Antidepressants

[Tammy]

I understand that the L form doesn't work for pain--physical or emotional.

It worked for my depression. (L-phenylalanine)

 

[YippeeKi YOW !!]

the kind of dried out I am referring to cannot be rectified by drinking water.

When the body and its systems are stressed by being forced to metabolize and eliminate a lot of ..... we'll call 'em toxins ... it pulls water from everyplace in your body, leaving your brain til last. But it will cautiously and judiciously pull from that resource, too, if it has to. It just would rather not, for obvious reasons.

It may seem that drinking water doesnt help with that kind of dryness, but the problem is that it takes so long to replenish the water shortages in your cells, organ systems, soft tissues, skin, etc, that it's hard to connect those dots. Your skin and soft tissues like gums and some of the mucosa (excepting the intestines) generally gets attention last, since its functions become superfluous if you go into organ failure, and as a result, you know, die ....

I read that under those conditions, and especially with ongoing heavy water use by your system, it can take as long as 2-4 weeks to come back up to a normal level, and that's assuming that you're drinking AT LEAST 3 liters of water a day .... some sources say 4 liters minimum.

 

[YippeeKi YOW !!]

Insert Cheerleader Emoji.

Thank you, Red ... that made me feel a little less like a thundering bore ....

 

[uglevod]

Antidepressants are another class of immune suppressing drugs. Forget everything you read on them in plain media/pharma controlled "science" for your own good.

Antidepressants normalize elevated Toll-like receptor profile in major depressive disorder
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828490/
Abnormalities in Toll-like receptor (TLR) expression in depression have been inferred in part from observed increases in TLR4 levels in peripheral blood mononuclear cells (PBMCs) and postmortem brains of depressed and suicidal patients. Our previous study found differences in the TLR expression in PBMCs between healthy controls and patients with major depressive disorder. Normalization of increased TLR4 in PBMCs by cognitive behavior psychotherapy has been reported.
...
TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 were expressed at elevated levels in patients with MDD(major depressive disorder) and were significantly decreased by treatment with antidepressants for 4 weeks. Antidepressant treatment completely normalized TLR3, TLR5, TLR7, TLR8, and TLR9 levels, whereas TLR1, TLR2, TLR4, and TLR6 were decreased to below normal levels.
...
These findings suggest that antidepressant treatment exerts anti-inflammatory effects in patients with MDD(major depressive disorder) and identify TLR profiles as a predictor of response to antidepressant therapy. Further studies investigating the effects of manipulating individual TLRs on depression are needed to fully elucidate the underlying mechanism.
...
This study has provided novel insights into relationships among TLR expression, antidepressants, and clinical response for a well-characterized MDD. Beyond confirming that the expression levels of certain TLRs are decreased in PBMCs among MDD patients, we have also described—to the best of our knowledge for the first time—distinctive effects of antidepressants on TLRs. In summary, the observed decrease in TLR expression and its association with treatment outcome in depressive patients implies a link between inflammation, depression, and treatment. Further animal studies are needed to test antidepressive effects using antagonists of specific TLRs.



Serum levels of peptide cathelicidin LL-37 in elderly patients with depression
https://www.researchgate.net/public...din_LL-37_in_elderly_patients_with_depression

Cathelicidin LL-37 is a small cationic that plays an important role in antimicrobial defense, as it kills a broad spectrum of infectious agents by disrupting their membranes, including gram-positive and gram-negative bacteria, some viruses and fungi; and it neutralizes activity of bacterial endotoxins. Moreover, cathelicidin LL-37 exerts proinflammatory effect, while numerous reports indicate the role of inflammation in the development of depression. The purpose of this study was to evaluate the circulating levels of cathelicidin LL-37 in elderly depressed patients. Thirty-nine elderly (age ≥ 60 years) women with major depressive disorder and thirty-eight non-depressed elderly (age ≥ 60 years) women were included into the study. The mean serum cathelicidin LL-37 concentration in patients with depression and in healthy subjects were 2.40 ± 3.00 ng/mL and 1.17 ± 3.04 ng/mL, respectively, and the difference was statistically significant. No significant differences between mean serum CRP level and WBC count in MDD patients and control group were documented. There were no correlations between LL-37 level and age, BMI, GDS score, CRP level or WBC count. It can be assumed that elevated serum LL-37 levels in depressed patients may reflect inflammatory activation associated with depression.

 

[lenora]

I have found both supplements and drugs to be tricky, in terms of trying to find things which do not make my depression and mental health worse.

Quite a few supplements substantially worsen my depression, usually anything that boosts the immune system (which makes sense, given the latest theories on depression suggest it may be underpinned by inflammation and immune activation in the brain). Echinacea strangely I am fine with.

But the yeast supplement Epicor (Saccharomyces cerevisiae) makes me miserably depressed, and I also get depressed from the immune boosters beta sitosterol, transfer factor and BioBran MGN-3. I am not sure if other people with pre-existing low mood are made further depressed by these supplements, but if depression is a common side effect, perhaps there should be warning labels on the jars. So now I approach any immune booster with caution.

Wise thinking as it so often seems that what works for one person, is bad for another. Trial and error with larger numbers. I agree, anything new should be looked at as a "perhaps" measure. Check our all side-effects and how long they're expected to last. Emotions are hard to control at times....I, for one no longer cry, I'm sad for certain, but tears no longer appear.

Why? I think in my case it's just that I've had too much heavy-duty sadness at one time. I do feel all of the necessary emotions though,. Joy is a part of my life, so I don't feel that the meds, vitamins, etc., have left me blunted. I'm actually grateful to them and what I'm on now seems to work just fine.

People totally underestimate emotional problems....and how much they can disturb lives, destroy them even. So we constantly have to battle both ends of our day to day beings. Yours, Lenora.

 

[lenora]

@YippeeKi YOW !!


I really want to use an AD for now. Coping is quite hard. I will try it for 2 weeks and see how it feels. A friend of mine backed out pretty easy. I'm not a fan of consuming a lot of drugs at the same time.



No worries, A read a lot about Abilify (Stanford study as well) and talked to some people in a FB Group. My Psychiatrist is supporting me in a very good way. She doesn't know about the escilatopram (from GP) yet, because she's on holiday, but I will realign with her when she's back. I will take max 2 drugs at a time. Therefore I'm considering to tap off the doxepin for sleep. I already checked contraindications. Lexapro can amplify the effect of Abilify but it is highly unlikely to happen due to the low dose of Abilify. My first priority right now is mood and anxiety (with whatever drug or herb). As soon as I think that I'm in a stable state I will trial Abilify.

I need to work on my grief and give my body time to heal. I'm so short in this and hope that I still have a good window of recovery or remission if I don't overdo things. Trials are secondary to a good state of mind. I got better the last couple of days and hoping to improve more while working on my mood.

Thank you so much for your Input. I really appreciate it

It sounds like a sensible plan. Grief is something that does have to be dealt with...and we can't expect anything to remove it entirely. After all, love comes with its own built-in sorrow for a lot of us at sometime in our lives.
I'm sorry for whatever you're going through @Boba and wish you well. Yours, Lenora.

 

[YippeeKi YOW !!]

Grief is something that does have to be dealt with

I agree. But using an anti-depressant to suppress that grief can sometimes lead to a lot of issues and potential problems down the road, independent of the rewiring of the brain as well as some neurotransmitters, which can cause some pretty unpleasant, and often hard to undo, problems.

But we went into all this last week, ad infinitim, both above and on the previous page.

I think @Boba has thought this thru carefully, and has good medical oversight and input from two Drs, and, most importantly, has their head screwed on straight, so I'm a lot less concerned than I was at the start ....

@Boba, if you can, please check in and let us know how it's going with you, yes ?

 

[Boba]

Thanks for asking!

I stopped Lexapro after 3 days. I wanted to give Abilify a try and avoid flooding my body with too many drugs at once. I‘m not sure if I will add an antidepressant later on. Hope I don’t need it.

It was and is still very for me to get sick after Covid, it‘s been 6 months now with many ups and downs resulting in being bedridden for the last 3 months. I‘m getting used to it somehow, but also got a little better in the last couple of days. Still hoping to recover in the near future, but it seems unlikely from what I‘ve learned about my symptoms compared to stories of others and what science has to offer. My body is acting very weird...

 

[Boba]

@lenora Thanks for your kind words! I‘m pretty young and had many plans turned on hold due to CFS. It‘s been pretty stressful and the grief is real. I just feel it’s too early to be the end of the movie... I was about to marry my gf and have kiddos. I do grieve. A lot. But I simply can’t change the situation whatever I do, realizing this helps a little with coping.

 

[YippeeKi YOW !!]

I stopped Lexapro after 3 days.

Oh, thank God !!!! Lexapro seems to be the new medical go-to, and it can really turn on you in some nasty, nasty ways, so good, good, good .....

Not that it's any of my business ....

Hopefully Abilify will provide what you need, as it seems to for some people, and eliminate the need for a long-term anti-d ....

Still hoping to recover in the near future, but it seems unlikely from what I‘ve learned about my symptoms compared to stories of others and what science has to offer

I think there can be danger in comparing our condition to others, and then projecting that down the road. We really are all different, with different underlying potentiating issues and different genetic wiring, so dont let all that freak you out. Accept it as input that may or may not have any real bearing on you, personally, and keep looking for your own answers ....

My body is acting very weird...

Hopefully, it's part of its struggle to restabilize, rebalance, and rewire. It's been thru a lot, and it's not like it can undo all that overnight.

Keep a good thought, keep looking for answers, keep checking in, yes ?

 

[Boba]

Oh, thank God !!!! Lexapro seems to be the new medical go-to, and it can really turn on you in some nasty, nasty ways, so good, good, good .....

Not that it's any of my business ....

Hopefully Abilify will provide what you need, as it seems to for some people, and eliminate the need for a long-term anti-d ....

I think there can be danger in comparing our condition to others, and then projecting that down the road. We really are all different, with different underlying potentiating issues and different genetic wiring, so dont let all that freak you out. Accept it as input that may or may not have any real bearing on you, personally, and keep looking for your own answers ....

Hopefully, it's part of its struggle to restabilize, rebalance, and rewire. It's been thru a lot, and it's not like it can undo all that overnight.

Keep a good thought, keep looking for answers, keep checking in, yes ?

Sure! This place is my refuge these days.

 

[YippeeKi YOW !!]

But I simply can’t change the situation whatever I do, realizing this helps a little with coping.

Maybe not immediately, or even as quickly as you'd like, but things do change, and this will, too. And maybe your gf will wait for those changes and maybe she wont. And maybe there's someone even more perfectly attuned to you, hovering just out of sight.

Life is just a great steaming, simmering pot of 'maybes', and I agree with you, its very very frustrating.

 

[lenora]

@lenora Thanks for your kind words! I‘m pretty young and had many plans turned on hold due to CFS. It‘s been pretty stressful and the grief is real. I just feel it’s too early to be the end of the movie... I was about to marry my gf and have kiddos. I do grieve. A lot. But I simply can’t change the situation whatever I do, realizing this helps a little with coping.

Hi Boba.....I'm definitely sorry for your changes in life's status. I can only tell you that we all face it, although COVID may not necessarily be an additional factor, and little by little over time, you'll find things that you can smile about once again in your life.

Memories are always hard, and I have found that it takes time to process them...the sadness they once brought now brings a smile to our faces. Feel the joy, remind yourself that it's real and this may occur a number of times/day. I'd say that's fairly unusual. However, if you find yourself feeling suicidal, it's time to get help....and please be honest with your therapist or doctor. After all, they can't help if they don't know.

Like your body, your mind also needs time to heal. Patience, just a word, but a concept that is so hard to get used to. Do you have friends who can visit you and bring along a Starbuck's coffee for each of you? Your family....we also have to learn when to ask for help and to reach out to others. We all need someone to lean on at times. Can you watch TV, (not the news, please!), read or do anything that keeps your mind occupied? I don't know where your head is at the moment.

If someone had told me well over 35 years ago, that my life would continue, I would find a purpose and actually experience joy again, I would have thought they were insane. But time has its own timetable, new people come into our lives, new babies, new friendships, new memories are made. It's life and we can then look back on it as whole. Listen to youtube for inspirational stories if you can't read, books on tape....do whatever you have to. Ask for recommendations, if necessary. I do wish you well and want you to know that people here understand far more than you may think. I was still very young when this occurred, and there are many even younger than I was. Go forward. Yours, Lenora.

 

[pattismith]

I also do well on MAO inhibitors, in fact even when I was healthy I found the MAO-B inhibitor selegiline (which is famous in cognitive enhancement circles) really great for generating a zesty enthusiastic mood and increased creativity.

Unfortunately I found since getting ME/CFS that selegiline makes my ME/CFS feel worse, and no longer boosted my mood, so I stopped using it. It was a mystery to me why a dry like selegiline which used to make me feel so great stopped working once I was hit with ME/CFS.

Eventually I learnt that selegiline boosts the inflammatory cytokine IL-1beta, which is a major cytokine driving brain inflammation. Since brain inflammation is an issue in ME/CFS to begin with, you would not want to increase IL-1beta and further. So I think this explains why selegiline started making me feel worse.

So then I switched to another MAO inhibitor, moclobemide, which is an MAO-A inhibitor, and I was fine with that.

I like moclobemide because in one study on the sexual side effects of antidepressants, moclobemide came out as having the lowest risk of these side effects (only a 4% chance of getting these side effects, whereas for SSRIs, it's typically around 60%).
.

That's interesting. It was long thought that Selegiline was effective by directly increasing Dopamine, but it may not be right.

we demonstrate that MAO-A, but not MAO-B, mainly contributes to striatal dopamine degradation. In contrast, our whole-cell patch-clamp results demonstrated that MAO-B, but not MAO-A, was responsible for astrocytic GABA-mediated tonic inhibitory currents in the rat striatum. We conclude that, in contrast to the traditional belief, MAO-A and MAO-B have profoundly different roles: MAO-A regulates dopamine levels, whereas MAO-B controls tonic GABA levels.

Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis | Experimental & Molecular Medicine (nature.com)

That's really interesting as it means Selegiline could be a GABA blocker.

GABA itself inhibits Dopamine.

And this is consistent with my experimentation with Selegiline.

I don't feel the same if i take methylphenidate (dopaminergic) or Selegiline (GABA inhibitor), but I feel very similar (same kind of stimulation) if i take Selegiline or a combo of Clarithromycin/Amoxicillin, two antibiotics that are GABA-A antagonists !!

As you have difficulties falling asleep, you may have lower GABA now than before your ME, which may explain why Selegiline stopped working.

Moclobemide as you wrote is a MAO A inhibitor so it raises both your NE, 5HT and DA, it's very different:

Monoamine oxidase A (MAOA) generally metabolizes tyramine, norepinephrine (NE), serotonin (5-HT), and dopamine (DA)

 

[lenora]

@Boba......Hello. This site popped up this a.m., and I just wanted to check and see how you're doing?

Have you been able to find a med that is better for you? It can/does take time and also time for the body to adjust. So many people give up after one or two days when it takes much longer than that for the side-effects to lessen and the body adjust.

@pattismith & @Hip....interesting exchange above. Yours, Lenora.

 

[Hip]

It was long thought that Selegiline was effective by directly increasing Dopamine, but it may not be right.

Selegiline does increase dopamine, but selegiline also boosts the inflammatory cytokine IL-1beta.

Increasing IL-1beta may not be an issue in healthy people, but in ME/CFS patients who already have brain inflammation, it will make the brain inflammation worse. My ME/CFS started after a viral brain infection, and I think brain inflammation is part of my ME/CFS.


When I was healthy, I had no problem with selegiline. But once I developed ME/CFS, I found selegiline had adverse effects, like because of the IL-1beta boosting.

As you have difficulties falling asleep, you may have lower GABA now than before your ME, which may explain why Selegiline stopped working.

I am not sure if the GABA effects would relate to mood boosting.

I found selegiline stopped boosting my mood once I developed ME/CFS. This antidepressant mood boost arises from the dopaminergic effect of selegiline.

I suspect that selegiline may still raise my dopamine, but the benefits may be countered by the increase in brain inflammation from IL-1beta.

 

[pattismith]

@Hip if you had ADHD before ME, you likely had low GABA (I do)

These are the antidepressants I take (and these have continued working for me):

Effects kick in within a couple of hours:

• Amitriptyline 10 mg — TCA antidepressant, a reuptake inhibitor of serotonin and norepinephrine

It may be that Amitriptyline helps you because of it's effect on GABA?

"Additionally, several studies reported increased GABAB receptor binding sites in frontal cortex and hippocampus in rats, after chronic treatment with various antidepressant drugs (ie amitryptyline, imipramine, desipramine, maprotiline, viloxazine, fluoxetine, citalopram),1"

4001362.pdf (nature.com)

Selegiline does increase dopamine, but selegiline also boosts the inflammatory cytokine IL-1beta.

Increasing IL-1beta may not be an issue in healthy people, but in ME/CFS patients who already have brain inflammation, it will make the brain inflammation worse. My ME/CFS started after a viral brain infection, and I think brain inflammation is part of my ME/CFS.


When I was healthy, I had no problem with selegiline. But once I developed ME/CFS, I found selegiline had adverse effects, like because of the IL-1beta boosting.
I am not sure if the GABA effects would relate to mood boosting.

I found selegiline stopped boosting my mood once I developed ME/CFS. This antidepressant mood boost arises from the dopaminergic effect of selegiline.

I suspect that selegiline may still raise my dopamine, but the benefits may be countered by the increase in brain inflammation from IL-1beta.

I agree Selegiline is dopaminergic, but indirectely.

According to the latest research (the article was released on july 2021), MAO-B does not metabolize dopamine, it is involved in GABA production.

So Selegiline improves the dopamine circuit function by stopping the GABA inhibition on the dopaminergic neurons.

 

[Hip]

I agree Selegiline is dopaminergic, but indirectely.

According to the latest research (the article was released on july 2021), MAO-B does not metabolize dopamine, it is involved in GABA production.

So Selegiline improves the dopamine circuit function by stopping the GABA inhibition on the dopaminergic neurons.

OK, I just had a good look at the paper you linked to, and now I understand what you are saying.

That's a very interesting finding, that MAO-B does not degrade dopamine, but synthesizes GABA.



Looking at the Wikipedia page on selegiline, it says selegiline also inhibits MAO-A in large doses:

In larger doses (more than 20 mg/day), it loses its specificity for MAO-B and also inhibits MAO-A,

However, years ago when I was healthy, and regularly took selegiline for its mood and creativity (lateral thinking) boost, I used fairly low doses of 1 or 2 mg daily. Yet this still had a strong dopaminergic feel; so I think low-dose selegiline may still boost dopamine, but by another mechanism.

So maybe as you suggest, selegiline's inhibition of GABA then resulted indirectly in the release of dopamine.



I recently tried the drug rasagiline, which is an MAO-B inhibitor like selegiline. Unlike selegiline, I don't think rasagiline has any pro-inflammatory effect on IL-1beta.

I was hoping rasagiline would give me the same nice mood and creativity boost as selegiline.

However, when I tried a low dose of rasagiline (one eight of a 1 mg tablet), I felt unusually tired all day long. This might have been a coincidence, but I have not yet tried rasagiline again.

I don't feel the same if i take methylphenidate (dopaminergic)

Methylphenidate also boosts norepinephrine, so it gives stimulant effects as well as dopaminergic effects.

 

[pattismith]

However, years ago when I was healthy, and regularly took selegiline for its mood and creativity (lateral thinking) boost, I used fairly low doses of 1 or 2 mg daily. Yet this still had a strong dopaminergic feel; so I think low-dose selegiline may still boost dopamine, but by another mechanism.

So maybe as you suggest, selegiline's inhibition of GABA then resulted indirectly in the release of dopamine.

I recently tried the drug rasagiline, which is an MAO-B inhibitor like selegiline. Unlike selegiline, I don't think rasagiline has any pro-inflammatory effect on IL-1beta.

I was hoping rasagiline would give me the same nice mood and creativity boost as selegiline.

However, when I tried a low dose of rasagiline (one eight of a 1 mg tablet), I felt unusually tired all day long. This might have been a coincidence, but I have not yet tried rasagiline again.

Don't you think that if IMAO-B inhibition fails to have dopaminergic effect for you, it could mean you have low GABA?
(I don't mean you have any schizophrenia, but here a picture that shows some interactions between GABA, GLUTAMATE AND DOPAMINE)

from Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia: Trends in Neurosciences (cell.com)

 

[Hip]

Don't you think that if IMAO-B inhibition fails to have dopaminergic effect for you, it could mean you have low GABA?

It's possible I guess. Certainly for many years I had moderate-to-severe generalized anxiety disorder (GAD), and GAD might be due to high NMDA or low GABA (NMDA excites neurons and GABA relaxes neurons).

But is is hard to increase the GABAergic system in a safe way. Benzodiazepines can do it, but have issues of tolerance and withdrawal.

Kava kava may be the best option: this increases the number of GABA binding sites over time.



My anxiety levels greatly increased after catching coxsackievirus B4. It's interesting that CVB4 might trigger an autoimmune attack on the enzyme GAD65, which synthesizes GABA for neurotransmission. I posted about this in this post.