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NRI's (norepinephrine reuptake inhibitors)

nri depression anxiety adhd antidepressant

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#1 CWF1986

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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.  

 



#2 Stinkorninjor

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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.


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#3 Adam Karlovsky

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Posted Today, 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. 



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#4 Stinkorninjor

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Posted Today, 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?







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