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bubbles

Delayed withdrawal symptoms & "late onset" depression as a WD effect -- looking for journal articles

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bubbles

Hi everyone

 

I'm trying to gather some resources - primarily journal articles or perhaps official guidelines. I am specifically after resources on two topics, but I'll make separate threads for them.

 

I have observed that many people seem to be okay for a bit after dropping meds - a bit being 2-3 months - and then there is a crash. This was my experience with my too rapid taper off Lexapro. (This isn't about me, so I'm not putting it into my personal thread. I was unable to get anyone to see it my way though. :) Absolutely no providers were prepared to entertain the possibility of a delayed withdrawal reaction. Still, it has come up so often that I feel it must exist.

 

I have been looking through the journal articles and trying to find some on my own too. So far I have found nothing that specifically documents this phenomenon. Is anyone aware of anything that I might have missed?

Cheers everyone,
Bubbles

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bubbles

I should say that that crash is probably after a too-fast taper.

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Altostrata

bubbles, this is a great question. In fact, I've tried to pursue it lately.

 

The assumption that withdrawal symptoms start immediately upon cessation appears in Schatzberg, 1997

 

You need to look at the citations for this assertion and trace it back through the years. Schatzberg, 1997 got its information from an earlier paper. Where did that paper get its information? And so forth.

 

By picking apart the trail of evidence, we might be able to show that the assumption in Schatzberg, 1997 is groundless and open up the question to new study.

 

This would be very valuable to a research project I'm working on right now (with CEPUK, Luke Montagu and Dr. James Davies), to be presented to a UK parliamentary committee.

 

If anyone wants to get involved in this, please let me know.

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bubbles

Thanks Alto. That's a great starting point. If I find anything useful for you I'll pass it on.

Cheers!

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InvisibleUnless
On 5/3/2018 at 9:19 AM, Altostrata said:

The assumption that withdrawal symptoms start immediately upon cessation appears in Schatzberg, 1997

 

You need to look at the citations for this assertion and trace it back through the years. Schatzberg, 1997 got its information from an earlier paper. Where did that paper get its information? And so forth.

 

i would be entirely unsurprised if you trace this back to someone importing it from the descriptions of other psychotropic withdrawal syndromes without doing any sort of representative trials to vet its application to antidepressant withdrawal symptomology.

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bubbles
5 hours ago, InvisibleUnless said:

i would be entirely unsurprised if you trace this back to someone importing it from the descriptions of other psychotropic withdrawal syndromes without doing any sort of representative trials to vet its application to antidepressant withdrawal symptomology.

 

That's a really good angle to take in my searching - thank you!

 

 

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Altostrata

bubbles, if you find anything about the origin of the immediate-onset theory, please let me know.

 

The citation in Schatzberg, 1997 appears to be incorrect. It is a report from the Australian government about withdrawal reactions and does not mention onset.

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bubbles

Thanks Alto. I'll keep looking. It's a slow process because I'm fitting it in among other things and this is a busy time. I'll let you know if I find anything.

 

That 1997 article - says there is "free full text" but I can't get it. :( I don't think I have enough information to find that Australian report, which might be useful, because it is clearly 20 years old.

 

 

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InvisibleUnless

the "psychiatrist.com" free full text links are to a page which requires you to enter in some personal information and credentials--you can only access the full article if you sign in.  i gather they use this information for data commercialization.  i feel like this was not always the case, but my memory may just be foggy on the notion.

 

libraries (especially school libraries or inter-library loan programs), asking your healthcare provider to snag you a copy, or writing to one or more of the authors can be tenable ways of accessing full texts.  databases like deepdyve can also provide free access to some articles in a roundabout way.

 

there are also manners in which you can allegedly infringe upon 'intellectual copyrights' in order to secure a pdf, but if you want to keep things squeaky clean then i would avoid those methods even though nobody is getting hurt and it is sometimes a legal grey area (only sometimes!).

 

i think you will probably have to end up writing to someone anyhow--someone involved with the government report, or who can at least tell you more about it.  such reports, at least in the versions offered online to the public, rarely reveal the sources of facts like the ones being incorporated in the Schatzberg article.

 

and even if you bedrock at 'expert opinion', that doesnt really tell us how that opinion came about.  prescribing experiences?  unpublished trials?  talking with other doctors?  it is a rabbithole, for sure.  if youd like to delegate anything to me, i can put some of my time into digging around, just let me know what would be most helpful.  i cannot guarantee enduring contributions, but i would like to help in what ways i can.

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bubbles

Thanks InvisibleUnless

 

I've come up to a busy time at work and school, so I've had to park this bit of research, but I still want to follow it up. I didn't know about deepdyve, so I'll follow that up.


I will get back to it, but I have to prioritize some other stuff first.

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Barbarannamated

This is what happened to me in a sloppy taper of Pristiq in 2010-11 (if I recall correctly).  I was waiting for brain zaps like I had when I was late with a dose of Effexor, but they never happened, so I marched on.  I recall that I actually felt energized and, judging by the screen name and crazy heading I came up with, perhaps a bit hypomanic..?  In retrospect, I was very disconnected, dissociated...weird. There was also someone i know stalking me online, which was 100% factual, but added to the weirdness. 

 

I don't know when I crashed, but I think it was roughly 3 months out and I've never fully recovered.  There are several drugs involved, but this was specifically after Pristiq *taper*.  I even ended up hospitalized for bradycardia. 

 

If I can help in any way, I certainly will.  I have far too much free time and have to be careful about what I focus on.  Social media (Facebook) is not my friend. 

 

I was mildly fatigued and a bit "blah" (not depressed) when I was given Zoloft samples by an MD friend long ago.  I have no basis of comparison for this withdrawal state.  

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bubbles

@Barbarannamated I often wonder whimsy made me choose Bubbles as my name here. I am not the Bubbles type! Bubbles seem optimistic so that's probably it.

 

Unfortunately, I think it is going to be a long project, trawling through papers and following citations back to their papers and so on. It may also be that I have to accept papers calling it relapse without explanation. Perhaps comparing relapse rates for unmedicated people, people with wd and people staying on. I think Robert Whitaker has looked at that. 

 

Stuart Shipko mentions it, but I think he is talking observationally about his clients, not research. Still, perhaps it is worth contacting him to ask.

 

Also, Robert Whitaker talks about worsening chronicity with them, which might have to do with WD but I don't think that's considered - I think he's looking more at population level data about being on disability etc. I don't have his book, I should see if I can get it through my library.

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Henosis

I’ve also been baffled by this and always searching for new information. Some of the newer Fava papers mention “late onset” or “delayed onset”, but I’ve never seen anything concrete.

 

Shipko and others think it’s a tardive reaction, but I have always been skeptical after experiencing it. When I stopped Paxil, the months leading up to full-blown withdrawal were uneventful and I didn’t experience any change in anxiety or OCD symptoms. I would have assumed I would have at least returned to a baseline, pre-SSRI state during this period. It seemed like the drug was still active in my brain during this time.

I did find an interesting paper examining Celexa washout. They only had six people, but it showed an approx. 3x longer half-life in the brain than blood plasma. Obviously that doesn’t explain a multi-month delay, but perhaps with some people with genetic variations / long duration of use, this actually gets extended to weeks or months.  Food for thought anyways, I am not a neurobiologist.

 

 

 

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bubbles

It is an interesting thought.

 

A related idea is the thought that the drug might be stored in our fat for a while. I have read something by Healy, I think, suggesting this, and that it might soften the withdrawal for a bit. If that is the case, I imagine it could have the effect of a delayed withdrawal. That is - it might give you effectively an extra long "half life" so you did discontinue it in March, but you've still got a bit in your system until June or July and then it's all gone.  However, I think Healy's just hypothesizing, not that he has anything concrete. Or, frankly, how you even measure that! Or the mechanism by which it might come out of our fat etc.

 

I think it is only a hypothesis, but I wonder if it might have some merit. I have a vague idea I've seen an issue somewhere that babies might still have somewhat increased risks if mom discontinued the drug even some time before the pregnancy. I'm not sure where I saw this, or how the timing worked out - ie, if it was up to a year, or if the taper was rapid etc etc. Still, it stuck in my mind and when I recently read Healy's thoughts it made me think. Worth following that up, come to think of it.


I might get in contact with Healy and ask if he has anything more on the topic.

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Bee5

Hi bubbles,

I am fascinated with this topic. I have experienced the akathisia/terror/suicidal ideation combination symptom three times in my life. I want to share these events with you in the hope that they might provide some leads for you to follow:

  1. Cold turkey off escitalopram when I found out I was pregnant. Pregnancy was fine (people speak of the phenomenon of the 'protective effects of pregnancy'), got a bit of anxiety toward the end of pregnancy. Full-on akathisia-terror-suicidal ideation within 6 days of baby's birth.
  2. Benzo cessation withdrawal following polypharmacy for postnatal depression. Full-on akathisia-terror-suicidal ideation within a period of days, not weeks or months. 
  3. Tapered off paroxetine, over 6 months (too fast), was "fine" except for some brain zaps. Four months after cessation, full-on akathisia-terror-suicidal ideation.

From the above three events, I have some ENTIRELY ANECDOTAL theories, which might help you with which directions to pursue in your research:

  • I have not encountered any overweight moms that got postpartum anxiety/depression. Therefore, I wonder if increased body fat percentage has some protective effects?
  • The akathisia I experienced was the same 9 months after cessation of escitalopram, few days after cessation of benzos, and 4 months after cessation of paxil, so it seems to me that the akathisia is a CNS regulation effect, rather than specific to certain receptors, since benzo/SSRI receptor modulation is different (to my knowledge)
  • I have read that brain zaps are linked to central temperature regulation (this is why some people get brain zaps when they have fever as a result of illness).
  • I hypothesise that SSRIs 'fill up' some storage system in the brain, which takes months to 'drain' and I think this is why people get protracted withdrawal.

Please keep us posted on this thread if you find anything related to why withdrawal is protracted/delayed.

 

Thank you for helping us find answers.

 

Regards,

Bee

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marconyc

Is it possible that the delayed onset of withdrawal is related to the effect of SSRIs on neurogenesis? If these drugs work in large part through promoting neurogenesis, that might help explain the delayed onset of effect and the delayed onset of withdrawal. I imagine that neurogenesis would take longer to increase and decrease than, say, the effect on reuptake.

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bubbles

Hi @Bee5 and @marconyc

 

Bee5, I certainly thought I was fat after my babies (gosh, I wish I could be as "fat" now, lol) but wasn't. I did know an overweight mom who had PPD though, and she was the only person I knew who was medicated for it back then (20 years ago they weren't handed out like candy quite as much).


I experienced the feeling of wellbeing from pregnancy. I've read a journal article that said that it didn't exist, or at least not in the case of antidepressant withdrawal, so I wonder if the WD can be too much (at least sometimes) for the wellbeing to cope with. If that makes sense... There is so much (hormonally) going on during a pregnancy and after the birth.

 

I have described the feeling of the delayed reaction as "the brain having enough of a store of whatever, and then running out", which is much the same as what you're saying. I do think the incidence of delayed WD is massively understated. I've seen a bunch of youtube videos where people "successfully" get off them over a few weeks, then a few months later they've "relapsed" and are back on meds. This was the case with one of the gentlemen who have "invented" the tapering strips - he used them (and presumably avoided the zaps/acute stage) but then ended up depressed and back on them again. He interpreted it - as I think most people do - as their next episode. Maybe it is. My own experience, according to the likes of Glenmullen, was more likely relapse than withdrawal. But it is so common that there must be more to it than that.

 

Marconyc, there just hasn't been any research into any of this, so I don't think anyone could comment. It would be something worth considering though - maybe in light of the next sentence. "Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death)" - from this link:

 

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peng

In my 2-year taper of effexor ending this summer with a crash, and back on 100mg XR today, I was certainly feeling good until below 60-70mg.

There was a definite lag of several weeks in depression/anxiety flashes/extreme fatigue/loss of appetite returning.  

The same thing happened in 2006 when I tapered rapidly to zero without the knowledge we have today with, e.g, SA.

I was doing outside work in frosty weather in February 2006 for part of that time.  Possibly a bit manic?  A few days later I found myself weeping during - of all things - a tv documentary about a hero of mine, Quincy Jones.  Stuff about his early youth, IIRC.

Next day or so I found myself at my GP's who implied that if I had stopped the reduction at, say, 75mg, "we wouldn't be having this conversation now".

 

As for the 2016/2018 taper from 225mg. I find myself wondering if I was as conscientious as I think I was in carrying it out.

It is easy to press on with dose reductions when you are feeling "not too bad"?

Thus, essentially, tapering too fast.

Saw the same GP as 12 years ago (who is senior man with knowledge and experience that I respect)and from my excel spread sheet of dosage/mood, confirmed that I seem to be at my best at 150mg dose - one of the threshholds at which effexor can work best.  (Curse it.)

 

 

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Bee5

Allow me to use the analogy of the brain being a sponge. Considering the fact that something causes the sponge to fill up, and then a few months after cessation the sponge becomes empty, how were we functioning before the first "fill"? Or did life events drain the sponge initially?

And if we look at the stories on this site, it seems impossible to come off these meds because once the sponge is empty, horrific symptoms ensue, and most people end up reinstating (except those fortunate enough to have a support structure/system that allows them to become housebound).

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bubbles

Hi @Bee5

 

The way I think it happens - when the brain is unmedicated, it makes the right amount of chemicals. When we take meds, it seems that the brain reduces its output of the chemicals to compensate for all of the extra chemicals coming from the brain. The brain/sponge - after an initial stage - reduces output so that the "correct" amount of chemical is floating around. We remove the meds and the brain can't go back to normal quite fast enough, so the filling is too slow. The emptying continues as usual but this is going to


I'm confident that it does eventually go back to normal, or I wouldn't be tapering, but I have no idea how long it might take to return to normal.

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Bee5

I am holding thumbs for both us of to be able to come off the meds eventually. I am just astounded that there isn't more research going into the topic of protracted WD, and on finding 'markers' to understand what is happening chemically.

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peng
2 hours ago, Bee5 said:

Or did life events drain the sponge initially?

 

Yes.  For myself, I have come to the view that childhood/youth trauma/PTSD did do that.

One can read of the brain being altered/remapped during early life by such occurrences.

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Bee5

Thanks for the insight @peng. I would certainly be interested in finding answers for how/why external experiences (university and family stress in my case) can change/affect neurotransmitter production and/or receptor modulation.

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