Pharmacologic Treatment of Heroin-Dependent Patients

Illicit drug use is responsible for more than 25 000 deaths and $100 billion in total economic costs annually in the United States (1). Recently, heroin has emerged as the major contributor to these societal problems and costs. Persons suffering from heroin abuse and dependence are an important patient population for general internists. Although patients may present with medical problems that relate directly to heroin or its route of administration (for example, injection), physicians are often unaware of the underlying drug abuse problems (2) and thus may miss the opportunity to offer drug treatment services. Over the past decade, research on heroin dependence has demonstrated that treatment is effective, and new pharmacologically based treatments show promise for the expansion of treatment options (3). Most recently, research has suggested that internists may have a direct role in the provision of drug treatment services for heroin-dependent persons in their offices (4). In this paper, we review the treatment of heroin dependence and emphasize recent developments in pharmacologically based treatment approaches. Methods All relevant English-language articles identified through the MEDLINE database from 1968 through January 2000 were systematically searched by using the following key words: heroin, heroin dependence, narcotics, opioids, substance-related disorders, substance withdrawal syndrome, and narcotic antagonists. Selected references from these articles and appropriate textbooks were also reviewed. Definitions and Epidemiology The most commonly used terms to describe the clinical phenomena of illicit drug use (as well as use of nonillicit substances) are substance abuse and substance dependence (Table 1) (5). Thus, these criteria are used when diagnosing opioid abuse and opioid dependence. Heroin, a pure opioid agonist derived from morphine, was initially manufactured in the 1800s for use as an antitussive. Currently, illicit heroin is sold as a white or brownish powder in bags or bundles (10 bags) and is commonly mixed (cut) with adulterants, such as sugar or quinine. The availability of increasingly pure heroin has been responsible for an increased incidence of heroin overdose in some locations (6). Increased purity and the risk for HIV infection have resulted in a shift from heroin injection to smoking (7). According to the 1997 National Household Survey on Drug Abuse, approximately 2.5 million Americans have used heroin and the number of persons reporting heroin use over the past month increased fivefold between 1993 and 1997 (8). In addition, data from the 1996 Drug Abuse Warning Network (DAWN) survey documented a 108% increase in heroin-related emergency department episodes between 1990 and 1996 (9). Table 1. Diagnostic and Statistical Manual of Mental Disorders-IV Criteria for Substance Abuse and Dependence Common Clinical Problems in Heroin-Dependent Patients Heroin-dependent patients are at risk for a wide variety of medical, psychiatric, and behavioral health problems. Thus, patients should be routinely screened in clinical practice for heroin abuse and dependence, as well as other substance use disorders (2). Although well-accepted screening instruments (for example, the CAGE questionnaire) have been developed and tested for identifying patients with alcohol use disorders, no parallel instruments have been as rigorously tested for the identification of heroin abuse and dependence (10). However, modifications of existing instruments (for example, the CAGE-D) have been developed and are under evaluation (2). In the meantime, routine inquiry about past and current use of heroin and other drugs should be performed in all patients. Additional questions on symptoms related to heroin use (such as overdose and withdrawal), routes of administration, and complications associated with heroin use should be asked if indicated. The medical problems that may result from heroin use are numerous and have been discussed in detail elsewhere (11-14). Psychiatric comorbidity is also highly prevalent among persons who use drugs (15). In a study of 716 treatment-seeking opioid abusers, 47% were found to have psychiatric comorbid conditions (including personality disorders, depression, and anxiety disorders) and psychiatric problems were associated with more severe substance abuse problems (16, 17). Heroin users are also at high risk for abusing other substances, including benzodiazepines, alcohol, and cocaine (16, 18). The problem of dependence on multiple substances can be particularly vexing for patients, physicians, and drug treatment programs, given the complexity of multiple drug effects (for example, different patterns of dependence and withdrawal) seen in these patients. In addition, unlike with heroin, no pharmacologic agent has been demonstrated to effectively treat cocaine dependence (19). Thus, because many opioid-abusing patients concurrently use other drugs with heroin, such as cocaine and alcohol, physicians need to keep in mind that heroin detoxification and methadone maintenance do not necessarily effectively treat withdrawal or reduce the use of other drugs in these patients. Other behavior-related problems, such as family dysfunction, unemployment, and legal problems, are highly prevalent among heroin-dependent patients (20). In addition, accidents and injuries, criminal behavior, and domestic violence are associated with illicit drug use (21-23). Because of the wide variety of health problems experienced by heroin-dependent patients, internists are in a unique position to provide enhanced screening and preventive health services to these patients. This includes screening for medical conditions, such as HIV disease and hepatitis; provision of appropriate vaccinations; screening for psychiatric problems, including depression; and assessment for behavior-related problems, such as high-risk sexual activity or physical abuse (Table 2). Patients identified as having psychiatric, behavioral, or physical abuse problems should be referred for appropriate services as indicated. Similarly, social complications should be addressed by referral to social work, family counseling, or other social service agencies if needed. Table 2. Routine Screening and Prevention Activities for Clinicians Caring for Drug Users Treatment Approaches for Patients with Heroin Dependence Heroin-dependent patients require a thoughtful management approach if they are to be successfully engaged in substance abuse treatment. Once such patients are identified, it is critical for the physician to assess patients' readiness to change their drug-using behaviors (24). Prochaska and DiClemente's six-stage model describing the stages of patients' readiness to change their behaviors has been widely accepted as useful for guiding physicians' initial treatment approach (24, 25). In the precontemplation stage, patients are not thinking of their substance use as problematic and are thus unlikely to see a need for treatment. Physicians must help patients overcome denial and move them into the precontemplation, contemplation, and determination stages rather than referring them to treatment that they believe they do not need (25). After a patient has entered the action phase, physician support for behavior change and treatment is crucial. Of interest, one study of primary care patients who screened positive for alcohol abuse and dependence determined that 63% of patients were in the action phase (26). This suggests that supporting relapse prevention is a very important role for physicians (27). Once patients indicate an interest in treatment, their appropriateness for opioid detoxification or opioid agonist maintenance should be determined. We discuss these two aspects of treatment in detail and emphasize pharmacologic approaches to detoxification and maintenance. Heroin Withdrawal: Diagnosis and Management The Opioid Withdrawal Syndrome The opioid withdrawal syndrome consists of signs and symptoms that result in part from neurophysiologic rebound in the organ systems affected by opioids. These systems (and signs and symptoms) include the cardiovascular system (tachycardia, hypertension), central nervous system (pupillary dilatation, restlessness, irritability, insomnia, craving), gastrointestinal system (nausea, vomiting, diarrhea), skin (piloerection), and mucous membranes (rhinorrhea, lacrimation). Although no widely accepted assessment instrument is available for managing opioid withdrawal, brief, easy-to-use assessment tools that may be useful in clinical practice have been developed (28). Unlike patients undergoing alcohol withdrawal, patients experiencing opioid withdrawal do not typically have such severe complications as seizures, arrhythmias, or delirium tremens. In opioid withdrawal, both subjective (for example, craving) and objective (for example, vomiting) phenomena, especially intense craving, frequently lead to relapse. Thus, the effective management of opioid withdrawal is a critical first step in treating patients. Subsequent referral of detoxified patients to ongoing drug treatment services is also essential for proper and effective management. The time of onset, peak symptoms, and duration of opioid withdrawal vary, depending on the specific opioid drug being used. For example, symptoms of heroin withdrawal usually begin 4 to 6 hours after last use, peak within approximately 24 to 48 hours, and may last for 7 to 14 days. In contrast, symptoms of withdrawal from methadone, a longer-acting opioid, generally begin 24 to 36 hours after last use and can last for several days to a few weeks. The management of opioid withdrawal combines general supportive measures and pharmacologic treatments. Supportive measures include a safe environment, adequate nutrition, and careful monitoring. Pharmacologic therapies, including opioids and nonopioids, can be provided to alleviate withdrawal symptoms. Detoxification Using Opioid Agonists Opioid-ba