• N&PD Moderators: Skorpio | thegreenhand

Can somebody explain the mechanism? (Damage after Antidepressant/Antipsychotic Use)

Yes I did. They said it's not from the medication, lol.
I suggest you go to another doctor then, hopefully one who's more competent. I think the meds definitely played a role in this, because all of this sounds disturbingly similar to the sort of benzo withdrawal could expect after several months of continuous heavy (ab)use. But even then the duration is usually a matter of days not months, and it's hard to understand how any drug, no matter how potent, could ever trigger such severe WD symptoms after barely a week of use (let alone ones that last this long)...some sort of atypical PAWS perhaps?

Why were you put on those meds in the first place? Bipolar and drug-induced psychosis are the two obvious possibilities that come to mind, but it's also not unheard of for either of those meds to be given for severe insomnia (although I would think not both of them at the same time, and certainly not both started on the same day). Those symptoms could be part of an agitated depressive episode, possibly precipitated by the sudden discontinuation of the meds.
Were you taking anything else prior to taking those two meds? If so, had you had a bad reaction to it, and did you stop it abruptly at the same time you were put on the meds?
Did you have a history of insomnia or any sort of sleeping problems beforehand?
 
Seroquel in particular has a high rate of restless legs syndrome/akathisia. I believe this is thought to be due to its high affinity for D1 dopamine receptors, compared to e.g. Risperidone which has a much higher D2 > D1 ratio.

The Ventral Tegmental Area (a target of anti-psychotics) is known to play a role in sleep/wake behavior (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519826/) and of course a pivotal role in the development of antipsychotic related dyskinesia
 
Yeah, it definitely sounds like he was put on way too high a dose, and most likely not titrated properly either (I've heard of people going from 0-800mg in 3 days, which is utterly insane). But I'm still not entirely confident that even all of that, alone, could be the only thing responsible the kind of protracted and extreme withdrawal he's going through.
 
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Mirtazapine and such can cause some issues with RLS etc as well, so that may not have helped. That was probably a whole lot of 5-HT2C antagonism/inverse agonism between those two meds. 5-HT2C being the most populous 5-HT receptor and being expressed on midbrain neurons is certainly in a position to cause a lot of adverse effects, especially when combined with dopamine antagonism I suppose.

Some of the adverse effects (dyskinesias) from chronic neuroleptic use seems to be due to hypertrophy of some midbrain areas, perhaps as a compensation for receiving reduced dopaminergic input. Part of the hypertrophy is though to be due to induction of DeltaFosB, which antipsychotics are known to induce in some cell types.

Induction of DeltaFosB via drugs of abuse can cause behavioral changes pretty fast in animals but I wonder what the timeline is for DeltaFosB induction via antipsychotics -> behavioral change is in humans, especially in someone predisposed or who has already seen some DeltaFosB induction. If that's partly the issue, then HDAC inhibitors would be something to talk to doctors about I suppose, Depakote does get used for odd insomnias anyways.

What the OP describes kinda reminds me of the persistent increase in locomotion/behavioral sensitization after giving an animal one dose of amphetamine - the animal still displays increased locomotion many months later. But I think the report of (apparently persisting) restless legs is important and may help docs get to the root cause (I would be sure to mention the restless legs).

CY
 
What if the meds you took for seven days months ago have nothing to do with this?

Why where you in a psych ward? I was in a psychward and they made me take like trazadone or mitrizapine i dont remember when i couldnt sleep and seroquel but i was on them for suicide. So if i stopped them would it be more likely meds i took a few times causing nonspecific brain damage or my brain having a mental disorder causing issue months later
 
What if the meds you took for seven days months ago have nothing to do with this?
I understand what you're saying and agree that that possibility should be brought up but what stands out to me is that the drug initiation caused apparently severe akathisia/dyskinesia and the OP has lingering restless legs. Issues with restless legs are supposedly higher with seroquel than some other antipsychotics (although I believe risk of extrapyramidal side effects and tardive dyskinesia is supposed to be a bit lower with seroquel/quetiapine compared to other antipsychotics)

Its possible that two different persisting effects of the drugs are causing both the insomnia and RLS independently but my hunch is that they are not so independent, and thus if the RLS is believed to have been caused by the drugs then chances are the insomnia is also related in both original cause and pathology
 
oh man.

i have some pretty serious life-long sleep issues myself, but nothing as fucked up as this. i don't know how you're coping at all. only thing i can really relate it to is 5 days awake from opiate withdrawal or something.'

watch this space - i'll talk to my friend and report back. be interesting to know if this is "a thing" that happens to many people. you're only the second i've heard of, but it's fascinating/terrifying.

I've been looking at some antidepressant drug withdrawal forums. This problems doesn't seem too uncommon but nobody can actually explain what is happening exactly or provide a solution except to wait it out.
It got better for people but they say it takes years..

I suggest you go to another doctor then, hopefully one who's more competent. I think the meds definitely played a role in this, because all of this sounds disturbingly similar to the sort of benzo withdrawal could expect after several months of continuous heavy (ab)use. But even then the duration is usually a matter of days not months, and it's hard to understand how any drug, no matter how potent, could ever trigger such severe WD symptoms after barely a week of use (let alone ones that last this long)...some sort of atypical PAWS perhaps?

Why were you put on those meds in the first place? Bipolar and drug-induced psychosis are the two obvious possibilities that come to mind, but it's also not unheard of for either of those meds to be given for severe insomnia (although I would think not both of them at the same time, and certainly not both started on the same day). Those symptoms could be part of an agitated depressive episode, possibly precipitated by the sudden discontinuation of the meds.
Were you taking anything else prior to taking those two meds? If so, had you had a bad reaction to it, and did you stop it abruptly at the same time you were put on the meds?
Did you have a history of insomnia or any sort of sleeping problems beforehand?

I too think that it could be some kind of PAWS, especially since I have tons of other symptoms beyond that. All my senses are messed up too.

I got to the psych ward to rule out neurological issues, I had insomnia and sleep problems before due to indoor allergies & stress but I could handle that easily as I could recuperate & make up for that later in the day,
but what those meds this is just not in a natural realm anymore. The insomnia got really bad after I got a reflux problem & so I thought maybe meds could help out, I wasn't even aware that the side effects could be this insane...
When I got the akathisia & dyskinesia I just though I have a neurological disease... It was weeks later that I understood it was the medication... lol

I haven't been taking anything else before. I didn't even do drugs, lol.

I think of maybe reinstating very small amounts to see if it might be withdrawal related.

Thanks a lot for participating. Really appreciate it.

What if the meds you took for seven days months ago have nothing to do with this?

Why where you in a psych ward? I was in a psychward and they made me take like trazadone or mitrizapine i dont remember when i couldnt sleep and seroquel but i was on them for suicide. So if i stopped them would it be more likely meds i took a few times causing nonspecific brain damage or my brain having a mental disorder causing issue months later

I was there to rule out neurological conditions & because of the sleep issues. It does seem like damage from taking & from stopping & withdrawal. I'm not really sure. Funny thing is, those meds made me extremely
suicidal on day 3... I remember googling methods & seeking for ways to so so which was very unusual for me. I didn't realize I had akathisia at that point.

I understand what you're saying and agree that that possibility should be brought up but what stands out to me is that the drug initiation caused apparently severe akathisia/dyskinesia and the OP has lingering restless legs. Issues with restless legs are supposedly higher with seroquel than some other antipsychotics (although I believe risk of extrapyramidal side effects and tardive dyskinesia is supposed to be a bit lower with seroquel/quetiapine compared to other antipsychotics)

Its possible that two different persisting effects of the drugs are causing both the insomnia and RLS independently but my hunch is that they are not so independent, and thus if the RLS is believed to have been caused by the drugs then chances are the insomnia is also related in both original cause and pathology

Thanks a lot for your very valuable input & trying to connect things.

The restless legs thing I am literally having half of the day. But I am almost oblivious to it because I'm barely aware most of the time. However since I'm slowly tapering the benzo I was taking it seems to aggravate issues a bit. I definately know that taking flurazepam seemed to have given me back cognitive function. I almost couldn't speak the first 2 months. If think the benzo masked some issues but didn't help at all with shutting my brain or the part of my brain down that causes the inappropriate wakefulness & doesn't allow for deeper rest/relaxation/sleep.

Also it does make a lot of sense relating RLS with insomnia because I haven't had the RLS... insomnia was mild-moderate before... but on top of that it's not only the excessive wakefulness... I have like 30-40 other symptoms...

I have extreme visual problems. I can barely read normal because the scope of what I can focus with my eyes is partially focused and partially unfocused... My vision is unfocused all the time. I have an unfocused stare at nothing... the whole day... like I can't read the words straight, my brain is compensating like crazy... all this also got worse month by month... I've been to 10 ophthalmologists everybody told me my eyes are fine. The last one said it's a perception issue caused by the meds I took..

Also my vestibular sense, balance & hearing is off... altough my ears and balance organs and my brain based on MRI scans are all fine... altough all senses are messed up... so it really makes me wonder.

My idea is that based on my genetic report is that due to COMT++ I'm breaking down stress hormones 300% slower... that means high norepi levels... Also I have some serotonin transporter mutations that suggest higher serotonin levels...

I also assume I have rather lower dopamine because I would have all the symptoms that would indicate that... but again it's just an assumption.

Combining high norepi & serotonin with drugs that increase serotonin & norepinephrine would have caused this disaster because dopamine would end up too low in some of the brain areas that control wake/sleep homeostasis & that messed up all my senses, to connect everything together.

But not sure how to reverse now. I am thinking of reinstating micro doses of the medication because all those problems got worse week by week, month for month & or take L-Dopa every day or wait it out, lol.

Also I developed TMJ pretty much instantly after stopping the meds. Maybe also acetylcholine/dopamine imbalance there as I've never had that before.
 
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My idea is that based on my genetic report is that due to COMT++ I'm breaking down stress hormones 300% slower... that means high norepi levels... Also I have some serotonin transporter mutations that suggest higher serotonin levels...

I also assume I have rather lower dopamine because I would have all the symptoms that would indicate that... but again it's just an assumption.

Combining high norepi & serotonin with drugs that increase serotonin & norepinephrine would have caused this disaster because dopamine would end up too low in some of the brain areas that control wake/sleep homeostasis & that messed up all my senses, to connect everything together.
I see a lot of these kinds of notions, and I really have to warn you away from them

What is actually happening in your brain most likely cannot be summarized with "low dopamine, high serotonin, too many stress hormones" - the true cause of your symptoms is probably much more nuanced. Actual transmitter levels are probably within fairly normal ranges (at least whatever you had going on before the meds). For example, it could be that a certain cell type is expressing too much of a particular protein or something.
I am thinking of reinstating micro doses of the medication because all those problems got worse week by week, month for month & or take L-Dopa every day or wait it out, lol.
I would avoid doing this. With movement disorders relating to akathisia, restless legs syndrome and tardive dyskinesia, doctors generally seem to want to avoid neuroleptic medications that can cause and worsen such symptoms/conditions. Once again, I think categorizing what you're experiencing as a withdrawal type condition is totally barking up the wrong tree, in my personal opinion.

If anything, conditions like persisting akathisia after antipsychotics seems to be due to a compensatory effect that occurs while dopamine transmission is low, therefore decreasing dopamine transmission again (with more seroquel) would be a bad idea.

I think what some other people are saying is that you must have had some level of messed up physiology before the drugs, and this I have to agree with, it could just be that the drugs raised something above the symptomatic threshold.

In the meantime I recommend practicing mindfulness meditation, practice with free apps such as Headspace and 10% Happier, and look for guided mindfulness meditations on youtube. Give it some practice. Mindfulness has proven effective for insomnia and is likely what you should have been told to practice before you ever had to go on meds.

The other thing is that religious cardio can be very helpful for many issues, and if you aren't sleeping then avoiding chronic deconditioning while the insomnia improves will also be very important. This means exercise, stretching and consuming enough carbs/proteins/fats/vitamins to avoid wasting.
 
Mirtazapine did the same thing to me but slowly over a year and a half. On top of that it gave me terrible nightmares. My sleep/awake switch is fromm all I can tell permanently broken. My circadian rhythm is non-existant!
has been 3 years since I stopped taking it. The first year off was the worse as it got so frustrating that I developed insomnia from the stress of not n sleeping properly. But my nightmares abate in the first few months until now I no longer have them. Slowly I tried myself to have 9 to 9.5 hours of broken sleep every night.
I have been to sleep clinic and had all their tests. They cant find anything wrong. I have tired everything and some mumbo jumbo too out of sheer desperation. I've tired meditation, psychoanalysis, yoga, general exercise and all different times of the day, EMDR, catapres, valdoxyn, circadian/melatonin and compound melatonin, weed, CBD oil, 5-HTP, magenesuim, herbal stacks, acupuncture, Chinese meds. Nothing can fix the sleep cycle.
I am permanently broken from this shitty drug. The only thing that stops me waking 15 to 30 times a night is temazepam and seroquel but seroquel hits me like a brick and has me too zonked to do anything and if I took it would result in being too stupid to go to work. So ultimately I am left battling to not take temazepam regularly so as not to build tolerance.
I am really interested in suggestions to this affliction
 
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I see a lot of these kinds of notions, and I really have to warn you away from them

What is actually happening in your brain most likely cannot be summarized with "low dopamine, high serotonin, too many stress hormones" - the true cause of your symptoms is probably much more nuanced. Actual transmitter levels are probably within fairly normal ranges (at least whatever you had going on before the meds). For example, it could be that a certain cell type is expressing too much of a particular protein or something.

I would avoid doing this. With movement disorders relating to akathisia, restless legs syndrome and tardive dyskinesia, doctors generally seem to want to avoid neuroleptic medications that can cause and worsen such symptoms/conditions. Once again, I think categorizing what you're experiencing as a withdrawal type condition is totally barking up the wrong tree, in my personal opinion.

If anything, conditions like persisting akathisia after antipsychotics seems to be due to a compensatory effect that occurs while dopamine transmission is low, therefore decreasing dopamine transmission again (with more seroquel) would be a bad idea.

I think what some other people are saying is that you must have had some level of messed up physiology before the drugs, and this I have to agree with, it could just be that the drugs raised something above the symptomatic threshold.

In the meantime I recommend practicing mindfulness meditation, practice with free apps such as Headspace and 10% Happier, and look for guided mindfulness meditations on youtube. Give it some practice. Mindfulness has proven effective for insomnia and is likely what you should have been told to practice before you ever had to go on meds.

The other thing is that religious cardio can be very helpful for many issues, and if you aren't sleeping then avoiding chronic deconditioning while the insomnia improves will also be very important. This means exercise, stretching and consuming enough carbs/proteins/fats/vitamins to avoid wasting.

Thanks for the info. I already do excercise and breathing excercises.

Can you recommend something to resolve this issue though?

I literally try my best to cope but it got worse and worse every single day... I don't get to a point where I am stable with this... or where I can compensate...

I'ts been 5 months and there seems no end to it...

I can't handle this anymore... because I wake up in an akathisia like state and I am already beyond exhaustion. My brain is hyperawake but my senses can't process anything anymore.

I could cope like weeks ago but now it gets to a point where my awareness gets more and more dim and it's impossible to do stuff because I am hyperwake and completely asleep at the same time. The thresold there
gets smaller and smaller where I more and more inbetween this states and I literally can't process stuff because I am out of my mind exhausted but my brain keeps me awake...
 
I find it hard to believe you've had sleep studies done and nothing shows up on them... that would seem to imply you're having restful sleep but you wake up and your brain starts into panic mode.

Maybe get a second diagnosis?
 
I find it hard to believe you've had sleep studies done and nothing shows up on them... that would seem to imply you're having restful sleep but you wake up and your brain starts into panic mode.

Maybe get a second diagnosis?

I haven't had a sleep study done. It was another member talking about that.
 
I find it hard to believe you've had sleep studies done and nothing shows up on them... that would seem to imply you're having restful sleep but you wake up and your brain starts into panic mode.

Maybe get a second diagnosis
So I've actually had a little disagreement with the president of the American Academy of Sleep/director of University of Washington's sleep medicine clinic about a similar subject:

Current polysomnography seems to work by approximating one's EEG/info readings to categorize a person absolutely into one of the phases of sleep (I, II, NREM, REM). There seems to be a condition called sleep state misperception wherein one subjectively claims to be awake/conscious, or have insomnia, while polysomnography would indicate the individual is asleep/sleeps fairly normally.

The issue with polysomnography seems to be that people can have phenomenon such as "alpha wave intrusion" - wakefulness brain activity interjecting that doesn't cause the polysomnography technology to change which sleep phase it thinks you're in, but which very likely affects sleep quality. Part of the idea is that some parts of our brains can be "awake" and not getting restorative sleep, but the software picks up on the parts that are indeed asleep and then it categorizes our entire brain as asleep.

The polysomnography software typically works by using 30 second epochs, if the raw data shows you're in a fragmented/disrupted phase NREM for 16 seconds, and phase I/II for 14 seconds, then it can still categorize the whole 30 seconds as "You were getting 30 seconds of normal NREM" as far as the percentage readout of how much time you spent in different phases of sleep that night (which is all the doctors really look at).

Polysomnography seems largely meant to detect sleep apnea, and the actual quality of sleep seems to fall by the wayside. Its been shown that humans, much like other animals, can essentially sleep with one hemisphere of our brains at a time. It seems to be the case that polysomnography technology won't actually report this very well when just looking at the percentage readout.

What one doctor did for me at one point was actually go in and look at the raw EEG data, which tells a very different story than the computerized readout. If someone's doctor is insisting that someone has normal sleep after they've only looked at the percentage readout, time to find a new doctor.

Sleep fragmentation doesn't seem to be picked up by the percentage readout, the doctor will have to go in manually and look at the raw data.
 
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