• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
LongeCity .                       Advocacy & Research for Unlimited Lifespans

Photo
- - - - -

NRI's (norepinephrine reuptake inhibitors)

nri depression anxiety adhd antidepressant

  • Please log in to reply
37 replies to this topic
⌛⇒ LongeCity grant support for self-testing

#1 CWF1986

  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 06 October 2017 - 08:48 PM


I'm curious about other people's experiences and knowledge with NRI's.  

 

The one's that I know of are Desipramine (Norpramin), Nortriptyline (Pamelor), atomoxetine (Strattera), and reboxetine (Edronax).

 

I have personal experience with Nortriptyline at 150mg a day which puts my blood levels on the lower end of the therapeutic window.  I'm a fast metabolizer of this medicine so most people wouldn't take as much as me to get the same blood levels.

 

Nortriptyline has significant antihistamine effects, granted no where close to that of the older tricyclics like amitriptyline or imipramine.  For me, this helps me fall asleep and the sedation has worn off by the time I'm ready to wake up. 

 

In the day, it provides a very subtle and mild mental stimulation that helps me stay on task and focus and I can drive a car in rush hour traffic without blasting heavy metal and/or having coffee before hand.  This is probably the NRI effect and also might have something to do with it's 5ht2a/c properties.

 

It does have some alpha1 activity which causes orthostatic hypotension which in turn can cause dizziness upon standing.

 

There is also it's muscarinic antagonism which for me in addition to the antihistamine effects eliminates my nervous stomach syndrome syptoms entirely.  For others, it might cause brain fog, constipation, sedation, and weight gain.  This mach antagonism very well might be a significant part of it's antidepressant effect given the much lower effectiveness for reboxetine and strattera.  

 

It does help a ton for anxiety and gives me a lot of relief but not full relief (on it's own) from depression.  It does cause an increased pulse for me but blood pressure is unaffected.  

 

It has no more overdose potential than most SSRI's.  The same is true of Desipramine.  The same cannot be said of the older tricyclics.  

 

I haven't taken Desipramine, but my understanding is that it's usually mildly to moderately activating and is more selective for NRI than nortriptyline which may or may not be a good thing depending on individual.  Both of these are probably the most effective NRI's for depression and anxiety. 

 

Desipramine used to be prescribed a lot more for adhd before the stimulants became popular.

 

Both Nortriptyline and Desipramine have poten 5ht2a/c antagonism effects which make them pair very well with SSRI's since that effect will mitigate some of the SSRI side effects.  The stomach easing effect of nortriptyline gets rid of the stomach problems lexapro gives when I take them at the same time.  

 

Arguably, both these tricyclics don't have any more sides or safety issues than the SSRIs.  

 

 

I don't know much about Strattera or Edronax and have taken neither.  I know Strattera was developed to be an antidepressant that had the NRI effects of tricyclics but without as many bad sides and it failed on both counts despite being much more selective.  But it was effective for treating adhd so that's what it marketed for.  This is one of the pieces of evidence that suggest the broad spectrum of effects in tricyclics might be part of it's therapeutic effect, not just the sides.  

 

I know Edronax wasn't proven effective enough for depression to be marketed as such in the USA.  When I read reports of it, it's usually used to augment other antidepressants or help with the sides of other antidepressants.  I haven't found trials for adhd, but anecdotal reports suggest some success.  

 


  • Informative x 1

#2 Stinkorninjor

  • Registered User
  • 1,358 posts
  • 104
  • Location:Scandinavia
  • NO

Posted 06 October 2017 - 09:16 PM

Funny actually, I was reading up on NRI's earlier today - there's certainly many, many compounds not currently in use which might have therapeutic potential, which I feel were left off too soon! Some of them are fairly exotic compounds, with strange chemical structures.

 

I have extensive knowledge with Atomoxetine, and some limited experience with Reboxetine.

 

There's, imho, quite a bit of difference between the two in effects - possibly as a result of the NMDA-antagonism from ATX for instance, but there also seems to be different effects on the Autoreceptors. (alpha-2)

 

Reboxetine is definitively the more activating of the two - and if you check the common side-effects, you will find that SEDATION is NOT one for RBX, but it's definitively one for ATX. This was my experience as well - ATX could sometimes make me so tired that I would almost fall asleep standing. RBX has some problematic peripheral side-effects for me though... it causes sweating, intense headache increased heart-rate and a SPIKE in blood-pressure...!

 

Because of down-regulation of Alpha-2-receptors from previous Guanfacine-use, RBX actually induced a mild form of Adrenergic storm in me! : O (I had similar symptoms when I discontinued Guanfacine at first, but they went away with a more gradual taper)

 

It's the equivalent of Serotonin-syndrome, so I suppose one could also call it "Norepinephrine Syndrome" - too much NE in circulation starts causing some rather unpleasant effects.

 

I intend to test out RBX again once I have Guanfacine in my possesion though, to keep the peripheral effects at bay - at times it did have efficacy - similar to ATX I would say - which is actually VERY good! I find ATX more effective than stimulants, you see  - well, dopamine-selective stimulants, at least.

 

 

There's actually quite a bit of research proving efficacy in ADHD, so I say it's definitively worth a shot for those of us that presents with the hypoactive form of the disorder - which may actually be another disorder all together - Sluggish Cognitive Tempo.

 

https://en.wikipedia...tivity_disorder

 

https://www.ncbi.nlm...pubmed/25415763

 

 

The results on depression, are as you say though, fairly weak - similar to those of ATX. Small side-note - something which I did NOT experience with RBX, was a lessening of anxious symptoms - however, I definitively experienced this with ATX - possibly related to the NMDA-antagonism there.


  • Informative x 2

sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#3 Adam Karlovsky

  • Member, Moderator
  • 114 posts
  • 169
  • Location:Victoria, Australia

Posted 19 October 2017 - 06:49 AM

The reason Strattera is better for ADHD is that the "sedation" effects helps with hyperactivity and racing thoughts. It's a specific kind of sedation though, not like sleeping medications. one appropriate for ADHD. This is why I think Reboxetine and Nortriptyline are less likely to help with ADHD, even though they all might effect dopamine reuptake via NET in the frontal cortex to some extent. But then that's also why Nortriptyline is often more appropriate for plain depression without comorbid ADHD. 



#4 Stinkorninjor

  • Registered User
  • 1,358 posts
  • 104
  • Location:Scandinavia
  • NO

Posted 19 October 2017 - 08:40 AM

The reason Strattera is better for ADHD is that the "sedation" effects helps with hyperactivity and racing thoughts. It's a specific kind of sedation though, not like sleeping medications. one appropriate for ADHD. This is why I think Reboxetine and Nortriptyline are less likely to help with ADHD, even though they all might effect dopamine reuptake via NET in the frontal cortex to some extent. But then that's also why Nortriptyline is often more appropriate for plain depression without comorbid ADHD. 

 

Aha, aha. Interesting thoughts - certainly might be some merit to it - Guanfacine for instance, seems to work in a similar way, with the sedation - through activation of alpha-2-receptors.

 

However, you didn't discuss those that do not present with hyperactivity, but are still diagnosed with an attention disorder - what is your thoughts on ATX compared to RBX regarding these people?



#5 RedStaR

  • Registered User
  • 14 posts
  • 2
  • Location:Universe
  • NO

Posted 19 October 2017 - 04:48 PM

Atomoxetine gave me some serious spontaneous ejaculations and mild ED.

 

It was the weirdest thing ever, I could ejaculate if I tried at will. But that's expected of NRIs.

 

I feel like it cured my ADHD, I self-medicated for 3 months, along with Bupropion, but the serotonin effects were too much for me, so I eventually stopped and continue now with only BUP.

 

I loved how well it made you sleep and dream though, and the anxiolytic effects.


Edited by RedStaR, 19 October 2017 - 04:49 PM.


#6 YoungSchizo

  • Registered User
  • 604 posts
  • 14
  • Location:I Have No Clue

Posted 19 October 2017 - 05:53 PM

@ CWF1986 (I can't quote for some reason, how do you tag someone?)

 

I have no experience with NRI's or don't know anything about them since I never took one. Thanks for the informative post about Nortriptyline.

 

As you may know I'm schizophrenic and am using Parnate with fairly good results, however I can't go any higher as 20mg or my positive symptoms / depression get worse. I was thinking of adding Nortriptyline in the hopes it'll mix well with Parnate and further alleviate some of my symptoms (also because it'll eliminate the 'cheese effect' of MAOI's).

 

My questions: Which one do you recommend Nortriptyline or Desipramine? Also, did you gain any weight on Nort? Is it a activating drug? Interesting that you sleep well on it. I have some form of sleep maintenance insomnia.. Are the antihistamine properties only in large dosages like you take or even on low dosages? (I've read on several sites Nortriptyline actually could cause sleep problems instead of "curing" it.)


Edited by YoungSchizo, 19 October 2017 - 06:28 PM.


#7 CWF1986

  • Topic Starter
  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 19 October 2017 - 07:26 PM

@ CWF1986 (I can't quote for some reason, how do you tag someone?)

 

I have no experience with NRI's or don't know anything about them since I never took one. Thanks for the informative post about Nortriptyline.

 

As you may know I'm schizophrenic and am using Parnate with fairly good results, however I can't go any higher as 20mg or my positive symptoms / depression get worse. I was thinking of adding Nortriptyline in the hopes it'll mix well with Parnate and further alleviate some of my symptoms (also because it'll eliminate the 'cheese effect' of MAOI's).

 

My questions: Which one do you recommend Nortriptyline or Desipramine? Also, did you gain any weight on Nort? Is it a activating drug? Interesting that you sleep well on it. I have some form of sleep maintenance insomnia.. Are the antihistamine properties only in large dosages like you take or even on low dosages? (I've read on several sites Nortriptyline actually could cause sleep problems instead of "curing" it.)

 

I metabolize the nortriptyline at around double the rate the average person does.  So when you see me taking 150mg, that's more like 75mg for most people.  My 'large' dose puts my blood levels of the drug within the low end of the therapeutic range.  This therapeutic range is well documented and known.  

 

For most, nort. will be more on the sedating side especially within the first 8-10 hours.  This is from the antihistamine effect, but that effect wears off with the rest of the effects still in play.

 

For me, the first 8-10 hours are sedating, and then after that it's very subtly activating.  It's not in your face like wellbutrin or a stimulant, it's a very clean mental energy and stimulation.  

 

I've never taken desipramine.  I do know that it is much more likely to be activating for most, but it can still be a little sedating for some.  

 

I don't know what sleep maintenance insomnia is exactly, but the Nort. might help you sleep at night whereas desipramine is actually known to cause insomnia.

 

Keep in mind that for the first couple to few weeks, nortriptyline may actually be activating until you adjust to its effects.  It may also be that it will initially keep you sedated 24/7 until you adjust to its effects.  My point is to give it a chance.  The sides I experienced while adjusting to higher doses were:  mild bloating and constipation,  halos around lights at night were more prominent, orthostatic hypotension to the point where I had to consciously stand up slowly, increased appetite, nightmares, and just a little daytime sedation.  All of those went away after 5-6 weeks with about half the severity of the sides gone in about 2 weeks.  

 

So yes, I did gain weight.  But once I was past the adjustment period I didn't gain anymore and I was able to shed that weight fairly quickly.  


  • Informative x 1

#8 CWF1986

  • Topic Starter
  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 19 October 2017 - 07:49 PM

The reason Strattera is better for ADHD is that the "sedation" effects helps with hyperactivity and racing thoughts. It's a specific kind of sedation though, not like sleeping medications. one appropriate for ADHD. This is why I think Reboxetine and Nortriptyline are less likely to help with ADHD, even though they all might effect dopamine reuptake via NET in the frontal cortex to some extent. But then that's also why Nortriptyline is often more appropriate for plain depression without comorbid ADHD. 

 

I'm not speaking to theoreticals, only my personal anecdotal n=1 experience.

 

Nortriptyline does help a lot with my ADHD PI.  It helps with focus and attention a lot and helps a little with restlessness.  So once I'm on task I can stay on task.  Granted, I still take Adderall for motivation, energy, and consciousness.  It isn't that hard to find trials where Nort. is tested for efficacy with adhd and it actually does a pretty decent job.  So for those that can't tolerate the sides of reboxetine or atomoxetine it might be worth a try.  

 

Given the low efficacy of roboxetine or amotoxetine for depression, if one wanted to give one med to fix both adhd and depression it would seem like imipramine, nortriptyline, or desipramine would be the way to go.  

 

Would love to see a head to head comparison of the newer NRIs versus the TCA NRIs for treatment of adhd.  I've looked for it, but couldn't find it so let me know if any of ya'll ever see such a study.  

 

So because of Nort's broad spectrum effect it effectively treats my:  

Depression

Anxiety

ADHD

Nervous Stomach Syndrome (very similar to IBS; primary symptoms were discomfort/pain, diarrhea, feeling of having to go when I don't need to go)

And it even fixes my allergies!


  • Informative x 1

#9 Kinesis

  • Registered User
  • 236 posts
  • 25
  • Location:Pennsylvania USA
  • NO

Posted 20 October 2017 - 03:50 AM

Nortriptyline isn’t really an NRI ... or it’s a very dirty one at best ...

https://en.m.wikiped...i/Nortriptyline

Besides norepinephrine, it inhibits serotonin reuptake, it’s antihistaminergic, anticholinergic ...

Edited by Kinesis, 20 October 2017 - 03:52 AM.

  • Disagree x 1

#10 CWF1986

  • Topic Starter
  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 20 October 2017 - 06:45 AM

Nortriptyline isn’t really an NRI ... or it’s a very dirty one at best ...

https://en.m.wikiped...i/Nortriptyline

Besides norepinephrine, it inhibits serotonin reuptake, it’s antihistaminergic, anticholinergic ...

 

You have to look at it's selectivity for NRI and compare that to the activity at other sites and compare that to other meds.  Compared to any SNRIs and the overwhelming majority of all other ADs, nortriptyline is very selective for NRI.  Are there more selective ones?  Yes, but only a few and higher selectivity isn't necessarily good or bad. 

 

At the very least, nortriptyline has 10x more affinity for the NET than the SERT.  There's also heaps of clinical evidence where nortriptyline is safely combined with SSRIs and even irreversible MAOIs.  This by itself suggest that the serotonergic effects are clinically insignificant.

 

The antihistamine effect as I mentioned already is not necessarily a bad thing and actually something in common with more modern more commonly used antidepressants.  This can actually be a good thing because it can help a person fall asleep and stay asleep.  The anticholinergic effects as I mentioned already may very well be part of the therapeutic effect.  Try looking up 'cholinergic-adrenergic hypothesis of mania and depression'.  There is a lot of evidence that suggests that this might be the reason nortriptyline and desipramine are such effective ADs while reboxetine and atomoxetine are not.  

 

Did you know that at a high enough dosage, acetaminophen can alter serotonin levels to point that it could be an antidepressant.... except that it's highly toxic at those doses.  That's how important selectivity is.  

 

All antidepressants have some affinity for sites other than there targeted ones.  So other than saying that nortriptyline has some affinity at these sites, do you have any other evidence suggesting that nortriptyline is not an NRI or even that it's a dirty NRI?


  • WellResearched x 1

#11 RedStaR

  • Registered User
  • 14 posts
  • 2
  • Location:Universe
  • NO

Posted 20 October 2017 - 09:02 AM

The reason Strattera is better for ADHD is that the "sedation" effects helps with hyperactivity and racing thoughts. It's a specific kind of sedation though, not like sleeping medications. one appropriate for ADHD. This is why I think Reboxetine and Nortriptyline are less likely to help with ADHD, even though they all might effect dopamine reuptake via NET in the frontal cortex to some extent. But then that's also why Nortriptyline is often more appropriate for plain depression without comorbid ADHD.


I'm not speaking to theoreticals, only my personal anecdotal n=1 experience.

Nortriptyline does help a lot with my ADHD PI. It helps with focus and attention a lot and helps a little with restlessness. So once I'm on task I can stay on task. Granted, I still take Adderall for motivation, energy, and consciousness. It isn't that hard to find trials where Nort. is tested for efficacy with adhd and it actually does a pretty decent job. So for those that can't tolerate the sides of reboxetine or atomoxetine it might be worth a try.

Given the low efficacy of roboxetine or amotoxetine for depression, if one wanted to give one med to fix both adhd and depression it would seem like imipramine, nortriptyline, or desipramine would be the way to go.

Would love to see a head to head comparison of the newer NRIs versus the TCA NRIs for treatment of adhd. I've looked for it, but couldn't find it so let me know if any of ya'll ever see such a study.

So because of Nort's broad spectrum effect it effectively treats my:
Depression
Anxiety
ADHD
Nervous Stomach Syndrome (very similar to IBS; primary symptoms were discomfort/pain, diarrhea, feeling of having to go when I don't need to go)
And it even fixes my allergies!

ATX is very effective for depression IME. It is a SERT inhibitor after all.

#12 Kinesis

  • Registered User
  • 236 posts
  • 25
  • Location:Pennsylvania USA
  • NO

Posted 20 October 2017 - 05:38 PM

Nortriptyline isn’t really an NRI ... or it’s a very dirty one at best ...

https://en.m.wikiped...i/Nortriptyline

Besides norepinephrine, it inhibits serotonin reuptake, it’s antihistaminergic, anticholinergic ...

 
You have to look at it's selectivity for NRI and compare that to the activity at other sites and compare that to other meds.  Compared to any SNRIs and the overwhelming majority of all other ADs, nortriptyline is very selective for NRI.  Are there more selective ones?  Yes, but only a few and higher selectivity isn't necessarily good or bad. 
 
At the very least, nortriptyline has 10x more affinity for the NET than the SERT.  There's also heaps of clinical evidence where nortriptyline is safely combined with SSRIs and even irreversible MAOIs.  This by itself suggest that the serotonergic effects are clinically insignificant.
 
The antihistamine effect as I mentioned already is not necessarily a bad thing and actually something in common with more modern more commonly used antidepressants.  This can actually be a good thing because it can help a person fall asleep and stay asleep.  The anticholinergic effects as I mentioned already may very well be part of the therapeutic effect.  Try looking up 'cholinergic-adrenergic hypothesis of mania and depression'.  There is a lot of evidence that suggests that this might be the reason nortriptyline and desipramine are such effective ADs while reboxetine and atomoxetine are not.  
 
Did you know that at a high enough dosage, acetaminophen can alter serotonin levels to point that it could be an antidepressant.... except that it's highly toxic at those doses.  That's how important selectivity is.  
 
All antidepressants have some affinity for sites other than there targeted ones.  So other than saying that nortriptyline has some affinity at these sites, do you have any other evidence suggesting that nortriptyline is not an NRI or even that it's a dirty NRI?

 
The fact that it inhibits the reuptake of norepinephrine (among other things) technically may make it an NRI, but that's a poor way to characterize its action because of all the other things it does.  That's why the literature classifies it as a tricyclic.  It's like calling your grocer a banana salesman ... it may be technically correct, but there are far better ways to describe a grocer.

Conversely, there are other drugs with much better standing to be referred to as NRIs.  Take bupropion, for example.  Virtually no anticholinergic properties, no antihistamine properties, little or no serotinergic properties ... you get the picture.

Other evidence?  We already have all we need.  It's stipulated that it does a lot of stuff other than inhibit norepinephrine uptake.  This makes it a dirty NRI at best.  There is a reason its classified as a tricyclic ... it just has a lot more in common with other tricyclics than drugs whose primary MOA is inhibition of norepinephrine.  Meanwhile if you have any evidence that experts in the field prefer characterizing nortriptyline as an NRI over a tricyclic, that would go a long way towards supporting your claim.

Don't confuse whether or not it is an antihistamine or does this or that with value judgments.  It may be good in some situations, bad in others, but it's always an antihistamine.  Rather get bogged down in situational and subjective judgments about merit, I'd rather just stick with the facts.  But if being an antihistamine is "good" then amitriptyline would be even better.  It's a stronger antihistamine.  It’s already more balanced so you wouldn't need an SSRI with it.  You wouldn't need nortriptyline either ... because with ami you get both.  Amitriptyline is metabolized into nortriptyline.
 

https://en.wikipedia...i/Amitriptyline


What's more, amitriptyiline has a unique neurotropic mechanism:
 

The Antidepressant Amitriptyline is a TrkA and TrkB Receptor Agonist that Promotes TrkA/TrkB Heterodimerization and Has Potent Neurotrophic Activity

https://www.ncbi.nlm...les/PMC2844702/


This is one of the reasons amitriptyline is the classic gold standard antidepressant.

And if being an anticholinergic is "good", then you're better off with ami on that count too.  If on the other hand being an anticholinergic is "bad", then why take one at all, when you could take bupropion or any one of other newer drugs that are not anticholinergic and have vastly better qualifications as an NRI.

#13 YoungSchizo

  • Registered User
  • 604 posts
  • 14
  • Location:I Have No Clue

Posted 20 October 2017 - 05:56 PM

I've tried Amitriptyline for my insomnia, didn't do anything. If I wasn't aware of Tardive Dyskinesia symptoms I would've probably developed it on Amitriptyline. When my tongue felt really heavy and started moving involuntarily I quit it right away. Never taking that shit again.



#14 Kinesis

  • Registered User
  • 236 posts
  • 25
  • Location:Pennsylvania USA
  • NO

Posted 20 October 2017 - 06:18 PM

I've tried Amitriptyline for my insomnia, didn't do anything. If I wasn't aware of Tardive Dyskinesia symptoms I would've probably developed it on Amitriptyline. When my tongue felt really heavy and started moving involuntarily I quit it right away. Never taking that shit again.


I hope it's clear no one here has claimed amitriptyline was appropriate for you. But an unfavorable reaction to amitriptyline makes it less likely you would react favorably to other tricyclics like nortriptyline. As noted above, amitriptyline is metabolized to nortriptyline and they are structurally similar.

What worked for you?

Edited by Kinesis, 20 October 2017 - 06:33 PM.

  • Agree x 1

#15 YoungSchizo

  • Registered User
  • 604 posts
  • 14
  • Location:I Have No Clue

Posted 20 October 2017 - 06:35 PM

 

I've tried Amitriptyline for my insomnia, didn't do anything. If I wasn't aware of Tardive Dyskinesia symptoms I would've probably developed it on Amitriptyline. When my tongue felt really heavy and started moving involuntarily I quit it right away. Never taking that shit again.


What worked for you?

 

 

How do you mean? For insomnia? I've tried almost every antidepressant with antihistamine or sleep inducing properties nothing worked except for Mirtazapine. It makes me fall asleep but doesn't keep me at sleep (anymore). I have some sort of sleep maintenance insomnia but idk, going to a sleep-study soon to find out why I have a interrupted sleep. And I'm trialing Gabapentin right now (just the second day) and that worked last night.

 

And idk why Ami almost caused TD, could be because I'm also on 2 antipsychotics (maybe they interacted with Ami) but I never had TD symptoms in 12 years that I'm on antipsychotics (except for some innocent muscle twitches now and then).



#16 CWF1986

  • Topic Starter
  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 20 October 2017 - 06:49 PM

 

 

Nortriptyline isn’t really an NRI ... or it’s a very dirty one at best ...

https://en.m.wikiped...i/Nortriptyline

Besides norepinephrine, it inhibits serotonin reuptake, it’s antihistaminergic, anticholinergic ...

 
You have to look at it's selectivity for NRI and compare that to the activity at other sites and compare that to other meds.  Compared to any SNRIs and the overwhelming majority of all other ADs, nortriptyline is very selective for NRI.  Are there more selective ones?  Yes, but only a few and higher selectivity isn't necessarily good or bad. 
 
At the very least, nortriptyline has 10x more affinity for the NET than the SERT.  There's also heaps of clinical evidence where nortriptyline is safely combined with SSRIs and even irreversible MAOIs.  This by itself suggest that the serotonergic effects are clinically insignificant.
 
The antihistamine effect as I mentioned already is not necessarily a bad thing and actually something in common with more modern more commonly used antidepressants.  This can actually be a good thing because it can help a person fall asleep and stay asleep.  The anticholinergic effects as I mentioned already may very well be part of the therapeutic effect.  Try looking up 'cholinergic-adrenergic hypothesis of mania and depression'.  There is a lot of evidence that suggests that this might be the reason nortriptyline and desipramine are such effective ADs while reboxetine and atomoxetine are not.  
 
Did you know that at a high enough dosage, acetaminophen can alter serotonin levels to point that it could be an antidepressant.... except that it's highly toxic at those doses.  That's how important selectivity is.  
 
All antidepressants have some affinity for sites other than there targeted ones.  So other than saying that nortriptyline has some affinity at these sites, do you have any other evidence suggesting that nortriptyline is not an NRI or even that it's a dirty NRI?

 

 
The fact that it inhibits the reuptake of norepinephrine (among other things) technically may make it an NRI, but that's a poor way to characterize its action because of all the other things it does.  That's why the literature classifies it as a tricyclic.  It's like calling your grocer a banana salesman ... it may be technically correct, but there are far better ways to describe a grocer.

Conversely, there are other drugs with much better standing to be referred to as NRIs.  Take bupropion, for example.  Virtually no anticholinergic properties, no antihistamine properties, little or no serotinergic properties ... you get the picture.

Other evidence?  We already have all we need.  It's stipulated that it does a lot of stuff other than inhibit norepinephrine uptake.  This makes it a dirty NRI at best.  There is a reason its classified as a tricyclic ... it just has a lot more in common with other tricyclics than drugs whose primary MOA is inhibition of norepinephrine.  Meanwhile if you have any evidence that experts in the field prefer characterizing nortriptyline as an NRI over a tricyclic, that would go a long way towards supporting your claim.

Don't confuse whether or not it is an antihistamine or does this or that with value judgments.  It may be good in some situations, bad in others, but it's always an antihistamine.  Rather get bogged down in situational and subjective judgments about merit, I'd rather just stick with the facts.  But if being an antihistamine is "good" then amitriptyline would be even better.  It's a stronger antihistamine.  It’s already more balanced so you wouldn't need an SSRI with it.  You wouldn't need nortriptyline either ... because with ami you get both.  Amitriptyline is metabolized into nortriptyline.
 

https://en.wikipedia...i/Amitriptyline


What's more, amitriptyiline has a unique neurotropic mechanism:
 

The Antidepressant Amitriptyline is a TrkA and TrkB Receptor Agonist that Promotes TrkA/TrkB Heterodimerization and Has Potent Neurotrophic Activity

https://www.ncbi.nlm...les/PMC2844702/


This is one of the reasons amitriptyline is the classic gold standard antidepressant.

And if being an anticholinergic is "good", then you're better off with ami on that count too.  If on the other hand being an anticholinergic is "bad", then why take one at all, when you could take bupropion or any one of other newer drugs that are not anticholinergic and have vastly better qualifications as an NRI.

 

Bupropion is very anticholinergic.  Granted, it's anticholinergic at the NAchR sites rather than the MAchR sites.  This is arguably bupropion's more important AD effect, granted the jury is still out on this one.  We also don't have a full understanding of how bupropion is metabolized so there may or may not be a direct dopaminergic effect and there may be an indirect one from the NAch.  

 

Sometimes, the greater antihistamine and anticholinergic effects of older TCAs like amitriptyline or imipramine will be better for some people.  For most it's too much and something cleaner like nortriptyline would be more advantageous.

 

Nortriptyline with an SSRI will probably actually have fewer sides than something like ami, imi, or clomipramine.  

 

I'm not sure why you're drawing a dichotomy between the TCA label and NRI label.  



#17 YoungSchizo

  • Registered User
  • 604 posts
  • 14
  • Location:I Have No Clue

Posted 20 October 2017 - 07:56 PM

 

I've tried Amitriptyline for my insomnia, didn't do anything. If I wasn't aware of Tardive Dyskinesia symptoms I would've probably developed it on Amitriptyline. When my tongue felt really heavy and started moving involuntarily I quit it right away. Never taking that shit again.


I hope it's clear no one here has claimed amitriptyline was appropriate for you. But an unfavorable reaction to amitriptyline makes it less likely you would react favorably to other tricyclics like nortriptyline. As noted above, amitriptyline is metabolized to nortriptyline and they are structurally similar.

What worked for you?

 

 

Oh you edited your answer.. Didn't see it. My point was that Ami isn't that "clean" of a drug either. I might react different to Nortriptyline because I'm on Parnate. Also, your claim raises a question though, then why is Parnate allowed and not contraindicated with Nort but it is with Ami because of a potential serotonin-syndrome? 



#18 CWF1986

  • Topic Starter
  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 21 October 2017 - 04:20 AM

 

 

I've tried Amitriptyline for my insomnia, didn't do anything. If I wasn't aware of Tardive Dyskinesia symptoms I would've probably developed it on Amitriptyline. When my tongue felt really heavy and started moving involuntarily I quit it right away. Never taking that shit again.


I hope it's clear no one here has claimed amitriptyline was appropriate for you. But an unfavorable reaction to amitriptyline makes it less likely you would react favorably to other tricyclics like nortriptyline. As noted above, amitriptyline is metabolized to nortriptyline and they are structurally similar.

What worked for you?

 

 

Oh you edited your answer.. Didn't see it. My point was that Ami isn't that "clean" of a drug either. I might react different to Nortriptyline because I'm on Parnate. Also, your claim raises a question though, then why is Parnate allowed and not contraindicated with Nort but it is with Ami because of a potential serotonin-syndrome? 

 

 

Amitriptyline at least in practice has enough affinity for the SERT relative to other sites it affects to the point that it's clinically significant.  Nortriptyline in practice does not.  So the reason amitriptyline is contraindicated with irreversible MAOIs is because of the likelihood of serotonin syndrome.  



#19 CWF1986

  • Topic Starter
  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 21 October 2017 - 04:53 AM

I'll give you this much Kinesis,  nortriptyline is not a pure NRI.  Most accurately stated I see it best said that it's an NRI with activity at other sites in addition to its TCA label.  Keep in mind that are very few medications that come close to Nortriptyline's potency or selectivity for NRI.  This is why I strongly believe that the NRI label is a good one for nort.

 

https://en.wikipedia...ptake_inhibitor

 

But of the four NRI's that have been discused the most in this thread, it is safe to say that nortriptyline is the most broad-spectrum.  I choose not to say 'dirty' to avoid the negative connotations that the word conveys since the broad spectrum effects of nort. may or may not be a good thing depending on the individual.  

 

To further clarify the 2nd generation TCA's that are highly selective for NRI, nortriptyline and desipramine, are tolerated much better than their predecessors and are arguable as safe and just as tolerable as most SSRIs.  Given the bias of the studies of the tolerability of SSRIs, it's very difficult to determine for sure if they actually are any more tolerable than nort, or desipramine.   

 

 



#20 RedStaR

  • Registered User
  • 14 posts
  • 2
  • Location:Universe
  • NO

Posted 21 October 2017 - 11:38 AM

 

 

 

Nortriptyline isn’t really an NRI ... or it’s a very dirty one at best ...

https://en.m.wikiped...i/Nortriptyline

Besides norepinephrine, it inhibits serotonin reuptake, it’s antihistaminergic, anticholinergic ...

 
You have to look at it's selectivity for NRI and compare that to the activity at other sites and compare that to other meds.  Compared to any SNRIs and the overwhelming majority of all other ADs, nortriptyline is very selective for NRI.  Are there more selective ones?  Yes, but only a few and higher selectivity isn't necessarily good or bad. 
 
At the very least, nortriptyline has 10x more affinity for the NET than the SERT.  There's also heaps of clinical evidence where nortriptyline is safely combined with SSRIs and even irreversible MAOIs.  This by itself suggest that the serotonergic effects are clinically insignificant.
 
The antihistamine effect as I mentioned already is not necessarily a bad thing and actually something in common with more modern more commonly used antidepressants.  This can actually be a good thing because it can help a person fall asleep and stay asleep.  The anticholinergic effects as I mentioned already may very well be part of the therapeutic effect.  Try looking up 'cholinergic-adrenergic hypothesis of mania and depression'.  There is a lot of evidence that suggests that this might be the reason nortriptyline and desipramine are such effective ADs while reboxetine and atomoxetine are not.  
 
Did you know that at a high enough dosage, acetaminophen can alter serotonin levels to point that it could be an antidepressant.... except that it's highly toxic at those doses.  That's how important selectivity is.  
 
All antidepressants have some affinity for sites other than there targeted ones.  So other than saying that nortriptyline has some affinity at these sites, do you have any other evidence suggesting that nortriptyline is not an NRI or even that it's a dirty NRI?

 

 
The fact that it inhibits the reuptake of norepinephrine (among other things) technically may make it an NRI, but that's a poor way to characterize its action because of all the other things it does.  That's why the literature classifies it as a tricyclic.  It's like calling your grocer a banana salesman ... it may be technically correct, but there are far better ways to describe a grocer.

Conversely, there are other drugs with much better standing to be referred to as NRIs.  Take bupropion, for example.  Virtually no anticholinergic properties, no antihistamine properties, little or no serotinergic properties ... you get the picture.

Other evidence?  We already have all we need.  It's stipulated that it does a lot of stuff other than inhibit norepinephrine uptake.  This makes it a dirty NRI at best.  There is a reason its classified as a tricyclic ... it just has a lot more in common with other tricyclics than drugs whose primary MOA is inhibition of norepinephrine.  Meanwhile if you have any evidence that experts in the field prefer characterizing nortriptyline as an NRI over a tricyclic, that would go a long way towards supporting your claim.

Don't confuse whether or not it is an antihistamine or does this or that with value judgments.  It may be good in some situations, bad in others, but it's always an antihistamine.  Rather get bogged down in situational and subjective judgments about merit, I'd rather just stick with the facts.  But if being an antihistamine is "good" then amitriptyline would be even better.  It's a stronger antihistamine.  It’s already more balanced so you wouldn't need an SSRI with it.  You wouldn't need nortriptyline either ... because with ami you get both.  Amitriptyline is metabolized into nortriptyline.
 

https://en.wikipedia...i/Amitriptyline


What's more, amitriptyiline has a unique neurotropic mechanism:
 

The Antidepressant Amitriptyline is a TrkA and TrkB Receptor Agonist that Promotes TrkA/TrkB Heterodimerization and Has Potent Neurotrophic Activity

https://www.ncbi.nlm...les/PMC2844702/


This is one of the reasons amitriptyline is the classic gold standard antidepressant.

And if being an anticholinergic is "good", then you're better off with ami on that count too.  If on the other hand being an anticholinergic is "bad", then why take one at all, when you could take bupropion or any one of other newer drugs that are not anticholinergic and have vastly better qualifications as an NRI.

 

Bupropion is very anticholinergic.  Granted, it's anticholinergic at the NAchR sites rather than the MAchR sites.  This is arguably bupropion's more important AD effect, granted the jury is still out on this one.  We also don't have a full understanding of how bupropion is metabolized so there may or may not be a direct dopaminergic effect and there may be an indirect one from the NAch.  

 

Sometimes, the greater antihistamine and anticholinergic effects of older TCAs like amitriptyline or imipramine will be better for some people.  For most it's too much and something cleaner like nortriptyline would be more advantageous.

 

Nortriptyline with an SSRI will probably actually have fewer sides than something like ami, imi, or clomipramine.  

 

I'm not sure why you're drawing a dichotomy between the TCA label and NRI label.  

 

We do know how BUP is metabolized, and it does have a direct DAT effect.



#21 Kinesis

  • Registered User
  • 236 posts
  • 25
  • Location:Pennsylvania USA
  • NO

Posted 21 October 2017 - 03:13 PM

I'll give you this much Kinesis, nortriptyline is not a pure NRI. Most accurately stated I see it best said that it's an NRI with activity at other sites in addition to its TCA label. Keep in mind that are very few medications that come close to Nortriptyline's potency or selectivity for NRI. This is why I strongly believe that the NRI label is a good one for nort.

https://en.wikipedia...ptake_inhibitor

But of the four NRI's that have been discused the most in this thread, it is safe to say that nortriptyline is the most broad-spectrum. I choose not to say 'dirty' to avoid the negative connotations that the word conveys since the broad spectrum effects of nort. may or may not be a good thing depending on the individual.

To further clarify the 2nd generation TCA's that are highly selective for NRI, nortriptyline and desipramine, are tolerated much better than their predecessors and are arguable as safe and just as tolerable as most SSRIs. Given the bias of the studies of the tolerability of SSRIs, it's very difficult to determine for sure if they actually are any more tolerable than nort, or desipramine.


Bupropion is very anticholinergic. Granted, it's anticholinergic at the NAchR sites rather than the MAchR sites. This is arguably bupropion's more important AD effect, granted the jury is still out on this one. We also don't have a full understanding of how bupropion is metabolized so there may or may not be a direct dopaminergic effect and there may be an indirect one from the NAch.


Burpropion is not anticholinergic.

The Psychopharmacology Institute states:
 

Bupropion is generally not sedating, it doesn’t have antihistaminic or anticholinergic properties.

https://psychopharma...hopharmacology/


It further states:
 

Bupropion is a non competitive antagonist of nicotinic acetylcholine receptors.


So how can the Psychopharmacology Institute recognize competitive antagonism at NAchR and still say it’s not anticholinergic? Because that’s not what "anticholinergic" means.
 

I'm not sure why you're drawing a dichotomy between the TCA label and NRI label.


It’s a similar situation here. These terms have certain meanings in the field. Take a look at the Wikipedia entry for nortriptyline: https://en.wikipedia...i/Nortriptyline

In this entry, I count nine occurrences of the term "tricyclic". For the term "NRI", there are zero. Why do you suppose this is? The answer is simply that nortriptyline is not considered an NRI. I tried to explain why above (too many other activities), but that part’s just my interpretation. The bottom line is that it’s not.

In other words, it’s not me that’s drawing a dichotomy. I’m not making these things up. I’m not asking people to take my word for anything. I’m citing independent authorities. Unfortunately many people who post in internet forums don’t do their homework first, and other people read what they post and repeat. This is how urban legends and other misconceptions originate and propagate. Ones like "bupropion is anticholinergic". I’m afraid a partial understanding of something often leads people to feel more informed than they are, probably accounting for the cliche "a little knowledge is a dangerous thing".
  • Ill informed x 1

#22 Kinesis

  • Registered User
  • 236 posts
  • 25
  • Location:Pennsylvania USA
  • NO

Posted 21 October 2017 - 03:47 PM

 

 

I've tried Amitriptyline for my insomnia, didn't do anything. If I wasn't aware of Tardive Dyskinesia symptoms I would've probably developed it on Amitriptyline. When my tongue felt really heavy and started moving involuntarily I quit it right away. Never taking that shit again.


I hope it's clear no one here has claimed amitriptyline was appropriate for you. But an unfavorable reaction to amitriptyline makes it less likely you would react favorably to other tricyclics like nortriptyline. As noted above, amitriptyline is metabolized to nortriptyline and they are structurally similar.

What worked for you?

 

 
Oh you edited your answer.. Didn't see it. My point was that Ami isn't that "clean" of a drug either. I might react different to Nortriptyline because I'm on Parnate. Also, your claim raises a question though, then why is Parnate allowed and not contraindicated with Nort but it is with Ami because of a potential serotonin-syndrome?

 


That seems likely, YS. None of the tricyclics are what we could call "clean" drugs. This is why they aren't classified in neurotransmitter terms in the field.  Yes, it's probably the greater SRI activity of ami that accounts for the Parnate cautions. Although we have to recognize the incompleteness of our knowledge about these things. For example, similar warnings persist about using St John's Wort with serotinergic pharmaceuticals ... but they are based on an old theory that St John's acted mainly through an SSRI type of mechanism. That theory probably gained currency because at the time SSRIs had just become popular so there was a tendency to try and explain the AD properties of little-understood St John's in those trendy terms.

Yet once notions like those get out, it's hard to get rid of them, even when the theory upon which they were based is superseded by newer understanding. BTW this is not to recommend taking St John's with other drugs ... there may be good reasons for caution (e.g. St John's action on drug metabolizing liver enzymes) ... rather the point is we can't take for granted that we have the final word on these things.

 

The "dirty" nature of the tricyclics is one of the reasons they've fallen out of favor and have largely been superseded by SSRIs and newer drugs.  But there are too many different people with different individual biochemistries to draw blanket conclusions like this or that is a "good" drug or "bad" drug.  My doctor prescribed one (ami) to me and I think he did so for good reasons.  In your case, I would think your doctor would know whether nortriptyline would be an acceptable candidate in your circumstances.  I'm just saying that the similarities between nortriptyline and amitriptyline are greater than the differences - they literally differ by only one methyl group and greatly overlap functionally.  They're both triptylines.  And I'm afraid for reasons of record that this thread is not the most reliable place to be looking for medical advice.  Sure, if you think nortriptyline is a good candidate for your situation, mention it to your doctor.  But I wouldn't assume that just due due to lesser serotonergic activity it's going to be safe, and I certainly wouldn't run out and start taking it based just on something I read on the internet.  Drug-drug interactions are serious business and require real expertise and an individual assessment.

 

Dose makes a difference too,  A drug that might cause conflicts or prompt negative sides at one dosage might work well at a lower one. 

 

In any case, I hope you find relief.

 


Edited by Kinesis, 21 October 2017 - 04:07 PM.


#23 CWF1986

  • Topic Starter
  • Registered User
  • 51 posts
  • 8
  • Location:Houston, Texas

Posted 21 October 2017 - 06:05 PM

I just want to clarify that any advice I've given shouldn't be taken as a stand alone, just something you want to discuss with your doctor.

 

Irreversible MAOIs are heavy hitters with many interactions and potential sides so combining one of them with anything is definitely something you should talk to a trained doctor about.

 

If I were in your shoes, I would be looking for a psychiatrist as opposed to a general practitioner if I haven't found one already and it's at all possible.  

 

Here's some relevant food for thought for all in this thread:

 

https://www.ncbi.nlm...es/PMC2014120/ 

-A little about nort's effects on the pressor response and receptor affinities and selectivity

Especially check out this section:

The relationship of receptor affinity and therapeutic effect: noradrenaline reuptake inhibition and the pressor response to tyramine

 

https://psychotropic...pressants/snris

-this one covers similar subjects, but is a lot more digestible

 

https://academic.oup...er-occupancy-by

-an interesting study about nortriptyline and it's NET occupancy

 

 

 

 

 



#24 RedStaR

  • Registered User
  • 14 posts
  • 2
  • Location:Universe
  • NO

Posted 21 October 2017 - 08:10 PM

Burpropion is not anticholinergic.

The Psychopharmacology Institute states:
 

Bupropion is generally not sedating, it doesn’t have antihistaminic or anticholinergic properties.

https://psychopharma...hopharmacology/


It further states:
 

Bupropion is a non competitive antagonist of nicotinic acetylcholine receptors.


So how can the Psychopharmacology Institute recognize competitive antagonism at NAchR and still say it’s not anticholinergic? Because that’s not what "anticholinergic" means.

 

 

Or maybe you just don't know what it means.

 

Bupropion is clearly an antinicotinic agent. No one said it had antihistaminic properties, unless that unintentionally came along with the quote.

 

And what the fuck is the Psychopharmacology institute? Because that is a stupid thing to say.


Edited by RedStaR, 21 October 2017 - 08:11 PM.

  • Pointless, Timewasting x 1

#25 Stinkorninjor

  • Registered User
  • 1,358 posts
  • 104
  • Location:Scandinavia
  • NO

Posted 21 October 2017 - 09:02 PM

Hmm.

As someone who's currently STILL feeling the most minor of Adrenergic Storm -symptoms, ak a Drug-induced Hypertensive crisis, ak a NOREPINEPHRINE Syndrom, I find myself somewhat sceptical regarding allowing an NRI as powerful as Nortriptyline to be prescribed with an MAOI... Most people, and Dr's for that matter, seem to be very unaware of how dangerous excessive norepinephrinergic activity can be - I myself can attest that it's an experience similar in some ways to both psychosis and serotonin syndrome.

 

Why is there such a focus on Serotonin, when, clearly, multiple MAOI's have acute hypertension as a common side-effect? (apparently this goes away fairly quickly though, and is not consistent most times)

 

Trust me when I say this: the pain from the headache caused by Adrenergic Storm is almost unbelievable - I've broken multiple bones, including my ribs, and this was, imho, WORSE! Too much blood in your skull, reversed migraine, basically.

 

 

I wouldn't use an NRI with an MAOI selective for MAO-B - quite frankly, you'll probably DIE!

 

Unless you have Clonidine at hand, of course. (beloved clonidine...)

 

 


  • Enjoying the show x 1

#26 Kinesis

  • Registered User
  • 236 posts
  • 25
  • Location:Pennsylvania USA
  • NO

Posted 22 October 2017 - 04:29 PM

Or maybe you just don't know what it means.

Bupropion is clearly an antinicotinic agent. No one said it had antihistaminic properties, unless that unintentionally came along with the quote.

And what the fuck is the Psychopharmacology institute? Because that is a stupid thing to say.


No it didn't unintentionally come along with the quote. The issue is similar to the one of classifying nortriptyline as an NRI ... may be technically correct, but clinically misleading.

Practicing physicians are often concerned with anticholinergic properties ... sometimes they are wanted and sometimes they are not. Negative effects of chronic use of anticholinergics have come into focus recently due to a study published in JAMA Neurology:
 

The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia.

https://www.ncbi.nlm...pubmed/27088965


So when considering alternatives for a given chronic condition, all else being equal, if one drug is more anticholinergic and another one is less, so, the latter may be preferred. The following link is to a physician’s guide intended to be used as a prescribing aid:
 

http://prescribersle...=3860&dd=271223


Several classes of drugs are listed along with their anticholinergic activity. In the left column are drugs with "MEDIUM/HIGH Activity", and in the right are those with "LOW Activity". Under the Drug Class heading "Antidepressant" we have on the left several familar names: tricyclics such as Amitripyline, Clomipramine, Imipramine, Nortriptyline, the SSRI Paroxetine, etcetera. On the right we have most of the rest of the SSRIs, Citalopram, Fluoxetine, Sertraline, the tetracyclic Mirtazapine, and notably, listed in the top spot, Bupropion.

In short, this guide advises doctors considering antidepressant meds and wishing to minimize anticholinergic effects to consider bupropion, right along with well known SSRIs and other meds.

So if your doctor is looking for an antidepressant and looking to avoid anticholinergic risks, bupropion is one of the drugs likely to be prescribed.
  • Good Point x 1
  • Informative x 1

#27 Kinesis

  • Registered User
  • 236 posts
  • 25
  • Location:Pennsylvania USA
  • NO

Posted 22 October 2017 - 04:40 PM

Hmm.
As someone who's currently STILL feeling the most minor of Adrenergic Storm -symptoms, ak a Drug-induced Hypertensive crisis, ak a NOREPINEPHRINE Syndrom, I find myself somewhat sceptical regarding allowing an NRI as powerful as Nortriptyline to be prescribed with an MAOI... Most people, and Dr's for that matter, seem to be very unaware of how dangerous excessive norepinephrinergic activity can be - I myself can attest that it's an experience similar in some ways to both psychosis and serotonin syndrome.
 
Why is there such a focus on Serotonin, when, clearly, multiple MAOI's have acute hypertension as a common side-effect? (apparently this goes away fairly quickly though, and is not consistent most times)
 
Trust me when I say this: the pain from the headache caused by Adrenergic Storm is almost unbelievable - I've broken multiple bones, including my ribs, and this was, imho, WORSE! Too much blood in your skull, reversed migraine, basically.
 
 
I wouldn't use an NRI with an MAOI selective for MAO-B - quite frankly, you'll probably DIE!
 
Unless you have Clonidine at hand, of course. (beloved clonidine...)


Glad you called that to our attention ... in fact MAOIs are listed as contraindicated for nortriptyline use.
 

Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with Pamelor or within 14 days of stopping treatment with Pamelor is contraindicated because of an increased risk of serotonin syndrome.

https://www.rxlist.c...amelor-drug.htm


 
Although this reference cites concern about serotonin syndrome, I'd be at least as concerned about the norepinephrine syndrome you report ... you may be on the cutting edge of the next big thing!



#28 RedStaR

  • Registered User
  • 14 posts
  • 2
  • Location:Universe
  • NO

Posted 22 October 2017 - 05:34 PM

Or maybe you just don't know what it means.

Bupropion is clearly an antinicotinic agent. No one said it had antihistaminic properties, unless that unintentionally came along with the quote.

And what the fuck is the Psychopharmacology institute? Because that is a stupid thing to say.

No it didn't unintentionally come along with the quote. The issue is similar to the one of classifying nortriptyline as an NRI ... may be technically correct, but clinically misleading.

Practicing physicians are often concerned with anticholinergic properties ... sometimes they are wanted and sometimes they are not. Negative effects of chronic use of anticholinergics have come into focus recently due to a study published in JAMA Neurology:



The use of anticholinergic (AC) medication is linked to cognitive impairment and an increased risk of dementia.

https://www.ncbi.nlm...pubmed/27088965

So when considering alternatives for a given chronic condition, all else being equal, if one drug is more anticholinergic and another one is less, so, the latter may be preferred. The following link is to a physician’s guide intended to be used as a prescribing aid:



http://prescribersle...=3860&dd=271223

Several classes of drugs are listed along with their anticholinergic activity. In the left column are drugs with "MEDIUM/HIGH Activity", and in the right are those with "LOW Activity". Under the Drug Class heading "Antidepressant" we have on the left several familar names: tricyclics such as Amitripyline, Clomipramine, Imipramine, Nortriptyline, the SSRI Paroxetine, etcetera. On the right we have most of the rest of the SSRIs, Citalopram, Fluoxetine, Sertraline, the tetracyclic Mirtazapine, and notably, listed in the top spot, Bupropion.

In short, this guide advises doctors considering antidepressant meds and wishing to minimize anticholinergic effects to consider bupropion, right along with well known SSRIs and other meds.

So if your doctor is looking for an antidepressant and looking to avoid anticholinergic risks, bupropion is one of the drugs likely to be prescribed.
It's called the ACB scale. Two poor sources suggest BUP has weak AC effects. That's it.

BUP has given me, and many others, severe dry mouths, muscle weakness, and memory loss.

Edited by RedStaR, 22 October 2017 - 05:35 PM.

  • Ill informed x 1

#29 Finn

  • Registered User
  • 116 posts
  • 26
  • Location:Finland
  • NO

Posted 22 October 2017 - 05:34 PM

Hmm.

As someone who's currently STILL feeling the most minor of Adrenergic Storm -symptoms, ak a Drug-induced Hypertensive crisis, ak a NOREPINEPHRINE Syndrom, I find myself somewhat sceptical regarding allowing an NRI as powerful as Nortriptyline to be prescribed with an MAOI... Most people, and Dr's for that matter, seem to be very unaware of how dangerous excessive norepinephrinergic activity can be - I myself can attest that it's an experience similar in some ways to both psychosis and serotonin syndrome.

 

Why is there such a focus on Serotonin, when, clearly, multiple MAOI's have acute hypertension as a common side-effect? (apparently this goes away fairly quickly though, and is not consistent most times)

 

Trust me when I say this: the pain from the headache caused by Adrenergic Storm is almost unbelievable - I've broken multiple bones, including my ribs, and this was, imho, WORSE! Too much blood in your skull, reversed migraine, basically.

 

 

I wouldn't use an NRI with an MAOI selective for MAO-B - quite frankly, you'll probably DIE!

 

Unless you have Clonidine at hand, of course. (beloved clonidine...)

 

http://www.longecity...ng/#entry827800

 

I'm too busy right now, jacked up on Reboxetine, NSI-189, Tianeptine and MODAFINIL to have a closer look at Nortriptyline,

 

 

 

https://www.nature.c...l/4001648a.html

Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine

--

Chronic tianeptine administration did not alter the concentration and affinity of alpha2, beta1, 5-HT1, 5-HT2, benzodiazepine, or GABA-B receptors but increased the responsiveness of the alpha1-adrenergic system.

 

 

http://www.sciencedi...0079X?via=ihub 

 

Effect of repeated treatment with tianeptine and fluoxetine on the central α1-adrenergic system

--

The obtained results showed that TIA administered repeatedly potentiated the methoxamine- and phenylephrine (PHEN)-induced exploratory hyperactivity in rats and clonidine-induced aggressiveness in mice, the effects mediated by α1-adrenoceptors.

---

The above results indicate that repeated TIA administration increases the responsiveness of the α1-adrenergic system (behavioural and biochemical changes).

 

This article is also can be found in sci-hub . P<0.001 was reached in many alpha1 response categories, so effect was quite clear and strong. Tianeptine may have contributed to that unpleasant effect of reboxetine.


Edited by Finn, 22 October 2017 - 05:36 PM.


sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#30 YoungSchizo

  • Registered User
  • 604 posts
  • 14
  • Location:I Have No Clue

Posted 22 October 2017 - 06:09 PM


That seems likely, YS. None of the tricyclics are what we could call "clean" drugs. This is why they aren't classified in neurotransmitter terms in the field.  Yes, it's probably the greater SRI activity of ami that accounts for the Parnate cautions. Although we have to recognize the incompleteness of our knowledge about these things. For example, similar warnings persist about using St John's Wort with serotinergic pharmaceuticals ... but they are based on an old theory that St John's acted mainly through an SSRI type of mechanism. That theory probably gained currency because at the time SSRIs had just become popular so there was a tendency to try and explain the AD properties of little-understood St John's in those trendy terms.

Yet once notions like those get out, it's hard to get rid of them, even when the theory upon which they were based is superseded by newer understanding. BTW this is not to recommend taking St John's with other drugs ... there may be good reasons for caution (e.g. St John's action on drug metabolizing liver enzymes) ... rather the point is we can't take for granted that we have the final word on these things.

 

The "dirty" nature of the tricyclics is one of the reasons they've fallen out of favor and have largely been superseded by SSRIs and newer drugs.  But there are too many different people with different individual biochemistries to draw blanket conclusions like this or that is a "good" drug or "bad" drug.  My doctor prescribed one (ami) to me and I think he did so for good reasons.  In your case, I would think your doctor would know whether nortriptyline would be an acceptable candidate in your circumstances.  I'm just saying that the similarities between nortriptyline and amitriptyline are greater than the differences - they literally differ by only one methyl group and greatly overlap functionally.  They're both triptylines.  And I'm afraid for reasons of record that this thread is not the most reliable place to be looking for medical advice.  Sure, if you think nortriptyline is a good candidate for your situation, mention it to your doctor.  But I wouldn't assume that just due due to lesser serotonergic activity it's going to be safe, and I certainly wouldn't run out and start taking it based just on something I read on the internet.  Drug-drug interactions are serious business and require real expertise and an individual assessment.

 

Dose makes a difference too,  A drug that might cause conflicts or prompt negative sides at one dosage might work well at a lower one. 

 

In any case, I hope you find relief.

 

 

Thanks! Luckily these sort of sites exist, it's actually great for advice! I don't quite much understand pharmacology of medications to the extend like you guys do but know just enough that whenever I get advice from you guys on which drug does what that I can research it myself. All the pdocs I had don't understand shit about pharmacology or are not up to date to current research. I have to tell them which drug does what. I have learned so much ever since hanging around these types of forums that I don't leave my which-drug-to-try-next-decisions to my pdocs, I make the decisions on which drug suites me or not and as long as I'm asking for psychiatric medication (that's in the guidelines of the DSM-IV) I usually get it since I'm able to convince my pdocs of my knowledge. 

 

 

Hmm.

As someone who's currently STILL feeling the most minor of Adrenergic Storm -symptoms, ak a Drug-induced Hypertensive crisis, ak a NOREPINEPHRINE Syndrom, I find myself somewhat sceptical regarding allowing an NRI as powerful as Nortriptyline to be prescribed with an MAOI... Most people, and Dr's for that matter, seem to be very unaware of how dangerous excessive norepinephrinergic activity can be - I myself can attest that it's an experience similar in some ways to both psychosis and serotonin syndrome.

 

Why is there such a focus on Serotonin, when, clearly, multiple MAOI's have acute hypertension as a common side-effect? (apparently this goes away fairly quickly though, and is not consistent most times)

 

Trust me when I say this: the pain from the headache caused by Adrenergic Storm is almost unbelievable - I've broken multiple bones, including my ribs, and this was, imho, WORSE! Too much blood in your skull, reversed migraine, basically.

 

 

I wouldn't use an NRI with an MAOI selective for MAO-B - quite frankly, you'll probably DIE!

 

Unless you have Clonidine at hand, of course. (beloved clonidine...)

 

Mirtazapine is also contraindicated with MAOI's, even on a high dose like 30mg nothing happened. Luckily over at the social anxiety forums they pretty much tried any combination of contraindicated drugs with MAOI's. Knowing that so many people successfully tried Nort + Parnate I should practically be safe. Also, can't find it at the moment, there was an article that stated that the dangers of MAOI's are exaggerated and out-dated. It also stated that some docs are actually revisiting the use of MAOI's as first line treatment instead of last because they're more effective than any other antidepressant drug on the market with a response rate of 80% 

 

Anyway, I probably don't even need Nort, my Gabapentin trial was a big success, not for my sleep but as an add-on treatment for depression, anxiety and negative symptoms.


  • Cheerful x 1





Also tagged with one or more of these keywords: nri, depression, anxiety, adhd, antidepressant

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users