DRUGS (RX) ~~ Used for Treating Peripheral Neuropathy:
 

This is just a huge subject. There are primarily two ways PN may be "treated".

1) Most of the people with PN can only be helped palliatively. This means by reducing symptoms of pain, burning and numbness.

2) The second way is by using agents to modify the disease process. IVIG and Rituxan are examples of this. Also if the PN is secondary to autoimmune issues, reducing autoimmune antibodies may modify the disease process in some patients.
Those agents are classed as autoimmune drugs, which suppress antibody production in the body.

3) Patients with hereditary PN, do not have treatments yet other than symptom reduction types.

This is an old list of treatments I made years ago. It does not include supplements, because we have a separate thread now on this forum for that: statements in red are added today by me.
This thread will deal with the treatments by group and the next thread will start with the AED... anti-seizure drugs. These can block signals being passed on by nerves from reaching the brain.
I found some technical explanations for some of the drugs, which may be helpful in the post for those taking them.

edit: quick link to amitriptyline and nerve growth factors:
http://neurotalk.psychcentral.com/sh...=amitriptyline

I work with Deplin and just want clarify a few things. Metanx is part of the Pamlab family along with Deplin. Deplin, which is high L-methylfolate, has indication for depression symptoms. Metanx, has the unique indication specific for DPN. Metanx works by addressing the inadequate nutrition which may lead to nerve damage. Please visit the Metanx or Deplin website for more patient information. Hope this helps.

Thank you David.... we are very very familiar with Metanx.

I only include Deplin here as an RX version of methylfolate since this list is RX examples. People with MTHFR mutation may use Deplin also.

FDA requires an RX category of any folate 1mg or over.
People can purchase methylfolate OTC from the Solgar supplement company at 800mcg/tablet (.8mg).

Folate BTW is not a huge player in PN management. Metanx's
main benefit is the methylcobalamin.
Those with the MTHFR mutation however have higher homocysteine levels and can benefit from Metanx (and folate in general). Some drug treatments deplete folate, and may be used by patients with PN.... methotrexate, NSAIDs, Prednisone, H2 antagonists, HRT, Sulfasalazine, etc.

This is an interesting discussion, but as always consult with your doctor. For eample, Aleve(naproxen) moved me very close to chronic kidney failure.

Yes, all the NSAIDs carry risks. In fact all the drugs on this list are risky in some way. NSAIDs also increase the risk of cardiovascular incidents.

This list is not for people to self medicate with....it is to illustrate the various types of medications that may work to relieve some
pain of neuropathy.

As I get time I am going to make individual posts on each group. But the holidays have delayed me somewhat. :rolleyes:

There is one more disease modifying drug that is very common in autoimmune disease/neuropathies...Plaquenil. It's an anti-malarial used as a DMARD.

It may not actually 'fix' the neuropathy, but it does aid in control/slowing progression of autoimmune disease...therefore possibly indirectly helping the neuropathy.

Maybe I should have waited to comment when you address that particular group. Anyway, I'd be interested in hearing your comments on Plaquenil.

Neurons:
 

It is really not possible to discuss how many drugs work for symptoms of neuropathy, without understanding how neurons work and their anatomy.

This Wiki article is very good, and I suggest readers here read this before I get into the various types of drugs.

http://en.wikipedia.org/wiki/Neuron

Damage to the axon, can occur in PN. This can be autoimmune antibodies that attack the insulation, or a toxin. Some inflammatory cytokines produced by the body, may attack axons. There is a nice diagram on the Wiki link showing what an axon is. There are some very LONG axons in the body, so damage can happen anywhere along it. It can be severed or compressed. Sciatica is one common example.
This link explains the myelin sheath, how it may be injured and how it may regenerate:
http://en.wikipedia.org/wiki/Myelin

Statin drugs that are used to lower cholesterol, affect they myelin production in the body and the repair of myelin in nerves.
This article by Dr. Graveline MD explains this:
http://www.spacedoc.com/neuropathy_statins.htm
And this explanation explains why this family of drugs can lead to nerve damage both in the periphery and brain.

Also this article explains "inhibitory" actions some nerves have and this concept is important to understand. Inhibitory nerves are affected by benzodiazepines-- drugs like Xanax and Valium.
This link explains inhibitory functions of neurons.
http://en.wikipedia.org/wiki/GABAA_receptor

This is one reason why benzodiazepines work for PN pain in some patients. And why when discontinued, the inhibition is removed and activity is restored, often with very uncomfortable results. Benzos also are given following seizures, to reduce hyperexcitable neurons from starting up again. They can also be used to prevent certain types of seizures. When patients are taking them for anxiety or psychiatric reasons, and suddenly discontinue, a seizure may result. Hence, discontinuance of Benzos should be montiored carefully by a doctor. I have read in some places that it can take weeks to months to successfully wean off them. Klonopin is the worst offender in this regard.

While PNers here are mostly concerned about peripheral nerves, there are nerves in the brain too, that participate in the perception of pain. Some of the drugs used to treat symptoms of PN work in the brain mostly, and are the antidepressants.
One older drug, amitriptyline (and nortriptyline) have shown in a recent study to help peripheral nerve growth factors. But the newer SSRIs and SSNIs work mostly in the brain to affect the perception of pain. The pain loop in the brain is quite large and covers a large area while it is working.

This Medscape article illustrates this:
http://www.medscape.com/viewarticle/568704_9
If you are not a member of Medscape you can join easily for free. There are some wonderful articles there on many medical topics.
The SSRI drugs therefore work on this complex pain loop and may reduce pain for some patients. Cymbalta is the newest, and Lilly did studies with it to prove this effect so the FDA would approve it for pain. It however, is not the only one that works.
The antidepressants with dual actions like Cymbalta are Effexor and Savella. These seem to work better than the old SSRIs like Prozac.

I will be attending the big pain conference this spring that is given every year... and any new information on central pain research I typically pick up there. I'll bring that to this board when that conference is held. It is usually in April or May.(Michigan Head-Pain and Neurological Institute sponsors it)

Edit -- This Medscape link describes the various treatments for neuropathic pain.
http://www.medscape.org/viewarticle/754961
You may have to join which is free, to view this video, and you may have to pause the video when the slides come up, as they don't remain on the screen for long. But the graphics are very good and illustrate the pain pathways in the dorsal roots and spinal cord.

Neurontin and Lyrica:
 

I am going to do a whole post on just these two. The other anti-seizure drugs will follow in their own post.

Neurontin (gabapentin) and Lyrica (pregabalin) are cousins.
They are both made by Pfizer, and have both been involved with fines and fraud claims against Pfizer who plead guilty and paid them.

Here are some links for that history: Neurontin
http://articles.sfgate.com/2004-05-1...tin-pfizer-fda
This is a long article.

http://en.wikipedia.org/wiki/Gabapentin

The Neurontin issue was inherited from ParkeDavis, who initially sent sales reps to doctors to encourage experimentation on patients off label for bipolar and chronic pain. They got caught eventually not long after Pfizer took over ParkeDavis.

I found an interesting PubMed review article from 2011, with some facts about the "effectiveness" of Neurontin in treating pain:
http://www.ncbi.nlm.nih.gov/pubmed/21412914
For those reading here not getting much relief--- this is why.
Only found useful in about 1/3 of patients.

This is the side effect profile for Neurontin from FDA reports:
http://www.drugcite.com/?q=Neurontin

This is Neurontin's monograph at Rxlist.com
http://www.rxlist.com/neurontin-drug.htm

Many people cannot tolerate this drug, and its nicknames over the years include Morontin, and Neurotten.

The Wiki article on Neurontin offers this mechanism of action, which still remains murky:
http://en.wikipedia.org/wiki/Gabapentin

Edit to add.... this link explains how gabapentin works in the brain:
http://www.wellnessresources.com/stu...rain_synapses/
While this may be crucial for children... adults still may be affected in ways we haven't explained yet. It is something to think about, certainly.

************************************************** ********

Lyrica is a more potent form of Neurontin: It is not generic yet, and remains very expensive.
And it, also, has been in scandals involving Pfizer:
http://www.bloomberg.com/apps/news?p...d=a4h7V5lc_xXM
fraud for Lyrica

Here is the Wiki on Lyrica:
http://en.wikipedia.org/wiki/Pregabalin

And the FDA reports:
http://www.drugcite.com/?q=Lyrica

Both of these drugs are highly sedating, and interact with other sedating drugs. So be careful with them if you use opiates or benzos.

They are mostly excreted whole through the urine by the kidneys, and for that reason do not enhance or block liver metabolism of other drugs. This makes them very attractive to doctors, who think this trait is safer than other anti-seizure drugs. Hence these are offered today FIRST in most PN treatments.

Many people find they cause weight gain. Also some people are appearing on these boards with rotten teeth. (I cannot find that yet in reports however). Both these drugs may cause edema, severe fatigue/brain fog etc. And both have FDA warning regarding suicidal ideation and depression.
This is the RX information for Lyrica:
http://www.rxlist.com/lyrica-drug.htm

So if you are taking one of these and feel they are not working, they probably aren't. Discuss this with your doctor. These drugs cannot be stopped cold turkey after being used for a long time...
that may result in seizures. So any change in therapy should be monitored by your doctor closely.

edit to add this information on two new recent studies showing
Lyrica not effective for pain (no better than placebo)
http://health.yahoo.net/news/s/nm/pf...o-pain-studies

http://www.foxbusiness.com/industrie...-lyrica-trial/

edit to add an example of a taper schedule:
This is a taper from Neurontin with Lyrica added that Nide44 has posted in the past. I have his permission to copy it here:
This is a taper specific to Nide44's medical condition. Tapers may vary,
according to patients needs and symptoms resulting from the change in dosing.
I recently found this paper, which suggests a slower taper for gabapentin because some people are very uncomfortable with this situation.:
from http://www.ncbi.nlm.nih.gov/pubmed/15898970

So based on patient response to a taper, I suggest you keep your doctor informed of any discomfort or alarming symptoms, so that your taper fits your specific needs.

Other anti-convulsants:
 

Most of the anticonvulsants affect nerves by changing the way ions (potassium, sodium, calcium) work on the membranes of the nerves to chemically induce a signal.
(Some cardiac drugs like Mexetil, and Tambocor also affect membrane potentials, but have little if any antiseizure effects)

This is an explanation of how this works:
http://en.wikipedia.org/wiki/Voltage-gated_ion_channel

Historically anti-seizure drugs were found to affect pain perception over time postmarketing. The first was Tegretol, which was initially used for trigeminal neuralgia. It was never a first line drug for seizures, because it has some long term toxic effects. But over time Dilantin was used for cardiac conduction problems the same way.

I would encourage anyone here taking an anti-seizure drug to look it up on www.rxlist.com and read the precautions and side effects carefully. I won't be going into detail here because of space considerations.

All of the anti-seizure drugs are slightly different in the way they work for chronic pain. Here is a good overview of the subject:
http://pain.about.com/od/treatment/a...onvulsants.htm

Some of them are more commonly used for PN, and I think that is based on some studies that various drug companies have done, or that doctors have seen in their CME classes. (continuing medical education for relicensure).

All of the anti-seizure medications typically have long term potentially serious side effects. So I will point those out, in case your doctor is not monitoring you closely.

Tegretol/Trileptal have potential to cause a sodium imbalance
which is called hyponatremia and lowering of white cells.
http://en.wikipedia.org/wiki/Carbamazepine
Trileptal was designed to have fewer liver metabolic complications, but Tegretol interacts with many other drugs' metabolism in the body. A good drug checker to test your specific combinations can be found here:
http://www.drugs.com/drug_interactions.html
As you can see there are MANY potentials for getting into difficulties taking Tegretol!

Topamax is another often used to prevent migraine.
It can also be used for chronic pain management and sometimes helps to lower the need for opiates. It too, has many serious potentially damaging qualities. Doctors were sent warning letters over the years about them, but still today some do not test for bicarbonate depletion-- which leads to metabolic acidosis in about 30-40% of patients. Also kidney stones and glaucoma are possible. Typically Topamax is started at a low dose and slowly increased. Keeping at the lowest possible level is a very good idea. This drug does affect cognitive abilities and has been nicknamed Dopamax as a result. If your doctor is NOT monitoring you and you feel ill taking this, demand a test for bicarbonate levels.

The others listed at the About.com link all have potential to help. This seems to be very personally unique to individuals, and there is no way really to predict who will respond to which unless you try them.

The two cardiac drugs, Mexetil and Tambocor are used infrequently. Mexetil is sometimes called "oral Lidocaine" because it works on sodium channels. It is not commonly given unless patients don't respond to other drugs, because it can be very upsetting to the stomach, may cause ulceration, or damage to the esophagus. So staying upright after taking may minimize reflux and burning this causes. But many people discontinue it because of GI side effects.

Tambocor can be problematic mixed with other drugs:
http://en.wikipedia.org/wiki/Flecainide

So use the drug checker, to test out your combinations for your own safety. Some online or pharmacy databases may not have all of them listed equally, so checking yourself is important.
Both of these heart drugs have a narrow therapeutic index, meaning errors in administration, or taking too much can be dangerous or fatal. So strict adherence to directions is a MUST for them.

Here are some other links about using these medications for chronic pain. I found these interesting and they may be helpful for some here:

http://www.mayoclinic.com/health/pai...SECTIONGROUP=2

http://en.wikipedia.org/wiki/Sodium_channel_blocker

http://www.bayareapainmedical.com/sodiumchnlblk.html

http://www.cvpharmacology.com/antiar...m-blockers.htm

Many of the anti-seizure drugs interfere with nutrients in the body. Most commonly calcium, Vit D, and folate.
The newer ones like Lamictal, Zonegran, Keppra don't have studies yet on this. But often doctors lump them into the family category and you may be counseled to have a Vit D test, and or use a calcium supplement.

Valproate (Depakote), is rarely used for PN, but may be tried when others fail. It specifically blocks folic acid and carnitine.
It also is suspected of affecting zinc because it causes hair loss in some patients.
Tegretol can cause low folic acid too.

I have not run across anyone using Gabitril on this forum yet. I suspect the side effects for this limits its use.

Discontinuing these drugs suddenly can have serious consequences.
If you need to discontinue any of them, they should be tapered off carefully, with doctor supervision.

edit: A new article has appeared in Science News this week. 6-2012:
It discusses a specific sodium channel target in the peripheral nervous system to block pain:

http://www.sciencenews.org/view/feat...e/Hurt_Blocker

We may see drugs developed to target this area, eventually.

The new gabapentin:
 

We have a recent post on this subject, gabapentin enacarbil:

http://neurotalk.psychcentral.com/thread162932.html

This drug has be recently approved for RLS and had been in the pipeline for a LONG time. It does not at this time have FDA approval for either epilepsy, or chronic pain however, because studies were not submitted for those conditions.

I don't expect that many if any insurance plans will pay for this
for off label use for anything other than RLS.

If anyone here does try this drug, I think we all would like to
see if it helps, or not. So please share that experience here.