How are you doing on the cymbalta? Did you get all of the drug interactions worked out?

Not so good...sad to say. The solution from the pharmacy was to NOT fill the Tramadol so I am off that now. And the cymbalta does NOT seem to agree with me AT ALL. I started taking it last Friday and 30-45 minutes after I take it I get violently sick. I was already having problems with vomitting but this hits me SO much worse and it is like clockwork. I have tried taking it with food, without food, with my other meds, seperately from the other meds...nothing seems to change the fact that I get violently ill. Today I actually started choking (lasted about 30 seconds) while I was sick so now I am actually scared. On top of which the pain is significantly worse than it was before...though not sure if that's because the meds don't work or because I can't keep them down. Either way...if it's the cymbalta making me sick then it doesn't matter.

Oh well...trial and error continues...

Hello again. Sorry to hear what you are going through. You say the "trial and error continues." Forgive me, but that seems about right.

In essence, I think you're being treated for fibromyalgia or a peripheral neuropathy, but not CRPS, whether you've been let in on this bit of information or not. If I may, the proper name for Cymbalta is Duloxetine. And if you run a PubMed search for "Tramadol Duloxetine," you'll get 34 hits, almost all of them dealing with fibromyalgia or peripheral neuropathies. And of the 34 articles, only four are freely available through "PubMed Central," and then only three are in English:

Fibromyalgia: presentation and management with a focus on pharmacological treatment, Sumpton JE, Moulin DE, Pain Res Manag. 2008 Nov-Dec; 13(6):477-83, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti...f/prm13477.pdf

Management of fibromyalgia syndrome--an interdisciplinary evidence-based guideline [Behandlung des Fibromyalgiesyndroms – eine interdisziplinäre S3-Leitlinie], Häuser W, Arnold B, Eich W, et al, Ger Med Sci. 2008 Dec 9; 6: Doc 14, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti.../GMS-06-14.pdf

Effects of treatments for symptoms of painful diabetic neuropathy: systematic review, Wong MC, Chung JW, Wong TK, BMJ 2007 Jul 14; 335(7610): 87, Epub 2007 Jun 11, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti...s-00087-el.pdf

And what do each of them suggest by way of pharmacological therapies? With minor variations it's (1) Duloxetine (Cymbalta) ("FDA-approved indication for fibromyalgia"), (2) Tramadol and (3) Gabapentin (Neurontin) or Pregabalin (Lyrica). Sound familiar?

What sticks out here is the universality of Tramadol, whereas RSD/CRPS patients are treated with a host of opioids, most of us blowing through Ultram (Tramadol) in a few weeks on our way to much harder sauces. And the funny thing is that Tramadol has a particularly bad rap with nausea. By way of example, if you compare the FDA approved Prescribing Information sheets for oxycodone and Ultram, you'll see that oxycodone is associated with nausea in less than 3% of those participating in trials, while nausea with is dose-dependent with Tramadol, ranging from 15.1 to 26.2%!!! Compare, http://pain-topics.org/pdf/PI/PI_Oxy...blets-30mg.pdf with, http://www.ortho-mcneil.com/ortho-mc...r.pdf#zoom=100.

In fact, there's a whole sub-industry devoted to combining Tramadol with Acetaminophen (Tylenol or Paracetamol in the U.K) just to cut down on the side-effects of Tramadol, primarily nausea. See, e.g., Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial, Rawal N, Macquaire V, Catalá E et al, J Pain Res. 2011 Apr 8; 4:103-10, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pubmed/21559356:

Adverse events (mainly nausea, dizziness, somnolence, vomiting, and increased sweating) occurred less frequently in patients under combination treatment (P = 0.004).

So if your doctors aren't going to give you oxycodone, why not cut the Tramadol with a little of your old friend, Tylenol? [In the U.S., the product is marketed under the trade-name Ultracet.] I would submit it's because they are slavishly adhering to the Groupthink on treating fibromyalgia and/or peripheral neuropathies. To the letter, thank you.

So, unless you have already done so, can't you please just get an ASAP consultation with Timothy Lubinow, MD at Rush, just in the name of a second opinion on CRPS? I'm on bended knee on this one, where all of the evidence suggests that no one's changes of going into permanent remission on ketamine improve over time, to put it mildly, but I think we've been over that ground before.

Please.

Mike

"why not cut the Tramadol with a little of your old friend, Tylenol? [In the U.S., the product is marketed under the trade-name Ultracet.]"

Hi, in what way does the tylenol enhance the tramadol?
cheers

In the US, historically Tylenol has been used in combination with other pain relievers.

Tylenol with Codeine
Tylenol with oxycodone (Percocet)
Tylenol with Darvon (Darvocet)

In OTC products Tylenol with just about EVERYTHING.

This is now changing as the US FDA is trying to cut Tylenol mixtures completely off the approval lists.

In the past Darvocet was released when the patent for Darvon expired. The same is true for Ultracet. It did not come on the market until Ultram went generic.

While it might be true that mixing Tylenol with tramadol results in more efficient pain relief, I think it is just basically a marketing ploy. Drug companies do this all the time with their drugs, even to the point of massaging data in studies to get the FDA to approve the new mixture.

We are seeing a change in the US about this trend with Tylenol. And in fact it may even result with some OTC brands including Tylenol Extra strength 500mg tabs being removed from the OTC market in the future and becoming RX only.

Ultram was a huge money maker for McNeil when it came out. Going generic really was painful for them. Adding their own Tylenol to make a new product restored a lucrative situation to their balance sheets!

As far as the nausea issue...all opiates cause nausea. I received far more complaints about nausea side effects than I ever did regarding Tramadol (which was never). Opiate nausea may occur when doses are too high for that particular patient, and dose adjustments often take care of them.

The nausea of Tramadol is different IMO and more connected to the serotonin actions of this drug. SSRIs are also reported high in nausea when first starting them.

And it is correct that Tramadol is recommended for Fibro patients specifically. This is because some studies show that the pain receptors for opiates are blocked by high endogenous endorphins in this disorder. I saw this mentioned at a chronic pain seminar during the Fibro portion. Opiates are no longer being recommended for Fibro patients for this reason. Also opiates have a checkered past for not working well for peripheral neuropathies.

When I was given Tramadol last year, I had one brief episode of nausea at the 50mg dose level, that lasted briefly...about 30 minutes. I haven't had any recurrance of that since. I don't take Tramadol every day, and only use it on very bad nights in fact with no further problem.

I worked many years in night shifts and never once had a nausea question regarding Tramadol. But nausea with opiates? Very very common.

mrsD -

I inadvertently posted the link to only the abstract of Tramadol/paracetamol combination tablet for postoperative pain following ambulatory hand surgery: a double-blind, double-dummy, randomized, parallel-group trial, Rawal N, Macquaire V, Catalá E et al, J Pain Res. 2011 Apr 8; 4:103-10, ONLINE TEXT @ http://www.ncbi.nlm.nih.gov/pmc/arti.../jpr-4-103.pdf, however that abstract included its own link to the full text article, which does a very good job of explaining the mechanism of 325 mg. of Acetaminophen/Tylenol/Paracetamol in supplementing the analgesic effect of 37.5 mg. of Tramadol, which has significantly fewer side effects than the analgesia equivalent ("monotherapy") dose of 50 mg. of Tramadol, although both were significantly higher than what could have been acheived by using oxycodone alone:

Nausea was the most common event in both groups (25.8%
for tramadol/paracetamol vs 36.4% for tramadol) followed
by dizziness (15.9% vs 18.6%) and somnolence (9.1% vs 14%).

At 108.

But I found the comparisons between the Prescribing Information sheets for Oxycodone and Tramadol the most instructive, however you didn't comment on that information as such.

Nevertheless, I think the most important point of clarification is that we cannot lump opioids - such as Oxycodone - and true opiates together in looking at their profiles for side effects. See, e.g., Epidural oxycodone or morphine following Ggynaecological surgery, Yanagidate F, Dohi S, Br J Anaesth. 2004 Sep;93(3):362-7, 366, Epub 2004 Jun 25, ONLINE TEXT @ http://bja.oxfordjournals.org/content/93/3/362.full.pdf:

Undesirable side-effects such as pruritus and nausea are common with epidural morphine and are believed to be caused via mu-opioid receptor stimulation at the supraspinal level.23–25 It is not clear why the need for anti-emetics was significantly less in those who received epidural oxycodone 12 mg day−1 in our study. Since patient characteristics were similar between the three groups, it may be that oxycodone, when administered in the epidural space, is less emetogenic than morphine. Although oxycodone has effects at both mu- and kappa-opioid receptors, the affinity of oxycodone for the mu-opioid receptor has been reported to be one-tenth that of morphine.26 This may account for the fewer side-effects and less analgesia when compared with the same dose of epidural morphine.

Notes
23 Gustafsson LL, Schildt B, Jacobsen K. Adverse effects of extradural
and intrathecal opiates; report of a nationwide survey in Sweden.
Br J Anaesth 1982; 54: 479–86.
24 Martin WR. Clinical evidence for different narcotic receptors and
relevance for the clinician. Ann Emerg Med 1986; 15: 1026–9.
25 Yaksh TL. Opioid receptor systems and the endorphins: a review of
their spinal organization. J Neurosurg 1987; 67: 157–76.
26 Kalso E, Vainio A, Mattila MJ, Rosenberg PH, Seppala T. Morphine
and oxycodone in the management of cancer pain: plasma levels
determined by chemical and radioreceptor assays. Pharmacol
Toxicol 1990; 67: 322–8.

I spent most of last night looking for any published study showing that Tramadol had a dose equivalent level of nausea less than or equal to that of Oxycodone, when all the evidence I saw was to thew contrary. If you or anyone else knows of such studies, I would be most appreciative.

Mike

That looks like alot of effort, you put in to this discussion.

I only look at studies when I have no personal experience in an area, or when an area is "new" or rare.

For 40 yrs I've dealt with patients who complain or worry about their medications. Who have negative experiences, or who are not getting what they expected, etc.

Prescribing data, and data off the drug insert is typically taken off short lived studies. Post operative pain, is rather unique and short lived for most patients. Also it can be subject to fraud as we learned about Pfizer and Celebrex, and Dr. Reuben:
http://www.theday.com/article/201001...100119833/1047
I tend to think these post operative studies are drug company funded to give them leverage with sales/marketing etc.

Insert reports do not often include post marketing data, unless it is extreme and dangerous, and getting that added may take a decade or more in some cases. Nausea? not like aplastic anemia or metabolic acidosis. The latter two might get added more quickly.

Basically when people get discharged home, with meds, and it is late at night and they cannot call their doctors, etc, they call me. I've had many many opiate side effects including Sphincter of Oddi attacks which are alarming in the extreme.

But nausea, is a biggie and more common with codeine, and morphine. Oxycodone and hydrocodone may cause nausea in high doses, and also severe itching spells at moderate doses.

But I never had an Ultram/tramadol call! These would be emergency calls. Over the long haul people may call their doctors the next day and ask for another medicine. But I did not see many discharged surgical patients on Ultram at all in fact. It is more of a chronic long term intervention. People coming to me with trauma and other painful things in the night, always had Vicodin at least. Maybe Percocet. Sometimes Darvocet, which is no longer available finally.
Many people with trauma are given Toradol (an NSAID) injection in the ER or hospital, to augment the narcotic given. Ultram? Seems like a foolish choice for acute or severe issues.

I forgot to list Hydrocodone +Tylenol = Lortab and Vicodin, Norco etc.
In this case, I believe the tylenol was added to prevent abuse of the hydrocodone portion which when used alone is a CII narcotic.

The Tylenol also functions in the other mixes as an abuse deterent but for determined abusers really isn't effective and just becomes a poison to the liver instead.

Let's look at Ultracet:
This drug is 37.5mg of tramadol and 325mg of Tylenol. The typical starting dose of tramadol plain is 50mg. But many people use 100.

Why 37.5mg tramadol? This is a trick used by drug companies so the doctor cannot give regular 50mg tramadol and tell the person to take a tylenol with it. It forces the dosing to use TWO tablets to give 75mg of tramadol to get a therapeutic dose + 650mg of Tylenol. TWO tablets for a response that maybe one tablet of plain tramadol 50mg would accomplish for many situations.

This is a frequent thing, drug companies do to sell more product.
In the case of tramadol, it also protects the patent, because any generic company would be forced to spend $$ to provide studies for the new 37.5mg dose.

Here is another example of manipulation of doses, with a well known brand name: Soma:
http://www.soma250.com/
This product really bombed because the insurance companies refused to pay for it. Generic Soma 350mg has been on the market almost for 20 yrs! I read about the launch of this bomb on Cafepharma.com and it was very amusing and enlightening!

So while I don't dispute the PubMed articles you found, empirically, they don't often reflect real life situations.
Today, unfortunately, if a drug company does something we need to look very carefully at the result, because often it is for THEIR edification, and not for the patient at all. I keep hoping we are turning a corner in this regard, but I have yet to see much improvement!

I had been taking the Tramadol with Tylenol (1000mg of Tylenol with each 100mg of Tramadol). But now they have me off Tramadol completely and the pain is through the roof...though even before it wasn't doing very much to control the pain. And if they're not really treating me for CRPS then it would make sense that they haven't been able to get the pain under control.

I want to go to Rush...but I can't afford it. I know that sucks and it's my decision...but it's just not covered by my insurance and work comp isn't doing ANYTHING while my case is in appeal (THEY appealed it, not me). So, I am doing the best I can for now with what I can afford. When all the "legal" stuff gets taken care of then I will most likely be able to go to Rush...but I just can't right now. When you deal with work comp, you're stuck with going to doctors that are referred by other doctors and then waiting for approval. When you go through regular insurance, you're stuch with what's either in network or what you can afford. There are even some places that won't let me make an appointment at all since it is a work related injury and work comp isn't going to approve ANYTHING until the appeal is done (which could take years if they take it all the way to the end..don't think they will since they have absolutely no evidence for anything since even THEIR doctors agree with what mine said)...but work comp won't comply with what the doctor's offices require in order to run it through my regular insurance. It's frustrating...cause I just want to get better and focus on my health...but it just isn't going to work out that way for me.

Anyway...have a call out to my doctor to see what they can do about this now because I cannot continue with the Cymbalta given how violently ill I get. I still am dizzy and nauseous all the time and vomit several times a day besides what happens with the Cymbalta, but I think that other stuff is my reaction to the pain because I have always been one to throw up when I am in a lot of pain and these past few months have been worse than anything I remember in the past.

I wonder if some of your unpleasant symptoms are from suddenly discontinuing the Tramadol?

This drug is known to cause habituation in patients. Even though it is not a controlled substance, it does need to be tapered off, in a similar way, antidepressants (SSRIs) do. We are seeing with all the new drugs from the last 20 yrs, that those affecting neurotransmitter receptors, need careful tapering when being discontinued whether they are controls or not.

[QUOTE=catra121;777549]

Please seek immediate evaluation for withdrawal from Tramadol. I was only on Tramadol for about six months and was told by three doctors that it is not particularly difficult to come off of. I tapered for a little over a week and then had the exact same violently ill symptoms that you have described.

I went to the emergency room and was told that Tramadol is every bit as addictive as heroin, and that many physicians who prescribe it don't know the facts. I continued to experience severe symptoms for the two weeks following my ER visit bur was given medication to ease the vomiting etc.

Take Care!!!!!!