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Dr Lowe Q&A – Medicines Commonly Prescribed for Fibromyalgia

August 11, 2003

Question: Im reading a book of yours. In it, you say that narcotics could increase heart rate and prevent patients from reaching their therapeutic dose of thyroid medication. Is this true for Ultram, which I take daily?

I also take 2.5 grains (90 mg) of Armour and feel that I should increase it further. I dont because my heart rate is 90-to-105 in the mornings. Could the Ultram and Armour be interacting to cause the rapid heart rate?

Im frustrated, depressed, and feel hopeless because I havent had any improvement yet. I have Hashimoto’s thyroiditis and fibromyalgia and havent been able to work for six years. All other possible health problems have been ruled out. Ive eaten a good diet and taken tons of supplements for years, although I cant exercise much. Thanks for answering my questions.

Dr. Lowe: Yes, Ultram can increase ones heart rate. It may also interact with thyroid hormone to cause a rapid heart rate so that the patient isnt able to reach an effective dose of the hormone.

Ultram is an opioid like morphine, but it is 5-to-10 times less effective than morphine in reducing pain.[8] It is less effective than morphine probably because it binds less readily to opiate receptors than does morphine. Ultrams advantage over morphine is that it doesnt cause life-risking respiratory depression.[1] Ultram has few adverse effects. The most common ones Ive seen listed in the research literature are dizziness, vomiting, nausea, and dry mouth.[2][4] Some patients have had seizures and convulsions, especially those who also take tricyclic antidepressants, other tricyclic compounds, and selective serotonin reuptake inhibitors.[10] The pharmacy websites Ive looked at list rapid heart rateamong the potential “serious side effects” of Ultram.[11][12][13][14] But for reasons I give below, Im surprised that rapid heart rate isn’t more prominent among adverse effects reported in the research literature.

Effects of Ultram on the Heart. Interestingly, reports of the effects of Ultram on the heart rate are mixed. In anesthesized rabbits, small doses of Ultram slightly increased the heart rate.[4] In one study, when doctors gave children Ultram for pain following surgery, their heart rates didnt change.[1] In contrast, when patients took Ultram following major orthopedic surgery, their heart rates increased by a maximum of 17%.[5] In another study, though, Ultram slowed theheart rates of rats.[3]

There is little point in citing other studies. My quick review in PubMed suggests that other studies are consistent with the ones I just cited; they are mixed, with some reporting no change in heart rate, others reporting an increase, and othersreporting a decrease.

Ultram Increases the Norepinephrine Level. As I said above, the mixed results of studies of Ultrams effect on heart rate surprise me. I say this because of the way Ultram works to relieve pain.

The chemical structure of Ultram is similar to that of antidepressants that increase the levels of serotonin[7] (such as Proazc) and norepinephrine (such as desipramine).[3][6][9][7] By increasing the levels of these nerve-transmittingchemicals, Ultram enhances mood. Some researchers speculate that Ultram reduces pain mainly through this mood enhancing effect which decreases the emotional component of pain.It is the increase in the norepinephrine level thats of most concern regarding patients heart rates. I would expect an increase in norepinephrine to raise the heart rate. Researchers report that Ultram increases the force of contraction of the heart muscle,[4] but I havent found studies reporting that the increased norepinephrine level increases the Ultram-users heart rate.

On principal, however, the patient taking Ultram should be cautious when she also takes thyroid hormone. Thyroid hormone increases gene transcription for the proteins (called beta-adrenergic receptors) that norepinephrine binds to on cell membranes. When norepinephrine binds to the receptors, metabolic processes accelerate. The acceleration sets off excitatory physiological reactions,such as increased heart rate. When a patient increases the number of these receptors by taking thyroid hormone, and she increases her norepinephrine let by using Ultram, she may get a combined effectan increase in the force and rate of contraction of the heart.

Mood Effect of Ultram. That Ultram works partly by improving mood raises another issue that Im concerned about with you. You wrote that youre depressed and feel hopeless. Despite these feelings, you may be getting some antidepressant effect from Ultram. If thats true, and you reduce your dosage of Ultram too quickly, or if you stop it abruptly, your depression may temporarily worsen. We call this “rebound” depression.

To avoid rebound depression, it will be prudent for you to reduce your dosage or stop Ultram only under two conditions: first, that youre guided by a physicia who knows how Ultram works and is experienced in its use; and second, y have immediate access to a mental health professional experienced at helping patients get through severe episodes of depression.

Summary. Ultram may have increased your norepinephrine level, and Armour has probably increased the density of beta-adrenergic receptors on your cell membranes. These two effects of the medications may be interacting to cause your rapid heart rate. Increasing your Armour dosage may speed your heart rate even more by further increase the density of beta-adrenergic receptors on your cell membranes. If you intend to increase your Armour dosage, its important that you first talk with your doctor about possibly decreasing your Ultram dosage or stopping it altogether. But I cant overemphasize the importance of you doing this only with the guidance and support of your doctor and possibly a mental health professional.

References:

[1] Schaffer J, et al.: Nalbuphine and tramadol for the control of postoperative pain in children. Anaesthesist, 35(7):408-413, 1986.

[2] Fu YP, et al.: Epidural tramadol for postoperative pain relief. Ma Zui Xue Za Zhi, 29(3):648-652, 1991.

[3] Nagaoka E, et al.: Tramadol has no effect on cortical renal blood flow==despite increased serum catecholamine levels==in anesthetized rats: implications for analgesia in renal insufficiency. Anesth. Analg., 2002. Mar;94(3):619-625, 2002.

[4] Muller, B. and Wilsmann, K.: Cardiac and hemodynamic effects of the centrally acting analgesics tramadol and ppentazocine in anaesthetized rabbits and isolated guinea-pig atria and papillary muscles. Arzneimittelforschung, 334(4):430-433, 1984.

[5] Hopkins D, et al.: Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery. Can J Anaesth., 45(5 Pt 1):435-442, 1998.

[6] Rojas-Corrales MO, et al.: Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats. Life Sci., 72(2):143-152, 2002.

[7] Hopwood, S.E., et al.: Effects of chronic tramadol on pre- and post-synaptic measures of monoamine function. J. Psychopharmacol., 15(3):147-153, 2001.

[8] Franceschini, D, et al.: Effect of acute and chronic tramadol on [3H]-norepinephrine-uptake in rat cortical synaptosomes. Prog. Neuropsychopharmacol. Biol. Psychiatry, 23(3):485-496, 1999.

[9] Reimann, W. and Hennies, H.H.: Inhibition of spinal noradrenaline uptake in rats by the centrally acting analgesic tramadol. Biochem. Pharmacol., 47(12):2289-2293, 1994.

[10] Gibson, T.: Executive Director, Ortho-McNeil Pharmaceutical:
http://www.fda.gov/medwatch/safety/ultram.htm.

[11] http://ultram.phentermine-rx.net/

[12] http://www.prescriptionfiller.com/buy_ultram.html

[13] http://www.rxlink.net/ultram50mg.html

[14] http://www.diet-pill-fun.com/_buy_ultram.htmlAugust 12, 2002

Question: Im interested in your treatment of fibromyalgia as hypothyroidism. I already take Armour desiccated thyroid hormone therapy. But I also take a daily regimen of a narcotic. I take it for pain caused by nerve damage from cervical and lumbar discs bulges. If I read your report correctly, in your treatment program, I couldnt use the Armour without stopping the use of my narcotic. Is this true?

Dr Lowe: Weve found that some patients taking maintenance doses of narcoticsthat is, doses through the day each dayarent able to use doses of thyroid hormone high enough to be effective. These patients cant do so becauselow doses cause what appears to be thyroid hormone over-stimulation. Of course, some patients who take maintenance doses of narcotics don’t have the problem. Nor, in our experience, do patients who use narcotics on an occasional as-needed basis.

If you must use a daily narcotic regimen, hopefully it won’t interfere with your thyroid hormone therapy. But if you do have what seems to be thyroid hormone over-stimulation at a low dose of Armour, I encourage you to discuss with your doctor a potential interaction of the narcotic with the Armour. We work with each patient as an individual, and when a patient must use a narcotic (as the rare patient must), we do everything possible to help him or her recover while respecting that special need. In the end, however, some patients must make a choice between continuing their narcotic use and recovering from their fibromyalgia symptoms.

April 24, 2002

Question: I read that you dont work with patients taking narcotic medications for fibromyalgia. Since many fibromyalgia patients must use narcotics for pain relief, why do you feel this way?

Dr. Lowe: First, let me clarify our position regarding patients’ use of narcotic medications. We make no value judgments about patients using narcotics, and we personally have no objections to patients choosing to do so. When patients use narcotics on an occasional, as-needed basis, this doesn’t interfere with them improving or recovering when they go through metabolic rehab. We’ve learned, however, that most patients using maintenance doses of narcotics (taking them each day at intervals through the day) fail to benefit from metabolic rehab.

We have roughly an 85% success rate with fibromyalgia patients; that is, only about 15% of patients who fully cooperate with our protocol and complete treatment fail to markedly improve or fully recover. Prominent among this 15% who fail to recover are patients using maintenance doses of narcotic medications. We’ve tried to learn why these patients fail to improve and found two main problems.

The first problem is that narcotics appear to sensitize some brain centers to thyroid hormone. The evidence for this is sketchy, but the little evidence we’ve found provides a plausible explanation for an observation of ours: Some fibromyalgia patients taking maintenance doses of narcotics develop symptoms of over-stimulation at doses of thyroid hormone too low to enable them to recover. The apparent over-stimulation makes it impossible to raise their doses of thyroid hormone to therapeutic levels. When this becomes obvious, the only practical choices for the patients are to stop their narcotics or discontinue metabolic rehab.

With some patients who must make one of these choices, the second problem then arises. These patients don’t want to stop the narcotics. Without hesitation, they choose to forgo the chance to improve or recover with metabolic rehab rather than give up the narcotics.

When we and our cotreating doctors have pressed these patients to stop the narcotics, they come to exhibit a complex of “drug-seeking behaviors.” One behavior is hostility toward us for suggesting that they’ve become addicted to the narcotics. Objective measures may indicate that the pain of some of them has improved, but they’ll insist that theyre still in pain and must continue using the narcotics. On the other hand, some patients indicate that theyre in 100% pain even with narcotic use. Despite this, they refuse to consider that since the narcotics haven’t improved their pain at all that they should cease using themat least temporarilyto give a promising alternative approach a chance to work.
Were convinced that some of these patients want to maintain a diagnosis of fibromyalgia as a ploy to continue their narcotic use.

As a pain management specialist, I was slow to face the reality of narcotic addiction of some fibromyalgia patients. The reason is that several years ago, I agreed that doctors were too restricted in their privilege of prescribing narcotics for patients in incorrigible pain, and I favored loosening of the restrictions. But as a fibromyalgia specialist determined to get each of our patients well, I have no choice but to face the fact that narcotic addiction becomes an obstacle to some patients’ recovery.

I want to emphasize an important point: We know that narcotic use is a boon to many patients who live with chronic pain from which there is no available escape, and we have no objection to such patients using narcotics. Most patients’ fibromyalgic pain, however, is escapable, although narcotic addiction often becomes a roadblock to the escape.

Unfortunately, discussing this subject openly carries a distinct risk. Many patients using narcoticsincluding some doctors with a diagnosis of fibromyalgia who liberally prescribe narcotics for their patientspromptly join campaigns of
hostility toward doctors who express concern about narcotic addiction. We have no choice, though, but to be honest with patients using narcotics who inquire about treatment with us. For us not to discuss the subject forthrightly would be unethical.

The patient using narcotics and who wants to undergo treatment with us has twooptions. First, she can, before starting treatment with us, enlist the cooperation of the doctor who prescribes her narcotics in helping her stop the medication. Or she can commit to stopping the narcotic (again with the cooperation of the prescribing doctor) shortly after beginning metabolic rehab. If a patient chooses to continue taking maintenance doses of a narcotic, the chance of treatment failure with us is high. Again, we make no value judgment about a patients choice either way, but professional ethics compel us to be honest about the issues involved. I hope this clarifies our position on fibromyalgia patients use of narcotic medications.

January 24, 2002

Question: Are you aware of the fibromyalgia drug called milnacipran that Cypress Bioscience is working on? If you are, what do you think of it?

Dr. Lowe: Milnacipran is a drug that acts on two neurotransmitters, serotonin and norepinephrine, involved in pain modulation. The intent of this drug as a fibromyalgia treatment is to decrease patients pain.

Im certainly in favor of fibromyalgia patients, if they must, prudently using some drugs to control their symptomsat least until they undergo effective metabolic rehab to correct their symptoms underlying cause. I dont question that Cypress Bioscience is motivated by a desire to relieve the suffering of fibromyalgia patients. And I dont doubt that the corporation believes that providing milnacipran is an expeditious way to accomplish that desire.

At the same time, projects such as Cypress Biosciences development of milnacipran cause me grave concern. To develop milnacipran as a fibromyalgia treatment, and to get FDA approval for the drug, involves a huge financial investment by the corporation. For me, that investment represents a troubling implication. The corporation (if its run competently) must recoup its investment and produce profits. For this to happen, the corporation must count on the drug working well as a stop-gap method for reducing fibromyalgia patients’ pain. The corporation must also either be (1) unaware that an effective treatment that corrects the underlying causes already exists, or (2) count on an indefinite delayin patients becoming aware of that cause-correcting treatment.

My personal belief is that the project by Cypress Bioscience is exactly what we dont need in the field of fibromyalgia: another corporation developing a patentable drug that does nothing more than reduce fibromyalgia patients pain. Instead, we need to focus on the underlying causes of the pain. Only by focusingon underlying causes can we truly free fibromyalgia patients from their pain and other symptoms. The approach of Cypress Bioscience (if milnacipran is effective)will only reduce patients pain while the causes continue apace.

Merely providing drugs that diminish symptoms rather than eliminating causes has long been a strategy of medically-related corporations for providing themselves long-term financial profits. Typically in modern medical science, a corporation comes up with a drug that modestly controls the major symptom of a disorder. Then the corporation begins to successfully market the drug. At that point, market forces come to militate against researchers eliminating the cause of the disorder. The corporation usually heavily funds a group of researchers in the field, and this group conducts steadily more studies related to that particulardrug. These researchers study results are readily published in major medical journals where the corporation pays lavishly to advertise the drug. In addition, the corporation sponsors (through financial-donations) well-publicized conferences where these researchers present their study results. The minds of practicing doctors are potently influenced by the highly visible published reports and conference presentations of these corporate-sponsored researchers. The practicing doctors presume that the drug represents the cutting-edge of science in the field.

This collaborative venture of corporations, researchers, major medical journals, and conferences effectively controls the minds of practicing mainstream doctors and their patients. Through this control, the venture easily undermines the work of other researchers studying the underlying causes of the disordercauses that may be totally unrelated to the drug. Subverted in this way, the other researchers work at best dimly shows through a veil of obscurity; their work remains poorly funded and largely ignored. Hence, the causes of the disorder persist and patients remain ill, yet those involved in the venture reap continuing financial rewards.

These observations bring me personally to conclusions that Cypress Bioscience probably wont like. First, to develop milnacipran as a fibromyalgia treatment is an expenditure of time, energy, and money that could be far better spent in clarifying the underlying causes of fibromyalgia. Second, this effort by Cypress Bioscience (and similar ones by other corporations) forebodes an ominous future for fibromyalgia patients under mainstream medical care.

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