Amitriptyline Downregulates Chronic Inflammatory Response to Biomaterial in Mice, 2020, Scheuermann et al

Dolphin

Dolphin

Senior Member (Voting Rights)
https://link.springer.com/article/10.1007/s10753-020-01356-0

Amitriptyline Downregulates Chronic Inflammatory Response to Biomaterial in Mice
Abstract

Recent data has signaled that in addition to its therapeutic indications as antidepressant and analgesic, amitriptyline (AM) exerts anti-inflammatory effects in humans and experimental animal models of acute inflammation.

We tested the hypothesis that this compound could also modulate the chronic inflammatory process induced by synthetic matrix in mice.

Polyether-polyurethane sponge disks were implanted subcutaneously in 9-week-old male C57BL/6 mice.

The animals received by oral gavage 5.0 mg/kg of amitriptyline for seven consecutive days in two treatment regimens.

In the first series, the treatment was initiated on the day of surgery and the implants removed at day 7 post-implantation.

For the assessment of the effect of amitriptyline on chronic inflammation, the treatment was initiated 7 days post-implantation and the sponge discs removed 14 after implantation.

The inflammatory markers evaluated, myeloperoxidase - MPO, nitrite content, IL-6, IFN-γ, TNF-α, CXCL1 and CCL2 levels, and NF-κB transcription factor activation were reduced in implants when the treatment began 7 days post-implantation (chronic inflammation).

In contrast, only mast cell number, MPO activity and activation of NF-κB pathway decreased when the treatment began soon after implantation (sub-acute inflammation) in 7-day old implants.

The anti-inflammatory effects of amitriptyline described here, extend its range of actions as a potential agent able to attenuate long-term inflammatory processes.
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I know some people are very anti-this type of drug (i.e. a tricyclic) but I have found it very useful both for sleep and also various types of pain symptoms, e.g. IBS, TMJ, muscle and joint pains, headaches, et cetera. I think they've also helped me with noise and light sensitivity.
 
Dolphin said:
I know some people are very anti-this type of drug (i.e. a tricyclic)
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I think it's often just that they've tried it and found that it did nothing, or made them worse.

Personally, the tricyclics I've tried (including amitriptyline at everything from 5mg to 30mg) caused significant depersonalisation, which led to feelings of depression. I never got past that stage even after more than a year, and as there are no benefits to balance out the negatives, I don't take them.

I would suggest people try amitriptyline if it's suggested by their GPs, though, because some patients clearly do benefit.
 
I saw benefit from it but it isn't the be all and end all, certainly.

It stopped working as well as it used to for a while, then I accidentally took two one night, and the benefit came back. So occasionally, I nudge myself back into the 'it's working' zone by taking an extra dose at nighttime (usually if my PEM has been accumulating or my sleep has been worsening over any length of time). That seems to do the trick for now and avoids the side-effects of an increased dose daily.

For me, the main benefit is waking up without the stiffness that I usually have and feeling more refreshed. Getting the right dose means I don't need to take any OTC painkillers for that, which I would have done without it.

But there's definitely a grogginess that it can cause. Sometimes it verges on being like a hangover. I think that side-effect varies but is common among people who take it.

For me, moving the drug forward an hour in the evening helped me overcome that, as did one cup of really strong coffee first thing, but others can't get rid of it.

I think it's possibly related to how bad your brain fog is generally. Anecdotally, people have reported a link between sensitivity to TCAs and the severity of alcohol intolerance, though SSRIs are the most commonly linked in this way.
 
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Yes @adambeyoncelowe sedative hangover of amitryptiline and the fact it stopped being effective for sleep made me give it up.
I can’t tolerate caffeine although I did rely on caffeine when I was in my long (7+) undiagnosed period. If I have any caffeine I will be awake all night in a tired but wired state.
Also not to underestimate the weight gain side effect of amitryptiline.

The hangover ugh very sluggish. I wonder sometimes if some of the people with ME who need to sleep a lot (especially those with milder ME) are experiencing sedation from amitryptiline and other commonly prescribed drugs. It took me over a year to become aware that amitryptiline hangover existed. When I raised it with the gp she was well aware of it yet never mentioned it when starting me off on the drug......

I don’t think there is any research evidence that any medications are effective in people with ME and what side effects are experienced. It is rather a Russian roulette approach to prescribing and doesn’t take account of the reports that PWME don’t tolerate medications well.

and don’t get me started about Pregabalin ........
 
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By the way, I get more sleep on Surmontil (8-10.5 hours) than Amitriptyline (7-8.5 hours). I switched away from Surmontil when they stopped making the 10mg tablets but switched back so have spent 25 years or so on one or the other.
 
I have got my weight down to a low level on Surmontil (BMI of 20). My weight did go up on Amitriptyline which may or may not have been related to the drug (I was a bit of a workaholic and didn’t focus on my weight).

I do feel a bit groggy on it but it’s not like I’m going to feel well off it: I will likely feel overstimulated by everything off it. And with less sleep I will feel more malaise so I accept the grogginess.
 
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I just started low dose amitriptyline for nocturnal bruxism which is affecting my jaw and my teeth. It seemed to help the first day or two, but I'm not sure after that. It is helping my IBS though, as it has done in the past, with dialing down any sense of urgency I usually get in the first hour after waking.
 
I very much recognise your experience @adambeyoncelowe . It's a staple of my medication at 10mg and has contributed (a bit) to me being able to work part time from home.
Also, previously been presrcibed SSRI's (doctor thought I had anxiety when I was first falling ill with ME) and I've never had such a range of side effects from medication before. Even worse when weening off it, even very gradually, and it took a three months before all the related issues went away (brain zaps particularly).
 
Dolphin said:
By the way, I get more sleep on Surmontil (8-10.5 hours) than Amitriptyline (7-8.5 hours). I switched away from Surmontil when they stopped making the 10mg tablets but switched back so have spent 25 years or so on one or the other.
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I’m surprised that Surmontil doesn’t get mentioned more in comparison to Amitriptyline. I remember reading Dr Myhill saying it was the only one of its type that didn’t have a negative effect on sleep architecture.
 
My GP had me on them around the late 90s.

When I missed an appointment, made to inform her of the zombieism they caused, because I was so sedated I couldn't get out of the chair (couldn't see the point of it), I was told off, told I should no longer make appointments and only use the morning emergency surgery, and had my dosage increased from 75mg to 125mg.

This was/is the only GP appointment I have ever missed.

I still have enough to tranquilise a small to medium sized herd of elephants, as I stopped taking them after that, and she kept prescribing.

For me they can be useful, occasionally, at much lower doses.

ETA - AFAIK everything else I've ever been prescribed for sleep makes me itch, which keeps me awake.
 
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to add . . .

I'm not sure why the ME doctor prescribed it for me in the first place? I didn't have pain or any issues that would require any prescription except for a viral infection that was pretty much resolved by the time I saw him as a patient.
 
ringding said:
I very much recognise your experience @adambeyoncelowe . It's a staple of my medication at 10mg and has contributed (a bit) to me being able to work part time from home.
Also, previously been presrcibed SSRI's (doctor thought I had anxiety when I was first falling ill with ME) and I've never had such a range of side effects from medication before. Even worse when weening off it, even very gradually, and it took a three months before all the related issues went away (brain zaps particularly).
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SSRIs were awful for me. Never again.
 
I've tried all sorts amitriptyline, SSRIs, NSRIs. Prescribed for both pain and sleep problems.

Couldn't get on with any of them. I might feel a bit drowsy temporarily and then suddenly wide awake and absolutely exhausted. Very prone to "hangover" effects even from drugs that supposedly disappear quickly from the system.

Frankly, if they worked, I wouldn't give a rats whether they were usually described as anti depressants or not. I have ME so there's been an immediate assumption of mental health problems due to the diagnosis alone. Taking a tri-cyclic, SSRI or NSRI won't make much difference.

In some ways it might have made life easier as I'm sure some doctors thought I was just against taking an anti depressants & in some sort of denial. Being difficult about it. That then reinforces the view of a mental health patient who is resistant to treatment. :banghead:

My attitude, if you find a drug that helps even if it is classed as an anti depressant then you're lucky. Why wouldn't you take it?
 
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