not really be considered a new drug. I've read many posts on this forum which have claimed that clonazepam binds more tightly to the GABAA receptors, or words to that effect, but I haven't been able to find any studies which show that. There is a study from 1987, the same year the above-cited BBC documentary was made, which seems to refute that hypothesis.

 

Compared to other benzodiazepines, the reportedly unique clinical properties of clonazepam are neither associated with unusual/unexpected pharmacokinetic properties or with a qualitatively different in vivo interaction with the presumed benzodiazepine binding site.

https://pubmed.ncbi.nlm.nih.gov/2822672/

 

If anyone knows of a study which actually shows that clonazepam binds more tightly to the GABAA receptors, or to any other receptors, I'd be very interested in reading it. I took clonazepam for about three years, and I tapered off it directly, having tried and failed to switch to diazepam. I don't know whether my taper was worse than anyone else's, but my recovery did take a very long time - about 10 years, all told. So I'm very open to any actual evidence that clonazepam is harder to withdraw from.

 

I think any benzodiazepine at any dosage is clearly dangerous and it has mostly to do with a person's genetics and sensitivity as to how easily you can withdraw from them or not (in general to class of benzos but also others in particular like some just don't do well on certain ones). I'm supersensitive so it's why I was refusing all these benzos because I knew strong meds would not be good for me (just never expected the therapist, GP and psychiatrist to then give me another one "more secretly" especially since every other doctor I talked to afterwards finds it insane). Never even drank coffee, drank alcohol maybe once or twice a year one glass, no redbull, nothing. Anyway, I need to try and stop looping over how this was even possible and accept that it is now.

 

I'm suffering from benzo brain and months of no sleep but here are some links about the serotonin:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/#!po=30.7143

Chouinard G, Young SN, Annable L. Antimanic effect of clonazepam. Biol Psychiatry. 1983 Apr;18(4):451–466.

 

I don't remember where I got this from about tightly binding receptors, maybe even some links or posts on this exact forum? (I'm not that kind of scientist, I was doing a PhD in economics).

 

I don't know if I can share the name of the scientist openly but I'm willing to answers pms about this. He actually explained something I personally found very interesting. He said that most of the patients he speaks to with regard to neurological degenerative diseases have been on a CNS depressant med at some point in their life. I don't want to scare anyone (including myself) but he just mentioned it.

 

Do you consider yourself healed after these 10 years, Redevan? I cannot imagine. I already find it so scary to be sick for half a year with no end in sight after 12 days of use. I guess it's true when I think my youth is taken away from me because of this. Sucks.

 

 

 

 

 

 

...

I'm suffering from benzo brain and months of no sleep but here are some links about the serotonin:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/#!po=30.7143

Chouinard G, Young SN, Annable L. Antimanic effect of clonazepam. Biol Psychiatry. 1983 Apr;18(4):451–466.

 

I don't remember where I got this from about tightly binding receptors, maybe even some links or posts on this exact forum? (I'm not that kind of scientist, I was doing a PhD in economics).

...

 

Do you consider yourself healed after these 10 years, Redevan? I cannot imagine. I already find it so scary to be sick for half a year with no end in sight after 12 days of use. I guess it's true when I think my youth is taken away from me because of this. Sucks.

 

I do consider myself completely healed now, for all practical purposes; although, I still have some what you might call "weak spots" or "scar tissue", such as less tolerance for stress - but that's still improving - and less tolerance for alcohol - also improving, because I keep trying. 

 

Thanks for the link to that study. It's interesting that in the same paragraph that talks about clonazepam's serotonin-agonist activity, I also found this:

 

Clonazepam also has a relatively weaker binding affinity for GABA-A receptors than the other high-potency BZDs.

 

So that says just the opposite of the rather common (on this forum, at least) assertion that clonazepam binds more tightly to the GABA-A receptors. But also notice, that quote compares clonazepam's binding affinity only to other high-potency BZDs, i.e., alprazolam and lorazepam. It doesn't say whether it has a stronger binding affinity that diazepam, for example.

 

Bottom line: if there is any worst benzo, in terms of withdrawal difficulty, I'd still have to guess that it's lorazepam. But I'm still open to evidence to the contrary. I think we'd all like to know.

Oh you are right and seem quite healed to me because my brain is gone lately haha 

 

I do think I came across some study stating the opposite but I don't find it atm.

 

It's definitely an interesting discussion but tbh I don't think it matters that much as this experience really shows how wildly individuals differ.

 

I actually have another question/remark relating to this. To me it seems that if you would not suffer from interdose withdrawal that it would be interesting to taper from a shorter acting benzo - despite the leveling out and all that of longer acting ones - for the practical reasons that you would be able to "dance" more during your taper, realizing the effects of the cuts faster and adjusting faster.

 

I also wonder how diazepam's active metabolites plays into this? Is it really the easiest one to come off of because it doesn't necessarily seem that way.

When it comes to switching over to diazepam for the taper, I think we're really relying on the experience of clinicians such as Heather Ashton. But even she said some people might have to taper off their original benzo if they couldn't tolerate diazepam. I think the longer half-life is one advantage of diazepam, but the main advantage is its lower potency, which allows smaller cuts and tapering down to a smaller effective dose before jumping. I think I might have healed faster had I tapered off of diazepam. But I could not tolerate its side-effects, especially the depression.

But its duration of action isn't longer than clonazepam right? Or have I understood it wrong?

 

I understand the smaller cuts but they seem less of a big deal if you can use liquid titration (I have liquid rivotril and pharmacists can dilute it) or if other types of benzos would be available in smaller dosages.

But its duration of action isn't longer than clonazepam right? Or have I understood it wrong?

 

I understand the smaller cuts but they seem less of a big deal if you can use liquid titration (I have liquid rivotril and pharmacists can dilute it) or if other types of benzos would be available in smaller dosages.

 

Diazepam has a markedly longer half-life than clonazepam. While clonazepam has a half-life of 18 to 50 hours, diazepam's half-life is 20 to 80 hours. But more importantly, diazepam has a number of active metabolites, while clonazepam has none. One metabolite of diazepam is desmethyldiazepam, which has a half-life of 40 to 120 hours. Two other metabolites, temazepam and oxazepam, have half-lifes of 5 to 15 hours. So diazepam has a much longer duration of action than clonazepam.

See the chart here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/

 

As for ease of dosing during your taper, clonazepam is said to be about 20 times more potent than diazepam. But the smallest dosage of clonazepam commonly available, in pill form, is 0.5 mg - which is equivalent to 10 mg of diazepam. As for diazepam, you can get pills containing 2 mg of the drug, and those pills can be split in half to 1 mg, and each half can fairly easily be divided in half to 0.5 mg. Now to get the equivalent dose of clonazepam, you'd have to take 1/20 of a 0.5 mg pill - a practical impossibility. Of course, there are orally disintegrating tablets in doses as small as 0.125 mg, though I'm not sure how easy they are to find. So yes, it is possible to taper directly off clonazepam pills and tablets, but ceteris paribus it's easier to get down to the smallest doses with diazepam. And as you say, using liquid clonazepam makes it even easier to make small cuts and taper down to very small doses. So then the only advantage of diazepam would be the longer duration of action. You just have to decide what's easiest for you. I've seen a lot of people switch over to diazepam and have very successful tapers. Sadly, I wasn't one of them. I had to taper off clonazepam. And I'm sure I could have done a better job of it.

Redevan, since you are so knowledgeable on all of this, could you please explain me what the active metabolites mean exactly and then what it means that clonazepam doesn't have them?

Redevan, since you are so knowledgeable on all of this, could you please explain me what the active metabolites mean exactly and then what it means that clonazepam doesn't have them?

 

An active metabolite is a drug which is derived from the metabolism of another drug, and which has its own pharmacological activity. So for example, one active metabolite of diazepam is desmethyldiazepam, which itself has amnesic, anticonvulsant, anxiolytic, muscle relaxant, and sedative properties. Desmethyldiazepam has a half-life of 40-120 hours - although I have seen other figures, such as 30-90 hours or 36-200 hours. I can't say which figures are most accurate, but the point is that even after diazepam is metabolized, its active metabolites continue producing many of the same effects as diazepam itself. For that reason, diazepam's total duration of action is quite long.

I'm a 100% sure Klonopin has a much longer Half life in me, personally, than Valium... Half lifes are just variables...

In Valium I felt every reduction after 5 days... in Klonopin it  was at least 10 or more days... Peak was day 14... in acute...

 

Valium was easier to taper than Klonopin... but maybe that's because it was my first taper... and in Klonopin I tapered too rapidly and jumped from a too high dosage (in Valium I did Ashton Manual)

 

I had more Windows in Klonopin withdrawal though and didn't feel as depressed as with Valium...

But Klonopin was nasty with me... withdrawal hit me unexpectedly hard in acute after complete cessation which was not in Valium. ... I think Klonopin's higher Potency makes it more problematic to taper... but if done Ashton Style in aquivalent to 0.5mg Valium before jumping should actually be another option for if someone doesn't tolerate Valium....

 

But Ashton also describes Klonopin as particularly difficult to withdraw from in her Manual...

 

I think short acting Benzos like Ativan and Xanax are much harder to taper than long acting ones... due to interdose withdrawal .. For me impossible...

Everyone reacta different to them i think. Theres alot of people on klonopin/clonazopam... i was on that for like 2 weeks and it made me furious and depressed....

 

If i had to pick the most dangerous all around i would say xanax..  just because its so effective and cheap. Seems majority of people respond really well to it. Just as hard to quit as the rest of them.

Diazepam has a markedly longer half-life than clonazepam. While clonazepam has a half-life of 18 to 50 hours, diazepam's half-life is 20 to 80 hours. But more importantly, diazepam has a number of active metabolites, while clonazepam has none. One metabolite of diazepam is desmethyldiazepam, which has a half-life of 40 to 120 hours. Two other metabolites, temazepam and oxazepam, have half-lifes of 5 to 15 hours. So diazepam has a much longer duration of action than clonazepam.

See the chart here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/

 

As for ease of dosing during your taper, clonazepam is said to be about 20 times more potent than diazepam. But the smallest dosage of clonazepam commonly available, in pill form, is 0.5 mg - which is equivalent to 10 mg of diazepam. As for diazepam, you can get pills containing 2 mg of the drug, and those pills can be split in half to 1 mg, and each half can fairly easily be divided in half to 0.5 mg. Now to get the equivalent dose of clonazepam, you'd have to take 1/20 of a 0.5 mg pill - a practical impossibility. Of course, there are orally disintegrating tablets in doses as small as 0.125 mg, though I'm not sure how easy they are to find. So yes, it is possible to taper directly off clonazepam pills and tablets, but ceteris paribus it's easier to get down to the smallest doses with diazepam. And as you say, using liquid clonazepam makes it even easier to make small cuts and taper down to very small doses. So then the only advantage of diazepam would be the longer duration of action. You just have to decide what's easiest for you. I've seen a lot of people switch over to diazepam and have very successful tapers. Sadly, I wasn't one of them. I had to taper off clonazepam. And I'm sure I could have done a better job of it.

 

This is great information. Well grounded in how it's relayed.

for the practical reasons that you would be able to "dance" more during your taper, realizing the effects of the cuts faster and adjusting faster.

 

This is an interesting question, although more frequent variations may sensitize your nervous system more, as explained by my sleep specialist (psychiatrist). If our CNS doesn't like change, then I wonder if pushing it to the extremes may contribute to some of the extreme symptoms we get -- ie., the hypersensitization. I think that I'd go for the stability but that doesn't mean it's right.