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12 Articles in Volume 16, Issue #1
A New Look at Sphenopalatine Ganglion Blocks for Chronic Migraine
Can Weight Loss Help Reduce Psoriatic Arthritis Symptoms?
Chronic Back and Neck Pain in America 2015 Survey Results
Efficacy of Acupressure Plus Manipulation for Lumbar Disc Herniation: A Clinical Report
Is Tapentadol a Glorified Tramadol?
Letters to the Editor: Naloxone, Opioid Tolerance, Polyarthropathy
New Research Into Psoriatic Arthritis
New Technique Shows Promise as Adjunct In Chronic Pain Management
Pharmacogenetic Testing in Pain Management: Where Do We Stand?
Reinventing IM and Procedural Injections: The Sota Omoigui Short Needle Technique
Timely- versus Delayed-Use of TNFi’s: Which Approach Is Better?
Undiagnosed Atlas Subluxation in Patient with Pain and Poor Myofascial Function

Letters to the Editor: Naloxone, Opioid Tolerance, Polyarthropathy

January/February 2016

Rest Easy—Naloxone Is in the House

I have been practicing pain management using medication protocols, interventional techniques, and pain relief surgical endeavors for almost 10 years in the academic and solo practice setting.

In the last 8 months, I have been happily surprised with the uptake and reception of my suggestion to my chronic pain patients that they keep in their home, an auto-injectable syringe of naloxone (Evzio). I describe it as the antidote to a suspected opioid overdose.

For the most part, the patients report that they sleep better at night knowing that this medication is accessible and “can save the day” before the paramedics arrive to deliver the same medication.

I insist that patients receive this medication (via my prescription) if they are on long-acting opioid medication, high doses of opioid medication, have a history of addiction or alcoholism, or have children in the home.

In my clinic, the patients listen to a presentation that myself or a team member delivers and then they have a chance to demonstrate their understanding by using the trainer device. The presentation includes signs of overdose, and the training is performed in a “crisis” role-play so that the patient feels comfortable if and when the time comes to use the medication.

Rajni Jutla, MD

Dr. Jutla,

We thank you for sharing your insightful experiences with naloxone. As a follow-up to your letter, we thought it apropos to take a step back and share our experiences with qualifying patients for in-home naloxone. Last July the American Medical Association (AMA) advocated for dual therapy of opioids and naloxone for all patients at risk that receive chronic opioid therapy.1

Dr. Fudin and I have worked extensively with risk mitigation when caring for patients on opioid therapies. Zedler et al developed the risk index for overdose or serious opioid-induced respiratory depression (RIOSORD) score, a risk stratification tool that was originally validated in the veteran population to determine probability of an overdose of serious opioid-induced respiratory depression.2

Opioid dependence, psychiatric disorder, pulmonary disease, liver disease, use of an extended-release opioid, use of an antidepressant, use of a benzodiazepine, daily morphine equivalents per day, and recent hospitalization or emergency department visit were all identified as relevant factors that contribute to a patient’s opiate overdose risk.

The RIOSORD score is a 17-question survey with a total maximum score of 115. Each aforementioned variable contributes a certain percentage to the score and each RIOSORD score correlates with an average predicted probability of an opiate overdose or serious opioid-induced respiratory depression.

More recently, Zedler and colleagues validated a slightly revised RIOSORD in a retrospective case-control study in civilian patients consisting of approximately 18 million patients.3

Currently this score is being used in our clinics to determine which patients should be targeted for access to in-home naloxone. This report and use of the score help to streamline the process of identifying patients most in need and also hopefully help providers become more comfortable with prescribing this life-saving medication.

Our goal is to proactively identify patients who are at increased risk of an opioid-related overdose. Patients who generate a certain RIOSORD score of 25 or higher (correlating to a 14% risk of overdose or serious opioid-induced respiratory depression) are deemed appropriate to receive naloxone and commensurate training, which is generally completed by a pharmacist.

This strategy also affords a double check for dispensing pharmacists to foster dual therapy for naloxone in patients for whom it was not prescribed by the physician. The additional number of high risk patients with opioid dependence that are precluded from non-opioid therapy because of multiple medical comorbidities is astounding; this is a population of patients that requires further scrutiny.

An effort has recently ensued to educate off-site providers within communty-based outpatient clinic affiliates in rural locations. Our work could be broadened and further automated far beyond what we have achieved thus far. Currently our project is moving towards imbedding the RIOSORD score and associated percent risk into our electronic medical records system.

This effort is aimed to help all clinicians quickly and easily identify patients who are most at risk for an un-intentional opioid associated respiratory depression.

Editor's Note: The FDA approved an intranasal formulation of naloxone (Narcan) in November, 2015.

Jacqueline Pratt Cleary, PharmD.
Jeffrey Fudin, PharmD
Samuel Stratton, VA Medical Center
Albany, New York
Drs. Fudin and Cleary disclosed that their involvement with this article was not prepared as part of their official government duties.

Tolerance to Opioids

Practical Pain Management and Dr. Tennant, thank you for your article on Legacy Pain Patients, which detailed your clinical experience of patients safely consuming opioid medications for 30 years with stable dosing.4

Your clinical experience of absence of tolerance to opioid pain relieving properties is buttressed by 2-year studies,5,6 3-year studies,7-9 a 10-year study with “opioid dose escalation in only a few patients,”10 and your invaluable published study.

Some patients truly require a high-dose regimen that is commensurate with agonizing pathology, but fabrications of tolerance seems to have been a tool by which abusers achieved high dosing. Certainly over the past decade, too many clinicians prescribed opioids without proper study and patient pre-selection with monitoring, causing the predictable slingshot repercussions that all compassionate, careful, studious clinicians must now correct.

Pain management has regressed to an era where previously hard working, chronic pain patients are facing needless suffering from opioid phobia. In some cases, this has led to dangerous excessive consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and ethanol, as well as functional regression and less contribution to society.

However, when viewed as an opportunity, that which doesn’t kill you makes you stronger.

The repercussions of the excessive prescribing era, hopefully, will result the creation of a nationwide Prescription Drug Monitoring Program. Such a program could help identify poor prescribers, who are averse to abuse-resistant opioid prescribing as well as the vast numbers of sub optimally trained prescribers.

Perhaps this will be the time when THC, in a non-oncogenic form, will be endorsed by lawmakers.11,12 With supportive evidence-based literature, law enforcement endorsement of Marinol’s supra-additive analgesia may result in greater anti-nociception, lower opioid dosing, less euphoria risks, better facilitation of objective functional benefit.

Less addiction, more pain relief may ensue.

Aaron S. Geller, M.D.
Assistant Professor
Tufts University School of Medicine—New England Medical Center
Boston, Massachusetts

Dr. Geller,

Your question is a critical one. Yes, we have some patients still alive and on opioids for over 30 years. Their daily dosage has remained remarkably stable in terms of morphine equivalents. (Note: I began accepting some intractable pain patients already on opioids in 1975). Interestingly, Howard Hughes took a relatively high opioid dosage and lived 30 years (1949 to 1977).13

I thank you for your concern because the anti-opioid crowd says there is “no-evidence” that you can safely take opioids, since opioid maintenance “always” ends in addiction, aberrant behavior, or toxicity. My experience is that some patients can live a pretty normal, long life because of opioids, and they are very willing to talk about it and be examined.

Your letter is inspirational in that it’s time to pull the 30-year patients together and do a summary as it’s been some time since we’ve done so.14

Forest Tennant, MD, DrPH

Tolerance to Catecholamines?

I would like to know if tolerance develops to the use of catecholamines over time, requiring increased doses in the treatment of centralized pain. I appreciate your work and your kind response to my question.

J. Randall Underwood, MD

Dear Dr. Underwood,

The use of adrenergic agents, in my hands, has followed what we see with opioids—some patients develop tolerance to side effects quite rapidly. For example, I recently started a patient on phentermine 37.5 mg divided into a morning and afternoon dose. After a week, the patient raved about the additional pain relief she had received and that she had decreased her opioid usage. After 2 weeks, however, the phentermine quit working due to tolerance and she required a higher dosage regimen.

In other patients, I have slowly raised the initial dose over a 6- to 12-week period, at which time the patient reached a plateau dosage regimen. After this time, the dosage remained stable for as long as 1 year. This has been the usual case with methylphenidate, dextroamphetamine, phentermine, and modafinil (Provigil).

Clinically, it appears that the adrenergic drugs are making up for a deficiency of catecholamines, which usually can be demonstrated by low serum levels. Dose escalation has not been a usual observation once the patient reaches their plateau or maintenance dosage.

In dealing with adrenergic agents, I believe in the old adage, “Start low and go slow.” The benefits of adrenergic agents are quite obvious in the majority of patients and are highly recommended in order to spare opioids, obtain enhanced pan relief, and provide more energy and mobility.

Forest Tennant, MD, DrPH


I have enjoyed Practical Pain Management and have found it extremely beneficial in recent years as I suffer from a seronegative polyarthropathy. NSAIDs and acetaminophen have not been helpful. I do take a dose of oral opiates and a small dose of Vyvanse. I have responded well to this regimen.

I would not have known about this regimen had it not been for an article in your journal that I shared with my physicians. Thank you for the work you have done and PPM.

Roy D. Elterman, MD
The Pediatric Epilepsy Foundation

Dear Dr. Elterman,

Your letter could not be more instructive relative to the trend in ambulatory pain care. You should be our “poster” child.

Before long-acting opioids and risky interventions should be entertained, a regimen of low-dose, short-acting opioids combined with an adrenergic agent (such as lisdexamfetamine [Vyvanse]) makes more sense from a safety and efficacy standpoint. Adrenergic agents provide pain relief, spare opioids, and prevent a great deal of depression, fatigue, lethargy, and weight gain.

Thanks for sharing. When a physician is willing to reveal their personal regimen, it means a lot.

Forest Tennant, MD, DrPH

Sublingual HCG

Dr. Tennant, I see that you prescribe sublingual human chorionic gonadotropin (HCG). Do you really think it works?

Nelson Vergel

Dear Nelson,

Your question about sublingual HCG is most cogent. I think it works in SOME!! Without question the injectable form is superior. I’m experimenting with a 1,000 to 1,500 unit/mL dose given via the sublingual route. If the patient does not have a response within a month, I switch to the injectable formulation.

The primary reason I start patients with sublingual is purely practical. I can quickly get a patient started on sublingual HCG in my clinic, and I am able to instruct them on usage, the benefits of HCG, and the goals of its use. In addition, there are more compounding pharmacies in my area that will make sublingual HCG, but not injectable HCG.

My use of HCG is strictly in centralized, intractable pain patients. Those primarily encompass patients who have RSD/CRPS, post-traumatic brain injury, post-viral headaches, Ehlers-Danlos, chronic abdominal pelvic neuropathies, and inflammation/arachnoiditis.

To date we’ve had little to offer these tragic pain cases, and HCG has, in my opinion, great benefit in pain relief, reduction of opioid use, and increase in quality of life.

Forest Tennant, MD, DrPH

Last updated on: March 15, 2016
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