Ssri/snri?

[HopefulLady]

I am just wondering does anyone know how SSRI'S or SNRI'S help with dysautonomia? What exactly are they supposed to do to treat it? I take Effexor XR mostly because I couldn't tolerate the other one's I tried. And it just so happened to control those terrible dizzy spells/pre-syncope that I was dealing with as well as some other symptoms. I am just curious as to what these drugs do in the brain to control the dizziness and why they can be so effective for some of us? I have always wondered this and can't really find too much information about it online.

Also I don't tolerate beta blockers too well ... Plus I have exercised induced asthma so I can't take them. My regular Doctor was going to try Clonidine?

Does Clonidine mix well with Snri's? Does anyone currently take both and find them to be a good combo?

Thank You

[ramakentesh]

SNRIs will decrease sympathetic outflow and so will clonidine so together it might tip you into hypotension.

[erik]

Tough question! I'm tempted to say "nobody knows", and certainly I don't. If you can tolerate "rambling" here is a partial response (otherwise just ignore :

There are the initial known effects of these drugs (synaptic reuptake inhibition in select locations)... and then there are the counter and cascading effects. Although they initially increase the duration of presence post-firing ("umph" is my word for it) of the neurotransmitter in the synapse (the primary "active region"... but not the only active region), the body can tend to respond with a down-regulation to things like this... so longer term result can be opposite/mixed. Also, folks are finding that not only are nerves populated with receptors for these and other messengers right at the synapse, but also in other adjacent places and even on adjacent "support" cells.

Needless to say, there are many factors involved beyond synaptic umph. For example, the little pods of neurotransmitter are made more or less potent or populated by some stuff going on inside the nerve cell (and mitochondria)... and even the rate of migration of these little protected pods toward the synaptic surface where they get released is said to affects things. If less is "reuptaken" then there could be more "washout" or loss... and a tendency to depletion, but maybe not if the reuptake is simply delayed/slowed. Also, on the "receiving" side of the synapse (either the next nerve in the chain or the slower responding receptor that might be triggering production of some substance, like a hormone perhaps) can decide to make itself less or more populated with receptors! So even with more neurotransmitter umph... a down-regulation can push opposite. Whatever signals this down-regulation may or may not be localized... so it might be just that specific spot that gets down-regulated or perhaps whatever signals that is more global.

Then there is the obvious! If the nerve doesn't reach threshold and fire, the neurotransmitter doesn't get spit out into synapse in the first place... so regulating the nerve threshold is hard to ignore. That is an "upstream" decision, most directly influenced by ion flows... a.k.a. key electrolytes, but indirectly by neuroregulators. Those regulators tend to be things binding to little channels through which specific ions flow... and acting as "valves" for this flow. Also, I suppose overall concentrations come in to play but maybe not often (just depletion or overt electrolyte imbalance???).

One other (semi-new) curveball is that the gaseous neurotransmitters (nitric oxide & carbon monoxide) are now though to even travel backward UP the nerve in some cases (presumably a form of rapid feedback loop) in addition to their other localized signaling roles. Also, there are other localized messengers not constricted to nerves but "floating" or even "migrating" in bodily areas... such as kinins and friends.

Long story short... for a "clinician" the only thing that matters is the end result in the patient. For a researcher, it almost seems too complicated to know "big picture" stuff... they just pin down specific pathologies mostly... then spin endless theories which may or may not be true (it almost doesn't matter, as in philosophy).

[flop]

I haven't done any research into this myself and always went with the "we don't know why SSRIs help but they do" line. In the DINET documentary one of the doctors talks about SSRIs and he mentions that serotonin spikes cause autonomic symptoms, he says that by using SSRIs to elevate but level-out serotonin levels, apparently this gets rid of the symptoms associated with serotonin spikes.

Flop

[ramakentesh]

Exactly - they dont really know how they help in depression and panic disorder, let alone in POTS. Ive heard that they level out fluctuations in brain chem, that they increase blood pressure and that they decrease sympathetic outflow from the brain.

[summer]

Why have some of us reacted very badly to SNRIs?

[pat57]

can someone expailn sympathetic outflow to me?

I did wiki it and still don't get it. I have a mental block on sympathetic and parasympathetic.

I can never retain which is which on that either.

I have OH and NCS - snris are a godsend for me. I can stand still without symptons, thanks to

SNRIs

thanks,

pat

[wareagle]

Hi Pat-

Ram or Erik will have a better answer for you but here's the difference b/w sympathetic and parasympathetic in a nutshell.

Sympathetic NS prepares the body for Fight or flight. It's primary primative function is to help us survive life / death situations by getting us ready to fight or run away. So it increases heartrate ect.

Parasympathetic does the opposite of the Sympathetic. It returns your body to it's "normal" state once the threat is gone. So it's responsible for getting your heartrate back down and relaxing you other functions after a fight or flight situation.

For us out Sympathetic nervous systems are often overstimulated all of the time leading to tachycardia ect....and b/c of this our parasympathetic NS can respond inappropriately to try and bring balance back and can lead to episodes of bradycardia.

Of course with POTS the tachycardia isn't just a result of the sympathetic over stimulation it's often a compensatory response the the decreased blood flow to the brain. I just use it here as an example of the syptoms caused by over stimulated sympathetic response.

[erik]

I think wareagle nailed it. I'd just add an example: when I stand up and still for too long I will start to sweat, shake, feel anxious (or just plain horrible), yawn, need to pee suddenly, get tingly & numb in spots, and a few other things I'm forgetting. Several of those are related to sympathetic stimulation being "ramped up" either erroneously (as in "too sensitive" or "amplified") or perhaps "appropriately" as a crude attempt to keep me conscious & functional. Subtler things should have happened to keep the blood flow stable and systems operating, but they probably fail for me in my style of POTS. Therefore, the body resorts to the big "sledghammer" to fix the problem and starts a cascade of signals... sympathetic stimulation and parasympathetic withdrawal.

As others have made clear. The quick answer is... nobody knows. Remember, nobody even knows (with certainty) what each cause of POTS is!!! So no way to know what is being fixed if don't know specifically what is broken. Some things are known, others are just well informed theories (which fail often enough in science .

I also like the "catch-all"... that since "anything goes" with dysautonomia it follows that "anything goes" with treatment. The other thing that I keep in mind is that researchers do not even know what causes high-blood pressure ("essential hypertension") yet. That condition affects millions and costs lives. I expect it gets some priority in terms of pinning down exact cause... to keep the "little guys" like dysautonomias from getting neglected there are rare disease organizations, which helps. But my personal hope is that things like POTS might actually cross over enough with "simple stuff" like hypertension that things get solved together.

Clinically, In the case of things more like NMH rather than POTS... there seem to be cases where even NRI's (like Strattera) can reduce fainting. For some other folks, Strattera will actually induce POTS-like symptoms, since it ramps up norepinephrine activity (perhaps mimicking NET deficiency, one of the potential subtypes of POTS). Yet, SSNRI given to a subset of POTS folks can ironically also help with POTS. Also, many folks with POTS take stimulants, which enhance norepinephrine & dopamine activity and even have reuptake effect on these just like NRI or SSNRI.

It seems that almost all the meds that POTS folks take are either known for creating the very symptoms they are treating or are seeking a delicate balance between pro & con effects. There are also known cases where a drug will respond very very differently in the context of known nervous system damage (as in MSA, parkinsons, or other known denervations). This means that although a drug might tend to boost something in the general public, and be though to create a problem symptom in general public, in a patient that lacks those nerves it will not have same overall effect!

[mvdula]

Hi Erik,

Some of those symptoms you describe, I have felt...like the shakiness, weakness, need to pee, hot, etc. BUT I do not get them from standing....and sitting or lying down does not solve them. I get those from too much aerobic activity (threshold changes, but is generally pretty low) usually. My episodes cannot be resolved by anything I do - tho I think Klonopin helps and walking around. So, I feel a little different from most POTS patients since lying down does not resolve my issues...in fact, lying down is usually less tolerable, since I can feel the racing/pounding hr more and I feel the need to move around despite the weakness....any thoughts?

[pat57]

thanks for the replies.

does this sound reasonable then, based on my DX of orthostatic hypotension and neurocardiogenic syncope.

Standing still causes hypotension and activates the sympathic NS. Before the NRI I would then stagger, lay down or go jogging. Assumeing the stagger and need to lay down is from the NCS reflex inducing bradycardia. The jog ,when I can ,increases either the BP or HR and I recover. I normally do either A Laydown or B jog. The stagger is the onset. A or B allow recovery.

ok so.............. the NRI perhaps governs the sympathic NS so that it is buffered and the para sympathic does not "freak out" and drop my bp like a rock. Or to say it another way, the BP increase is not so much that it trips -on- the parasympathic response.

I did not know, by the way, that I am on an NRI right now. I never heard of them before. I was put on Pristiq (an SNRI) for depression when I discovered that it enabled me to stand still without symptoms.

It caused tachycardia, tho and I was switched to wellbutrin.

thanks again

[Guest tearose]

I was told NOT to take ssri or snri.

I suppose we all need to discuss the pros and cons with our doctor.

[HopefulLady]

WOW !! These are some great responses! Thank You very much. I had read too that doctors are not sure exactly how they help or how they effect our bodies over long term use. I just know if it wasn't for this effexor xr I would be a dizzy dame all day long not being able to stand and do normal things comfortably without my heart racing out of my chest. It also seems to help with the GI symptoms I was having too. I just wanted to know how this stuff works in the brain. And doctors don't seem to be able to give you a really good explanation. LOL perhaps it's because they don't really know.

[HopefulLady]

I wanted to add that when I am not on my SNRI I feel those adrenaline surges all the time. They are the most dreadful feeling and I noticed I would get them when I stood up or if I was lifting my hands over my head like to hang curtains. My pupils would get really big I felt really hot in my face and I could feel my heart race a million miles an hour. My vision would dim and I would get really dizzy to the point I felt like I would faint. The only thing that seemed to help without medication was cool water on my face a fan and a bed. But I always felt like my body was producing mass amounts of adrenaline. Somehow the Effexor seemed to level these things out. I can stand now and I don't feel my heart racing a million miles an hour. And I only get dizzy every once in awhile. I would also shake too!!! Benzodiazapines do nothing for me other than make me sleep. They never took the edge off. And Ativan would drop my blood pressure way too low and it gave me hives.

But then what really puzzles me is I can only take the effexor .. When they put me on lexapro I broke out in full hives that lasted for 2 months!!! When they gave me paxil it caused some really unsettling symptoms. And prestiq! That crap sent me to the ER with tachycardia and HBP ... I don't understand why I can take the effexor xr but not the others.

My doc and I were talking about it and we came up with the fact the extended release may be better for people who have really sensitive nervous systems because it only releases a bit of the drug at a time instead of the non time released meds. So because I know how overly sensitive I am to drugs I always ask for the extended release if available. I know they have serums too for the ssri's/snri's. I guess it just depends sometimes you have to try a few before you can find one that your body will tolerate. And some people just can't tolerate them at all.

[HopefulLady]

can someone expailn sympathetic outflow to me?

I did wiki it and still don't get it. I have a mental block on sympathetic and parasympathetic.

I can never retain which is which on that either.

I have OH and NCS - snris are a godsend for me. I can stand still without symptons, thanks to

SNRIs

thanks,

pat

Pat that's awsome!! I find they work for me too I can now stand and do normal things without feeling like I am going to pass out. The pre-syncope scared the living daylights out of me because it was happening several times a week. I just felt useless. Like I couldn't do anything to control the symptoms they were controlling me. And then add ER docs and other Docs on top of it telling you that your causing these symptoms and you just feel hopeless. I am so grateful that the SNRI helps give me a better quality of life back. It's good to see it's helping other's too.

[ramakentesh]

POTS is confusing - in some the tachycardia is an appropriate response to decreased thoratic (chest) blood perfusion. In others its caused either by sympathetic excess (body overreacting to normal levels of norepinephrine or too much norepinephrine) or from parasympathetic withdrawal.

Sympathetic outflow is the amount of sympathetic activity being driven or stimulated by the brain. High norepinephrine levels in the body, in the sympathetic nervous system and in the blood stimulate activcity of the sympathetic system.

high norepinephrine in the brain stem does the opposite - it reduces overall sympathetic activity as does high serotonin in the brain.

When you take an SNRI the high norepinephrine levels are everywhere, but the brain stem usually dominates so it reduces sympathetic activiuty and reduces the jittery, speedy, fast heart rate side of POTS. But if the body norepinephrine predominates then it will further increased sympathetic activity and make you worse.

In most cases I think it would be helpful. In nearly all cases probably.

But POTS is caused by different mechanisms - some patietns just have faulty cerebral vascular autoregulation ( the system that keeps blood pressure steady in spite of heart rate and BP fluctuations), others have more complicated abnormalities.

[HopefulLady]

POTS is confusing - in some the tachycardia is an appropriate response to decreased thoratic (chest) blood perfusion. In others its caused either by sympathetic excess (body overreacting to normal levels of norepinephrine or too much norepinephrine) or from parasympathetic withdrawal.

Sympathetic outflow is the amount of sympathetic activity being driven or stimulated by the brain. High norepinephrine levels in the body, in the sympathetic nervous system and in the blood stimulate activcity of the sympathetic system.

high norepinephrine in the brain stem does the opposite - it reduces overall sympathetic activity as does high serotonin in the brain.

When you take an SNRI the high norepinephrine levels are everywhere, but the brain stem usually dominates so it reduces sympathetic activiuty and reduces the jittery, speedy, fast heart rate side of POTS. But if the body norepinephrine predominates then it will further increased sympathetic activity and make you worse.

In most cases I think it would be helpful. In nearly all cases probably.

But POTS is caused by different mechanisms - some patietns just have faulty cerebral vascular autoregulation ( the system that keeps blood pressure steady in spite of heart rate and BP fluctuations), others have more complicated abnormalities.

Question for you .. Before I got to a doctor who actually thought what I had was an autonomic issue. I remember being in the ER and the doctor discharged me saying that he thought I was sensitive to my bodies own adrenaline which is why I was having abnormal HR increases upon movement or standing. He said it's rare but it happens is that another way of saying you have an autonomic problem? Is that something that happens to people with dysautonomia in general? Or is it possible to not have dysautonomia but still be sensitive to your bodies own adrenaline? You would think a normal person's body would not be sensitive to their own chemicals/hormones LOL.

[Chaos]

It also seems to help with the GI symptoms I was having too.

I think I remember reading (or being told by my doctor) that you have more receptors for these neuro-transmitters in your gut than you have even in your brain. I know when I started Wellbutrin it helped some of my GI issues a lot. It was also the only med of this type that I could tolerate. Had terrible side effects from all the others they tried.

[ramakentesh]

Nearly all POTS patients - or most are overreactive to epinephrine/adrenaline and norepinephrine/noradrelanine. So yes definately your doctor is right. This also occurs in inappropriate sinus tachycardia and in the later case its caused by autoantibodies attacking or stimulationg beta 2 or beta 1 receptors.

Blair Grubb has some work coming out that suggests that this occurs in some POTS patients as well.

It could also be that one of the two beta or alpha receptors. alpha 1s constrict, alpha 2s kind of vasodilate or reduce constriction, beta 1s kind of constrict, increase heart rate and other stuff, beta 2s vasodilate the stomach and thorax and stop mast cell degranulation.

If one is faulty then the others will be activeated without the balance of the other, throwing the whole system out of whack. Beta 2 receptor disfunction has been implicated in POTS. Beta 1s constrict the hands and feet, but beta 2 are supposed to vasodilate the stomach. if they dont work the whole body becomes constricted and activated by unapposed beta 1 and alpha 1 vasoconstriction.

[HopefulLady]

Nearly all POTS patients - or most are overreactive to epinephrine/adrenaline and norepinephrine/noradrelanine. So yes definately your doctor is right. This also occurs in inappropriate sinus tachycardia and in the later case its caused by autoantibodies attacking or stimulationg beta 2 or beta 1 receptors.

Blair Grubb has some work coming out that suggests that this occurs in some POTS patients as well.

It could also be that one of the two beta or alpha receptors. alpha 1s constrict, alpha 2s kind of vasodilate or reduce constriction, beta 1s kind of constrict, increase heart rate and other stuff, beta 2s vasodilate the stomach and thorax and stop mast cell degranulation.

If one is faulty then the others will be activeated without the balance of the other, throwing the whole system out of whack. Beta 2 receptor disfunction has been implicated in POTS. Beta 1s constrict the hands and feet, but beta 2 are supposed to vasodilate the stomach. if they dont work the whole body becomes constricted and activated by unapposed beta 1 and alpha 1 vasoconstriction.

WOW ramakentesh I sure wish I had some like you to be at my doctors appointments with me LOL ! You really know your stuff!! About IST ... Usually patients who have this have high resting heart rates over 100? So typically you would not see someone with IST laying down and their heart rates be in the 60's? They tend to run over 100 all the time even at rest? I am printing all this stuff out! I really appreciate all of your knowledge regarding this. I have always had a hard time understanding how this Effexor stuff works in the brain. And when you ask a doctor they can never seem to give you an answer that makes any sense! So thank you for taking the time out to answer my questions!!

[ramakentesh]

Obviously the interaction of those receptors is a bit more complex than what ive described. But I wrote it that way to describe the basics.

In IST the tachycardia occurs at all times - sometimes all day every day, in bed, standing, doesnt matter. It is not postural related.