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Pdoc says I take a "HUGE" dose of clonazepam??......I don't agree


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As most people on here might know, different pdocs have their own personal opinions about benzos.....I had to change pdocs in 2020 because my previous pdoc retired. so I've been seeing current pdoc for about a year and a half.

I know current pdoc rarely ever "starts" someone on benzos as a first line treatment, he tries many other things before starting a benzo, and stated to me that when he starts someone on clonazepam, he starts at .25 mg, and rarely goes over half a milligram for anyone.

Now, since he did "inherit" me from another pdoc, I was already on 3mg clonazepam per day, and have been stable on that for awhile.....So since I am so low-functioning anyway, he did not want to "destabilize" me by changing my benzo dose.....

But I can tell he doesn't like me being on this dose....Recently he suggested substituting 1mg of my 2mg benzo bedtime dose, for 5mg of Sonata......I told him I had already tried 2 meds from the z-drug class (Lunesta and Ambien at max doses), and they did not work at all for me.

He then said that if I was not comfortable trying Sonata, that was okay......But then said "You are taking a huge benzo dose. and that he would never personally escalate a dose to that much (3mg), and that my former pdocs were "irresponsible" doctors for escalating my  dose that high".......WTF..??

He is continuing my 3mg/day dosage, because he says he will not "force" me to reduce if I don't wish to.

But I just don't think 3mg/day of clonazepam is "huge"......I've seen and heard of people on higher doses, although I know that 4mg per day is the max recommended dose for anxiety and panic disorders.

Any thoughts, experiences, or opinions welcome.............Thanks!!

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I don't know about dosages.  I took 1 mg klonopin and when I was hospitalized they took  me off. That dr did not think i needed it.  I took it at night.  I have since been able to sleep without it, but i don't remember how long that took.  Sorry, no help.  I am of the if it ain't broke don't fix it mindset and it is working for you.

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CRH, I think it depends on the hospital.  I was discussing this with my therapist the other day and he talked about a hospital that gave benzos out like they were candy.

To be fair to the hospital I was at, I was taking 1mg klonopin am and bedtime, 0.5mg xanaxXR am, 0.25mg XanaxIR afternoon, and valium 10mg at bedtime.  Or something roughly like that.  So it really didn't make sense.  I don't understand why they didn't just cut me back to one--rather than dropping them all--but they dropped everything.  They did it with a benzo withdrawal program, so it wasn't like I went from taking them to nothing.  They used a long-acting benzo (serax) prn and measured what anxiety symptoms I was having to determine how much was needed. 

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I don't think 3mg is a huge dose really.  I think if something works at the dose you take then keep it at that dose.  Honestly I think it should be up to you what med you put in your body but it does seem that some pdocs are anti benzo.  Seems weird to me.

I was on 2mg klonopin for quite some time but went off it not long ago because I couldn't deal with some of the side effects.

My pdoc never had a problem prescribing klonopin and I was thankful at the time.

Since it's a med that helps you I wouldn't worry about what dose you are on unless it is causing side effects you find unmanageable.

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3 hours ago, CrazyRedhead said:

@confused and @dancesintherain, I'm just wondering why both of you were taken off clonazepam while in the hospital?......Is that something hospitals do with everybody on a benzo?............Just curious.

The psychiatrist at the hospital did not like to have patients on it.  I don't know his reasoning.  I was pretty symptomatic at the time and did not ask many questions

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@CrazyRedhead

I took anywhere from 0.5 to 3 mg clonazepam for probably 15 years or more. I took 3 mg for many, many years. My old pdoc had no issues with prescribing it. But I got a new Dr and she is against benzos so she took me off my 3 mg clonazepam daily dose. Now I take 1,200 mg gabapentin daily instead and 1 mg clonazepam only as needed. Which gabapentin for me personally, doesn’t work as well for my extreme anxiety but is better than nothing (which was my alternative).

When I was hospitalized the hospital pdocs were always very eager to take me off clonazepam too. In fact, that’s the first thing they did! Cold turkey take me off 3 mg clonazepam! They didn’t care about seizure risk or bad anxiety disorder resurfacing or anything! Did that happen to you whenever you were in the hospital CRH? Just curious. It is strange we all have had this experience! I wonder why!

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5 hours ago, CrazyRedhead said:

@confused and @dancesintherain, I'm just wondering why both of you were taken off clonazepam while in the hospital?......Is that something hospitals do with everybody on a benzo?............Just curious.

I think that benzos have fallen out of fashion in a lot of hospitals. The first hospital I was in gave Thorazine instead of benzo (that place was a shit  hole) and the second and third times they left it PRN but at a reduced dose. It also depends on the formulary of the hospital. They once switched me to ativan because the hospital just didn’t use klonopin. 
To the original question - I don’t think it’s huge but I do think it’s outside of what’s considered typical. I know that older pdocs I’ve had have been more comfortable with higher benzo doses, but also I burned through most of the typical first line meds relatively quickly so I think that forced their hand in some cases 

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14 hours ago, Wonderful.Cheese said:

When I was hospitalized the hospital pdocs were always very eager to take me off clonazepam too. In fact, that’s the first thing they did! Cold turkey take me off 3 mg clonazepam! They didn’t care about seizure risk or bad anxiety disorder resurfacing or anything! Did that happen to you whenever you were in the hospital CRH? Just curious. It is strange we all have had this experience! I wonder why!

I've been hopitalized 2 times since my MI started up, both at the same hospital.

The first time I was hospitalized, in 2013, they let me take my clonazepam dose prescribed by my pdoc, which I was taking 2mg at the time.

Fast forward a bit to 2018, when I was hospitalized the second time, and they didn't let me take ANY clonazepam.....They replaced it with phenobarbital to protect against seizures, and also put me on low-dose Thorazine PRN, which pretty much zombified me.....I was in there a week, and it sucked.

After I got out, from the second hospitalization, my pdoc resumed my clonazepam, which by then I was taking 3mg per day.

I feel like 3mg is enough for me--I would never ask for more............I have no idea why the same hospital did such a different approach in 2018, compared to 2013......It's a mystery to me, too, Cheese.

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13 hours ago, Iceberg said:

To the original question - I don’t think it’s huge but I do think it’s outside of what’s considered typical. I know that older pdocs I’ve had have been more comfortable with higher benzo doses, but also I burned through most of the typical first line meds relatively quickly so I think that forced their hand in some cases 

I tried a lot of things before pdoc would put me on a benzo.......But the benzo was the only thing that helped me to sleep, so my first two pdocs got me to 3 mg.....First 2 docs were older, so I guess they were more comfortable with benzos.....And I never abused them, never filled early, never asked for an increase, either.....

My 3rd pdoc was older, too, and she saw no reason to change something that was working, so she maintained my 3mg clonazepam.

It seems my current doc (4th pdoc) is less comfortable with benzos, but he's a bit younger than previous pdocs.....But they are working well for me, and since I am pretty low-functioniing anyway, he doesn't want to destabilize me.

I'm scared though......He has tried gabapentin on me (a miserable fail), and wanted to try to replace 1mg of of my bedtime dose with Sonata.....The hypnotics just don't work for me, I've tried 2 z-drugs that failed, so I didn't even want to go there with the Sonata......**SIGH**

Why does he want to "fix" something that's not broken??........**SIGH**

From all I've read and heard, it seems benzos are now sort of the bad guy......But they work to help me sleep like nothing else does......Still scared though, because benzos do seem to have fallen out of favor, especially with the younger pdocs.......I'm scared this pdoc might one day decide he wants to reduce my dose way down, or altogether.

If I have to change pdocs again one day, I'm very scared of what might happen.

Edited by CrazyRedhead
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On 1/21/2022 at 1:49 PM, CrazyRedhead said:

I know current pdoc rarely ever "starts" someone on benzos as a first line treatment, he tries many other things before starting a benzo, and stated to me that when he starts someone on clonazepam, he starts at .25 mg, and rarely goes over half a milligram for anyone.

Your doctor's method is somewhat conservative, but also safe and simultaneously effective. Clonazepam can be dosed up to 4mg a day for panic disorder. It is certainly dosed higher for epilepsy, but it's also rarely used that way in epilepsy for the same reason it isn't used that way in anxiety: tolerance. For maintenance, effort really should be made to reduce to 0.5mg-1mg per day if possible. However, it's also certainly unreasonable to say that 1mg doesn't have a place in acute panic disorder management. In my own experience, my pdoc similarly likes to have patients take 0.5mg at bedtime. In situations where anxiety is heightened for several days, increase the dose to include another 0.5mg during the day in divided doses (0.25mg AM, 0.25mg PM, 0.5mg bedtime). However, after 2 weeks or so, the dose should then be minimized in favor of other medications that don't lose their efficacy over time the way that clonazepam can. That isn't to say clonazepam should be eliminated from medication regimens, just that it should be minimized in favor of other available options.

On 1/21/2022 at 1:49 PM, CrazyRedhead said:

Now, since he did "inherit" me from another pdoc, I was already on 3mg clonazepam per day, and have been stable on that for awhile.....So since I am so low-functioning anyway, he did not want to "destabilize" me by changing my benzo dose.....

But I can tell he doesn't like me being on this dose....Recently he suggested substituting 1mg of my 2mg benzo bedtime dose, for 5mg of Sonata......I told him I had already tried 2 meds from the z-drug class (Lunesta and Ambien at max doses), and they did not work at all for me.

The suggestion is harmless, really. Your pdoc is trying to find ways for you to ease off of clonazepam, and it may be worth trying. I question whether 5mg of zaleplon is sufficient to truly substitute for 1mg of clonazepam, but there's always room to adjust dosage. What's critical with zaleplon is what are you trying to address? You indicated that in the past zaleplon hasn't worked for you, but what precisely hasn't it worked for? Sleep? Anxiety? Consider that if the problem was sleep, then maybe it can work in combination with clonazepam, unless of course the clonazepam/zaleplon combination specifically is something that you've already tried.

On 1/21/2022 at 1:49 PM, CrazyRedhead said:

He then said that if I was not comfortable trying Sonata, that was okay......But then said "You are taking a huge benzo dose. and that he would never personally escalate a dose to that much (3mg), and that my former pdocs were "irresponsible" doctors for escalating my  dose that high".......WTF..??

Consider that the 3mg dose that you were escalated to was done so in a time when using higher dosing (3-4mg) was more acceptable than it is today, where doses of 0.5mg-1mg are more common. Given this, I do think it is a bit of a stretch to refer to your previous doctors as irresponsible given the ignorance of medicine pertaining to benzo use until more recently. Additionally, using words like irresponsible to prescribe prior doctors could be dangerous to the wrong patient who might read into things the wrong way. So that perhaps wasn't the most professional thing of your pdoc to say.

On 1/21/2022 at 1:49 PM, CrazyRedhead said:

He is continuing my 3mg/day dosage, because he says he will not "force" me to reduce if I don't wish to.

But I just don't think 3mg/day of clonazepam is "huge"......I've seen and heard of people on higher doses, although I know that 4mg per day is the max recommended dose for anxiety and panic disorders.

Any thoughts, experiences, or opinions welcome.............Thanks!!

You said it. 4mg is the max. So 3mg is on the high-end. But it's certainly not huge if that's what your body has adjusted to over the past few years.

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59 minutes ago, browri said:

What's critical with zaleplon is what are you trying to address? You indicated that in the past zaleplon hasn't worked for you, but what precisely hasn't it worked for? Sleep? Anxiety? Consider that if the problem was sleep, then maybe it can work in combination with clonazepam, unless of course the clonazepam/zaleplon combination specifically is something that you've already tried.

Consider that the 3mg dose that you were escalated to was done so in a time when using higher dosing (3-4mg) was more acceptable than it is today, where doses of 0.5mg-1mg are more common. Given this, I do think it is a bit of a stretch to refer to your previous doctors as irresponsible given the ignorance of medicine pertaining to benzo use until more recently. Additionally, using words like irresponsible to prescribe prior doctors could be dangerous to the wrong patient who might read into things the wrong way. So that perhaps wasn't the most professional thing of your pdoc to say.

You said it. 4mg is the max. So 3mg is on the high-end. But it's certainly not huge if that's what your body has adjusted to over the past few years.

Actually, I've never tried zaleplon before, alone or in combo with anything...........He just suggested it because I've already tried Lunesta and Ambien.....Neither Lunesta or Ambien worked for me for sleep at max doses, and Sonata is just basically another hypnotic class z-drug........Sleep is the critical thing.....

Through extensive trial and error with numerous other meds,  the combo of 2mg clonazepam and 200mg Trazodone was found to be the combo that worked for me to sleep through the night.......I can't sleep without that combo.....If I was put on a careful, slow, taper, I might be able to give up my morning dose of 1mg clonazepam, but the 2mg sleep dose I really would hope to keep.

If you look at my "Ex-Meds" list below in my sig, you can see that there's really nothing much left for me to try (for sleep)......My insurance doesn't cover Belsomra or Dayvigo (yet).....I know those 2 have a different mechanism of action than the z-drugs like Lunesta, Ambien, or Sonata.

Yes, I thought it was very unprofessional for my pdoc to call my previous docs irresponsible.....I couldn't believe he said it.......

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Is it a huge dose? No. I don't think I'd use that word, but I think it's high compared to the average. 

If it were me, I think I'd be more concerned about the 2mg at HS every night. But if, as you say, it's the only thing that's worked, then maybe that's the only thing that worked.

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And this is probably why your pdoc is hesitant to take you off of it. Because of their dependent nature, discontinuing benzos has the chance of destabilizing the patient more than discontinuing many other drugs. There tends to be more distress associated with benzodiazepine discontinuation. Therefore, your pdoc probably sees no reason to further complicate an already complex situation. 

I would still recommend giving the z-drugs another try in tandem with the clonazepam, but as I said in my previous post, I have reservations that 5mg zaleplon will sufficiently substitute for 1mg clonazepam. I imagine you'll likely need 10mg of zaleplon. Your pdoc probably won't be willing to let you try the max dose of 20mg because of the 200mg trazodone, 1mg clonazepam, and 1mg risperidone. 

Another thing to consider is that zaleplon can sedate without causing too much destruction of sleep architecture. Broad-spectrum GABAergic sedatives like benzodiazepines can have negative impact on sleep architecture, but the z-drugs, particularly zaleplon, seems to not have this negative effect. The same can be said for 5HT2 antagonists like trazodone and risperidone, both of which can improve sleep architecture. Your doctor's hope, as well, is that perhaps he can improve your sleep architecture and give you more restful sleep. 

Remember that the goal isn't to have zaleplon replace clonazepam, just to minimize your clonazepam dose and still keep you asleep, and hopefully give you more restful sleep.

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57 minutes ago, browri said:

I would still recommend giving the z-drugs another try in tandem with the clonazepam, but as I said in my previous post, I have reservations that 5mg zaleplon will sufficiently substitute for 1mg clonazepam. I imagine you'll likely need 10mg of zaleplon. Your pdoc probably won't be willing to let you try the max dose of 20mg because of the 200mg trazodone, 1mg clonazepam, and 1mg risperidone. 

Found out yesterday that my pdoc had called in the Sonata to my pharmacy anyway, even though I said I was hesitant to try it.....They called and said it was ready..

So I gave in, and decided to try what pdoc suggested........Last night, I took the 5mg Sonata, 1mg clonazepam, 200mg Trazodone, and 1mg Risperdone.

Well, here I sit, this morning, having had only 3-3.5 hours of sleep last night.......That's roughly about half the hours I would get with my usual 2mg clonazepam dose............! feel like shit........I felt my heart racing and very anxious until I took my 1mg morning dose a little while ago.....I sort of feel like a freak of nature, because I  stacked 4 sedating meds together and still didn't sleep but a few hours.

So should I call pdoc today and tell him it didn't work, or give the Sonata a few more days before giving up?.....I don't know.....I'm just tired.....**SIGH**.........

@browri @psychwardjesus @Iceberg

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41 minutes ago, Iceberg said:

Do you think being anxious about Trying the new med could have contributed to sleep issues ?

It's certainly possible.....I'm just trying to figure out should I try it a few more times before writing it off....

I like to give meds a fair trial, but a few more nights of (possibly) very poor sleep is not very inviting....

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3 minutes ago, CrazyRedhead said:

It's certainly possible.....I'm just trying to figure out should I try it a few more times before writing it off....

I like to give meds a fair trial, but a few more nights of (possibly) very poor sleep is not very inviting....

you could do both... call doc and try it one more night until you hear back 

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5 minutes ago, Iceberg said:

you could do both... call doc and try it one more night until you hear back 

I've already put in a call to pdoc....He almost always gets back to me the same day.....I guess I could try one more night with the Sonata.

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6 minutes ago, CrazyRedhead said:

I've already put in a call to pdoc....He almost always gets back to me the same day.....I guess I could try one more night with the Sonata.

i woudl just defer to pdoc then- he might be more comfortable letting you go back to klonopin if he feels that your failed trial is definitely adequate. Also, you have lots of room to go up from 5 mg. Of course, whether going up while also on two other sleep meds is advisable is another issue 

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22 hours ago, Iceberg said:

i woudl just defer to pdoc then- he might be more comfortable letting you go back to klonopin if he feels that your failed trial is definitely adequate. Also, you have lots of room to go up from 5 mg. Of course, whether going up while also on two other sleep meds is advisable is another issue 

Spoke to pdoc late yesterday, and he told me to try 10mg Sonata with the 1mg clonazepam......Said if that did not work, go back to the 2mg clonazepam.

So, last night I took 1mg clonazepam, 10mg Sonata, 200mg Trazodone, and 1mg risperdone.

Same results--did not get but about 3.5 hours sleep last night.......**SIGH**.......Anyway, tonight I'll be back to my usual sleep cocktail--No more Sonata for me.........I looked up the half-life of Sonata, and according to what I read here, it has the shortest elimination half-life of any of the z-drugs, only about 1 hour:

.https://www.uptodate.com/contents/image?imageKey=SLEEP%2F117510&topicKey=SLEEP%2F97868&source=see_link

Already put in a call to pdoc to let him know I'll be back on my usual meds tonight......Oh well, at least I tried....

Edited by CrazyRedhead
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i take 4mg/day of clonazepam and i know that i'm at the highest end of the fda-recommended daily intake for the drug. it does do something, albeit it's lost quite a bit of efficacy. the problem with getting off high amounts of benzodiazepines, particularly for those who suffer from severe anxiety disorders, is what you mentioned previously: destabilization.

my psychiatrist just retired, and i'm to have an appointment with a new psychiatrist on the 2nd of february. an interim psychiatrist tried to pull me off pregabalin cold turkey and i went straight to my general practitioner and explained that that would be devastating to daily functioning and she prescribed me enough of the medication to last until the appointment with the new psychiatrist.

if it comes down to it and i cannot find a psychiatrist within my health insurance group who will support the cocktail i'm currently on, i'll seek an out-of-network private psychiatrist who will continue treatment as is for now.

i should make it aware that i'm not opposed to reducing clonazepam if i am able to tolerate it, but i recently finished tapering pregabalin to as low as i could manage without fear of major relapse, from 900mg/day to 50mg/day and also roughly two weeks ago decreased escitalopram from 25mg/day to 20mg/day. it's been rough and i'm not stable so making any change to anything right now would be debilitating. i'm not even sure that i'll be able to stabilize on 20mg/day of escitalopram.

listen to your body and don't compromise stability.

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24 minutes ago, basuraeuropea said:

If it comes down to it and i cannot find a psychiatrist within my health insurance group who will support the cocktail i'm currently on, i'll seek an out-of-network private psychiatrist who will continue treatment as is for now.

i should make it aware that i'm not opposed to reducing clonazepam if i am able to tolerate it, but i recently finished tapering pregabalin to as low as i could manage without fear of major relapse, from 900mg/day to 50mg/day and also roughly two weeks ago decreased escitalopram from 25mg/day to 20mg/day. it's been rough and i'm not stable so making any change to anything right now would be debilitating. i'm not even sure that i'll be able to stabilize on 20mg/day of escitalopram.

listen to your body and don't compromise stability.

I really hope you find a pdoc in your health insurance group, who is agreeable to your current cocktail..... I also agree with seeking a private psychiatrist if you need to.

Stability is very important.........Thanks for your input.!!

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On 1/24/2022 at 9:07 AM, CrazyRedhead said:

Found out yesterday that my pdoc had called in the Sonata to my pharmacy anyway, even though I said I was hesitant to try it.....They called and said it was ready..

So I gave in, and decided to try what pdoc suggested........Last night, I took the 5mg Sonata, 1mg clonazepam, 200mg Trazodone, and 1mg Risperdone.

Well, here I sit, this morning, having had only 3-3.5 hours of sleep last night.......That's roughly about half the hours I would get with my usual 2mg clonazepam dose............! feel like shit........I felt my heart racing and very anxious until I took my 1mg morning dose a little while ago.....I sort of feel like a freak of nature, because I  stacked 4 sedating meds together and still didn't sleep but a few hours.

So should I call pdoc today and tell him it didn't work, or give the Sonata a few more days before giving up?.....I don't know.....I'm just tired.....**SIGH**.........

@browri @psychwardjesus @Iceberg

Did you take the Klonopin along with the Sonata? If you didn't, no wonder why you slept like shit; and even if you did, I'd still imagine it'd be difficult if you slept well because of it alone. 

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12 hours ago, psychwardjesus said:

Did you take the Klonopin along with the Sonata? If you didn't, no wonder why you slept like shit; and even if you did, I'd still imagine it'd be difficult if you slept well because of it alone. 

Yes, I took 1mg klonopin, along with 5mg Sonata, the first night I tried Sonata, and 1mg klonopin along with 10mg Sonata the second night I tried it, and slept like crap both nights..........Also, both nights I took my usual doses of 200mg Trazodone, and 1mg risperodone

After those 2 nights of very poor sleep with the Sonata, I stopped the Sonata and took my usual sleep combo with 2mg klonopin, and slept great for about 7 hours.

I called pdoc about it , and he said go back on the 2mg klonopin at bedtime, if the combo of 1mg klonopin and 10mg Sonata didn't work.

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3 hours ago, basuraeuropea said:

are you taking klonopin for both insomnia and your anxiety disorders? i see that you take 1mg in the morning, so i'm assuming so, but the larger dose is in the evening which may be to prevent daytime sedation aaaand put you to sleep. i'm just curious.

Yes, I'm taking klonopin for both anxiety and insomnia.....My former pdocs believed that my insomnia is probably being caused by the anxiety, so that's why bigger dose in evening--so I can sleep...

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  • 2 months later...

 

lots of misinformation wrt benzos. Other than being hard for some to get off they really are effective medicines and few side effects.

https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.20040375

they suggest that benzodiazepines are not a risk factor for dementia, and in fact there may be a protective effect of long-term benzodiazepine use on dementia risk in patients with affective disorder. This may be, as suggested, attributed to an inhibitory effect of benzodiazepines on excitotoxic or other pathological lesions or symptoms (6). Anxiety and insomnia are frequent in these patients and are also associated with risk of dementia. Thus, benzodiazepines may also exert a beneficial effect through treatment of these comorbidities

 

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On 1/22/2022 at 4:41 PM, CrazyRedhead said:

@confused and @dancesintherain, I'm just wondering why both of you were taken off clonazepam while in the hospital?......Is that something hospitals do with everybody on a benzo?............Just curious.

I had heart surgery 5 years ago and I was on Xanax 2 .5 mg tablets daily. The hospital A top rated hospital never took me off. The nurse even encouraged me to take them

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16 hours ago, Psychomike said:

 

lots of misinformation wrt benzos. Other than being hard for some to get off they really are effective medicines and few side effects.

https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.20040375

they suggest that benzodiazepines are not a risk factor for dementia, and in fact there may be a protective effect of long-term benzodiazepine use on dementia risk in patients with affective disorder. This may be, as suggested, attributed to an inhibitory effect of benzodiazepines on excitotoxic or other pathological lesions or symptoms (6). Anxiety and insomnia are frequent in these patients and are also associated with risk of dementia. Thus, benzodiazepines may also exert a beneficial effect through treatment of these comorbidities

 

I have read this study before, and their argument does make sense. However, for every study that indicates benzodiazepines don't contribute to dementia, there is at least one more that does. And one could argue it either way really.

When we think of dementia associated with Alzheimer's, we think of dementia that is caused by beta-amyloid and tau proteins building up on and eventually killing cholinergic neurons. So we give them acetylcholinesterase inhibitors to increase cholinergic activity to hopefully improve cognition (and probably give you diarrhea).

However, the "dementia" that can occur from benzodiazepines isn't your traditional dementia in the sense that benzodiazepines don't kill cholinergic neurons in the way that beta-amyloid and tau plaque do. It isn't a progressive, neurodegenerative dementia. So while they may not cause your traditional dementia, they can certainly contribute to cognitive decline.

The argument that the scientists made in the study quoted is that because benzodiazepines enhance GABA signaling and thus suppress glutamate signaling, benzodiazapines could potentially prevent neuron death caused by glutamate excitotoxicity. However, this assumes that glutamate signaling was overactive to begin with. In addition, glutamate is critical in neuron outgrowth and dendritic branching. Proper glutamate signaling is important to a healthy brain.

So with benzodiazepines, it is possible to suppress glutamate signaling to an unhealthy level, which can reduce brain connectivity in various regions, and a less connected brain often leads to things like depression and/or cognitive dysfunction. So the argument really isn't that benzos cause traditional cholinergic dementia, but rather cognitive decline that is downstream of reduced brain connectivity.

Trintellix (vortioxetine), for example, has been shown to promote glutamate signaling without excitotoxicity (mostly via 5HT3 antagonism), and it actually promotes neuron growth and dendritic branching, creating a more connected brain, which is postulated to be how it promoted cognitive function even in non-depressed patients.

In fact, both ketamine and psilocybin are believed to mediate their effects in depression by promoting glutamate signaling, which increases neuron connectivity.

So more neuronal connections = greater cognitive function. Benzos increase GABA signaling, which in the long term reduces neuronal connectivity = reduced cognitive function (not dementia).

Edited by browri
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16 hours ago, Psychomike said:

I had heart surgery 5 years ago and I was on Xanax 2 .5 mg tablets daily. The hospital A top rated hospital never took me off. The nurse even encouraged me to take them

It was smart of them to recommend you continue taking them. In your situation, continuing anxiolytic medication is a good thing, because with reduced anxiety means reduced strain on the heart.

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6 hours ago, browri said:

The argument that the scientists made in the study quoted is that because benzodiazepines enhance GABA signaling and thus suppress glutamate signaling, benzodiazapines could potentially prevent neuron death caused by glutamate excitotoxicity. However, this assumes that glutamate signaling was overactive to begin with. In addition, glutamate is critical in neuron outgrowth and dendritic branching. Proper glutamate signaling is important to a healthy brain.

So with benzodiazepines, it is possible to suppress glutamate signaling to an unhealthy level, which can reduce brain connectivity in various regions, and a less connected brain often leads to things like depression and/or cognitive dysfunction. So the argument really isn't that benzos cause traditional cholinergic dementia, but rather cognitive decline that is downstream of reduced brain connectivity.

Trintellix (vortioxetine), for example, has been shown to promote glutamate signaling without excitotoxicity (mostly via 5HT3 antagonism), and it actually promotes neuron growth and dendritic branching, creating a more connected brain, which is postulated to be how it promoted cognitive function even in non-depressed patients.

In fact, both ketamine and psilocybin are believed to mediate their effects in depression by promoting glutamate signaling, which increases neuron connectivity.

So more neuronal connections = greater cognitive function. Benzos increase GABA signaling, which in the long term reduces neuronal connectivity = reduced cognitive function (not dementia).

This is interesting about Glutamate.... I've been on Lamotrigine for a long time (despite not being Bipolar, no mania) which supresses Glutamate... I often wonder if it is over-suppressing my Glutamate function (and long term, this is not so good)?? sorry to hijack this thread, but you make some interesting points here.

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On 4/13/2022 at 4:51 PM, Blahblah said:

This is interesting about Glutamate.... I've been on Lamotrigine for a long time (despite not being Bipolar, no mania) which supresses Glutamate... I often wonder if it is over-suppressing my Glutamate function (and long term, this is not so good)?? sorry to hijack this thread, but you make some interesting points here.

Well lamotrigine is an interesting one in that it modulates glutamate more than anything. By blocking different electrical channels, it can suppress excitatory activity (glutamate). However, while lamotrigine is an anticonvulsant it actually happens to also modestly block the 5HT3 receptor (an ion channel) like vortioxetine. Lamotrigine can promote glutamate signaling in one way, and suppress it in another. Thus modulation.

However, I'll also point back to what I said earlier about <baseline> glutamate levels. If your baseline glutamate signaling is high this COULD cause excitotoxicity. Best analogy is a dog that pees on grass that eventually burns and goes brown from nitrate poisoning. It starts out growing really fast and looking really green, but in the center it's all burnt out from too much of a good thing.

So, if you look at it that way, it's actually a good thing to reduce glutamate signaling in someone whose glutamate signaling is too high, because while glutamate can promote neuronal growth, it's no good if your neurons are all burning out. And in fact suppressing this excessive growth can actually normalize function. 

On the flip-side, a significant amount of depression can be contributed to glutamatergic hypofunctioning. Promoting glutamate WITHOUT causing excitotoxicity is the name of the game in depression. This is why the industry is so interested in ketamine and psilocybin.

Ketamine blocks glutamatergic NMDA receptors, which are responsible for throttling dopamine release when they are activated. By blocking these receptors, ketamine increases dopamine release. Normally, when dopamine receptors are activated, this causes a release of glutamate, which would normally activate NMDA receptors and then slow dopamine release. Feedback loop. Without this loop, dopamine release continues, but with NMDA receptors blocked, this actually prevents excitotoxicity from increased glutamate and dopamine signaling. With continued infusions, this causes brain structure changes over time similarly to the way that receptors desensitize after a few weeks of taking an SSRI.

With psilocybin, activation of 5HT2A receptors (which are serotonin <forward>) increases release of serotonin, which activates 5HT1A receptors. It's believed that activation and desensitization of 5HT1A receptors over time leads to increased serotonin signaling. The activation of 5HT2A receptors causes significant increases in glutamate signaling as well, and psilocybin has been shown to have this neurogenic (neuron supporting) effect similarly to ketamine. Mirtazapine's efficacy in depression is even said to be downstream of its direct effects. Blocking 5HT2, 5HT3, and alpha-2 receptors increases release of glutamate, serotonin, norepinephrine, and dopamine. This direct effect causes indirect activation of 5HT1A receptors, and thus antidepressant effect.

All this to say basically that even though lamotrigine is traditionally known as a glutamate reducing agent, it should probably be more appropriately known as a glutamate modulator due to the spectrum of impact that lamotrigine can have on glutamate signaling. A more true and pure glutamate reducing agent would be something like topiramate, which is a classic example of what happens when you efficiently reduce glutamate signaling. It's called "Dopamax" for a reason, and I'll use it as Exhibit A for drug-induced cognitive dysfunction. However, even lamotrigine could be exhibit B. I can confirm from experience that it caused me to have issues with word recall. That's about it though. :wtf:

Edited by browri
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