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10 Articles in Volume 17, Issue #6
A Plea for Proper Opioid Tapering
Centers of Excellence in Pain Management: Past, Present, and Future Trends
Comorbid Pain and Childhood Obesity
Discussing Migraine With Your Patients: A Common Sense Guide for Clinicians
Justification of Morphine Equivalent Opioid Dosage Above 90 mg
Letters to the Editor: Dependence vs Addiction, Opioid Metabolism
Opioid Rotation From Opana ER Following FDA Call for Removal
Psoriatic Arthritis: Established, Newer, and Emerging Therapies
Sleep-Wake Disorders and Chronic Pain: Reciprocal and Interactive Effects
What are Nav1.7 inhibitors and how are they used in the treatment of neuropathic pain?

Letters to the Editor: Dependence vs Addiction, Opioid Metabolism

July/August 2017

Dependence Does Not Equate to Addiction

In the article, “Trump Orders Commission to Examine Opioid Addiction,” published online,Kelly Pfeifer, MD, director of high value care for the California Health Care Foundation, stated, “Today we know that the percentage of people becoming addicted when taking opioids for pain is anywhere from 10% to 50%, not 1%.” She continued with, “the length of time it may take to develop an addiction to opioids is startlingly brief…there is a big jump up after taking opioids for 5 days, 30 days, and 90 days.”

Are these statistics accurate?    

Anonymous PPM Reader

What is on the minds of Practical Pain Management readers?

Dear Reader, 

Unfortunately, these statements oversimplify the problem and perpetuate a common mistake in properly distinguishing between “addiction” and “physical dependence,” a  misunderstanding that needs correcting. Dr. Pfeifer’s figures of 10% to 50% actually refer to the likelihood of developing physical dependence, not addiction. Also, what is “startlingly brief” is not “the length of time it may take to develop an addiction” to opioids but the length of time it takes to develop tolerance to certain opioid effects. 

For the past 5 years, I have been teaching a national remedial/proactive prescribing course,2 during which I have observed the beliefs of hundreds of physicians, physician assistants, and nurse practitioners with regard to opioids. Before the course, for example, attendees were asked to complete an online assessment. In response to “I anticipate that my patient will become addicted to the opioid that I am prescribing for him/her for chronic pain,” 150 out of 379 prescribers (40%) answered “always” or “frequently.” This response supports a widespread need for education about the nature of addiction, physical dependence, and the meaning of “dependence on drugs.” 

I have addressed this confusion in terms twice in PPM—in an Ask the Expert columnand, more recently, in “The 5 most misunderstood pain terms.”4 To review, “dependence,” as in drug dependence, was the term used in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV),5 the reference book widely used by psychiatrists. In the updated DSM-5, the name for addiction was changed to “opioid use disorder.”6 Currently, the concept of dependence or, more clearly, physical dependence, is defined as “a state in which the body responds to the chronic use of a drug such that when the medication is stopped suddenly, a specific set of symptoms develops (withdrawal syndrome).”6

Some withdrawal syndromes—for example, following an abrupt discontinuation of corticosteroids—can be serious or even fatal, while other experiences, such as acutely stopping the use of opioids, may be very uncomfortable but not life-threatening. The body’s response to some drugs may result in sedation, respiratory depression, and nausea when opioids are taken, leading to tolerance, or a response such that an increased dose may be required to get the same effect. However, this is not the same as addiction.

It is essential that pain practitioners recognize the significant distinction between addiction and dependence, and understand the relationship between tolerance and withdrawal in order to most effectively manage patients with chronic pain.

Jennifer P. Schneider, MD, PhD

Hormone Therapy

As a certified family nurse practitioner (FNPc) in the Northern California Kaiser Health Care System, I regularly work with patients in chronic intractable pain to taper their opioids while continuing to manage their symptoms. Many of these patients develop centralized pain, which I have heard Forest Tennant, MD, DrPH, lecture on and write about in PPM.7,8

I do not share the belief that opioids are bad for everyone or medication doses of 100 mg or more are lethal, as this goes against 17 years of chronic pain management experience. As such, I believe that the guidelines from the Centers for Disease Control and Prevention9  were poorly conceived with insufficient science to back the recommendations. While I follow the practice of prescribing the lowest possible dose for meaningful improvement in function, pushing doses up without knowing what the patients’ hormone levels are or their resultant m-receptor response is an ineffective Band-Aid approach when it would be more efficient to check for and correct a hormone deficiency.

A new challenge has arisen for me with a patient who has centralized pain, has transitioned from female to male, and is on testosterone therapy. Would I need to make any adjustments to hormone treatment—dehydroepiandrosterone (DHEA), estradiol, and progesterone, to meet the specific needs of this patient? 

In addition, I want to promote the value of hormone therapy to the physicians in my practice so we can maximize patients’ comfort while avoiding the need for long-term use of opioids. Alas, it is a hard sell despite the evidence.10-12 While the use of ketamine and bisphosphonates has required some convincing as well, these medications have been more readily accepted.

I find it frustrating that Dr. Tennant’s treatment approach is not embraced as mainstream medicine—at least not yet—and welcome your unique approach to chronic pain management that employs the use of cutting- edge practices to help our pain community. 

Darrel Brown, FNPc 
San Rafael, California

Dear Darrel,

Your interest in the beneficial use of hormones for pain management is greatly appreciated. It is my observation that the limited use of hormones in pain care stems from a lack of familiarity with this approach. Since an evidence basis for hormone replacement to manage pain is of recent origin, mainstream acceptance that both pain and opioids will suppress a number of hormones is still evolving.

As part of the learning curve, pain practitioners should begin to recognize that the central nervous system (CNS), among other things, is an endocrine organ. There is a set of neurohormones, including pregnenolone, estradiol, DHEA, progesterone, testosterone, oxytocin, human chorionic gonadotropin, and human growth hormone that are essential for neuroprotection, neurogenesis, and analgesia.10,12

The greatest misunderstanding in pain care is the failure to recognize that this therapeutic class of hormones works indirectly, over time, to reduce pain rather than providing short-term analgesia by stimulating receptors and enzyme systems similar to that of opioids, gabapentinoids, and ketamine.

Pain treatment, as practiced today, is basically the daily, regular administration of symptomatic, short-acting agents with analgesic properties. In contrast, neurohormones produce long-term, anti-inflammatory, neuroregeneration, and healing effects that are useful in treating the underlying cause of centralized pain,10,12 which is primarily the result of microglial activation and neuroinflammation. These neurohormones can be administered intermittently as a replenishment measure or given regularly for potent therapeutic effect.12,13

I encourage pain practitioners to consider prescribing hormone therapy in severe, chronic pain patients to enhance the effect provided by standard symptomatic treatment. Clinicians who add hormone therapy to their patients’ usual regimens routinely report better pain control and find that patients use fewer opioids and experience improvement across a variety of mental and physical functions.10

Forest Tennant MD, DrPH

Managing Long-Term Opioid Use

I am a physical medicine and rehabilitation specialist working in a relatively rural area of northern California where there is limited access to comprehensive and alternative pain management services due to distance, insurance coverage, and cost.

Over the years, I have inherited a volume of legacy pain management patients who are on higher dose opioid regimens (100-400+ MME daily). What do you suggest for these patients given that insurance companies and pharmacies are increasingly limiting provision of high dose opioids, and many patients are begrudging or unwilling to consider tapering off their current regimen?

In addition, I hope to retire in time and there are few, if any, local physicians who are willing or able to take over the care of these patients. A feature article on managing patients on long-term, high-dose opioid regimens would be very helpful.

Phillip R. Fillbrandt, MD
Chico, California

Dear Dr. Fillbrandt,

You raise a problem faced by many pain practitioners who care for the most serious, intractable pain patients. Thousands, if not a few million, chronic pain patients were started on opioid dosages over the past 20 years that exceed the CDC recommended maximal opioid dosage guideline of 90 mg morphine milligram equivalents (MME) per day.9

As you state, these legacy patients have done well, are stable, and don’t want to give up what they perceive as a successful treatment. Unfortunately, some insurance companies and physicians are misappropriating the CDC guideline of 90 MME to refuse to pay for opioids and/or discharge these patients.9 These patients then seek out those of us who continue to treat intractable pain patients with high opioid dosages, placing us in a difficult position. The challenge comes in that the CDC guidelines are intended for primary care practitioners but they don’t prohibit going over 90 MME.

My first recommendation is to make sure that every patient receiving more than 90 MME is fully justified. This is a topic recently covered in PPM11 and is the focus of a feature article in this issue. Once you are satisfied that a patient’s chart shows ample validation for a high opioid dosage, the insurance company can be notified of the rationale for coverage.

At this point in history, both patients and physicians should accept that insurance companies will limit opioids simply on a cost basis, and sometimes due to the heightened public attention to opioid abuse. Patients with intractable pain should be encouraged to contact their health insurer to provide a detailed explanation of their painful disease and why coverage for their opioid prescription should be approved. Insurers are much more likely to respond favorably to a physician’s request as a follow up to advocacy by the patient first.

Too many legacy patients, unfortunately, are rejecting the new non-opioid therapies or even a slow opioid taper, much to their possible, future detriment. In these cases, I’ve found that ketamine, stimulants, and some neurohormones may help to reduce opioid dosages. Also, I try to get patients to switch from the most expensive (fentanyl, oxycodone, brand names) to less costly generic opioids.

Although it may be unacceptable to you, some physicians feel justified in refusing to do prior authorizations for opioids, which will leave these patients to accept whatever their insurance will cover. This is a “tough love” approach, but it is difficult to imagine that legacy patients will be able to return to the days of unlimited opioids at any dose and cost as prescribed by any physician.

In summary, pain patients pay for their insurance, not the doctor. Therefore, it will fall to the pain patients and their families to lobby their health insurer for opioid coverage and not to rely on their physician to do more than support the diagnosis and recommend pain therapy. Sadly, we have arrived at a time in which insurance companies today have the legal right to make all coverage decisions without any physician input. The legacy opioid challenge has no easy solution that will please all parties.

Forest Tennant, MD, DrPH

Opioid Malabsorption

I want to express my gratitude for the article on opioid malabsorption,14 which helped to restore my life! I have been suffering from malnutrition, low iron, and anemia, as well as, low vitamin D and B12 due to undiagnosed, untreated celiac disease. In addition, I have had severe osteoporosis since the age of 33 years, and no pain specialist would work with me locally due to my narcolepsy.

My physician and I struggled for years with different medications in an effort to manage my pain. After trying everything, including OxyContin (oxycodone, 80 mg twice daily), nothing proved effective until I brought the article on malabsorption to my doctor, and we followed the recommended protocol, starting on a lower dose (10 mcg) of Butrans (buprenorphine). It was as effective if not more so than the oxycodone and we both were amazed at how easily I was able to taper off the opioid.

I just wanted to let you know how much you are touching lives.

Summer Roundtree

Dear Summer,

Our studies have found that about 20% of patients with chronic pain who require opioids can’t properly absorb the medication when taken by the oral route. There are several circumstances in which oral opioids may be poorly absorbed; among them are:15

  • Abdominal/pelvic surgeries with adhesions
  • Bowel/stomach resections including bariatric surgery
  • Head or neck trauma that interferes with autoimmune/vagal nerve innervation
  • Intrinsic bowel diseases, such as celiac, or an autoimmune disease such as Crohn’s disease
  • Multiple cytochrome P450 defects


The inability to transport opioids from the stomach and intestinal lumen into the serum is common enough that every chronic pain patient could be screened for “opioid malabsorption.” A simple screen is to ask a patient if they obtained pain relief with oral tramadol, codeine, or hydrocodone. Practically all adult pain patients have had experience with these opioids. If they didn’t get pain relief with these opioids, they deserve investigation for opioid malabsorption.

Forest Tennant, MD, DrPH

Last updated on: August 16, 2017
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What are Nav1.7 inhibitors and how are they used in the treatment of neuropathic pain?

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