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Has any one read this study? Tricyclics

In one of my search flurries that I occassionally do, to find causes of neuropathy, I ran across the following citation. I have to go find the journal if I want to read the results. That doesn't surprise me, given the plethora of articles on how much TCAs benefit people in pain. The study is 10 years old, and it seems to be the only mention of TCAs as a potential cause of neuropathy. Hmmm, wonder why?

Interestingly, I was treated with TCAs, and zoloft concurrently, back in the '90s, and my TCA blood levels were never monitored. Of course, I felt awful the entire time, and slowly weaned myself off them and back into life. I can't tell you how bad my restless leg was back then as there are no words. The worse I felt the more they gave me and the more they gave me the worse I felt, and I had an 'a ha' moment. that perhaps this stuff wasn't good for me.

Anyway, here I find this Italian study, only one, and I can't find even the abstract, let alone the full text.

I have a very strong opinion on TCAs and I won't get into it. TCAs were replaced by SSRIs in the treatment of depression...and the psych profession was ever so glad, as TCAs can be lethal and SSRIs are not as lethal if overingested. So what to do with TCAs...hey, why not use them as pain meds. (Like people in pain don't think of doing themselves in at times..hmmm)
Big Pharma's reasoning has me stumped, other than, how to have a rummage sale with drugs we no longer really need....Repurposing!!

Lately, SSRIs are being repurposed for pain relief, well, what isn't these days. I suppose it is cost effective to find new uses for old 'research and development' as new drugs hit the market.

Anyway, if any one has access to this study, I would like to read what it says. Of course, 'correlation is not causation' and the title says, associated with, not causes. It isn't a case that would stand up in court, :winky:

I do think that we do need to ponder about what medications we take. Seriously. At times, I do not know what is worse, the cure or the disease or even more ominous if the cure for one thing, brings on another.

Neuropathy Associated with Tricyclic Antidepressants

Int J Geriatr Psychiatry. 1997; 12(8):868-9 (ISSN: 0885-6230)
Benazzi F; Ciucci G

PreMedline Identifier: 9283933

Nice to see that you are posting. I agree with you on the cure and the disease analogy. When I first came down with PN, my first neuro said I suffer from "spreadical cortical depression". He put me on a high dose Tryciclic. That was my very first time on any such meds. The first 2 weeks I was having heart rythym issues from the Tryciclic,and then he put me on beta Blockers. That again was my first time on such meds. The tryciclic gave me a strong case of Bruxism,and some other bizarre mouth/jaw issues.

Not too long after I was on the Tryciclics I also developed anxiety/panic in which case the answer was to increase my dose even higher.

I wonder if this Tryciclic use didn't mess up my brain chemistry to a permanent extent. I haven't been on Tryciclics for over a year now but I still have bruxism and to a lesser extent anxiety.

Holy cow! If the correlation is true, it is certainly disturbing.

I was placed on an SSRI ten years ago and developed chronic insomnia and uncontrollable muscle twitching that are with me to this day. Guess what I was given to make me sleep while I was on the SSRI? A tricyclic! By the time I got completely off both meds in 2000, I was flopping around like a marionette without strings.

My neuropathy started in 1998. It had never occurred to me that there might be a connection between that and the meds, although I have certainly had enough ill effects from the meds to consider that a possibility.

If anyone has any more info on this subject, please post it.

fanfaire
:cool:

Just while on the subject

The TCA side effect list reads it can cause extrapyrimidal symptoms. Within 12 months I developed the bruxism,but I also had this other issue where my top teeth and bottom teeth would collide shut right on top of each other when I was speaking to someone.

It was as if I was taking a bite of air,and then I would grind my teeth around like I was rabbid or something like.

I then read up on the sideffects and my neuro now,advised that I have developed extrapyrimidal symptoms of which tongue/mouth/jaw are the most common. I then read on about other worse symtoms such as lick smacking,thrusting hips and the like.

Holy Cow... Holy Sheep is right!:eek:

That's when I decided TCA's are not a good thing for me. By that stage I was on 300mg divided dose. That could have sedated a horse. I'm lucky all I have is the bruxism and teeth slamming. It could have been worse.

Hmmmm don't think I will be taking the amitriptyline that was prescribed for my neuropathy even if it flares up again or starts to get worse over time,especially after reading this thread :eek:

Quote:

Originally Posted by fanfaire (Post 149948)

I was on Celexa a number of years ago. I made the connection to the RLS then. I'd had bouts of RLS off and on in the past but nothing like happened on the Celexa. I was on Effexor XR for a little over 3 years. The PN started during the Celexa along with the RLS. The RLS was far worse than the PN for me on Celexa. The Effexor, the PN was *much* worse and the RLS was there also but not as badly as it was on the Celexa. I've been off of Effexor for going on maybe 6 months? I'd have to look back through my posts here to pinpoint a time frame but that feels about right. My PN seems, slowly -ever so slowly - to be getting better. I *know* there's a correlation to the SSRI's and SSNRI's there! What I'm waiting to find out is if this is a permanent state of affairs? Will I ever only get so much better but never back to 100%? I don't know. But I do know that my experiences with medications over the past couple of years has made me extremely leery of using most any prescription drug. The drug companies *don't* test properly, IMO. The so-called trials are a joke. They lie and cheat and do whatever is necessary to make that dollar. Meds are big business. So as far as I'm concerned unless it's absolutely life threatening if I *don't* take a specific drug....they can count me *out*!

Currently I take generic Ultracet as needed for the PN pain and Atarax for a number of reasons: Anxiety, itching and because the Ultracet gives me a speed buzz and since I usually take it at night I have to have help to sleep. That's it...besides sudafed when needed and Ibuprofen and things like that.

Barbara

I agree with Cycleops that we should ponder about what medications we take, side affects can be completely differant from one person to another though, waying up the side affects against the benefits is the important thing to my way of thinking, seeing some can't even function properly without there choice of relief drugs.

I have used Endep since the begginning of my PN, in that 4 years i found Endep helped me tremendously with the burning with only very little side affects, of a dry mouth and a crave for sweet things but more so on higher doses, then again i have seen posts that some PN'ers get knocked rotten with extreemly small doses of amitriptline, like 25 mg.

Seeing the way i am going these days, in my case i personally can't see any correlation between Amitriptline and PN, i can only say that it was a wonder drug for me, that helped me through some really rough times and now fortunatly i am weening my way off them, as i think i do not have the need for them now, in the last couple of weeks i have already halfed the dose with no problems at all but if i had to go back on them, i wouldn't hesitate.

i think the pamelor that i am taking is helping about 1 or 2 points and it is a tca. it has some side effects, but i will do just about anything to get rid of some pain. i would like to know more about this study.
steff

Quote:

Originally Posted by Steff (Post 150269)

Hi Steff, i found this abstract that relates to people that started take TCA's from and over 65 years of age.
http://www.springerlink.com/content/45437757l1421286/

Amitriptyline has appeared for a long time in lists of agents that can cause axonal injury.

example:

Quote:

Anesth Analg. 2006 Jun;102(6):1728-33.Click here to read Links
The neurotoxic effects of amitriptyline are mediated by apoptosis and are effectively blocked by inhibition of caspase activity.
Lirk P, Haller I, Hausott B, Ingorokva S, Deibl M, Gerner P, Klimaschewski L.

Department of Anesthesiology and Critical Care Medicine, Innsbruck Medical University, Austria. philipp.lirk@uibk.ac.at

Oral tricyclic antidepressants, widely used as adjuncts in the treatment of chronic pain, block sodium channels in vitro and nerve conduction in vivo. However, toxicity of amitriptyline has been observed after neural application. We therefore investigated the mechanism and possible prevention of amitriptyline neurotoxicity. To assess dose-dependent neurotoxicity of amitriptyline, we incubated neuron cultures from adult rat dorsal root ganglia with amitriptyline and quantified neuronal survival. Additionally, we investigated accepted markers of apoptosis (mitochondrial membrane potential, cytosolic cytochrome c, and activated caspase-3) and co-incubated amitriptyline with an inhibitor of caspase activity, z-vad-fmk, to assess the effect on cell survival. We found a dose-dependent neurotoxic effect of amitriptyline. Neurons incubated with amitriptyline exhibited loss of mitochondrial membrane potential, release of cytochrome c into the cytoplasm, and activation of caspase-3. Co-incubation with z-vad-fmk substantially improved neuronal survival in culture. In conclusion, amitriptyline-induced neurotoxicity is mediated by apoptosis and is attenuated by inhibition of caspase activity, suggesting that inhibition of apoptotic pathways may be efficient at alleviating local anesthetic-induced neurotoxicity. In vivo studies will have to corroborate whether the co-injection of anti-apoptotic drugs with local anesthetics decreases neurotoxic side effects.

PMID: 16717317 [PubMed - indexed for MEDLINE]

Now there are reports that TCA's are the best agents to use for selective norepi reuptake (useful for chronic pain)

Quote:

Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30.Click here to read Links
Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.
Gillman PK.

PsychoTropical Research, Bucasia, Queensland, Australia. kg@matilda.net.au

New data on the pharmacology of tricyclic antidepressants (TCAs), their affinities for human cloned CNS receptors and their cytochrome P450 enzyme inhibition profiles, allow improved deductions concerning their effects and interactions and indicate which of the TCAs are the most useful. The relative toxicity of TCAs continues to be more precisely defined, as do TCA interactions with selective serotonin reuptake inhibitors (SSRIs). TCA interactions with monoamine oxidase inhibitors (MAOIs) have been, historically, an uncertain and difficult question, but are now well understood, although this is not reflected in the literature. The data indicate that nortriptyline and desipramine have the most pharmacologically desirable characteristics as noradrenaline reuptake inhibitors (NRIs), and as drugs with few interactions that are also safe when coadministered with either MAOIs or SSRIs. Clomipramine is the only available antidepressant drug that has good evidence of clinically relevant serotonin and noradrenaline reuptake inhibition (SNRI). These data assist drug selection for monotherapy and combination therapy and predict reliably how and why pharmacodynamic and pharmacokinetic interactions occur. In comparison, two newer drugs proposed to have SNRI properties, duloxetine and venlafaxine, may have insufficient NRI potency to be effective SNRIs. Combinations such as sertraline and nortriptyline may therefore offer advantages over drugs like venlafaxine that have fixed ratios of SRI/NRI effects that are not ideal. However, no TCA/SSRI combination is sufficiently safe to be universally applicable without expert knowledge. Standard texts (e.g. the British National Formulary) and treatment guidelines would benefit by taking account of these new data and understandings.

PMID: 17471183 [PubMed - in process]

So it is a conundrum ... and may be dose dependent.