With the passage of the Harrison Narcotics Tax Act in 1914, the United States federal government put states, as well as physicians, nurses, and patients, on notice that treatment of those with “narcotic addiction” with drugs, specifically opiates and cocaine, was outside the purview of medical practice and was henceforth illegal.¹ Those who championed the Harrison Act saw a distinction between those with addiction and those with pain and saw the law as necessary to halt what many in the United States saw as a headlong slide into producing generations of opioid, cocaine, and marijuana addicts. Several years later, a political coalition of many of the same advocates saw the Volstead Act ratified as a Constitutional amendment banning the use of alcohol for recreational purposes. That “Great Experiment” lasted barely 13 years; drug prohibition, however, has continued.²

It was not until 60 years later with the adoption of the Narcotic Addict Treatment Act of 1974 that physicians could prescribe opioids to those with opioid addiction, but only in the context of federal and state licensed methadone treatment programs. In the interim 60 years, the use of prescribed opioids to treat pain was generally limited to acute pain of injury or surgery and in patients with chronic pain related to cancer and other terminal conditions. Even for these latter groups, great concern was expressed about the addictive nature of these medications, and such drugs were used sparingly.

In the last four decades, however, there has been a growing movement to extend pain treatment, particularly with opioids (as well as sedatives/benzodiazepines and other potentially dependency-producing medications) to those with nonterminal painful conditions.^3,4 In the last 10 years, the prescribing of opioids has increased fourfold, with a similar increase in overdose deaths, with grave concerns among the public, government officials, and the medical profession about these trends. A growth industry of pain clinics, many of which were no more than for-profit opioid and benzodiazepine dispensaries, has prompted some law enforcement and regulatory action, with calls for more.^5–7

Original concerns expressed about the increasing availability of opioids for pain treatment were muted by assertions from experts that the prevalence of addiction in those who were treated for pain was astonishingly low.⁴ Portenoy et al. asserted that undertreatment of pain and specifically “opiophobia” were greater concerns than overprescribing.^3,8 The Joint Commission on Accreditation of Health Care Organizations (JCAHO) declared pain as “the fifth vital sign” and judged hospitals by how well they addressed it.⁹ However, in recent years, many experts have expressed concerns and admitted that overprescription and misuse, as well as outright abuse, have become significant problems, with associated mortality and morbidity^5–7 They advocate specially trained physicians to prescribe opioids in long-term nonmalignant pain,^10–11 and/or to develop risk evaluation and mitigation strategies for opioid prescribers.^12–14

As a physician specializing in the treatment of patients with chemical dependency (CD), the author has developed some expertise in pain management and has treated a number of patients with both addiction and pain. A number of pain physicians may feel the need to recognize and assist in the management of CD in their patients, and some have become experts in this field as well. Many of our colleagues in CD treatment, including anesthesiologists, psychiatrists, internists, family physicians, and others, are now active in both treatment and research in this area.

A new interface in CD and addiction treatment came with the approval of buprenorphine alone (Subutex and generics) and with naloxone (Suboxone^®, Zubsolv^®, BunavailR and generics). Although buprenorphine is not approved for the treatment of pain except for the preparation for injection; however, for patients with the combination of pain and actual or potential opioid addiction, it has proved helpful in the management of both problems.^15,16

This chapter will: 1) describe the diagnostic criteria for CD; 2) assist those who treat pain to set up practices which will discourage and perhaps eliminate those “drug-seekers” who attempt to obtain medications solely for diversion and profit; 3) educate pain physicians about appropriate screening measures to detect those who are chemically dependent or at high risk of developing CD; 4) discuss methods to detect the development of aberrant behaviors associated with addiction; 5) present the importance of appropriate referral for CD treatment, including the importance of determining that referral sources are expert in the appropriate management of these patients; and 6) describe potential tools available to pain physicians that will assist in the management of patients with CD.

The Diagnostic and Statistical Manual of the American Psychiatric Association, 5th edition (DSM-5), is the American standard for the diagnosis of CD.¹⁷ The DSM-5 shows particular concern regarding the differentiation of physical dependency, which occurs in virtually all patients who regularly take drugs that produce receptor dysregulation, from substance use disorders (SUDs), including abuse and dependency. The differentiation between abuse and dependency may be changed in the new edition, perhaps with the use, once more, of the term “addiction.”¹⁸

It is important to emphasize that the amount of drug used and frequency of use are not the dominant issues in CD; it is rather the effects of the drug use on the individual and society, in a persistent and consistent manner, and the inability of these individuals to change their maladaptive behaviors. Of course, as drug use escalates and becomes more frequent, one commonly sees these behavioral issues, and ultimately pathological physical and mental changes. However, there are individuals who may use larger amounts of a particular drug without ill effects, while others who use smaller amounts, perhaps even less frequently, still develop serious problems with its use.

DSM-5 eliminates the sometimes confusing distinction between the “Dependency” and “Abuse” categories, replacing them with a unitary “Substance Use Disorder” category for each class of drugs, where the criteria are put together into the 11 existing criteria, with the replacement of recurrent legal problems with the criterion of “drug craving.” The specifiers are “absent” for 0 to 1 criterion, “mild” for a total of 2 to 3 criteria, “moderate” for 4 to 5 criteria, and “severe” for 6 or more criteria.¹⁶ The moderate to severe category may become synonymous with “addiction.” The presence of only tolerance and withdrawal in a patient taking appropriately prescribed medications in an adherent manner will not result in a SUD diagnosis.¹⁸

The use of screening instruments, such as the screener and opioid assessment for patients with pain (SOAPP), is discussed elsewhere (Chapter 19), and tables of “aberrant behaviors” often divided into “yellow flags” and “red flags” (Table 70-1) are based on criteria that are enunciated in the DSM criteria for CD. The diagnosis of CD, however, should not be based on screening tools but on application of the DSM-5 criteria. However, the pain physician must be aware that many of the behaviors associated with addiction can also be present in pain patients (so-called “pseudo-addiction”), particularly in those who have been previously undertreated with opioids, as well as those who have had adverse experience with opioid tapers.^19,20 These behaviors may include drug hoarding, doctor shopping, lack of adherence to dosing schedules, and others.

This term “drug-seeking” patient has become so widely and inappropriately used as to become meaningless. All pain patients are concerned with relief of their pain, and often that relief involves a number of drugs; some patients are inordinately fixated on obtaining those medications. However, the term “drug-seeking” refers here to individuals who are not patients, do not have pain problems, and who attempt to obtain opioids and other controlled substances solely for the purpose of abusing the drugs for euphoria and/or diverting them for profit. Individuals who are solely diverting and selling these drugs are criminals and can and should be referred to appropriate authorities.

Drug-seeking patients who attempt to obtain opioids from physicians solely with the intent of abusing them for euphoria, however, are very likely to be CD. In some cases, patients may be obtaining medications and selling them to obtain their drug of choice. Although these activities are illegal, efforts to direct these patients to CD treatment should be encouraged. Unlike the former group of diverting individuals, patients, if successfully treated, are far less likely to reoffend. Drug courts that specialize in drug-related nonviolent crime may be very useful in motivating patients into treatment, with a very high rate of successful completion.

It is recommended that the pain physician has a “no prescription” policy on a patient’s first appointment. The referring physician and/or patient calling for appointment who is self-referred is informed that, if the patient is on controlled substances, those prescriptions must cover the patient through the evaluation process and that the pain physician will not write such prescriptions except under emergency circumstances, if at all. Unfortunately this is not always possible, but a clear statement of such a policy and its emphasis found in telephone directories and websites may discourage pure “drug-seekers” from seeking their drugs at your practice.

Physicians should be alert to the creative ways that patients create “emergencies,” for example, stating that they are visiting from out of town, or calling late on Friday afternoons or weekends, calling only when on-call physicians are available, and many other techniques. Physicians and their staffs should not be persuaded by these urgent requests and insist on a proper intake process, including contact with prior prescribers. If such patients are referred to emergency facilities, a clinical member of the staff should contact the emergency department and speak to the triage nurse or physician regarding concerns.

An interesting study looked at the number of lifetime aberrant behaviors manifested by patients in pain treatment programs and found that the total of aberrant behaviors was a better predictor than the specifics of each aberrant behavior. Patients who manifested four or more aberrant lifetime behaviors were highly likely to have an underlying SUD and have current illicit drug use, whereas those with three or fewer lifetime aberrant behaviors were extremely unlikely to have SUD and current drug use (9.9% vs 1.1%). A positive urine cocaine toxicology test was associated with a fourteenfold increased rate of a SUD.²¹

Pain programs should also utilize state prescription monitoring programs (PMPs) in states where they exist, and physicians should work with colleagues to encourage other states to create them and have them available only to the medical profession (some have only been available to law enforcement and not to physicians, but most are now available to both). PMPs are web-based programs that allow appropriately credentialed individuals to review the prescription records for controlled substances of both new and current patients and can determine whether they are receiving additional prescriptions from other providers, including dates and numbers of pills. This can be enormously helpful in identifying doctor-shoppers and drug-seekers.

Drug testing is also appropriate at the first visit. Toxicology monitoring is dealt with elsewhere in this text (Chapter 19). However, urine or salivary screens, with confirmation of results by more advanced methods, are used to provide confirmation of patients’ statements about what they are being prescribed to look for nonconcordance with toxicology results. In patients on certain drugs (e.g., methadone, fentanyl, oxycodone), assays for the measurement of serum concentrations of the drugs are commercially available and provide information as to whether patients are taking the approximate doses which they state are being prescribed. In some cases, proportions of metabolites may indicate the original drug used by the patient. However, many factors may impact the serum concentrations of these drugs.

Many addiction medicine physicians hold to a “unitary model” of addiction, in which a patient who has developed addiction to any drug, including alcohol, is at high risk of development of addiction to other mood-altering or dependency-prone drugs, whereas others (including the author) believe that there is a spectrum of risk in these patients. At lowest risk of addiction are those with a distant history of CD other than opioids, followed by those who are using mood-altering substances or medications in appropriate and controlled ways. At intermediate risk of addiction are those who actively abuse mood-altering drugs, including tobacco, alcohol, and marijuana, as are those with past histories of opioid abuse. At highest risk of addiction are those who are actively abusing illicit opioids or illicitly obtaining licit opioids.

A. PATIENTS WITH PRIOR CHEMICAL DEPENDENCY HISTORY OF DRUGS OTHER THAN OPIOIDS

Patients with a history of CD, particularly those who have been involved in self-help treatment, particularly 12-step programs, may identify themselves initially as being “in recovery” and express their concerns regarding dependency or addiction on pain medications or anxiolytic agents. Other patients may not identify their addiction or dependency and may go to some lengths to deny a prior history. Denial may be in part because of their shame regarding the stigma of a CD diagnosis and in part because of their fear that pain physicians may not be accepting of their pain history and/or believe that they are drug seeking.

Patients with prior histories of CD may be at higher risk of abuse of opioids and benzodiazepines. Although it is important for all patients to explore maximizing nonpharmacologic treatment as well as non-opioid pharmacotherapy, it is most important for patients with prior history of alcohol, cocaine, and/or other stimulants, cannabis, or other CD. Again, many patients will urge doing so. Some patients will resist starting opioids or benzodiazepines even when clearly indicated.

The pain physician, when working with a patient in recovery, should review the patient’s support system. If the patient is not involved in active counseling or a self-help group (including a sponsor and a “home” group), the physician should urge the patient to increase the level of support. If the patient’s family system is intact, involving and educating the significant other(s) to the risks of opioid or benzodiazepine abuse may be of benefit. Although informed consent of all patients involves a frank discussion or risks/benefits, particularly those of physical dependency and addiction, this discussion is important in the patient with prior CD history.

In a patient with prior alcohol abuse, the pain physician should consider following the patient not only with usual toxicology studies but also with existing biomarkers for alcohol abuse, including a baseline CBC (with MCV), uric acid, triglycerides, ALT/AST, and γ-glutamyl transpeptidase (GGT). Newer biomarkers, commercially available, include carbohydrate-deficient transferrin (CDT), a reliable indicator of recent heavy alcohol consumption even if the individual has been abstinent for several days before the test. A test, which can be obtained together with a urine toxicology test, is the measurement of ethyl glucuronide (EtG), which can detect alcohol consumption for up to 48 hours prior to testing; ethyl sulfide (EtS) is complementary test and may be used instead of or in addition to EtG, with a slightly longer period of detection.²²

It has been the author’s practice to recommend that the patient who is actively involved in a 12-step program inform his or her sponsor or obtain a sponsor if one is needed and have the sponsor be actively involved in the patient’s care. For patients in another support system (e.g., SMART Recovery, LifeRing, Women for Sobriety, and others), a more senior treatment “colleague” or the facilitator of their group may be similarly helpful.²³ For patients not so involved, discussion of the risks of relapse should include strong recommendation for developing a professional therapeutic relationship, either individual or group with a CD support group or with a pain support system. Some addiction programs have developed combination pain/addiction support groups.

Pain practices vary in their approaches to “social” drinking in patients receiving opioids. In patients with a prior history of alcohol abuse, any “social” use is significant and indicates relapse, with the likelihood of heavier drinking in the future. Many programs recommend total abstinence because of potential synergistic effects of alcohol with opioids and benzodiazepines, as well as drug-drug interactions secondary to alcohol effects on P-450 cytochrome enzymes. However, few programs routinely inquire about alcohol use at each visit; fewer still do any testing for alcohol metabolites or effects. Use of urinary EtG and/or EtS tests may indicate alcohol consumption within the 1 to 3 days prior to testing, which may be useful if the levels are high or if the patient has not given a history of alcohol use. Low levels of EtG and EtS may, however, occur with exposure to mouthwashes, alcohol in medications or foods, or even inhaling the vapors of alcohol-based skin sanitizers, which are over 60% ethyl alcohol.

Patients with prior histories of abuse of other drugs, particularly cocaine and amphetamines, as well as men younger than 35 years of age, are at higher risk of developing addiction to opioids. Treatment agreements clearly state that use of nonprescribed controlled substances or illicit substances will result in potential detoxification or immediate discharge; therefore, follow-up of those with prior histories should include ongoing toxicology studies, perhaps on a more frequent basis, including random call-backs (often with a 24-hour window) for toxicology studies, sometimes with pill counts.

A particularly difficult and controversial area involves patients who are using forms of cannabis, including marijuana and hashish. Many states have “medical marijuana” laws that permit patients to receive a “prescription” from medical professionals to allow them this use without state or local authorities charging them with criminal offenses. In some states, marijuana “dispensaries” are licensed where patients with medical marijuana cards can purchase it legally. However, others (particularly in states without dispensaries) obtain marijuana through the illegal sales systems.

Many pain physicians are concerned that patients who are using marijuana “medically” are still engaging in illegal activity by purchasing it, as well as having contact with other illicit drugs which may be sold by the same individuals. Others are concerned about the violation of federal laws by such patients. Still others have concerns about the potential for drug-drug interactions. Finally, many programs are concerned about DEA surveillance and prescribing controlled substances to those who are using cannabis or any illicit drug.^24,25 Some patients have prescriptions for medical dronabinol (Marinol), which makes determining the origin of positive THC urine drug screens problematic. Prescribing for opioids and other controlled substances for those using cannabis products remains a judgment call for each health professional.

B. PATIENTS ACTIVELY ENGAGED IN SUBSTANCE ABUSE

Patients who actively engage in substance abuse, whether with alcohol or with other substances, may present with serious painful conditions either from the underlying disorder (e.g., chronic pancreatitis, neuropathy from medications used to treat HIV) or from the causes of chronic pain. Some patients may be functional when abusing drugs and alcohol, and detection may be difficult. Standard screening instruments (e.g., AUDIT, MAST, DAST) may be helpful in some patients,²⁶ as well as screening tools developed to look for those at risk of abusing medications prescribed for pain, such as the SOAPP-R.²⁷ Pain physicians, specifically those in general medical practices who treat pain in their patients, may continue to treat patients who are known to be abusing other substances, depending on the severity of the abuse and drug(s) involved. However, these physicians do not use controlled substances in their treatment and focus on nonpharmacologic treatment and non-opioid pharmacologic treatment, as well as avoiding benzodiazepines and other sedatives.

In most cases, it is appropriate to refer such individuals to a treatment facility for CD. In those who are without physical dependency or withdrawal risks and who do not need a higher level of care, outpatient treatment may be appropriate. For those with more significant CD, referral to either free-standing or hospital-based detoxification facilities may be necessary. Upon discharge, there should be consideration for the use of anticraving drugs which are available for alcohol and for other drugs as well. Both detoxification and these agents are further discussed in the section on termination later in the chapter. One option for opioid treatment of pain in at-risk patients for chemical dependency, is the use of buprenorphine. While this can be done in the form of transdermal preparations approved for the treatment of pain, the use of buprenorphine or buprenorphine/naloxone sublingual preparations can also be considered off-label (Heit, H. DEA letter, personal communication, 2004). There may be insurance or pharmacy issues with such off-label prescribing.

C. PATIENTS WITH PRIOR HISTORY OF OPIOID ABUSE

The American Pain Society (APS), the American Academy of Pain Medicine, and the American Society of Addiction Medicine issued a joint policy statement in 2004, asserting that although physicians knowingly giving opioids to patients at high risk of diversion and/or abuse without medical necessity is inappropriate, it is equally problematic to deny appropriate treatment to patients with past or current histories of opioid abuse.²⁸ Of course, appropriate evaluation as well as careful monitoring is necessary in these patients.

As with patients with histories of other types of CD, every effort should again be made to maximize the use of nonpharmacologic therapies, as well as non-opioid drug therapy. The pain physician should inquire as to the patient’s support system, and as with others with CD, every effort should be made to have the patient in appropriate treatment. For those already in a program, whether formal or informal (e.g., 12-step programs, SMART Recovery), recommendations to obtain and involve a sponsor and/or therapist, as well as appropriate family and friends, may be helpful in providing support during what will likely be an increased likelihood for craving and relapse. If the patient feels he or she is not in need of treatment, the physician may consider requiring the patient entering and remaining in treatment as part of the initial treatment agreement, or it may be presented initially as a contingency at the first sign of aberrant behaviors.

In patients with a prior opioid abuse history, it may be advisable to avoid use of the primary drug that the patient abused, particularly forms of oxycodone, as they have little hepatic first pass, can easily be used by nasal insufflations, and cross the blood-brain barrier rapidly, producing more euphoria. The patient’s drug(s) of choice may also be triggers, further increasing the chance of abuse. The use of slow-acting agents such as continuous-release (CR) morphine or transdermal fentanyl should be considered when long-acting drugs are needed. Similarly, use of drugs with slower blood-brain barrier passage for acute or breakthrough pain, such as immediate release (IR) morphine, should be considered if such agents are required. Methadone can be legally prescribed for pain, and buprenorphine (an off-label use except for the injectable and transdermal forms) may be an option and is discussed in more detail later in the chapter.

D. PATIENTS WITH ACTIVE USE OF ILLICIT OPIOIDS

Chronic treatment of patients who are actively abusing opioids or other dependency-prone medications, is rarely, if ever appropriate. In the presence of moderate to severe acute pain, administering or dispensing an opioid for relief may be appropriate, but long-term prescribing is fraught with hazard. Such patients are likely to take excessive doses at shorter intervals or may divert licit opioids to obtain their drugs of choice. The clinical, ethical, and medical-legal implications make such prescribing dangerous for the patient and prescriber. In cases where patients are found to be actively abusing illicit opioids (or obtaining licit drugs illicitly), as is the case with other dependency-producing drugs, consideration of the level of use and the likelihood of a withdrawal syndrome should require referral to an appropriate detoxification program. Not all programs are equal, and further discussion of this matter can be found in the section on termination later in the chapter.

In cases involving patients who are taking opioids, pain physicians may want to assess them in an opioid-free state to determine the status of their pain. In those patients who are illicitly using “street” opioids (heroin) and those who are inappropriately using prescribed opioids (e.g., multiple prescribers, frequent early refills, obtaining licit drugs from nonmedical sources), referral to a detoxification facility should also be considered. Such determination may be made on the basis of the level of admitted use and/or the appearance of withdrawal signs and symptoms, as well as their severity. Conventional opinion holds that opioid withdrawal, although uncomfortable, rarely if ever has severe morbidity or mortality; however, the author has seen many cases of severe withdrawal resulting in vomiting, aspiration, pneumonia, myocardial infarction, Mallory-Weiss syndrome, and severe dehydration with renal failure. This is particularly true in older or more debilitated patients (HIV disease, hepatitis C). This is further discussed below.