• N&PD Moderators: Skorpio | thegreenhand

How long does it take for an upregulated serotonin transporter to get back to normal?

Kdem

Bluelighter
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Mar 14, 2015
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Skipping some issues - one of the things clonazepam does, is upregulating the serotonin transporter.
I have wondered if that very thing would be responsible for some of my issues.

Anyway, assuming complete discontinuation of the drug - how long till it is back to 'normal' ?
If this is a simpler way to put it: SSRIs downregulate the sertotonin transporter. I could ask as well how long it takes for SERT to get back to normal.
 
I would bet you the GABA mediated effects are producing a larger effect on serotonin than the up regulation of SERT, but I would guess if there is significant up regulation of the SERT it will probably take about 2 weeks for things to be back to 90% normal concerning solely the SERT. But honestly if the SERT is up regulated then the serotonin receptors are probably up regulating to achieve homeostasis.

Care to tell us what kind of issues you're having? If you really think that SERT up regulation is giving you problems then you could talk to your doc about adding Citalopram.
 
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LOTS of issues.

I´ve wondered if serotonin depletion (with a secondary effect on other neurotransmitters, like norepinephrine) would cause some of the extreme reactions after exercise (example: massive increase in treshold to fall asleep, lasting for days, subjective slowing of time, cognitive issues). For that, no other benzo works, only clonazepam.

Muscle tissue breakdown, whether exercising or not. These days, regardless of dose. Note: not muscle weakness, but breakdown.

Shutdown of normal appetite.

Motor issues, maybe serotonin (depletion) to acetylcholine or (indirectly) dopamine to acetylcholine.
Unfortunately, there is no such thing as a fast clonazepam taper. Generally, using SSRIs during a taper is contradindicated.
 
benzos do not cause muscle breakdown,you mentioned that your diet is out of order,i think thats the reason your muscles are degrading
 
Yeah I would be wary of SSRIs lowering the seizure threshold.

Sleep is extremely important, in my opinion most of your muscle wasting problems are probably due to a combination of not eating and not sleeping (most of your growth hormone is released during sleep, this is also where your body does all of its repair). If you're having trouble sleeping after working out this is probably due to excess adrenaline, a medication like Clonidine will help lower your sympathetic response so you can sleep after exercise.

I think you should get yourself some Clonidine (very often prescribed for withdrawals, works great for opiate withdrawals), and begin a slow carefull taper if you're having so many problems. You can find yourself some lunesta/ambien for sleeping but Clonidine is great for sleep as well. Though withdrawals are indeed withdrawals.

Any questions are welcome.
 
I have eaten enough ... what my body does with that food is a different matter.
Sleep is much more of a problem.

Excess adrenaline ? Not really, adrenaline feels different. Norepinephrine, yes. Probably released from the peripheral nervous system, and it must get in the CNS as well. (Blood levels, brain levels)
And there can be cortisol, cortisone, whatever glucocorticoids my body feels like making.

I don't know if clonidine works for that. Aside from other issues, I think it's pretty much a broken feedback system (HPA axis and more)
 
Clonidine will help you with your sleep and decrease noradrenaline tone in your brain as well as periphery, it will decrease the excitability of your brain over all. There are also things like Belsomra for sleep which is a bit expensive because there's no generic out yet but it's not addicting.

If you think that low serotonin is at the root of your issues then you could slowly taper the klonopin (I don't know how it's not helping you sleep anyways) once you get a script of some Clonidine or something to help you sleep during withdrawls, and then once withdrawals are through you could try Citalopram (should be exactly what you need if serotonin levels are low), but I must warn here that typically serotonin promotes wakefulness so I doubt that you're running horribly low on serotonin, on that note usually SSRIs cause insomnia and reduce REM sleep because serotonin can be activating. Most serotonergic sleep meds like Mirtazapine and Trazadone (which you might also try) actually shut down serotonin.

Anyways fix your sleep and everything will fall into place. I also really recommend mindfulness meditation, don't knock it until you've tried it for a while (cognitive behavioral therapy for insomnia is more effective long term than medication). But there are lots of other drugs out there besides GABA drugs, Belsomra is definitely one you should look into it you have the money.
 
I can see that you've been struggling with getting off clonazepam for quite some time now. The truth is you must prepare yourself for some withdrawal if you want to get off, if you've been dependent on it for a long time, then chances are it's not working properly anyway, so there is no way you could just eliminate all symptoms of withdrawal with or without additional medications. Recovery is hardly about getting into the state of your SERT or GABA receptors, firstly you just need to give it a time and make sure you've got the right conditions to recover, for instance it's certainly much easier to recover when you simply look after yourself and have close people beside you, loneliness can fuck up everything and make you relapse in no time. Whatever the reason why you got dependent on benzodiazepines is, as long as it is still there, getting off benzodiazepines won't magically put you back into a healthy state of mind either. I was postponing quitting for a long time, in the end I just went through a withdrawal and then I started recovering. I'm not telling you to stop abruptly, tapering down to a reasonable dose to jump off is necessary to avoid seizures and probably other neurological complications, but otherwise getting into details about the state of your nervous system that won't help you in getting off anyway is pointless in my opinion. When I was at 0.5-0.25mg of clonazepam, I switched to 10-15mg of clorazepate a day and an equivalent dose actually lasted for longer than clonazepam did. Wish you strength.
 
adder,

The right conditions to recover ? They are probably never going to occur ...
There are some health issues that I couldn't get treatment for, and truth is that after all this time I'm pretty much on my own.
I must do what I can do ... whatever that will be.

It's good to hear that about Tranxene, people always recommend Valium. Valium is so short acting.
When the clonazepam (at a dose of 2 mg) leaves the body, the diazepam is barely a match for the withdrawal from clonazepam.
I was foolish enough to go along with a taper by lorazepam, when tolerance/dependence to that drug occurred it just became not taper-able. If that had not happened, I probably would have opted for Tranxene rather than diazepam, but I doubted if Tranxene was strong enough to cover for the withdrawal from both drugs. Lorazepam had much stronger hypnotic, sedative and amnestic properties than clonazepam.

Actually, general (and up to a point, specific) health issues was what made tapering clonazepam so hard. It's just a very 'physical' drug. And how do you taper when you don't have a more or less normal functioning body ? (that's rhethorical)

Would you have any clue if Tranxene could cover for 2 mg clonazepam at 'equivalent' doses ? Did you take the Tranxene once a day ? (of course, you were already at a low dose of clonazepam)
 
I really think you should try to get someone to prescribe you a sodium channel blocker like Depakote (great medication, very cheap too) or a newer one with less side effects and better long term outlook like Eslicarbazepine (trade name Aptiom), these are primarily anti epileptic drugs but they've found great use in chronic pain syndromes and mood disorders like bipolar mania. They are well kept secrets - there are better drugs out there than benzos.

Would you care to enlighten me on your health issues? It's okay if it's cathartic, I've been there <3
 
What's the function/rationale of a sodium channel blocker ? For me, it's mostly getting off the clonazepam and getting my body back to normal. Which is not going to happen fast, no matter what ...

Without getting into the details of my health issues (which started a few years ago): serious sleep deprivation/fragmented sleep (medical cause that has been resolved by now), followed by exhaustion. Now, I was also taking this clonazepam at the time. Experiencing that while taking clonazepam is completely unlike experiencing that when not on clonazepam ... that set a lot in motion. 'medical circus' General deterioration of health, muscle breakdown, stupid lorazepam taper, incompetent/dismissive docs, exercise intolerance as defined by problems that start after the exercise, hormonal issues, unknown problems (?) etc. Some symptoms of CFS, some issues resembling dysautonomia. I could not have believed this would be possible five years ago. I should be young, strong and healthy before tapering ... Back to positive thinking.
 
So basically what a sodium channel antagonist primarily does is acts to reduce your brains overall excitability, depending on the drug in question sometimes they have specific affinity that helps them shut down mostly epileptic activity, so the main function will be to help your sleep and help curb your brain's excitability rebound as you taper off the benzos. I think Depakote is exactly what you need, it's very good for medical issues (pain syndromes and mood disorders related to health disorders) and it's what I would want if I was in your position. You're still going to have to taper really slowly and carefully but it'll help take the edge off of it if you can wait for the depakote to normalize in your system before you taper. It's not a drug I would want to take for more than a decade but a couple years on it is fine.

Do you have orthostatic intolerance, and other problems with lightheadedness standing up/exercising and such that you didn't have before benzos? Clonazepam is known to cause hypotension by slowing the heart and reducing the force of the hearts contractions, if you are exercise intolerant because of this I suspect the clonazepam is to blame. It's important for the heart to be able to speed up and increase contractility to a signicantly level to cope with exercise. Benzos also dilate the cardiovasculature and this could be contributing to problems as well.

I'm personally an insomniac so I'm of the school of thought that most health issues often times are the fallout of poor sleep, including hormonal disturbances because most anabolic hormones like testosterone, insulin, and growth hormone are released during sleep. I think if we fix your sleep lots of other things will fall into place, and it will be a lot easier for you to exercise (which is extremely important) when you are getting genuine body repair at night.

I get you on the incompetent docs. Unfortunately at some point I feared I must become my own doctor, and it has become so.
 
Here is an excerpt from a study about the use of depakote (valproate) in benzo withdrawl - " At 5 weeks post-taper, 79% of sodium valproate and 67% of trazodone, but only 31% of placebo patients were BZ-free", and an excerpt from a study concerning valproate use in alcohol withdrawal "Treatment with sodium valproate (1200 mg daily) was continued for one week. The occurrence of seizures and other withdrawal symptoms (tremulousness, nausea, sweating, disorientation) were noted daily. Forty-nine episodes of withdrawal have been included in the trial - 22 in the sodium valproate group and 27 in the control group. Five patients, all in the control group, had seizures. Other withdrawal symptoms disappeared more quickly in the sodium valproate group even though fewer patients were receiving chlormethiazole."

I would say that the studies support the use of Depakote in GABA drug withdrawal.
 
adder,

The right conditions to recover ? They are probably never going to occur ...
There are some health issues that I couldn't get treatment for, and truth is that after all this time I'm pretty much on my own.
I must do what I can do ... whatever that will be.

It's good to hear that about Tranxene, people always recommend Valium. Valium is so short acting.
When the clonazepam (at a dose of 2 mg) leaves the body, the diazepam is barely a match for the withdrawal from clonazepam.
I was foolish enough to go along with a taper by lorazepam, when tolerance/dependence to that drug occurred it just became not taper-able. If that had not happened, I probably would have opted for Tranxene rather than diazepam, but I doubted if Tranxene was strong enough to cover for the withdrawal from both drugs. Lorazepam had much stronger hypnotic, sedative and amnestic properties than clonazepam.

Actually, general (and up to a point, specific) health issues was what made tapering clonazepam so hard. It's just a very 'physical' drug. And how do you taper when you don't have a more or less normal functioning body ? (that's rhethorical)

Would you have any clue if Tranxene could cover for 2 mg clonazepam at 'equivalent' doses ? Did you take the Tranxene once a day ? (of course, you were already at a low dose of clonazepam)

Well, I did mention the right conditions to taper as they can change a lot, though I can't say I had the right conditions to quit either and even now 2 years after I quit, I still don't have them, any positive change in my life is still only a result of quitting benzodiazepines itself, that is better memory and generally better cognitive functioning, yet it's far from what a normal person experiences and lives like, I'm sure. My life hasn't really improved much since I quit benzodiazepines, the only benefit I have now is that I can somehow study and work, certainly that's a privilege in today's world, but not really what makes you happy/satisfied, so I've been diving deeper and deeper into my psyche/ego to understand what's going on wondering what generally makes people keep going on, what makes them happy. After all happiness or serenity is the state of mind that people chase by default, everything else stems from it. Having gone through my past traumas again I've come to a simple conclusion that you can't really consider the state of your mind leaving the external, basically the external boils down to one's relations with other people, they need to be positive, they need to be reinforcing, without them hardly anything can make you happy, peaceful, serene. Loneliness at its extreme not only makes an extremely sad unmotivated person, but also impairs you cognitively. Quitting any drug is essentially learning, so the more favourable conditions you have to form new neuronal paths, the more likely you are to succeed.

Anyway, as for clorazepate, I'm not really sure whether it would cover for 2mg of clonazepam at an equivalent dose, I don't think there is any reason why it wouldn't, even if nordazepam, its active metabolite, have a lower efficacy at benzodiazepine receptors, its ceiling certainly isn't at an equivalent dose of 2mg of clonazepam. I suppose it's kind of easier to taper off clorazepate because its effects are much milder. I'm not sure if I ever made it down to 0.25mg of clonazepam as I had problems staying at 0.5mg, but that's when I switched to 15mg of clorazepate and then decreased it to 10mg. My psychiatrist wanted me to jump off 0.5mg of clonazepam, I organized some clorazepate for the taper-off myself, so my supply was limited. A single dose of clorazepate lasted considerably longer than a single dose of clonazepam, I didn't really dose once a day, due to limited supply I took another dose when I felt I had to and on average it was probably around every 36 hours or so. When I ran out of it, I didn't really feel my taper was complete, the way I felt wasn't the way I should have felt after a proper taper, I imagined, but I might have been wrong. If you can get it prescribed, then you should get down to 5mg a day if you feel that's necessary. Honestly speaking, I was quite surprised clorazepate substituted so well for clonazepam, I had no worse mental and physical discomfort than at my equivalent clonazepam dose, and when a dose was wearing off, it was much milder and spaced out in time compared to clonazepam wearing off. Perhaps a different ratio in activity at different subunits might explain why clorazepate felt quite refreshing for me when I switched from clonazepam, hard to say.

Like I said, I don't believe there is a 100% painless way to quit benzodiazepines after being dependent on them for a long time, limiting the withdrawal symptoms with proper taper schedule is necessary to diminish neurological complications that may result from abrupt discontinuation, I imagine, but otherwise there will always be discomfort associated with the transition from taking benzodiazepines and then not taking them at all while your GABA and glutamate systems are completely out of balance. Perhaps a partial agonist could both provide some activity and at the same be fixing problems with active conformation of benzodiazepine receptors as flumazenil supposedly does, it could be a way to finish the taper, but I don't think it will be an option any time soon.

I can tell you from experience that my recovery was much faster than I expected, ~3 months after I quit my anxiety was at bearable levels so I could go out, and ~10 months after I quit I was back at the university. If I hadn't taken any drugs during the first few months after quitting, I'm sure I would have been recovering even faster. I did experience similar problems as you do when I was still on clonazepam (like slow movement, lack of energy, hormonal problems, slow thinking, memory problems) and these actually started improving fairly quickly after the first month, what takes much longer to resolve is general anxiety, muscle tremors, and quality of sleep. But generally right now what I'm suffering from are problems that I had before I even started taking benzodiazepines, if I could fix that, I suppose I could almost forget about what my benzodiazepine use did to me. Looking back, it was well worth it to go through all the pain, at least now I can face the real problems, it was virtually impossible when I was on clonazepam.
 
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Maybe I'l get back to the valproate later. I've heard of carbamazepine and oxcarbazepine being used for benzo withdrawal. Carbamazepine seems to act on sodium channels too. Any particular reason you prefer vaproate ?

Nordiazepam is a partial agonist. Is that relevant ? Tolerance, and the strength to 'cover' for both the lorazepam and the clonazepam ?

I didn't have any physical problems before I took clonazepam, except certain vulnerabilities ... I lose muscle easily, it's hard to gain, once I got some kind of cardiac arrythmia ... Sensitive to insomnia ...
I'm not sure how to get insomnia 'under control' in benzo withdrawal ... I did try low dose Seroquel a few times while I was tapering lorazepam, and it would only work when the lorazepam was near tolerance, and even then only 50 % of the time ...
 
The scientific part of me says Valproate/Depakote did a bit better in the studies, there was a study showing carbamazepine was not effective for benzo withdrawal though I couldn't look at the details, but I'm honestly very sure that any sodium channel blocker will help. Valproate is better for bipolar mania so it's a bit more calming and sedating compared to some like Lamictal that I believe tend to be better for bipolar depression but I've heard good things about oxcarbazepine and carbamazepine too, but there is a new version of those two that it a lot better called Eslicarbazepine that is even safer and has proved efficacy for neuropathic pain among other things, after recently discovering it I am trying to get this drug myself.

I used to be on depakote and that worked very well for my insomnia which I usually take antipsychotics plus three other meds at once for, had insomnia since birth so I'm told but it got pretty bad after some ecstasy binges when I was 14 so I know what you're dealing with <3 other people I've talked to that had chronic insomnia liked Depakote as well. It has some better properties that keep certain bad genetics in check that the other sodium channel blockers don't have as much of, and it helps your brain grown new brain cells essentially. It has some properties that release something things that are like growth hormone for your brain. I've looked but can't see any evidence of these properties in carbamazepine line of drugs, though there is one currently ongoing study to check for this so it's a possibility.

I'm thinking about going back on depakote myself. There is the muy intelligente Atara, the mod in the Neuroscience and Pharmacology forum that takes Depakote as well if it means anything to you. I think it's a great drug.
 
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