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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Prefect on December 1, 2012, at 9:34:27
My understanding of SSRI mode of effect is this:
1. They inhibit reuptake of serotonin, making it abundant in the brain
2. Your receptors first compensate by dropping serotonin levels (which is why anxiety/depression gets worse in first few days of administration)
3. At some point, your receptors "give in" to this serotonin abundance and stop trying to regulate it. Serotonin levels get back up.
4. In reaction, the number of the receptors themselves are downregulated. This is aparently where the bulk of mood improvement is observed (which sounds counter intuitive to me).My question is this: Is the eventual amount of receptor downregulation dosage dependent, ie, is there a linear relationship, or is there a dosage before which there is hardly any downregualtion, past which, say, 90% of your receptors downregulate?
I ask because I'm dosing up (just relapsed) and trying to hit that sweet spot where my anxiety is no longer catastrophic, and yet I can still feel enough anxiety so that the bulk of my improvement comes from desensitization during exposure therapy. I seem to have done this 7 years ago on 50 mg/day Luvox and the result was exactly that. My panic during exposure was manageable, but still present enough that I developed real coping skills. I believe this is why I was panic free for 7 years on 50 mg /day Luvox alone. And I felt real emotions too.
I dropped the dose 3 months ago and relapsed, and now the 50 mg/day doesn't seem to work anymore. I want to raise the dose and find that exact point again. Will it be possible for me to find a higher dosage that will be as calming as my original dose and still allow some feeling, by experimenting, or will the receptor downregulation be exponential past a certain point and zombify me useless?
Thanks for attempting to answer this awkwardly presented question from a layman.
Posted by Phillipa on December 1, 2012, at 9:57:28
In reply to SSRI receptor downregulation. Linear relationship?, posted by Prefect on December 1, 2012, at 9:34:27
I did the same same med only also benzos but irreguardless the same problem so hopefully an expert with the answer will answer this. I just think that when the serotonin regular receptors are no longer needed as you are taking a med that saturates them they stop working your own and let the med take over bringing you back to what you previously were which could be poop out. Don't know. Phillipa
Posted by linkadge on December 1, 2012, at 10:19:38
In reply to SSRI receptor downregulation. Linear relationship?, posted by Prefect on December 1, 2012, at 9:34:27
The receptor downregulation may or may not have anything to do with the efficacy of SSRIs.
This is a very early observation in the history of antidepressants - i.e. that chronic exposure toe the TCAs resulted in downregulation of serotonin and norepinephrine receptors. The problem is that there is no consistently documented 'upregulation' of these receptors in unmedicated depressed individuals, nor an explaination as to why such downregulation would result in a theraputic effect.
Really, its more of an observation that when you flood the brain with a particular neurotransmitter, the brain responds by making less receptors for that particular neurotransmitter. The same has been observed after chronic exposure to say cocaine or amphetamines. However, chronic exposure to stimulants works opposite to that of antidepressants, i.e. initial improvement in mood followed by progressive mood worsening.
I don't think that there would be a linear relationship between SSRI dose and receptor downregulation. The reason being is that SSRI dose is not related linearly to drug concentration, drug concentration is not linearly related to SERT receptor occupancy and SERT receptor occupancy is not linearly related to increase in serotonin levels.
The antipanic effect of SSRIs may be more related to the increase in gaba levels that occurs after adniminstration of the drugs. Such increase may occur because of drug interaction with neurosteroid synthesis.
If a higher dose is needed to get back to remission, i wouldn't worry about it. Sometimes after improvement, a lower dose can retain the effect.
Linkadge
Posted by ssritaker on December 1, 2012, at 13:54:34
In reply to Re: SSRI receptor downregulation. Linear relationship?, posted by linkadge on December 1, 2012, at 10:19:38
To put it more simple, you stopped a med that worked an now it wont.This happens near every time with an ssri, just change to a different ssri no need to wash out an hope the new one works.I did the same with prozac many years ago an i get violently ill if i try that med now. You were a long time on a low dose that was your theraputic dose, going up wont work only more side effects.
Posted by linkadge on December 1, 2012, at 14:05:45
In reply to Re: SSRI receptor downregulation. Linear relationship?, posted by ssritaker on December 1, 2012, at 13:54:34
>You were a long time on a low dose that was your >theraputic dose, going up wont work only more >side effects.
Thats not necessarily true.
Linkadge
Posted by ssritaker on December 1, 2012, at 15:15:14
In reply to Re: SSRI receptor downregulation. Linear relationship?, posted by linkadge on December 1, 2012, at 14:05:45
Not always no, but starting a med you stop after years of useing can a lot of times rejects you when you try again. Not every time i agree but it seem,s to happen to many.
Posted by Prefect on December 1, 2012, at 18:09:57
In reply to Re: SSRI receptor downregulation. Linear relationship?, posted by ssritaker on December 1, 2012, at 15:15:14
Yes, I'm begining to consider that possibility (med won't work because I stopped it), but I'm shocked if this is the case, because I did't actually stop. I went from 50 mg to 37.5 mg, and then back up when I relapsed. So bloody unforgiving a process if that's the case!
I started 75 mg yesterday. I understand it's still low dose for Luvox, but I want to find that point where I still have some panic but it's manageable, so that the bulk of the therapy happens from exposure, CBT, and coping skills. I believe in this method, because I think that's why last time I was anxiety free for so many years at such a low dose.
If I don't get the effect I want by 100 mg/day I might try something new. Maybe Imipramine? etc.
Posted by jono_in_adelaide on December 1, 2012, at 19:07:16
In reply to SSRI receptor downregulation. Linear relationship?, posted by Prefect on December 1, 2012, at 9:34:27
For most people, SSRI's have a fairly flat dose-response curve, that is, doubling the effective dose gives only a modest increase in effect.
Posted by jono_in_adelaide on December 1, 2012, at 19:09:47
In reply to Re: SSRI receptor downregulation. Linear relationship?, posted by Prefect on December 1, 2012, at 18:09:57
It might be wise to try pushing the dose to see what happens, if this fails, consider switching to mirtazapine (Remeron) 30mg at bedtime
Posted by Phillipa on December 1, 2012, at 20:43:31
In reply to Re: SSRI receptor downregulation. Linear relationship?, posted by linkadge on December 1, 2012, at 10:19:38
Link so at times you can increase the dose and later then drop to lower dose and the effects of the higher dose will remain? Phillipa
Posted by ssritaker on December 2, 2012, at 3:46:09
In reply to Re: SSRI receptor downregulation. Linear relationship? » linkadge, posted by Phillipa on December 1, 2012, at 20:43:31
It can take months of a higher dose of a med to take effect specialy ssri,s. You dont like go from say 50mg to 100mg an you get an instant responce, well you will get a responce but not the one your looking for. You may get side effects like when you first started the med, this is when people give in. But you have to ride it out like when you started, Plus any med with an anti anxierty agent wont work on anxierty for months. Depression is its first priorty
This is the end of the thread.
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