what is causing adverse reactions to SSRI class of drugs?

[justy]

From: assesment and treatment of patients with M.E/C.F.S:clinical guidelines for psychiatrists. By Eleanor Stein MD FRCP(C)

"Drug Dosage and Drug Sensitivity
It is widely accepted that some patients with ME/CFS are more sensitive to the adverse
effects of medication than most healthy people. They share this trait with chronic pain
and fibromyalgia patients......SSRIs which are generally
well tolerated for the treatment of depression and anxiety are not tolerated by a subgroup
of ME/CFS patients. The mechanism of these reactions is unknown."

I have had this problem, having had a catastrophic reaction to Citalopram 3 years ago, which took me nearly a year to recover from. Does anyone here know why this happens or what is going on physiologically to cause this. Also does anyone have any more info on the "subtype" she refers to?

Any other experiences of this?

Justyx.

 

[alex3619]

I too have reacted badly to an SSRI. The exact reason is unknown, but I can think of four possibilities:

1. Many drugs require enzymatic activation. If the enzymes that activate them are too active, either from genetics or disease, then too much of the drug is converted, an instant overdose. This is an absorption problem.

2. Many drugs require enzymatic detox. If you lack the enzymes or the chemicals needed to make them work (which frequently includes glutathione or similar chemicals) then the drug is not broken down - a slow overdose. This is an excretion problem.

3. We may be sensitive to the intended chemical pathway - in other words the serotonin neurology might induce your symptoms.

4. We may be sensitive to other pathways the drug activates. We don't know all of them, and they will differ drug by drug. Don't be fooled by the word "selective" in SSRI. They are NOT selective in biochemical terms - that is a marketing ploy. They are a little more selective than some older drugs, that is all.

A given patient might also have more than one of these problems. The science of pharmacogenetics is looking at the genetics part of this, but this is a multidisciplinary research area with not enough research, again.

Don't get hung up on subgroups - that just means that some of us have these problems to a particular drug, and some don't.

Bye
Alex

 

[Tammie]

some of us may have too much serotonin to start with

and I have also read that these drugs can cause mitochondrial damage and since many PWMEs may already have problems with their mitochondrial function, this certainly would not help

 

[liquid sky]

some of us may have too much serotonin to start with

and I have also read that these drugs can cause mitochondrial damage and since many PWMEs may already have problems with their mitochondrial function, this certainly would not help

I can't take them either. I think Tammy is correct about having too much serotonin.

 

[justy]

I think for me the effects where similar to serotonin syndrome which would imply a type of overdose, which makes sense with what you mention Alex. I only took 2 pills over 2 days but it was like i had seriously overdosed. I also have very low Glutahione so that could be implicated also. I agree that this could be a problem with multiple issues, i have succesfully taken SSRI's in the past so i was lulled into thinking they might help again.

The mitochondrial issue also interests me, i have documented mito problems shown on the Acumen labs test from Dr Myhill. On the other hand i have had to take SSRI's twice in the past for postnatal depression and had no problems with them (other than prozac made me manic and i had to switch to another one) i wonder if they contributed to my later mito problems. Postnatal depression itself is hormonal issue anyway so could have been linked to my M.E i guess - i have had it severely with 3 out of 4 of my children.
Interesting replies, thanks! Justy.

 

[Lala]

I do not know what causes adverse reactions, but I am not able to tolerate antidepressants as well. I am on mirtazapine now, which caused me extremely rare side effect- depression of bone marrow. Millions of people are taking it without problems and my doctor told me he has never seen anything like this. In leaflet the producer claims in rare cases it can happen. Now I am tapering of it and hope I will be able to stay with natural products.

 

[Snow Leopard]

There have already been a variety of papers suggesting serotonic abnormalities. (seretonic overactivity)
Most of the RCTs of SSRIs in depression in patients with CFS have not had significant results (whereas several MAOIs did).

http://www.bmj.com/content/315/7101/164.extract "Increased brain serotonin function in men with chronic fatigue syndrome"
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(96)91345-8/abstract "Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome"
http://www.ncbi.nlm.nih.gov/pubmed/8938208 "Increased prolactin response to buspirone in chronic fatigue syndrome."Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome."
http://www.ncbi.nlm.nih.gov/pubmed/1586780 "Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome."
http://www.ncbi.nlm.nih.gov/pubmed/8550954 "Contrasting neuroendocrine responses in depression and chronic fatigue syndrome."

And http://www.ncbi.nlm.nih.gov/pubmed/9226729 "Blunted serotonin-mediated activation of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome."

I personally think these findings are of secondary significance - they are as a response to primary symptoms (and potentially the adoption of low stress lifestyles by some individuals).

 

[justy]

Thanks Snow Leopard for those links, im going to have a look through them later.
One issue that concerns me greatly is that many people with M.E are misdiagnosed with depression and given SSRI's which could have a potentially damaging effect and offer no help with symptoms -unless there is underlying clinical depression.
I was not depressed when i was given SSRI's, and had been seeking a diagnosis for my M.E for 16 years, i was misdiagnosed again and again as having depression. When i finally relented and took the SSRI it had a devastating impact on my health -both physically and mentally.

 

[Snow Leopard]

Ironically, the reason why SSRIs are overprescribed vs other antidepressants is because medical practitioners are repeatedly told they are much safer than the others.

 

[taniaaust1]

As Tammie said, they damage the mitochondria. I myself think the mitochondria play a big part in our illness.

Also as some said.. in our illness we may have high serotonin levels (I often wonder if its possibly actually dysregulated serotonin levels with levels going all over the place).

I once had a doctor in NZ put me onto Citalopram. I got a terrible extreme reaction with it. I only lasted on it for 3-5 days due to the reaction.

 

[justy]

Hi Taniaaust1 -its interesting to hear about your reaction to Citlopram, usually when i mention this to doctors or anyone they looked shocked as its considered such a safe drug. I agrree re the mitochondria issues too, ive been reading up on this a lot recently and my symptoms are very very similar to mitochondrial disorder.

This is a great website about mito disorders http://www.amdf.org.au/mito-info.htm

 

[Tristen]

From: assesment and treatment of patients with M.E/C.F.S:clinical guidelines for psychiatrists. By Eleanor Stein MD FRCP(C)

"Drug Dosage and Drug Sensitivity
It is widely accepted that some patients with ME/CFS are more sensitive to the adverse
effects of medication than most healthy people. They share this trait with chronic pain
and fibromyalgia patients......SSRIs which are generally
well tolerated for the treatment of depression and anxiety are not tolerated by a subgroup
of ME/CFS patients. The mechanism of these reactions is unknown."

I have had this problem, having had a catastrophic reaction to Citalopram 3 years ago, which took me nearly a year to recover from. Does anyone here know why this happens or what is going on physiologically to cause this. Also does anyone have any more info on the "subtype" she refers to?

Any other experiences of this?

Justyx.

One of my oldest and unchanging symptoms over the years is medication intolerance. Antidepressants, are much worse than any other drug. Something happens that should not be labeled a "sensitivity". I know sensitivities, and that's not it. It's not a crash from pushing my system to hard. It's not toxic overload either because I know what that feels like, and I wouldn't get toxic that fast anyhow. For me it is more like my entire system locks up and won't let go for 2 days. I think the Serotonin overload theory sounds most likely. Whatever it is, I believe the answer to this question would kick the door wide open for discoveries on the pathology of me/cfs, and it should be researched.

 

[justy]

Hi Tristen, yes i agree that it would be great to see this area researched, as you say it could hold an important key fpr discovering the underlying mecahnisms of our disorder.
I ts the same for me that it is more than a sensitivity and not just toxic overload. I had a severe reaction after just one tablet! The doctor convinced me to take another one the next day and it took me over a year to recover. When i asked him how long it woukld take to get the drug out of my system he said about day but as i said it took me over a year to recover.
I also have sensitivites to other drugs but the question remains why such a strong reaction to anti depressants?

 

[Tristen]

Hi Tristen, yes i agree that it would be great to see this area researched, as you say it could hold an important key fpr discovering the underlying mecahnisms of our disorder.
I ts the same for me that it is more than a sensitivity and not just toxic overload. I had a severe reaction after just one tablet! The doctor convinced me to take another one the next day and it took me over a year to recover. When i asked him how long it woukld take to get the drug out of my system he said about day but as i said it took me over a year to recover.
I also have sensitivites to other drugs but the question remains why such a strong reaction to anti depressants?

In the beginning I went through a couple years trying multiple different antidepressants because all the docs kept saying it was depression. The accepted protocol with those drugs is that it may take multiple attempts to get the right one. Because of this, it me 2-3 years of trying every anti-depressant in the book, before I figured out that I wasn't having just an inadequate response, I was having very dangerous and detrimental reactions to these meds.

This horrible reaction to this drug class in particular suggests to me a Neurological problem simple because that's the drugs target. Don't know what's wrong in there, but I do know that antidepressants are poison to me.

 

[kurt]

Citalopram is metabolized by the P450 system, in particularly, by Cytochrome 2C19. A reaction to Citalopram might be caused by a problem with 2C19. We know that CFS patients often have problems with P450 metabolism (this is the liver enzyme system that detoxifies most drugs). If you have 2C19 problems then you could have a major serotonin balance issue while the drug is being detoxified. Also, there is a group of drugs you might also react to, all drugs metabolized by 2C19. You can get a list of the P450 system drug reactions at:

http://medicine.iupui.edu/clinpharm/ddis/table.aspx

I have a similar problem with a different Cytochrome, with 2D6, and as a result get terrible overdose reactions to several drugs, including Paxil and even Benedril. However, I worked on this and learned I can tolerate tiny doses, at one time I took about 1/8-1/16 of the tiniest tablet of Paxil, when I was experimenting. That dose was therapeutic, but eventually I could not tolerate the serotonin excess either.

 

[Tristen]

Thanks for that link Kurt. Interesting that some of my earliest research attempting to diagnose the cause of my illness, led me to Cytochrome disorders. The physiology is out of my league, but it seemed plausible at the time that my extreme med intolerance may have to do with some kind of faulty metabolism and detox of the meds. I guess the one thing that cooled me to the idea is that I can be completely floored from just one pill....just one Zoloft, or one Paxil, at any strength, and I'm laid out for days. That doesn't seem like a toxicity problem.

 

[justy]

Thanks Kurt for that info, theres loads of stuff on wikipedia about the p450 system which is really interesting even to my unscientific mind. One thing that jumped out at me was there action in mitochondrial membranes, my mito membranes where shown on testing to be partially blocked with xenobiotics (dont know what yet) which could poitn to a problem with drug metabolism of certian types of drugs. Interestingly certain class of antibiotics are a;lso listed -these are the only ones i cannot tolerate -they make me wickedly sick.
Im not sure what this all means though and how you put it together into a bigger picture.
Justyx

 

[Carola]

I wish I'd come across this thread before starting my trial of low-dose amitriptyline. After only 4 days on .25 mg. a day (I cut a 10 mg. tablet in quarters), I was in the emergency room with serotonin syndrome. I had the full range of mental, autonomic and muscle symptioms but fortunately no fever, so they assessed it as "mild" and sent me home with lorazepam to help stop the tremor and shaking. Tincture of time is the prescription for the other effects.

None of the three physicians who recommended amitriptyline to me cautioned me about these symptoms and how serious the syndrome is.

 

[heapsreal]

Thats a low dose too get serotonin syndrome, normally doses in the hundreds of milligrams are needed with tricyclic antidepressant but then nothing suprises me with cfs. Sometimes other meds u are on can contribute to this too like tramadol and supplements like 5htp and tryptophan. Something that can help with serotonin syndrome is the antihistamine periactin, which has anti-serotonin effects that can help with serotonin syndrome. Also tricyclics can worsen restless leg syndrome(RLS), so maybe it can cause muscle tremors related to RLS.

cheers!!!

 

[Enid]

Thanks for interesting question and answers here - never put onto any of them by my Docs (luckily it seems).