Case Objectives

• Define opioid dependence and opioid withdrawal syndrome.
• Describe the treatment of opioid withdrawal syndrome including the use of the Clinical Opioid Withdrawal Scale (COWS) and pharmacologic treatments.
• Appreciate the stigma associated with opioid dependence and the potential impact on the quality of care provided.

Case & Commentary: Part 1

A 56-year-old man with a long history of heroin use presented to the hospital with abdominal pain, nausea, and vomiting. He said he had been using less heroin than usual because of the gastrointestinal complaints and felt that his symptoms were probably from heroin withdrawal. On initial evaluation, he was dehydrated, but his vital signs were unremarkable and his abdominal examination was benign. His complete blood count, liver function tests, amylase, and lipase were all normal, and an upright KUB radiograph showed no clear cause for his abdominal pain. He was admitted to the hospital for treatment of dehydration and opiate withdrawal and was given intravenous fluids, methadone, and low doses of morphine intravenously for the abdominal pain.

Later in the evening of admission, he complained of increasing diffuse abdominal pain. He also complained of excessive yawning and increased lacrimation. On physical examination, he was tachycardic, tachypneic, and generally restless, but had a nontender abdominal examination. He was given increased methadone to treat presumed worsening opiate withdrawal.

Opioid dependence is a treatable chronic medical illness that afflicts as many as 6 million persons in the United States. Unfortunately, many providers are uncomfortable caring for patients with opiate dependence, unwilling to do so, or simply uninformed about appropriate treatment strategies. This case provides an opportunity to discuss the basics of opiate dependence and opiate withdrawal.

The medical disorder opioid dependence is defined as a maladaptive pattern of use of illicit or prescription opioids leading to clinically significant impairment or distress as manifested by three or more diagnostic criteria in the past 12 months.(1) These diagnostic criteria include physical dependence, tolerance, taking opioids in larger amounts or for longer periods than intended, desiring to cut down or control use, dedicating a large amount of time to procuring opioids or recovering from their effects, giving up important activities because of their use, and using opioids despite knowledge of harm. Unfortunately, the terminology for this disorder is confusing. Physical dependence on an opioid is just one of the seven criteria for the diagnosis of opioid dependence, and patients who are not physically dependent on opioids can still have opioid dependence if they meet three other criteria. A common illicit opioid is heroin, but any opioid pain medication can be "diverted" to illicit use, including hydrocodone and long-acting oxycodone.

Opioid dependence is not a trivial problem. More than 3 million Americans have used heroin in their lifetime.(2) According to the Office of National Drug Control Policy, there were an estimated 810,000 to 1,000,000 individuals addicted to heroin in the United States in the year 2000, representing the highest number of heroin-addicted persons in this country since the late 1970s.(3) Furthermore, the National Institute on Drug Abuse (NIDA) Monitoring the Future Survey reported that as many as 10.5% of 12th graders reported using hydrocodone within the last year.(4) Several factors contribute to this increased use. First, in the late 1990s, the purity of heroin increased—heroin purity now may be as high as 80%–90% in large urban areas. The increase in purity has increased use of heroin by noninjection routes of administration, including snorting and smoking. Indeed, one survey found that only one third of new users of heroin actually inject it.(3) Not only are illicit opioids available and pure, they are cheap: it is not unusual to be able to buy a supply of heroin (for one "hit") for less than $10. Interestingly, this "street price" is much cheaper than that of diverted prescription opioid medications.

Another reason for the increase in opioid dependence is the dramatic increase of drug diversion (use of a drug outside the scope of its intended purpose). In 2000, 2 million people used prescription pain relievers for nonmedical reasons for the first time (5), and from 1999 to 2000, the Drug Abuse Warning Network (DAWN) reported a 68% increase in illicit use of oxycodone products.(6) Furthermore, according to the DAWN Mortality Data Report, hydrocodone ranked among the 10 most common drugs related to deaths in 18 cities. Also, persons who misuse prescription opioid medications are more likely to eventually use illicit and illegal opioids that include heroin.

This increase in opioid addiction has exacted tremendous medical and societal costs. Illicit opioid use—either heroin use or prescription opioid misuse—is associated with significant harm to individuals and burdens limited health care resources. Major medical and psychiatric illnesses often coexist with opiate addiction. For example, depression, hepatitis infection (primarily hepatitis C), and HIV are all common in patients who have opioid dependence. Violence and crime are also associated with opioid dependence.

We are told that the patient in this case has a long history of heroin use and likely suffers from the disorder of opioid dependence. The patient's symptoms as described are consistent with classic opioid withdrawal. Opioid withdrawal is defined diagnostically as three or more symptoms that include dysphoric (negative) mood, nausea or vomiting, muscle aches, runny nose or watery eyes, dilated pupils, goose bumps or sweating, diarrhea, yawning, fever, and insomnia. In my clinical experience, patients sometimes complain of abdominal cramping or bony pain ("Doc, it's in my bones"), but overt abdominal pain (as seen in this case) is less common. The withdrawal symptoms cause significant distress to the individual and often impair functioning in activities of daily living. Opioid withdrawal symptoms may be so severe and aversive that many opioid-dependent individuals continue to use the drugs only to avoid withdrawal. The nature and severity of the opioid withdrawal syndrome depend on the individual, the opioid pharmacology (short- vs. long-acting), and the standard dose used. Research has recently shown benefit for monitoring opioid withdrawal using objective measures such as the Clinical Opioid Withdrawal Scale (COWS).(7) An objective measure was not used in this case, but given the constellation of symptoms, a presumptive diagnosis of opioid withdrawal was made.

How should this patient's opiate withdrawal be treated? Because opioid withdrawal syndrome, while aversive, is not deadly, many insurers will not pay for a hospitalization for only treatment of opioid withdrawal. Partly for this reason, opiate withdrawal is generally managed in the outpatient setting in methadone treatment facilities (or in licensed opioid agonist therapy [OAT] programs). Occasionally, patients like this one are admitted to a nonmethadone facility (e.g., hospital) for another illness, and opioid dependence treatment using opioids is necessary to help treat the primary illness (e.g., an acute myocardial infarction in a patient with heroin withdrawal). Management of opioid withdrawal in these patients can be difficult. The primary concern should be managing the acute medical illness and stabilizing the patient undergoing opioid withdrawal. In the case of a patient with an acute illness and opioid withdrawal (like the patient who presented in our case) who does not want long-term treatment for their opioid dependence, a short, tapering "detoxification" course of opioids is often used. In both outpatient and inpatient settings, both methadone and buprenorphine can be used to treat opioid withdrawal as well as to provide longer term maintenance treatment for opiate dependence.

Emerging evidence suggests that a short, decreasing dose course of either methadone or buprenorphine can ameliorate the symptoms of withdrawal while acute medical issues are addressed. Doses used depend on several factors including the patient's level of physical opioid dependence, the type of opioids illicitly used, and the nature of the acute medical illness. Typically, detoxification treatment lasts less than 2 weeks, and there are several protocols available and studied.(8) Emerging research has also outlined detoxification protocols using buprenorphine and its potential preferential benefits as a first-line pharmacologic agent.(9-17)

If long-term treatment of opioid dependence is a goal for patients needing detoxification for an acute medical illness, patients should be offered maintenance OAT during their hospitalization. It is well established that maintenance OAT is preferred over detoxification to reduce the morbidity and mortality of the disease of opioid dependence.(18) Most providers are aware that methadone is the mainstay of pharmacologic treatment of opioid dependence, but methadone can only be prescribed for opioid dependence treatment within OAT programs or when patients with opiate dependence are admitted to an acute care hospital for other medical issues. Buprenorphine is another effective medical treatment of opioid dependence (e.g., maintenance OAT) and can also be used as a pharmacologic treatment of opioid withdrawal syndrome. In 2002, Congress amended the Drug Abuse Treatment Act (DATA 2000), allowing credentialed and Drug Enforcement Administration (DEA)-waivered physicians to prescribe buprenorphine and buprenorphine/naloxone (both Schedule III medications) for OAT in office-based practices.(19) Like methadone OAT for use in licensed methadone OAT programs, buprenorphine administered in office-based practices is effective at reducing illicit opioid use, drawing patients into treatment, and reducing harm associated with comorbid medical and psychiatric illnesses.(20-26) Clinical studies suggest that patients maintained on buprenorphine for a period of time do better than patients who are merely "detoxified" using buprenorphine.(18)

In this case, the provider's original working diagnosis was opioid withdrawal syndrome. Even when this diagnosis is strongly suspected, a full and complete history and physical examination as well as appropriate laboratory studies should be performed. Other medical disorders, such as pain syndromes, can mimic opioid withdrawal syndrome. In addition, many patients with opiate dependence present with comorbid conditions of HIV, hepatitis C, or skin infections—all consequences of intravenous injection of illicit opioids. These disorders may require specific treatment or may influence the treatment of other illnesses.

In the patient in this case, the overt abdominal pain would lead me to consider other diagnoses. The patient's yawning, lacrimation, tachycardia, tachypnea, and general restlessness are consistent with opioid withdrawal. His nontender abdominal examination also would be consistent with this diagnosis. However, prescribing intravenous morphine would generally not be my initial treatment of choice for opioid withdrawal if that was the only medical condition needing attention. Detoxification using buprenorphine (or potentially methadone) would better assist in transitioning care from a detoxification treatment to longer term maintenance therapy using buprenorphine or methadone. Although that would represent my usual practice, in this case, because the patient has abdominal pain of unclear etiology, intravenous morphine may be a good option. As a short-acting treatment, I would be able to monitor the acuity of abdominal pain to determine whether it was due to atypical opioid withdrawal. In addition, introduction of buprenorphine in this patient, who may need surgical management of his acute condition, may complicate his perioperative pain management. Buprenorphine is a partial opioid agonist, and as a result of its high receptor affinity, traditional doses of perioperative pain medications may not readily displace buprenorphine from the opioid receptor and thus may not have the necessary analgesic effect.(27)

The bottom line is that, at this point, it would be appropriate to evaluate the patient for other causes of his abdominal pain and worsening condition.

Case & Commentary: Part 2

Despite increasing the methadone, the patient's abdominal pain persisted and worsened. A covering physician was contacted overnight about the abdominal pain. The nurse told the physician that the patient had asked for something stronger for the pain. Because the daytime physician had earlier described the patient as a "strung out shooter," the covering physician believed that the patient was either drug seeking through his complaints of pain or not receiving enough methadone. Instead of reevaluating or reexamining the patient, the covering physician ordered another increase in the dose of methadone. Overnight, the patient continued to have diffuse abdominal pain and tachycardia.

In the morning, the patient's abdominal pain became severe, his tachycardia worsened, and his blood pressure decreased, indicating a possible infection (septic shock). He was given aggressive intravenous fluids, and his abdominal computed tomography scan (CT) revealed a perforated colon, likely from diverticulitis. The patient then underwent successful colonic resection and was discharged from the hospital 2 weeks later.

The patient's worsening condition in the face of opioid agonist therapy should have given the covering physician pause, and another diagnosis should have been strongly entertained. Unfortunately, the stigma associated with having an alcohol or drug use problem can contribute to misdiagnosis or delays in diagnosis. There is general consensus that physicians and other health care providers have negative perceptions about patients with alcohol and other drug disorders (28-30)—attitudes that may result in worse health outcomes. For example, 23% of HIV-infected patients had physicians with negative attitudes toward patients who were injection drug users. Injection drug users who were cared for by physicians with negative attitudes had a significantly lower adjusted rate of treatment with highly active antiretroviral therapy than non–injection drug users who were cared for by such physicians or injection drug users who were cared for by physicians with positive attitudes.(28) Although not stated explicitly in the case presentation, the covering provider may have been biased by the description of the patient as a "strung-out shooter" and treated him differently.

Physicians also have lower satisfaction in treating patients with alcohol and other drug disorders than in treating those with other medical illnesses.(31) This is somewhat surprising. Comparing alcohol and drug disorder diseases with other chronic care diseases, relapse rates to unhealthy behavior (e.g., alcohol use in an alcohol-dependent patient; poor diet control in a patient with diabetes) are comparable.(32) Fewer than 40% of patients adhere to their antihypertensive regimens, fewer than 30% of patients adhere to the recommended diet or behavioral changes, and 50%–70% of hypertensive patients experience a relapse of their disease annually. These rates are comparable to a relapse rate between 40%–60% for alcohol and other drug use disorders.(32-34)

Considering the effects of alcohol and other drug use disorders on patients and their environment, and the effective evidence-based treatments that are available for these disorders, it is unfortunate that health care providers may not appropriately screen, identify, and treat them. How do clinicians ensure that patients with alcohol and other drug use receive equal, high-quality care? In my experience, the first step is to recognize that alcohol and other drug disorders are chronic medical illnesses that are never quickly fixed. Improved education in substance abuse disorders for trainees and practicing clinicians may also improve the quality of care. Hospitals and health care systems should consider structured mechanisms to ensure appropriate treatment of opioid dependence and opioid withdrawal.

Take-Home Points

• Opioid dependence is a chronic, treatable medical condition.
• The Clinical Opioid Withdrawal Scale (COWS) can be a useful objective measure of opioid withdrawal.
• Methadone and buprenorphine treatments are available for both opioid dependence and opioid withdrawal syndrome.
• Providers should be suspicious of atypical presentations of opioid withdrawal and evaluate patients accordingly.

Adam J. Gordon, MD, MPH Assistant Professor of Medicine, Advisory Dean University of Pittsburgh School of Medicine

Faculty Disclosure: Dr. Gordon has declared that neither he, nor any immediate member of his family, has a financial arrangement or other relationship with the manufacturers of any commercial products discussed in this continuing medical education activity. In addition, his commentary does not include information regarding investigational or off-label use of pharmaceutical products or medical devices.

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV. 4th ed. Washington, DC: American Psychiatric Publishing; 1995:196-205.

2. Substance Abuse and Mental Health Services Administration. Summary Findings from the 1999 National Household Survey on Drug Abuse. Rockville, MD: Substance Abuse and Mental Health Services Administration, US Dept of Health and Human Services; 2000. DHHS Publication No. SMA 01-3514.

3. National Household Survey on Drug Abuse. Rockville, MD: Substance Abuse and Mental Health Services Administration, US Dept of Health and Human Services; 1999.

4. Substance Abuse and Mental Health Services Administration. Emergency Department Data from the Drug Abuse Warning Network: Final Estimates 1995-2002. Rockville, MD: Substance Abuse and Mental Health Services Administration, US Dept of Health and Human Services; 2003. DHHS Publication No. SMA 03-3780.

5. National Household Survey on Drug Abuse. Rockville, MD: Substance Abuse and Mental Health Services Administration, US Dept of Health and Human Services; 2001.

6. Substance Abuse and Mental Health Services Administration. Year-end 2000 Emergency Department Data from the Drug Abuse Warning Network. Rockville, MD: Substance Abuse and Mental Health Services Administration, US Dept of Health and Human Services; 2001. DHHS Publication No. SMA 01-3532.

7. Wesson DR, Ling W. The clinical opiate withdrawal scale (COWS). J Psychoactive Drugs. 2003;35:253-259. [go to PubMed]

8. Fishbain DA, Rosomoff HL, Cutler R. Opiate detoxification protocols. A clinical manual. Ann Clin Psychiatry. 1993;5:53-65. [go to PubMed]

9. White R, Alcorn R, Feinmann C. Two methods of community detoxification from opiates: an open-label comparison of lofexidine and buprenorphine. Drug Alcohol Depend. 2001;65:77-83. [go to PubMed]

10. O'Connor PG, Carroll KM, Shi JM, et al. Three methods of opioid detoxification in a primary care setting. A randomized trial. Ann Intern Med. 1997;127:526-530. [go to PubMed]

11. Johnson RE, Fudala PJ, Collins CC, Jaffe JH. Outpatient maintenance/detoxification comparison of methadone and buprenorphine. NIDA Res Monogr. 1989;95:384. [go to PubMed]

12. DiPaula BA, Schwartz R, Montoya ID, Barrett D, Tang C. Heroin detoxification with buprenorphine on an inpatient psychiatric unit. J Subst Abuse Treat. 2002; 23:163-169. [go to PubMed]

13. Marsch LA, Bickel WK, Badger GJ, et al. Comparison of pharmacological treatments for opioid-dependent adolescents: a randomized controlled trial. Arch Gen Psychiatry. 2005;62:1157-1164. [go to PubMed]

14. Seifert J, Metzner C, Paetzold W, et al. Detoxification of opiate addicts with multiple drug abuse: a comparison of buprenorphine vs. methadone. Pharmacopsychiatry. 2002;35:159-164. [go to PubMed]

15. Gowing L, Ali R, White J. Buprenorphine for the management of opioid withdrawal. Cochrane Database Syst Rev. 2004:CD002025. [go to PubMed]

16. Ling W, Wesson DR. Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug Alcohol Depend. 2003;70(suppl 2):S49-S57. [go to PubMed]

17. Amass L, Ling W, Freese TE, et al. Bringing buprenorphine-naloxone detoxification to community treatment providers: the NIDA Clinical Trials Network field experience. Am J Addict. 2004;13(suppl 1):S42-S66. [go to PubMed]

18. Kakko J, Svanborg KD, Kreek MJ, Heilig M. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: a randomised, placebo-controlled trial. Lancet. 2003;361:662-668. [go to PubMed]

19. Jaffe JH, O'Keeffe C. From morphine clinics to buprenorphine: regulating opioid agonist treatment of addiction in the United States. Drug Alcohol Depend. 2003;70:S3-S11. [go to PubMed]

20. Sullivan LE, Barry D, Moore BA, et al. A trial of integrated buprenorphine/naloxone and HIV clinical care. Clin Infect Dis. 2006;43:S184-S190. [go to PubMed]

21. Fiellin DA, Pantalon MV, Chawarski MC, et al. Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence. N Engl J Med. 2006;355:365-374. [go to PubMed]

22. Johnson RE, Strain EC, Amass L. Buprenorphine: how to use it right. Drug Alcohol Depend. 2003;70:S59-S77. [go to PubMed]

23. Johnson RE, Chutuape MA, Strain EC, et al. A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. N Engl J Med. 2000;343:1290-1297. [go to PubMed]

24. Fudala PJ, Bridge TP, Herbert S, et al. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. N Engl J Med. 2003;349:949-958. [go to PubMed]

25. Strain EC, Stitzer ML, Liebson IA, et al. Buprenorphine versus methadone in the treatment of opioid dependence: self-reports, urinalysis, and addiction severity index. J Clin Psychopharmacol. 1996;16:58-67. [go to PubMed]

26. Stein MD, Cioe P, Friedmann PD. Buprenorphine retention in primary care. J Gen Intern Med. 2005;20:1038-1041. [go to PubMed]

27. Roberts DM, Meyer-Witting M. High-dose buprenorphine: perioperative precautions and management strategies. Anaesth Intensive Care. 2005;33:17-25. [go to PubMed]

28. Ding L, Landon BE, Wilson IB, et al. Predictors and consequences of negative physician attitudes toward HIV-infected injection drug users. Arch Intern Med. 2005;165:618-623. [go to PubMed]

29. Wilson L, Kahan M, Liu E, et al. Physician behavior towards male and female problem drinkers: a controlled study using simulated patients. J Addict Dis. 2002;21:87-99. [go to PubMed]

30. Karam-Hage M, Nerenberg L, Brower KJ. Modifying residents' professional attitudes about substance abuse treatment and training. Am J Addict. 2001;10:40-47. [go to PubMed]

31. Saitz R, Friedmann PD, Sullivan LM, et al. Professional satisfaction experienced when caring for substance-abusing patients: faculty and resident physician perspectives. J Gen Intern Med. 2002;17:373-376. [go to PubMed]

32. McLellan AT, Lewis DC, O'Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000;284:1689-1695. [go to PubMed]

33. Finney JW, Moos RH. The long-term course of treated alcoholism: II. Predictors and correlates of 10-year functioning and mortality. J Stud Alcohol. 1992;53:142-153. [go to PubMed]

34. Hubbard RL, Craddock SG, Anderson J. Overview of 5-year followup outcomes in the drug abuse treatment outcome studies (DATOS). J Subst Abuse Treat. 2003;25:125-134. [go to PubMed]