Jump to content
CrazyBoards.org

Recommended Posts

Hi, I'm looking for some insight into the interaction between ketamine and benzos, specifically clonazepam. I am on a clonazepam taper right now, currently at .75mg/day down from 1.5mg. I have read that benzos can dampen the affects of ketamine (for depression), but most of the websites as well as the clinic where I'm set to go next week say it's "not that big a deal" and that it's better to still come than not, while on the benzos. I'm wondering to what extent this is true - ketamine therapy is of course extremely expensive, and I don't want to waste it if it's not going to work - or work significantly less well - bc of the clonazepam. I know this all has something to do with glutamate, but I can't really figure out the science, let alone how significant it is, and if I should wait until my taper is lower, or over altogether, to try the ketamine treatment. Or if it's still worth it to go ahead with it now. 

Additionally, any chance the ketamine could make this taper any less awful? 

Looking in the direction of @mikl_pls , @browri & anyone else who might be able to shed some neurotransmitter-genius light on this for me. 

Thanks!!! ❤️ 

Share this post


Link to post
Share on other sites
2 hours ago, Selkie said:

Hi, I'm looking for some insight into the interaction between ketamine and benzos, specifically clonazepam. I am on a clonazepam taper right now, currently at .75mg/day down from 1.5mg. I have read that benzos can dampen the affects of ketamine (for depression), but most of the websites as well as the clinic where I'm set to go next week say it's "not that big a deal" and that it's better to still come than not, while on the benzos. I'm wondering to what extent this is true - ketamine therapy is of course extremely expensive, and I don't want to waste it if it's not going to work - or work significantly less well - bc of the clonazepam

Have you discussed any of your concerns with your pdoc?......That would be a good idea if you haven't already done so.

 

Edited by CrazyRedhead

Share this post


Link to post
Share on other sites

Have you called the ketamine center and asked? That might be the best first move cuz they are the experts... I don’t remember what I did but I don’t think I had to totally stop any of my meds...that said, there is a lot of variation in how the centers work so it’s important to get in contact with them as to not delay your treatment 

Share this post


Link to post
Share on other sites

I've talked to the clinic about it, but my point of contact there is a psychotherapist and nurse, I had a screen with the pdoc last month. To be clear, it's absolutely safe to take these meds together - that's confirmed by all literature, the pdoc, the nurse. But they all also say that taking benzos concurrently might mean I don't get the full effects of the ketamine. I'm trying to figure out the science behind this, and how significant it is. The treatments are $600 each and they recommend six of them, and this isn't really something I can afford to have a do over with. So I'm just trying to figure out of I should wait or not. Not concerned about safety, as that's all clear. 

Thanks for your replies :)

Share this post


Link to post
Share on other sites

Technically the nurse who deals with patients should be aware of the possible interactions... or at least run them by a doctor/np/Pa or whoever that is aware of potential issues 

They do tell you to avoid alcohol (mine was none 48 before to 48 after) and Benzos act similarly. What does your regular pdoc think about the scheduling? They may have insight/a way to alter your taper to make things easier 

Edited by Iceberg

Share this post


Link to post
Share on other sites

Hey thanks @Iceberg , after reading as much as I can find, I have decided to wait. The thing is there's not a ton of research about it, so since it's safe they just say it might affect the ketamine's effectiveness, but they don't really know to what extent, and since it's safe they just say go ahead with it or not take the klonopin 24 hours before, but I can't really do that right now. I don't have a regular pdoc, I live in Canada, where psychiatrists are really hard to get access to, I have a GP who works with a psychiatrist as part of their network, but it's impossible to actually talk to him, always have to go through my GP. 

 

 

Share this post


Link to post
Share on other sites
21 hours ago, Selkie said:

Hi, I'm looking for some insight into the interaction between ketamine and benzos, specifically clonazepam. I am on a clonazepam taper right now, currently at .75mg/day down from 1.5mg. I have read that benzos can dampen the affects of ketamine (for depression), but most of the websites as well as the clinic where I'm set to go next week say it's "not that big a deal" and that it's better to still come than not, while on the benzos.

I'm wondering to what extent this is true - ketamine therapy is of course extremely expensive, and I don't want to waste it if it's not going to work - or work significantly less well - bc of the clonazepam. I know this all has something to do with glutamate, but I can't really figure out the science, let alone how significant it is, and if I should wait until my taper is lower, or over altogether, to try the ketamine treatment. Or if it's still worth it to go ahead with it now. 

Additionally, any chance the ketamine could make this taper any less awful? 

Looking in the direction of @mikl_pls , @browri & anyone else who might be able to shed some neurotransmitter-genius light on this for me. 

Thanks!!! ❤️ 

I can describe a few different pieces to a puzzle with trillions of pieces. What I know is that clonazepam is depressogenic. It doesn't matter that it may reduce anxiety and thus make someone more at ease and potentially LESS depressed. If I'm having anxiety, I take it regularly. After about 2-3 weeks, I start to feel depressed. The point is that the way clonazepam works is by depressing the brain via GABA-A receptors, GABA being the chief inhibitory neurotransmitter in the brain.

Glutamate, on the other hand, is the chief excitatory neurotransmitter in the brain. The brain tends to release more of it when other receptor systems are activated, and activation of the glutamatergic system subsequently inhibits the release of neurotransmitters, creating a feedback loop. Glutamate is GABA's opposite. Like day and night.

When you take amphetamine, it activates TAAR1 receptors which cause neurotransmitter efflux. Activation of central dopamine receptors leads to increased release of glutamate, which in turn slows down the release of dopamine. So if you block the glutamate receptors (NMDA receptors, specifically), what happens? You've just cut the brake line, leading to a complete disinhibition of the brain and subsequently release of neurotransmitters, particularly dopamine.

Ketamine, furthermore, is not just an NMDA receptor blocker, but interacts with many other receptor systems like the sigma receptors and opioid receptors. It does even have some affinity for dopamine receptors as well.

Glutamate, while excitatory and an important part of the nervous system, is toxic in high levels and not modulated properly. Inhibiting NMDA receptors with a substance like ketamine would not only disinhibit the brain and encourage nerve growth, but because the brain detects no glutamate binding to NMDA receptors, it will increase glutamate output. While glutamate can be neurotoxic in high levels, when modulated correctly, it can actually have positive effects on depression. This is part of the reason why some people respond to no antidepressants, but they try lamotrigine or ketamine and it's a game-changer. Those are both glutamatergic agents meant to increase glutamate output, dampen glutamate signaling (simultaneously), and subsequently activate numerous other neurotransmitter systems both directly and indirectly. Additionally, this may be why vortioxetine may be more effective for some people than other antidepressants. It potently antagonizes 5HT3 receptors which increase glutamate output as well.

The problem with clonazepam is that as an activator of the GABA inhibitory system. It could potentially dampen the positive response from ketamine. While ketamine blocking NMDA receptors may help the brain to reset, any neurotransmitter outflow downstream of ketamine would be dampened by clonazepam. So when the nurse says it's "not that big a deal", what they mean to say is for ketamine, you ideally want to do it with as clear a head as possible. The goal with ketamine infusions is to hopefully reduce polypharmacy. You may even find that ketamine infusions make it easier to go without clonazepam, but make sure you always discuss these things with your pdoc.

Edited by browri

Share this post


Link to post
Share on other sites

Thank you so much @browri, this is super helpful and also very interesting! I love that you have all this knowledge. I'm curious about lamictal's similarity to ketamine in terms of being glutamatergic - lamictal is one of the drugs that also appears as being contra-indicated for ketamine treatments (infusions, or in the case of the clinic I'll be going to, sublingual). Is that because it would just cause an overflow of glutamate? 

I don't take lamotrigine but it's one I've been curious about for a while, interested in to what extent it's going to work similarly to the ketamine treatments. 

Again, thanks so much! 

Share this post


Link to post
Share on other sites

Lamotrigine is predominantly a glutamate-reducing agent. But it has been shown to increase glutamate signaling in some ways such as very weak 5HT3 antagonism. There is a fringe group of patients whose depression is glutamatergic in nature versus serotonergic. Those patients typically respond to lamotrigine over typical antidepressants that focus on increasing serotonin signaling.

You wouldn't want to take lamotrigine with ketamine infusions because lamotrigine would interfere with that subsequent glutamate outflow caused by ketamine's NMDA receptor antagonism. Just a guess really. But you wouldn't want to block NMDA glutamate receptors (ketamine) AND reduce glutamate output (lamotrigine) even if either on their own could result in improvements in glutamate signaling.

Share this post


Link to post
Share on other sites
On 9/9/2020 at 11:55 AM, browri said:

Lamotrigine is predominantly a glutamate-reducing agent. But it has been shown to increase glutamate signaling in some ways such as very weak 5HT3 antagonism.

Wow, this is all so fascinating!!! Thank you so much for sharing your knowledge!

Share this post


Link to post
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.

Guest
Reply to this topic...

×   Pasted as rich text.   Paste as plain text instead

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.


×
×
  • Create New...