50 replies to this topic

[Un chien andalou]

Hi guys, I was researching fluoxetine (Prozac) and discovered this: http://en.wikipedia....harmacodynamics
 

Fluoxetine's effect on neurosteroids is primarily related to an increase in allopregnanolone, a potent GABAA receptor positive allosteric modulator;[65] a reduction in circulating brain (primarily mesocorticolimbic) allopregnanolone has been associated with both depression and anxiety disorders.[65] Improvement in depressive symptoms in medicated individuals is correlated with fluoxetine-induced increases in allopregnanolone levels.[65] Norfluoxetine, a primary active metabolite of fluoxetine, produces a similar effect on allopregnanolone levels in the brain, and has therefore also been characterized as a selective brain steroidogenic stimulant.[65]

According to these study, fluoxetine could be an anxiolytic in low doses (where the SRI action is almost 0), with little to no sexual side effects (or the typical SSRI anhedonia):
http://www.ncbi.nlm....pubmed/19157982
http://www.ncbi.nlm....pubmed/25498416
As you can see from the first link, Prozac's metabolite Norfluoxetine (the left enantiomer in particular, S-norfluoxetine) is even better in that regard, but Wikipedia unfortunately says it is cardiotoxic :(

Fish oil and fluoxetine have a synergistic effect, even in microdoses: http://www.ncbi.nlm....pubmed/25174836

Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels.

I've never taken Prozac before but I might try this. What you think?

Other related links:
http://peatarian.com...id-biosynthesis
http://www.longecity...supermicrodose/

Edited by Un chien andalou, 14 April 2015 - 04:54 PM.

[noos]

What dose will you take?

[Un chien andalou]

0,5 or 1 mg.

The problem with Fluoxetine is that has an extremely long half life so once I've decided the dose I can't change it, otherwise the results are not reliable

[noos]

The dose supposed to work for PMS increasing allo is 2 mg. Maybe you want to try that.
 

 

Thelma Lovick, a neuroscientist at the University of Birmingham, thinks she has evidence that a 2mg daily dose of fluoxetine in the final week before menstruation could alleviate PMS.

 

 

http://www.theguardi...dose-prozac-pms

[Un chien andalou]

Thanks, that was really useful!

[stillwater]

I took Prozac at the full dosage for 4 months 20 years ago, It gave me the best response out of any antidepressant, but the side effects were intolerable. I stopped everything all together shortly afterwards, but still suffer from GAD and depression. I think the bulk of my problems were brought on by using finasteride/propecia at that time. Depression and anxiety are side effects of 5α-reductase inhibitors such as finasteride, and are thought to be caused, in part, by interfering with the normal production of allopregnanolone. If my 5AR is impaired then Prozac's effects may not work to create more ALLO, but I'm considering give this a try anyway, at a low dose of .5 mg.  Perhaps the liquid form will be the easiest way?

 

Something else worth looking at is  a new drug called  Ganaxolone  http://en.wikipedia....wiki/Ganaxolone  when it becomes cheaply available. It's an analog of allopregnanolone.

 

[noos]

stillwater

I did not know about that side effect of finasteride. One more reason not to take it.

 

If Prozac gave you bad side effects why don't you try pregnenolone in supplement form?.

 

.5 mg fluoxetine is too low, what is the reason? Do you mean 5 mg?

Edited by noos, 17 April 2015 - 12:43 AM.

[stillwater]

stillwater

I did not know about that side effect of finasteride. One more reason not to take it.

 

If Prozac gave you bad side effects why don't you try pregnenolone in supplement form?.

 

.5 mg fluoxetine is too low, what is the reason? Do you mean 5 mg?

 

I have tried pregnenolone, it did nothing at all, which probably furthers the belief that there may be some 5AR impairment.  

 

Trying Prozac at .5mg or 1mg as this thread suggests would be almost purely for an anxiolytic outcome by trying to raise Allo levels, while hopefully avoiding the negative side effects that occur with dosages typically used for depression.

 

 

As a separate issue I think in many circumstances drug dosages are prescribed in levels too high for certain people, we all metabolize them differently and the aim is to hit that break point where positive effects are felt with the least side effects at the minimum dose, instead of always going overboard and hammering with immediate high dosages.  People will often do well on 1/10th or quarter of recommended dosages but most never try it out because they're pushed to increase to the supposed one size fits all "therapeutic" dose.

[noos]

Thanks stillwater

 

I agree that one should use the dose that fits but how do you know that .5-1 mg fluoxetine will increase allopregneolone? For women with PMS it seems to be 2 mg.

 

Will you dilute the pill in water and use a dropper?

Edited by noos, 17 April 2015 - 01:31 AM.

[Un chien andalou]

Allopregnanolone in itself is no bioavailable.
Ganaloxone is, but it's hard to find and likely expensive.

I found this that also supports our hypothesis:
 

 

Several reviews support the low-dose approach to treatment, claiming that existing guidelines are over-inflated. Cohen reported (2001b, 2004) that, when establishing the dosing recommendations, members of industry and regulatory agencies suppressed or ignored the early low-dose fluoxetine studies (Cain, 1992; Louie, et al., 1993; Wernicke, 1988) and reviews (Salzman, 1990; Schatzberg, 1991; Schatzberg, Dessain, O'Neil, Katz, & Cole, 1987; Stewart, Quitkin, & Klein, 1992; Wood & Gram, 1994).
A number of other antidepressants seem to have inflated dosing guidelines for example, drugs such as buproprion, citalopram, escitalopram, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, and venlafaxine prompting recommendations to start them at doses as low as one eighth of the guidelines appearing in the product monographs (Cohen, 2001a, 2001b, 2004).

http://razlab.mcgill...peuticDoses.pdf

[Flex]

I took Prozac at the full dosage for 4 months 20 years ago, It gave me the best response out of any antidepressant, but the side effects were intolerable. I stopped everything all together shortly afterwards, but still suffer from GAD and depression. I think the bulk of my problems were brought on by using finasteride/propecia at that time. Depression and anxiety are side effects of 5α-reductase inhibitors such as finasteride, and are thought to be caused, in part, by interfering with the normal production of allopregnanolone. If my 5AR is impaired then Prozac's effects may not work to create more ALLO, but I'm considering give this a try anyway, at a low dose of .5 mg.  Perhaps the liquid form will be the easiest way?

 

Something else worth looking at is  a new drug called  Ganaxolone  http://en.wikipedia....wiki/Ganaxolone  when it becomes cheaply available. It's an analog of allopregnanolone.

 

I guess Youre lucky to not to have perresistent sexual side effects form Prozac (PSSD)

[stillwater]

 

I took Prozac at the full dosage for 4 months 20 years ago, It gave me the best response out of any antidepressant, but the side effects were intolerable. I stopped everything all together shortly afterwards, but still suffer from GAD and depression. I think the bulk of my problems were brought on by using finasteride/propecia at that time. Depression and anxiety are side effects of 5α-reductase inhibitors such as finasteride, and are thought to be caused, in part, by interfering with the normal production of allopregnanolone. If my 5AR is impaired then Prozac's effects may not work to create more ALLO, but I'm considering give this a try anyway, at a low dose of .5 mg.  Perhaps the liquid form will be the easiest way?

 

Something else worth looking at is  a new drug called  Ganaxolone  http://en.wikipedia....wiki/Ganaxolone  when it becomes cheaply available. It's an analog of allopregnanolone.

 

I guess Youre lucky to not to have perresistent sexual side effects form Prozac (PSSD)

 

 

I do have them unfortunately but I'm fairly certain they were caused by the Finasteride as I took if for years and the Prozac only for 4 months.

[mandible]

In the article it speaks of 1mg/kg as non antidepressant dose.

I don't get it. 1mg/kg would mean an adult with 80 kilos would take 80mg prozac and 80mg prozac would be a very high dose!

 

I also wonder does prozac have these anxiolytic effects ONLY when taken in tiny amounts or also when used in normal amounts?

Cause if prozac was that great against anxiety shouldn't it be much more popular?

[stillwater]

It must have been a typo.  20mg is the standard dose across the board.  It does have fairly decent anxiolytic effects at that amount, I noticed it and I have GAD, but the downside is that it has a large side effect profile, as Flex mentioned above it does dramatically affect sexual function and can cause agitation, anger, suicidality, etc... So I guess the intention strictly as an anxiolytic is to take the smallest possible dose that provides that effect while negating most of the sides seen in the standard 20mg depressive doses.

 

 

[Area-1255]

0,5 or 1 mg.

The problem with Fluoxetine is that has an extremely long half life so once I've decided the dose I can't change it, otherwise the results are not reliable

It also has horrible withdrawal effects..why not just take pregnenolone supplements or a transdermal like RS Transaderm..then you don't have to worry about all the other side-effects those drugs cause.

Edited by Area-1255, 02 May 2015 - 02:01 AM.

[mandible]

Fluoxetin has horrible withdrawal side effects? I thought that since it has a long halflife withdrawal is easier than with other ssri.

 

If fluoxetin really works as an antidepressants then shouldnt higher doses work even better than low doses?

[Un chien andalou]

I started taking 4 mg of fluoxetine 16 days ago and I'm having good results. The first 10 days were terrible, but I expected that.

I also had benzo PAWS and severly downregulated GABA-A receptors though so I don't know if everybody would benefit with low dose fluoxetine.

 

Today I started taking fish oil, it supposedly enhances fluoxetine effect:

In the new study, researchers tested rats with salmon oil and one of two different antidepressants — fluoxetine (also known as Prozac) and mirtazapine (sold under the brand name Remeron). Although low doses of these antidepressants were ineffective by themselves, combining them with omega-3 fatty acids produced antidepressant-like activity that was similar to full-strength doses of the drugs. The results are published electronically ahead of print this month in the European Journal of Pharmacology.

http://www.medicalda...ressants-234314

 

 

Sixty patients were recruited from referrals to the Roozbeh Psychiatric Hospital in Tehran and randomized to consume 20 mg of fluoxetine or 1 g EPA or a combination daily for 8 weeks. Each participant consumed either a fluoxetine placebo or a rapeseed oil placebo to mimic the type of capsules taken in each group. No placebo-only group was included for ethical reasons. Patients were assessed by the Hamilton Scales at baseline and every 2 weeks thereafter. Of the 60 patients enrolled, 48 completed at least 4 weeks of the study.

Over the course of the 8-week study, all patient groups exhibited significant reductions in their Hamilton depression scores as early as 2 weeks from baseline. Scores for patients treated with fluoxetine or EPA did not differ throughout the study. At 4 and 6 weeks, those consuming both EPA and fluoxetine showed a significantly greater improvement in their Hamilton ratings (as determined by analysis of covariance) compared with either treatment alone. Depression scores continued to improve from the 4th to the 8th week. Response rates for achieving at least a 50% reduction in depression score were 50% for fluoxetine, 56% for EPA and 81% for those taking both fluoxetine and EPA. More adverse events occurred in the fluoxetine and combination groups than in the EPA group and ranged from gastro-intestinal effects, anxiety and decreased appetite to single reports of tremor, nightmare and constipation.

http://www.takeomega...ajor-depression

 

I wouldn't worry too much with fluoxetine w/d symptoms: this is a low dose and fluoxetine doesn't have the w/d of paroxetine or venlafaxine.

Edited by Un chien andalou, 09 May 2015 - 04:45 PM.

[Un chien andalou]

In the article it speaks of 1mg/kg as non antidepressant dose.

I don't get it. 1mg/kg would mean an adult with 80 kilos would take 80mg prozac and 80mg prozac would be a very high dose!

 

I also wonder does prozac have these anxiolytic effects ONLY when taken in tiny amounts or also when used in normal amounts?

Cause if prozac was that great against anxiety shouldn't it be much more popular?

1mg/kg is the rat dose. You need to convert it to the human equivalent dose, which is lower ofc.
A fluoxetine anxiolytic dose is 2-20 mg. At >20mg it becomes too stimmy (Zoloft and Prozac are the most "activating" SSRIs), which is counter intuitive for anxiety.

Edited by Un chien andalou, 09 May 2015 - 04:17 PM.

[nowayout]

 

I guess Youre lucky to not to have perresistent sexual side effects form Prozac (PSSD)

 

 

I do have them unfortunately but I'm fairly certain they were caused by the Finasteride as I took if for years and the Prozac only for 4 months.

 

It seems an SSRI would be the last thing to take when one has persistent sexual side effects from propecia, since SSRIs can only the compound the sexual problems.  If I were you, I would not even try to go down that avenue. 

 

Have you tried non-SSRI antidepressants or anxiolytics that don't come with sexual side effects?  Buspar and Vilazodone come to mind.

[stillwater]

 

 

I guess Youre lucky to not to have perresistent sexual side effects form Prozac (PSSD)

 

 

I do have them unfortunately but I'm fairly certain they were caused by the Finasteride as I took if for years and the Prozac only for 4 months.

 

It seems an SSRI would be the last thing to take when one has persistent sexual side effects from propecia, since SSRIs can only the compound the sexual problems.  If I were you, I would not even try to go down that avenue. 

 

Have you tried non-SSRI antidepressants or anxiolytics that don't come with sexual side effects?  Buspar and Vilazodone come to mind.

 

 

Yes I have, quite a few. Including maoi's and ones that haven't been released yet such as NSI-189 etc..as well as the old tricyclics. 

 

I'm not singling you out, you are only trying to help, but it seems like the point of this thread is lost on many.  It's about examining the effect of microdosing certain meds and in this case Prozac. I'm curious about microdosing many other substances, but since this thread is about Prozac, I'll stick to that.

 

Some who have taken an SSRI ,  see the words  SSRI or Prozac and think of all the well known side effects they cause and in turn think why would you want that?  This thread isn't about that, it's about discussing the possibility that taking very tiny doses might allow you to escape all those side effects and still see benefits. Drug marketing has pounded into everyone's heads that therapeutic doses start at  XXmgs, for depression. But after all these years that's cleary not the case , as in life there are shades of gray. I know plenty of people who through trial and error found that say taking 1-2 mgs of Lexapro is the exact break point whereby their symptoms are relieved with the very least amount of side effects.It works for them. Their psych's can argue all they want that they're not even taking therapeutic levels, but very few psych's take these meds and even if by chance it was a placebo effect, who cares, it still works.

 

This thread isn't even about depression or treating it, it's about anxiety and activating the possible anxiolytic effects of Prozac by taking very small amounts and possibly bypassing the well known sides that occur in higher doses. I'm at a loss as to why people would come in and say, but the therapeutic dose for depression is 20mg !!   Maybe it's a waste of time and doesn't really work and ends up going nowhere, but that's what this thread is trying to determine.  I'm curious about it because I have a feeling finasteride permanently knocked out my ability to produce normal amounts of allopregnanolone, If microdoses of fluoxeine raised those levels with little to no side effects then I might be happy. Maybe it doesn't, I don't know.  Low levels of allopregnanolone is not about sexual dysfunction, it governs, mood, sleep, etc. which are my dysfunctions, the things I want to fix.  The next post will be from someone telling me to just take pregnenolone then, the precursor to allo, but again finasteride has knocked out that ability to make the conversion, so no it doesn't work, I've tried. Go on the finasteride forums there's a million trials and suggestions but to this date, nothing works for most.

 

I look forward to hearing from anyone trying microdoses of prozac or even other ssri's. Once I'm done this second round of NSI-189 and baclofen for sleep, and microdosing caapi root that's on it's way, I might try the prozac microdosing myself.

[nowayout]

Their psych's can argue all they want that they're not even taking therapeutic levels, but very few psych's take these meds and even if by chance it was a placebo effect, who cares, it still works.

 

This thread isn't even about depression or treating it, it's about anxiety and activating the possible anxiolytic effects of Prozac by taking very small amounts and possibly bypassing the well known sides that occur in higher doses. I'm at a loss as to why people would come in and say, but the therapeutic dose for depression is 20mg !! 

 

 

FWIW, not all psychs argue that.  My previous psychiatrist suggested microdosing prozac for depression/anxiety.  If you want to try it, be aware that the drug keeps accumulating for about four half lives of the drug (i.e., 4-16 days for its active metabolite norfluoxetine times 4, which gives 16-64 days) before reaching steady state in the body.  Any dose changes will take about the same time to stabilize. 

 

In other words, for any given dose, wait at least two months before making any changes in regimen, unless side effects force you to reduce the dose or drop it altogether before then.  Front-loading (taking a higher dose initially then continuing with the microdose) can theoretically be done to reduce the wait time for attaining stable levels when initiating therapy and for dose increases; however, dose reductions will still take a long time to stabilize. 

 

Why fluoxetine, though?  Shorter half life SSRIs can also be microdosed and will be faster to adjust up and, especially, and to eliminate in case of side effects. 

 

Edited by nowayout, 12 May 2015 - 06:43 PM.

[stillwater]

 

Their psych's can argue all they want that they're not even taking therapeutic levels, but very few psych's take these meds and even if by chance it was a placebo effect, who cares, it still works.

 

This thread isn't even about depression or treating it, it's about anxiety and activating the possible anxiolytic effects of Prozac by taking very small amounts and possibly bypassing the well known sides that occur in higher doses. I'm at a loss as to why people would come in and say, but the therapeutic dose for depression is 20mg !! 

 

 

FWIW, not all psychs argue that.  My previous psychiatrist suggested microdosing prozac for depression/anxiety.  If you want to try it, be aware that the drug keeps accumulating for about four half lives of the drug (i.e., 4-16 days for its active metabolite norfluoxetine times 4, which gives 16-64 days) before reaching steady state in the body.  Any dose changes will take about the same time to stabilize. 

 

In other words, for any given dose, wait at least two months before making any changes in regimen, unless side effects force you to reduce the dose or drop it altogether before then.  Front-loading (taking a higher dose initially then continuing with the microdose) can theoretically be done to reduce the wait time for attaining stable levels when initiating therapy and for dose increases; however, dose reductions will still take a long time to stabilize. 

 

Why fluoxetine, though?  Shorter half life SSRIs can also be microdosed and will be faster to adjust up and, especially, and to eliminate in case of side effects. 

 

 

Thanks, did you try his suggestion? 

 

Fluoextine, because it seems to be the only one mentioned or cited as raising allopregnanolone levels. Otherwise yes if something cleaner like escitalopram was proven to do the same I'd go with it.

 

 

[Un chien andalou]

In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine.
http://www.ncbi.nlm....pubmed/12571361

Prevention of the stress-induced increase in the concentration of neuroactive steroids in rat brain by long-term administration of mirtazapine but not of fluoxetine.
http://www.ncbi.nlm....pubmed/12095071

The second study confuses me... so fluoxetine increases allopregnanolone acutely, but not with chronic use?

Edited by Un chien andalou, 12 May 2015 - 10:27 PM.

[nowayout]

 

 

Their psych's can argue all they want that they're not even taking therapeutic levels, but very few psych's take these meds and even if by chance it was a placebo effect, who cares, it still works.

 

This thread isn't even about depression or treating it, it's about anxiety and activating the possible anxiolytic effects of Prozac by taking very small amounts and possibly bypassing the well known sides that occur in higher doses. I'm at a loss as to why people would come in and say, but the therapeutic dose for depression is 20mg !! 

 

 

FWIW, not all psychs argue that.  My previous psychiatrist suggested microdosing prozac for depression/anxiety.  If you want to try it, be aware that the drug keeps accumulating for about four half lives of the drug (i.e., 4-16 days for its active metabolite norfluoxetine times 4, which gives 16-64 days) before reaching steady state in the body.  Any dose changes will take about the same time to stabilize. 

 

In other words, for any given dose, wait at least two months before making any changes in regimen, unless side effects force you to reduce the dose or drop it altogether before then.  Front-loading (taking a higher dose initially then continuing with the microdose) can theoretically be done to reduce the wait time for attaining stable levels when initiating therapy and for dose increases; however, dose reductions will still take a long time to stabilize. 

 

Why fluoxetine, though?  Shorter half life SSRIs can also be microdosed and will be faster to adjust up and, especially, and to eliminate in case of side effects. 

 

 

Thanks, did you try his suggestion? 

 

Fluoextine, because it seems to be the only one mentioned or cited as raising allopregnanolone levels. Otherwise yes if something cleaner like escitalopram was proven to do the same I'd go with it.

 

No.  I couldn't bring myself to take the risk of taking a long half life SSRI at the time.  I didn't feel like I wanted to spend so many months to recover from it if I had side effects. 

 

[jacobjerondin]

Giving this old thread a nice bump because I'm incredibly fascinated by allopregnanolone- it's nature's benzo and I believe it could be one of the most promising anxiolytics around if we could figure out how to raise it properly. 5A-DHP seems like a good option but I didn't notice much from it, likewise with Pansterone.

 

I would very much hope that Prozac aka fluoxetine could be better for this purpose, and additionally, it very nicely raises BDNF as well at the 1/10 microdose of 2 mg! I really should make a seperate thread about this. Anyway, I believe the OP misinterpreted the study he shared 2 posts above mine.

 

As I understand things, that study was saying that mirtazapine does not raise allopreg. chronically, in contrast to Prozac, which in fact does!

 

Does anyone have experience microdosing SSRIs, or would anyone be willing to try doing so for anxiolytic and/or nootropic purposes! I think there is immense potential here, and these drugs are very easily legally purchasable from internet pharmacies like buy-pharma.md !

[jack black]

i did microdose paxil for a week breaking 1 tab in 8 pieces, felt good, stopped it, and felt like shit the week after. maybe it was too high dose but it was still changing my brain. YMMV.

[pamojja]

https://www.sciencea...otic-resistance

[cat-nips]

Out of Celexa, Cymbalta, Lexapro, Luvox, Effexor and Prozac, I found Prozac to be the least troublesome in terms of side effects, but only at the 10mg dose.  Any higher than that, and the side effects became too prominent.  I was not aware that it came in lower doses than 10mg, but since it has such a long half-life and since it's a capsule with beads, you could consider taking one every 2 /3 days to stay within the micro dose levels.  I remember being able to skip a day and not being too affected, going off and on again a few times, changing dosages and quitting cold turkey without too much pain. Withdrawal issues existed that were slightly annoying, but not as much in comparison to some others.    

 

At 10mg, the sexual side effects were minimal and the usual numbing effect of SSRI treatment presented as just mild anxiety and depression relief. For the first 2 weeks, it gives a lot of physical energy, but not necessarily focus. Its the type of energy that takes you out of hyperfocus mode and makes you feel more social and able to shift attention more easily.  In some folks the initial phase gets translated to anxiety, but seems to calm down after 2 weeks.  I generally found it more helpful than not, going no higher than 10mg, but not significant enough to continue after an insurance/med/doc change. May revisit that someday.  

[jacobjerondin]

Appreciate all the information guys. I do worry a lot about the potential from withdrawals even from microdosing, potentially from downregulating natural allopreg. production? SSRI withdrawals are notoriously bad and jack black's anecdote makes me feel like we should be even more careful.

[cat-nips]

Sorry, correction. It's a smallish capsule with fine powder, not beads, making it messy and somewhat challenging to control microdosing.