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Fluoxetine microdosing as long term anxiolytic?

fluoxetine gaba microdosing anxiety allopregnanolone

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#31 Delton

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Posted 16 July 2019 - 06:24 PM

I know I am late to the party but I am microdosing prozac right now. I was proscribed 5 mg / day about 5 weeks ago but decreased to 2.5 mg after feeling very fuzzy the first 2 weeks. Concommitant with starting prozac I have had a lot of sleep issues (early morning awakening, trouble getting into deep sleep, waking up for 1-2 hours each night) but I'm not sure how much of that was caused by the Prozac (could be a side effect of depression / stress). Recently I decreased further to 2mg / day. I can provide an update in a few week if anyone is interested. 

Here's the study on socially isolated mice showing how Prozac increases "allo" at low ("sub SSRI") doses - which can help with anxiety
 

 

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#32 jacobjerondin

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Posted 17 July 2019 - 02:44 AM

Wouldn't using etifoxine and/or pregnenolone +DHEA (or 5a-DHP) be a much cleaner way to replicate a lot of the good results of this boosting neurosteroids like allopreg without the potential side effects and withdrawals of SSRIs?



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#33 KingBrown

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Posted 31 July 2019 - 10:35 AM

 

I know I am late to the party but I am microdosing prozac right now. I was proscribed 5 mg / day about 5 weeks ago but decreased to 2.5 mg after feeling very fuzzy the first 2 weeks. Concommitant with starting prozac I have had a lot of sleep issues (early morning awakening, trouble getting into deep sleep, waking up for 1-2 hours each night) but I'm not sure how much of that was caused by the Prozac (could be a side effect of depression / stress). Recently I decreased further to 2mg / day. I can provide an update in a few week if anyone is interested. 

Here's the study on socially isolated mice showing how Prozac increases "allo" at low ("sub SSRI") doses - which can help with anxiety
 

 

 

How are you doing with this now?

 

Are you still on the same dose?



#34 Delton

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Posted 07 August 2019 - 01:28 AM

How are you doing with this now?

 

Are you still on the same dose?

 

 

Thanks for asking... I am still taking 2.5 mg but I've been experiencing constant insomnnia. I keep up at 4-5 am and then never get fully back to sleep. I can't tell if the insommnia comes from depression or the prozac, but I suspect the prozac because it started around when I started taking it. Im taking trazodone 40-50mg a night now which has helped but some nights I'm still not sleeping well. I'm thinking of disconintuing prozac soon and just take supplements and 5-htp to ward off any bounce-back depression. 



#35 genX

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Posted 10 August 2019 - 03:38 AM

I've been taking 10 mg Prozac for about 15 months which is considered a rather low dose (initially to stop my blood pressure from constantly raising in the afternoon/evening after I had an adrenal crash which led to anxiety).   It caused me more anxiety during the day for the first few months but did stop my blood-pressure from rising in the afternoon/evening  but then I couldn't tolerate it (it gave me "kidney" pain and too much stress if I took it 2 days in a row) so I stopped it completely for a month.  I might add that it also increased my libido - I would get horny after taking it - and I was already taking Ativan to sleep before I started taking it.  

 

Getting back to what I was saying,  I stopped taking Prozac for a month but then found that my mental state was degenerating (I assume that this was a withdrawal effect) and so went back on it (10 mg) and found that it did not bother me any more, and my mental state improved.  I might add that a Genesight test showed that SSRIs are generally not so good for me (and my problem was not depression but anxiety) because I have low serotonin transport.  However, Prozac was the best of the SSRIs for me according to  Genesight (although apparently I metabolize it slowly so a low dose makes sense).   Also, I think it's generally believed to be one of the safest SSRIs with the least side-effects (although other people I know who had depression found that Paxil worked better for them).   One interesting thing about Prozac, besides the very long half-life, that may put it in a different class is that apparently it increases BDNF (brain-derived neurotrophic factor) so it has some good attributes as well.

 

Getting back to my story, I went back on 10 mg Prozac in November and found its effectiveness as an anxiolytic reached a peak around May and then appeared to decline somewhat and I had more trouble sleeping (also probably the Ativan has become less effective as time goes on).  I recently tried doubling the dose for 4 days as an experiment but felt more zombie-like and more "anti-sexual" side-effects which I didn't like so went back down to 10 mg/day for the past few weeks.   My plan now is to go down to 5 mg day and I'm guessing that will be more effective at (a) reducing anxiety (b) improving my sleep due to the reduced "activating" effect © perhaps assisting me in eventually weaning myself from the Ativan to sleep... we'll see.    While everyone is different, I would also point out that all medications typically have a "U-shaped" response curve, e.g. there is an optimal amount such that more than this amount or less than this amount is less effective or causes more side-effects.   My conclusion is that the premise of this thread, e.g. microdosing Prozac for anxiety, is very interesting and makes a lot of sense to me, but the actual optimal "microdose" depends on the person.  

 

 



#36 genX

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Posted 10 August 2019 - 03:45 AM

One other point which I forget to make since some questions were raised regarding this.   Prozac can also be obtained in a 10 mg tablet form which can be split (it has a notch) to reduce the dose easily to 5 mg.  Also a compound pharmacy can provide lower doses (by liquid dilution).  Useful for gradual withdrawal or microdosing.   There's also the possibility I suppose of only taking part of a capsule, or pulverizing the tablet and using this to reduce the dose further.  These alterations may affect the kinetics however.  For the person whose now taking 2.5 mg/day (Delton) I'm curious to know how you are taking it.... is it in pill or liquid form?

 



#37 noos

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Posted 14 August 2019 - 09:22 PM

"However, Prozac was the best of the SSRIs for me according to Genesight (although apparently I metabolize it slowly so a low dose makes sense"

Do you have an abcb1 gene variant ? Iread prozac is the only ssri that crosses BBB in same variant.

#38 genX

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Posted 15 August 2019 - 02:44 AM

noos,

     This is an interesting question.  I'm not sure which abcb1 gene variant you're referring to.   My rs1045642 genotype is GG while my rs2032583 genotype (which apparently controls BBB effect on SOME medications) is AG. 

 

See also:  https://www.survivin...-snri-response/ which lists 9 abcb1 sites which affect BBB transport.  

 

See also: 

Polymorphisms in the Drug Transporter Gene ABCB1 Predict Antidepressant Treatment Response in Depression

 
Here's a quote from above article which indicates that Prozac (fluoxetine) and mirtazapine BBB transport may not be affected by abcb1 variant:
 
"The mouse model reported herein allowed us to show in earlier studies that citalopram, venlafaxine, paroxetine, and amitriptyline were substrates of P-gp at the blood-brain barrier, while mirtazapine and fluoxetin were not. "

 

 

I still didn't know which variant I have.  The only other SSRI I've tried was Sertraline (Zoloft) and I only tried it for one day since it gave me stress and horrible stomach pains.

 

See also:

 

Curr Pharm Des. 2011;17(26):2843-51.
The clinical impact of ABCB1 polymorphisms on the treatment of psychiatric diseases.
Author information
1 Max Planck Institute of Psychiatry, Munich, Germany. rosenhag@mpipsykl.mpg.de
Abstract

Polymorphisms in the drug transporter gene ABCB1 account for differences in the clinically efficacy of the most drugs, most likely by influencing their access to the brain. The majority proportion of depressed patients, given a regular dose, do not respond properly or experience severe side effects. One explanation may be the polymorphisms in the drug transporter gene ABCB1, which account for differences in the clinical efficacy of antidepressants, neuroleptics or mood stabilizers most likely by influencing their access to the brain. If patients are treated with a substrate of P-gp, functionally relevant genetic variants in the ABCB1 transporter could influence intracerebral drug concentrations and, thereby, clinical response. The review shows recently investigated clinical impact of ABCB1 variants including the three most important SNPs rs1045642, rs2032582, and rs2032583. In the paper, with respect not to go beyond the scope of this review, we will focus on these three SNPs. The final goal of pharmacogenetics is to help clinicians to choose the best treatment for each individual patient. >From the evidence reviewed in this publication, it is likely that combination of metabolizing and drug target polymorphisms will produce the best prediction for the selection of the optimal dose and optimal drug as a function of the individual` s genetic profile.

 

Also:

 

s2032583 is a SNP in the ABCB1 gene (also known as the MDR1 gene), which encodes a protein that transports certain molecules across the blood-brain barrier. SNPs in ABCB1 may thus influence the intracerebral concentrations of certain drugs and thus their efficacy or potential for adverse side effects. rs2032583 is one of 9 SNPs found within a tight linkage block (r2 >= 0.8 ) such that the minor allele at any one of them predicts (with ~80%+ accuracy) that the other SNPs will also be the minor allele. The list of the 9 SNPs is shown below.

When treated for depression with substrates of the protein encoded by ABCB1, carriers of one or two minor alleles at these ABCB1 SNPs have been reported to respond better than non-carriers. The antidepressant drugs that are known to be substrates include citalopram, paroxetine, amitriptyline, and venlafaxine. The relative odds of better response for rs2032583© carriers is 7.72 (CI: 2.8-21.3, p=0.000065) based on a study of ~400 primarily Caucasian patients.10.1016/j.neuron.2007.11.017

The 9 SNPs in the linkage block identified are 10.1016/j.neuron.2007.11.017:

 



#39 Delton

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Posted 15 August 2019 - 03:14 PM

I've been taking 10 mg Prozac for about 15 months which is considered a rather low dose (initially to stop my blood pressure from constantly raising in the afternoon/evening after I had an adrenal crash which led to anxiety).   It caused me more anxiety during the day for the first few months but did stop my blood-pressure from rising in the afternoon/evening  but then I couldn't tolerate it (it gave me "kidney" pain and too much stress if I took it 2 days in a row) so I stopped it completely for a month.  I might add that it also increased my libido - I would get horny after taking it - and I was already taking Ativan to sleep before I started taking it.  

 

Getting back to what I was saying,  I stopped taking Prozac for a month but then found that my mental state was degenerating (I assume that this was a withdrawal effect) and so went back on it (10 mg) and found that it did not bother me any more, and my mental state improved.  I might add that a Genesight test showed that SSRIs are generally not so good for me (and my problem was not depression but anxiety) because I have low serotonin transport.  However, Prozac was the best of the SSRIs for me according to  Genesight (although apparently I metabolize it slowly so a low dose makes sense).   Also, I think it's generally believed to be one of the safest SSRIs with the least side-effects (although other people I know who had depression found that Paxil worked better for them).   One interesting thing about Prozac, besides the very long half-life, that may put it in a different class is that apparently it increases BDNF (brain-derived neurotrophic factor) so it has some good attributes as well.

 

 

 

 

Hi.. I apologize for taking so long to respond. Are you male? I have found it completely crashed my libido. About a week ago I increased to 5mg. I've been having a lot of trouble sleeping since I started prozac and the past 2-3 weeks I've also been taking 50 mg of trazodone each night to sleep. I feel fatigued and sleep deprived during the day even though I'm getting ~7 hours of sleep. (before starting prozac I usually got 8 hours). 

You mentioned BDNF - that is very exciting. My understanding is that all SSRIs increase BDNF but it would be interesting if Prozac is somehow special in this regard. 

 

 

 

One other point which I forget to make since some questions were raised regarding this.   Prozac can also be obtained in a 10 mg tablet form which can be split (it has a notch) to reduce the dose easily to 5 mg.  Also a compound pharmacy can provide lower doses (by liquid dilution).  Useful for gradual withdrawal or microdosing.   There's also the possibility I suppose of only taking part of a capsule, or pulverizing the tablet and using this to reduce the dose further.  These alterations may affect the kinetics however.  For the person whose now taking 2.5 mg/day (Delton) I'm curious to know how you are taking it.... is it in pill or liquid form?

 

The tablets are 10mg, scored for cutting in half - and my psychiatrist said I should cut them in half. The tablets are not enteric coated. So the pharmacodynamics should not be effected. 



#40 cat-nips

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Posted 22 August 2019 - 04:09 PM

Plan on revisiting Prozac microdosing in the near future as I'm currently going through increasing periods of agitation and irritability of which I can't determine the cause of.  Currently don't take anything serotonin based at the moment.  Of all the SSRIs, I found Prozac to be the most helpful and least bothersome but only at 10mg.  Anything more turned me into a total zombie, much more akin to being content just staring at the wall type of thing.  

 

10mg is enough to improve energy, outlook, mood, social functioning.  The negatives:  sexual side effects even at that dose, and I lose the ability to hyperfocus or even sustain focus on anything for very long.  It seems to be a tradeoff that I have to make over and over at various times. 

 

This time, I'm going to try 5mg by opening the capsule and weighing the contents and halving them.  I'll start by dosing every day for a few days to get levels up and then go to every other day due to the 5-day half-life.   

 

@ Delton: Anecdotally, any SSRI I've ever tried has the early morning awakening effect for me.  Could be that serotonin has effect on circadian levels?  I've had this happen with even 5-htp, but not consistently the way that SSRIs do.  As for the fatigue, I'd consider looking at the 50mg Trazadone.  I don't know about chronic use, as people say it gets better over time, but 50mg Trazadone was enough to put me out for 18 hours and left me foggy for 2 days, even with taking stimulants to counteract it in the morning.  Repeated dosing only made mornings worse and more exhausting and intolerable.  When I trialed Trazadone for sleep, I was lucky to get 3-4 hours and was desperate for relief, but a couple days on it was enough for me to never want to touch it again, and go back to my sleepless ways while exploring other alternatives.  I'd be awesome with 7 hours, but I know everyone is different.  These days, I get around 5-6.  I take Magnesium blend at night at full dosage which seems to help, and cycle things like Lemon Balm tea and Melatonin.  Way more subtle but still better than dealing with the fatigue the next day.

 

  



#41 Delton

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Posted 31 August 2019 - 08:23 PM

 

 

@ Delton: Anecdotally, any SSRI I've ever tried has the early morning awakening effect for me.  ...  These days, I get around 5-6.  I take Magnesium blend at night at full dosage which seems to help, and cycle things like Lemon Balm tea and Melatonin.  Way more subtle but still better than dealing with the fatigue the next day.

 

Update - about a week ago I went down to 2.5 mg because I couldn't get more than 6 hours of sleep on 5mg. I have been feeling much better and after talking to my psychiatrist I think I will stay on this dose for a while. I am also experimenting with SAM-e, which seems to boost my mood / energy level. 

 

I will probably try magnesium again soon to further help with sleep , it can't hurt. 

 

The most important thing for me to do in order to sleep is running - I'm trying to get up to running every day. 

 

I also just want to say thank you to everyone who has helped me !



#42 Daniel Cooper

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Posted 10 January 2020 - 04:11 PM

Did anyone trying this feel like they got a sustained benefit?

 

How many are still doing it?

 

 



#43 Delton

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Posted 17 January 2020 - 09:15 PM

Did anyone trying this feel like they got a sustained benefit?

 

How many are still doing it?

 

I'm still doing it, taking about 2mg per day. It's mostly because I'm afraid to go completely off it. It definitely lowers my libido, but not too much. It's hard to tell if I'm getting a lot of benefit from it since there are many other factors. theoretically it's supposed to have an anti-anxiety effect at these low doses due to the neurosteroid "allo".

 

Possible confounds are that I'm also taking SAM-e, lots of fish oil and creatine, and a small amount of wellbutrin instant release (18.75 mg 3 times a day). I'm thinking of going completely off the prozac since it always has seemed it made it harder to sleep (even more so than wellbutrin!) .

 

The small dose of wellbutrin I think has been helpful in boosting my energy levels. I may go higher soon.  



#44 Daniel Cooper

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Posted 17 January 2020 - 09:44 PM

I'm looking for an anti-anxiety effect with I would hope minimal side effects.

 

I do believe that fish oil is supposed to be synergistic with fluoxetine so maybe that isn't a confounding factor.

 

I'm 5 years recovering from a prescribed z-drug and I've got to do something about a completely trashed gabaergic system that has left me in quite a bit of physical pain and with very bad anxiety.  Kind of running out of options.

 

 



#45 cat-nips

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Posted 27 January 2020 - 12:23 AM

Still microdosing, myself.  Always at 5mg or less.  Sometimes every day, sometimes every other day.  When I stop I get some discontinuation - chills, fatigue that last for a week or two at most, but nothing too crazy.  A few weeks go by before I notice that I am nearly chronically exhausted, irritated and unhappy and unable to enjoy life at all in ways that I used to. So I start again, and within the first dose or two, get some relief from fatigue, depression and IBS symptoms.  Also get the near obliteration of libido and the early morning awakenings happen to me as well.  This isn't a bad thing for me because I'm a chronic insomniac and mornings are usually an issue.  When on Prozac, I fall asleep before 12, and wake up by 5-6a and for me, this is a great thing because I'm used to way less and never feeling fully awake until the evenings, which makes it habitually difficult to sleep.  So it fixes circadian rhythms in some ways, but I take it pretty much first thing in the AM, and have noticed that it keeps me up when taken later.

 

I've tried Pregenelone.  It's mildly helpful.  Maybe I didn't dose highly or consistent enough, but I'm leery of tinkering too much with the hormones.  Still, at 25 or 50mg sublingual, it still didn't compare to what <10mg of daily Prozac does.  DHEA helps mildly, but raises blood pressure and heart rate too much.  Again, it's a hormone so I really can't tell how safe it is to supplement for depression or anxiety issues.  

 

I've seen the conflicting info and have had a mixed relationship on and off this med at various dosages over the last two decades.  Have also tried countless others, yet I still stick to microdoses of Fluoxetine and continually come back to it for periods.  It's the only thing that I take for depression/anxiety symptoms that consistently works for me at smaller dosages.  Anything over 10 and under 40mg, provide that same fuzzy zombied out effect of most other SSRIs, maybe because of the 5ht2c antagonism weakens?  At 60-80mg, it also changes and acts differently, but for me that translated into a total loss of inhibition and engaging in behavior that was too reckless to be considered healthy.  

 

Sam-E looks interesting.  Glad to hear it doesn't interact with the Prozac.

 

Not sure what z-drug is, Zoloft?  If so, maybe it could help, but otherwise, I would think there are better options than Prozac to treat physical pain, and high anxiety.  It can actually increase anxiety for a few weeks when you start taking it as I believe it's one of the more activating SSRIs.  

 

If there is a safer alternative then I'd be very curious to hear about it. 

 

 

 

 

 

 

 



#46 Daniel Cooper

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Posted 27 January 2020 - 03:31 PM

Z drugs are "non-benzodiazipines".  They essentially do the same things as benzos, bind to the same receptors (but are alleged to be more selective), but they are chemically distinct from benzos.  Normally prescribed for sleep.   Zopiclone, Zopidem, Zaleplon, etc.

 

They were touted as having the same effects as benzos with none of the downsides.  That was of course total bullshit. You can't bind to the same receptors without causing the same problems.

 

Z-drugs are the third generation of gabaergic drugs that have had similar problems - barbiturates, benzos, z-drugs.  Now that the problems with the z-drugs are becoming recognized, I don't doubt we'll get a 4th generation drug in a few years and it will have similar issues as well.  Basically, taking a positive allosteric modulator of GABA receptors for any extended time is probably going to be a bad idea.

 

 

 

 



#47 cat-nips

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Posted 27 January 2020 - 05:53 PM

Had no idea. Thanks for the info. Have you looked into Ashwagandha? That works on GABA, I believe, but probably not to the effect of the Z-meds. Anything else I can think of that works on GABA comes with a whole bunch of other problems, so agreed on that. Withdrawals suck so I’m sorry for the pain and hope you find a workable solution. Best of luck.

#48 Delton

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Posted 04 February 2020 - 12:29 PM

I have an update -- I am stopping microdosing. 

 

Takeaway is it helps with anxiety and depression. however, these are the issues I've had and still have which I've decided I'm sick of:  

 

I keep waking up in the morning after 5-6 hours of sleep and then can't get back to sleep.

Low libido

 

I think one or both of these are related to the microdosing of prozac. So I'm tapering down to see if it helps. Also just read a workbook on CBT for insommnia and trying to put things into practice (consistent bedtime, don't nap during day, etc). 

I'm also taking 75 mg of wellbutrin instant release, split through the day (I know this is odd, but I'm very sensitive to stufff). 

The early morning awakening problems started before the wellbutrin, so I believe it's related to the prozac. I'm not feeling depressed, so I don't think the early morning awakening is from depression. 

 

Finally.. I'm experimenting a bit with 100mg 5-HTP before bed. Seems to help. I don't think my brain is used to not being on a serotonergic agent. 



#49 DaveX

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Posted 04 February 2020 - 02:16 PM

Fluoxetine definitely does have sexual side-effects, I don't know where someone always digs up this or that (e.g. Risperidone) supposedly has no side-effects. It does. Don't jump on any vague, speculative claim that it might have less side-effects, when concrete reports of side-effects are always systematically ignored and thrown into a "what is real anyway"-doubt (kind of inconsistent methodology or agenda). I always had sexual anhedonia on Fluoxetine.

Edited by DaveX, 04 February 2020 - 02:19 PM.


#50 Delton

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Posted 04 February 2020 - 04:41 PM

Fluoxetine definitely does have sexual side-effects, I don't know where someone always digs up this or that (e.g. Risperidone) supposedly has no side-effects. It does. Don't jump on any vague, speculative claim that it might have less side-effects, when concrete reports of side-effects are always systematically ignored and thrown into a "what is real anyway"-doubt (kind of inconsistent methodology or agenda). I always had sexual anhedonia on Fluoxetine.

 

Amen! 

 

Yes a vast majority of early studies only made note of side effects *** that people reported***. A lot of people don't report sexual side effects!  What dose were you taking? 

 

For some the sexual anhedonia is a trade off worth accepting but no longer for me!



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#51 DaveX

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Posted 06 February 2020 - 10:06 PM

I don't remember the dose, it was a normal dose, no micro-dosing. And while there are certainly studies confirming the side-effects, the side-effects still tend not to be taken seriously, and quite often there is projective speculation about some side-effects being less severe (also by laypersons, of course), which often gets disproven. Especially long-term sexual side-effects are disputed with almost ideological fervour.

There are also different generations of neuroleptic drugs, with the newer ones obviously having a better reputation about side-effects, although this means very little, only that the earlier versions must have been truly horrid.


Edited by DaveX, 06 February 2020 - 10:20 PM.






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