New Federal Initiatives To Enhance the Medical Treatment of Opioid Dependence

Opioid dependence is a chronic medical disorder that is manifested by the repeated self-administration of opioids (1-6). Research has demonstrated the neurobiological changes in cellular and molecular systems that result from repeated exposure to short-acting opioids. These changes include perturbations in opioid receptor kinetics, transmembrane signaling, postreceptor signal transduction, and intracellular messengers (5, 6). The physiologic dependence and addictive behavior that are diagnostic of opioid dependence result from these neurobiological changes and form the rationale for prescribing opioid agonist medications for the treatment of opioid dependence (3). These medications stabilize brain neurochemistry by replacing short-acting euphorigenic opioids (for example, heroin) with long-acting noneuphorigenic opioids [for example, methadone]. They have two main mechanisms of action: 1) cross-tolerance at the opioid receptor, which prevents opioid withdrawal, and 2) competition for opioid receptor binding sites, which blocks the effects of exogenously administered opioids (3, 7). Historical Role of the Federal Government in the Treatment of Opioid Dependence During the 20th century, the U.S. federal government played a considerable role in regulating the medical treatment of opioid-dependent patients (8). The Harrison Narcotic Act, adopted by Congress in 1914, resulted from a series of legislative efforts designed to control the medical practice of using opioid medication, such as morphine, for the treatment of opioid-dependent patients. This early legislation set the stage for future federal control over this aspect of practice (9). Successful treatment of opioid dependence with methadone by Dole and colleagues in the 1960s (7, 10) was followed by a series of federal regulations and legislation, such as the Narcotic Addict Treatment Act (NATA) of 1974, with a twofold agenda: to ensure the quality of maintenance treatment with methadone and to prevent diversion of methadone for illicit use (4). The NATA created joint responsibility for methadone between the U.S. Food and Drug Administration (FDA), which had responsibility for the public health and safety, and the U.S. Drug Enforcement Administration (DEA), a branch of the Department of Justice, which had responsibility for law enforcement and diversion control (8). These federal regulations, which are unique for an approved and effective medical therapy (1, 11, 12), have engendered criticism that they do not reflect clinical research on the effectiveness of methadone or the current understanding of opioid dependence (8, 13). Designed almost 30 years ago when there was a different understanding of opioid dependence and the role of opioid agonist treatment, the regulations and laws were originally developed to limit inappropriate prescribing practices and methadone diversion. Recent reviews of the narcotic treatment system by federal agencies (for example, by the General Accounting Office) and independent bodies (for example, the Institute of Medicine), however, have determined that the system by which the FDA regulates and monitors the use of opioid medications is too heavily oriented toward administrative requirements and focuses too little on treatment outcomes (13). These reviews cite the large variability in treatment outcomes with methadone (13, 14) and fault a regulatory system that promotes process-oriented evaluations that lack clinical orientation over medical judgment and patient outcomes. At the end of the 20th century, federal regulations for methadone maintenance treatment, which were codified in the Federal Register, delineated medical practice for methadone: which patients could receive treatment, the appropriate amount of counseling support, medication dosing limits, frequency of monitoring for illicit drug use, physician and staff qualifications and ratios, and criteria for determining which patients were candidates for unsupervised use of medication (8). In addition, these regulations specified special licensure for physicians prescribing methadone for maintenance treatment and mandated a separate registration from the DEA. These regulations have resulted in a system that is restricted primarily to large urban narcotic treatment programs that primarily provide care for opioid-dependent patients, some of whom continue to use illicit drugs (14). In this system, receiving medication for opioid dependence meant visits to a clinic 6 of 7 days per week for medication dispensing, often for as long as 2 years, which created significant logistical constraints (15). Unobserved dosing of medication was generally contingent on evidence of abstinence through urine toxicology analysis. This treatment system, rather than promoting treatment entry and retention, was perhaps partly responsible for the fact that only 170 000 of the estimated 810 000 opioid-dependent patients in the United States were receiving medication for this medical condition (16). We describe the new federal initiatives that have been implemented over the past 2 years, which are designed in part as a response to the deficiencies of this situation. New Federal Initiatives New federal initiatives for the care of opioid-dependent patients come at a time of increasing heroin use and high rates of HIV and hepatitis C virus transmission among injection drug users (17). Although funding for traditional narcotic treatment programs could be raised in an effort to expand treatment capacity, this solution would not necessarily increase involvement of the medical profession in the care of opioid-dependent patients or serve the subset of patients who choose not to enter narcotic treatment programs. The current initiatives are designed to meet the dual objectives of treatment expansion and the involvement of physicians in the care of opioid-dependent patients. The changes are designed to create a new and more clinically oriented treatment system for the 21st century that reflects the recognition that opioid dependence is a medical disorder and that methadone and other pharmacotherapeutic agents are currently the most effective treatments for this disorder (13). The unifying theme among these unique initiatives is the movement toward a system that resembles care provided for other chronic medical conditions and that allows more clinician involvement. These important federal legislative and regulatory efforts reflect a desire to rethink the clinical and public health implications of federal policy to help achieve several critical goals. These goals include 1) increasing the participation of the medical community in the treatment of opioid-dependent patients, 2) increasing the focus on patient needs, 3) improving treatment outcomes, 4) reducing variability in the quality of services, 5) making federal oversight more effective, and 6) expanding access to treatment (13). In the following sections, we discuss three recent landmark changes to federal regulation that will facilitate office-based medical maintenance and the use of independent physicians' offices to coordinate opioid agonist therapy and the medical care of opioid-dependent patients (Table 1). Table 1. Federal Initiatives To Enhance the Medical Treatment of Opioid Dependence Exemptions for Office-Based Opioid Agonist Treatment A federal advisory, released jointly on 30 March 2000 by the FDA and the Center for Substance Abuse Treatment (CSAT), voiced support for narcotic treatment program-based exemptions to allow for office-based methadone maintenance (18). Under the exemption process, a narcotic treatment program may apply to the CSAT for an exemption from any regulatory requirement. This would allow, for instance, an exemption to be granted to establish office-based methadone maintenance. These requests for exemptions will be reviewed and action taken after consultation with the DEA and the state methadone authority. Successful office-based demonstrations using research mechanisms (19-22) and ongoing programs in New York, Baltimore, and Seattle have provided information about the appropriate conduct of these types of programs and have contributed to the CSAT's process of developing clinical practice guidelines and training curricula for office-based practitioners (18). This advisory represents an evolution of these programs from research into clinical practice. New rules governing opioid agonist medication provide for longer periods of unobserved medication dispensing and favor a system with linkages between narcotic treatment programs and physicians' offices. The text accompanying the new rules supports the development of additional information and experience with office-based care to evaluate and refine these treatment models (23). Prescribing New Medications for Office-Based Maintenance and Detoxification On 17 October 2000, PL 106-310, the Drug Addiction Treatment Act of 2000, was signed into law (Table 2). This legislation allows qualifying physicians to prescribe schedule III, IV, and V narcotic medication or combinations of such medications for treating opioid dependence (24). The Act stipulates that physicians must use medications that have been approved by the FDA for maintenance and detoxification treatment of opioid dependence and must notify the Secretary of the Department of Health and Human Services (DHHS) of their intention to provide this treatment. The first medications anticipated to be approved by the FDA for this indication are the partial opioid agonist buprenorphine and the buprenorphinenaloxone combination (25). Table 2. Summary of Federal Legislation Included in the Drug Addiction Treatment Act of 2000 The Drug Addiction Treatment Act defines qualified physicians as those with state licenses and certification in addiction medicine through subspecialty boards or medical societies. In addition, physicians may become qualified by participating in a minimum of 8 hours of approved training (through the American Society of