The Pain Relief Network

Frank Fisher, M.D.;
Practical Pain Management.,
5(6), 33-41; 2005; (Sept.-Oct. issue

This article examines a disturbing pattern of conflict existing between expert testimony offered against pain-treating physicians during regulatory assaults, and scientific evidence and medical principles upon which the rational standard of care for pain management is based.

In the pathogenesis of chronic pain, ongoing pain is the single condition prerequisite to the development of this disease state. In this context, the term “pain” identifies the disease vector as well as the illness. Chronic pain is a malignant disease in the sense that when it goes untreated, or under treated, it tends to metastasize to areas of the nervous system it did not previously affect. Thus, the obligation to control pain lies at the core of the physician’s ethical commitment to his patients. A government witness testifying against a pain-treating physician appears unconcerned by this imperative.

Well, it’s hard to make a judgment how much pain a person is having unless you wait while they’re off pain medication for a year or so. And that’s — and we as doctors are being told these days that you should never allow a patient to have any pain and so you get into a catch 22. We’re not supposed to allow them to have pain, and yet you can’t make a good judgment of whether they really have excessive pain or not.[1]

The prospect of this sort of attack, occurring in a court of law, represents a menace to every physician who attempts to treat chronic pain in good faith.

THE STANDARD OF CARE FOR PAIN MANAGEMENT

The standard of care for pain management consists in its broadest outlines of 1) medical indications for treatment, 2) clinical practices, and 3) therapeutic goals.

INDICATIONS & THERAPEUTIC TRIALS

No tools exist that allow a physician to predict which individual pain sufferers might benefit from treatment with opioid analgesics, or to predict which specific medications might be of benefit. Consequently, these questions must be resolved empirically, on a patient-by-patient basis. This is accomplished through the implementation of a therapeutic trial.

This clinical strategy is imminently reasonable because, in the vast majority of cases, if a beneficial response to treatment doesn’t occur, opioids may be safely and uneventfully withdrawn.[2] Consequently, a diagnosis of incurable pain is an absolute indication for a therapeutic trial of opioid analgesics.

In the following testimony, a government witness rejects this wisdom, and instead accuses a well-intentioned physician of recklessly exposing patients, carrying histories of substance abuse, to unacceptable risks of addiction.

It’s clear that a number of his patients were drug use potential. Potential candidates. Particularly, patients addicted to cigarettes or who had habits of alcoholism. These are already abusive individuals and they are more likely than someone else to have an abuse problem with a — with a powerful analgesic medication.[1]

“This is why in the American Society of Addiction Medicine, as part of my training and to be qualified as an Addictive Medicine Specialist, and as part of the American Society of Addiction Medicine, there’s a whole section on management of pain and patients with addictive disease because patients with addictive disease that have pain are at particularly high risk when you use opiates.”[1]

A review of the medical literature reveals that a history of substance abuse does not in fact reliably predict a poor therapeutic outcome, when chronic pain in this population is treated with opioids.[3,4]

Titration To Optimal Therapeutic Effect

Titration to optimal therapeutic effect is the central practice element within the standard of care for pain management. Its implementation is required in order to effectively execute a therapeutic trial of opioids.

Titration is accomplished by incrementally raising the dose of an opioid analgesic to one of two possible end points. These are, 1) optimal therapeutic response occurs, or 2) intolerable side effects intervene, preventing further dosage increases. If the latter occurs, the physician should then employ clinical practices such as combination treatment, or opioid rotation.

A ground rule for titration allows for a doubling of opioid dosages from one interval to the next.[5] This represents a geometric progression, and allows for an 800 percent increase within a time frame of 3 dosage intervals. Below, a government witness expresses misgivings over a far slower rate of titration.

“In April of one year she was on 400 milligrams of OxyContin. It — it doubled in May, a month later. I don’t know if that was 30 days. I don’t have the — it went from 400 to 960. That’s more than doubled. I’m talking about milligrams a day. The numbers themselves don’t mean much to me, but the rate of getting to a total number means something. Then the very next month, June, it went up to 2400 hundred. So from April to May to June, say two months, 60 days, it went up 6-fold or six hundred percent. That’s an exceedingly high rate of titration, in my experience.”[1]

According to accepted guidelines, the above titration could have been accomplished within 2 1/2 dosage intervals. This would have required a maximum of 36 hours. Instead, the patient whose care was in dispute experienced this dosage increase over 60 days, or 1440 hours.

During the proceedings in which the above testimony was offered, it represented the high water mark for understanding by government experts of the subject of titration. Testimony offered by a second government witness demonstrated an even more profound ignorance of this essential clinical practice.

Titrated appropriately is a little strong because titrate appropriately means come down. There was more of a pattern of up.[1]

One might note that if a physician failed to titrate to therapeutic effect when employing insulin in the treatment of diabetes, or when treating hypertension with blood pressure medications, this professional misconduct would be characterized as reckless negligence.

Finally, because there is no arbitrary upper limit to dosage at which opioid analgesics become toxic, titration is an open-ended practice. This phenomenon is placed into clinical context by the fact that dosages as high as 35 grams, (35,000 mg), of morphine per day have been safely administered.[6] In spite of this, Dr. Michael Ashburn, a former president of the American Pain Society offered the following testimony against his colleague, Dr. William Hurwitz, in federal court.

morphine at a dose of 195 mg/day constitutes a high dose.[7]

Before Dr. Hurwitz’s trial ended, six former presidents of the American Pain Society publicly rejected Dr. Ashburn’s testimony. In a letter to the court, they made the following remarks addressing Dr. Ashburn’s statement about opioid dosages.

This statement is without foundation in the medical literature and we believe that it is, on its face, absurd.[8]

The jury was not provided with this evidence, and Dr. Hurwitz was convicted. In early 2005, he was sentenced to 25 years in federal prison.

Patient-Controlled Analgesia

Because the experience of pain is a subjective phenomenon, only the patient can accurately assess his own pain levels, and responses to treatment. Consequently, for effective pain management to occur, patients must be empowered to participate both in the selection of their medications, and in the titration of their dosages.

The practice of patient-controlled analgesia expresses the fundamental clinical principle of individualization of medical treatment. It also conforms to the bioethical pillars that form the basis of modern medical practice. These pillars include informed consent, patient autonomy, and the understanding that the existence of a partnership between the physician and the patient favors positive treatment outcomes.

For more than a decade, patient-controlled analgesia has been accepted as the standard in the management of acute post-surgical pain.[9] In this setting, the practice has proven to be safe and effective.[10,11,12] Patients treated with this approach are typically more satisfied with their pain control, use less medication, and leave the hospital sooner than patients treated with the conventional approach.[9]

Patient-controlled analgesia is also widely used in the management of chronic pain in outpatients. Immediate-release formulations of opioid analgesics are routinely prescribed to control breakthrough pain. These dosages are self-administered by patients on an as-needed basis. Perusal of product literature reveals that this common clinical practice enjoys FDA approval.

All of the above conditions establish patient-controlled analgesia as an essential element of the standard of care in the management of chronic pain. However, an expert testifying against a pain-treating physician rejects the practice as dangerous:

So in essence, he was advancing, in my opinion, a self-medication regimen which is — which is dangerous.[1]

This attack overlooks the significance of the physiological phenomenon of tolerance. In patients accustomed to opioids through regular exposure, tolerance effectively precludes the occurrence of significant respiratory depression.[13] A consensus statement from the American Academy of Pain Medicine and the American Pain Society confirms this.

It is now accepted by practitioners of the specialty of pain medicine that respiratory depression induced by opioids tends to be a short-lived phenomenon, generally occurs only in the opioid-naive patient, and is antagonized by pain.[14]

THERAPEUTIC GOALS

Therapeutic goals for the management of chronic pain are two-tiered. 1) Pain relief is the first tier. (In the treatment of acute pain, achieving below 4 on a scale of 10 satisfies the standard of care.) 2) The second tier is the achievement by the patient of optimal functioning. When optimal therapeutic response has not occurred, the treating physician is obligated to titrate dosages of opioids upwards.

When a physician faces accusations based on his controlled substances prescribing, testimony by government experts typically promote rationales for why the targeted physician should have arbitrarily limited dosages. An exchange between a prosecutor and a government witness illustrates how these sorts of accusations conflict with the standard of care.

Q There were many chart notes indicating that she was doing well on her current medication, so the whole course of the time in which these are being escalated, there not only is no justification for increasing it, there appears to be justification for leaving it exactly as it was; would you not agree, Doctor?

A Not only do I agree with what you said, but I also noted it in a number of other patients whose charts I reviewed, that patients were doing fine. Medication was adequate. Painkillers were adequate. Whatever those these are in the typed notes. Yet at the same time the dosage was being escalated and escalated and escalated during the period of time when the statement made in the chart was pain coverage adequate.[1]

If the patient had achieved optimal functioning and dosages were titrated upwards anyway, the expert might have had grounds for dispute.

The sort of testimony excerpted above, raises the disturbing possibility that the discipline of pain management, as it currently exists, is only nominally engaged in pain control. This testimony raises instead the disturbing possibility that the overriding but unspoken agenda within the field is the accomplishment of drug control through the arbitrary limitation of opioid dosages.

THERAPEUTIC OPTIONS

Therapeutic options in the management of chronic non-malignant pain are distinguished from the previously discussed essential practices by the fact that their utility must be determined on a patient-by-patient basis. Evidence favoring one therapeutic option over another doesn’t exist. A statement found in a position document posted on the American Pain Society Web site confirms this state of affairs.

APS acknowledges that there are currently no evidence-based guidelines, nor widely accepted consensus guidelines, for the management of chronic benign pain conditions.[15]

Controlled-Release vs. Immediate-Release Formulations

A controversy exists around the clinical issue of choosing between different formulations of a given opioid. Current dogma promises that controlled-release formulations offer superior pain control, and are less prone to abuse than their immediate-release counterparts. A government expert articulates these suppositions, as if they represented an element of the standard of care.

The standard of practice is to prescribe short acting opioids in limited amounts and then convert to a long acting opioid such a Methadone, Oxycontin, levorphanol or MS Contin to reduce the likelihood of euphoria/anxiolysis as inducements to develop addictive behaviors (running out early, multiple prescribers, losing prescriptions, etc.)[1]

There is in fact no evidence indicating that prescribing extended-release formulations in the treatment of chronic non-malignant pain offers any advantages beyond convenience to the patient.[16]

In the following testimony, a government witness speculates about the potential for misuse of immediate-release formulations.

The short-acting analgesics definitely promote pain behavior because they have this rebound phenomena where the blood level gets low and patients get irritable and they feel their pain and they want to take more. Patients start watching the clock. The whole pattern of pain behavior is increased when you deal or dish out these short-acting pain — pain killers.[1]

The above position is not supported by evidence. It is based instead on the misguided assumption that pain sufferers are at substantial risk to engage in substance abuse. They aren’t, and the medical literature indicates that selected patients may in fact be effectively managed with immediate-release formulations of opioids.[17]

Gratuitous Abuse

The use by a government “expert” of expressions such as “deal” and “dish out” heaps gratuitous aspersions upon the physician against whom he is testifying. The potential effect on a jury is a lurid mischaracterization of well-intentioned medical practice. Any physician unfortunate enough to be prosecuted on this basis may anticipate this sort of character assassination, delivered in the courtroom by a rogue subset of his academic colleagues.

Previous Alcohol Abuse

Attacks by government experts against physicians, who prescribe immediate-release opioids, become more strident when these formulations are used in the management of pain in patients carrying histories of alcohol abuse.

an extreme departure from the standard of care that represents a consistent ignorance of the usual practice of: avoiding highly addictive opioids (Norco, Vicodin ES, Demerol) in a patient with a history of alcoholism.[18]

This assertion is contradicted within the medical literature by evidence indicating that a remote history of alcohol abuse holds little or no predictive value for the success or failure of treatment.[3,4]

COMBINATION TREATMENT

Combination therapy, employing more than one medication, is a widely accepted clinical practice. It is applied in the treatment of a variety of medical conditions, ranging from high blood pressure to infections. In the context of pain treatment with opioid analgesics, this practice is a source of controversy. A government expert asserts that its use represents a deviation from the standard of care.

a departure from the standard of care that represents an ignorance of the usual practice of: using more than one type of short acting opioid.[18]

The medical literature contains no clinically based evidence to either support or discourage the use of this approach to the management of chronic pain. Basic science has however established the existence of a heterogeneous array of opioid receptors, as well as the existence of a multitude of endogenous opioids, otherwise known as endorphins, which interact with these receptors. [19]

This evidence derived from basic science research, suggests that combination therapy with opioids will ultimately prove to be an effective pain treatment strategy. Until that occurs, the approach should be employed in the care of those individual pain sufferers who clearly benefit from it.

The Use Of Adjuvants

Adjuvants such as tricyclic antidepressants and anticonvulsants are commonly employed in the management of chronic pain. The stated intent of this approach is often to minimize opioid dosages.

When employed for this purpose the use of adjuvants is grounded neither in evidence, nor in principle. It is generally preferable to treat patients with the smallest number of medications possible, because when multiple medications are employed the odds favoring the occurrence of adverse drug interactions multiply.

Additionally, the use of adjuvant drugs is accompanied by an alarming array of adverse, and potentially lethal side effects. In contrast, opioids are relatively safe when used as directed by a physician. A government expert articulates a conflicting viewpoint.

I just happened to notice that in the 30 some odd cases I reviewed I didn’t see much adjuvant or helping medications to help with the analgesic so that they act together on the pain.

But it’s wise to titrate also by adding adjuvant drugs that would take the edge off pain as well rather than push up one drug solely.[1]

In addition to violating accepted medical principles, this testimony runs counter to academic wisdom, which states that employing opioids in combination with adjuvants is an option to be considered after titration with opioids has failed.[2]

Psychiatric Referrals & Behavior Modification

The importance of recognizing chronic pain as a disease cannot be overstated. Confusion often arises because the disease state typically expresses itself through an array of psychological symptoms including insomnia, anxiety, and depression. The following assertion, made by a government expert, assumes that psychological symptoms signify comorbid psychiatric diseases:

a departure from the standard of care that represents a consistent ignorance of the usual practice of: in not referring the patient to a mental health practitioner when he recognized that the patient was suffering from anxiety/depression.[18]

This misconception is harmful because mistaking the symptoms of one disease as a diagnostic of another predictably leads to inappropriate treatment. Furthermore, insult is added to injury by the implication that rather than suffering from an illness with an organic basis the pain victim is psychiatrically deranged.

Multimodal Treatment

A government expert testifies that the treatment of chronic pain with opioids alone is not acceptable:

Chronic pain has to be managed by multiple modalities. Exercise, other devices. And, certainly, consultations with people who specialize in behavioral modification.[1]

This dogmatic one-size-fits-all approach is not supported by evidence. It overlooks the fact that many pain victims, treated exclusively with opioids, resume normal functioning. Through the accomplishment of treatment goals, this outcome, by definition, satisfies any rational standard of care. The expense and inconvenience accompanying the imposition of additional therapeutic modalities would represent only hardship to these patients.

Finally, for lack of funding sources, if not for lack of demonstrable cost-effectiveness, multidisciplinary treatment programs are headed for extinction. [20]

Behavioral Modification

The assertion that behavioral modification is a necessary element in the treatment of chronic pain suggests that this government “expert” regards chronic pain as a behavioral disorder, rather than as a disease with an organic basis. This is understandable in the following context.

Complaints of inadequate treatment represent a threat to the self-interests of physicians who wish to avoid scrutiny by law enforcement. If these complaints are conceptualized as undesirable behavior, and then eliminated through a program of behavioral modification, the physician is freed to pursue, through the limitation of opioid dosages, a socially determined agenda of drug control. In this manner, a program of behavioral modification replaces the physician’s obligation to titrate to optimal therapeutic effect.

CONCLUSION

Drug control is safer than pain control — for physicians

It is an unpleasant reality that unscrupulous physicians may offer corrupt testimony against their colleagues. It is also generally believed that physicians from highly regarded academic institutions can be counted upon to base their testimony on scientific evidence. Analysis of the testimony excerpted above reveals that within the field of pain management this is not a given. In fact, the examples reveal an astonishing measure of scientific illiteracy on the part of otherwise reputable academic physicians.

The common thread uniting their erroneous testimony is an apparent agenda to restrict the use of opioids in the treatment of chronic pain. This compulsion is held out in the courtroom as if it were a legitimate goal of treatment. It isn’t. The benefits accrue only to the physician who endeavors to avoid regulatory scrutiny, not to the interests of his under treated patients.

The preceding observations create a conundrum for the conscientious physician inclined to base his treatment of pain on scientific evidence and principle. Within the current regulatory environment, the physician who pursues a humanitarian, evidence-based approach to the management of chronic pain increases the risks that he might become the target of an unwarranted prosecution.

REFERENCES

1. State of California v. Fisher, Miller (1999 – 2003). Shasta County Superior Court, Criminal Case No. #-99F1134. Transcript from preliminary hearing,

2. Portenoy RK. Opioid Therapy for Chronic Nonmalignant Pain: clinicians’ perspective. Journal of Law, Medicine & Ethics. (1996);24(4): 296-309.

3. Chabal C, Erjavec MK, Jacobson L, Mariano A, Chaney E. Prescription opiate abuse in chronic pain patients: clinical criteria, incidence, and predictors. Clin J Pain 1997;13(2):150-155.

4. Dunbar, SA, Katz NP. Chronic opioid therapy for non-malignant pain in patients with a history of substance abuse: report of 20 cases. J Pain Symptom Manage 1996;11:163-171.

5. Indelicato RA, Portenoy RK. Opioid rotation in the management of refractory cancer pain. J Clin Oncol 2002: Vol 20, No 1, 348.

6. Portenoy RK, Payne R. Acute and Chronic Pain. In: Substance Abuse: A Comprehensive Textbook Ed. 3. Lowinson, Joyce H. ed. Philadelphia: Lippincott Williams & Wilkins 1997. 563-584

7. United States v. William Hurwitz. December, 2004.

8. Portenoy RK, Campbell JN, Foley K, Cleeland C, Miaskowski C, Payne R. Communication of past presidents of the American Pain Society to the Federal Court in Alexandria, V 2004, Dec. 10.

9. AHCPR Archived Clinical Practice Guidelines. 1. Acute Pain Management: Operative or Medical Procedures and Trauma Available at: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat6.chapter.8991 (Last visited March 19, 2005)

10. Chapman CR, Hill HF. Prolonged morphine self-administration and addiction liability: evaluation of two theories in a bone marrow transplant unit. Cancer. 1989; 63:1636-1644.

11. Owen H, Szekely SM, Plummer JL, Cushnie JM, Mather LE. Variables of patient controlled analgesia: concurrent infusion. Anaesthesia. 1989; 44:11-13.

12. Schug SA, Torrie JJ. Safety assessment of postoperative pain management by an acute pain service. Pain. 1993; 55(3):387-91.

13. Light AB, Torrance EG. Physical characteristics and physical fitness of addicts during administration of morphine. Arch Intern Med 1929; 43:327-334.

14. The Use of Opioids for the Treatment of Chronic Pain: A consensus statement from the American Academy of Pain Medicine and American Pain Society; 1997. Available at: (Last visited March 19, 2005)

15. Pain Assessment and Treatment in the Managed Care Environment, A Position Statement from the American Pain Society. Approved by the APS Board of Directors on January 11, 2000 Available at: http://www.ampainsoc.org/managedcare/position.htm> (Last visited March 19, 2005)

16. Katz NP. At Department of Health and Human Services Food and Drug Administration center for Drug Evaluation and Research, Anesthetic and Life Support Drugs Advisory Committee. Bethesda, M 2003: Sept 9-10. Available at: http://www.fda.gov/ohrms/dockets/ac/cder03.html#AnestheticLifeSupport (Last visited March 19, 2005)

17. Fishman S, Wilsey BL. Chronic opioid therapy, drug abuse, and addiction. In: Ballantyne J, Fishman SM, Abdi S, eds. The Massachusetts General Hospital Handbook of Pain Management. Philadelphia: Lippincott Williams & Wilkins, 2003:495-505.

18. Wilsey B. Review and Evaluation of the Treatment Rendered by Frank B. Fisher M.D. Case No. #-02-99-95522. For the Medical Board of California 1999: May19.

19. Pasternak, GW. Molecular Mechanisms Of Morphine Action: From the Clinic to the Bedside 1996. Available at: http://www.ampainsoc.org/societies/epa/east7.htm (Last visited March 19, 2005)

20. Guzman J, Esmail R, Karjalainen K, Malmivaara A, Irvin E, Bombardier C. Multidisciplinary Rehabilitation for Chronic Low Back Pain: Systematic Review. BMJ 2001; 322:1511-1516

July 1, 2005
By: Arline Kaplan
PsychiatricTimes.com

Alarmed by escalating abuse of prescription drugs during the past five years, the National Institute on Drug Abuse (NIDA) is intensifying its research in two areas–understanding mechanisms that underlie the reinforcing, addictive and toxic properties of the drugs and developing medications with less abuse potential.

Marijuana is the number one illegal drug of abuse in the United States; in second place is the nonmedical use of prescription medications such as pain relievers, tranquilizers, stimulants and sedatives, said NIDA director Nora D. Volkow, M.D., at a recent National Institutes of Health lecture (Volkow, 2004).

“[We] need to explore why it is that we are observing such a high abuse of these medications, and how can we prevent the abuse,” she said.

According to newly released findings from the 2003 National Survey on Drug Use and Health, an estimated 6.3 million people (2.7% of the population aged 12 or older) currently use psychotherapeutic drugs nonmedically. An estimated 4.7 million use pain relievers, 1.8 million use tranquilizers, 1.2 million use stimulants and 0.3 million use sedatives (Substance Abuse and Mental Health Services Administration [SAMHSA], 2004).

Particularly worrisome for NIDA is the dramatic increase in the use of opioid painkillers.

“From 1995 until now, [there has been] almost a threefold increase in the abuse of these substances,” Volkow said. The steep increase is especially unsettling, because there has been a decrease in abuse of most illegal drugs during the past few years.

National Survey on Drug Use and Health researchers recently stated that the number of Americans aged 12 or older who reported having ever taken a prescription pain medication for recreational use rose from 29.6 million in 2002 to 31.2 million in 2003. Pain relievers with statistically significant increases in lifetime use included such hydrocodone-combination products as Vicodin, Lortab or Lorcet (from 13.1 million to 15.7 million); such oxycodone-combination products as Percocet, Percodan or Tylox (from 9.7 million to 10.8 million); hydrocodone (from 4.5 million to 5.7 million); the oxycodone product OxyContin (from 1.9 million to 2.8 million); methadone (from 0.9 million to 1.2 million); and tramadol (Ultram) (from 52,000 to 186,000) (SAMHSA, 2004).

The 2003 Monitoring the Future Survey–a survey that assesses the extent and perceptions of drug use among 8th, 10th and 12th grade students nationwide–revealed that 10.5% of high school seniors had used Vicodin for recreational use during the past year and 4.5% had used OxyContin (NIDA, 2004).

“We are dealing with not only a problem of the abuse and diversion of these substances, but we are dealing with toxic compounds,” Volkow said. “Opioid analgesics can produce death from overdose.”

From 2001 to 2002, drug abuse-related emergency department (ED) visits involving narcotic analgesics increased 20% (from 90,232 to 108,320 visits), with hydrocodone and oxycodone being the narcotic analgesics most frequently mentioned (Drug Abuse Warning Network, 2004). Looking at motives underlying drug abuse-related ED visits involving narcotic analgesics, dependence headed the list (47%; 50,623 visits), followed by suicide (22%; 24,308 visits), psychic effects (15%; 16,153 visits), other motives (2%; 1,790 visits) and unknown motive (14%; 15,446 visits).

Common Characteristic

The reason that alcohol; cocaine; marijuana; heroin or prescription medications such as opioid analgesics, benzodiazepines or stimulants can produce addiction is that all of them have a common characteristic. They increase the concentration of dopamine, Volkow pointed out in her lecture. Methylphenidate (Ritalin, Concerta, Metadate), for example, increases the synaptic concentration of dopamine by blocking the dopamine transporters.

Volkow was among the first researchers to use positron emission tomography (PET) to investigate the nature of acute brain changes in dopamine activity induced by drugs of abuse as well as long-term brain changes in dopamine activity and the functional consequences of these changes in drug-addicted subjects (Volkow et al., 2004a, 2004b).

Such studies, she explained, have corroborated the role of dopamine in the rewarding effects of drugs of abuse in humans and also its involvement in motivation. Imaging studies have shown that the reinforcing effects of drugs of abuse in humans are contingent upon large and fast increases in dopamine that mimic but exceed in the intensity and duration those induced by dopamine cell firing to environmental events (e.g., food, sex, social interaction). In addition, imaging studies have documented a role of dopamine in motivation, which appears to be encoded by fast as well as smooth dopamine increases. Since dopamine cells fire in response to salient stimuli, the supraphysiological activation by drugs is likely to be experienced as highly salient (driving attention, arousal, conditioned learning and motivation) and may also reset the thresholds required for environmental events to activate dopamine cells (Volkow et al., 2004b).

In a recent article, Volkow et al. (2004b) explained that dopamine function is markedly disrupted in drug-addicted individuals. There are decreases in dopamine release and in dopamine D2 receptors in the striatum. This hypodopaminergic state may lead to deregulation of reward, motivation and inhibitory control circuits.

“So what happens when that individual who is addicted is exposed to a natural reinforcer such as food or sex? Well, the amount of dopamine to start with is significantly reduced, and then the receptors are also lower. Therefore, the probability of an interaction of dopamine with a receptor is significantly decreased, and the likelihood of a person who is addicted to perceive a natural reinforcer as pleasant is going to be dramatically affected … They won’t be motivated for basic, natural reinforcers,” she said in the lecture.

On the other hand, an addicted person will be motivated by the drug of abuse. “That is one of the basic changes that trigger the aberrant behavior that you see in a person who is addicted,” Volkow said. Such behavior is “the compulsion to take the drug, despite the fact there are severe, adverse consequences,” she added.

Confounding Variables

“If [psychotherapeutic] prescription medications have the potential for producing abuse and addiction, why don’t they do it frequently?” Volkow asked. The answer lies in the fact that the drug’s effects are not just a function of the drug itself but other factors such as dose, frequency of dosing, route of administration, expectations and context of administration.

Volkow cited the example of a patient being prescribed a stimulant for attention-deficit/hyperactivity disorder and being told to take three tablets a day or 10 mg of the drug every three hours. If the patient is addicted to cocaine or methylphenidate, the patient will likely take it every 30 minutes at 30 mg doses.

“When individuals abuse methylphenidate, they don’t take it in a tablet, they inject or snort it. The route of administration determines the speed by which the drug gets into the brain,” she said. If individuals inject intravenous methylphenidate, “they will feel a high, which cocaine abusers say is indistinguishable from that they get with intravenous cocaine. However, when you give them oral methylphenidate, they don’t feel anything, even though you may be delivering as high a dose as when delivered intravenously.”

The effects of expectation on brain responses to drugs of abuse also have been studied. In drug abusers, the subjective responses to a drug are more pleasurable when the person expects to receive the drug than when they do not. Volkow cited an imaging study she and colleagues conducted examining the response of brain glucose utilization to intravenous methylphenidate in cocaine abusers under distinct conditions of expectation and no expectation (Volkow et al., 2003).

Four conditions were tested: 1) individuals expected and received methylphenidate; 2) individuals expected methylphenidate but received placebo; 3) individuals expected placebo but received methylphenidate; and 4) individuals expected and received placebo.

The increases in metabolism were approximately 50% larger when methylphenidate was expected than when it was not, and these differences were significant in the cerebellum (vermis) and thalamus. Methylphenidate-induced increases in self-reports of “high” were also approximately 50% greater when subjects expected to receive it than when they did not.

Studies have also shown that a drug’s effects are influenced by the context in which it was given, for example, school versus party environment. Volkow cited a study where methylphenidate was administered while individuals were in a boring context as compared to when they were in an exciting context (Volkow et al., 2004c). Dopamine increases were larger when methylphenidate was given with a task that required cognitive performance that was remunerated than when it was given with a task that did not require performance and was not remunerated.

In looking at other factors influencing the abuse of prescription medications, Volkow pointed to the tremendous increase in availability, media coverage and the World Wide Web. “Prescriptions for stimulant medications, for example, have doubled every five years over the past 15 years,” she said. “Last year, one of the most frequently prescribed drugs in this country was Vicodin. So the increase in prescribing has contributed to the increased availability of these drugs.”

Awareness of the drugs has increased through television advertisements and such magazine stories as Newsweek’s “Ritalin: Are We Overmedicating Our Kids?” and the New York Times’ “The OxyContin Underground: How a Prescription Painkiller is Turning Into a Pernicious Street Drug,” she added.

“The Web, of course, is a very valuable tool in terms of disseminating information,” Volkow said. “Unfortunately, it [also] is a valuable tool for the diversion of drugs. If you go to Google tonight and enter ‘prescription drugs’ and then enter ‘prescription drugs, no prescription required,’ you will get thousands of sites where you can actually get prescription medications without the need for a prescription … The only thing you need is a credit card number. You could be 10 or 12 years of age, nobody will check that … Now we have access to these pharmacies, many of them illegal and many of them in other countries where the quality control of the medications cannot be assured, increasing the likelihood of toxicity.”

NIDA’s Role

What is the role of NIDA in fighting prescription drug abuse? Volkow said, “We have a multi-target approach that involves multiple projects.”

These projects include developing medications to treat the problem of addiction to opioid analgesics; developing medications that can treat pain but do not have the abuse potential; and educating the public and health care professionals about prescription drug abuse.

Volkow noted that NIDA has launched a very large educational campaign to alert the public and health care professionals on the most frequently prescribed drugs that have the potential for abuse and to provide them resources for more information such as NIDA’s Web site .

According to Volkow, one of the initiatives they are pushing to do with their sister agencies, SAMHSA and the Office of National Drug Control Policy, is the education of physician specialists about the dangers of narcotic analgesics and proper management of pain. Many specialists believe that if an opioid analgesic is given for pain, the patient is not going to become addicted.

“That is what they teach you in medical school,” Volkow said. “That’s true if they give you the opioid analgesic for a very short period of time, such as one week. The problem starts when an opioid analgesic is given for a chronic condition such as back pain. Anywhere from 5% to 7% of people prescribed opioid analgesics for chronic pain are going to become addicted. So there is this false belief that you are not going to become addicted if you have pain, and that has led some physicians to prescribe opiates much more than they should.”

On the other hand, Volkow said, we have also been hearing for many years about patients with severe pain who never get the proper medications and as a result suffer a lot of handicaps. To help, NIDA is promoting the development of compounds that have analgesic properties yet are not addictive.

Non-Addictive Pain Treatments

Frank Vocci, Ph.D., NIDA’s director of the Division of Pharmacotherapies and Medical Consequences of Drug Abuse, told Psychiatric Times that NIDA is looking at drugs that are cannabinoid agonists. Cannabinoids diminish responses to painful stimuli. There are two types of cannabinoid receptors, according to Vocci: CB1 receptors are found in the brain, while CB2 receptors are found primarily in peripheral tissues with immune functions. Through the research of medicinal chemist Alexandros Makriyannis, Ph.D., of Northeastern University, NIDA is exploring whether CB2 receptor agonists may hold the promise for medical treatment of pain without central nervous system effects. The research is still in the preclinical stage.

There is another project with a drug called resiniferatoxin (RTX) that has been shown to be effective for treatment of severe pain in several animal models, Vocci said. “Hopefully, we will have clinical studies in 2005. We are in the final stages of discussing this with the [U.S. Food and Drug Administration]. A package has been sent to them, and we are going to have a conference with them about this,” he added. The medications will be tested in terminal cancer patients for whom opiate analgesics no longer provide pain relief.

The lead researcher on that study is expected to be Andrew Mannes, M.D., anesthesiologist at NIH’s Warren Grant Magnuson Clinical Center.

For individuals suffering from chronic pain, who have become addicted to opioid analgesics, NIDA is evaluating alternative medications.

“NIDA has developed buprenorphine [Subutex or Suboxone when combined with naloxone] that has much less potent effects than heroin, morphine or Demerol [meperidine],” said Volkow. “It is an opiate that has analgesic properties. We are going to be launching a large clinical trial to evaluate the benefit of this medication in the treatment of individuals who have pain but are also addicted to opiate analgesics.”

According to Vocci, the protocol for the clinical trial is being developed. The trial is expected to be underway in the summer of 2005.

Vocci was asked what other medications besides buprenorphine are being developed to treat problems of addiction to opioid analgesics. One approach is a “depot” formulation of naltrexone (ReVia), an opiate receptor antagonist. The oral form of naltrexone is indicated for use in the treatment of alcohol dependence and for the blockade of exogenously administered opioids.

The depot formulation, currently being studied for treatment of alcoholism, was studied by NIDA for opiate addiction. “We actually funded three separate companies to do research on it,” Vocci said, and at least one of the companies is clearly working toward a drug application with the FDA.

Another drug being developed with NIDA’s help is called lofexidine. Lofexidine is an -2 adrenergic agonist that is increasingly used in the management of opiate withdrawal–notably in the United Kingdom.

“We have done one major clinical trial with it, and we are going to help a company develop a second major clinical trial,” Vocci said. “We will start between April and June of 2005. The sites are still being picked, and we are determining who the lead researcher will be.”

Vocci was asked what psychiatrists could be doing to help reduce prescription drug abuse. He said they need to “be aware of the addiction potential of certain drugs,” and they could become more educated about dealing with individuals who have histories of drug abuse, adding that he would like to see more psychiatrists move into treatment of addictions as a subspecialty.

For physicians, generally, Vocci said they need to identify patients with prior histories of any kind of substance abuse. If years ago a patient drank too much or abused amphetamines or other drugs then that patient may have problems with prescription opiates.

Urine monitoring is also an aid. “Oftentimes, people who abuse prescription drugs take them by mouth, so they don’t have track marks or other stigmata of using drugs. They may appear healthier looking that those who inject drugs, yet they may be taking large amount of prescription opiates,” Vocci said. “Use of urine drug monitoring might keep them more honest.”

Physicians also need to assess what is actually going on with patients and whether patients actually need narcotics for a certain duration. Look for patterns that do not match the clinical situation, Vocci advised. For example, patients who postoperatively should be gradually feeling better yet they ask their physicians to increase their dose of painkillers.

If a physician feels a patient is developing chronic pain problem or addiction to medication, Vocci suggested the physician consider referring the patient to a chronic pain specialist.

Volkow was asked during her lecture about the role of 12-step groups, given the biochemical underpinnings of addiction. She explained that when individuals become addicted to illicit or prescription drugs, they often lose their jobs and their families and start to isolate themselves. The biochemical changes in their brains make them much less sensitive to natural reinforcers, and they become socially isolated.

“Basically, the addicted individuals are cornered into the utilization of drugs as the only mechanism by which they can escape the state of discomfort,” she said. “But bringing them to [Alcoholics Anonymous], you are doing a therapeutic intervention. Why? One of the most powerful social drives we have as humans is that of belonging to a group,” she said. “You are giving the individual an alternative behavior other than the drug. Also, you are decreasing the stresses associated with the loss of control that they feel vis-à-vis their intake of the drug. So those two components are likely to play an extremely important role in helping the person who is addicted to overcome the compulsion to take drugs.”

References

Drug Abuse Warning Network (2004), The DAWN Report: Narcotic Analgesics, 2002 Update. Available at: http://dawninfo.samhsa.gov/old_dawn/pubs_94_02/shortreports/
files/DAWN_tdr_na2002.pdf. Accessed Dec. 16.

NIDA (2004), NIDA InfoFacts: Prescription Pain and Other Medications. Available at: www.nida.nih.gov/infofax/painmed.html. Accessed Nov. 22.

SAMHSA (2004), Overview of Findings from the 2003 National Survey on Drug Use and Health (NSDUH Series H-24, DHHS Publication No. SMA 04-3963). Rockville, Md.: Office of Applied Studies.

Volkow ND (2004), Addiction to medications: what are the risks and who is vulnerable? NIH Clinical Center, Medicine for the Public: 2004 Lecture Series. Available at: http://videocast.nih.gov/PastEvents.asp?c=55. Accessed Nov. 16.

Volkow ND, Fowler JS, Wang GJ (2004a), The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies. Neuropharmacology 47(suppl 1):3-13.

Volkow ND, Fowler JS, Wang GJ, Swanson JM (2004b), Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Mol Psychiatry 9(6):557-569.

Volkow ND, Wang GJ, Fowler JS et al. (2004c), Evidence that methylphenidate enhances the saliency of a mathematical task by increasing dopamine in the human brain. Am J Psychiatry 161(7):1173-1180.

Volkow ND, Wang GJ, Ma Y et al. (2003), Expectation enhances the regional brain metabolic and the reinforcing effects of stimulants in cocaine abusers. J Neurosci 23(36):11461-11468.
http://www.psychiatrictimes.com/showArticle.jhtml?articleId
=168601171

Feb 2, 2005
Author Unknown
American Pain Society

Jan 1, 2003
By: Frank B. Fisher, MD
Painreliefnetwork.org

ABSTRACT

Diagnosis of opioid addiction in chronic pain sufferers is often triggered by occurrence of what have been called aberrant drug-related behaviors. Ambiguities inherent in this approach affect patient care adversely. Rather than consistently signifying abuse or addiction, these behaviors are often motivated by undertreated pain. Appropriate clinical responses are suggested here, as well as a diagnostic approach prioritizing recognition of undertreated pain.

Introduction

Use of opioid analgesics in treatment of chronic pain has recently gained acceptance as a concept, but its effective implementation is often thwarted by lingering, unwarranted concerns about addiction. The accuracy of the use of certain behaviors as a test for diagnosing addiction hasn’t been validated, and won’t be, because they consist merely of a series of anecdotal observations concerning a diverse group of individuals who, for a variety of reasons, attempt to obtain opioids from medical sources. Uncritical acceptance of these behaviors as diagnostic of opioid abuse casts the net too wide, ensnaring in the process pain victims motivated to engage in these behaviors only by the desire to live their lives more fully.

In order to understand why these supposedly aberrant drug-related behaviors are commonly mistaken as indicators of addiction, it is necessary to consider the social context in which this approach is implemented. The ongoing “War on Drugs” sponsors an atmosphere of fear and panic that permeates the discussion of opioids. In this environment, pain sufferers are readily stigmatized as opioid addicted, although they usually are not, regardless of the legitimacy of their need for treatment. Physicians, eager not to overlook any behavior that could later be pointed to as evidence of their failure to recognize opioid addiction often rush to judgment, to their patients’ detriment.

Pseudoaddiction

The term pseudoaddiction was coined in 1989 to describe chronic pain victims mistakenly diagnosed as suffering from opioid addiction after they were driven, by undertreated pain, to display certain drug-related behaviors.1 Simply stated, pseudoaddiction is a misdiagnosis that results from undertreatment of chronic pain. When this diagnosis is made, the medical system has erred. Recognition that patients are frequently harmed by misdiagnosis of addiction should prompt an aggressive search for undertreatment of pain. Unfortunately, this usually does not happen. Instead, when a patient displays certain behaviors, he is typically threatened with termination of his treatment, rather than questioned about its effectiveness.

Incidence of Opioid Addiction

Over the past 25 years a body of scientific research has developed that reveals that the prevalence of opioid addiction among patients treated for chronic pain is far lower than previously believed. A multitude of studies indicate that the rate of opioid addiction in populations of chronic pain sufferers is similar to the rate of opioid addiction within the general population, falling in the range of one to two percent or less.2-12 Other studies indicate that a history of previous substance abuse isn’t predictive of treatment failure in chronic pain sufferers treated with opioids.13,14 An understanding of the neurobiology of opioids makes sense of the information these studies offer. A rational approach to categorizing and interpreting drug-related behaviors follows.

Drug-Related Behaviors Suggestive Primarily of Undertreated Pain

Undertreatment of chronic pain should be considered first on the list of differential diagnoses when considering the cause of worrisome drug-related behaviors. Some of these behaviors include:

* Borrowing another patient’s drugs
* Obtaining prescription drugs from non-medical sources
* Unsanctioned dosage escalations
* Aggressive complaining about need for higher doses
* Drug hoarding during periods of reduced symptoms
* Requesting specific drugs
* Acquisition of similar drugs from medical sources

Drug-Related Behaviors Possibly Suggestive of Undertreated Pain

When these behaviors occur, undertreated pain should still be suspected first, but these behaviors are more serious than the first set above and may indicate other problems, occurring either by themselves or in addition to undertreated pain:

* Prescription Forgery
* Stealing Another Patient’s Drugs
* Recurrent Prescription Losses

If these behaviors do indicate a substance abuse problem, this should be recognized. It is important to determine whether the abused substance is opioids or something else. Often this doesn’t occur because of a socially ordained predisposition on the part of physicians to automatically attribute the drug-related behaviors to opioid abuse. However, this is not a rational assumption because other substance-abuse problems have a much higher prevalence in society than opioid abuse. Correctly diagnosing substance abuse when it is present is important because a mistaken diagnosis of opioid addiction when another substance is actually to blame may result in the patient being denied pain treatment as well as treatment for the real substance-abuse problem.

Behaviors Suggestive of Opioid Addiction

The occurrence of the first two behaviors listed below leaves little doubt that the patient displaying them is engaged in abuse of opioids, but the occurrence of these behaviors does not preclude the existence of a true pain problem. The third item, sale of prescribed drugs, is the most flagrant form of diversion. This may indicate addiction to opioids or the abuse of some other substance, or it may simply reflect a profit motive. The problematic behaviors are:

* Injection of substances prescribed for oral use
* Concurrent use of related illegal drugs
* Selling prescription drugs

Implications for Pain Management

When the aberrant-drug-related-behaviors approach to diagnosis of opioid addiction originated, it was the only tool available to the discipline of pain management with which to address the potential problem of opioid abuse in pain sufferers treated with these substances. The problems that resulted from use of this approach were not anticipated, but probably should have been. Whenever medical interventions are based on assumptions rather than on science, unforeseen and often adverse consequences are almost guaranteed.

By observing behavior alone, it is impossible to distinguish between undertreated pain sufferers and people exhibiting suspect behaviors for other reasons, such as substance abuse or financial gain. This uncertainty invalidates the conclusions of studies relying on purportedly aberrant drug-related behaviors as indicative of opioid abuse, which have reported rates as high as 34 percent13 and 45 percent15 in populations of chronic pain sufferers. Estimated opioid abuse rates are wildly inflated in these studies by the presence of victims of undertreatment of pain, as well as by the inclusion of patients in whom the behaviors stem from the abuse of substances other than opioids.

Undertreated pain predictably triggers suspect drug-related behaviors, which include unsanctioned dosage escalation. Countless pain victims have been accused of drug addiction, and their treatment terminated, simply because they were bold or naive enough to admit that they used up their medication sooner than they were instructed. As a result, patients who have suffered from chronic pain for any extended period of time have generally learned from bitter experience not to reveal to their doctor that they have engaged in unsanctioned dosage escalations, although it is often necessary for them to do so in order to function. Patients often continue to engage in this behavior surreptitiously after learning that revealing it will be held against them. This has serious implications for the quality of the patient-physician relationship.

Legitimate patients are frequently suspected of drug addiction when they exhibit problematic behaviors, such as requesting treatment with a specific opioid, which they already know, from experience, will help them. This eliminates honest communication in the patient-physician relationship and substitutes a don’t-ask/don’t-tell charade. It is a tragedy when such behaviors come to the attention of a physician who mistakenly diagnoses addiction, and ends treatment as a result.

The academically recommended response to possibly aberrant drug-related behaviors is imposition of a structured program of opioid prescribing.16 This is based on the concern that patients who display these behaviors are at risk for abusing their medications, and consequently must be tightly controlled in order to prevent their descent into addiction. This response itself needs to be restructured, because undertreatment of pain is common, and the risk of opioid addiction low. When the described drug-related behaviors show up, doctors should think first about the “horses” of undertreatment, not the “zebras” of addiction.

The current definition of addiction is based on function. Central to this definition is that addicts engage in continued substance abuse, in spite of harm.17 In contrast, pain sufferers treated with opioids function better, and their lives improve.18 This dichotomy, based on functioning, should marginalize the observation of certain drug-related behaviors as a diagnostic tool for addiction in pain sufferers, because it allows physicians to objectively discern whether a patient is benefiting from treatment with opioids, or may be engaging in substance abuse with detrimental consequences.

A paradigm shift must occur before drug-related behaviors can be interpreted correctly. The physician finding these behaviors in a clinical setting, before making any assumptions about substance abuse or addiction, must first determine whether the principle of titration to optimal functioning has been correctly applied. In this manner, diagnosis of undertreated pain will be facilitated, as it should be. Substance abuse issues can then be considered in an appropriate secondary manner, if the suspect behaviors continue following effective titration.

Titration

Titration of medications to desired effect is a central principle in clinical practice. Treatment of chronic pain with opioids resembles the treatment of Type I diabetes with insulin, because in both disease states a deficiency of naturally occurring substances is corrected through the process of titration of medications.

Similarities between the conditions include the facts that patients suffering from diabetes and those suffering from chronic pain are monitoring their own symptoms; a sliding scale is used; and patients are instructed to self-adjust their dosages according to their fluctuating requirements.

The major difference between the treatments is that insulin is a potentially dangerous drug, whereas opioids are comparatively safe, when used by well-informed, opioid-tolerant, chronic pain sufferers. If the principle of titration is to be implemented in chronic pain treatment, review and clarification of titration issues is needed.

Opioid titration in the treatment of chronic pain has two end-points.19 If one or the other is not reached, the patient has not received a fair opportunity to experience titration’s potential benefits. The endpoints are (1) optimal patient functioning or (2) intolerable side effects that preclude further titration. The second is more often a problem when using medications with relatively unfavorable side effect profiles, such as morphine or methadone.

Key Points of Titration

The concept of unsanctioned dosage escalation should be replaced with the principle of patient-controlled analgesia (PCA). Just as patients are educated about the use of rescue doses in the treatment of their pain, they should also be given limits within which to titrate opioids toward the goal of optimal functioning. This will eliminate the unfortunate practice of requiring patients to suffer from undertreated pain while waiting for their next appointment, when the possibility of an increment in titration may finally be discussed.

When treatment with one opioid fails to achieve therapeutic goals, a trial with a different opioid should be initiated, a concept recognized as rotation.20 If the first medication has been of any benefit to the patient, it should be continued during the trial of the second. Otherwise, if the second agent proves ineffective, the patient is left with no pain relief. Patients perceive this as an unacceptable risk to their well-being, and understandably become fearful of suggesting any sort of change in their treatment regimens.

The fact that combination treatment with opioids is not widely accepted is a socially driven aberration from this otherwise generally accepted medical principle. If treatment were for hypertension rather than pain, and the first medication produced a less than optimal response, it would typically be continued within the therapeutic regimen while another agent was added.

Titration is, of necessity, a fluid and continuing process. As patients recover from long periods of debilitation, caused by years or even decades of undertreated chronic pain, gradually increasing activity levels provoke increasing pain levels along with a corresponding requirement for further titration. This phenomenon must not be considered abuse or addiction. The dosage curve in the treatment of severely debilitated patients recovering from long-term undertreated chronic pain is often bell-shaped, because as the patient achieves full physical activity, the nervous system can begin to recover, and opioid dosages may be expected to diminish while gains in functioning persist.

Pain victims who have not experienced effective titration of their medications often remain unaware of the qualitatively different realm of functioning in which they would exist if this were accomplished. This creates a mandate to apply titration aggressively. In the future, failure to apply the principle of titration will probably be perceived as a violation of the standard of care.21

Physiology of Pain and Opioids

Many fear that an aggressive implementation of the principle of titration, in combination with the principle of PCA, will result in dangerous programs of self-medication. These misgivings are based on superstitions about opioids, and are contradicted by science.

Basic physiology effectively precludes occurrence of opioid addiction in patients treated with these substances because chronic pain compels its victims to take their medications regularly, and the result is the development of tolerance. Tolerance dictates that when constant blood levels of opioids are maintained, the reward pathways in the brain aren’t activated by these medications. This phenomenon also dictates that in order to get high on opioids, the abuser must space his doses far enough apart in order to partially lose his tolerance, so that he can achieve a psychological reward from the next dose. When pain sufferers have sufficient access to opioids, they use them continuously. Abusers who desire the psychological effects partake sporadically.

Physiology of Opioid Tolerance and Reward

Beyond a relatively low dosage ceiling, tolerance to the reward-producing effects of opioids is complete. The existence of this ceiling effect has been established by experience in methadone maintenance programs.22 This physiologically determined reality should negate lingering concerns that chronic pain sufferers are likely to abuse their medications, or are even capable of doing so.

Physiology of Respiratory Tolerance

Evidence indicates that a dosage ceiling exists for the phenomenon of respiratory depression as well. This hypothesis is supported by a study in which tolerant subjects were administered opioids in amounts 600 to 900 percent larger than their usual dosages. No respiratory depression or changes in level of consciousness were noted.23 This consensus statement from major pain organizations supports the existence of a ceiling dosage for respiratory tolerance:

It is now accepted by practitioners of the specialty of pain medicine that respiratory depression induced by opioids tends to be a short-lived phenomenon, generally occurs only in the opioid-naive patient, and is antagonized by pain.24

The knowledge that psychological reward and respiratory depression do not ordinarily occur in opioid-tolerant subjects assures that the principle of titration can be safely applied, along with the principle of PCA, in the treatment of this population.

Legal Implications of Misinterpretation of Drug-Related Behaviors

Beyond harm to patients’ health and to the patient-physician relationship, misinterpretation of drug-related behaviors has resulted in unintended legal consequences. The criminal justice system has incorporated these behaviors into a system of “red flags”as law enforcement calls themused to target physicians for criminal prosecution. These red flags are routinely offered in the courtroom as evidence of criminal intent on the part of doctors accused of drug trafficking.25

Conclusions

Continuing misinterpretation of behaviors resulting from undertreatment of pain, despite long-term awareness of the pseudoaddiction phenomenon, can reasonably be characterized as aberrant drug-related behavior on the part of the medical profession. Misunderstandings about the significance of drug-related behaviors disrupt the therapeutic relationship between patient and physician, contribute to the widespread undertreatment of chronic pain, and place legitimate practitioners at risk for unwarranted administrative and criminal prosecutions. It is therefore important not to jump to mistaken conclusions when potentially aberrant drug-related behaviors are observed.

The solution to this problem depends on recognizing the problem of undertreatment of pain when it occurs, and placing it at the top of the differential diagnosis, when suspect drug-related behaviors are observed. The diagnosis of opioid addiction should be based on observation of deteriorating function, which can be directly attributed to opioid abuse, rather than inferred from an anecdotal set of behavioral criteria derived from medical folklore.

Frank B. Fisher, M.D. is a Harvard-trained general practitioner with extensive experience in treatment of chronic nonmalignant pain with opioids, for which endeavor he has been relentlessly prosecuted. frankbfisher@earthlink.net

REFERENCES

1 Weissman DE, Haddox JD. Opioid pseudoaddictionan iatrogenic syndrome. Pain 1989;36:363-366.
2 Brookoff D, Palomano R. Treating sickle cell pain like cancer pain. Ann Intern Med 1992;116:364-368.
3 Chapman CR, Hill HF. Prolonged morphine self-administration and addiction liability: evaluation of two theories in a bone marrow transplant unit. Cancer 1989;63:1636-1644.
4 Friedman DP. Perspectives on the medical use of drugs of abuse. J Pain Symptom Manage 1990;5(1 Suppl):S2-5.
5 Kanner RM, Foley K. Patterns of narcotic drug use in a cancer pain clinic. Ann NY Acad Science 1981;362:161-172.
6 Medina JL, Diamond S. Drug dependency in patients with chronic headaches. Headache 1977;17:12-14.
7 Moulin DE, et al. Randomized trial of oral morphine for chronic non-cancer pain. Lancet 1996;347:143-147.
8 Perry S, Heidrich G. Management of pain during debridement: a survey of US burn units. Pain 1982;13:267-280.
9 Portenoy RK, Foley KM. Chronic use of opioid analgesics in non-malignant pain: report of 38 cases. Pain 1986;25:171-186.
10 Porter J, Jick H. Addiction rare in patients treated with narcotics. N Engl J Med 1980;302:123.
11 Schug SA, Zech D, Grond S, et al. A long-term survey of morphine in cancer pain patients. J Pain Symptom Manage 1992;7:259-66.
12 Zenz M, Strumpf M, Tryba M. Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage 1992;7:69-77.
13, Chabal C, Erjavec MK, Jacobson L, Mariano A, Chaney E. Prescription opiate abuse in chronic pain patients: clinical criteria, incidence, and predictors. Clin J Pain 1997;13(2):150-155.
14 Dunbar, SA, Katz NP. Chronic opioid therapy for non-malignant pain in patients with a history of substance abuse: report of 20 cases. J Pain Symptom Manage 1996;11:163-171.
15 Passik SD. Opioid Treatment in Chemically Dependent Patients. Presented at the Fifth Annual International Conference on Pain & Chemical Dependency. New York, N.Y.; June 6-8, 2002.
16 Portenoy RK. Opioid therapy for chronic nonmalignant pain: a review of the critical issues. J Pain Symptom Manage 1996;11:203-217.
17 Definitions related to the use of opioids for the treatment of pain. A consensus document from the American Academy of Pain Medicine, the American Pain Society, and the American Society Of Addiction Medicine; 2001.
18 Fishman S, Wilsey BL. Chronic opioid therapy, drug abuse, and addiction. In: Ballantyne J, Fishman SM, Abdi S, eds. The Massachusetts General Hospital Handbook of Pain Management. 2002
19 Portenoy RK. Evolving Role Of Opioid Therapy. Presented at the Fifth Annual International Conference on Pain & Chemical Dependency. New York, N.Y.; June 6-8, 2002.
20 Indelicato RA, Portenoy RK. Opioid rotation in the management of refractory cancer pain. J Clin Oncol. 2002;20:348-352.
21 Furrow, BR. Pain Management and Provider Liability: No More Excuses. J Law Medicine & Ethics 2001;29:2851.
22 Seidenberg A, Honegger U. Methadone, Heroin and other Opioids: A Medical Manual for Outpatient, Opioid-Supported Treatment; 1997. Available at: http://www.druglibrary.org/schaffer/heroin/ase/index.htm. Accessed Sept 6, 2003.
23 Light AB, Torrance EG. Physical characteristics and physical fitness of addicts during administration of morphine. Arch Intern Med 1929;43:327-334.
24 The Use of Opioids for the Treatment of Chronic Pain: A consensus statement from American Academy of Pain Medicine and American Pain Society; 1997.
25 Bolen J, Ramseyer R, Wood G. Evidence Issues In Drug Diversion Cases. Presented at the Health Care Fraud Special Issues Symposium National Advocacy Center, U.S. Department of Justice, Office of Legal Education; July 16-18, 2002.

Jan 1, 2003
Author Unknown
Painreliefnetwork.org

Aberrant Drug Related Behavior lists are used by doctors in pain management to observe “addictive tendencies” in patients and ultimately – to judge whether a patient is a “real” patient or an addict. If a doctor observes one or several of the listed behaviors in a patient, there is the possibily that they will decide you are not a pain patient, and instead are an addict who is seeking drugs for illicit use.

Although in common use in pain management practices around the country, and accepted by academic medicine as a viable tool in pain management, physicians are not required to inform you about these “behavioral tools.” The use of these behavioral tools are veiled behind the physician privilege, and patients rarely, if ever, understand that this system is being used to judge their normal day-to-day activity, including the way they appear, what they say, how they fill their medications, and what their family thinks about them. Thus, many patients make the mistake of exhibiting these behaviors without an understanding of the implication to their access to pain care. We at PRN feel it is vital that these lists are made common knowledge to pain patients. Without knowing these systems, pain patients are set up to fail. Understanding the systems in play in the doctor’s office will help explain the fear, feelings of failure, and strange and unpredictable physician behavior that pain patients describe to us every day.

This comprehensive list has been culled from several different sources. Some behaviors are “more aberrant” and some are “less aberrant.” All patients should be aware that if you exhibit ANY of these behaviors, you could be denied pain care. A patient who shows any of these behaviors can be “red flagged.” When you are “red flagged” your doctor or pharmacist will not tell you about your “flagged” status and it is almost impossible to have the designation removed from your record. Patients are left in the dark as to why no doctor will treat them, why the pharmacy doesn’t seem to carry their meds, and why they are shut out of ER’s…

How to Get Red Flagged:

* Complain to your doctor when your medications don’t seem to ease your pain
* Have a preoccupation with getting your medication
* Report effects like increased energy, raised mood, or euphoria since you started taking pain medication
* Primarily find oxycontin, percocet, dilaudid, or lortab to be the most effective drug that helps your pain symptoms
* Express anxiety or depression about your pain when it doesn’t go away
* Look “unkempt”
* Have piercings and/or tattoos
* Talk to your doctor specifically about your medication during more than three visits
* Don’t tolerate many medications well
* Don’t get any relief from anything other than opioid medication
* Fill prescriptions of a similar kind by another doctor
* Have had problems in work, family, or other important family roles where people have said you have failed in your responsibilities
* Have problems with close relationships in your life
* Have a psychiatric history (Done therapy in the past)
* Have legal problems
* Have family who have a history of drug or alcohol abuse
* Have family members who suspect that your drugs may make you an addict
* Have family members who believe you are addicted
* Use more than 180mgs of opioids per day
* Prefer one type of medication administration than another (Prefer slow-acting pills instead of daily injections at the ER, or expressing an aversion to having a morphine pump installed in your body, for example)
* Become angry when your physician refuses to treat your pain
* Use other drugs at the same time as your pain meds (Including alcohol)
* Get medication from someone, not a doctor, for your pain
* Taken someone else’s pain medication
* Switch doctors until you find one who will treat your pain
* Call or visit your doctor often
* Have used more than one pharmacy to get your medication filled
* Ever miss appointments with your doctor
* Ever loose your medication or your prescriptions
* Only see a doctor a few times before you switched to a doctor who would treat your pain and reported that to your doctor
* Have a previous doctor who believed you are or were addicted to your medications
* Request specific medication for your pain
* Request your medication by name
* Request more medication
* Report no effects of other medications
* Have bad reactions to your medications
* Go to the ER a lot to get your pain treated
* Believe you might become addicted to medication
* Have contact with “street culture” or other “subcultures”
* Raise your dose once or twice before you see your doctor again because of increased pain
* Use your medication to treat another symptom that you have not previously mentioned to your doctor
* Save your medications even if you do not need them anymore
* Refuse some treatments or tests suggested by your doctor

PRN’s Position:

Denying patients pain treatment based on the observation of these behaviors is systematic abuse. The denial of pain care leads to worsening of the patient’s disease, causes irreparable damage to the patient’s brain and nervous system, destroys the patient’s interactions with their families and work environments and ultimately leads to patients’ untimely deaths. Also, these behaviors are not medical tools – yet they have the medical establishments’ full approval, when they amount to nothing more than pseudo-science.

Imagine if a diabetic patient had to prove that he had never lost a prescription, that his sugar cravings were not “aberrant”, and he were forced, through non-treatment, into comas. Americans would be up in arms. If diabetics were kept at the minimal level of insulin to just barely keep them alive and then given antidepressants and required to go to psychotherapy to help them stop exhibiting insulin craving behaviors — you would have a fair approximation of what patients in pain currently endure.

These aberrant drug related behaviors are being used by physicians to deny suffering people access to ethical and non-abusive medical treatment. Beyond that, by having to pass muster with a doctor who can judge their worth based on these behaviors, patients in pain have absolutely no control over their health, or their quality of life. They often have to switch doctors multiple times to find someone who will treat them, and if they are fortunate to be able to travel across the country to find a doctor, they have committed aberrant behavior. The lack of medical care can also force patients into buying drugs on the street, on the Internet or in Mexico, which keeps the vicious cycle continuing and puts patients in the realm of illegal activity, which can lead to their imprisonment or death due to fake or tainted medications. Any move a pain patient makes leads to being turned down, turned away, or forced to jump through an unending series of hoops. It is a rare patient who does not exhibit at least one of these behaviors, so it is a miracle that anyone is getting treated today. Physicians have to resist these prejudicial ideas in order to treat patients appropriately. The doctors who treat the patients as though they were human beings are the very ones prosecuted by the DEA and law enforcement.

The aberrant drug-related behaviors only add to the traumatic experience of pain patients. Currently, patients are thrown into an Orwellian universe that compounds their pain and misery and forecloses their options for continued survival. From our experience, this heaping of insult and exclusion from care often leads to patient suicide. As suicides from undertreated pain are not recorded and if a patient commits suicide by overdose, such a death is counted as a drug abuse death. As a result, the current system guarantees numbers for the DEA to point to in order to justify their existence. Until patients are not judged by how they look, what they say, or the amount of knowledge they posses regarding their own care and medicines, pain care will continue to be nothing more than systematic abuse pretending to be medical practice.