The management of active heroin users in the inpatient setting is often challenging. A clinical scenario of an active heroin user who is hospitalized for a medical illness is used to illuminate issues pertinent to the successful treatment of opioid addiction as part of a comprehensive management plan. Central to achieving a successful outcome is recognizing and addressing heroin addiction early in the physician–patient encounter. Other important elements include developing an appropriate plan to treat withdrawal symptoms and communicating it to the patient and other caregivers, monitoring the patient to ensure the treatment is effective, and exploring opportunities for linkage to primary care and substance use treatment at discharge. The use of methadone for the treatment of moderate-to-severe opiate withdrawal is addressed and regulations surrounding the use of methadone in the hospital setting are clarified.

Effective care of the hospitalized patient with a comorbid opioid addiction is often challenging. This article highlights essential elements of the assessment and management of the hospitalized opiate-addicted patient, focusing on the use of methadone in the treatment of moderate-to-severe withdrawal symptoms and clarifying hospital regulations about the use of methadone.

Hypothetical Clinical Scenario
A 30-year-old man is admitted for evaluation and treatment of suspected endocarditis. He has a 10-year history of heroin addiction (administered by injection), and records indicate that during previous hospitalizations he left against medical advice. During this hospitalization, he repeatedly leaves the floor, presumably to use heroin. This is interfering with the timely evaluation and treatment of his current medical condition and creates concerns about possible infection of his intravenous (IV) line. How can you work with this patient to achieve a successful therapeutic outcome?

In this scenario, the patient accepted hospitalization, because he desired appropriate medical treatment for endocarditis. A competing priority for him, however, is to avoid opiate withdrawal symptoms, and thus he continues to secretly inject heroin while in the hospital. Recognizing and addressing the patient’s addiction early in the course of the medical treatment is crucial. Inadequate attention to withdrawal symptoms by the medical staff may frustrate efforts to evaluate and treat his presenting problem, and failure to establish a therapeutic alliance with this patient represents a missed opportunity to counsel him about ways to reduce his risks for medical complications of IV drug use, to facilitate referral to drug addiction treatment, and to refer him to primary care.

Opioid Withdrawal
In contrast to alcohol and sedative withdrawal, heroin withdrawal is generally not thought to be life-threatening. It can, however, be very distressing, physically and psychologically. The signs and symptoms associated with opiate withdrawal are listed in Table 1. Withdrawal from heroin typically begins 3 to 6 hours after the last use, peaks within 36 to 72 hours, and subsides over 7 to 10 days. Mild withdrawal is described as a flulike syndrome that includes gastrointestinal (GI), autonomic, and psychological symptoms. Moderate-to-severe withdrawal is characterized by inconsolable restlessness; persistent nausea, vomiting, and diarrhea; and intense cravings, anxiety, and dysphoria. Many addicts rapidly return to drug use at the onset of withdrawal symptoms.

Assessing addiction
Physicians may think that patients who use illicit drugs will attempt to withhold information about their drug use patterns, and many patients indeed do, with good reason—once they reveal their addiction, the approach to their treatment often changes; they are usually treated worse than patients not suspected of abusing illicit drugs. An active heroin user facing hospitalization is likely to have significant concerns about the prospect of undergoing drug withdrawal. Displaying an understanding by the physician of the anticipated withdrawal can go a long way toward establishing a therapeutic alliance with the patient. With direct, nonjudgmental questions, the physician should be able to obtain enough information to anticipate symptoms and adequately manage them. Drugs used on a daily basis (especially alcohol, opioids, and benzodiazepines) should be determined, as well as the quantity and frequency of use, the route(s) of administration, and the time of last use. Previous episodes of withdrawal should be assessed, including information about what did and did not help alleviate symptoms.

Forming a therapeutic alliance
Patients at risk for opiate withdrawal should be assured that withdrawal symptoms will be managed as part of the overall treatment plan. It is often helpful to explicitly outline an agreement about the goals of the overall hospitalization, including symptom relief and any anticipated tapering of medications before discharge. This discussion may include an agreement to manage withdrawal symptoms by standing orders rather than reliance on the patient’s request for as-needed medications. This may serve to better manage patient discomfort and avoid the perception of “drug-seeking behavior” by the staff. To prevent miscommunication and frustration, it is extremely important to communicate to other caregivers (eg, night floats, nursing staff) the plan for how to manage the specific patient’s withdrawal.

Managing Withdrawal Symptoms
Although hospitalization of an opioid-addicted patient represents an opportunity to address the addiction, the primary goal of the management of withdrawal symptoms in this setting is to minimize patient discomfort to facilitate the evaluation and treatment of the presenting acute medical condition. Treatment of opiate withdrawal should be based on the severity of the symptoms and the severity of the patient’s underlying medical condition (Table 2). Specifically, withdrawal in the presence of life-threatening conditions, such as acute coronary syndrome, tachyarrhythmias, increased intracranial pressure, respiratory compromise, or upper GI bleeding, requires careful monitoring and aggressive treatment to avoid autonomic instability that can exacerbate these conditions.¹

Before initiating treatment, all vital signs should be recorded, because fluctuations can occur secondary to opiate intoxication and withdrawal, or secondary to medications used to treat withdrawal symptoms, such as clonidine HCl (Catapres) or methadone. A mental status examination focused on the level of alertness and mood will assist in adjusting treatment to minimize anxiety and dysphoria. In addition, it is important to assess the patient’s level of pain (eg, caused by trauma, infection), and determine whether opiates will be required for pain management. Consultation with an addiction medicine specialist is recommended whenever possible.

Mild symptoms
The autonomic, GI, and psychological manifestations of mild withdrawal may be managed primarily symptomatically. Clonidine may help decrease opiate cravings.²

Moderate-to-severe symptoms
Patients who have moderate-to-severe withdrawal symptoms or who are medically unstable may best be managed with opiates, particularly with methadone.³ An initial dose of 20 to 30 mg daily is an appropriate starting point for many patients; consider 40 to 60 mg daily for an individual who uses 1 g/day of average-purity heroin. Patients who use high-purity heroin or synthetic opioids may ultimately require much higher doses.⁴

Methadone is effective within 30 minutes, and doses can be gradually increased over 4 to 12 hours, based on symptoms. Peak doses of methadone should be reached on withdrawal day 2 or 3. If no plan for long-term substance treatment is established, methadone can be tapered, with a 15% to 20% dose reduction daily, as tolerated.³ Methadone may be administered intramuscularly (as one half the oral dose, divided twice daily) in patients who cannot take oral medications. The methadone maintenance dose ranges from 60 to 100 mg/day; the physician must start low to avoid the respiratory depressant effect of opiates.⁵ Reassessment is essential to titrating up.

Methadone
Adverse effects
Methadone is metabolized by the cytochrome (CY) P-450 enzyme system in the liver and thus should be used with caution in patients with severe liver disease. In addition, methadone can interact with several drugs, some of which are listed in Table 3. Coinducers of CYP-450 (eg, antiretrovirals, anticonvulsants) may accelerate metabolism rate, thereby decreasing the effect of methadone. Conversely, CYP-450 inhibitors (eg, azoles, macrolides, selective serotonin reuptake inhibitors) may decrease metabolism of and potentiate the effect of methadone.

Common adverse events associated with methadone include constipation, sweating, and mild nausea. Less common effects are facial flushing, pruritus, insomnia, urinary retention, and bradycardia. Biliary spasm, urticaria, syncope, fatal overdose, and torsades de pointes are rare occurrences.^6,7

Outpatient maintenance
Patients receiving methadone maintenance in the outpatient setting should continue with their usual dose while in the hospital. Most patients will be able to provide the name and location of the treatment program, their usual dosage, and the time of their last dose. This information should be verified with the program. In addition, the program should be notified that the patient is receiving methadone in the hospital to avoid subjecting the patient to penalties. Outpatient treatment programs can be located at www.findtreatment.samhsa.gov.

Pain control
Some physicians hesitate to use opioids for pain control in patients addicted to opiates or those using methadone maintenance, but opioids can be safely and effectively used in these individuals.⁸ It is important to keep in mind, however, that such patients may be tolerant to the analgesic effects and will likely require higher doses of short-acting opioids for pain control. Frequent monitoring and appropriate titration of medications is necessary. In general, standing instructions with “patient may refuse; hold for sedation” are better than “as needed” for the patient and for the nursing staff.

Regulations governing the use of methadone
Methadone is a highly regulated substance in the United States. Uncertainties regarding these regulations may serve as a disincentive for physicians to prescribe the drug in the hospital setting. Methadone maintenance treatment for opiate addiction emerged in the 1960s, but by 1974 restrictions were put in place that greatly limited the ability of physicians to treat opiate-addicted individuals in the outpatient setting.⁹

Current federal regulations governing the use of methadone state that outpatient detoxification or maintenance treatment must occur in a licensed outpatient treatment program. However, if an opiate-dependent person is admitted to a hospital because of a medical condition, any physician with an unrestricted Drug Enforcement Administration (DEA) license may prescribe methadone to treat withdrawal symptoms. No additional licensure or credentialing is required. “Certification as an opioid treatment program will not be required for the maintenance or detoxification treatment of a patient who is admitted to a hospital or long-term care facility for the treatment of medical conditions other than opiate addiction and who requires maintenance or detoxification treatment during the period of his or her stay in that hospital or long-term care facility.”¹⁰

Of note, because methadone can be used to treat withdrawal only in the inpatient setting or in a specially licensed methadone treatment program, it is critical that the physician and the patient understand that methadone must be completely tapered before discharge unless the patient is being transferred to a methadone treatment program.³ Local methadone programs may choose to accept or refuse patients immediately upon hospital discharge (depending on space availability or varying admission policies and procedures). If possible, however, it is acceptable under current regulations to discharge a patient using methadone directly to an outpatient treatment program. Consultation with the hospital’s social services department may facilitate direct contact with a methadone treatment program to coordinate a counselor’s evaluation before discharge. This is extremely beneficial when patients are open to change.

Buprenorphine
A second medication that may be considered for the opioid-addicted patient is sublingual buprenorphine HCl (Subutex), a partial opiate agonist/antagonist. As a partial agonist, its opioidlike effects plateau with increasing dosages. Because of its antagonist properties, buprenorphine should be used only when the patient is in withdrawal, to avoid precipitating an acute withdrawal syndrome. The initial recommended dose is 4 to 8 mg/day, which can be doubled if needed, and then tapered over several days.

Like methadone, buprenorphine can be prescribed by physicians in the hospital for opiate withdrawal. Unlike methadone, however, buprenorphine is also approved for outpatient opiate addiction treatment. Physicians may prescribe buprenorphine in outpatient clinics after completing a minimum of 8 hours of addiction medicine training.

Training is provided by a variety of organizations, including the American Society of Addiction Medicine, the American Academy of Addiction Psychiatry, and the American Medical Association (www.buprenorphine.samhsa.gov/training.html).

Addressing Harm Reduction
Hospitalization presents a unique opportunity for the substance-using patient to access services for addiction. Although the risk for relapse after short-term detoxification is high, referral to a substance abuse treatment center from the hospital can be effective. One study found that 52% of the 67 referred patients completed the 6-month outpatient program.¹¹ Successful linkage to substance abuse treatment may be the most important service a physician can provide to an active heroin user. Methadone maintenance treatment is highly effective for opiate dependence, and individuals maintained on methadone demonstrate superior outcomes, including reduced mortality, decreased criminality, and improved social functioning.¹²

A “harm reduction” approach should be adopted to educate addicts who are unprepared to consider abstinence or addiction treatment. Harm reduction involves recognizing the reality of a patient’s ongoing drug use and providing education about ways to reduce the health risks associated with continued use. The patient should be given information on methods of safe injection, including the use of clean needles and works (ie, the paraphernalia for injecting heroin, such as spoons and syringes), sterile injection techniques, and the safe disposal of needles. Depending on local regulations, sterile syringes may be available by physician prescription, for purchase from pharmacies without a prescription, or through needle exchange programs (for more information visit www.harmreduction.org).

Conclusion
Substance-using individuals often distrust the medical system. They may have had unsatisfactory experiences, or they may fear having to endure withdrawal symptoms. Assessing the patient’s risk of withdrawal and discussing the plan for managing the symptoms are critical components of a therapeutic alliance with the patient. Any physician with a standard unrestricted DEA license may prescribe methadone or buprenorphine in the hospital. Hospitalization for a serious illness may serve as a catalyst for a substance-using patient to consider treatment. Caring for a patient who is also struggling with addiction involves offering resources for the treatment of substance abuse.

Grant Support
This manuscript was supported in part by a grant from the Medicine as a Profession Program of the Open Society Institute and by grant number P30-AI-42853 from the National Institutes of Health, Center for AIDS Research (NIH/CFAR).

Self-assessment test
1. Which of these statements about withdrawal from heroin is NOT true?
A. It usually begins 3-6 hours after the last use
B. Symptoms peak within 24 hours
C. Symptoms subside within 7-10 days
D. It is generally not life-threatening

2. Which sign or symptom is NOT typical of opioid withdrawal?
A. Constipation
B. Abdominal cramps
C. Lacrimation
D. Hypertension

3. All these statements about methadone treatment for opiate withdrawal are true, except:
A. Initial dose is 20-30 mg/day
B. Effects are felt within 30 minutes
C. Peak doses should be reached on withdrawal day 4 to 5
D. Any physician with an unrestricted DEA license can prescribe methadone to a patient hospitalized with a medical condition

4. All the following drugs potentiate the effects of methadone, except:
A. Phenytoin
B. Fluconazole
C. Azithromycin
D. Fluoxetine

5. Buprenorphine should be initiated:
A. Within 1 hour of last opioid use
B. When symptoms of opioid withdrawal occur
C. No sooner than 24 hours after last opioid use
D. Only by a federally licensed substance abuse treatment program

(Answers at end of references list)

References
1. Hopper JA, Shafi T. Management of the hospitalized injection drug user. Infect Dis Clin North Am. 2002;16: 571-587.

2. Ling W, Amass L, Shoptaw S, et al. A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network. Addiction. 2005;100:1090-1100.

3. O’Connor PG, Samet JH, Stein MD. Management of hospitalized intravenous drug users: role of the internist. Am J Med. 1994;96:551-558.

4. Payte JT, Khuri ET. Principles of methadone dose determination. In: Parrino MW. State Methadone Treatment Guidelines. Rockville, Md: US Department of Health and Human Services, Public Health Service, Substance and Mental Health Services Administration, Center for Substance Abuse Treatment. Treatment improvement protocol (TIP) series, 1993; DHHS publication no. (SMA) 93-1991:47-58.

5. Faggiano F, Vigna-Taglianti F, Versino E, et al. Methadone maintenance at different dosages for opioid dependence. Cochrane Database Syst Rev. 2003;(3):CD002208.

6. Krantz MJ, Mehler PS. Treating opioid dependence. Growing implications for primary care. Arch Intern Med. 2004;164: 277-288.

7. Methadone hydrochloride injection, USP [package insert]. Newport, Ky: Xanodyne Pharmaceuticals; 2006.

8. Scimeca MM, Savage SR, Portenoy R, et al. Treatment of pain in methadone-maintained patients. Mt Sinai J Med. 2000;67:412-422.

9. 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(suppl 2): S3-S11.

10. Certification of opioid treatment programs. 66 Federal Register 4090, January 17, 2001, as amended at 66 Federal Register 15347, March 19, 2001 (codified at 42 CFR §8.11).

11. Aszalos R, McDuff DR, Weintraub E, et al. Engaging hospitalized heroin-dependent patients into substance abuse treatment. J Subst Abuse Treat. 1999;17:149-158.

12. Appel PW, Joseph H, Kott A, et al. Selected in-treatment outcomes of long-term methadone maintenance treatment patients in New York State. Mt Sinai J Med. 2001;68:55-61.

Answers: 1. B; 2. A; 3. C; 4. A; 5. B.