Amytriptiline causing EM, could this be possible?

I started taking 12.5 mg of amytriptiline at night for insomnia and anxiety. I can´t recall the exact date, but it was probably mid august
On o the 28th i went out for drinks with a friend when i got home i noticed my feet swollen and bright red. They weren´t painful at that point. In the next days i noticed the same symptoms in my hands, ears and sometimes my face.
I continued taking amy till October the 10ths, and my symptoms are still here. Could this be a coincidence? o Can amytriptiline cause erythromelalgia? I haven´t found any article relating amytriptiline to EM as a cause, i did find several stating amy as a treatment option.

I found this article relating SSRIs to erythromelalgia in two patients with raynaud´s.

What do you think?

I´m curently undiagnosed, no doctor i visited has even heard of EM :confused: so kinda on limboland here.

Yes Amitriptyline is the first they normally try for nerve damage which is one of the causes of EM. There are a few causes of EM part of the problem and there is also a primary reason for it which is genetic.

You are not alone in seeing doctors that have never heard of EM! In fact I think most of us here have struggled. It’s extremely rare as well. The only way I managed to get doctors to take notice of me was to take along my iPad and show them these pages. So, if you could do something like that or even print out some pages to take it might help.

Mine has turned out to be rheumatoid vasculitis as the cause. I am currently being treated for that and it is actually doing some good. However it’s taken me around 12 years to find out!

Thanks for replying!
But was i was asking is if amytriptiline, the drug itself, could cause EM by altering serotin levels ! i´ve read that serotin has an effect in pathogenesis of
both Raynaud’s phenomenon and erythromelalgia!
Trying to figure this out by myself it´s quite a puzzle !
I don´t think i have nerve damage, at least i haven´t had any symptoms that could indicate that! I was prescribed amytriptiline because i could´t sleep that well and because i had body aches, and i guess the thought i had fybro or stress.

Wow 12 years, that a lot of patience! I´m glad you finally figured out what was causing you EM. I hope by treating the cause, the EM gets better!
By the way, how did you finde the cause? And more importantly how did you find a doctor willing to listen?

I realise you said could amytripytiline cause EM, but I was thinking if it did then they wouldn’t prescribe it for nerve damage with nerve damage being one of the things that can cause EM, but then again I don’t know the answer really.
Certainly my EM is nowhere near as bad as it was since they started the treatment for vasculitis, so I am hoping that in the end it goes away altogether but time will tell.

I have been seeing a rheumatologist for a long time now as I have rheumatoid arthritis. Last year I asked could it be vasculitis and he said no! It was pure luck that I found out. I had wrist drop, which means that my hand just hung from my wrist and I couldn’t move it at all. He did blood tests as one of the main reasons for wrist drop is vasculitis. Up to now they have blamed it on nerve damage at first as it was thought I was diabetic, but I wasn’t really it was a tumour on my adrenal gland that was pushing my glucose levels up. I had that removed 2 and a half years ago and then my glucose level was normal. Then they said it was poor circulation. I think they were just stabbing in the dark really.

So, sorry I don’t know the answer to your question maybe someone else will answer.

Thanks for taking an interest in my question. :slight_smile
It makes sense that doctors would’t prescibe it for nerve damage pain if they knew it could cause EM, but since most doctors are oblivious about the existence of EM it makes me wonder.
I took 12.5mg amytriptiline for about a month, wich i believe is a very low dose, but i experienced a few side effects like blury vision and it was like my heart was skipping a bit, after only one week of taking it.
Another weird thing about my EM is that it started everywhere, feet,hands,face and ears. The most frecuently affected areas are my hands and feet. Being my hands by far the most painful. I’ll make a new topic about how EM started for other people.

It’s funny how you had to have a symptom for them to order blood test for vasculitis, knowing that vasculitis is complication of arthritis.
It seems to me that most doctors don’t really care in making patients life better or are to arogant to admit that a patient can come up with their own diagnosis based on their research.

Hope you’re are well :slight_smile:

I am one who has EM as a result of taking an SSRI. It started 24 hours after taking my first pill. It can happen with any med as our bodies all react differently. I am still struggling 4 months later - it never went away. I hope your symptoms go away.

SHORT ANSWER: I think it can. Details and reasons are as follows, but this is from our case and only a little bit of study.

I’m thinking that some can get EM symptoms or even EM from Amytriptiline. My reasons for wondering this are based on just a few things, some reported to have had it happen to them. But these are my primary reasons.

  1. In my mom’s case, she had hot flares from Xanax, and discontinued it, but these were minor flares. She had other medical problems at the time and was being “treated” for “fear and anxiety” at least that is what we were told at the time. She ended up getting off that nerve pill. Well the nerve pills pass the blood brain barrier and our bodies seem to have a barrier that may cause drugs that don’t pass the blood brain barrier to not fully reach the peripheral nerves, so my “lay” theory is that drugs that can affect the brain, probably can cause side effects in nerves anywhere in your body. The Xanax in mom’s case caused minor burning and the side effect went away once she got off that drug. Now Xanax doesn’t seem to affect Serotonin much it affects other things, so it’s a clue that she reacted to nerve pills with EM, but it’s not liked to what caused mom’s full blown EM. Which was another nerve pill.
  2. Risperdone or Risperdal was later prescribed by a doctor to help her get off other nerve pills she had been taking. This when added to the mix caused her onset of EM around 2002 six weeks into taking the Risperdal the flares were at a constant 10 level. We have only gotten her flares down to zero with super cold chilling or freezing of the feet, or down to a level of 7 during her waking hours with heavy opiod drugs.

A rare side effect of Risperdol is it can cause the body to lose control of it’s temperature regulation. Mom seemed to display rare side effect of almost any medication at times, at least that seemed to be the case. So maybe she was more sensitive to medications, and maybe that’s something that is genetically rare for her, who knows? Just a guess. In any event the Serotonin receptors (there are 7 of them) that control blood flow and the contraction and expansion of blood vessels are receptor sites like the 5-HT 7 site. And these seven sites can in theory cause the body to get more or less blood flow and also control body temperature. Risperdone is an antagonist to these seven Neurotransmitter sites which can affect blood flow or temperature. Does it have the capacity to damage them in a permanent way? Most doctors and professionals would reply “no” and claim it was safe. But most people who gave to their young male children Risperdol didn’t expect them to grow breasts either. So my thought is the rare side effect of losing control of the bodies temperature is a result of permanent damage from Risperdol in my mom’s case. Now how does this relate to Amytriptiline?
3. Some who have tested the Ketamine/Amytriptiline cream have reported that their feet will “heat up” and after an application and then quickly go numb from the Ketamine. At first they may experience heat from the compounded cream that contains this mix. Typically a very low mix of .5% Ketamine and 1% Amitriptiline has been used for EM. Sometimes the Ketamine cream might be 1% or 2%, but usually EM patients in tests seem to use a very low dose. And we tried this after getting a prescription from a foot doctor. 1% Amytriptiline, 1/2 percent Ketamine.)

My mom had some heat with her first application of the cream that she tried. She also takes Ativan and many other pills so some of her “side effects” from the cream could be difficult to trace as different dosages or missing a dose of Ativan for example could change the balance of things acting on her nerves. Ativan will likely mitigate the results of restlessness of the Ketamine that one might experience when the cream starts to wear off. It seems and most of this is from very little research so you’ll need to vet my remarks with your doctors or those with more information. It seems that the Amytriptiline can help people deal with the side effects of the Ketamine. It may even work to relieve certain pain of certain diseases, but this is only from some notes or accounts I have read. In my mom’s case the Amytriptiline may have caused some of the side effects or some other things could have caused them as much as the ketamine. For example blurred vision can happen from something that is affecting your nerves and may cause your eyes muscles to start to not function as well. Relaxing the nerves, may effect your vision. In the case of my mom, some of the side effects we thought were from the Ketamine could have been from the Amytriptiline.

So how will we know for sure? We will know more when we do a test with Ketamine cream without the Amytriptilne in the mix, which will happen perhaps in the next week or two. We were able to get her Neurologist to prescribe the Ketamine cream and also ran that idea by her MD.
4. For mom’s case it seems Serotonin is “the smoking gun” clue. The smoking gun for me is a little bit of research I did reading about the Amytriptiline on Wikepedia. Notice the interactions it has with the Serotonin or 5-HT receptors. Six of the same seven receptors that control blood flow and body temperature which are affected as antagonists for Risperdol is also effected as antagonists with the Amytriptiline. This could mean that the mechanism that in our case caused mom’s EM from Risperdol could be present in Amytriptiline (Risperdol being the cause is our theory as we saw this happen, and although her MD at the time said the Risperdol caused it, he didn’t go into details as how the Risperdol caused it.)

Six of those same Serotonin/5-HT receptor sites which caused her problem could be affected in the same way with the Amytriptiline. Ironically the EM cream we were going to test, had something in the mix that was almost the same in it’s actions on the Serotonin receptors as the Risperdol that caused her EM damage.

This means Amytriptiline is going to be off our list of medications for mom’s condition for now. We will avoid it like the plague. If mom has nightmares or mood swings from the Ketamine, I believe the Ativan will be sufficient to help her deal with that side effect. We will cross that bridge when we come to it.

However, keep in mind my mom’s condition is really rare. It’s one of many versions of EM and could even be so very unique, perhaps hardly any EM suffering person has had onset with the same drugs. Those reporting EM from Amytriptiline however would seem to bolster the small amount of research I have done which seems to point to the 5-HT damage being done with Risperdol.

My suggestion to people who take a nerve pill and get minor burning foot symptoms from it, is to beware of taking other nerve pills. This is just a bit of friendly advice, but vet it with your doctor for your case.

I think if the medications do the same basic thing to your nerves, they may cause the same EM results or maybe do something worse. Of course this is just my opinion and I’m just a care giver so you can’t take this as medical advice. Please see trained doctors and specialists and run this by them if it seems like this would be applicable to your symptoms.

My mom suffers from large fiber neuropathy 50% reduction in nerve velocity, but not Small Fiber Neuropathy. She only gets burning, but some drug mixtures may bring a temporary onset of Raynauds like chilling of the feet. She may feel burning and heat up to her knees, but it’s usually confined to her feet. She may have cold or hot hands, she may have hot flares in her face as well, but the flares in her face and hands almost never have pain with the temperature changes.

Her constant pain level that she describes is a 7 on scale of one to ten and the flares are ten. She gets an average of 3 flares a day, that being a 10 level flare from a more or less constant flare of 7. If her feet are chilled enough the pain my subside, but it’s because the nerves are almost frozen. Her blood pressure will rise from pain, which is an easy thing to measure to confirm a bad flare, but at times her flare and pain can co-exist with low blood pressure.

In her case with the cream with two elements in them Amytriptiline and Ketamine she had the following side effects. (from 7 days of testing, a 3 day test, a 3 day test with lower dosage and a one day test.)
Racing heart, restless legs and tremors, mood changes which were very brief, a nightmare. She was upbeat much of the time and reported pain levels were down to 2 or 3, so low she could ignore the pain. So we want to try Ketamine cream again and hope removal of the Amytriptiline will give better results.

When her heart was racing she thought she might be on the verge of dying. She was missing a dose of Ativan however before that side effect/episode and it could have been a withdrawal. Ketamine may increase the effectiveness of other medications and mom was on a Fentynl 50mg pain patch and taking 10/325 norcos so the additive effects could cause more powerful side effects from the Opiod pain medication. We didn’t stop the opiod doses when using the cream as it seemed the cream would be a very low dose and not affect her system much away from the topical site.

One of the problems with our tests were things happened with a very short test and we often will quit a drug quickly if side effects are bad. We don’t wait and try to tough out the side effects, as we are quite afraid of bad side effects. . . wouldn’t you if you had EM flares for 15 years almost constantly after six weeks of Rispedone?

What is especially baffling is I don’t know if anyone has had the bad onset of EM symptoms from Risperdal that we have had. I have no idea. When I called the pharmacy company to see if they had any ideas, they sent me a “report form” to report the side effects, which is not really telling me anything or giving me a clue as to what we might do to negate the effects of that drug which likely can’t be fixed.

When I talked to her Neurologist and asked if an agonist for the Serotonin could exist, I had a feeling that nothing could be used to “reverse” permanent antagonist damage to the Serotonin receptor sites. This was just my own internal theory. I also know that agonists are drugs like Amphetamines. The doctor confirmed with his remarks that any agonist approach would affect her mind in a bad way. And I think that the damage in our case is permanent and not something that can be easily reversed.

PUSHING EM to cold symptoms via drug mixes.
Perhaps some mild forms of Serotonin Syndrome with mixtures of pills that affect that can cause cold symptoms Raynauds to happen. Cymbalta and flexerol for example with other drugs may cause Serotonin Syndrome. Serotonin Syndrome may cause a wide variety of symptoms and none of our doctors have said we need to worry about it with her pill mix, but a pharmacist said, be careful.

But we rarely push that level of medication with mixtures that could cause that side effect. Only twice in 15 years have we seen that possible “cold foot” side effect from drugs alone.

(The Ketamine and a few Tibial Nerve block tests caused her feet to be cold in areas and experience more Raynaud’s like symptoms with much less pain. But in both cases the block and ketamine cream didn’t cause her feet to get cold without environmental chilling. The feet would still get warm, they would not cause as much pain but be warm.)

We have had other issues and are trying to get mom back on her baseline of medication, which was another nightmare of the past couple of months. But that’s another story.

I really can’t give a medical conclusion as I’m not a doctor, but I think Amytriptiline can cause EM for a very small minority out there. I base that on the side effects I’ve seen and heard about, and what Risperdol seemed to do to my mom’s EM. I’m 95% certain that Risperdol caused her EM.

Also I want to point out that Ketamine is a NMDA blocker/ antagonist. This means it will slow Glial cell over-activity. What are the other drugs that can do this and may work with some forms of nerve damage or nerve malfuction. Other NMDA blockers include Memantine and DMX. DMX however is a weak NMDA blocker or antagonist. These have been used in some CRPS therapies and may be used with other drugs in the mix. They may be used with Opiods fail for those who suffer from advanced forms of pain RSD like pain. I found it interesting that mild creams with Ketamine can help some with EM and it seems that EM for some may have an overlap of symptoms that could almost be CRPS like. Perhaps there is enough overlap to have the same drug treatments eventually tried for EM suffering patients that is used for advanced CRPS therapy.

Memantine can be used for some with CRPS and may help some with EM. Ketamine is often used as an infusion for CRPS patients who have RSD like symptoms. But ketamine creams for EM are more mild and may have less side effects and may work better or at least offer some relief.

DMX is a weak NMDA blocker and it had no effect on CRPS according to one presentation I saw by a neurologist on a CRPS youtube video. DMX is not used as effective for CRPS.

I wondered if DMX could be used as a homemade cream or solution for EM, but have never had a doctor say it would be a good idea. From the little bit of research I did, it seems that the DMX would never make it past the skin barrier even if it could be dissolved in a water solution and the patient tried to soak their feet in it. All NMDA blockers can cause symptoms that are a kind of “high” so it’s better to use a lower dosage and use it topically and apply it to the nerves if “glial” cells around them are perhaps contributing to your problem. This is my guess and seems to be the way the stuff is prescribed and tested.

I don’t think anyone has tried DMX as a EM treatment. I know my mom took some cough syrip with other Serotonin affecting drugs and may have had Raynauds symptoms with the DMX in the mix. As DMX can be a way to enhance and bring on Serotonin syndrome, it may be that you would be told to avoid Tussin cough syrup when using some pill combinations for your EM disease. Mom had been taking Cymbalta and Flexerol (muscle relaxer) for a while for another injury.

I would never try a home remedy or suggest it, but I wanted to mention the DMX as a NMDA blocker to make the list complete and mention these other NMDA blocker therapies which seem to help some painful diseases out there. Most doctors will be very cautious before going to that route and some may worry about even going that far in treatment and leave you stuck with Opiods as your only pain solution.

Sometimes Low Dose Naltrexone (LDN) works as well for some, but that’s for a CRPS approach and not necessarily and EM approach. So there are different approaches to these rare diseases and we can’t try LDN for example unless we get off the Opiod drugs.
(which is another subject.)

I still very much doubt that Amytriptiline can cause EM. In your moms case she was on so many things it’s hard to tell which was the cause. The reason I don’t think it could be Amytriptiline is that I used to be on that for my EM and it certainly helped. The only reason I had to come off it was I found out I had Cushing’s Syndrome caused by a pheochromocytoma a tumour on my adrenal gland. What was happening was that my noradrenaline was sky high due to this and the Amytriptiline pushed it up higher so I had to come off it. This will be the reason for your moms fast heart rate. I had my left adrenal gland removed 2 and a half years ago so there was a possibility of going back on the Amytriptiline but I was scared that it had caused my tumour as it pushes your noradrenaline up.

Since then I have found out as I said before that the cause of my EM is rheumatoid vasculitis. Since I had my two infusions of Rituximab my EM has improved dramatically.

It’s very difficult when people are on quite a few drugs to find out which one if any is causing it. The only way I suppose is to stop each one and see if it makes any difference, but of course not without speaking to a doctor first.

Hey! I´ve just read you post again. Well now almost 2 months after quiting amytriptiline and my EM being at its worst, I´m starting to wonder if my EM was caused by taking amytriptiline!!
How is your mom doing?

Brief bullet points.

Mom is about the same, the second Ketamine test didn’t help her enough and caused one side effect which caused us to abandon that medication.

  1. I think Risperdol (I know in moms case) can cause EM, and I think Amytriptiline might also but this is probably an exceedingly rare side effect. Maybe 1 percent or less than all EM suffering patients could have been affected by these drugs. So I think there’s a chance, but it’s extremely small. This is just my guess.

  2. I found out in old records mom had Amytriptiline in her pill mix but this was in 2003 less than a month, and that didn’t help her and that mixture of pills was dropped. She was taking oral morphine which worked a bit better than some other pain killers, but that was dropped for other reasons. She was taking the Elivil as a part of her EM treatment plan however, it wasn’t the “cause” of her onset of symptoms. I’m guessing it was ineffective and can only speculate it could make her symptoms worse. With the cream below it seemed to only have a “warming effect”, perhaps masked with the Ketamine kicking in.

  3. Mom had a warming of the feet when the Mixture cream with both Amytriptiline and ketamine were applied. She also had four side effects: mood changes, more shaking in legs, blurred vision, rapid heart beats. . . and a feeling that her heart might quit. With the mixture of both in her foot cream tests. These were brief side effect but worried her enough to cause us to stop.

  4. When we tried Ketamine cream alone, she didn’t have any of the four side effects listed in the point above. She had one bad side effect from the Ketamine cream alone and we stopped using the cream again.

  5. Ketamine cream alone caused relief of pain and lower temperature, but she was not more active and was more sleepy, taking longer naps. She had problems controlling her legs and claimed she might fall and stumble with the Ketamine cream alone being used. This could have been from enhanced effects on other pain killers, irregardless of the reason we stopped using it again. It was to troubling.

Mom is off the cream, which we only applied for 5 days out of seven days during out test of the pure 1/2 percent ketamine cream (compounded). In both cases the cream didn’t have a greasy base for the cream which would hold in heat and not allow the feet to breath. Some creams or gells we have tried will warm her feet by sealing in the heat and not allowing the feet to breath.

I could send you a much longer private message if you want more details. And I’ve thought about posting some pictures with more documentation which would go along with the logic and thinking I’ve had.

Briefly Wikepedia- a search on 5-HT will show you information on the 5-HT neurotransmitter site. Amytriptiline will affect 7 of the 8 5HT sites that can cause blood flow, or temperature regulation issues. 5-HT site 7 can be permanently changed with Risperdol it seems. . . at least that what it looks like in reading about it. Amytriptiline can affect that same site, but I don’t know if it’s as bad or dangerous as Risperdol as an antagonist of 5-HT site 7.

(5-HT is just a functional name for Serotonin.)

I have to also say Risperdol is supposedly exceedingly safe. . . (and as a bonus, it can give young boys breasts if that’s what you want). . . .

But seriously, Risperdol is supposed to be very safe, and it may not affect many and perhaps only a very few in the world with EM symptoms. I think the thermal regulation side effect quote was something like .04 percent in their literature, if my memory is good.

Unfortunately my mom seems to be one of the “lucky few” that may exist in the world who had Risperdol give her EM, but not just EM symptoms that are temporary and resolve, but EM symptoms from some kind of damage. (Perhaps damage to the 5-HT 7 site?) This is my working theory, and it’s only based on my mom’s experience and what we’ve seen. And other information is more speculative based on the Serotonin activity theory.

Also Serotonin syndrome can cause Raynauds like symptoms which could include cold and chilling of the limbs. In mom’s case a mixture of pills that could become a kind of trigger to Serotonin syndrome have rarely given her cold feet, but this only happened once or twice in 15 years. That’s a further data point, that I use for my logic. (Also : The tibial nerve block tests and first ketamine test caused a kind of raynauds like look on parts of her toes with “white” cold areas on parts of her toes.) She at times shows those symptoms on her hands, but this may be tied to environmental chilling as well from cold air. Sometimes she gets cold hands from certain pill mixtures, my observation.

Risperdol literature says a rare side effect is the body’s inability to control it’s own temperature.

When mom had the mixture of both Ketamine and Amytriptiline as the foot cream - her feet felt warm at first - meaning the first time she had it applied. Months later Ketamine cream alone, her feet never warmed up from the cream application. So that to me is a small clue.

Mom now has more response to the opiod drugs, Norco and Fentynl pain patch. She responds to them and sleeps more since she had the ketamine cream. It seems for her the ketamine cream resets her opoid tolerance and she can taper off some doses. I think that tolerance reset is perhaps the only long lasting benefit of the Ketamine cream. Perhaps it’s a good side effect. I think (the tolerance reset/amplification) lasts perhaps a month, but this is based on the first application test.

Lastly mom had mild burning foot symptoms from a drug called Xanex back in the mid 1990’s and the symptoms resolved when the Xanax was abandoned. Xanax doesn’t seem to cause any changes in Serotonin that mimic Risperdol, so that EM like mild episode was likely caused by a different activity on the nerves. It also resolved when she stopped using that drug.

Mom was on nerve pills for “anxiety and fear” at least that was the outward story that the psychiatrist was giving us. He prescribed Risperdol to get her off Thorozaine. This in 2002.

She unfortunately was going to a get nerve medications for physical ailments which were causing her problems and once the physical ailments left her from real operations that resolved real problems, her need for nerve pills (fear and anxiety) disappeared.

Now we not only have physical problems to deal with. We have the mental health complications from things like “cognitive decline” that can occur from pills she takes to “calm the nerves” and calm them for her feet. Ativan for example can cause cognitive decline. She’d like to get off that, but we have to find a good way to get rid of that without it affecting her feet. The pill mix may not help her much, but it still is better to have constant 7 level pain while awake vs constant 10 level pain. So we have a baseline of pills we can’t easily leave unless we find a better combination.

The following is a list of pills that did not work for mom:
Tramodol and Asprin.
Vicodin (alone)

The following worked a bit
Oral Morphine.

Fentynl and Norco.
Oxybutinin (reduce bathroom trips.)

Ketamine cream with Amitriptilne (with bad side effects)
Ketamine cream (bad side effect, enhanced drowsiness)

Tibial Nerve block (worked three out of four times, but last time
worked the least) It can’t be used over and over again due to
tissue destruction and permanent block of nerves with injection might cause loss of function, need for braces on legs, etc.

Oral Mexilitine (she’d have to get off much of the pain medication and have the test under hospital care.)

Lanacane cream
Mixed with Camille Backman’s French Vanilla cream.

Zinc ointment (held in heat, massive flare)
Hawaian tropic cooling gel (gel holds in heat and doesn’t let feet breath).
Burn Relief Jell (same as other two holds in heat)

Cool air blown over feet from AC.
Elevation of feet. (They are either elevated or in cold water now)
Ice packs
Cold water spraying over feet for cooling and evaporated cooling
Cold spray (from Quick Freeze aerosol can. quick chilling but way to risky of frostbite and not something available over the counter.)
Cold water immersion in water 40 to 58 degrees. Water will warm up with no fear of frostbite. Sometimes her feet will get cold however.
EB cooler - it’s an ice pack system that used ice water. But these are only available used as the company went out of business from lawsuits regarding “frostbite”. You have to be careful with ice packs.
Cold air “box” using feed of cold air in a chill box. Works but is bulky and can use ice for swamp cooling designs or a design that feeds AC from an air conditioner to the box using aluminum vent tubes from a clothes dryer. (The box is something I threw together, but only deployed in a nursing home, where the temperatures were 89 degrees in the room.)

Mom has had some luck with diabetic pressure socks which are wet
and become cold from evaporation of water.

My mom’s em worsened with that drug. She also has raynauds… She stopped that drug weeks ago and is not better, your article was good, it said the symptoms should hopefully go away in about 3 months… At least the worsening part. Fingers crossed