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 morbidity5-7 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.
IDENTIFICATION OF CHEMICAL DEPENDENCY
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.
||Download (.pdf) TABLE 70-1
YELLOW FLAGS – Behaviors less suggestive of addiction
Aggressive complaining about the need for more drug
Drug hoarding during periods of reduced symptoms
Requesting specific drugs
Openly acquiring similar drugs from other medical sources
Unsanctioned dose escalation or other non-adherence with therapy on one or two occasions
Unapproved use of the drug to treat another symptoms
Reporting psychic effects not intended by the clinician (e.g., increased energy, euphoria)
Mildly impaired cognition or subtle signs of impaired function
RED FLAGS – Behaviors probably more suggestive of addiction
Selling prescription drugs
Stealing or “borrowing” drugs from others
Injecting oral preparations
Obtaining prescription drugs from non-medical sources
Concurrent abuse of alcohol or illicit drugs
Multiple dose escalations or other non-adherence with therapy despite warnings
Multiple episodes of prescription “loss”
Repeatedly seeking prescriptions from other clinicians or from emergency rooms without informing prescriber or after warnings to desist
Evidence of deterioration in the ability to function at work, in the family, or in society that appear to be related to drug use
Repeated resistance to changes in therapy despite clear evidence of adverse physical or psychological effects from the drug
THE “DRUG-SEEKING” PATIENT
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.
PATIENTS WITH CHEMICAL DEPENDENCY AND THOSE “AT-RISK”
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.
E. PATIENTS ON OPIOID AGONIST THERAPY
A potentially more difficult decision involves the treatment of pain in opioid-dependent patients who are in treatment, particularly those in methadone agonist treatment. Many pain physicians are not aware of the strictures under which methadone maintenance treatment programs (MMTPs) operate. The basic requirement for admission to MMTPs is that the patient be Opioid Dependent by the old DSM-IV standards, which involves more than physical dependence and essentially labels the patient as a “narcotic addict.” There are many other requirements as well, including being able to pay for the treatment, which may range from $4000 to $6000 per year, usually payable by the week. Most private insurance, despite the recent passage of federal mental health/substance abuse parity acts, will not pay for methadone treatment or will pay only for a brief detoxification. In addition, MMTPs are specifically enjoined from using methadone in the primary treatment of pain.
Methadone is given once daily in MMTPs, which is rarely, if ever, adequate for pain treatment. Patients must come daily for dosing until and unless they earn “take-home” privileges, in which they are initially given one take-home dose and then every 60-90 days may earn an additional take-home. Take-home doses require complete adherence to all clinic rules and regulations. Methadone programs may “split” the doses in patients who are hypermetabolizing the drug, such as pregnant women in their second or third trimester or patients on P-450 enzyme-inducing medications; however, there are legal restrictions on doing this, and it must be approved by both state and federal authorities on a case-by-case basis. Therefore, opioid-dependent patients dismissed from pain treatment who are admitted to MMTPs may continue to experience significant pain. In addition, being in a program with those using heroin and other street drugs may be entirely unacceptable to many patients.
The management of such patients represents a challenge to the pain physician, the MMTP, and the patients themselves. Many of these patients have significant real pain but cannot be depended upon to take medication safely and as directed without dose escalation and without the use of other drugs of abuse. Unfortunately, many of these patients, particularly those in treatment for HIV and hepatitis C complications, receive opioids from their other physicians with little or no consultation with the MMTP medical staff. In addition, opioids may be readily available from nonmedical sources or unscrupulous providers in so-called “pill mills.”
The prescription of long-acting opioids in these patients can result in overlapping peak levels of both methadone and the other prescribed opioid, with risks of oversedation, overdose, and death. In addition, the program is often unable to use urine drug screens effectively, because most program budgets do not permit use of gas chromatography/mass spectroscopy (GC-MS) or other confirmatory tests, so that it becomes difficult or impossible to determine if the patient is taking only the prescribed drugs. Use of short-acting, rapidly absorbed opioids for breakthrough pain similarly makes monitoring the patient for illicit use problematic.
There is a certain irony in individuals who are in methadone treatment programs precisely because they have abused street drugs, whether heroin or illicitly obtained prescription drugs, and cannot be trusted to manage their medication who then receive as much as a month's worth of drugs similar or identical to their drugs of choice. In many cases, patients are selling the prescribed drugs in order to obtain their drugs of choice, particularly heroin, cocaine, or methamphetamine.
As stated above, all physicians treating pain in patients with addiction should exhaust all nonpharmacologic and non-opioid drug treatments in the management of chronic pain. If opioids are needed for acute pain, prescribers need to be aware of methadone-induced tolerance, which will likely require a higher dose of opioid. If the prescription is for fixed-dose acetaminophen combinations, the patient may escalate the dose and have potential problems with acetaminophen toxicity, as well as opioid-related issues. Every effort should be made to contact the MMTP and consult with its medical or nursing staff. Prescribers also need to be aware that prescribing mixed agonist-antagonists in these patients may result in both hyperalgesia and withdrawal. The author has seen several cases of this with tramadol and, more recently, tapentadol (Nucynta®).
Increasing the dose of methadone is rarely an effective means of treating acute pain both because methadone takes 2 to 4 hours to peak and because reaching a steady state of the increased dose will not take place for 4 to 7 days. Treating acute pain in an emergency department or medical office setting is not generally problematic; however, prescriptions of opioid medication for a week or longer is not without significant risk for these patients. The lowest effective dose should be given for the shortest possible time, with reevaluation every 2 to 3 days. The MMTP nurse and/or physician should be notified as soon as possible of such prescription; ideally, consultation with MMTP staff should be considered prior to prescribing.
For subacute and chronic pain, treatment of methadone-maintained patients should involve collaboration with the MMTP medical staff. In cases of socially rehabilitated MMTP patients who have been in treatment for several years and have extended take-home status and particularly in those with severe and potentially life-threatening medical problems, consideration should be given to turning over the opioid prescribing entirely to the pain physician. Intermediate steps, such as providing split doses, may be possible but are again associated with legal restrictions. Lower-risk opioids, such as methadone (in divided doses), CR morphine, and fentanyl transdermal patches (all of which have potential for abuse), may provide replacement for the methadone dose as well as satisfactory analgesia.
Patients who are on either methadone or buprenorphine preparations for treatment of their narcotic addiction present particular challenges in the treatment of significant pain.25 In the case of methadone, tolerance may be very high, and patients may require doses of either other longer-acting opioids or short-acting rapidly absorbed opioids that are many times higher than the usual patients’ doses. In some cases, it is both medically and logistically more logical to include the maintenance dose with the added needed doses for pain together, through the pain physician, either by using methadone as the maintenance pain drug or by converting the methadone dose into the dose of the other drug being used. Such conversions may be difficult, and equivalency tables are notoriously inaccurate, because individual absorption, tolerance, and metabolism play significant roles, often affected by pharmacogenomic differences among patients. “Starting low and going slow,” always an appropriate paradigm, is appropriate for these titrations.
Buprenorphine presents difficulties in addition to tolerance. Unlike methadone, which does not block other opioids—it only increases tolerance to them—buprenorphine has such high receptor affinity and slow receptor dissociation that it keeps other opioids from acting at receptor sites. It will even displace prior opioids from those same sites, and because buprenorphine has lower receptor activity despite its high affinity, the end result can be the development of a withdrawal syndrome in patients on other opioid agonists who are given buprenorphine. This is mistakenly thought to be secondary to the naloxone component but is directly attributable to buprenorphine, particularly since no significant amount of naloxone is absorbed transmucosally or by ingestion.
Physicians prescribing either methadone or buprenorphine should have a preliminary discussion with their patients regarding contingencies for increased pain. If patients are facing elective procedures that will likely produce at least moderate pain, it is the author's preference to have a discussion with the proceduralist or the anesthesiologist regarding pain management in patients on methadone or buprenorphine. In patients on methadone, the task is relatively simple. The maintenance dose of methadone should be continued in a single morning dose when possible. If the patient is to have nothing by mouth, methadone can be given intramuscularly, but the total dose should be approximately half the oral dose, because of a 50% hepatic first-pass metabolism, and then given in divided doses (e.g., an individual on 120 mg of oral methadone who is NPO may receive a total of 60 mg, given as 15 mg every 6 h or 20 mg every 8 h).
The patient can then be given the acute pain drug the physician prefers, but required doses may be at least 50% higher than usual and are often two to three times the usual doses for opioid-naïve patients (and occasionally may be even higher). If the pain is likely to be of relatively short duration, the maintenance dose of methadone may not need to be changed; however, if the patient is on appreciable doses of short-acting drugs for several weeks, an adjustment in methadone dose may need to be ordered as the acute pain drug is tapered. Giving multiple long-acting opioids has the potential for overlapping peaks and producing over-sedation and should be avoided when possible. If multiple long-acting drugs are used, patient education regarding the timing of the doses is important.
There are several strategies which may be successful in the treatment of short-term pain in the methadone or buprenorphine maintained patient.29 The simplest of these is to maintain the buprenorphine dose prior to and through the period of postoperative or traumatic pain while adding a very high affinity, high potency opioid (fentanyl, sufentanil, hydromorphone), usually in significantly elevated doses, although it should be carefully titrated, starting at doses 50% to 100% higher than usual, and evaluating response and adjusting accordingly. This may particularly be appropriate in patients maintained on relatively low doses of buprenorphine, from 2 mg to 12 to16 mg per day.
In patients on higher doses of buprenorphine (i.e., >16 mg per d), it is thought best to discontinue buprenorphine, tapering it so that the last dose is given at least 48 hours (and the author's experience has shown that 72 hours or longer is desirable) prior to the planned procedure. The patient may then be maintained on a standard agonist, such as oxycodone IR, in doses ranging from 5 to 30 mg four times daily. Following the procedure, higher doses or a more potent drug (sufentanil, fentanyl, hydromorphone) can be used for analgesia. When the need for the acute pain treatment has passed, the medication may be tapered, and the patient referred back to the buprenorphine provider to resume treatment.
A third option is to use buprenorphine itself for pain treatment in these patients. However, this is rarely successful in patients already on higher doses of buprenorphine (24-32 mg/d) because of the ceiling effect of the drug and because buprenorphine is not as effective in moderate-severe to severe pain. However, in patients undergoing dental surgery or other moderately painful procedures or in those who are trauma victims, the use of additional buprenorphine 4 to 8 mg sublingually every 4 to 6 hours may be an effective pain management tool if the total dose does not exceed approximately 32 mg per day. One drawback to this strategy is that if buprenorphine is not effective in treating the pain, very high doses of fentanyl, sufentanil, or hydromorphone may be necessary to manage the pain. In some cases, patient monitoring with careful attention to respiratory rate and effort, as well as oxygenation, may become critical.
Patients on agonist treatment for addiction are at very high risk of relapse to “street” opiates or their other drugs of choice during these times of both severe pain and high stress. Involvement of supportive family and/or significant others, sponsors, and therapists may be important proactively, with the patient having a “safety plan” spelled out in advance.
Acute trauma may be more difficult to deal with because of the immediacy of the issue and the inability to plan in advance. It is wise to have the patient carry an emergency card or have a Medicalert® bracelet to provide treaters with necessary information, as well as an emergency number to contact the involved medical personnel. The use of injectable nonsteroidal anti-inflammatory drugs, such as ketorolac, as well as local anesthetic in regional or field blocks, may all be highly useful. The rapid titration of short-acting opioids such as fentanyl or hydromorphone can provide appropriate analgesia, starting near usual doses and escalating as needed, even in patients on high doses of methadone or buprenorphine. In severe cases, conscious sedation or achieving a light anesthetic state with benzodiazepines may be necessary, and rarely general anesthesia is required to achieve control of pain and pain-related behaviors. Again, careful monitoring of respiratory status, oxygenation, and mental status may be necessary. One particularly difficult group of patients is those who are on buprenorphine and present with major trauma or the need for emergency major surgery. Because tapering of buprenorphine is not an option, the buprenorphine may be stopped on admission and pain treated with high doses of potent opioids. However, these patients need close monitoring since they will be susceptible to respiratory depression when the buprenorphine wears off.
CONTRACT VIOLATION AND TREATMENT TERMINATION
The author has given a series of talks for many years titled “Don't put people on meds you don't know how to take them off of” but has settled on the shorter and perhaps more elegant title “Don't take off when you don't know how to land.” Pain physicians and those dealing with patients with opioid addiction have had very different experiences in discontinuing opioids (and other dependency-producing drugs, especially benzodiazepines) in their patients. Review articles and textbooks frequently recommend relatively short tapering schedules for patients having opioids reduced and discontinued. This may be particularly effective in patients with opioid-induced hyperalgesia, where dose reduction may actually result in improved pain relief.
It has been the author's experience that patients with CD are far more sensitive to the dysphoria as well as to the physical manifestations of opioid withdrawal. The average patient undergoing therapeutic methadone detoxification may be withdrawn over a period of 6 to 12 months. However, shorter periods of detoxification may be well tolerated, but rarely at reductions of more than 10% of the dose per week, resulting in an approximately 3-month taper. This becomes an issue in those patients who are being dismissed because of problematic or aberrant behaviors, when continued prescribing is deemed unwise and/or dangerous.
Every pain physician or program should and must come up with treatment agreements that fit the needs of patient and the program. Sometimes, however, pain physicians do not differentiate between “yellow” flags, which should require refinement of the treatment agreement, and the use of predescribed contingencies (e.g., increased visits, more urine screens, involvement in counseling, or others), and “red” flags that may require dismissal from treatment. The period of dismissal may range from immediate and without detoxification for severe infractions to 30-day supplies of medication with instructions to find a different provider.
There is a widespread and incorrect assumption that opioid withdrawal is relatively minor and has few medical consequences. It is frequently compared with having a moderate viral syndrome, with diffuse pain, myalgias, arthralgias, shaking chills, nausea, vomiting, and diarrhea, and lasting a relatively short time. This may be true for younger, healthier patients taking only short-acting opioids. However, in older and more medically/psychiatrically complex patients, and in particular with the use of longer-acting SR opioids in higher doses, withdrawal may be severe and protracted, lasting weeks and even months.
Elevated pulse and blood pressure may be present and result in cardiac decompensation in those with underlying heart disease, including the development of angina and myocardial infarction. Vomiting may be severe and result in aspiration, esophageal tears with bleeding (Mallory Weiss syndrome), volume contraction, and severe electrolyte and acid-base balance issues, including acute tubular necrosis with renal failure. This may also occur with severe diarrhea. True informed consent should require that the prescribing pain physician discuss these possibilities with patients early in the treatment course and when treatment agreement violations are noted so that it may have a deterrent effect on further aberrant behaviors.
An issue that may result in treatment agreement violation is that of positive urine or salivary drug screens. Such positive screening tests should be subjected to appropriate confirmatory testing before taking action, as appropriate. Gas chromatography and mass spectroscopy (GC-MS) are the usual confirmatory tests, but other tests (such as double liquid chromatography followed by mass spectroscopy or in some cases thin layer chromatography, depending on the substance involved) may be appropriate. Chain of custody issues and false-positives from interfering substances should be considered as well. Drug testing is ideally an adjunctive test, and in cases where the clinical behaviors have not been aberrant and a positive drug test occurs with the patient denying its validity, consideration should be given to the potential for a false-positive.
Termination, particularly without detoxification, should be the final decision when no safe and effective treating of the patient remains. Adjunctive medications to ameliorate withdrawal, such as the use of α-2 agonists (clonidine, guanfacine, and guanabenz), as well as antidiarrheal and antiemetic agents, should be strongly considered and prescribed.30-32 If a 30-day supply of opioid medication is given, it may be appropriate that it be written in a tapering dose schedule over that period of time. If benzodiazepines are prescribed, tapering doses of longer-acting, more slowly absorbed agents such as clonazepam or chlordiazepoxide may be indicated. Use of diazepam, alprazolam, and lorazepam, which are more rapidly absorbed and have high abuse potential, should be avoided. Anticonvulsants, such as carbamazepine, valproic acid, and gabapentin, in usual therapeutic doses for seizures, may also be used to aid patients in withdrawal from benzodiazepines.33-35
It is not uncommon for patients to be referred to a detoxification facility. If this occurs, it is worthwhile for the pain physician to have determined programs in advance that would meet the patients’ needs. Many detoxification settings are managed by nursing staff, often licensed practical nurses with registered nurse supervision, having an off-site physician and prewritten protocols, with very little ability to individualize care. The author has seen hundreds of patients on appreciable doses of SR morphine, oxycodone, and other opioids given the same 5-day protocols using methadone, at doses no higher than 30 mg, then tapered over an additional few days. Such tapers are rarely, if ever, effective and leave patients with a moderate to severe and often protracted course of opioid withdrawal.
Many physicians are not aware of the nature of free-standing (so-called “public”) detoxification facilities. Patients are evaluated and treated by nursing staff (often licensed practical nurses, with no registered nurses on site) on the basis of standing orders, and many, perhaps most (or even all) patients in these programs are not seen by a physician. The facility may have a very limited formulary, so that patients on medications they do not stock have to arrange to bring these medications, or have them brought by friends or family. Many facilities take a “one size fits all” approach and will take patients off all dependency-producing medications even if one or more of those medications has not been problematic (e.g., the physician may refer the patient because of benzodiazepine or alcohol abuse and the patient has been adherent to the opioid treatment; however, the program will taper them off of all their drugs, including the opioids).
There are generally hospital-based detoxification programs with on-site physicians and stronger nursing presence where a more individualized approach to these complex patients can be taken. Pain physicians and programs should take the time and effort to familiarize themselves with appropriate detoxification settings and trained physicians in their community, or within referral distance, where there is a greater likelihood of a safe and successful outcome. The American Society of Addiction Medicine (www.asam.org), the American Academy of Addiction Psychiatry (www.aaap.org), and the American Osteopathic Academy of Addiction Medicine (www.aoaam.org) have listings of members on their websites for referral.
In patients for whom opioids have been effective in management of pain but where the patient self-escalates doses or engages in other aberrant behaviors necessitating treatment termination, consideration should be given to referral to a buprenorphine prescriber. In some pain programs, the pain physicians have colleagues who have taken an approved buprenorphine training course and have a prescribing waiver. The sublingual forms of buprenorphine, Suboxone (available now only in the proprietary filmtab), and Subutex (available recently as a generic preparation), are not approved for pain treatment. However, in the patient with combined pain and addiction, they may prove useful in overall patient management, and as long as the patient has documentation of opioid dependency, buprenorphine can be legally prescribed. The combined buprenorphine/naloxone preparation is thought to be safer and less likely to be misused/abused, particularly by injection, and should be the first choice of most patients.
The author has treated many patients who were difficult or impossible to manage with usual SR opioids (particularly OxyContin and generic immediate-release and/or sustained-release oxycodone preparations), who became well managed without dose escalation and with tremendous improvement in compliance and quality of life with the use of usual doses of buprenorphine. In management of addiction, buprenorphine can usually be given once daily, but as with methadone, pain management is better accomplished with multiple divided doses. Again, combination buprenorphine/naloxone (Suboxone filmtabs) is considered safer, has less abuse potential, and is preferred.
Pain physicians may prescribe sublingual buprenorphine for pain, with or without a waiver, as an off-label use of the medication. However, it must be emphasized that there are few studies of its use for this indication, and full informed consent by the patient is important. In addition, both insurance companies and pharmacists may be unwilling to dispense the medication when the prescriber does not have a federal buprenorphine waiver or if it is for an off-label indication However, since these patients have both pain AND addiction, appropriate prescribing can generally be accomplished. Therefore, writing the words “for pain” on the prescription may be helpful. A letter from the Drug Enforcement Agency (DEA) to the chair of the ASAM pain committee indicated that physicians may legally use buprenorphine for pain treatment off label and without a special waiver.36
TOOLS FOR DEALING WITH PATIENTS WITH CHEMICAL DEPENDENCY
Unfortunately, it has been all too frequent in the author's experience that the identification of past or present CD is tantamount to dismissal of the patient as inappropriate for a pain management program. Such identification should ideally lead to the creation of an appropriate treatment agreement that applies the necessary contingencies so that these patients can be safely managed. As has been previously stated, the American Pain Society, the American Academy of Pain Management, and the American Society of Addiction Medicine in a common public policy statement, emphasized this point several years ago.28 Fear of regulatory action, legal problems, and civil lawsuits are not adequate reasons to deprive patients in need of adequate pain management. Strategies for doing so have been discussed in the appropriate sections above.
There has been a dramatic increase in the number of medications available to treat chemically dependent patients for many different drugs of choice. While most of the approved drugs have been for combating alcohol use and craving (Table 70-4), there are several approved for opioids as well (buprenorphine and methadone have been discussed). Several medications have been studied for other forms of CD, such as cocaine and other stimulants, which have not yet been approved but are available off-label, and may be useful in specific patients. Table 70-2 lists the approved medications for treatment of opioid dependency, as well as investigational agents for other indications. There are several excellent reviews of these medications.37,38
Drugs Used in the Treatment of Other Chemical Dependencies
||Download (.pdf) TABLE 70-2
Drugs Used in the Treatment of Other Chemical Dependencies
FDA-approved 1974 for use in opioid dependency
Must be licensed program. Usual opioid SEs. Many drug interactions.
Naltrexone (ReVia, generics)
FDA-approved 1992 for opioids
Hepatic black box warning: nausea, vomiting, diarrhea. Monitor LFTs; patients must be fully detoxified from opioids.
Buprenorphine (Suboxone, Subutex)
Special training, DEA waiver. Usual opioid SEs, fewer drug interactions; may precipitate opioid withdrawal in patients dependent on pure agonists; ceiling dose 16-24 mg/d for addiction treatment, may be higher (>32 mg/d) in divided doses for pain.
FDA-approved 2010 for opioids
Same as Naltrexone above; patients must be fully detoxified from opioids or severe/protracted withdrawal may occur.
Cocaine and Stimulants
OFF LABEL FOR THIS INDICATION.
Multiple studies have shown significant reduction in craving and use of cocaine and other stimulants, including methamphetamine.
OFF LABEL FOR THIS INDICATION.
Limited studies show modest reduction in craving and use of cocaine.
OFF LABEL FOR THIS INDICATION.
Limited studies show modest reduction in craving and use of cocaine.
Investigational, early results promising.
The oldest medication developed for the treatment of alcohol craving and abuse is disulfiram (Antabuse). This medication works by blocking acetaldehyde dehydrogenase, which is produced by alcohol dehydrogenase in the metabolism of alcohol to acetic acid and water. Acetaldehyde accumulates and causes nausea, vomiting, headache, flushing, and lightheadedness and may result in significant hypotension and syncope.39,40
Disulfiram does not have direct effects on craving but rather works as a deterrent to drinking. However, studies of self-administration have shown little effect, and in order to be effective, disulfiram should be monitored by a third party, which may be a motivated spouse, friend, supervisor, or coworker. Disulfiram should be prescribed only when there is no ethyl alcohol present; a blood alcohol concentration (BAC) should be checked, or a minimum of 24 hours should have passed since the last drink.
Although it is generally effective in a dose of 250 mg daily, patients may require doses of 500 mg per day. In monitored settings, disulfiram may be given in doses of 500 mg on Monday and Wednesday, with 750 mg on Friday. However, GI intolerance, with nausea, vomiting, and diarrhea, may increase at higher dose levels. It is critical to discuss with prospective patients disulfiram side effects and to warn against accidental alcohol exposure, which may be associated with foods (wine vinegar, alcohol used in cooking), liquid medications preserved with ethyl alcohol (cough and cold medications and others), and rarely exposure to alcohol in perfumes and colognes. In addition, breathing in the fumes of alcohol-based skin sanitizers (Purell and others) by washing hands close to the face, can result in absorption of alcohol.
Unsupervised disulfiram treatment has relatively poor results.39 However, monitored treatment where a responsible individual in the home, workplace, or elsewhere directly observes the patient taking the medication daily (or three times weekly in higher doses) may have better results. This has been especially effective in impaired professional programs, in which physicians, nurses, and other health care professionals with alcohol addiction are mandated by their licensing boards to take disulfiram under supervision.
Disulfiram reactions are usually self-limited but in severe cases may require IV fluids, and there are anecdotal reports of the benefit of antiemetics, antihistamines, and ascorbic acid; the author has had good experience giving sublingual aspirin.41 In individuals with underlying coronary heart disease, peripheral arterial disease, and cerebrovascular disease, however, hypotension associated with disulfiram reactions may be more problematic. Disulfiram also blocks dopamine β-hydroxylase, an enzyme involved in cocaine metabolism, and there are ongoing studies of its use for this indication.
Acamprosate is a homotauric acid derivative that modulates glutamatergic transmission by antagonizing the N-methyl-D-aspartate (NMDA) pathway in the CNS and appears to reduce the severity of postacute withdrawal syndromes in newly recovering alcoholics. This has an important effect on reducing alcohol craving. Several studies42,43 have shown benefit of acamprosate. However, a large multisite study, Project Combine, failed to show statistically significant benefits of acamprosate.44 The author believes that acamprosate resulted in a higher level of complete abstinence in a smaller group of individuals, while naltrexone (see below) resulted in more sustained reduction in drinking in a larger group of patients; however, there was a lower rate of total abstinence.
Acamprosate is remarkably free of side effects, with mild GI symptoms only, which generally abate. However, it has to be taken as 666 mg (two 333-mg tablets) three times daily for efficacy. It has no known drug interactions and may be combined with disulfiram or naltrexone to increase effects on alcohol craving. Although there are no published studies showing benefit of such drug combinations, the author has used them in many patients with good effect.
Naltrexone has been discussed above and obviously is contraindicated in patients who are receiving opioids or for whom opioid treatment is contemplated. However, in alcoholic patients at high risk for relapse in whom non-opioid pain treatment is contemplated, naltrexone may be very useful in preventing relapse.44-46 Although the mechanism is not clear, it appears that alcohol works, in part, by the production of adduction products, tetrahydroisoquinolones (THIQs), which have opioid activity. Blocking this effect reduces the reinforcing activity of consuming alcohol, and individuals on naltrexone, if they have a brief drinking episode (a “slip” or “lapse”), are far less likely to develop a full relapse (a fall). Doses of 50 mg daily, or 100 mg on Monday and Wednesday with 150 mg on Friday in a monitored setting, are generally effective. Nausea and vomiting are the major side effects, and these decrease with continuing use in most patients.
While there is a “black box” liver warning in the prescribing information, there are no reported cases, of this drug causing hepatic toxicity in current doses; prior studies using 250 to 500 mg per day were associated with rare cases of very high transaminase levels, and it is recommended that ALT/AST be monitored prior to administration and that three times upper limits of normal (ULN) be considered a relative contraindication to prescribing or continuing naltrexone.
Naltrexone is also available as a SR injection (Vivitrol®), which is given every 4 weeks. It is a deep IM injection, generally given in the gluteus maximus muscle, and injection site pain, swelling, and rarely infection may occur.47,48 The monthly injection has fewer gastrointestinal (GI) side effects and is generally well tolerated and eliminates the compliance issues with daily use of the medication. Pain in those on naltrexone can be treated similarly to that described for patients taking methadone and buprenorphine (see above and reference 29).
While disulfiram, naltrexone, and naltrexone ER (Vivitrol®) are approved for the treatment of alcoholism, there are several medications in clinical trials that have shown benefit but would be off-label if given for that indication. Topirimate has been extensively studied for alcohol49 and cocaine and other stimulant abuse.50,51 Dosing for topirimate is similar to that used in treatment for seizure disorders and migraine prophylaxis, and the side effects and precautions are similar. Ondansetron has had results comparable to naltrexone, but only in Cloninger type 2 (Babor type B) alcoholics (e.g., men with strong family histories of alcoholism, early onset disease, and high levels of psychopathology and criminality).52
A large number of medications and herbal preparations have shown some effects in small, open label studies (e.g., St. John's Wort, kudzu root), but the risk/benefit ratios for these are unknown, and they should all be considered investigational at this time. Combinations of antidepressants (particularly SSRI and SNRI agents) with anticraving drugs have been used successfully, particularly in patients with underlying mood disorders. Studies of combinations of gabapentin and naltrexone have also yielded positive results. However, many of these studies are smaller, open-label trials and have not been replicated in larger multicenter randomized controlled trials. Caution is indicated, and these agents should not be first-line considerations at this time.
COCAINE AND OTHER STIMULANTS
There are no approved medications for individuals who abuse cocaine and stimulants. Psychosocial treatment, with medication as needed supportively (e.g., brief use of anxiolytics), and treatment of underlying psychiatric disorders are the standards of care. In individuals whose triggers to abuse cocaine and stimulants are other drugs, such as alcohol or opioids, the use of agents to reduce craving may result in reduction of cocaine and stimulant use.
Topirimate has shown positive early results in trials for decreasing cocaine use and craving50 as well as methamphetamine use.51 In patients who may have alternative indications for topirimate, such as a seizure disorder or migraine prophylaxis, it may be more of a first-line drug in the presence of cocaine or other stimulant abuse. Disulfiram, described above for alcohol dependence treatment, may have utility in reducing cocaine craving, perhaps secondary to its effects on blocking dopamine-β-hydroxylase as well as acetaldehyde dehydrogenase.53
The use of amantadine, rimantadine, bromocriptine, and tricyclic antidepressants (particularly desipramine) has waned because of little evidence of sustained effects from any of these agents. There is ongoing investigation of N-acetylcysteine,54 baclofen,55 and other agents, but their use is considered investigational at this time. Early work on a cocaine vaccine has yielded positive results.56 A large number of agents have been tried with initial success in small, open-label studies, but positive results have not been found in larger, randomized, controlled studies. The physician is encouraged to follow the current literature.
DRUGS USEFUL IN TREATING OPIOID-DEPENDENT PATIENTS
In opioid-dependent patients who are in treatment for pain where prior experience has shown that opioids cannot be used safely or for those patients in recovery from opioid dependency who would prefer not to receive opioids, consideration can be given to opioid-blocking agents (Table 70-4). Oral naltrexone has been approved for this indication since 1992. The depot IM form (Vivitrol) was approved for this indication in 2010. Although oral naltrexone has a significant number of studies indicating its long-term safety and efficacy in this population,57,58 the depot form was approved on the basis of relatively limited studies59,60 and its long-term effects have not been reported, with caution being urged.61 It is critically important with both agents (oral and IM naltrexone) that patients are completely detoxified from opioids prior to administration, because each may precipitate a severe and potentially life-threatening withdrawal syndrome in the incompletely detoxified patient. Precipitated withdrawal is different from naturally occurring withdrawal, with delirium, seizures, severe agitation, vomiting, aspiration, and other complications, all of which have been witnessed by the author.
In patients who are leaving long-term residential treatment or those who have been incarcerated for long periods of time, the use of depot naltrexone may be useful in promoting abstinence from opioids, with no risk of precipitated withdrawal. However, in more recently detoxified individuals, the author has seen several cases of severe, intractable, and psychotic depression in patients receiving depot naltrexone; the cause, however, is not clear. In addition, the use of these agents may foreclose the option of using opioid treatment, particularly with the depot form, since the blockade may last 4 or more weeks. However, techniques as described above can be used to treat acute or subacute moderate to severe pain in these patients.29
Physicians who prescribe opioids to patients on long-term agonist therapy should be aware that there may be a receptor hypersensitization in these patients, with exaggerated responses to even small, therapeutic doses of opioids. If patients who have been on naltrexone or depot naltrexone are to be treated with opioids, caution should be used, with very low doses of medication prescribed, even lower than those given to opioid-naïve patients. A recent event in the Boston area involved a physician who had prescribed depot naltrexone to several hundred patients and had to leave his practice immediately. A number of the patients were unable to locate alternative prescribers and relapsed to opioid use. There were several anecdotal reports of serious overdoses in these patients, sometimes with extremely modest doses of opioid.
MISCELLANEOUS DRUGS OF ABUSE
Other drugs, including cannabinoids, hallucinogens, inhalants, and others, generally do not require detoxification, and no approved medications are shown to improve outcomes. Treatment of target symptoms, using neuroleptic agents, benzodiazepines, and supportive human contact in a calming environment, is generally sufficient. In most cases, intoxication is self-limited, and drug craving is treated supportively. Again, careful evaluation and treatment for underlying psychiatric disorders are essential. In addition, many drugs can produce neuropsychiatric abnormalities, and therefore, specialized evaluation and testing may be necessary.
The world of patients with pain and the world of patients with CDs are not two separate universes but rather a Venn diagram with significant overlap. Many patients develop CD as a response to unremitting chronic pain. A number of patients being treated for pain have underlying CD or its risk factors or develop CD during their pain treatment. The pain physician and the addiction medicine/psychiatry practitioner need to develop and use the tools to deal with the alternative problem in their patient population.
This requires both types of practitioners to develop a greater expertise in both areas than might be expected of the average generalist. It also should require a familiarity with the needed expertise that is available in the immediate vicinity of the practitioner in the form of individuals and programs that are well suited for the management of addiction in the pain patient and pain in the patient with addiction. Because neither pain programs nor addiction programs are created equal, it is well worth the time and effort to familiarize oneself with the available resources and refer to the most appropriate resource when needed.
There has been exciting progress in the development of personal medicine, with evidence that response to some anticraving medications may relate to genetic host factors. The efficacy of naltrexone, for example, differs among individuals with different single nucleotide polymorphisms (SNPs) of the dopamine gene.62 Pain and addiction treatment clinicians should remain current with progress in this important area. All too often, the recognition of underlying or newly developed CD in a patient in a pain program is seen as an indication for dismissal rather than as a challenge and an opportunity to treat both issues. Pain physicians and addiction medicine physicians need to interact formally and informally to a far greater degree than is now the case in most programs. The prescription drug epidemic, which has increased since the late 1990s, will not allow for a fragmented approach to this population. It is hoped that this chapter will contribute in some way to that increased collaboration.
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ADDITIONAL GENERAL READINGS IN ADDICTION MEDICINE/PAIN
The following are the three major American textbooks on substance abuse and addiction medicine. The most recent editions now have several chapters on pain management in the patient with addiction, the neurobiological connections of addiction and pain, and other topics of interest. I have also listed a very widely used handbook on the prescribing of opioids.
E, eds. Substance Abuse: A Comprehensive Textbook. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2011.
KT, eds. Textbook of Substance Abuse Treatment. 5th ed. Washington, DC: American Psychiatric Publishing; 2015.
R, eds. The ASAM Principles of Addiction Medicine. 5th ed. Philadelphia, PA. Wolters Kluwers; 2014.
SM. Responsible Opioid Prescribing. Washington, DC: FSMB Foundation, Waterford Life Sciences; 2007.