The lnstitutional Matrix: Methadone Treatment, Science, and Research

2015

An appraisal of the consequences of heroin use, we suggested earlier, cannot be limited to the examination of the actors in the heroin scene. We reviewed several of the efforts to identify types of adaptations of heroin addicts; however, the conclusion we drew was that this was only a prolegomenon to what has to be done in the future. Our examination of a high risk community suggested that where rates of narcotic involvement are high, the problem can no longer be viewed as confined to a collection of individuals who happen to choose a particular mode of adaptation. Instead, it becomes an issue that reverberates throughout the community and influences the community’s ability to solve its problems of survival.

There is still another aspect to the consequence of heroin use, the organizational and institutional one, with its concomitant establishment of a complex public and private system to deal with narcotics. Expenditures for supply reduction alone represent over 350 million dollars annually. There are 276,000 treatment slots provided by federal and local governments and under private auspices (White Paper, 1975). A major industry has been spawned to cope with a problem that may involve between one-quarter to one-half percent of the population (The conclusions drawn from our review of epidemiological research have direct bearing on methadone therapy. Many individuals merely experiment with heroin; others abandon use without treatment intervention. Since there are no clear prognostic indicators to identify these individuals, many can become involved in methadone programs through criminal justice and community pressures. They, therefore, become more heavily invested in drug dependence than they otherwise might. The normal maturation out of drug use that probably characterizes most heroin users can be seriously interfered with. Here, however, we examine a different set of issues). To interpret the kinds of sums that are involved, since the overall figures defy comprehension, we limit ourselves to the amount spent on research at the federal level between 197 1 and 1975, almost a quarter of a billion dollars. This does not include large sums of money for research that derive from local government sources or from foundations.

A review of the system that has developed in response to heroin use is beyond the resources at our disposal. To get some handle on at least one important part of this diverse and amorphous system, a review will be made of the relationship between our cumulative information on research and its import for treatment, particularly methadone maintenance. Methadone maintenance is one of the major treatment thrusts that currently engages perhaps 90,000 patients nationwide.

We select methadone because we feel it is an appropriate paradigm for examining the complex relationship between science and large investments in research and the impact this may have on developments in the treatment system. Research on other treatment modalities, particularly the various drug-free efforts, is, on the whole, much less adequate and not nearly so abundant.

We are not here especially concerned with the question of whether methadone works or whether we can attribute successful rehabilitation to the modality, or whether crime is markedly attenuated as a consequence of the expansion of methadone therapy.’ Rather, we advance a different set of questions, focused on how knowledge cumulates and is absorbed by those who direct our programs. We also will address ourselves to the research itself and the way it has been used, or, in some cases, ignored.

We might cynically conclude that the failure to absorb contrary findings in an orderly and rational way is simply a consequence of organizational requirements for survival. Where research that is not congenial to the managers of our programs is spurned, it may be rejected only because changes would have to be made in program functioning, in staffing patterns, and – for perhaps the most compelling reason – in the reduction or even elimination of funding. We have no doubt that such processes are at work but they are not the only ones.

We suggest that the processes we observe are at least partly explicable in terms of the very particular context in which methadone therapy developed and the institutional and professional antagonisms that surrounded the inception of the method. The heroin epidemic ‘was beginning to flower, accompanied by an increasing crime wave that received abundant attention in the press and was becoming increasingly visible to the general public in many neighborhoods in New York City. At both the city and state levels there were study groups, commissions, and a constant stream of pronouncements. Most of the professional community, however, would have very little to do with addicts or addiction. Social agencies, largely unskilled in the treatment of addiction, failed to respond to the increasing dimensions of the problem. The initial New York City effort, aside from police activity, was to establish a Narcotics Register to provide some monitoring of the dimensions of the problem, and to appoint, as a commissioner of narcotics, a psychiatrist committed to psychiatric modalities for the treatment of addiction.

None of the sociological or psychological frameworks provided any remedies that could be translated into successful treatment regimens. One could talk about solving the problems of poverty, or about resocialization of disordered characters; neither the will was present to deal with the former approach – if indeed it would have worked – nor were most addicts likely to accommodate to efforts at resocialization through individual therapy or by various group-oriented methods (therapeutic communities).

Many of the early supporters of methadone were in various ways associated with the ill-fated Riverside Hospital program described earlier, perhaps the most substantial recorded failure in the history of drug treatment: at the end of a one-year follow-up they could record only one drug-free individual ()! Dr. Nyswander, a psychiatrist, was one of the few professionals attempting to deal with drug addicts, and her experience was one of failure. It was at this time that she became associated with Dr. Vincent Dole, who though a physician, was primarily engaged in research at the Rockefeller Institute.

Kuhn (1970), in his classic work, The Structure of Scientific Revolutions, reviews the hesitant progress of science whenever particular scientific paradigms encounter problems that are resistant to solutions where the model has previously had brilliant success. But even when a model encounters failure, those who may advance new conceptions or evolve radical solutions are not always embraced. In fact, it may take decades or even centuries – as in the case of Copernicus – before their formulations are finally legitimized by the scientific community. We may be stretching the analogy between science and theories of drug use, but the dismal failures encountered up to the early 1960s may also be seen as the failure of the theoretical underpinnings that existed up to that time; they were very vague, and could only by excessive charity be called scientific schema ensconced in a well-formulated paradigm. Certainly, they lacked the essential feature of a successful paradigm in that the puzzles they were supposed to solve, the rehabilitation of addicts, remained insoluble.

It is in such a context that a psychiatrist could begin to entertain a very contrary set of assumptions about addiction, such as the one we associate with Drs. Nyswander and Dole. Their solution was to maintain addicts on drugs, and they developed a rationale to justify their reformulation. Then, as now, there were those who retained enthusiasm for alternate methods, and who accepted only drug-free status as the legitimate objective of treatment. Yet, in many cases, those who were most hostile to methadone have made their peace with it. As with scientific paradigms, it became necessary to accommodate finally to the presentation of evidence that methadone seemed to work as no other therapeutic intervention system had before.

In addition, the problem of drug abuse appeared to be getting out of hand, and the clamor for solutions was great. And, as the first results on methadone treatment (both the early clinical trials and the early evaluations prepared by Dr. Francis Gearing) appeared to strongly document, a solution was at hand, one that appeared to transform the addict population into working adults who abandoned crime and no longer abused illicit drugs. A solution had been found to a difficult problem where no solution existed before.

To establish the scientific credibility undergirding methadone maintenance, we briefly review (a) the scientific status of the medical evidence that led to the resort to methadone (more specifically, the evaluation of morphine); (b) the theoretical underpinnings of methadone maintenance (including the metabolic disorder theory and the blockade concept); and (c) the critical research directed at methadone maintenance.

These issues are related to the current responses of the major actors in the methadone treatment scene to the critical issues that have been raised in a number of quarters.

The Evaluation of Morphine

Before Dole and Nyswander began their experiments with methadone they had maintained a few addicts on morphine. They found their patients became sluggish and passive and either slept or watched television until they received their next dose. It also seemed that when they developed a tolerance for a particular dosage level they began to demand increased quantities of drugs, so that stabilization was not possible. From this experience they concluded that morphine would not be an effective substitute for heroin, the drug of choice of their subjects.

Neither Drs. Dole nor Nyswander had been pharmacologists, and it would appear that their experience was a trial and error affair. Many people have been, and still are, maintained on morphine at stable dosage levels. Waldorf and his colleagues, in a review of the Shreveport clinic, report that for most patients a “balance” was achieved at 7.5 grains, with some individual variations. Further, the patients worked, and lethargy or inactivity was not a particular problem (). The LeDain report (Final Report, 1973) notes that morphine “does not necessarily produce marked sedation, gross intoxication or major impairment of motor coordination, intellectual functions, emotional control or judgment” (). Duster (1970) confirms this view as well; patients maintained on morphine “are able to lead an otherwise normal life with little change in work habits or ability to meet responsibilities” ().

There may be very good reasons for using methadone in a maintenance program, particularly because of its relatively long acting quality. What the above citations suggest, however, is that the collective experience of the pioneers was not particularly substantial in at least this branch of clinical pharmacology. Their peculiar results may have been an unfortunate consequence of their inexperience or the particular subjects they investigated. Or, more likely, these addicts were hospitalized and were not expected to work or carry on any normal routines, and their behavior could be explained on these grounds. Thus, it seems that methadone may have been used initially because of the inexperience with narcotics of the principle investigators. In some early experiments at Lexington with methadone the same observations about the reactions of patients were made as those Dole and Nyswander reported on morphine maintained patients!

Metabolic Disorder Theory

One view about drugs that still has cogency is that it might be expedient just to provide addicts with heroin and therefore minimize, if not altogether alter, many of the undesirable social and health consequences associated with drug abuse. Although this view may have been part of the motivation, it is not part of the formal justification for methadone. Instead, Dole and Nyswander have advanced a theory about drug use that maintains that there are no psychogenic origins of drug use, and instead, they insist that addict behavior “is a consequence and not a cause of addiction” ()

They advanced the explanation that repeated heroin use resulted in a metabolic disorder that was sated only by narcotics or a substance like methadone that behaved in a similar manner in the system. However, the precise mechanisms were not suggested, and metabolic disorders can involve a very large number of systems in the body. As an explanation it is in a league with those that say “culture” or the “social system” is a cause of something, which is tantamount to specifying almost everything as the cause of something – a trivial formulation.

It is surprising, then, that it took so long for the medical community to challenge this explanation. In 1972, Dr. Avram Goldstein, who also supervised a methadone program, noted that there were abstinent former addicts who could function without drugs, a fact that is incompatible with the premises of the metabolic theory. He further noted that if addiction were a metabolic disease then there would not be any relapses on the part of patients receiving methadone; yet there are episodic relapses, and alternate explanations were offered (). Vaillant also comments on the metabolic theory, that it“. . . is almost certainly [an] erroneous hypothesis that heroin addiction, like diabetes, reflects an underlying metabolic abnormality” ().

Yet, attractive explanations manage to survive years after they have lost their credibility. Kuhn notes that when a particular scientific system has been challenged there is a great deal of effort to modify older theories in an effort to maintain the essential structure of the original paradigm. Consequently, a new analogy is now coming into vogue that bypasses the criticisms directed at the reference to metabolic disorders. Addiction is now conceived as a chronic disorder which need not invoke the metabolic system (). At one stroke one kind of criticism is obviated, while the essential structure of the old argument is retained. The abundant evidence that for many thousands of persons addiction is self-limiting is simply ignored. It does not enter into the experiential world of the founders or many supporters of methadone treatment.

Dosage Levels/Blockade/Tolerance

In the early reports, Dole and Nyswander evolved the concept of blockade (). They insisted that once a person was given sufficient methadone, a quantity which may vary slightly depending on the individual, he or she could no longer respond to heroin: it would simply not perform its function, and eventually the craving for heroin would be extinguished. As Goldstein noted in the paper cited earlier, Dole confused tolerance with blockade. Only narcotic antagonists can block opiates by shutting off the sites in the nervous system where opiates (or methadone) might have their effect. But there has been no retreat on this issue, and the concept still finds favor among methadone supporters.

This is not merely a quibble, because there are several very important consequences that emerge from the assumption of a blockade effect. First, if the assumption concerning blockade is correct, then it serves as a rationale for high methadone doses. Yet, if there is one cumulative body of evidence that is reasonably clear, it is that high dosage does not result in better outcomes than lower levels of methadone. Goldstein reported in 197 1 and again in 1973 (), that no important differences in program outcomes could be attributed to dosage differences. Also, as early as 1969, Jaffee, Zaks, and Washington, and then in 1970 and 1971, Jaffee alone reported findings that were consistent with the Goldstein findings; and again, in 1973, Schut, Wohhnuth, and File confirmed essentially the same trends.

Each of these experiments contained technical flaws, but there is a cumulative impact from these and other studies not cited here.

Summary data from an experiment on dosage levels carried out jointly by Columbia University and a Yale University Medical Evaluation team support the findings cited above (). Patients were randomly assigned to high (100-mg) and low (50-mg) dosage groups. The experiment was double-blind so that neither staff nor patients knew who was receiving either dosage level. A small number of patients who had side effects (among high-dose patients), or whose codes were broken because the person had to be detoxified, or maintained while in jail, were removed from the experiment.

Two problems should be mentioned: (a) One-third of the patients had left treatment at the end of one year and half of them were gone by the end of 24 months; however, the dropout rates were almost identical for the two dosage groups! (b) Data derived from urine tapes contained some missing or otherwise unretrievable data on regularity of methadone pickups and on urine reports, although the amount of missing data was similar for both groups.

There were no significant differences in crime, retention, employment, missed methadone, or morphine positives. Patients were followed for up to 2 years on medication and morphine positives, and for 4 years on retention. Although patients were randomly assigned, there could still be some interactions between personal qualities of patients and dosage. We therefore performed a regression on retention and on arrests, using a large number of predictors of outcome, with dosage introduced as a dummy variable. The impact of dosage is negligible: the standardized beta weights are .02 for retention and -.05 for criminal activity, clearly insignificant. Along with the results cited earlier and the information we present here, it would seem that dosage does not play the role the methadone model assumes. Different dosage levels neither improve nor detract from the probability of continued drug abuse nor influence any other parameter used to assess the efficacy of treatment.

These cumulative results can have only one implication; namely, that the presumed advantage of high dosage has yet to be demonstrated. Other investigators have observed that high-dose patients abuse a variety of drugs (). There is also a rather odd fact in the debate. Although the programs affiliated with Dole and Nyswander have collected voluminous amounts of urine, and, although they and their colleagues have been among the more prolific publishers of research reports, they have made only very general statements about morphine positives. There is no detailed documentation on drug abuse presented in a decade-long series of reports.

The theory concerning the blockade effect and the consequences attributable to high dose has never been confirmed. But the avoidance of the negative findings we have cited has very direct implications for the population undergoing treatment in high-dose clinics. The statement is constantly reiterated that methadone is relatively benign, that most patients are able to accommodate to it after a short period of discomfort, and that it has no substantial side effects. However, Nash, using a set of questions developed by Goldstein, states that substantial, if declining, proportions report a whole range of symptoms even after they have been maintained on methadone for some period of time ().

Even more important, however, is the relationship of dosage to two particular issues. Many addicts wish to be detoxified and hope to become drug-free. An issue, which we can only raise, and for which we have no answer, is whether high-dosage maintenance, which appears to have no particular advantage, may make permanent detoxification even more difficult, if not impossible, for many patients. This can be especially pernicious when we note that most users of heroin, even those who were addicted, will eventually modulate or even cease drug use. After maintenance on a high dosage of methadone, the cessation of drug dependence may be even more difficult.

A recent NIDA publication reviewed the literature on methadone and pregnancy. We site from the summary:

It has been firmly established that infants born to methadone-maintained mothers display withdrawal signs at birth. Early investigation revealed neonatal heroin addiction to be more life-threatening than neonatal methadone addiction; but the most recent research results seem to contradict this previous conclusion. Methadone-addicted babies apparently exhibit more severe withdrawal symptoms with a significantly longer duration than heroin-addicted babies. (National Clearinghouse, 1974).

A recent New York Times article reported these findings, and several clinics revealed they would reduce dosage levels to pregnant patients. Dr. Dole, in an interview, objected on the grounds that low dosage would only encourage the mothers to seek heroin, which would be worse. Although the credibility of the blockade concept is no longer tenable, the vitality of the original conception appears undiminished.

An accumulation of evidence appears to refute the underlying assumptions made by the methadone pioneers. Yet, many who advocate the use of methadone persist in views where the evidence would appear to call for some revision in their formulations. Instead, we see the model restated, with only slight and insignificant changes.

Evaluative Research

The apparent success of methadone maintenance was dramatically confirmed in a series of reports prepared by Dr. Francis Gearing at the Columbia University School of Public Health (). All previous studies of treated addicts, as noted earlier, were documents of accumulated failures. From the first reports on methadone and a succession of studies over a decade, the evaluations of the pioneer program appeared to demonstrate an ability to retain most addicts in a community-based treatment program, and to promote improved employment, a marked decline in crime, and even improved prospects for longevity. Other programs tended to confirm the gist of these findings, although some evaluations reported less dramatic results. Nevertheless, the documentation prepared by Dr. Gearing provided the credence for the program that, through time, helped to make methadone maintenance acceptable and to vanquish, or at least modulate, those who had been opposed to the concept of drug maintenance. A long-demanded model for innovative programs was followed, wherein a pilot treatment program was evaluated before it was expanded to include other prospective patients.

One discouraging finding about the research activities that prevail in program evaluation in the field of drug abuse is that so much of it cannot withstand scrutiny. A simple example: We () assembled all the findings we could on retention rates in methadone maintenance programs, surely a reasonably simple datum. Yet, on close examination we had to conclude that we could rely completely on only one report, and that others had such obvious flaws or inconsistencies that the figures had to be viewed with suspicion. There are inherent problems in any long-term field trial, some of them not susceptible to easy solution, and we do not propose to ask for conformity to textbook standards that in reality cannot be accomplished. However, even where less demanding criteria are employed there still remains the question of whether the early results can be viewed with credibility.

This problem, it should be immediately noted, is not limited to drug research but applies to the whole field of evaluation research. In an assessment of 152 comprehensive evaluation projects, it was observed that only 10% met minimum scientific standards (). Another assessment of a sample of 179 projects selected from 532 studies indicated that only 6.7% were able to achieve their stated objectives; another 34% held some promise in light of contingencies not altogether under the control of the investigators (Minnesota Systems Research Inc., 1973). There is even a published experiment where some individuals who happened on the scene were able to demonstrate that the researchers had never determined whether the stimuli, various educational strategies, had ever taken place! They had not ().

We noted earlier that despite the hesitancy many of us may have about promoting the implications of our research for policy alternatives, that research does sometimes have such impact. I assume the various criticisms directed at Gearing’s series of reports are widely known to researchers. I would maintain, however, that the reports still serve as models of programmatic impact, that they reinforce those who are committed to methadone maintenance. They are therefore very important in the field of drug abuse.

Very trenchant criticisms have been directed at Dr. Gearing from the beginning, although they seem to have received very little attention. Perkins and Block (1970) demonstrated the impact of program selectivity on the early program results. Babst, Chambers, and Warner (1971) provided evidence from the same data bank used by Gearing, that clients who more closely resembled the kinds of addicts generally found in jails and on the street did not perform nearly as well as the first reports indicated. They also provided documentation, if any were needed, that more than the very simple tabulations provided by Gearing were needed if there were to be any understanding of what might be happening in the program. Maddux and Bowden (1972) were able to demonstrate that the use of survivor cohorts, where different groups of individuals are contrasted over time, seriously influenced the results presented by Gearing. In Drug Use in America (1973), the National Commission on Marihuana and Drug Abuse documented the way in which crime data were incorrectly analyzed – i.e., that the use of man-years in treatment exaggerates declines. Lukoff (1975) reviewed the research performed by Gearing and demonstrated the way in which her reports tended to provide excessively optimistic results, and also questioned her data base, particularly in the area of crime and drug use.

Obviously, these criticisms have had little impact. In the latest reports prepared by Dr. Gearing (1974), she continues to employ the faulty methodological tools that have been her armamentarium since the very first reports. Along with her colleagues at Beth Israel, she seems immune to the barrage of attacks, many of which appear well-founded.

For those who are unfamiliar with the research on methadone, we present a few figures that demonstrate how to show success even if changes that are something less than very important are actually taking place. Observe that we do not assert that no positive changes have taken place in the programs she studied. We are only stating that the presentation of results can, at a minimum, exaggerate positive outcomes even where one is not creating fictitious numbers.

In figure we present data on arrest rates for the first year after entering treatment from a methadone program in Brooklyn. We present the data for different age cohorts controlled by their preprogram criminal activity. As the results clearly demonstrate, two factors are operative: patients with less preprogram involvement in crime look better after treatment then those who have had more criminal involvement, certainly a nonstartling finding. As patients become older, even where their preprogram criminal activity is similar, their posttreatment crime markedly diminishes. All one has to do therefore, is select older patients, and if at all possible, those who were less criminally involved. There is ample evidence that this happened in the early years of the methadone maintenance treatment program. Where control groups cannot be located, then maturation can certainly account for the diminution of crime.

But controlled experiments are rarely possible in community-based treatment programs, particularly where the population is mobile and deviant, as it is among those who are in drug treatment. The only device to control false results, since patient mortality is a fact of life, is to avoid examining survivors at various points in time. Yet, this practice persists in much evaluation research in drug treatment. To demonstrate the impact this has, in Figure we present two curves (). The top curve reports on all patients at each point in time who missed 26% or more of their medication. If one examines only that curve, it appears that the longer patients remain in treatment the more behavior improves. In the bottom curve, however, we present only the group of patients who remained in treatment over the four years. Two observations can be made, both of them important: First, those who are retained behave substantially better from the very beginning, so that program impact would seem to be secondary to patient motivation and personal decorum; second, that those who remain actually get a bit worse through time. Yet such behavior is consonant with an aggregate finding that things look better! Nor is this a fluke. In all retention cohorts, patients actually missed more methadone the longer they remained in treatment, although they never quite reached the missed medication levels of the group that dropped out during the first year.

The issue we raised at the beginning of this section concerned the interrelationships between science, research, and treatment. Many explanations might be consonant with the review we have made of the conceptual foundations of methadone therapy and the resistance of some of the major actors in the scene to modify their basic themes, or even to attempt any improvement in the research documentation they present to the public. These are all individuals who were willing to enter a very dark arena, in which failure was the norm before they developed their modality, and to present that modality to the world. Most professionals avoided any involvement with addicts, and there would appear to have been few rewards for doing so; yet they were willing to take on an extraordinarily difficult task and to persist until they found a solution that seemed to work.

Although they had their share of calumny, they were finally able to convince large segments of the public, including thousands of addicts, that they had a solution to a problem that seemed to elude all prior attempts at effective action. A large part of the opposition had to back away because of their success. They finally became accepted, their work was rewarded by the largesse of local and federal governments, and their fame and their methods entered the international arena. Nor is there any question that the scientific ethos belongs to them as much as it does to anyone else.

If even some portion of the critique we have made bears any relationship to the truth, then some explanation must be offered for the failure of these devoted, competent, individuals to respond to the long history of criticism of their theoretical underpinnings and of their results. There may be room for some cynicism concerning treatment program managers and staff members whose only careers are related to their programs. When these are in jeopardy they may even twist the truth or simply ignore criticism. However, we suggest that Kuhn might provide a more satisfactory explanation for the reluctance of doctors and researchers to change, even if the drug treatment arena is not a scientific field comparable to those such as biology, physics, or chemistry, which have well-developed theories and technologies associated with them. Yet there is a reasonably coherent theory, one that asserts (a) that addiction is a metabolic disease; (b) that a particular drug – methadone – solves the physiologically based need; (c) that addict behavior can be viewed as a response to sustained heroin use; (d) that methadone is relatively benign; (e) that illicit drug use can be blocked; and (f) that prosocial behavior is a direct consequence of a regimen of methadone.

Like scientists ensconced in a paradigm, the methadone pioneers had evolved an explanation for a problem and translated this into a technology that seemed to work. Although we may be somewhat skeptical of their documentation and are able to offer some counterexplanations for their early successes, this was not the perspective that engaged them at the time. They are less vulnerable to criticism because they know whence they came and what they were able to achieve. Perhaps the best explanation is that the fact of possible failure is difficult to entertain when there is no competing paradigm that offers a solution to the problems their system is designed to treat. Kuhn notes that new paradigms can succeed only when they demonstrate “they can solve the problems that led the old one to a crisis” (). No competing paradigm with a workable technology appears on the drawing boards. Kuhn also observes that scientists must have what is tantamount to a conversion experience before’ they can alter allegiances, a rare occurrence, even in the so-called hard sciences. He states.

Lifelong resistance, particularly from those whose productive careers have committed them to an older tradition of normal science, is not a violation of scientific standards but an index to the nature of scientific research itself. The source of resistance is the assurance that the older paradigm will ultimately solve all problems, that natures can be shoved into the box the paradigm provides. Inevitably, at times of revolution, that assurance seems stubborn and pigheaded as indeed it sometimes becomes. ()

Selections from the book: “The Epidemiology of Heroin and Other Narcotics”. Joan Dunne Rittenhouse, Ph.D., editor. Task Force report on measurement of heroin-narcotic use, gaps in knowledge and how to address them, improved research technologies, and research implication. National Institute on Drug Abuse Research Monograph 16. November 1977.