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Prescription Drug Abuse: An Introduction Massachusetts NIDA Consortium

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1 Prescription Drug Abuse: An Introduction Massachusetts NIDA Consortium
Daniel P. Alford, MD, MPH * Jane Liebschutz, MD MPH Angela Jackson, MD *Benjamin Siegel, MD These curriculum resources from the NIDA Centers of Excellence for Physician Information have been posted on the NIDA Web site as a service to academic medical centers seeking scientifically accurate instructional information on substance abuse. Questions about curriculum specifics can be sent to the Centers of Excellence directly. November 8, 2009 This presentation may be delivered over 90 minutes to 2 hours, or in an abbreviated form. The slides that may potentially be deleted for a one-hour presentation appear with a (*) in the speaker’s notes. A “Faculty Guide” is provided with these slides.

2 Prescription Drug Abuse Outline
Overview of Prescription Drug Abuse (PDA) Framework for Safe Prescribing Identifying PDA The outline for this prescription drug abuse talk is 1) overview of prescription drug abuse, 2) framework for safe prescribing, and 3) how to identify prescription drug abuse. Daniel Alford, MD, MPH

3 1. Overview Daniel Alford, MD, MPH

4 Prescription Drug Misuse (Definitions)
Includes Non-medical use Substance abuse/PDA Dependence Addiction Diversion Does NOT include physical dependence There is no universally accepted terminology for the different aspects of prescription drug abuse. Here, we give some of the concepts and the rationale for their use: Prescription drug misuse – This term can serve as an umbrella term. Misuse refers to the use of a drug not consistent with medical or legal guidelines. It can include any of the following: non-medical use, substance abuse or dependence, addiction, or diversion. But it does not include physical dependence unless it is part of a pattern of symptoms as defined under the criteria below: Non-medical use – Defined as the use of prescription medication without a prescription or the use of a prescription medication for purposes other than those for which it is prescribed (e.g., for the feelings it produces or to get high). Substance Abuse/Prescription Drug Abuse – Defined as a pattern of non-medical use of prescription drugs that causes one or more of the following adverse consequences related to the repeated use of substances: Failure to fulfill major obligations Use even when it is physically hazardous to do so Recurrent legal problems Recurrent social or interpersonal problems (see next slide for additional notes) American Psychiatric Association. DSM IV-TR, 2000; Savage et al. J Pain Symptom Manage, 2003; Addiction Science and Clinical Practice, 2008; Weaver, Schnoll. J Addiction Medicine, 2007. Daniel Alford, MD, MPH

5 Prescription Drug Misuse (Definitions)
Additional notes provided for slide 4 (see below) Substance Dependence – A cluster of cognitive, behavioral, and physiological symptoms indicating that the individual continues use of the substance despite significant substance-related problems. There is a pattern of repeated self-administration that can result in tolerance, withdrawal, and compulsive drug-taking behavior. A problem with this definition is that patients with chronic pain who take opioids may appear to have a substance abuse disorder. “Addiction” as a term is often replaced by “substance dependence,” etc. However, many physicians feel that the term ADDICTION more clearly distinguishes compulsive drug use from physical dependence due to prolonged medical use. This definition was developed by the American Society of Addiction Medicine, the American Academy of Pain Medicine, and the American Pain Society. Addiction is defined as chronic relapsing brain disease, a primary, chronic, neurobiologic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Diversion – Defined as diverting opioids from therapeutic channels to share or sell them for recreational use, treatment of untreated pain in others, or for financial gain. *Physical dependence is a biological phenomenon, an adaptive physiological state that can occur with regular drug use and results in a drug class-specific withdrawal syndrome with abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. Most patients who are on chronic opioids or chronic benzodiazepines, or beta blockers, or clonidine will become physically dependent. During the first visit(s), it will be difficult to determine which chronic-pain patients have true addictions. However, with good monitoring in place, one will start to see aberrant medication-taking behaviors possibly suggestive of addiction. American Psychiatric Association. DSM IV-TR, 2000; Savage et al. J Pain Symptom Manage, 2003; Addiction Science and Clinical Practice, 2008; Weaver, Schnoll. J Addiction Medicine, 2007. Daniel Alford, MD, MPH

6 Opioid Dependence vs. Chronic Pain Managed with Opioids?
The diagnosis of Opioid Dependence requires 3 or more criteria occurring over 12 months Tolerance – YES Withdrawal/physical dependence – YES Taken in larger amounts or over longer periods – MAYBE Unsuccessful efforts to cut down or control – MAYBE Great deal of time spent to obtain substance – MAYBE Important activities given up or reduced – MAYBE Continued use despite harm – MAYBE The diagnosis of OPIOID DEPENDENCE requires 3 or more of these criteria to occur over a 12 month period. However, many of these criteria may be present in a patient with chronic pain who is treated with chronic opioids. This may be due to poor pain control, the patient’s concern that the physician will not believe his or her pain and thus under-prescribe pain medications, etc. American Psychiatric Association. DSM IV-TR, 2000. Daniel Alford, MD, MPH

7 Aberrant Medication-Taking Behavior
A spectrum of patient behaviors that may reflect misuse Health care use patterns (e.g., inconsistent appointment patterns) Signs/symptoms of drug misuse (e.g., intoxication) Emotional problems/psychiatric issues Lying and illicit drug use Problematic medication behavior (e.g., noncompliance) Implications Concern comes from the “pattern” or the “severity” Differential diagnosis “Aberrant medication-taking behavior” is another term that is commonly used to describe a spectrum of behavior that may reflect misuse, such as: Healthcare use patterns – inconsistent appointment patterns, lost or stolen prescriptions or medications, frequent early renewal requests Signs or symptoms of drug misuse such as intoxication; Lack of pain relief with any medication other than opioids; Evidence of lying; Illicit drug use, which would be indicative of addiction; and Non-adherence with follow-up appointments or other treatments. Our objective is to recognize these behaviors and then develop a differential diagnosis of the cause of the behaviors. Generally, it is not one single aberrant medication-taking behavior that is of concern but rather the pattern of multiple behaviors or the severity of one. Butler et al. Pain, 2007. Daniel Alford, MD, MPH

8 Prescription Drug Misuse
Addiction Abuse/Dependence Prescription Drug Misuse Aberrant Medication-Taking Behaviors (AMTBs) A spectrum of patient behaviors that may reflect misuse This diagram demonstrates that most patients with chronic pain on long-term opioid medications are not addicted (Manchikanti, Cash et al. 2006; Fleming, Balousek et al. 2007). In fact, the likelihood of patients with chronic pain becoming addicted to opioids is low (with the exception of those with a personal or family history of drug abuse or other mental illness). Others may be using medications non-medically by taking the medication for some indication other than what was prescribed (e.g., it was prescribed for back pain, but the person is taking it to help with depression). Regardless, any non-medical use of psychoactive medications can be harmful. Total Chronic Pain Population Daniel Alford, MD, MPH

9 Which Prescription Medications Are Most Likely to Be Abused
Which Prescription Medications Are Most Likely to Be Abused? Commonly Abused Medications Opioids CNS depressants Benzodiazepines Barbiturates Stimulants Others Opioids – Commonly abused opioids include Vicodin, Percocet, or the long acting OxyContin. CNS depressants include benzodiazepines such as Kloponin and Xanax and barbiturates such as Fiorinal, etc. Stimulants include methylphenidate (e.g., Ritalin) and amphetamines (e.g., Adderall). Others – Clonidine, which appears to have some centrally acting properties and is usually used in combination with other drugs. Daniel Alford, MD, MPH

10 Which Prescription Medications are Most Likely to Be Diverted
Which Prescription Medications are Most Likely to Be Diverted? Important Drug Characteristics Onset of action Intensity of effect Trade name > generic Cost and availability of illicit equivalent Which medications or drugs are the most likely to be abused or diverted? Important medication and drug characteristics to consider include the following: Onset of action – Those drugs that are short-acting or have a quick onset of action are much more rewarding and reinforcing and thus addicting than those that have a slow onset of action. Intensity of effect. Trade-name medications vs. generic equivalents – Trade-name medications are more recognizable “on the street” and thus are more divertible and have a higher street value than generic equivalents. The cost of the drug and the availability of its illicit equivalents – Daniel Alford, MD, MPH

11 SAMHSA Office of Applied Studies, NSDUH data, 2009.
According to the Substance Abuse and Mental Health Services Administration 2008 National Survey on Drug Use and Health, trends in past year initiation of non-medical use of prescription-type psychotherapeutics in those twelve or older showed remain at relatively sustained levels since 2002—with the most increase in the analgesics (past year initiation refers to taking for the first time as opposed to current, past year, or lifetime use)1. 1Note: this curriculum resource is to be regularly updated as new data becomes available; see Accessed October 8, 2009. . SAMHSA Office of Applied Studies, NSDUH data, 2009. Daniel Alford, MD, MPH

12 Consequences of Prescription Opioid Abuse
To highlight one consequence of increased analgesic use, the Drug Abuse Warning Network’s 2008 data1 demonstrates dramatic increases in ED-related visits for both hydrocodone and oxycodone use. The Drug Abuse Warning Network, or DAWN, is a public health surveillance system that monitors drug-related visits to emergency departments and drug-related deaths investigated by medical examiners or coroners from 13 metropolitan areas. This is accomplished through a retrospective review of all ED medical records or medical examiner case files. 1Note: this curriculum resource is to be regularly updated as new data becomes available; see Accessed October 8, 2009. SAMHSA Office of Applied Studies, Drug Abuse Warning Network, 2008. Daniel Alford, MD, MPH

13 Another Factor Leading to Prescription Drug Misuse
Physician Over-Prescribing In addition to medication characteristics described previously, another factor that may contribute to prescription drug misuse is physician over-prescribing. Daniel Alford, MD, MPH

14 Why Do Some Physicians Over-Prescribe?
Duped Dated Dishonest Medication mania Hypertrophied enabling Confrontation phobia Why do some physicians over-prescribe? There are multiple reasons – physicians may be duped, dated, or dishonest. Duped – Physicians in general are a caring, trusting group of professionals. Although this unwavering positive regard for patients is critical to building relationships, some physicians may be taken advantage of by individuals who are addicted and “drug-seeking.” Dated – Some physicians have outdated knowledge about pain management, the use of opioids, and diagnosing substance-use disorders. Dishonest – Though rare, some physicians are dishonest and run “script mills,” that is, they sell controlled substances for profit. Other reasons for over-prescribing involve the following concepts: Medication mania – The idea that medications should be prescribed for all ailments. There is a sense in both society and patients presenting to physicians that a medication exists to treat whatever ails them. We know about this with antibiotics. That is, patients come in with a viral symptom but are expecting antibiotics. Some patients and also some physicians believe that a medication must be prescribed by the end of the patient’s visit. Hypertrophied enabling refers to the powerful instinct in physicians to do anything medically possible to enable patients to gain a higher level of function. Confrontation phobia – Physicians are rarely trained to say “no” and often struggle to set limits. Thus, some physicians may try to avoid confrontation at all costs, and therefore prescribe medications even when it is not in the best interest of the patient. Smith DE, Seymore RB. Proc White House Conf on Prescription Drug Abuse,1980. Parran T. Medical Clinics of North America, 1997. Daniel Alford, MD, MPH

15 Why do some Physicians Under-Prescribe? “Opiophobia”
Overestimate potency and duration of action Fear being scammed Often prescribe too small of a dose and too long of a dosing interval Exaggerate addiction potential In contrast, some physicians under-prescribe. Morgan coined the term “opiophobia” in the 1980s to describe a fear of physicians to appropriately prescribe (e.g., too small of a dose, too long of a dosing interval) for pain. There are a number of reasons for this. Physicians may overestimate the potency and duration of action of opioids; they may fear being scammed or duped; or they may have an exaggerated fear of the addiction potential – a concern that “everyone exposed to opioids will become addicted.” By under-treating pain, patients may go to other sources to seek needed pain relief. Morgan, J. Adv Alcohol Subst Abuse, 1985. Daniel Alford, MD, MPH

16 2. Framework for Safe Prescribing
Daniel Alford, MD, MPH

17 What Is the Physician’s Role?
So what is the physician’s role when treating chronic pain with long-term opioids? A physician’s role is to be what we’re trained to be, that is a clinician, a diagnostician, and a healer. We should not enter the role of police officer or judge. We are not trying to catch people doing illegal activities. Rather, we are trying to determine if the benefits of the treatment (opioids, in this case) are benefiting the patient (improved pain and function) or harming the patient (i.e., worse pain or function; signs of misuse or abuse). Daniel Alford, MD, MPH

18 When Are Opioids Indicated?
Pain is moderate to severe Pain has significant impact on function Pain has significant impact on quality of life Non-opioid pharmacotherapy has been tried and failed Patient agreeable to close monitoring of opioid use (e.g., pill counts, urine screens) When are opioids indicated? When pain is moderate to severe and has significant impact on function and on quality of life; When non-opioids have been tried and failed; Importantly, when the patient is agreeable to close monitoring of opioids, which may include signing a controlled substance agreement and agreeing to pill counts and urine drug testing. Daniel Alford, MD, MPH

19 Opioid Efficacy in Chronic Pain
Pain relief modest Some statistically significant, others trend toward benefit One meta-analysis decrease of 14 points on 100 point scale Limited or no functional improvement Most literature surveys & uncontrolled case series Randomized clinical trials (RCTs) are short duration < 4 months with small sample sizes < 300 pts Mostly pharmaceutical-company sponsored What is the efficacy of long-term opioids in treating chronic pain? Overall, pain relief was modest in these studies. In one meta-analysis, the decrease of pain was 14 points on a 100 point scale. (Eisenberg et al. JAMA 2005.) So if your patient is expecting pain relief going from ten to zero with opioids, it’s very unlikely to happen. Better education is necessary regarding how effective opioids are and what is realistic in terms of pain relief goals. Also, and significantly, these studies show limited functional improvement, which is an important goal in pain management. The management of chronic pain is beyond the scope of this talk, but it is important for physicians and patients to realize that opioids ARE NOT a magic bullet and to understand the limitations of this therapy. Most literature that studies opioids in chronic pain are surveys and uncontrolled case series. Randomized clinical trials are short in duration (less than 4 months) and involve small sample sizes (less than 300 patients). Most are pharmaceutical-company sponsored. Balantyne JC, Mao, J. N Engl J Med, Martell et al. Ann Intern Med, 2007; Eisenberg et al. JAMA, 2005. Daniel Alford, MD, MPH

20 The Risk-Benefit Framework: Judge the Treatment, not the Patient
INAPPROPRIATE Is the patient good or bad? Does the patient deserve pain meds? Should this patient be punished or rewarded? Should I trust him/her? APPROPRIATE Do the benefits of this treatment outweigh the untoward effects and risks in this patient or to society? Use a risk-benefit framework. It is important to judge the treatment, not the patient. You’re not asking: Is the patient good or bad? Does the patient deserve pain medications, namely opioids? Should the patient be punished or rewarded? Do I trust him or her? Rather, the questions to ask are: Do the benefits of this treatment, e.g., opioids, outweigh the untoward effects and risks to the patient or to society (including the concern of possible diversion)? What is the risk-benefit framework that needs to be kept in mind when deciding whether to begin opioids to treat chronic pain and over time when monitoring patients—are they benefiting or is there harm? Daniel Alford, MD, MPH

21 Assess Potential Benefit of Opioids
Assess current function What can patient expect to do with opioids that s/he cannot do now? Set Specific, Measurable, Action-oriented, Realistic, Time-dependant (SMART) goals for next visit Think of opioid prescription as a TEST After you have decided to initiate opioid treatment, you need to think about a risk-benefit framework and assess for potential benefits. What is the person’s current function? What can he or she expect to do with opioids that he or she cannot do now? And then set Specific, Measurable, Action-oriented, Realistic, Time-dependent (SMART) goals for the next visit and think of the opioid prescription as a “test.” It’ is not something that you’re committing to forever; you’re testing it out to see whether it is going to benefit this patient. Nicolaidis, C. Oregon Health and Science University, SGIM precourse, 2008. Daniel Alford, MD, MPH

22 Assess Potential Risks of Opioids
Sedation, confusion, constipation, etc. Addiction or diversion Characteristics that affect risk Use consistent approach, but set level of monitoring to match risk You also need to assess potential risks, including sedation, confusion, constipation, addiction, or diversion. And what are the risks for this particular patient? Are there other medications or comorbid conditions that the opioids are going to interact with? And then use a consistent approach. Set the level of monitoring to match the risk. Nicolaidis, C. Oregon Health and Science University, SGIM precourse, 2008. Daniel Alford, MD, MPH

23 What Is the Addiction Risk?
Published rates of abuse and/or addiction in chronic pain populations are 3-19%1 Suggests that known risk factors for abuse or addiction in the general population would be good predictors for problematic prescription opioid use Past cocaine use, history of alcohol or cannabis use2 Lifetime history of substance use disorder3 Family history of substance abuse, a history of legal problems and drug and alcohol abuse4 Heavy tobacco use5 History of severe depression or anxiety5 So what is the addiction risk of opioid use? Unfortunately, we don’t really know. The published rates of abuse and addiction in chronic pain populations range between 3-19%. Current literature suggests that risk factors for drug abuse in the general population may also apply to prescription drug abuse. These risk factors include: Heavy tobacco use Past use of alcohol, cannabis, and cocaine Lifetime history of substance use disorder Family history of substance abuse History of legal problems History of severe depression and anxiety 1 Fishbain et al. Clin J Pain, 1992; Ives et al. BMC Health Services Research, 2006; 3 Reid et al. JGIM, 2002; 4 Michna el al. JPSM, 2004; 5Akbik H., et al. JPSM, 2006. Daniel Alford, MD, MPH

24 Screening Instruments for Addiction Risk
Specific for opioid prescription abuse Specific for other addictions (CAGE, “single” question for alcohol, NIDAMED, etc.) (*May be deleted for one-hour version of presentation) As part of assessing the risks of opioid use, one must assess the patient’s risk of developing opioid addiction or misuse. Specific tools that assess the risk of prescription opioid abuse can be helpful, as can tools that are specific for other addictions such as alcohol and drugs that, if present, increase the risk of opioid medication misuse as mentioned in the previous slide. The screening tool, CAGE, for example, can detect a lifetime history of alcohol abuse or dependence. Daniel Alford, MD, MPH

25 Opioid Risk Tool Provides 5-item initial risk assessment
Stratifies risk groups into low (6%), moderate (28%) and high (91%) Family History Personal History Age Preadolescent sexual abuse Past or current psychological disease (*May be deleted for one-hour version of presentation) This 5-item tool was designed for use on an initial visit, prior to prescribing opioid therapy, to assess for aberrant medication-taking behavior (AMTB). To review, AMTB is a spectrum of patient behavior that may reflect abuse/dependence. The tool was validated among patients in a pain clinic. Low risk group: 6% risk - 94% did not exhibit AMTB Moderate risk group: 28% risk - had at least 1 AMTB High risk group: 91% risk - had at least 1 AMTB The tool itself can be found on the Web site noted on this slide. Webster, Webster. Pain Med, 2005. Daniel Alford, MD, MPH

26 Screening for Substance Use Disorders
CAGE CAGE-AID Have you ever felt you should Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt bad or Guilty about your drinking? Have you ever taken a drink first thing in the morning (Eye-opener) to steady your nerves or get rid of a hangover? Or drug use? Or used drugs? (*May be deleted for one-hour version of presentation) Another questionnaire that you may be more familiar with is “CAGE,” first published in 1974 by Mayfield. CAGE questions screen for lifetime problems with alcohol (alcohol dependence), but may miss hazardous drinkers (Saitz, NEJM 2005). The “CAGE-AID” adds “drugs” to the questions. Have you ever felt you should cut down your alcohol or drug use? Have people annoyed you by criticizing your drinking or drug use? Have you ever felt bad or guilty about your drinking or drug use? Have you ever taken a drink first thing in the morning, an eye-opener, to steady your nerves or get rid of a hangover? Or have you ever used drugs to steady your nerves or get rid of feeling sick or hung over? The  CAGE questionnaire has been evaluated in several studies, showing sensitivities ranging from 43 to 94 percent for detecting alcohol abuse and alcoholism. CAGE is well suited to busy primary care settings because it poses four straightforward yes/no questions that the clinician can easily remember and requires less than a minute to complete. However, the test may fail to detect low but risky levels of drinking. In addition, CAGE often performs less well among women and minority populations ( Mayfield et al. Am J Psych, 1974; Brown RL, Rounds LA. Wisconsin Med J, 1995. Daniel Alford, MD, MPH 7

27 Screening for Substance Abuse Disorders Using “Single” Questions
“Do you sometimes drink beer, wine, or other alcoholic beverages? How many times in the past year have you had 5 (4 for women) or more drinks in a day?” (+ answer: > 0) “How many times in the past year have you used an illegal drug or used a prescription medication for non-medical reasons?” (+ answer: > 0) To check for addiction to alcohol and other substance abuse, there are multiple screening instruments. Many are long and not very practical for a primary care setting, but some newer instruments, called “single item questions,” have been recommended. For alcohol – “Do you sometimes drink beer, wine, or other alcoholic beverages?” If the patient says “yes,” then you ask, “How many times in the past year have you had five or more drinks in a day (if it’s a man) or four or more drinks in a day (if it’s a woman)?” And any number greater than zero would be a positive screen for unhealthy alcohol use. For illicit or psychotherapeutic drugs – “How many times in the past year have you used an illegal drug or used a prescription medication for non-medical reasons?” Again, if the number is greater than zero, it would be considered positive. NIAAA. Clinicians Guide to Helping Patients Who Drink Too Much, 2007. Smith et al. Alcohol Clin Exp Res, Daniel Alford, MD, MPH

28 Comprehensive Drug Use Screening and Assessment: NIDA-Modified ASSIST
Interactive online screening tool, includes tobacco, alcohol, prescription, and illicit drugs Pre-screens patients for lifetime use 4 questions about substance use in past 3 months; and 2-3 follow-up questions for each substance used in lifetime Generates a numeric Substance Involvement score that suggests the level of medical intervention necessary NMASSIST Clinicians Resource Guide, includes: Step by step instructions for screening tool Scripts on how to discuss drug use with patients; and Information on biological specimen screening, sample progress notes/ worksheets, additional resources, and links to treatment facility locators (*May be deleted for one-hour version of presentation) The National Institute on Drug Abuse, part of the National Institutes of Health, adapted the well validated World Health Organization’s Alcohol, Smoking and Substance Involvement Screening Test (ASSIST -- version 3) and created a very user friendly interactive screening tool designed for clinical practices. There is a lifetime pre-screening question to screen all patients, but only those with any use will be asked the follow-up questions. While this tool includes tobacco, alcohol, and 9 illicit and prescription drug categories, only those drugs that have been used will be carried through the subsequent questions—thereby enabling the clinician to conduct a comprehensive screen in a relatively short amount of time. Following the lifetime question, patients will be asked: How often have you used in the past three months? There are then three followup questions asked for each substance the patient reported using in the past 3 months: How often have you had a strong desire or urge to use? How often has your use of [first drug, second drug, etc.] led to health, social, legal, or financial problems? How often have you failed to do what was normally expected of you because of your use of [first drug, second drug, etc]? The following 2-3 questions asked for each substance used in their lifetime: Has a friend or relative or anyone else ever expressed concern about your use of [first drug, second drug, etc.]? Have you ever tried and failed to control, cut down, or stop using [first drug, second drug, etc.]? Have you ever used any drug by injection? (nonmedical use only) Only if a patient has entered a drug that may be injected will they be asked the last question. Once the screening is complete, the tool generates a Substance Involvement (SI) score that tells you if a patient is high risk (score of 27 or greater); moderate risk (sore of 4-26); or lower risk (3 or less) for substance use disorders. The patient will receive an SI score for each substance endorsed, not a cumulative score. Therefore, the patient’s risk level may differ from drug to drug. For each risk category, the NMASSIST provides suggestions on next steps. The tool doesn’t collect any personally identifiable information and doesn’t store responses. The tool and resources can be found on the website noted on this slide. Daniel Alford, MD, MPH

29 Setting Goals: the Four A’s
Analgesia Activities of daily living Avoid Adverse events Avoid Aberrant medication-related behaviors After you have determined that the benefits of opioid treatment are greater than the risks, you must determine what the goals are for you and for your patient. Passik coined the “four A’s,” which include analgesia or pain relief, activities of daily living or improved function, avoiding adverse affects, and avoiding aberrant medication-related behaviors. Passik et al. Clin Ther, 2004. Daniel Alford, MD, MPH

30 Management of Opioid Therapy
Assess and document benefits and harms To continue opioids: There must be actual functional benefit Benefit must outweigh observed or potential harms You do not have to prove addiction or diversion, only assess risk-benefit ratio After you have started opioid therapy, you need to assess and document any benefits and harms. To continue opioids, there must be some actual functional benefit. Benefits must outweigh observed or potential harms. Remember, you don’t have to prove that the person has an addiction or that they are diverting; only assess the risk-benefit ratio to determine if they are getting more benefit than risk. Nicolaidis, C. Oregon Health and Science University, SGIM precourse, 2008. Daniel Alford, MD, MPH

31 SAFE Score Clinician-generated Four domains over past month
Social functioning (marital, family, friends, etc.) Analgesia (intensity, frequency, duration) Physical functioning (work, ADLs, home, etc.) Emotional functioning (stress, mood, etc.) Each scored on 5 point scale 1 (Excellent) to 5 (Poor) Total score Not validated (*May be deleted for one-hour version of presentation) The SAFE score is a tool that can help with assessing the outcome of opioid therapy. Although not yet vigorously validated, it is simple and practical. Generated by the clinician, it is meant to reflect a multidimensional assessment of opioid therapy. At each visit, the clinician rates the patient’s functioning and pain relief in four domains. The domains assessed include Social functioning, Analgesia, physical Functioning, and Emotional functioning. Together, the ratings in each of the 4 domains are combined to yield a “SAFE” score, which can range from 4-20. Smith HS. J Cancer Pain Symptom Palliation, 2005. Daniel Alford, MD, MPH

32 SAFE Score Green Zone (4-12) Yellow Zone (13-16 or 5 in any category)
Continue current medical regimen Consider reducing total dose Yellow Zone (13-16 or 5 in any category) Monitor closely Reassess frequently Red Zone (> 17) Change treatment (*May be deleted for one-hour version of presentation) Scores can be broken down into three categories – GREEN, YELLOW, and RED zones. The GREEN ZONE, represents a score of In this “zone,” the patient is considered to be doing well and can continue the present medication. The YELLOW ZONE, a score of 13-16, suggests that the patient should be monitored closely and reassessed frequently. The RED ZONE represents a score greater or equal to 17 and suggests that a change in treatment is warranted. Treatment decisions depend on the pattern of the scores – if attempts are made to address problems in specific domains and the patient is still not showing improvement in the SAFE score, the patient may not be an appropriate candidate for long-term opioid therapy. Smith HS. J Cancer Pain Symptom Palliation, 2005. Daniel Alford, MD, MPH

33 Monitoring, Monitoring, Monitoring… “Universal Precautions”
Contracts/Agreement form Drug screening Prescribe small quantities Frequent visits Single pharmacy Pill counts After starting a patient on opioids, careful monitoring is key. The concept of universal precautions is well known from the infectious disease world – e.g., prevent contracting HIV in healthcare settings by using gloves for everybody when we’re drawing blood, etc. Similarly, universal precautions for using controlled substances means everybody is treated the same, as if they are at risk. Precautions for all patients receiving opioid pain medication include: prescribing small quantities of medications requiring frequent visits especially early on conducting pill counts using controlled substance agreements monitoring with routine drug testing requiring the use of a single pharmacy FSMB Guidelines, 2004 ( Gourlay DL, Heit HA. Pain Med, 2005. Daniel Alford, MD, MPH

34 Contracts/Agreements/Informed Consent
PURPOSE: Educational and informational, articulate rationale and risks of treatment Articulate monitoring (pill counts, etc.) and action plans for aberrant medication-taking behavior Take “pressure” off provider to make individual decisions (Our clinic policy is…) Prototype: LIMITATIONS: Efficacy not well established (although no evidence of a negative impact on patient outcomes) No standard or validated form Pain Management Agreements – They may also be called contracts or consents. These agreements serve an educational and an informational role by articulating the rationale and risks of treatment. They articulate monitoring and action for aberrant medication-taking behavior, and importantly, they take the pressure off the provider to make individual decisions. It is easier to say, “Our clinic policy is to do urine drug testing,” or “It is our clinic policy to do pill counts,” than it is for a physician to say, “That’s my policy.” Prototypical contracts and agreements can be found at Although they are more widely used than in the past, their efficacy is not well-established, and there is no standard or validated form. However, there is no evidence that they have a negative impact on patient outcomes. Fishman SM, Kreis PG. Clin J Pain, 2002; Arnold et al. Am J of Medicine, 2006. Daniel Alford, MD, MPH

35 Informed Consent PURPOSE: A process of communication between a patient and physician that provides patients with the opportunity to ask questions to elicit a better understanding of the treatment or procedure, so that he or she can make an informed decision to proceed or to refuse a particular course of medical intervention. (*May be deleted for one-hour version of presentation) This is the definition of INFORMED CONSENT taken from the AMA’s Web site. American Medical Association. Office of General Counsel, March 2008 ( Daniel Alford, MD, MPH

36 Informed Consent SPECIFIC RISKS OF THE TREATMENT (long-term opioid use): Side effects (short and long term) Physical dependence, tolerance Risk of drug interactions or combinations (respiratory depression) Risk of unintentional or intentional misuse (abuse, addiction, death) Legal responsibilities (disposing, sharing, selling) (*May be deleted for one-hour version of presentation) Paterick et al. Mayo Clinic Proc, 2008.

37 Monitoring: Pill (and Used Patch) Counts
Pill and used patch counts are an underutilized method of monitoring medication adherence. Patients should be asked to bring in their unused pills at each visit before their prescription runs out, to ensure that the right number of pills remain in their possession. Patients should also be asked to bring in their used patches, namely fentanyl, because of the concern for diversion. Used fentanyl patches contain enough fentanyl to be extracted, abused, and diverted. Daniel Alford, MD, MPH

38 Monitoring: Urine Drug Tests
Purpose Evidence of therapeutic adherence Evidence of non-use of illicit drugs Results of study from pain medicine practice (n=122) 22% of patients had aberrant medication taking behaviors 21% of patients had NO aberrant behaviors BUT had abnormal urine drug test Therefore, aberrant behavior and urine drug test monitoring are both important. Katz et al. Clinical J of Pain, 2002.

39 Monitoring: Urine Drug Tests
Implementation Considerations Know limitations of test and your lab Be careful of false negatives and positives Talk with the patient: “If I check your urine right now will I find anything in it?” Random versus scheduled Supervised, temperature strips, check Cr Chain-of-custody procedures Issues and considerations to keep in mind: What are the limitations of urine drug testing? Commonly used medications may result in cross reactions. Patients may intentionally alter the results by ingesting adulterants. There are no standard procedures in labs regarding the assays or cutoffs employed, etc. What, exactly, is your lab testing for and how are they doing the testing? It is important for you to communicate with your lab to review possible false negatives and positives and cross-reactivity between over-the-counter medications and some of the controlled substances. You should be able to ask your lab colleagues, “Will Drug X show up as Drug Y?” Talk to your patients before sending the urine by just saying, “If I check your urine right now, will I find anything in it?” Sometimes, you will not need to send the urine, for instance if your patient is forthcoming about a recent relapse. Are you going to test randomly or scheduled—that is, every time patients come in for their visits they’re going to be tested, or will they actually get called in during a non-appointment to give urine? Will they be supervised to avoid patients bringing in someone else’s urine, or are you going to use temperature strips to make sure it’s a fresh urine specimen or check creatinine to make sure the urine has not been diluted with water. It is important to remember that chain-of-custody procedures are not in place in primary care practices, so these urine results are to be used for clinical purposes but not for legal purposes. You can never be 100% sure that the urine results you are getting from your lab are your patient’s. Gourlay DL, Heit HA, Caplan YH. Urine drug testing in primary care: Dispelling myths and designing strategies monograph ( Daniel Alford, MD, MPH

40 Prescription Monitoring Programs
State-instituted programs Electronic access to history of prescribed (and filled) scheduled drugs Required pharmacy data reporting States vary Reporting of Schedules (II or II-IV) Response to inquiries: reactive or proactive Safeguards for patient confidentiality (*May be deleted for one-hour version of presentation) One external monitoring source is a state's prescription monitoring program. Prescription monitoring programs can be helpful in identifying patients who are doctor shopping or pharmacy shopping. Over 30 states have legislation that requires prescription monitoring programs, however, characteristics of state programs vary. These state-instituted programs have electronic access to the history of prescribed (and filled) scheduled drugs and required pharmacy data reporting systems. Some programs report schedules II while others report schedules II through IV. Some are reactive and generate solicited reports only in response to specific inquiries, while others are proactive and generate unsolicited reports when suspicious trends are detected. All of these programs safeguard patient confidentiality. Daniel Alford, MD, MPH

41 Status of State Prescription Drug Monitoring Programs (PDMPs)
AK AL AR CA CO ID IL IN IA MN MO MT NE NV ND OH OK OR TN UT WA1 AZ SD NM VA WY MI GA KS HI TX ME MS WI2 NY PA LA KY NC SC FL NH MA RI CT NJ DE MD VT WV States with operational PDMPs States with enacted PDMP legislation, but program not yet operational (*May be deleted for one-hour version of presentation) This slide shows a map of the various states which have operational drug-monitoring programs and which states are in the process of putting one together but are not yet operational. These data are current as of June 30, Accessed October 8, 2009. 1These data should be updated as new data become available. 1Washington has temporarily suspended its PMP operations due to budgetary constraints. 2Legislation has been proposed in Wisconsin that ,if passed, would establish a PDMP. © 2009 Research is current as of June 30, THE NATIONAL ALLIANCE FOR MODEL STATE DRUG LAWS (NAMSDL) Prince St. Suite 312, Alexandria, VA

42 Not Enough Benefit? Reassess factors affecting pain
Re-attempt to treat underlying disease and co-morbidities Consider escalating dose as a “test” No effect = no benefit; hence, benefit cannot outweigh risks – so STOP opioids (Okay to taper and reassess) If there’s not enough benefit, reassess factors affecting pain, reattempt to treat underlying disease and co-morbidities, and consider escalating the dose as a “test.” Remember, this treatment is just a test, not something you’re necessarily committed to. If there’s not an effect with the increased medication dose and therefore no benefit of the medication (the benefit does not outweigh the risks), taper the opioids and then reassess. Nicolaidis, C. Oregon Health and Science University. SGIM precourse, 2008. Daniel Alford, MD, MPH

43 Too Much Risk? Differential dx for aberrant medication –taking behavior, then match action to cause: Miscommunication of expectations: patient education Unrelieved pain: change of dosage or medication Addiction: referral to addiction treatment Diversion: STOP medication If there’s too much risk based on the presence of aberrant medication-taking behavior to continue the use of opioids, one needs to inquire more deeply about what is going on with the patient. Has there been a miscommunication of expectations? Does the person have unrelieved pain? Has the patient developed an addiction? Has he or she started to divert the medication (selling it for income)? After making the appropriate “diagnosis,” match the action to the most likely cause. This could include, for example, if miscommunication –educate the patient; if inadequate pain control –change the medication or dosage; if diversion –stop the medication; if addiction –refer to addiction treatment and consider taper, etc. Nicolaidis, C. Oregon Health and Science University. SGIM precourse, 2008. Daniel Alford, MD, MPH

44 Case 42-year-old male with h/o total hip arthroplasty (THA) presented for 1st time visit with c/o hip pain One year ago displaced left femoral neck fracture requiring THA with subsequent chronic hip pain Pain managed by his orthopedist initially with oxycodone and more recently with ibuprofen Recent extensive reevaluation of his hip pain was negative Let’s review a case which will highlight many important issues around the management of chronic pain using long-term opioids. A 42-year-old man with a history of total hip arthroplasty presented for first-time visit with complaints of hip pain. One year ago he had a displaced left femoral neck fracture requiring total hip arthroplasty with subsequent chronic hip pain. His pain was managed by his orthopedist, originally with oxycodone and more recently with ibuprofen. Recent extensive reevaluation of his hip pain was negative. Daniel Alford, MD, MPH

45 Case continued Requested that his orthopedist prescribe something stronger like “oxys” for his pain as the ibuprofen was ineffective Told to discuss his pain management with his primary care physician (you) On disability since his hip surgery and lives with his wife and 2 children Denies current or past alcohol, tobacco, or drug use He requested that his orthopedist prescribe something stronger like “oxys” for his pain, as the ibuprofen was ineffective. He was told to discuss his pain management with his primary care physician (you). He’s been on disability since his hip surgery and lives with his wife and two children. He denies current or past alcohol, tobacco, or drug use. Daniel Alford, MD, MPH

46 Case Continued Meds: Ibuprofen 800 mg TID
Walks with a limp, uses a cane, vitals normal, 6 ft, 230 lbs Large, well-healed scar over the left lateral thigh/hip with no tenderness or warmth over the hip, full range of motion Doesn’t want to return to his orthopedist because “he doesn’t believe that I am still in pain” Currently, he’s on ibuprofen 800 mg three times per day. He walks with a limp and uses a cane. His vitals are normal. He’s 6 feet tall and weighs 230 pounds. He has a large, well-healed scar over the left lateral thigh and hip area with no tenderness or warmth over the hip. He has full range of motion. He doesn’t want to return to his orthopedist, because “he doesn’t believe that I’m still in pain.” Daniel Alford, MD, MPH

47 Are opioid analgesics indicated?
Case Continued In summary, 42-year-old man on disability with chronic hip pain who is requesting “oxycodone” Is he drug seeking? Are opioid analgesics indicated? Summary: a 42-year-old man on disability with chronic hip pain who is requesting oxycodone. The questions are: is he drug seeking and are opioid analgesics indicated? Daniel Alford, MD, MPH

48 Is the Patient “Drug Seeking?”
Directed or concerted efforts to obtain medication It is difficult to distinguish… …inappropriate drug-seeking from… …appropriate pain relief-seeking Is the patient “drug seeking”? “Drug seeking” is a directed or concerted effort to obtain a specific medication. It is difficult if not impossible to distinguish between inappropriate drug seeking and appropriate pain relief-seeking during the initial visit(s). Group discussion – were there any red or yellow flags in the case presentation? Vukmir RB. Am J Drug Alcohol Abuse, 2004. Daniel Alford, MD, MPH

49 3. Identifying Prescription Drug Abuse
Daniel Alford, MD, MPH

50 Red Flags Aberrant Medication-Taking Behavior more likely to be Suggestive of Addiction Deterioration in functioning at work or socially Illegal activities – selling, forging, buying from nonmedical sources Injection or snorting medication Multiple episodes of “lost” or “stolen” scripts Resistance to change therapy despite adverse effects Refusal to comply with random drug screens Concurrent abuse of alcohol or illicit drugs Use of multiple physicians and pharmacies What are the behaviors that are suggestive of a substance use disorder? Serious behaviors that are considered red flags include the following: Deterioration in functioning at work or socially Illegal activities—selling, forging, buying from nonmedical sources Using the medication in an inappropriate way like injecting it or snorting it Multiple episodes of “lost” or “stolen” scripts Resistance to change in therapy despite adverse effects (that is, the person is overly sedated, yet he or she wants more medication) Refusal to comply with monitoring like random drug screens Concurrent abuse of alcohol or illicit drugs Use of multiple physicians and pharmacies (not discussed openly as in the yellow flag scenario, but you find out about it some other way) Daniel Alford, MD, MPH

51 Aberrant Medication-Taking Behavior less likely to be Suggestive of Addiction
Yellow Flags Complaints about need for more medication Drug hoarding Requesting specific pain medications Openly acquiring similar medications from other providers Occasional unsanctioned dose escalation Nonadherence to other recommendations for pain therapy Some less obvious behaviors certainly could be suggestive of addiction. These are referred to as yellow flags: Complaints about need for more medication; Drug hoarding (which patients may do when they are afraid that if you retire they will have a hard time finding another physician who will continue their opioid prescription); Requesting specific pain medications (patients feel like they’re helping you out because they know which medications work, but again this could be a sign of addiction or somebody who is trying to sell a brand name medication); Openly acquiring similar medications from other doctors (if they are open about going to other doctors it is a yellow flag; it could be a sign of addiction, but not necessarily so); Occasional, unsanctioned dose escalation and non-adherence to other recommendations for pain therapy (they don’t go to physical therapy or they don’t go to the behavioral therapist that you sent them to). These are yellow flags. None of them alone would predict addiction, but if you identify multiple yellow flags, that would be concerning. Daniel Alford, MD, MPH

52 Current Opioid Misuse Measure (COMM™)
17-item self report for ongoing risk assessment Questions based on 6 primary concepts underlying medication misuse Helps to identify patients at high risk for current aberrant medication-taking behavior A high score raises concern for PDA but is NOT diagnostic (*May be deleted for one-hour version of presentation) The Current Opioid Misuse Measure (COMM™) can help clinicians identify whether a patient, currently on long-term opioid therapy, may be exhibiting aberrant behaviors associated with misuse of opioid medications. Since the COMM examines concurrent misuse, it is useful for helping clinicians monitor patients' aberrant medication-related behaviors over the course of treatment. Accessed October 8, 2009. Additional information: Use if time is available Concept mapping identifies six primary concepts underlying medication misuse that are used to develop an initial item pool: Inconsistent appointment patterns (healthcare use patterns) Signs/symptoms of drug misuse (signs/sx of intoxication) Poor response to medications (evidence of poor response to medications) Emotional problems/psychiatric issues (emotional volatility) Evidence of lying and illicit drug use (addiction) Medication misuse/abuse as well as noncompliance with medication (problematic medication behavior) Butler et al. Pain, 2007. Daniel Alford, MD, MPH

53 Should you increase his dose of oxycodone?
One Month Later He is currently taking oxycodone 5 mg 1 tablet every 6 hours (120/month) as you prescribed He rates his pain as “15” out of 10 all the time and describes no improvement in function Should you increase his dose of oxycodone? Let's return to the case presented earlier: One month later: The patient is currently taking oxycodone 5 mgs, every six hours, 120 per month, as you have prescribed. He rates his pain as “15” out of 10 all the time and describes no improvement in function. Should you increase his dose of oxycodone? Daniel Alford, MD, MPH

54 Opioid Responsiveness/Resistance
Degree of pain relief with Maximum opioid dose In the absence of side effects, e.g., sedation Not all pain is opioid responsive Varies among different types of pain Acute > Chronic Nociceptive > Neuropathic Varies among individuals It’s important to remember that not all pain is opioid-responsive and that some pain is resistant to opioids. The way we define opioid-responsiveness is the degree of pain relief with maximal opioid dose in the absence of side-effects, mainly sedation. Opioid responsiveness varies among different types of pain: Acute pain is more responsive than chronic pain. Nociceptive (musculoskeletal) pain is more responsive than neuropathic pain. There is also variability among individuals in terms of their responses to opioids for any given pain. Daniel Alford, MD, MPH

55 Pseudo-Opioid Resistance
Some patients with adequate pain relief believe it is not in their best interest to report pain relief Fear that care would be reduced Fear that physician may decrease efforts to diagnose problem However, patients may be exhibiting pseudo-opioid resistance, which can occur when patients with adequate pain relief believe it is not in their best interest to report pain relief. Why is that? One reason involves fear that their care would be reduced. That is, they’re getting benefit from the opioid, but as soon as they report that their pain has improved, their opioid dose will be decreased. A second reason involves fear that their provider will stop looking for what is causing their pain. Evers GC. Support Care Cancer, 1997. Daniel Alford, MD, MPH

56 Case continued Transition to sustained release morphine and signed controlled substance agreement After a stable period of several months, he surprises you by presenting without an appointment requesting an early refill Is he addicted? Back to the case: The patient is transitioned to sustained-relief morphine, and he signed a controlled substance agreement. After a stable period of several months, he surprises you by presenting without an appointment and requesting an early refill. Is he addicted? Daniel Alford, MD, MPH

57 Aberrant Medication-Taking Behavior
Daniel Alford, MD, MPH

58 Aberrant Medication-Taking Behaviors Differential Diagnosis
Inadequate analgesia – “Pseudoaddiction”1 Disease progression Opioid resistant pain (or pseudo-resistance)2 Addiction Opioid analgesic tolerance3 Self-medication of psychiatric and physical symptoms other than pain Criminal intent – diversion He’s not necessarily addicted, but he certainly has aberrant medication-taking behaviors and might even raise a red flag by coming in without an appointment. But there is a differential diagnosis. Is he just looking for pain relief? Does he have inadequate analgesia, also termed “pseudoaddiction”? Pseudoaddiction describes a patient with behaviors suggestive of addiction, but these behaviors disappear when the patient has pain relief. There could also be disease progression. Whatever was causing the pain originally has gotten worse. Or he might have opioid resistant pain or opioid analgesic tolerance – the opioid was working but now needs to be increased in dose. He may be self-medicating for psychiatric and physical symptoms other than pain (the opioid seems to be helping his depression, so he’s taking more of it). The patient may have developed an addiction to the opioid – remember to look for loss of control, compulsive use, continued use despite harm, and craving. And there’s always the possibility of criminal intent, that is, selling the opioid for income. 1 Weissman DE, Haddox JD. 1989; 2 Evers GC. 1997; 3 Chang et al Daniel Alford, MD, MPH

59 Approaching Patient with Aberrant Medication-Taking Behavior
Take non-judgmental stance Use open-ended questions State your concerns about the behavior Examine the patient for signs of flexibility More focused on specific opioid or pain relief Approach as if they have a relative contraindication to controlled drugs (if not absolute contraindication) So how do you approach the patient with aberrant medication-taking behavior? Take a non-judgmental stance and use open-ended questions. For example, give the person feedback about what is concerning you: “I’m concerned that you have run out of your prescription early. Can you tell me about that?” State your concerns about the behavior: “You didn’t leave your urine last time. Can you tell me more about that?” Examine the patient for signs of flexibility: “Are you willing to go to physical therapy now, since you’re not getting adequate relief from the medication by itself?” Determine whether the person is more focused on obtaining medication than on receiving pain relief. It might help to comment to patients: “It sounds like you’re more interested in increased medication than you are in following my recommendations for pain relief.” Passik SD, Kirsh KL. J Supportive Oncology, 2005. Daniel Alford, MD, MPH

60 Discussing Lack of Benefit
Stress how much you believe in/empathize with patient’s pain severity and impact Express frustration re: lack of good pill to fix it Focus on patient’s strengths Encourage therapies for “coping with” pain Show commitment to continue caring about patient and pain, even without opioid rx Schedule close follow-ups during and after taper Tips for discussing a lack of benefit such as no improvement in function or pain scores: Stress your belief in how severe your patient’s pain is and any impact it’s having on his or her life; Express frustration re: the lack of benefit of the medication that is being prescribed; Focus on the patient’s strengths and encourage therapies for coping with pain; Show commitment to continue caring for the patient and his or her pain, even without an opioid prescription; and Schedule a close follow-up during and after the taper. Daniel Alford, MD, MPH

61 Discussing Possible Addiction
Explain why aberrant behavior raises your concern for possible addiction Benefits no longer outweigh risks “I cannot responsibly continue prescribing opioids as I feel it would cause you more harm than good.” Always offer referral to addiction treatment Stay 100% in “Benefit/Risk of Med” mindset If you think the person has an addiction, explain why. Explain to the patient why all of the aberrant medication-taking behavior raises your concern for possible addiction. Explain how the benefits no longer outweigh the risks. For instance, “I can’t responsibly continue prescribing opioids, as I feel it would cause you more harm than good.” Always offer referral to addiction treatment. And again, stay one hundred percent in the benefit-risk framework. This person has more risk than benefit. Daniel Alford, MD, MPH

62 Stopping Opioid Analgesics
Patient is not improving and may have opioid-resistant pain Some patients experience improvement in function and pain control when chronic opioids are stopped Patient may have a new problem – “opioid dependence (addiction)” and may need substance abuse treatment Be clear that you will continue to work on pain management using non-opioid therapy Taper patient slowly to prevent opioid withdrawal When you have decided to stop opioid analgesics: The patient is not improving; he or she may have opioid resistant pain (some patients may actually experience improvement in function and pain when the opioids have stopped). The patient may have a new problem—“opioid dependence” or addiction. He or she may need substance abuse treatment. Be clear that you will continue to work on pain management using non-opioid therapy. Taper the patient slowly to avoid opioid withdrawal, and refer him or her to addiction treatment if needed. Daniel Alford, MD, MPH

63 Summary The use of opioid analgesic therapy requires careful assessment and tailored monitoring approaches Diagnosing addiction during pain management is difficult and requires careful monitoring Usual substance abuse risk factors probably apply to prescription opioid abuse Manage lack of benefit by tapering opioids Manage addiction by tapering opioids and referring to substance abuse treatment In summary: Use of opioid analgesic therapy requires careful treatment and tailored monitoring approaches. Diagnosing addiction during pain management requires careful monitoring. Usual substance abuse risk factors probably apply to prescription opioid abuse. Manage lack of benefit by tapering opioids and manage addiction by tapering opioids, referring to substance abuse treatment, and continued follow-up. Daniel Alford, MD, MPH


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