56 replies to this topic

[michaelh]

What about something, like caffeine, that prevents stress-induced reductions in P-CAMKII, total CaMKII, and BDNF? Will chronic caffeine lead to trkb downregulation? I haven't seen much on here about CAMKII. Are there other areas of the brain that stress and depression lowers?

Is too much neurogenesis a bad thing?

Stimulating too much neurogenesis willy- nilly can cause seizures, says Phyllis Wise, who studies animal models of stroke at the University of Washington

too much neurogenesis would deplete all of the neural stem cells too quickly, resulting in a small brain and neurological abnormalities.

bump

Edited by michaelh, 21 January 2013 - 11:48 AM.

[michaelh]

Does trkb downregulation occur in the supplements that claim to normalise bdnf or reverse stress-induced decreases, like caffeine.

Is too much neurogenesis a bad thing?

Stimulating too much neurogenesis willy- nilly can cause seizures, says Phyllis Wise, who studies animal models of stroke at the University of Washington

too much neurogenesis would deplete all of the neural stem cells too quickly, resulting in a small brain and neurological abnormalities.

bump

[michaelh]

Turns out caffeine causes trkb downregulation, just like any other bdnf activator.

Is too much neurogenesis a bad thing?

Stimulating too much neurogenesis willy- nilly can cause seizures, says Phyllis Wise, who studies animal models of stroke at the University of Washington

too much neurogenesis would deplete all of the neural stem cells too quickly, resulting in a small brain and neurological abnormalities.

Edited by michaelh, 30 January 2013 - 05:17 PM.

[nowayout]

Why do you assume neurogenesis is necessarily a good thing?

There are various pathologies that appear to be a result of too much neural connectivity in certain areas of the brain, as opposed to too little. Also, remember that maturation of the human brain during adolescence relies on a lot of neural pruning, which accompanies a great improvement in mental functioning, impulse control, etc.

[michaelh]

I don't assume that. All I know is that stress halts neurogenesis. My interest is in drugs, like prozac, that mean you can push through the stress without affecting neurogenesis. I have a lot of stressful habits, like playing difficult videogames (enjoyable but very frustrating). Plus, I'm a student which is plenty stressful.

My interest's lie more in preventing the effects of stress on brain chemistry, then increasing neurogenesis.

Edited by michaelh, 30 January 2013 - 10:24 PM.

[nowayout]

I don't assume that. All I know is that stress halts neurogenesis. My interest is in drugs, like prozac, that mean you can push through the stress without affecting neurogenesis. I have a lot of stressful habits, like playing difficult videogames (enjoyable but very frustrating). Plus, I'm a student which is plenty stressful.

I doubt your assumption that these kinds of "stress" are bad for the brain. Rather the opposite, I should think.

[neurevived]

Actually, I'm thinking of prozac:
http://www.nytimes.c...len-prozac.html
http://www.drugs.com...de-effects.html
http://mistyhorizon2...uoxetine-Prozac

I'm not talking about loss-of-life, I'm talking about loss-of-clarity and fullness to life.
It scrambles your memory, but your brain doesn't care. There's a whole host of side-effects to go with it. Sure - not everyone suffers them as badly as others.

You'll think it's all peachy, even though everyone else around you can see how broken your life is - this is speaking as someone who has had relatives go on and off prozac. The effect is substantial.

If you're looking for neurogenesis, try one of the other options that doesn't potentially affect so many other facets of your life. There are some very, very effective alternatives listed on here.

Here's a "fullness to life" counterargument for you:

I take Prozac along with a couple other medications because of a type of neurological dysfunction I have. The neurogenesis aspect has saved my life. Without it, my brain function deteriorates. I originally went off it because I was wary of the side effects, too, and it was one of the biggest mistakes I've ever made. It was only when I got back on the Prozac and my dad and my neurologist did some research that they discovered the neurogenesis aspect that meds like Cymbalta don't have (a miracle drug, but not for neurogenesis).

I live what I consider to be a very fulfilling life, and as long as I'm on Prozac, I've had no loss of clarity. I'm a senior in college, an archer, a lifeguard, a swim instructor, and I participate in every cool extracurricular program I can. Because last semester was the semester I went off the Prozac, my GPA dropped from a 3.34 to a 3.16, but I still qualified for and will soon receive a Merit Bursary for academic achievement. All while on Prozac.

Prozac isn't the only med that saved me (first place goes to Lamictal), but without it - as proven last semester - I would be an absolute wreck. So forgive me if I strongly disagree with your assessment of the medication - as someone mentioned, it is one of the most prescribed medicines currently in existence, so it can't be THAT bad - and believe me when I say my brain "cares."

However, I'm advocating brand-name Prozac. Were the people you watched go on and off Prozac on brand name or generic fluoxetine? Generic meds can have between a 5% and 20% difference from the dosage they're supposed to have. I was on generic for awhile until I got them from a different company and later discovered - after suffering flu-like effects and mood swings - that some generic fluoxetine is produced in India and has God-knows-what in it. Stick to brand unless you know where the generic is made and, if you can find out, the possible dosage inaccuracy.

[MrHappy]

[size=4][font=arial, helvetica, sans-serif]What is trkb downregulation? Does this occur in the supplements that claim to normalise bdnf or reverse stress-induced decreases.

TrkB is there to balance BNDF. If you wanted to open that loop, I'd explore LM22A-4.

Edited by MrHappy, 05 February 2013 - 09:56 PM.

[nupi]

However, I'm advocating brand-name Prozac. Were the people you watched go on and off Prozac on brand name or generic fluoxetine? Generic meds can have between a 5% and 20% difference from the dosage they're supposed to have. I was on generic for awhile until I got them from a different company and later discovered - after suffering flu-like effects and mood swings - that some generic fluoxetine is produced in India and has God-knows-what in it. Stick to brand unless you know where the generic is made and, if you can find out, the possible dosage inaccuracy.

With the ridiculously long half life of Fluoxetine, small variances in dosage are not really much of a concern. Contaminants are but that's always the case. and I wouldn't be too surprised if brandname Fluoxetine was also partly made in India or China, BTW...

[neurevived]

I wouldn't be too surprised if brandname Fluoxetine was also partly made in India or China, BTW...

Generic fluoxetine is made in India. I found that out after I looked it up after some bad reactions to it, and the knowledge made me switch to brand immediately. God knows what was in that besides medicine...

[formergenius]

I think you're thinking of Stablon/Tianeptine.

Yeah I definitely think Tianeptine has more potential for doing this. I believe Tianeptine was the AD that lead to.... this hypothesis. (grab some popcorn boys and girls, you're in for a long one)
Could be mistaken on Tianeptine being the insightful agent on that theory though.

I would appreciate any one else sharing their fluoxetine experiences!

I had a trial of 20mg Prozac for 6 weeks. Mwe, what can I say? Slightly placebo anxiolytic effect perhaps?
Micromoments of vivid realization?
Then again, I have that weird stuff going on all the time.
IMHO smoking salvia is a better nootropic than Prozac. That's pretty self-explanatory.
That time spent on trial with Prozac is better spent on trial with something that has a yummy efficacy profile.

[MrHappy]

Actually, I'm thinking of prozac:
http://www.nytimes.c...len-prozac.html
http://www.drugs.com...de-effects.html
http://mistyhorizon2...uoxetine-Prozac

I'm not talking about loss-of-life, I'm talking about loss-of-clarity and fullness to life.
It scrambles your memory, but your brain doesn't care. There's a whole host of side-effects to go with it. Sure - not everyone suffers them as badly as others.

You'll think it's all peachy, even though everyone else around you can see how broken your life is - this is speaking as someone who has had relatives go on and off prozac. The effect is substantial.

If you're looking for neurogenesis, try one of the other options that doesn't potentially affect so many other facets of your life. There are some very, very effective alternatives listed on here.

Here's a "fullness to life" counterargument for you:

I take Prozac along with a couple other medications because of a type of neurological dysfunction I have. The neurogenesis aspect has saved my life. Without it, my brain function deteriorates. I originally went off it because I was wary of the side effects, too, and it was one of the biggest mistakes I've ever made. It was only when I got back on the Prozac and my dad and my neurologist did some research that they discovered the neurogenesis aspect that meds like Cymbalta don't have (a miracle drug, but not for neurogenesis).

I live what I consider to be a very fulfilling life, and as long as I'm on Prozac, I've had no loss of clarity. I'm a senior in college, an archer, a lifeguard, a swim instructor, and I participate in every cool extracurricular program I can. Because last semester was the semester I went off the Prozac, my GPA dropped from a 3.34 to a 3.16, but I still qualified for and will soon receive a Merit Bursary for academic achievement. All while on Prozac.

Prozac isn't the only med that saved me (first place goes to Lamictal), but without it - as proven last semester - I would be an absolute wreck. So forgive me if I strongly disagree with your assessment of the medication - as someone mentioned, it is one of the most prescribed medicines currently in existence, so it can't be THAT bad - and believe me when I say my brain "cares."

However, I'm advocating brand-name Prozac. Were the people you watched go on and off Prozac on brand name or generic fluoxetine? Generic meds can have between a 5% and 20% difference from the dosage they're supposed to have. I was on generic for awhile until I got them from a different company and later discovered - after suffering flu-like effects and mood swings - that some generic fluoxetine is produced in India and has God-knows-what in it. Stick to brand unless you know where the generic is made and, if you can find out, the possible dosage inaccuracy.

Going off any SSRI or MAO-I is likely to give you a drop in cognitive function for a number of weeks until things are balanced back up. I had that issue for 6 weeks after my first MB trial about 1.5 years ago.

There are many, many better options to induce neurogenesis and synaptogenesis without tolerance and unwanted effects.

[noos]

There are many, many better options to induce neurogenesis and synaptogenesis without tolerance and unwanted effects.

Like what?
Also, how does tianeptine compares to fluoxetine for neurogenesis?

[neurevived]

Going off any SSRI or MAO-I is likely to give you a drop in cognitive function for a number of weeks until things are balanced back up. I had that issue for 6 weeks after my first MB trial about 1.5 years ago.

There are many, many better options to induce neurogenesis and synaptogenesis without tolerance and unwanted effects.

It wasn't a number of weeks. It was two months and counting. My semester was ruined. And I only have unwanted effects when I'm on too MUCH of it, which is the case for almost every medication. I am very, very happy with Prozac, and as it is one of the most prescribed anti-depressants, I'm pretty sure a lot of other people are, too. I'm sorry you've had such bad experience with it, but I wouldn't call it the majority.

Lots of brilliant medicines will do terrible things to some people. That does not mean the medicine should be condemned. If Lamictal were condemned for its most terrifying side effect, a lot of people who can use it will suffer from its loss. It's a matter of weighing the good and the bad, and in my case, Prozac does more good. Also, I speak as someone who has been on and off many, MANY medications over the course of several years, and nothing measured up to the meds I'm on now.

[medievil]

SSRI's cause neurogenesis trough 5HT4 induced cyclic amp, selective agonists with a proposed much faster effect are available.

[MrHappy]

Going off any SSRI or MAO-I is likely to give you a drop in cognitive function for a number of weeks until things are balanced back up. I had that issue for 6 weeks after my first MB trial about 1.5 years ago.

There are many, many better options to induce neurogenesis and synaptogenesis without tolerance and unwanted effects.

It wasn't a number of weeks. It was two months and counting. My semester was ruined. And I only have unwanted effects when I'm on too MUCH of it, which is the case for almost every medication. I am very, very happy with Prozac, and as it is one of the most prescribed anti-depressants, I'm pretty sure a lot of other people are, too. I'm sorry you've had such bad experience with it, but I wouldn't call it the majority.

Lots of brilliant medicines will do terrible things to some people. That does not mean the medicine should be condemned. If Lamictal were condemned for its most terrifying side effect, a lot of people who can use it will suffer from its loss. It's a matter of weighing the good and the bad, and in my case, Prozac does more good. Also, I speak as someone who has been on and off many, MANY medications over the course of several years, and nothing measured up to the meds I'm on now.

Mine was 6 weeks and in the end, I fixed the issue by taking some nootropics that rapidly rebalanced the receptors involved.

I'm glad you respond well to prozac, but your described cognitive impairment experienced when stopping it is a common problem associated with discontinuing it and many other anti-depressants and tranquilizers.

It doesn't mean that you perform better on prozac, it means that you can't perform without it due to tolerance issues caused by taking it. The tolerance can be fixed.

[neurevived]

Going off any SSRI or MAO-I is likely to give you a drop in cognitive function for a number of weeks until things are balanced back up. I had that issue for 6 weeks after my first MB trial about 1.5 years ago.

There are many, many better options to induce neurogenesis and synaptogenesis without tolerance and unwanted effects.

It wasn't a number of weeks. It was two months and counting. My semester was ruined. And I only have unwanted effects when I'm on too MUCH of it, which is the case for almost every medication. I am very, very happy with Prozac, and as it is one of the most prescribed anti-depressants, I'm pretty sure a lot of other people are, too. I'm sorry you've had such bad experience with it, but I wouldn't call it the majority.

Lots of brilliant medicines will do terrible things to some people. That does not mean the medicine should be condemned. If Lamictal were condemned for its most terrifying side effect, a lot of people who can use it will suffer from its loss. It's a matter of weighing the good and the bad, and in my case, Prozac does more good. Also, I speak as someone who has been on and off many, MANY medications over the course of several years, and nothing measured up to the meds I'm on now.

Mine was 6 weeks and in the end, I fixed the issue by taking some nootropics that rapidly rebalanced the receptors involved.

I'm glad you respond well to prozac, but your described cognitive impairment experienced when stopping it is a common problem associated with discontinuing it and many other anti-depressants and tranquilizers.

It doesn't mean that you perform better on prozac, it means that you can't perform without it due to tolerance issues caused by taking it. The tolerance can be fixed.

You seem to be missing the point of some medicines working well for some and badly for others, but that's ok. I'm very happy with my life right now, and no sales pitch about the evils of Prozac is going to make me change medications. There's some ancient adage somewhere along the lines of "if it ain't broke, don't fix it."

[MrHappy]

Going off any SSRI or MAO-I is likely to give you a drop in cognitive function for a number of weeks until things are balanced back up. I had that issue for 6 weeks after my first MB trial about 1.5 years ago.

There are many, many better options to induce neurogenesis and synaptogenesis without tolerance and unwanted effects.

It wasn't a number of weeks. It was two months and counting. My semester was ruined. And I only have unwanted effects when I'm on too MUCH of it, which is the case for almost every medication. I am very, very happy with Prozac, and as it is one of the most prescribed anti-depressants, I'm pretty sure a lot of other people are, too. I'm sorry you've had such bad experience with it, but I wouldn't call it the majority.

Lots of brilliant medicines will do terrible things to some people. That does not mean the medicine should be condemned. If Lamictal were condemned for its most terrifying side effect, a lot of people who can use it will suffer from its loss. It's a matter of weighing the good and the bad, and in my case, Prozac does more good. Also, I speak as someone who has been on and off many, MANY medications over the course of several years, and nothing measured up to the meds I'm on now.

Mine was 6 weeks and in the end, I fixed the issue by taking some nootropics that rapidly rebalanced the receptors involved.

I'm glad you respond well to prozac, but your described cognitive impairment experienced when stopping it is a common problem associated with discontinuing it and many other anti-depressants and tranquilizers.

It doesn't mean that you perform better on prozac, it means that you can't perform without it due to tolerance issues caused by taking it. The tolerance can be fixed.

You seem to be missing the point of some medicines working well for some and badly for others, but that's ok. I'm very happy with my life right now, and no sales pitch about the evils of Prozac is going to make me change medications. There's some ancient adage somewhere along the lines of "if it ain't broke, don't fix it."

Actually - reread my last comment. I was happy it was working for you, but discussing the effects of coming off antidepressants in general, relative to cognitive function.

[nupi]

I'm glad you respond well to prozac, but your described cognitive impairment experienced when stopping it is a common problem associated with discontinuing it and many other anti-depressants and tranquilizers.

It doesn't mean that you perform better on prozac, it means that you can't perform without it due to tolerance issues caused by taking it. The tolerance can be fixed.

I am sorry, but that post is disingenious on multiple points
1) Lumping together anti depressants and tranquilizers is silly - the reasons should be obvious for anyone who ever tried both groups. I would actually argue that benzos also cause acute cognitive impairment - they might help overall by blocking anxiety. However that may be, getting of benzos is quite different than getting of an SSRI. The former might cause rebound anxiety which would definitely cause cognitive impairment whereas the later might go anyway (in my case, getting of Escitalopram would probably have increased cognitive capabilities by simply removing the incredible fatigue it was giving me).

2) Discontinuation resulting in cognitive impairment might just as well prove that you are not actually ready to get of the meds - depression after causes serious cognitive impairment on its own. Especially if its a case of dysthimia [1], the fact that you are not actually all that better yet may not even be all that obvious at the time.

3) Finally, if anything, what you argue is dependence/withdrawal, not tolerance. Tolerance would mean the need to up the Prozac dose (which may happen once or twice initially, but usually there is a steady state dose that can work for a long time)

[1] Which in some ways is nastier than MDD in which case it at least is blindingly obvious to others that you need to get treatment, dysthimia may well be perceived as your baseline by others as well...

[nowayout]

2) Discontinuation resulting in cognitive impairment might just as well prove that you are not actually ready to get of the meds - depression after causes serious cognitive impairment on its own. Especially if its a case of dysthimia [1], the fact that you are not actually all that better yet may not even be all that obvious at the time.

Not too sure about that. Various studies have shown that SSRIs make patients more likely to experience further depressive episodes and rebound depression than placebo. How is taking more SSRI an answer to this?

Your (and the Pharma companies') argument is a common one used by religions as well to entrap people, namely that if something bad happens to you, it's not the fault of the medication (or God), but because you were not sufficiently faithful.

Edited by viveutvivas, 09 February 2013 - 03:18 PM.

[nupi]

As for these studies, I have read the abstracts but never the entire thing so judging them is hard. Designing a good RCT study to actually prove that conjecture is rather nontrivial (there is a rather long list of confounding factors that are pretty hard to account for in an RCT).

If the medication works while you take it and you feel bad when you stop taking it, arguably it treats but does not cure the disease. Or to take a very obvious example: insulin, few people in their right mind would argue that it is not doing what it is supposed to be doing but stopping to take it is a recipe for disaster.. Or possibly an even better example: TRT where the exogenous supplementation of T will greatly diminish endogenous production (making a cold turkey withdrawal a rather unfriendly idea) but in principle improves quality of life and can do so for a long time.

As for religion, the day the church can prove that being faithful does anything at all (while you are it), they can claim that you might not have been faithful enough.

I for one will stay on my SSRI. On the off chance that it might result in a bad situation later on (AD can poop out after all), that still beats a bad situation now and with a fairly high likelihood of a bad situation later ontoo because the bad situation now screwed up your whole life...

Edited by nupi, 09 February 2013 - 04:19 PM.

[nowayout]

But to take your analogy and run with it: What if someone gets on TRT because some temporary illness or circumstance caused a drop in his testosterone? This happens a lot. That drop would have been temporary, and his natural testosterone production would have recovered, if he were not put on TRT, which now prevents recovery of T production and in fact causes atrophy of the hypothalamus-pituitary-testicular axis. His own testosterone production cannot recover unless TRT is stopped and then he will have to go through a withdrawal period of low testosterone, possibly with worse symptoms than before, before he gets better, and sometimes the atrophy induced by TRT in the hypothalamus-pituitary-testicular axis is not completely reversible when TRT is stopped.

I strongly suspect SSRIs are quite analogous in their induction of withdrawal and rebound depression, as well as the possible induction of irreversible atrophy in some aspects of neurotransmitter metabolism, and this is of course good for selling them but not good for patients whose depression was going to have been temporary without them (as most cases of depression are).

Edited by viveutvivas, 09 February 2013 - 04:51 PM.

[nupi]

Fair enough point.

Then again MDD might be temporary (but untreated, there is a however non negligible risk of suicde) but dysthymia almost by definition is not. Also, I am not entirely sure what the profit margin on generic ADs is but it cannot be that huge (a fair number of the usual supplements around here have a higher per day cost than my Fluoxetine, even if I buy the Eli Lilly branded one).

[MrHappy]

I'm glad you respond well to prozac, but your described cognitive impairment experienced when stopping it is a common problem associated with discontinuing it and many other anti-depressants and tranquilizers.

It doesn't mean that you perform better on prozac, it means that you can't perform without it due to tolerance issues caused by taking it. The tolerance can be fixed.

I am sorry, but that post is disingenious on multiple points
1) Lumping together anti depressants and tranquilizers is silly - the reasons should be obvious for anyone who ever tried both groups. I would actually argue that benzos also cause acute cognitive impairment - they might help overall by blocking anxiety. However that may be, getting of benzos is quite different than getting of an SSRI. The former might cause rebound anxiety which would definitely cause cognitive impairment whereas the later might go anyway (in my case, getting of Escitalopram would probably have increased cognitive capabilities by simply removing the incredible fatigue it was giving me).

2) Discontinuation resulting in cognitive impairment might just as well prove that you are not actually ready to get of the meds - depression after causes serious cognitive impairment on its own. Especially if its a case of dysthimia [1], the fact that you are not actually all that better yet may not even be all that obvious at the time.

3) Finally, if anything, what you argue is dependence/withdrawal, not tolerance. Tolerance would mean the need to up the Prozac dose (which may happen once or twice initially, but usually there is a steady state dose that can work for a long time)

[1] Which in some ways is nastier than MDD in which case it at least is blindingly obvious to others that you need to get treatment, dysthimia may well be perceived as your baseline by others as well...

Well, I'm lumping anti-depressants and tranqs, specifically benzos, into the same container labelled 'things that cause cognitive impairment when withdrawing' as the withdrawal process for them is extremely disruptive to normal moods, thought processes and life in general, albeit for totally different reasons.

I mention tolerance, as it's the receptor imbalance caused by taking a substance for a length of time that leads to the withdrawal symptoms experienced when discontinuing that substance. This is why taking something once or twice usually doesn't require any process to safely withdraw.

[nupi]

Well, I'm lumping anti-depressants and tranqs, specifically benzos, into the same container labelled 'things that cause cognitive impairment when withdrawing' as the withdrawal process for them is extremely disruptive to normal moods, thought processes and life in general, albeit for totally different reasons.

Except, anecdotally, that differs a lot for people. Personally, I neither had any real issues getting off benzos (after say 100 pills of lorazepam and diazepam - I may have had residual anxiety but it was definitely nothing major) nor any obvious issues getting off Effexor (which is notorious for discontinuation troubles) nor Wellbutrin (well except that my depression was still there)...

[neurevived]

I for one will stay on my SSRI. On the off chance that it might result in a bad situation later on (AD can poop out after all), that still beats a bad situation now and with a fairly high likelihood of a bad situation later ontoo because the bad situation now screwed up your whole life...

I cannot agree with this enough, as I am learning the hard way.

Since I can't seem to double quote,
MrHappy:"It doesn't mean that you perform better on prozac, it means that you can't perform without it"

Implying drug dependency isn't very nice.

[YimYam]

It could be argued that fluoxetine has a nootropic effect. It has been shown to improve cognitive measures in both animals [1] [2] [3] and humans [4] [5] [6], though there's some opposing data as well [7] [8] [9]. It's unclear how much of this might be generally applicable, and how much cognitive improvement might be due to 'clearing up' depression.

The effect on neurogenesis is a lot more solid. The effect seems mediated through its effect on serotonin [10], though other necessary mechanisms have been elucidated, as well [11] [12] [13] [14] [15] [16] [17]. Interestingly, the effect is completely blocked by diazepam [18], and in a switch with most neurogenics that interest us, it seems to work better in younger animals than old ones [19] [20] [21] [22] [23]. It protects against decreases in neurogenesis in some models [24] [25], but is also capable of decreasing it in some parts of the brain [26] [27]. Adult neurogenesis has received attention recently in the etiology of depression, but only some of fluoxetine's effects seem to depend on its neurogenic properties [28] [29]. Lastly, it is effective at complete incorporation of new neurons [30], as opposed to some substances which may simply generate non-surviving progenitor cells.

In general, I wouldn't suggest taking an SSRI just to achieve either of these effects. Their popularity is due more to marketing, and the perverse structure of the US prescription drug pipeline, than because they are necessarily the best options. Tianeptine and agomelatine are two options which are worth looking into, for people considering prozac for any of these reasons.

 

Superrrrbb post. Merci beaucoup!