WHY some need MORE pain med! EXC. RESEARCH & TEST

Discussion in 'Fibromyalgia Main Forum' started by victoria, Jan 7, 2010.

  1. victoria

    victoria New Member

    I wanted to post this separately (already in Fight's Research Thread) is this is new info that may get overlooked by some who need to know this/present to their doctors/etc....

    This explains a lot, hope this becomes easier for those in pain to get tested!

    I got it from Medscape - anyone can go there and register to read things there, btw...

    American Academy of Addiction Psychiatry (AAAP) 20th Annual Meeting & Symposium: Poster 5. Presented December 4, 2009.


    Nancy A. Melville

    December 17, 2009 (Los Angeles, Ca) — Genetic abnormalities in cytochrome P450 may cause some patients to metabolize opioids at an accelerated or retarded rate, prompting the need for higher doses of medication to control pain, according to a new research presented here at the American Academy of Addiction Psychiatry 20th Annual Meeting & Symposium.

    Chronic pain patients who require high doses of opioids may lead clinicians to suspect them as possible addicts or abusers, but Forest Tennant, MD, lead author of the study and a physician with the Veract Intractable Pain Clinic in West Covina, California, said other factors are at play.

    "I have long felt, as have others, that there could be genetic metabolic abnormalities in some people who require very high or unusual regimens to control pain," Dr. Tennant said.

    "The general idea has been that these people must be drug addicts and abusers, but some felt there was perhaps something behind all of this. A lot of these patients have no history of abuse; they don’t even smoke cigarettes and just don’t fit the profile of drug addict."

    To evaluate the issue, Dr. Tennant recruited 15 chronic pain patients who required 1000 mg or more of a morphine equivalent per day and who tested for deficiencies in one or both of the cytochrome P450 2C9 or 2D6 genotypes. The subjects’ opioid serum concentrations were determined about 1 hour after administration of their usual opioid dose.

    Lazy Gene?

    The results showed that all 3 patients with cytochrome P450 genotype abnormalities achieved only 1 to 2 hours of pain relief after receiving the medication. Two of 8 patients who tested for the 2C9 genotype were poor metabolizers, with both showing very high serum concentrations of fentanyl (8.1 and 16.4 ng/mL) 1 hour after dosing. One of the patients with the 2D6 genotype was also a poor metabolizer and had no detectable serum concentrations of oxycodone and its metabolite, oxymorphone, 1 hour after dosing.

    The findings offer some evidence, albeit highly preliminary, of genetic cytochrome P450 abnormalities in at least some high-dose pain medicine patients, Dr. Tennant said.

    "There are about 50 known genetic abnormalities of the cytochromes, and we can only test 3 or 4 of these at this time," he said. "But even with the tests we did here, the results suggest that there may be metabolic factors with these patients that need to be taken into consideration and may explain why these patients need odd [medication] regimens [requiring dosages that are higher than normal]," he said.

    Dr. Tennant added that he suspects that the abnormalities involve a "lazy gene" that only responds to higher doses of a medication.

    "We believe those very high blood levels of the drug may be necessary to make the lazy gene work — you need to sort of force feed it," he said. "This has been seen in other areas of pharmacology, such as blood thinners. You have to get a very high dose to make the defective gene work."

    Although the research is still in its early stages, genetic testing for such abnormalities may have the potential to help clinicians identify and more effectively treat this patient population.

    Possible Screening Tool

    It may also help clinicians better detect which patients may be at a greater risk of becoming opioid dependent.

    "That’s the corollary to this — high doses could cause dependence," Dr. Tennant noted. "I don’t know if it could be enough to cause people to go to the street and become addicts, but in order to get even a modicum of pain control, they may be extremely dependent on taking high doses on a regular, round-the-clock basis."

    The findings also raise the question of whether these genetic factors could prompt abuse of other substances, including alcohol. At least one of the study subjects fueled that suspicion, he said.

    "One of the 5 with the 2C9 genotype did report being an alcoholic at one point, and she said ‘It’s funny, I would go out and drink with friends and everyone would be getting drunk and nothing would be happening to me’."

    Dr. Tennant noted he has subsequently tested 25 additional subjects and found that about 20% of high-dose patients had these genetic abnormalities. He suggested that now that these genetic tests are available commercially, physicians may want to consider testing for these genotypes.

    "Eighteen months ago, I wouldn’t have been able to do this research because the test wasn’t available, but I feel every patient who is taking opioids for some pain should now be tested," he said. "Not just to add to a database but to give essential information to insurance companies and any other parties who are paying for the drugs."

    "They need to know what’s going on, why these people are taking higher doses of drugs, and they likely wonder whether these patients are addicts."

    Controversial Area

    With pain medication addiction widespread, the temptation to suspect addiction in many cases only makes sense however, and Jon Streltzer, MD, a professor of psychiatry at the University of Hawaii, Manoa, said he questions the very assumption that some patients "require" high-dose opioids to treat chronic pain.

    That is a controversial concept that has much evidence against it at the cellular, physiological, and clinical levels. It may be instead that patients have different susceptibilities to high-dose opioid dependence,” said Dr. Streltzer, who is president of the International College of Psychosomatic Medicine.

    That doesn’t mean genetic factors aren’t at play, but they may be part of a bigger puzzle involving multiple mechanisms, he suggested.

    "It has long been believed that genetic factors are involved in opioid dependence, although which genes are involved and what the mechanisms are is not understood," Dr. Streltzer told Medscape Psychiatry.

    "In addition, chronic opioid intake induces changes in the brain itself, changing the way the cells respond. This is thought to involve the development of craving, which in chronic pain patients can be experienced as pain and the need for more pain medicine."

    Patients can then in fact become more sensitive to pain — as a result of pain medications themselves. "Numerous reports demonstrate enhanced pain sensitivity results from chronic opioid intake by multiple overlapping mechanisms," Dr. Streltzer said. "Patients in programs to alleviate opioid dependence report that their pain improves."

    However, Dr. Tennant said clinicians should not rule out the possibility that patients who say they need high doses may have such genetic abnormalities.

    "The bottom line is that when we see a patient who claims to have severe pain and needs a very high dose, we shouldn’t jump to conclusion that this is abuse," Dr. Tennant said. "There may be metabolic factors here that have to be taken into consideration and may explain why these patients may need odd regimens."

    Dr. Tennant and Dr. Streltzer have disclosed no relevant financial relationships.

    [This Message was Edited on 01/07/2010]
  2. AuntTammie

    AuntTammie New Member

    I wonder if using a different method of taking the drugs (patch, sublingual, IV, rather than oral route) might make any difference - when one bypasses the GI system, the concentration of the med is higher AND it protects the liver and kidneys from damage
  3. satchya

    satchya New Member

    I imagine this works the same way with just about any medication. I know that for me muscle relaxants work about as effectively as m&m's. I have to take a very large dose to get any relief at all from them as chronic muscle spasms are about the only symptom of my fibro that is still "out of control."

    My father in law suffers from mild neck and back pain pretty much all the time. This summer when they came to visit us, the long plane ride really did a number on his pain and caused some bad spasms. He was obviously suffering. I know you're never supposed to share medication, but how could I watch this man who is part of my family suffer knowing that I had medication on-hand that could help? So I offered him some skelaxin, telling him that it shouldn't make him drowsy at all (because quite frankly I can take two and still be wide awake and barely even tell I took them). He started with a half a pill to be safe, and it knocked him out for six hours. He fell asleep right there on the family room couch, with the whole family running around, t.v. on, etc., and nothing woke him up. And he also said it got rid of the spasms completely.

    I admit I was jealous. Later this summer my husband had a bad back spasm from twisting his back wrong while working on the lawn and he took one cyclobenzaprine and half a lortab. Again, within half an hour he was out like a light.

    I can take two tizanidine (which is supposedly the most sleep-inducing of the muscle relaxants) and then go to aerobics class, if that gives you an idea of how NOT sleepy it makes me.

    It never really occured to me until I read this article, though, that there could be some kind of genetic metabolizing difference. That would make so much sense. Yet one more thing I can stop telling myself to feel bad about and that it's "all in my head".

    Don't you get tired, as a person with fibro, of feeling like you do everything "wrong?"
  4. MamaT1967

    MamaT1967 New Member

    Any medicine that says "may cause drowsiness" is like taking a handful of speed for me. Drugs never work the way they are supposed to. When I have surgery, I am given enough meds for a 300lb person and I only weigh 110lbs. I have always known there was a problem with how I process meds and new docs always challenge me, like I'm a "drug seeker".

    Yes it is so tiring to do everything "wrong" all the time and I know this is NOT a psychological illness, but I think some days I will end up a total "headcase" from all the accusations and lack of empathy for my "condition".
  5. gapsych

    gapsych New Member

    Thanks for the article.

    I have also heard, that people who need to drink more to feel the effect may become alcoholic. However, I have no idea if this is indeed true.

    In my case, I can get drunk from sniffing a wine cork (a slight exaggeration) and alcohol makes me sick. My sister and dad are the same way which is good in a way as there have been several alcoholics in the family.

    When my daughter had migraines, her doctor would have her go off the medication for a short period every once in a while to prevent the rebound effect.

    It's interesting how people will react differently to the same medication. Even people without our DDs.

    The risks and benefits have to be weighed as with any medication and that should be individualized.

  6. victoria

    victoria New Member

    individuals need to be treated as individuals by doctors, instead of 'one size fits all'.

    My poor DH suffered for years going to the dentist as the usual type of 'novocaine' was quickly metabolized by his system; ie, he'd be numb for maybe 5 minutes. Dentists would never believe him, thought he was just scared or something. One (a 'friend' at the time, if you can believe it) actually knicked him on the tongue to see if he actually reacted (of course he did).

    It wasn't till maybe 20 years ago that an GP friend happened to read about this, and what kind of local anesthesia to ask for. When he went back to the regular dentist, the dentist said, "Oh sure, I have it, some people need it."

    Grrrrrrrrrrrrrrrrrrrr! Obviously he never went back to him.

    Yep, I usually need 1/2 the dosage of any kind of pain med to work, have always started with 1/2 dosages! Makes total sense to me that many would need more!

    all the best,