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Amitriptyline caused my neuropathy

I have taken Amtriptyline for 20 years started on it for insomnia. I then developed burning skin pain, and no one ever thought it was the Amit. I wouldn't have either, except, I was put on Remeron an other anti-depressant , and first developed numb feet, and the the itching skin and then after a few weeks the burning skin pain. I am no off the Remeron, and the pain is back to the normal level. Now what to do about going off Amit is very scary. It helps the pain, but yet is causing the pain. does that make any sense. Wouldlove to hear from anyone else .

I am not a fan of amitriptyline. I was on it a long time ago, and am no better off for being on it. All my problems started after I took that drug. That doesn't mean it caused it....but, I haven't ruled it out either.

I used to take this drug in the mid-1980's. I think it was prescribed a lot back then... may still be. I was on a hefty dosage of 100 mg.

I agree with Cyclelops statement:

"That doesn't mean it caused it....but, I haven't ruled it out either."

Mere

i take amitriptylene at night. it has helped with the stabbing pains and keeps me asleep once i get asleep. the only side effect i have noticed is its hard to stay awake for a while once i get up.

This drug has some mixed history. It appears on lists from neuropathy sites as a "cause" of axonal neuropathy.

Here is an example:
http://www.wrongdiagnosis.com/t/toxi...line/intro.htm

However, I couldn't quickly find the studies that support this yet.
I'll look later in more detail.

Recently there have been studies showing amitriptyline actually enhances peripheral nerve regeneration.
Here is the link to that article:
http://neurotalk.psychcentral.com/sh...=amitriptyline

This might be dose dependent or a factor in those who do not metabolize this drug well. I do think this is very confusing.

Edit to add:
It appears that amitriptyline is being used as an injected anesthetic in some situations. So I found some neurotoxic in vitro (no in living subjects) on this subject. This would place the drug in high concentration near neurons:

Quote:

Eur J Anaesthesiol. 2007 Aug;24(8):702-8. Epub 2007 Apr 17.
Differential neurotoxicity of tricyclic antidepressants and novel derivatives in vitro in a dorsal root ganglion cell culture model.

Haller I, Lirk P, Keller C, Wang GK, Gerner P, Klimaschewski L.

Medical University of Innsbruck, Department of Anesthesiology and Critical Care Medicine, Innsbruck, Austria.
Abstract

BACKGROUND AND OBJECTIVE: Tricyclic antidepressants are commonly employed orally to treat major depressive disorders and have been shown to be of substantial benefit in various chronic pain conditions. Among other properties they are potent Na+ channel blockers in vitro and show local anaesthetic properties in vivo. The present study aimed to determine their differential neurotoxicity, and that of novel derivatives as prerequisite for their potential use in regional anaesthesia. METHODS: To directly test neurotoxicity in adult peripheral neurons, the culture model of dissociated adult rat primary sensory neurons was employed. Neurons were incubated for 24 h with amitriptyline, N-methyl-amitriptyline, doxepin, N-methyl-doxepin, N-propyl-doxepin, desipramine, imipramine and trimipramine at 100 mumol, and at concentrations correlating to their respective potency in blocking sodium channels. RESULTS: All investigated substances showed considerable neurotoxic potency as represented in significantly decreased neuron numbers in cultures as compared to controls. Specifically, doxepin was more neurotoxic than amitriptyline, and both imipramine and trimipramine were more toxic than desipramine or amitriptyline. Novel derivatives of tricyclic antidepressants were, in general, more toxic than the parent compound. CONCLUSIONS: Tricyclic antidepressants and novel derivatives thereof show differential neurotoxic potential in vitro. The rank order of toxicity relative to sodium channel blocking potency was desipramine < amitriptyline < N-methyl amitriptyline < doxepin < trimipramine < imipramine < N-methyl doxepin < N-propyl doxepin.

PMID: 17437653 [PubMed - indexed for MEDLINE]

from http://www.ncbi.nlm.nih.gov/pubmed/17437653

and this one :

Quote:

Toxicol Appl Pharmacol. 2006 Nov 15;217(1):100-6. Epub 2006 Aug 15.
A proposed mechanism for amitriptyline neurotoxicity based on its detergent nature.

Kitagawa N, Oda M, Nobutaka I, Satoh H, Totoki T, Morimoto M.

Department of Anesthesiology, Tsuruta Orthopedic Clinic, Ushizu, Saga 849-0306, Japan.
Abstract

Although amitriptyline has gained attention as a potent local anesthetic, recent animal studies showed that it can cause irreversible neural impairment. We hypothesized that nerve membrane disruption caused by solubilization, a common detergent property, accounted for amitriptyline neurotoxicity. We used a two-phase approach to test our hypothesis. Firstly, we determined (1) the molecular aggregation concentration of amitriptyline, (2) the concentration of amitriptyline that disrupts artificial lipid membranes and (3) the concentration of amitriptyline that causes hemolysis. Secondly, we compared these levels with neurotoxic concentrations determined from assessment in a rat model of spinal anesthesia using changes in cutaneous stimulus threshold (CST). Amitriptyline concentrations that caused molecular aggregation, model membrane disruption and hemolysis were 0.46%, 0.35% and 0.3%, respectively. Animal study showed a significant increase in CST at >or=0.3% of amitriptyline, indicating neurological impairment. Since amitriptyline caused model membrane disruption and hemolysis at the molecular aggregation concentration, solubilization plays a role in the destruction of artificial membranes and erythrocytes. Furthermore, these concentrations are also in good agreement with the minimum concentration causing neurological injury. Therefore, while additional studies, including histopathology, are necessary to clarify this observation, amitriptyline neurotoxicity appears to be associated with its detergent nature.

PMID: 16978678 [PubMed - indexed for MEDLINE]

and this one:
http://www.ncbi.nlm.nih.gov/pubmed/16717317

All involving injection as an anesthetic.

I am still looking for oral studies...

There are studies about SSRIs causing neuronal cell death...these have been around for few years. This paper includes amitriptyline with prozac (which has been most studied so far):
http://www.ncbi.nlm.nih.gov/pubmed/11996893

Now what do I do. Is there a doctor some place that knows about this link. I am decreasing the Remeron, and the depression is increasing, but the burning pain is less. This is such a catch 22 situation.

Janet

Typically amitriptyline is used in small doses for PN. It may be long term high dose for depression is more problematic. That is just my take on it.

I would not expect a regular doctor to know the details about this drug. Perhaps some neurologist or anesthesiologist might if they work in a teaching hospital.

Most doctors don't know that amitriptyline is on neuropathy lists as "toxic".

Quote:

Originally Posted by mrsD (Post 663519)

When I try to decrease it even by 10 mg the burning gets worse. I take 85 mg at night. I always new when I went higher my skin would burn more, and when I took 75mg my skin would burn more. 85 mg seemed to be the right dose for me.

Janet

You know Brian here, used it in I think 100mg and he didn't have any problem.

I don't know how often he visits now, that he is so much improved.

I see you are a new member with a low post count, so your PM privileges are not active yet. I'll PM him to come to this thread.

How's that?

Quote:

Originally Posted by mrsD (Post 663536)

Thank you , you are so kind

I tried to get an appt with my neurologist who I haven't seen in 8 years, and I need a new referral and he is booking into October. Is 85 mg considered a small dose, maybe I wouldn't have to go off of it ?

Sincerely,
Janet