37 replies to this topic

[Mind_Paralysis]

 

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.

 

 

Well, damn! : O Had no clue about that... rather unexpected, I must say! However, I am somewhat skeptical... mainly because I've actually used a HIGHER dosage of Tianeptine with a very high dosage of Atomoxetine - 40 mg TIA + 80 - 100 mg's worth of Atomoxetine (I think I used NSI-189 for a while as well there... but I cut it, because it was TOO sedating in combination with ATX - the combo really messed with my sleep too) - and I didn't actually get Adrenergic Storm from that. I've also used 100 mg Modafinil with 80 mg Atomoxetine (can't recall if I used Tianeptine as well... but I think it's possible) and I didn't get Adrenergic Storm back then either.

 

I did get Adrenergic Storm, of a milder variety, when I stopped Guanfacine almost cold turkey though - went from 3 mg per day to 0 mg in a total of 3 days - the results were about what one would expect... I was foolish there - since so many can stop Guanfacine without problem, and I had stopped 1 mg and 2 mg trials of the drug previously, I thought I could lessen the dosage the same with this higher dosage - not so.

 

My trial of Reboxetine was only about... 2 weeks after the successful taper of Guanfacine, so, most likely, direct agonism of my Alpha-2-receptors had caused significant down-regulation, and since they're auto-receptors... I felt the effects quite a bit.

 

 

Now, it's true though, that RBX and ATX can't be compared 1:1 - RBX is after all, many times stronger an NRI than ATX  - and their attachment-profiles may not be the same, perhaps they don't cause reuptake inhibition at exactly the same sites - after all, fatigue, sleepiness, dizzyness is much more commonly reported with ATX, implying affinity for alpha-2-receptor areas, while I do believe RBX has much more commonly reported high blood pressure as a side-effect.

 

 

But still... 40 mg Tianeptine + 80 mg Atomoxetine... for at least a week... (I started using tianepine because the ATX was making me depressed - Tianeptine did indeed abolish such feelings) and still no Adrenergic Storm? In comparison - I got adrenergic storm from only 3 mg's worth of Reboxetine, combined with the previously mentioned substances.

 

 

Still, I'll be taking it into account next time I trial it - and I did stop all substances when I got Adrenergic Storm, before retrialling RBX (admittedly only a few days apart), but no dice... still got Adrenergic Storm from the RBX.

 

 

I'm back on Guanfacine now though, and I'll be using it, and it alone, in combo with RBX when all adrenergic symptoms have decreased - still feeling a sort of pressure in my head, even after getting back on Guanfacine - that's not unusual for getting on Guanfacine though, so I'll give it a few days.

[RedStaR]

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.

Well, damn! : O Had no clue about that... rather unexpected, I must say! However, I am somewhat skeptical... mainly because I've actually used a HIGHER dosage of Tianeptine with a very high dosage of Atomoxetine - 40 mg TIA + 80 - 100 mg's worth of Atomoxetine (I think I used NSI-189 for a while as well there... but I cut it, because it was TOO sedating in combination with ATX - the combo really messed with my sleep too) - and I didn't actually get Adrenergic Storm from that. I've also used 100 mg Modafinil with 80 mg Atomoxetine (can't recall if I used Tianeptine as well... but I think it's possible) and I didn't get Adrenergic Storm back then either.

I did get Adrenergic Storm, of a milder variety, when I stopped Guanfacine almost cold turkey though - went from 3 mg per day to 0 mg in a total of 3 days - the results were about what one would expect... I was foolish there - since so many can stop Guanfacine without problem, and I had stopped 1 mg and 2 mg trials of the drug previously, I thought I could lessen the dosage the same with this higher dosage - not so.

My trial of Reboxetine was only about... 2 weeks after the successful taper of Guanfacine, so, most likely, direct agonism of my Alpha-2-receptors had caused significant down-regulation, and since they're auto-receptors... I felt the effects quite a bit.


Now, it's true though, that RBX and ATX can't be compared 1:1 - RBX is after all, many times stronger an NRI than ATX - and their attachment-profiles may not be the same, perhaps they don't cause reuptake inhibition at exactly the same sites - after all, fatigue, sleepiness, dizzyness is much more commonly reported with ATX, implying affinity for alpha-2-receptor areas, while I do believe RBX has much more commonly reported high blood pressure as a side-effect.


But still... 40 mg Tianeptine + 80 mg Atomoxetine... for at least a week... (I started using tianepine because the ATX was making me depressed - Tianeptine did indeed abolish such feelings) and still no Adrenergic Storm? In comparison - I got adrenergic storm from only 3 mg's worth of Reboxetine, combined with the previously mentioned substances.


Still, I'll be taking it into account next time I trial it - and I did stop all substances when I got Adrenergic Storm, before retrialling RBX (admittedly only a few days apart), but no dice... still got Adrenergic Storm from the RBX.


I'm back on Guanfacine now though, and I'll be using it, and it alone, in combo with RBX when all adrenergic symptoms have decreased - still feeling a sort of pressure in my head, even after getting back on Guanfacine - that's not unusual for getting on Guanfacine though, so I'll give it a few days.

ATX is a farily strong NRI, the sleepiness/drowsiness most likely come from the 5-HT/NMDA effects.

Edited by RedStaR, 22 October 2017 - 09:13 PM.

[CWF1986]

Can you send me some links to anything about 'adrenergic storm'?  

 

I take both adderall and nortriptyline and haven't experienced any of the symptoms you mentioned, but I do have a resting pulse of ~100bpm.  Blood pressure and EKG are fine.  

 

Funny you mention clonidine and guanfacine.  They both worked great for sleep and the restlessness aspect of adhd, but I actually like the restlessness and I gained weight on both so I quit them. 

[Mind_Paralysis]

 

 

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.

Well, damn! : O Had no clue about that... rather unexpected, I must say! However, I am somewhat skeptical... mainly because I've actually used a HIGHER dosage of Tianeptine with a very high dosage of Atomoxetine - 40 mg TIA + 80 - 100 mg's worth of Atomoxetine (I think I used NSI-189 for a while as well there... but I cut it, because it was TOO sedating in combination with ATX - the combo really messed with my sleep too) - and I didn't actually get Adrenergic Storm from that. I've also used 100 mg Modafinil with 80 mg Atomoxetine (can't recall if I used Tianeptine as well... but I think it's possible) and I didn't get Adrenergic Storm back then either.

I did get Adrenergic Storm, of a milder variety, when I stopped Guanfacine almost cold turkey though - went from 3 mg per day to 0 mg in a total of 3 days - the results were about what one would expect... I was foolish there - since so many can stop Guanfacine without problem, and I had stopped 1 mg and 2 mg trials of the drug previously, I thought I could lessen the dosage the same with this higher dosage - not so.

My trial of Reboxetine was only about... 2 weeks after the successful taper of Guanfacine, so, most likely, direct agonism of my Alpha-2-receptors had caused significant down-regulation, and since they're auto-receptors... I felt the effects quite a bit.


Now, it's true though, that RBX and ATX can't be compared 1:1 - RBX is after all, many times stronger an NRI than ATX - and their attachment-profiles may not be the same, perhaps they don't cause reuptake inhibition at exactly the same sites - after all, fatigue, sleepiness, dizzyness is much more commonly reported with ATX, implying affinity for alpha-2-receptor areas, while I do believe RBX has much more commonly reported high blood pressure as a side-effect.


But still... 40 mg Tianeptine + 80 mg Atomoxetine... for at least a week... (I started using tianepine because the ATX was making me depressed - Tianeptine did indeed abolish such feelings) and still no Adrenergic Storm? In comparison - I got adrenergic storm from only 3 mg's worth of Reboxetine, combined with the previously mentioned substances.


Still, I'll be taking it into account next time I trial it - and I did stop all substances when I got Adrenergic Storm, before retrialling RBX (admittedly only a few days apart), but no dice... still got Adrenergic Storm from the RBX.


I'm back on Guanfacine now though, and I'll be using it, and it alone, in combo with RBX when all adrenergic symptoms have decreased - still feeling a sort of pressure in my head, even after getting back on Guanfacine - that's not unusual for getting on Guanfacine though, so I'll give it a few days.

ATX is a farily strong NRI, the sleepiness/drowsiness most likely come from the 5-HT/NMDA effects.

 

 

Well, the NMDA-effects are possible, I suppose, Steven Stahl does list NMDA-antagonism as a possible mechanism of sleep-induction, but the 5ht-effects are not plausible, at least in my case - I've been on both Sertraline and Duloxetine, and I did not find them sedating at all. Sertraline in particular I've used up to 200 mg's, and it was never sedating.

 

 

In theory, ATX should be far more activating, which it sometimes was, but often it was just sedating. (it would be activating for one or two days, with every dose-increase, and then it would become immensely sedating all of a sudden - oddly enough, lowering dosage would also make it activating again, for about one day or so)
 

That suggests another mechanism behind it - affinity for the Alpha-2-receptors, is plausible here - for instance, the same phenomenon can be seen with some antipsychotics at some dosages - because of affinity for the auto-receptors, they actually become the OPPOSITE - they become activating, like stimulants, instead.

[RedStaR]

Well, the NMDA-effects are possible, I suppose, Steven Stahl does list NMDA-antagonism as a possible mechanism of sleep-induction, but the 5ht-effects are not plausible, at least in my case - I've been on both Sertraline and Duloxetine, and I did not find them sedating at all. Sertraline in particular I've used up to 200 mg's, and it was never sedating.
 
 
In theory, ATX should be far more activating, which it sometimes was, but often it was just sedating. (it would be activating for one or two days, with every dose-increase, and then it would become immensely sedating all of a sudden - oddly enough, lowering dosage would also make it activating again, for about one day or so)
 
That suggests another mechanism behind it - affinity for the Alpha-2-receptors, is plausible here - for instance, the same phenomenon can be seen with some antipsychotics at some dosages - because of affinity for the auto-receptors, they actually become the OPPOSITE - they become activating, like stimulants, instead.

I generally agree with this, but taking BUP with ATX negates its sedating effects to a large degree. Because of what I assume to be, no SERT inhibition

[Mind_Paralysis]

Can you send me some links to anything about 'adrenergic storm'?  

 

I take both adderall and nortriptyline and haven't experienced any of the symptoms you mentioned, but I do have a resting pulse of ~100bpm.  Blood pressure and EKG are fine.  

 

Funny you mention clonidine and guanfacine.  They both worked great for sleep and the restlessness aspect of adhd, but I actually like the restlessness and I gained weight on both so I quit them. 

 

Sure, check these links out:
 

https://en.wikipedia...drenergic_storm

 

http://www.sciencedi...drenergic-storm

(the info in the above link is rather scattered though, even if it describes some instances where it can occur)

 

People with dysautonomia, such as from diseases in the immune system, can also rarely get this - tumours and adrenergic insufficiency treatment... even hyperthyroidism can cause it. Basically, anything that impairs control of Adrenaline and norepinephrine, or which dramatically increases their production, can cause it.

 

 

Sometimes the terms "drug-induced hypertensive crisis", "hyperadrenergic state", "sympathetic storm" and "norepinephrine syndrome" is used, sometimes, interchangeably, so the literature is a little bit split between these definitions.

Most of the data is regarding overdose of Cocaine or Methamphetamine  - some subjects are actually resistant to the psychosis which these agents usually induce, since they are more selective for dopamine, long before you get adrenergic storm, hence, they can instead KEEP GOING with the dosing, and the NE-effects will be more prominent - hence Adrenergic storm.

 

 

 

Here is some more specific info regarding the mechanisms of my OWN issues:

----

Clinical experience with guanfacine in long-term treatment of hypertension

https://www.ncbi.nlm...les/PMC1430125/

 

A withdrawal syndrome occurred in about 3% of patients after discontinuation of prolonged treatment with Guanfacine.

 

 

(lucky me...)

 

Selective Impairment in Sympathetic Vasomotor Control With Norepinephrine Transporter Inhibition

http://circ.ahajourn...7/23/2949.short

 

 

The Pharmacology and toxicology of Reboxetine

http://www.acmt.net/...3_4/3_4_26.html

 

Although speculative, the potential for a serious adverse pharmacodynamic interaction is a concern when reboxetine is combined with other drugs. In particular, when reboxetine is combined with other agents that increase synaptic NE concentrations (e.g., TCAs, SNRIs, cocaine, amphetamines, phenylpropanolamine, pseudoephedrine), a life-threatening hyperadrenergic state could result. For instance, an adverse drug interaction cannot be excluded as the cause of the reported postmarketing fatality of a patient who ingested reboxetine in combination with amitriptyline. (31)

 

 

 

Norepinephrine Transporter Blockade With Atomoxetine Induces Hypertension in Patients With Impaired Autonomic Function

http://hyper.ahajour...t/50/1/47.short

 

In conclusion, atomoxetine induces a dramatic increase in blood pressure in patients with central autonomic failure even at very low doses.

 

 

The above actually sounds very similar to what happened when I took Reboxetine following Guanfacine discontinuation syndrome... the DS would induce the kind of central autonomic failure descriped above - through down-regulation of Alpha-2 auto-receptors. (direct agonism often causes down-regulation of neuro-transmitter receptors, although not universally)

----------

 

 

Interesting note here btw, how in some subjects, another NRI, Sibutramine, can actually LOWER blood-pressure in some ways, and increase it in others.

Paradoxical Effect of Sibutramine on Autonomic Cardiovascular Regulation

http://circ.ahajourn...6/19/2459.short

[Kinesis]

 

 

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.

 

 

Those references beat no references.  I got dry mouth from bupropion too, but that's not a sufficient effect to declare something anticholinergic.  Stimulants can do the same thing quite independently of anticholinergic activity.

 

[Kinesis]

Hmm ...

 

 

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...)

 

Yes, not a good combination ... generally I'd be leery of using substantial doses of any MAOI with any other monoamine enhancer outside of a doctor's explicit guidance.  Even clonidine shouldn't be taken as a free pass to do that ... although I share your affection for clonidine ... ;-)