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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by mtom on January 5, 2019, at 20:40:48
How is that I read Mirtazapine and SNRI's, which increase norepinephrine activity, are helpful in reducing anxiety when NE is a stimulatory neurotransmitter, involved in the fight-flight response, etc? It seems paradoxical....
Posted by rjlockhart37 on January 6, 2019, at 1:46:34
In reply to How can ADs increasing norepinephrine help anxiety, posted by mtom on January 5, 2019, at 20:40:48
yeah i've heard about that, mainly effexor which is a nor-epinephrine uptake, it's stimulating not sure if serotonin is leveled out with it.....cymbalta too, don't have an answer, this is for other posters to awenser and a research project for me
random thing i found out (not relating to anxiety, but .. panax ginseng is a serotonin and norepineprhine reuptake inhibitor, it's ginseng like caffeine and i had no idea it has antidepressant actions in boosting energy
Posted by linkadge on January 6, 2019, at 15:27:05
In reply to How can ADs increasing norepinephrine help anxiety, posted by mtom on January 5, 2019, at 20:40:48
This question is often asked, and I don't think there is single conclusive answer to it. However, having read a bit on this topic here's what I've found...
Most of these medications are primarily antidepressants (and their impact on anxiety was a secondary effect). Improving depression itself, has an ability to reduce anxiety for some people, regardless of the mechanism of the treatment.
The anti-anxiety effect of SNRIs can take some time to develop fully. In the short term, increasing norepinephrine can actually aggravate anxiety, as you mention. The key is the way that the medication (if it works) changes your outlook or behavior so that there is an adaptation to either resolve issues that are causing stress, respond in a more adaptive way, or avoid the stressor altogether.
Not everybody with anxiety responds to S/NRIs for anxiety.
However, consider somebody with a mixed depression / anxiety who gets trapped in a cycle of low self esteem / confidence, low energy, bad choices, avoidance etc. who ends up making their anxiety worse long term because they may let problems pile up, they have difficulty thinking longer term etc. Poor concentration and low energy are typical problems with depressed people, which understandably could lead to worse anxiety. Increasing serotonin and norepinephrine together tends to improve mood and increase energy. If the med works, the improved mood and energy allows the individual to tackle the issues that are causing anxiety and to learn a more adaptive response. For example, taking action (i.e. norepinephrine boost) to build an emergency fund, which provides a financial buffer against future stressors.
Another thing I gather is that it is more regulation of the system than the increasing action per se. Some research suggeests that while NRIs increase norepinephrine in the short term, there are compensatory effects which work to offset this. People with anxiety, typically have abnormal norepinephrine release patterns (i.e surges and then dropoffs). Many antiderepssants seem to normalize the firing patterns.
One could say the same with ritalin for ADHD. Why would a 'stimulant' calm a person with hyperactivity? The answer lies in the fact that, for individuals with ADHD, the stimulant (in the right dose) actually normalizes dopamine release patterns. People with ADHD typically have low dopamine firing, and then surges (i.e. hyperfocus) etc.
Linkadge
Posted by bleauberry on January 14, 2019, at 9:44:30
In reply to How can ADs increasing norepinephrine help anxiety, posted by mtom on January 5, 2019, at 20:40:48
The norepinephrine receptors will tend to adapt to the increased amount of norepinephrine. They are genetically programmed for a certain amount. If there is more than that amount, they will try what they can to adjust to that. One way is by becoming less sensitive to norepinephrine. So when that adjustment happens, and there is less sensitivity to norepinephrine, that is the point where anxiety goes down. But that takes a few weeks or even months to happen, and may not happen at all in some people.
What I got from that med was a mixed pro-anxiety and anti-anxiety at the same time! The antihistamine part of it was anti anxiety, the serotonin blocking was anti anxiety, but the norepinephrine part was pro anxiety, and it was a bizarre thing to feel all of that at the same time.
Posted by mtom on January 14, 2019, at 10:54:37
In reply to Re: How can ADs increasing norepinephrine help anxiety, posted by bleauberry on January 14, 2019, at 9:44:30
Interesting. Yet Mirtazpine is often prescribed off-label to treat anxiety along with depression, and there are many research reports (and anecdotal ones) attributing this effect to it. SSRIs increase my anxiety. Mirtazpine seems to stimulate some SSRI receptors and block others as far as I can figure out (mode of action is very hypothetical and complex). Perhaps it is the blocking of some Serotonin receptors that causes decrease in anxiety?
> The norepinephrine receptors will tend to adapt to the increased amount of norepinephrine. They are genetically programmed for a certain amount. If there is more than that amount, they will try what they can to adjust to that. One way is by becoming less sensitive to norepinephrine. So when that adjustment happens, and there is less sensitivity to norepinephrine, that is the point where anxiety goes down. But that takes a few weeks or even months to happen, and may not happen at all in some people.
>
> What I got from that med was a mixed pro-anxiety and anti-anxiety at the same time! The antihistamine part of it was anti anxiety, the serotonin blocking was anti anxiety, but the norepinephrine part was pro anxiety, and it was a bizarre thing to feel all of that at the same time.
Posted by Hordak on January 14, 2019, at 15:19:27
In reply to Re: How can ADs increasing norepinephrine help anxiety, posted by bleauberry on January 14, 2019, at 9:44:30
> The norepinephrine receptors will tend to adapt to the increased amount of norepinephrine. They are genetically programmed for a certain amount. If there is more than that amount, they will try what they can to adjust to that. One way is by becoming less sensitive to norepinephrine. So when that adjustment happens, and there is less sensitivity to norepinephrine, that is the point where anxiety goes down. But that takes a few weeks or even months to happen, and may not happen at all in some people.
Is it reversible?
Posted by porkpiehat on January 15, 2019, at 14:06:50
In reply to Re: How can ADs increasing norepinephrine help anxiety » bleauberry, posted by Hordak on January 14, 2019, at 15:19:27
I've often wondered this myself...I'm under the impression that I tend to get more feelings of emotional detachment, sadness, zoning, and sedation on NE drugs. My theory is that, as someone suffering from complex trauma, the activation of the sympathetic nervous system creates a trauma response of total numbness and dysphoria, almost dissociation, occasionally Anger too.
Then the pro-focus part of the drug locks me into this feeling and removes me from positive or exciting stimuli. haven't gotten a doctor to seriously address this theory.
The following meds did this to me:
wellbutrin
Parnate
desipramine
Nortriptyline
Cymbalta
Effexor
Nardil
probably one or two others. I never gave the TCAs longer than a couple of days. Wellbutrin felt good for a week before turning on me and dissociating the f*ck out of me. Two days on cymbalta flipped me out and I tore into family members.Meds that reverse this tendency included prazosin, trileptal, gabapentin...
Your theory, which I hadn't considered, does make sense that the body would desensitize to NE eventually. That's why people take cymbalta for sweating and eventually get overly sedated I guess.
depending on the receptor, serotonin can have an aggitating, numbing effect on people too.
Posted by bleauberry on January 23, 2019, at 7:58:08
In reply to Re: How can ADs increasing norepinephrine help anxiety » bleauberry, posted by Hordak on January 14, 2019, at 15:19:27
I don't know. My experience suggests there is partial recovery, but that with every drug we try there is some sort of permanent change to genetics or receptors.
> > The norepinephrine receptors will tend to adapt to the increased amount of norepinephrine. They are genetically programmed for a certain amount. If there is more than that amount, they will try what they can to adjust to that. One way is by becoming less sensitive to norepinephrine. So when that adjustment happens, and there is less sensitivity to norepinephrine, that is the point where anxiety goes down. But that takes a few weeks or even months to happen, and may not happen at all in some people.
>
> Is it reversible?
>
Posted by SLS on January 24, 2019, at 8:35:44
In reply to Re: How can ADs increasing norepinephrine help anxiety » Hordak, posted by bleauberry on January 23, 2019, at 7:58:08
> I don't know. My experience suggests there is partial recovery, but that with every drug we try there is some sort of permanent change to genetics or receptors.
This is probably true for a great many people. It is of me.
Anytime someone experiences poop-out or fails to respond to the same drug a second time, this indicates a persistent change in the brain.
- Scott
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