Zero Evidence That Depression Is Caused by Low Serotonin Levels.....

[Hip]

Note that this paper does not demonstrate that antidepressants are ineffective.

Nor does it conclusively prove that low serotonin is not involved in depression. That is still an open question.

The Science Media Centre actually have some good criticisms of this paper, such as:

Prof David Nutt, Edmond J Safra Chair and Head of the Centre for Neuropsychopharmacology, Imperial College London, said:

“This meta review covers much of the work done over the past 50 years to explore the relationship of the serotonin system to depression.

Unfortunately, all of these variables are indirect measures of serotonin function or even worse (as in the case if the gene-linkage studies) merely proxies for serotonin activity.

It is only recently that we have developed the technology to measure serotonin release in the living human brain and in the first study of this type (currently under review) we did find decreased serotonin release capacity in people with depression. So, to dismiss the serotonin hypothesis of depression at this point is premature.”

In other words, researchers are not able to directly measure serotonin in depression, they only used indirect measures. Thus their conclusions that serotonin is not involved in depression is shaky.

Furthermore, even if it were to be demonstrated that serotonin were not involved in depression, this would not prove that antidepressant drugs do not work. SSRIs work on serotonin, but they also have other effects in the brain, such as promoting neurogenesis (creation of new brain cells), and these other mechanisms might also explain their antidepressant effect.

And in any case, serotonin is not the only neurotransmitter implicated in depression; there is also dopamine and norepinephrine (amongst others), and some antidepressant drugs target these, rather than serotonin.



I find antidepressant drugs very useful for my depression, and take several of them at the same time on days when my depression gets worse. I am very grateful to have drugs which can take the edge of my depression symptoms.

Of course there can be adverse effects, and in teenagers, SSRI antidepressants have been associated with suicide in some cases.

But now that warnings about suicidal thought side effects have been placed on antidepressant packets, and because of these side effects concerns, fewer teenagers are taking antidepressants to treat their depression, the end result is that teenage suicide rates have actually increased. Which suggests that antidepressant do help prevent suicides in depressed teenagers. Ref: here

So the scaremongering about antidepressants may be causing more teenagers to die.

No doubt in future we will have more sophisticated and effective means of treating depression; but until then, we have to use what is available to us now.

 

[LINE]

I found that adjusting some of my supplements achieved much better results than drugs. Next step is trying some tyrosine to see if I can boost dopamine levels. PhosphatidylSerine (from Doctors Best) is promising, seems to wake up the memory and brain function a bit.

 

[hapl808]

In other words, researchers are not able to directly measure serotonin in depression, they only used indirect measures. Thus their conclusions that serotonin is not involved in depression is shaky.

Furthermore, even if it were to be demonstrated that serotonin were not involved in depression, this would not prove that antidepressant drugs do not work. SSRIs work on serotonin, but they also have other effects in the brain, such as promoting neurogenesis (creation of new brain cells), and these other mechanisms might also explain their antidepressant effect.

And in any case, serotonin is not the only neurotransmitter implicated in depression; there is also dopamine and norepinephrine (amongst others), and some antidepressant drugs target these, rather than serotonin.

This is the issue with many things. We do placebo controlled trials to see if something might work, not why it might work. Maybe SSRIs work for some people for depression, but we have no clue on the mechanism. As you mention, there are plenty of potential causes that we know about, and likely many others we don't understand.

Since we have no real way to measure these things in real time, it's mostly guesswork. Unfortunately by a community with a mediocre track record for objectively and compassionately helping people.

 

[heapsreal]

Low serotonin might not be the cause of depression but increasing serotonin may still help some. One way to look at it is if u have a broken leg and in pain and they give you morphine which helps with the pain and coping with the broken leg until it's better. We don't say they have a low morphine level that's why they have pain.

In saying that, I don't think they work particularly well in cfs but they do help some people. One major problem is drs start cfsers on too larger dose. For some reason the brain of a cfser is to sensitive.

Also if put on a large dose and on it for awhile and need to come off, it can cause other problems. Why I think the use of tiny doses should be used as they will be easier to come off. An example of a dose that is normally used for zoloft is 25-50mg. Personally I think they should start off at 12.5mg and probably stay at that dose. If it doesn't help then stop it by tapering eg once every 2nd day then every 3rd day etc

If someone can find one they tolerate well and they can all work very differently, the effects generally are that they make you feel better about feeling like shit. Not a bad thing as it can give some people some respite from this shit.

To be honest the older antidepressants, tricyclics, seem to work better for cfsers and can help sleep and pain some but they do take awhile to work on mood and side effects like weight gain are very common. I personally keep some doxepin in the cupboard and occasionally use it for sleep. That's probably their best use.

The problem with medication is its all very individual and add cfs to it and it makes people even more sensitive to meds. Like I say alot, trial and error but the odds of antidepressants helping cfsers are low but for some people they really help them.

cheers

 

[Hip]

Low serotonin might not be the cause of depression but increasing serotonin may still help some.

That's a good point.

I get antidepressant effects from high dose inositol (the B vitamin), taken at dose of around 15 grams daily. This is thought to increase serotonin levels in the brain.

5-HTP increases serotonin, and this is sometimes used to treat depression.

To be honest the older antidepressants, tricyclics, seem to work better for cfsers and can help sleep and pain some but they do take awhile to work on mood and side effects like weight gain are very common.

I get a rapid mood boosts from tricyclic antidepressants like amitriptyline. They work for me within an hour or two. Usually I only take a very low dose of 5 mg (normal dose is 50 mg to 100 mg daily).

When I took one SSRI antidepressant called citalopram it actually dramatically increased my depression levels, within hours of taking one tablet.

 

[Crux]

I tried about eleven antidepressants, most were SSRIs.

The side effects were depression, and even tics. SSRIs are mildly anticholinergic, but they still caused anticholinergic effects in me.

I began to take 5htp for a time, was fine for a while.
Now I take some tryptophan for sleep.

Now I have 3 eggs a day, and some meat for choline.

I suggest getting enough choline if you take antidepressants.

https://www.uptodate.com/contents/image?imageKey=PC/100289&topicKey=PC/3013

 

[Rufous McKinney]

The benzos were the only help, but I got off those as well.

we seem to just love those.......

something I"ve noticed and wonder about..so I Might take a tiny bit of Xanax now and then. What I notice is I am having sort of obsessive thoughts. I"M thinking the same thing for a Long time. (anxious about X or depressed about Y). A tiny bit of something GABA- I stop trolling over the same thought. (half of half of one)

I think this contributes somehow to the "depressed" state...something tried to GABA.

 

[hapl808]

we seem to just love those.......

Which you would hope might inform research on CFS. Some sort of focus on glutamate/GABA systems, etc. But I feel like when I want to discuss that with anyone in medicine, they just sort of glaze over or at best ask if I want some Valium. Which is not what I'm looking for.

 

[Rufous McKinney]

Some sort of focus on glutamate/GABA systems,

yes, a recent bout of Why Am I Not Asleep right now got pinned on a mush room triggered glutamate overdose.

 

[LINE]

Which you would hope might inform research on CFS. Some sort of focus on glutamate/GABA systems, etc. But I feel like when I want to discuss that with anyone in medicine, they just sort of glaze over or at best ask if I want some Valium. Which is not what I'm looking for.

The glutamate system is stimulated from immune reactions. NMDA receptors are involved. I have some other posts that might be helpful on how I modulated this without benzos. Let me know.

 

[hapl808]

The glutamate system is stimulated from immune reactions. NMDA receptors are involved. I have some other posts that might be helpful on how I modulated this without benzos. Let me know.

Sure, which posts? I've done just basic stuff with regards to NMDA (various schedules of magnesium, etc).

 

[YippeeKi YOW !!]

Sure, which posts? I've done just basic stuff with regards to NMDA (various schedules of magnesium, etc).

You might also want to look into the AMPA receptors, which are pretty much in charge of a large proportion of rapid excitatory synaptic transmission throughout the CNS, as well as the plasticity of excitatory transmission expressed in the brain ...

 

[LINE]

Sure, which posts? I've done just basic stuff with regards to NMDA (various schedules of magnesium, etc).

My posts LINE | Phoenix Rising ME/CFS Forums, see the Clonazepam (Klonopin) threads.

You could try some extra B6 (and take a general b complex) and see if that helps. Magnesium also impedes the glutamate cascade. In these posts, I mention sublingual GABA which for me was a game-changer.

Something I did not mention on those posts is the role of toxins. I use a wide array of different things to reduce toxins and by doing so, the anxiety drops. One theory is that immunity is triggered with toxins and by reducing immunity, I feel better.

 

[hapl808]

You could try some extra B6 (and take a general b complex) and see if that helps. Magnesium also impedes the glutamate cascade. In these posts, I mention sublingual GABA which for me was a game-changer.

Something I did not mention on those posts is the role of toxins. I use a wide array of different things to reduce toxins and by doing so, the anxiety drops. One theory is that immunity is triggered with toxins and by reducing immunity, I feel better.

Thanks. I've tried magnesium (glycinate, malate, threonate, etc). I've done a methyl B complex that is a bit helpful for energy, but doesn't make me feel more rested. Also tried a separate B6 P5P form, but wasn't sure if that did anything. My methyl B complex also has a small amount of B6 P5P and that seems like enough.

I recently bought the GABA Calm and tried it, but it didn't seem to do anything. Wasn't sure if I needed something else with it, but took it when I was having a bad day and just tasted like a mint.

I definitely wonder about toxins. I've tried various binders and can never tell if I'm making any progress or that's the issue. Chlorella, spirulina, cholestyramine, charcoal, clay, etc. I think charcoal and chlorella are the ones I tolerate the best and seem to do some good, but can't tell if it's doing anything beyond my GI tract. Although a lot of my crashes start with GI symptoms, so I think it's all connected.

 

[Zahr82]

one of the SSRIS was given specifically for inflammation to COVID patients...

perhaps its has some affect through this inflammatory route.

I won't be taking any......Zoloft almost killed me.

Fluvuxamine. They're trialling vortices for it aswell

 

[Zahr82]

Pharma lab geniusess will sometimes come up with random concoctions (Valium was one) that they have no idea what to do with. So they apply to their very large stable of medical researchers and writers, the ones who actually write the final draft of that research paper with the name of the high-powered Harvard (or Yale or in a pinch, Princeton) doctor on it as the author, and they ask The Stable to come up with a reasonable use for this .... thing ....based on its chemical composition.

Once that's settled, they go to the other Writer's Room, where they have a large staff of imaginative creative types with some chemistry credentials who invent names for drugs that haven't even been created yet, and submit them for trademark protection so no one else can beat them to the punch once the drug that matches up with the name turns up.

I mean, really ... Domperidone (Dom Perignon)? Cialis? Viagra (vigor + vitality + GRAtification)? Flonase (particularly cute, since its a nasal decongestant)? Pancuronium (Pan = Greek for 'all', cure is self explanatory, onium makes it sound, you know, official)?

Granted, most drug names contain hints about the chemical structure, but really? I mean, really? A whole stable of companies that rent out creative minds to pharmaceutical companies that dont already have their own guys that make up names for drugs that'll improve their salability and please the FDA?

It also often leaes you dead, frequently by suicide.

I'm so sorry about your mother, Red. It must have been a hard thing to grow up with and live with thereafter ...

EDIT .... typos, additional info ....

Theyre cheaper, shitty drugs. But they do save people sometimes. SSRIS can give you PSSD, where you become hyper anhedonic. Basically you become completely emotionless, loads of suicides as a result of it. Maoi,s are the best AD,s in my opinion, far from perfect though.

 

[heapsreal]

Theyre cheaper, shitty drugs. But they do save people sometimes. SSRIS can give you PSSD, where you become hyper anhedonic. Basically you become completely emotionless, loads of suicides as a result of it. Maoi,s are the best AD,s in my opinion, far from perfect though.

Never tried maoi but moclobemide is supposedly a safer version of an maoi?? Can you comment on the difference of moclobimide vs traditional maoi?

 

[YippeeKi YOW !!]

Never tried maoi but moclobemide is supposedly a safer version of an maoi?? Can you comment on the difference of moclobimide vs traditional maoi?

For one thing, maclobemide's monoamine oxidase inhibition is reversible, and it's inhibitory effect is primarily selective for MAOA. It's got a short half-life, and it increases brain concentrations of noradrenaline and serotonin. It's also much better tolerated than the older MAOIs, and the incidence of anticholinergic side effects is low. It's generally seen to be a safer alternative to the older MAOIs whose effect is more permanent, and whose side effects more pronounced, including to everyday foods, condiments, alcohol (especially fortified wines like brandy and sherries), aged cheeses, you name it.

 

[Zahr82]

Never tried maoi but moclobemide is supposedly a safer version of an maoi?? Can you comment on the difference of moclobimide vs traditional maoi?

Yes, although maclobamide is far weaker than the others, it did nothing for me, personally. For me, Nardil was the best, but it stopped working. I'm on parnate now, which is working well

 

[YippeeKi YOW !!]

Yes, although maclobamide is far weaker than the others,

On what do you base the statement that they're " .... far weaker than the others ...."?

Maclobemide has far fewer side effects, is both selective and reversible, requires no dietary restrictions (the old MAOIs came with long, daunting lists of foods and substances that, if you ingested them while taking one of the MAOIs, could send you to the ER or the morgue), has an infinitely lower profile of hypertensive crises, and have been shown to be as effective as tricyclics and far better tolerated, and are comparable to the SSRIs in efficacy and patient toleration.

Which isn't to say that they're a good idea, they're just not as bad as other options.

They do have a shorter half-life, which is part of their benefit, and any shortfall in treatment expectations can be remedied by titrating the dose up until it achieves the desired effect.

Glad that you found something that works for you. It's a long dark alley with constant disappointments and reversals in effectiveness, so that's no small accomplishment ....