Genetics and benzos

[[NE...]]

I would be curious if anyone has looked into detox genes (CYP) and how, as individuals, it may have affected your withdrawal and/or your tolerance to the different benzos.

[[La...]]

I've been curious about this too. There's an ongoing study at the Centre for Addictions and Mental Health (CAMH) in Toronto on pharmacogenetics and psychiatric medications such as antidepressants and antipsychotics (but not benzodiazepines). Have a look:

 

http://www.camh.ca/en/research/research_areas/campbell-institute/novel-therapeutics/Pages/Pharmacogenetics-Program.aspx 

 

http://impact.camhx.ca/en/home.php

 

It's obviously an area of interest for some researchers, but I haven't come across anything on benzos in particular.

 

 

[[NE...]]

If one has the CYP panel done (top 6 of 90+) one can find some of the benzos.......sadly the docs aren't there yet.......oncologists are at the top of the list for using this information.

 

I ran into exactly this prob with lopressor (another horrid drug!) following open heart surg for congenital issue......do NOT detox at normal rate so essentially poisoning me.

 

The 23andme test lists a slew of detox genes and you can pick out top six, in addition lists propensity for addiction to drugs bearing in mind even if the factor is there one is not nessesarily at risk.

 

My question would be mainly if one has a polymorphism that detoxes them quicker than normal thus making withdrawal even more difficult.

 

Was just hunting for someone in the same boat who may have more info on the subject.

[[La...]]

This topic has come up a few times around here, so perhaps there are others who might have useful info or experience for you. I think it's inevitable that our individual genetics play a role in how we metabolize various medications. How could it be otherwise? The study I mentioned is still ongoing, and it focuses on how to prescribe antidepressants and antipsychotics that will carry fewer side effects for a given individual. Withdrawal is a whole other ballgame!

 

If you've had testing done, then perhaps you can look around online to see where you fit. I came across charts that show where the various benzos lie with respect to the CYP enzymes. Perhaps a good pharmacist could provide useful info.

[[be...]]

I have no data to back this up, like lapis, but I've had a really easy time despite the fact that I was on a very high dose for a long period of time and Kindled twice and I have had no trouble at all  tapering my klonopin or my Valium so it's got to be Gene related to me.

 

Betsy

[[La...]]

It's really important to look at drug combinations too. Some drugs interact in ways that speed up or slow down the metabolism of another drug, so that's an additional factor -- that is, aside from the way an individual metabolizes one drug in particular.

[[Le...]]

If one has the CYP panel done (top 6 of 90+) one can find some of the benzos.......sadly the docs aren't there yet.......oncologists are at the top of the list for using this information.

 

I ran into exactly this prob with lopressor (another horrid drug!) following open heart surg for congenital issue......do NOT detox at normal rate so essentially poisoning me.

 

The 23andme test lists a slew of detox genes and you can pick out top six, in addition lists propensity for addiction to drugs bearing in mind even if the factor is there one is not nessesarily at risk.

 

My question would be mainly if one has a polymorphism that detoxes them quicker than normal thus making withdrawal even more difficult.

 

Was just hunting for someone in the same boat who may have more info on the subject.

 

[[be...]]

It's really important to look at drug combinations too. Some drugs interact in ways that speed up or slow down the metabolism of another drug, so that's an additional factor -- that is, aside from the way an individual metabolizes one drug in particular.

 

I agree with you on that one, Lapis . You said the exact same thing my pdoc said. Pls send me a bill.

[[La...]]

What's a "pdoc", benzogirl? Primary care doc? Psychiatrist? I'm never sure what people are referring to when they write that.

 

Anyway, I recently came across a little chart on the use of benzodiazepines for cases of insomnia. It had 100 little faces, only 7 of which were happy. Seventeen of them were sad, and the others were neutral. According to the blurb accompanying it, the chart represented how few people actually had a useful effect from taking benzos for sleep -- only 7 out of 100. The rest had either a negative or a neutral effect. It's just a guess, but I surmised that this might show the genetic differences in how 100 people might tolerate the same drug.

[[be...]]

What's a "pdoc", benzogirl? Primary care doc? Psychiatrist? I'm never sure what people are referring to when they write that.

 

Anyway, I recently came across a little chart on the use of benzodiazepines for cases of insomnia. It had 100 little faces, only 7 of which were happy. Seventeen of them were sad, and the others were neutral. According to the blurb accompanying it, the chart represented how few people actually had a useful effect from taking benzos for sleep -- only 7 out of 100. The rest had either a negative or a neutral effect. It's just a guess, but I surmised that this might show the genetic differences in how 100 people might tolerate the same drug.

 

Hey Lapis!

 

That seems interesting to me. I know my benzo helped me sleep for several years and then crapped out on me. Then it kept me awake. Pdoc stands for a psychiatrist.  You should know that by now as you're an old timer. I can't seem to login during the day as it always says server is too busy. Try again later . I try and catch up late a night. Bummer. So not many replies from me. This condo I am trying to buy has become a nightmare. Caution: never move!!!!

 

Betsy ❤️️

[[La...]]

Hi Betsy,

I sometimes get that "server too busy" message, but then I'd just try again a few minutes later. Sometimes I think it's my own computer because it's old.

 

On the "old timer" thing: I find the American BBs use a lot of lingo that I don't understand, so even if I've been around for awhile, I still don't get some of the abbreviations. Anyway, thanks for the translation! BBs hail from lots of different countries, and each country has a different medical system. I think ours is a bit like the UK model, but it's quite different from the US model.

 

 

[Guest [su...]]

I am have slow metabolism of CYP2C19 and ultra rapid of CYP2D6.Big problem with w/d from diazepam. And I cant take the most common antidepressiv...I had prolonged w/d from diazepam...CYP3A4 is working (lucky me)...

[[La...]]

It's good to have that kind of info about your liver enzymes, sundanceshaman. Did you know that before taper? I wasn't even aware of such enzymes before, so it certainly wasn't on my radar. But I think if someone knows what their profile is, they can do things accordingly. I couldn't taper directly from clonazepam, but diazepam was fine. Maybe it had something to do with my enzymes.

[[be...]]

Hi Betsy,

I sometimes get that "server too busy" message, but then I'd just try again a few minutes later. Sometimes I think it's my own computer because it's old.

 

On the "old timer" thing: I find the American BBs use a lot of lingo that I don't understand, so even if I've been around for awhile, I still don't get some of the abbreviations. Anyway, thanks for the translation! BBs hail from lots of different countries, and each country has a different medical system. I think ours is a bit like the UK model, but it's quite different from the US model.

 

I don't think anybody uses the US model.... :laugh:

[[Le...]]

I am have slow metabolism of CYP2C19 and ultra rapid of CYP2D6.Big problem with w/d from diazepam. And I cant take the most common antidepressiv...I had prolonged w/d from diazepam...CYP3A4 is working (lucky me)...

I'm the opposite of you...ultrarapid CYP2C19 (I have to dose V 4xs a day) and intermediate for CYP2D6. I cant take antidepressans either. Normal for CYP3A4/5.

[Guest [su...]]

It's good to have that kind of info about your liver enzymes, sundanceshaman. Did you know that before taper? I wasn't even aware of such enzymes before, so it certainly wasn't on my radar. But I think if someone knows what their profile is, they can do things accordingly. I couldn't taper directly from clonazepam, but diazepam was fine. Maybe it had something to do with my enzymes.

 

They dont have the same enzyme in their metabolism so probably yes. I was in a study on humans for testing drugs like omeprazol when they did the genetic test. My doctor knew about my enzyme problems but said it was OK anyway.It was not...It take really long time for me to get ride if diazepam and  they want me to change to clonazepam but I got horrible w/d . My doctor said my dose of clonazepam 0,5 mg was not equal to 10 mg of diazepam and they dont know how much diazepam it is in my blood system. Maybe up to the double...So I taper diazepam with really long w/d

[[La...]]

And are you doing better with your taper now, sundanceshaman? Do you feel better -- or, at least, stable? In my case, I didn't feel "good" during my taper, but I felt way more stable on diazepam than I did when I tried to taper from clonazepam. That was horrible!

 

I wish you well, sundanceshaman. 

[Guest [su...]]

And are you doing better with your taper now, sundanceshaman? Do you feel better -- or, at least, stable? In my case, I didn't feel "good" during my taper, but I felt way more stable on diazepam than I did when I tried to taper from clonazepam. That was horrible!

 

I wish you well, sundanceshaman. 

 

Thnx, no not really. I need to cut like every 3 weeks and I think I maybe cut way to much. I cut 1,25 mg each time. I did a rapid taper this spring and it was totally crazy cuts. I cut like 5 mg in a few cuts and the w/d caught me up and I got so sick. I thought I was going to die. Had almost 50 symptoms at the same time. Really bad DP and DR ...But they are gone now. I really listen to my body this time and if it take a year, well I guess I have to do this in a year...I need to do a slow taper so my body and brain can adjust. I hate this but I'm not afraid anymore of the w/d symptoms. I used to be. I have surrender and just accept this. It is out of my control my body is the boss  . No, I am never stable but almost. I can feel pretty good some days. With nice windows. The worst days are around day 8-10 and 12-18.  How about you, are you ok during cuts, when does the w/d hit you? I hope my English is OK. I am from Sweden...😇

 

[Guest [su...]]

I am have slow metabolism of CYP2C19 and ultra rapid of CYP2D6.Big problem with w/d from diazepam. And I cant take the most common antidepressiv...I had prolonged w/d from diazepam...CYP3A4 is working (lucky me)...

I'm the opposite of you...ultrarapid CYP2C19 (I have to dose V 4xs a day) and intermediate for CYP2D6. I cant take antidepressans either. Normal for CYP3A4/5.

 

When does the w/d starts for you? Duration? The w/d for me starts at day 3-5 and I feel pretty OK. Peak Day 8-10 & 12-18 horrible!! I cut every 3 week.

I take my Valium on the morning. Do you get w/d symptoms directly if you miss one dose?

 

[[La...]]

And are you doing better with your taper now, sundanceshaman? Do you feel better -- or, at least, stable? In my case, I didn't feel "good" during my taper, but I felt way more stable on diazepam than I did when I tried to taper from clonazepam. That was horrible!

 

I wish you well, sundanceshaman. 

 

Thnx, no not really. I need to cut like every 3 weeks and I think I maybe cut way to much. I cut 1,25 mg each time. I did a rapid taper this spring and it was totally crazy cuts. I cut like 5 mg in a few cuts and the w/d caught me up and I got so sick. I thought I was going to die. Had almost 50 symptoms at the same time. Really bad DP and DR ...But they are gone now. I really listen to my body this time and if it take a year, well I guess I have to do this in a year...I need to do a slow taper so my body and brain can adjust. I hate this but I'm not afraid anymore of the w/d symptoms. I used to be. I have surrender and just accept this. It is out of my control my body is the boss  . No, I am never stable but almost. I can feel pretty good some days. With nice windows. The worst days are around day 8-10 and 12-18.  How about you, are you ok during cuts, when does the w/d hit you? I hope my English is OK. I am from Sweden...😇

 

Hi SS,

First of all, your English is excellent! No worries about that.

 

Secondly, I did my taper quite awhile ago now, and I wasn't on BB at the time. I just followed the Ashton Manual and cut 1 mg of diazepam every two weeks -- except when a doctor suggested I start taking Prozac. I held the taper for awhile, but started up again after awhile. I had lots of symptoms, but I wanted to be off that medication so badly that I wasn't going to stretch out longer than I already had. Then 10 months later, I tapered off the Prozac.

 

I didn't keep a record of which part of the taper was the worst, so I can't really say much about that. I think it's different for everyone anyway -- especially because of genetics and our liver enzymes. No two people will experience a withdrawal the same way. I think you're doing the right thing by being patient yet determined. Those things will carry you through, and you will succeed in getting off the medication. I'm glad you're getting some windows, SS! That's great! Enjoy those times and remember them on your more difficult days.

 

You'll get there!

[[Le...]]

I am have slow metabolism of CYP2C19 and ultra rapid of CYP2D6.Big problem with w/d from diazepam. And I cant take the most common antidepressiv...I had prolonged w/d from diazepam...CYP3A4 is working (lucky me)...

I'm the opposite of you...ultrarapid CYP2C19 (I have to dose V 4xs a day) and intermediate for CYP2D6. I cant take antidepressans either. Normal for CYP3A4/5.

 

When does the w/d starts for you? Duration? The w/d for me starts at day 3-5 and I feel pretty OK. Peak Day 8-10 & 12-18 horrible!! I cut every 3 week.

I take my Valium on the morning. Do you get w/d symptoms directly if you miss one dose?

Hi sundanceshaman, usually w/d usually kicks in on day 2 and then again around day 8. I'm cutting.25 mg every 14 days...a very slow rate. Yes, I get intense w/d symptoms if I go longer than 8 hours between doses. I try to dose every 6 hours.

[[La...]]

I just posted this study on genetic variants and benzodiazepine-related fall risk in the Benzos in the News section. So interesting!

 

It's called "CYP2C9 Genotypes Modify Benzodiazepine-Related Fall Risk: Original Results From Three Studies With Meta-Analysis".

 

https://www.ncbi.nlm.nih.gov/pubmed/27889507 

 

[Guest [su...]]

I am have slow metabolism of CYP2C19 and ultra rapid of CYP2D6.Big problem with w/d from diazepam. And I cant take the most common antidepressiv...I had prolonged w/d from diazepam...CYP3A4 is working (lucky me)...

I'm the opposite of you...ultrarapid CYP2C19 (I have to dose V 4xs a day) and intermediate for CYP2D6. I cant take antidepressans either. Normal for CYP3A4/5.

 

When does the w/d starts for you? Duration? The w/d for me starts at day 3-5 and I feel pretty OK. Peak Day 8-10 & 12-18 horrible!! I cut every 3 week.

I take my Valium on the morning. Do you get w/d symptoms directly if you miss one dose?

Hi sundanceshaman, usually w/d usually kicks in on day 2 and then again around day 8. I'm cutting.25 mg every 14 days...a very slow rate. Yes, I get intense w/d symptoms if I go longer than 8 hours between doses. I try to dose every 6 hours.

 

Thnx for your answer. I had seen my slow metabolism as a problem. But maybe it isn't.  I can miss a dose in the morning and don't feel a thing. I tried to go CT and it hit me on day 4. Really bad of course. I guess my slow pace in my body is a smoother  "self taper" in some way than for normal metabolism. This time I did a cut after 14 days. Today is day 2. Feel OK. After day 8 is your body return to stable? Or do you feel some w/d? I am so sick and tired of this taper. It takes time. I am concern what will happen when I am done...Will it be a struggle from hell or will it just pass by...

[[Le...]]

I am have slow metabolism of CYP2C19 and ultra rapid of CYP2D6.Big problem with w/d from diazepam. And I cant take the most common antidepressiv...I had prolonged w/d from diazepam...CYP3A4 is working (lucky me)...

I'm the opposite of you...ultrarapid CYP2C19 (I have to dose V 4xs a day) and intermediate for CYP2D6. I cant take antidepressans either. Normal for CYP3A4/5.

 

When does the w/d starts for you? Duration? The w/d for me starts at day 3-5 and I feel pretty OK. Peak Day 8-10 & 12-18 horrible!! I cut every 3 week.

I take my Valium on the morning. Do you get w/d symptoms directly if you miss one dose?

Hi sundanceshaman, usually w/d usually kicks in on day 2 and then again around day 8. I'm cutting.25 mg every 14 days...a very slow rate. Yes, I get intense w/d symptoms if I go longer than 8 hours between doses. I try to dose every 6 hours.

 

Thnx for your answer. I had seen my slow metabolism as a problem. But maybe it isn't.  I can miss a dose in the morning and don't feel a thing. I tried to go CT and it hit me on day 4. Really bad of course. I guess my slow pace in my body is a smoother  "self taper" in some way than for normal metabolism. This time I did a cut after 14 days. Today is day 2. Feel OK. After day 8 is your body return to stable? Or do you feel some w/d? I am so sick and tired of this taper. It takes time. I am concern what will happen when I am done...Will it be a struggle from hell or will it just pass by...

I still have symptoms after day 8. Keep in mind it's not all about drug metabolism...yes knowing how you metabolize the med is useful information and can help you fine tune your taper. In the end you're  still dealing with a down regulation of your GABA system.

[[La...]]

I'm sure it's a very complicated situation. There are so many factors, e.g. which medication, what dosage, for how long, any other medication, alcohol, liver and kidney function, age, general health issues, etc., etc. Perhaps some day, all of this will be much clearer.