Methadone Treatment and Recovery
for Opioid Dependence
Ms. Kauffman is assistant professor of psychiatry in the Department of Psychiatry at Cambridge Hospital in Cambridge, Massachusetts, director of Addiction Psychiatry Service at Brigham and Women’s Hospital in Boston, and director of Substance Abuse Treatment Services at the North Charles Foundation, Inc., in Somerville.
Disclosure: The author reports no financial, academic, or other support of this work.
Please direct all correspondence to: Janice F. Kauffman, RN, Department of Psychiatry, Cambridge Hospital, 260 Beacon St, Somerville, MA 02143; Tel: 617-661-5700; Fax: 617-868-4840; E-mail: firstname.lastname@example.org.
• Methadone treatment developed as a response to increasing problems with opioid dependence and ineffective approaches to the problem.
• Methadone’s pharmacologic properties make it more efficacious than other, shorter-acting opioids.
• For a variety of reasons, methadone treatment remains controversial.
• Methadone is provided within a comprehensive treatment system.
Unlike any other medical treatment, methadone pharmacotherapy for the treatment of opioid dependence is still controversial despite 40 years of scientific work demonstrating its efficacy. Negative attitudes toward people with opioid dependence have been developing since the Civil War, and have become associated with methadone treatment. The stigma is partly attributable to the criminal behavior of some people with opiate dependence, but also results from factors such as poor education of the treatment community. This article briefly reviews the history of opioid dependence in the United States, the search for solutions, and the development of methadone. It considers the pharmacologic properties of methadone and how these relate to its efficacy. The article also reviews the elements of a comprehensive methadone maintenance program and factors to be considered in selecting patients.
Since the Civil War, opioid use and dependence has been a focus of attention for the medical community, society, and policy makers. Opinions about both the etiology of the problem and the efficacy of methadone treatment remain controversial despite the knowledge gained from scientific research, outcome data of treatment interventions, and clinical experience.1 Opioid dependence is one of the few illnesses for which public opinion overshadows scientific knowledge. Americans exhibit ambivalence about addictive disorders and their treatments. Although it is “in vogue” today to be addicted to something, it is clear that some addictions, such as shopping, food, movies, relationships, and even alcohol, are more acceptable than others, such as cocaine, ecstasy, heroin, and oxycodone HCl.Furthermore, some pharmacologic treatments, such as naltrexone or disulfiram, which deter alcohol- and opiate-dependent patients from relapsing, are more acceptable than pharmacologic treatments, such as methadone, which is perceived as maintaining addiction. The act of prescribing a synthetic morphine-like drug to patients with opioid dependence magnifies societal biases. This is particularly highlighted when the history of opioid dependence and efficacy of methadone maintenance treatment is examined.
History of Opioid Dependence: Reflecting the Views and Understanding of Addiction
The history of opioid dependence is rich and informative. Concerns about opioid addiction in the United States first emerged after the Civil War when narcotic drugs (opiates) were prescribed to alleviate acute and chronic pain, discomforts, and stress.2 The prototypical opiate misusers in the late 19th century were the upper- and upper-middle class white women who had been prescribed them for disorders such as menstrual pain and “female troubles,” and disabled and wounded veterans seeking pain management.3 By the turn of the 20th century, 300,000 people were opiate-dependent.3-5 In general, the medical community treated such people with tolerance and empathy.
At the same time, American society viewed opium use as socially unacceptable. Around the turn of the century, many Europeans immigrated to the US and the population of opioid users began to change. Many opioid users during this time were young, destitute men living impoverished lives in overcrowded tenements and ghettos. They had been using opioids since their adolescent or early adult years and often resorted to illicit activities to support their dependence. Society viewed these immigrants with social, religious, and political disdain.4 After World War II, many Europeans moved out of the northern and western cities to the suburbs, and were replaced by African Americans, Chinese, and Hispanics, who brought with them their culture, customs, and addictions. Class and ethnic biases merged with dissonance and fear, and opiate addiction became a threat, empathy evaporated, and negative attitudes toward opioid users prevailed.5,6
The Federal government attempted to resolve the problem with regulations such as the Harrison Narcotics Act in 1914, which prohibited physicians from prescribing opiates to treat or maintain “addicts.”3 For the most part, the medical community did not challenge the view that addiction was not a disease and that addicts were not patients. As a result, opiate-dispensing clinics were closed precipitously, crime increased, and in 1929 Congress established the US Public Health Service Hospital in Lexington, Kentucky, to incarcerate opiate addicts, either voluntarily or involuntarily, to allay fears about addiction-related crime.3,5,7,8 Interventions were expensive and unsuccessful. People with opioid dependence were detoxified in prison hospitals and offered social, psychological, and psychiatric services. However, a study following 1,912 inmates for at least 1 year, and some as long as 4.5 years, reported that 93% relapsed.3,5 Similarly, a follow-up on 453 inmates found that 97% relapsed in 6 months to 5 years.3,5
In response to the increasing number of heroin users, heroin-related crimes and deaths, the increase in needle-related hepatitis, overcrowded jails, and lack of effective treatment for heroin dependence, the American Medical Association (AMA) and American Bar Association (ABA) recommended that outpatient facilities prescribe opiates for maintenance (1958). Not long afterward, President Kennedy’s Advisory Commission on Narcotic and Drug Abuse recommended research to determine the effectiveness of dispensing narcotics to addicts.3
In 1962 Vincent Dole, MD, a specialist in metabolism at Rockefeller University, was appointed chair of the Narcotics Committee of the Health Research Council of New York City. He received a grant from the Health Research Council to establish a research unit to study the scientific, public health, and social ramifications of opioid maintenance. At the same time, Dole became interested in an article by Marie Nyswander, MD, a psychiatrist, which reflected the latter’s work with addicts at the US Public Health Service Hospital, and in her private practice in East Harlem, New York. She believed that many heroin addicts could function as productive citizens if maintained on opiates.3,5 Dole invited Nyswander and Mary Jean Kreek, MD, a young clinical investigator completing her internal medicine training in neuroendocrinology, to join his research team.
The new team initially administered low-dose morphine to opioid-addicted patients every 4–6 hours. Although these patients did not suffer withdrawal symptoms, they remained apathetic, sedated, and preoccupied with drugs. In addition, in order to maintain a steady state, they had to increase the dose as the patients experienced tolerance.9-11 Although this intervention provided medication access, unadulterated drugs, and clean syringes, it was not a satisfactory solution since it did not help patients improve their social functioning.
In 1964, with the advent of technology that could measure blood concentration of opiates and assess duration of action, methadone, with a long half-life, was administered to patients who had been maintained on morphine. The investigators discovered that methadone doses of 80–120 mg/dayallowed patients to achieve normal social function without drug craving. The patients also did not experience euphoric, tranquilizing, or analgesic effects. In addition, taken orally, methadone was safe and had minimal side effects.10-12 Finally, it was effective for patients tolerant to all opioid drugs, and blocked the euphoric and tranquilizing effects of short-term opioids when patients injected them on their own.
Methadone Meets the Challenges of Opioid Dependence
Several hypotheses have attempted to explain the chronic relapsing nature of opioid dependence. Kolb13 postulated that those who responded to the euphoric effects, which was considered an atypical response, had psychopathology. He also hypothesized that psychopathology was the basis for initial experimentation, initial euphoria, and continued use. Others believed that those who responded positively to opiates had an endorphin deficiency that was corrected by exogenous opiates.14 Repeated use created permanent dysfunction in the endogenous endorphin system, so that normal mood modulation and functioning required continued opioid pharmacotherapy.15 Thus, methadone can be understood as a corrective agent for the brain dysfunction related to chronic relapsing opioid dependence.
The implications for individual patients, public health, and public safety have been enormous. Methadone has reduced the severity of addiction and virulent drug use by allowing a dependent person to maintain an acceptable level of medical and social functioning.16 Methadone maintenance has resulted in a reduction in the spread of needle-borne disease, such as hepatitis, human immunodeficiency virus, and acquired immunodeficiency syndrome.17-20 Furthermore, methadone maintenance patients use fewer costly emergency healthcare resources, attending to their health needs in a less episodic and crisis-oriented fashion.16 With methadone, more former addicts attain and maintain employment and provide for their families. In addition, methadone is associated with a reduction in drug-related crime.21-24
The positive effects of methadone maintenance treatment do not result from the medication ingestion alone, as the treatment of any addictive disorder requires significant lifestyle change. Treatment involves adequate assessment and ongoing attention to the medical, psychological, social, environmental, cultural, and behavioral components of the patient’s life. Methadone without psychosocial treatment is not an effective treatment.25 This is the case for many medical disorders. For example, insulin and antihypertensive medications alone do not successfully treat diabetes and high blood pressure. Comprehensive treatment involves diet, exercise, and lifestyle change. Successful substance abuse treatment involves compliance and change toward a drug/alcohol-free lifestyle. Many patients require treatment for other substance-related problems as well as co-occurring psychiatric disorders, such as depression and anxiety. Therefore, successful treatment for opioid dependence involves addressing the same issues as treatment for patients with addictions involving alcohol, benzodiazepines, cocaine, and other substance- or nonsubstance-related addictive disorders (eg, gambling); it requires both professional interventions and recovery support.
Controversy Surrounding Methadone Maintenance Treatment
Despite the positive results associated with methadone treatment, and its use within well-designed treatment settings, the drug remains a controversial treatment modality.26 Even though science has demonstrated genetic predisposition to and brain changes following substance use, addiction, and especially opiate dependence, some still consider them to be moral weaknesses rather than medical problems. This view gained strength after enactment of the laws prohibiting the prescription of opiates for the treatment of opiate dependence. Criminal behavior increased and individuals with opioid dependence were considered not only morally weak, but criminals as well. Thus, the notion of giving opiate-dependent patients an opioid for the treatment of their addiction was considered heresy. As a result, despite the science, the outcome data, and the anecdotal reports of so many patients receiving methadone treatment, many continued to hold as much distaste for the treatment as for the addiction.27,28
The reasons for negative beliefs are multifold.29,30 Due to a lack of education and accurate information about methadone as a medication, many clinicians are fearful and mistrusting of the medication and the patients taking it. For healthcare professionals, addictions training is limited, and few certification and licensing bodies address opiate dependence and methadone treatment in their qualifying examinations. Other prescribing specialists are angry from past personal or professional negative experiences. Furthermore, there are clinicians whose treatment philosophy does not permit a treatment that they believe is not based on abstinence. For example, many believe that patients on methadone are “just getting high” or are “substituting one drug for another.” They are under the impression that heroin addicts are “bad characters” and that prescribing opioids is not an acceptable way to treat the addiction. Unfortunately, this view has received support from revelations about some unscrupulous methadone programs.
One reason for the negative beliefs lies with the patients themselves. Like patients with other substance use disorders, some opioid-dependent patients abuse alcohol and other drugs, and do not comply completely with the requirement for abstinence. However, relapse is part of the course of any addictive disorder. The treatment of substance dependence has many of the same compliance problems as treatment of obesity, diabetes, hypertension, and asthma.31
Challenging the Controversy: How Methadone Really Works
Methadone is very different from heroin, morphine, and other short-acting opiates. Patients using short-acting opiates (eg, heroin) are never stable; they experience fluctuating “highs” and “lows.” They are listless, unmotivated to improve their lives, and more focused on drug access, drug effect, and the relief of withdrawal, than on the tasks of recovery.32 Dole and colleagues9 demonstrated this when they tried treating heroin addicts with short-acting opiates.
The goals of methadone maintenance treatment are very straightforward. Methadone is a long-acting synthetic opioid that provides stability for 24–36 hours when orally administered for the treatment of opioid dependence. The pharmacokinetics and neurobiology of methadone treatment are beyond the scope of this article, but understanding the different actions of short and long-acting opiates is important to the careful prescription of this medication.33 When administered daily in adequate doses, methadone prevents or reduces drug craving, prevents or reduces signs and symptoms of opiate withdrawal, prevents relapse to the use of opiates, and restores the patient to the normal physiological functions disrupted by repeated short-acting opiate use.34
For many patients methadone maintenance is a long-term treatment. For some, methadone pharmacotherapy may be lifelong. Most importantly, the length of time in treatment should be individually determined and not predetermined by artificial timeframes. Research studies consistently report that the length of time in treatment is positively correlated with successful outcomes.35,36 For example, when patients are precipitously forced to withdraw from the methadone, relapse rates are as high as 82% after a 12-month abstinence period.24
Patients who have demonstrated that they meet the benchmarks of recovery may be considered for medically supervised withdrawal. These benchmarks include no alcohol or drug abuse; a stable living, social, or employment situation; no evidence of illicit activity; psychiatric and medical stability; developing a circle of friends and associates outside of the drug culture; and a system of drug-free support. A patient who reaches these goals might be appropriate for withdrawal from methadone. However, the most important variable is that they are highly motivated to recover. Even with motivation, some patients are unable to remain opiate-free without continued pharmacotherapy. This is likely related to significant changes in brain chemistry rather than to patient failure.
Methadone Maintenance: Where, When, and How
When considering methadone maintenance for an opioid-dependent patient it is important to consider several issues, mostly that the patient desires treatment. Admission to a methadone maintenance program is a commitment to a highly structured treatment intervention. It involves daily medication, urine toxicology screening, and regular attendance to a combination of individual, group, and perhaps family treatment.
Methadone maintenance treatment is most appropriate for the patient with a history of chronic relapse. The patient who has tried and failed other interventions such as inpatient and/or outpatient detoxification, residential treatment, and day treatment is a good candidate for methadone maintenance. Some patients report that they are unable to function without opiates. This may suggest that they are struggling with a biochemical disorder that needs long-term opioid pharmacotherapy to attain and maintain stability.11,15
Like other substance-dependent patients, those on methadone maintenance may have problems with alcohol or other drugs.37-39 In fact, intoxication with other substances may be misconstrued as intoxication from methadone. Thus, these other substance use problems and comorbid psychiatric and medical conditions must be addressed as well. Untreated problems affect the outcomes of the other disorders. At times, patients may require a more intensive level of care, such as the safety and structure of inpatient detoxification or residential care, to fully address environmental and social needs.40 Unfortunately, when a methadone-maintained patient needs inpatient detoxification or residential treatment, access is often denied by the addictions treatment community itself, because of resistance to methadone treatment. Consequently, a patient must give up a medication that stabilizes opioid dependence in order to get treatment for alcoholism or sedative dependence. Clearly, there is room for improvement in integrating methadone maintenance into other substance dependence treatment settings.
Despite studies demonstrating its efficacy, methadone maintenance treatment for people with opioid dependence is not fully embraced by either the treatment community or society. The findings of scientific studies are overshadowed by negative perceptions, which are determined partly by lack of education, divergent treatment philosophies, the behavior of some people with opioid dependence, and other factors. However, for sound pharmacologic reasons, methadone is an effective treatment for opioid dependence. When delivered within a comprehensive treatment program to the right patients, methadone results in improved outcomes on a variety of measures. Physicians owe it to their patients to make this treatment modality available and to better integrate it into other forms of treatment. PP
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