Can Snri's Cause High Serum Norepinephrine Levels?

[Kris4444]

I take pristiq for of all things my non-functioning colon. It has helped when nothing else has.

When I was at Mayo they had me discontinue pristiq for a few days so that they could do the supine/upright blood test. My NE levels were 656 supine and 1199 upright (sitting not standing).

They wanted to check my catecholomines because of the high reading and said that if that one was high as well that they would probably do an MIBG scan to look for a pheo or other endocrine type tumors. My normetenphrine levels were abnormally elevated but they decided that the scan was not necessary for some reason.

I am seeing my endo on Monday. He will be seeing the Mayo results and discussing them with me. Part of me really wants to demand an MIBG scan but the other part of me wonders how much of my symptoms may be caused by the pristiq. What if I wean off of it and repeat the NE test?

What else should I talk to the endo about? Would he be the one to ask about MCAS?

[ramakentesh]

SNRIs could definately increase NE levels, but most would say that they would reduce sympathetic outflow by stimulating alpha 2 adrenoceptors in the brain.

[Kris4444]

Could you explain that please?

[Chaos]

An allergist would be the best place to start with for MCAS probably. I'll PM you a link you can take with you that might be helpful if you can find one willing to work with you.

Since there are so many neurotransmitter receptors in your gut, it's not surprising that SSRIs or SNRIs might have a beneficial effect there.

[Kris4444]

I'm wondering though if my levels and symptoms could be caused by the meds and how long does it take for the meds to not show up in blood work.

[ramakentesh]

SNRIs theoretically increase NE levels because they block its reuptake back up into the transporter.

[Altruism]

Rama, does this mean SNRIs are bad for HyperPOTS with high NE? I mean.. we have enough high NE and if we block the reuptake, then we end up having even more?

[POTLUCK]

Not to confuse things more but....

In addition to, and seperate from what Rama is stating, there is the question could the SNRI cause an artifactual increase in your measured Norepinephrine, that is not real? I believe that would depend on the type of lab test used to look for NE. I had to look into this in great detail with my labs and had to have my doctor phone the lab etc. when my NE came out over 8000 at Quest.

[ramakentesh]

its weird - some studies suggest that SNRIs - which act mainly in the brain - actually reduce sympathetic outflow and calm down the sympathetic system, whereas other studies using medications that completely abolish NE reuptake create a phenotype almost identical to POTS - tachycardia, impaired baroreflex sensitivity and blunted vasoconstrictive responses to stimuli:

http://www.ncbi.nlm.nih.gov/pubmed/18187607

Norepinephrine transporter inhibition alters the hemodynamic response to hypergravitation.

Strempel S, Schroeder C, Hemmersbach R, Boese A, Tank J, Diedrich A, Heer M, Luft FC, Jordan J.

Source

Franz-Volhard Clinical Research Center, Medical University Charité, Campus Buch, Wiltbergstrasse 50, Haus 129, Berlin, Germany.

Abstract

Sympathetically mediated tachycardia and vasoconstriction maintain blood pressure during hypergravitational stress, thereby preventing gravitation-induced loss of consciousness. Norepinephrine transporter (NET) inhibition prevents neurally mediated (pre)syncope during gravitational stress imposed by head-up tilt testing. Thus it seems reasonable that NET inhibition could increase tolerance to hypergravitational stress. We performed a double-blind, randomized, placebo-controlled crossover study in 11 healthy men (26 +/- 1 yr, body mass index 24 +/- 1 kg/m2), who ingested the selective NET inhibitor reboxetine (4 mg) or matching placebo 25, 13, and 1 h before testing on separate days. We monitored heart rate, blood pressure, and thoracic impedance in three different body positions (supine, seated, standing) and during a graded centrifuge run (incremental steps of 0.5 g for 3 min each, up to a maximal vertical acceleration load of 3 g). NET inhibition increased supine blood pressure and heart rate. With placebo, blood pressure increased in the seated position and was well maintained during standing. However, with NET inhibition, blood pressure decreased in the seated and standing position. During hypergravitation, blood pressure increased in a graded fashion with placebo. With NET inhibition, the increase in blood pressure during hypergravitation was profoundly diminished. Conversely, the tachycardic responses to sitting, standing, and hypergravitation all were greatly increased with NET inhibition. In contrast to our expectation, short-term NET inhibition did not improve tolerance to hypergravitation. Redistribution of sympathetic activity to the heart or changes in baroreflex responses could explain the excessive tachycardia that we observed.

[ramakentesh]

Further, Ernie who has some of the highest NE levels ever measured I believe felt dramatic improvement from an SNRI medication. So who knows.

My doctor told me not to take an SNRI as the issue of whether they would worsen POTS if NET deficiency is present has not been resolved. But Blair Grubb now believes that combined SSRI/SNRI are the best medications for POTS (both neuropathic/autoimmune and 'select' hyper patients)

[Altruism]

Yeah, my doctor knew about the whole SNRI paradoxal effect on different patients which made me confident enough to trust her judgment. She suggested we stay on the safe side and try an SSRI first and I agreed.

[ramakentesh]

excellent sounds like your getting some good care there.

[Kris4444]

I am totally confused. I am on an SNRI for slow motility colon issues. I had the flushing symptoms before starting it but the sweating and vertigo came in after I believe. I have high NE 656/1199 but none of the doctors can tell me if it's from the SNRI or not. I had a waste of time appointment today at my endo. I honestly don't know what to think or do at this point.

[peregrine]

Weird... for me, an SNRI (Cymbalta) was what triggered the "spaciness" that then four months later developed into POTS. In my case, going back on the Cymbalta did worsen the lightheadedness, spaciness, and tachycardia somewhat even with beginning a beta blocker. What helps me the most right now is clonidine - a centrally-acting sympathiolytic that inhibits norepinephrine release - but it's hard to say if the SNRI worsened things because of the increased norepinephrine levels due to NE not being cleared in the synapse. Strangely, although I'd thought that Cymbalta was effective for chronic pain due to the NE effects, a 2010 paper says it's more likely the sodium channel effects, which is unexpected. So... in my case:

Imipramine (tricyclic antidepressant): central NE reuptake inhibition (more NE in the brain) -> no POTS symptoms but severe speech issues

Wellbutrin (dopamine/norepinephrine): central NE reuptake inhibition (more NE in the brain) -> no POTS symptoms

Cymbalta (serotonin/norepinephrine): central NE reuptake inhibition (more NE in the brain) -> spaciness and later POTS (causal role not entirely clear for POTS itself)

Clonidine: central NE release inhibition (less NE in the brainstem) -> less brain fog, perhaps less spaciness, general improvement

... I don't know what to make of the whole mess, but for me I just try to avoid things that increase norepinephrine. I unfortunately don't have serum NE levels to share!

[Kris4444]

I am taking clonidine too. Tonight I started my second dose of .1. They eventually want me on .2 3x's a day. I'm on a 30 day medical leave so I figure i will try it but I know it makes me tired so it will be interesting.

[peregrine]

Kris - I've been on 0.1mg twice daily for about four months now, and just started 0.15mg twice daily yesterday night. The postural hypotension (from standing up too fast) and sleepiness are stronger than earlier, but the postural hypotension had mostly gone away after a month, so I'm not surprised, and it's far less severe than the last time I changed the dose (when I started I would go from 110/70 sitting to 85/45 standing and nearly passed out very quickly several times, so watch out for that - just stand up slowly). I get some side effects from it - more clumsy in general, tremor, mild postural hypotension, and sleep attacks, but for me it's definitely worth it.

They want you on 0.2mg three times a day? That's the upper end of the dosing (max of 0.6mg a day) - it seems kind of strange to want you on a certain dose before figuring out if you respond to a lower dose, but who knows :^) If you end up staying on it, you might see if they would be willing to try the patch, which would keep you from having to take your pills three times a day. For me twice a day is fine (since I already take meds morning and night), but I keep wondering about the patch, since I know some folks really like it.

[Kris4444]

I don't know what I'm doing. All of this was decided at Mayo and then I was thrown back home and none of my docs at home even know about this stuff...do you think it's too soon to up my dosage? I've been on it almost a month now, just in the morning.

I have high blood pressure to begin with. Today after cooling down from a walk I took my pressure and it was 138/102 hr of 128. This was after taking my morning dose of clonidine and a losartan.

My rheumatologist is looking into things and I've made an appointment with my GP. I'm hoping someone will tell me what to do. I don't even have a true diagnosis at this point. Just "hyperadrenergic state". Whatever.

[peregrine]

Just 0.1mg a day in the morning? Hunh. A month is definitely a fine interval between dose adjustments, but - especially since you are taking something else that affects blood pressure - you really should check with a doctor or a pharmacist; my pharmacists always look freaked out when they refill either my atenolol (beta blocker) or clonidine (alpha agonist) since stopping the clonidine suddenly while taking the beta blocker can, in rare cases, cause pathologically high blood pressure that can kill you (rebound hypertension). I don't know how losartan interacts with that, but I would probably be careful with things. Did they give you tapering instructions (e.g. "after 1 week, increase by half a pill daily/switch to twice daily dosing/etc")? The single dosing per day seems odd to me, since it usually lasts about 12 hours and standard dosing is 2-3x/day, but since I'm not a doctor I would definitely consult someone who is about changing the dose unless they already gave you instructions.

My neurologist actually isn't really familiar with clonidine (he spent 10 minutes during yesterday's appointment trying to figure out the maximum dosage, which I could have told him in 2 seconds!). Amusingly, my psychiatrist says she is willing to manage it if he won't, since it's used for ADHD and thus she is more familiar with it.

[Kris4444]

Honestly my head is spinning. All of this is so new to me. I don't know. Maybe I should wait until I see my GP before I up the dose. Too late for tonight since I already took it. I have an appointment with my GP on Friday.

[~elizabeth~]

I'm confused about this stuff as well, I just seem to keep getting paradoxical results from whatever drug I try. My problems started off 2 year ago with what now seem like classic hyperadrenergic symptoms - sweating, severe flushing, prolongued diarrhoea episode, tachycardia, agitation. Clonidine did help with most of these symptoms, but not the painful flushing which has got worse. Last year my GP suggested trying nortripytline. This made my BP rise hugely, and made the postural aspect of my flushing much worse, I was unable to sit down for hours after taking otherwise I'd flush painfully within seconds (it also started up in new areas, including the insides of my mouth and nose). I also tried duloxetine, which was an immediate disaster, flushing much worse and onset of severe Raynaud's symptoms/pain in feet. Same thing with Citalopram, worsening of flushing even in tiny doses.

My first thought was I was experiencing problems with clonidine interacting oddly with other drugs. Then I wondered if Clonidine just not a strong enough drug to completely suppress hyperadrenergic symptoms completely, or whether the central effects were wearing off too soon for me (relief from flushing seems to only last about 4 hours, major pain in middle of night). Another possibility is that some of the facial flushing is actually the hyperemic phase of a Raynaud's reaction. Clonidine can apparently increase supersensitivity to catecholemines by increasing the number of alpha 2 receptors in peripheries (not sure if it's on just on platelets or blood vessels as well), and also increase their reactivity to cold. I guess this might explain why I have high BP despite blood pooling/peripheral denervation?

I've now come off clonidine to see what happens, as I think it was somehow causing confusion. I'm still in the withdrawal phase, which as been terrible. Not sure when it will be clear what is withdrawal and what is underlying hyperadrenergic state. Although I've had autonomic testing, and had POTS confirmed (secondary to denervation/EDS) no one has measured my norepinephrine, so it's still only speculation that the worst of my symptoms are due to hyperadrenergic state.

[Kris4444]

I am going to see an immunologist next week, I'm hoping this might answer some questions.

There is a big part of me that wants to get off of just about everything including the SNRI which makes my colon work better. I just want to see if any of the symptoms go away when off the meds. At this point I can't even keep track of when symptoms started because I have been on so many medications over the past few years.