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I I I I I I I I I I I I I I I I I I I The AmeriCan Academy of Psychiatrists in Alcoholism and Addictions 1991 Annual Meeting ' Session V - Critical issues in Addiction Psychiatry 1st Speaker: Dr. Jerome Jaffe, Associate Director for the Office of Treatment Improvement 2nd Speaker: Dr. Thomas McClellan, Research Professor of Psychiatry - University of Pennsylvania Address to Audience: I'd like to welcome everyone to the final session which is very much a summation and overview of the themes that we've been covering in our annual meeting this year. The two questions that we've been trying to address are fairly simple. First is that, "What is Addiction, and how do we define our appropriate areas of diagnostic and treatment expertise?" This is a particular focus of our first session, and we looked at sex, gambling, and various other potential addictions; and then, second, "Are our treatments for the more clearly defined substance abuse disorders effective?", and this will be the second talk by Dr. McClellan. The answers to these questions are clearly complex, but certainly our two speakers are well matched to the task. I certainly look forward to hearing from them and I would like to now introduce our first speaker in a second. One thing I do want to emphasize though is even though we already gave you your certificates, we ask that you fill out these forms for the CME credits. It's very important for our future livelihood with the APA in them giving us CME certification that we can in fact have as much of a response as possible so that when we file our report with them we in fact have some data to expound on. I'd like to introduce now, Dr. Jerome Jaffe, who is the Associate Director for the office of Treatment Improvement, part of the Alcohol, Drug Abuse and Mental Health Administration. He's a psychiatrist and pharmacologist by training and has devoted most of his professional career in research, treatment, teaching, scientific writing, policy formation, and really in the use of.psychoactive substances. His years in academia began at Albert Einstein College of tz Medicine where he completed his training in psychiatry and ~ pharmacology and held his first faculty position. He continued ~ at the University of Chicago where he served simultaneously as ~ the director of the State of Illinois' drug abuse programs. He ~ was then appointed by President Richard Nixon to serve as Special,-,o Consultant to the President for Narcotics and Dangerous Drugs and W 00 t"D iND

I I I I I I I I I I 1 I I I I I I I confirmed by the Congress of the United States as the first director of the Special Action Office for Drug Abuse Prevention. Many of the basic and epidemiological research programs that formed the.basis for current efforts in research and treatment were initiated during his tenure in that office. Returning to academia, Columbia University College of Physicians and Surgeons, and then at the University of Connecticut School of Medicine, Dr. Jaffe carried out studies on nicotine arid alcohol dependence and continued to write widely on issues related to drug abuse and dependence. He than became director of the Addiction Research Center and senior science advisor for the National Institute on Drug Abuse. Dr. Jaffe serves as member and consultant to the World Health organization Expert Committee on Drug Dependence, numerous advisory boards and editorial boards. He's therefore particularly well-qualified to address the current concepts of addiction and put in perspective some of the issues raised at this meeting. These are issues about other addictions such as sex, gambling, eating disorders, as well as the disease model of drug use and how it impacts on the managed care aspects of treatment reimbursement. Finally, I would like to mention that Jerry's really been very helpful and really provided a very important impetus to the careers of many young clinical investigators and clinical researchers, certainly including myself, and I'd like to acknowledge the key role that he has played in guiding substance abuse treatment in the United States throughout his long and outstanding career. without trying to embarrass Jerry any more than that, what I'm gonna do is simply have him talk. Dr. Jaffe: Thank you, Tom . . . a pleasure to be here to speak to this distinguished group. I think that what I'm gonna say is just slightly redundant because I'm going to expand on some ideas that John Tamerin introduced so eloquently and succinctly in the opening session of this meeting. Do the words and concepts we use to describe the problem we deal with make a difference? Do they have significance for the way we treat people or the way policy-makers respond to social problems related to drug or alcohol use? Tamerin said that the concepts we use do make a difference because they help to shape the way we treat people and they help to shape the way we develop hypotheses when we conduct research. And I certainly agree with this. But I think that we have to recognize it as academics, and as researchers and scientists we sometimes forget that the definitions we develop and the models that we use to explain the nature of dependence as we see it, may not correspond to either the definitions or the models that are useful or acceptable to other groups in society. What's useful 2 I

~ ' to a psychiatrist may not be useful to a judge o r to a legislator, or to an archbishop. I've just returned from a ~ conference at the Vatican where the topic was "Drugs Against Life," and.I can assure you that psychiatrists were in the minority at that conference, and their perspective on drugs was , distinctly different from the perspective that we entertain here. Sometimes we, ourselves, use different definitions and ' models in the course of a day as our social roles change: from scientist, to clinician, to advisors, to other groups, and to agencies. But most important neither our definitions nor our models are as independent of our culture and our history as we , might wish to believe. Certainly, in contemporary American  society, science has been given no exclusive or proprietary right to use terms such as, "drug dependence" or "addiction." Other , sectors of society appear to believe that whatever addiction is, it is not just something that is seen with drugs such as morphine, cocaine or alcohol. Now, can we see the first slide, please? Not long ago, Time magazine wanted us to believe that, for Americans, eating salt was an addiction. The Baltimore Sun told ' its readers that the citizens of Maryland were addicted to the - state lottery. The New York Times would have us believe that Americans are addicted to oil, and the Post's Hobert Rowen ' believes that our President is addicted to imported oil. Fortune magazine says we're addicted to corporate grand strategy. The New York Times has some of us addicted to taking educational courses, the Wa11-Street Journal cautions us about getting ' addicted to foreign capital, The Washington Post tells us that our legislators are not only addicted to special interest money, but they also get high on it, Today blames the recession on ' addiction to cost cutting, Madison Avenue tells us to buy a new magazine named Fame and tells us that Fame is addicting. It's apparently not too addicting -- the magazine has recently gone , bankrupt -- an author in an investment magazine tells us how he tried to break his addiction to the Financial News Network using satiation strategies that consisted of watching it for an entire day. A university claims that winning is addictive and suggests j that we can acquire this desirable condition by enrolling in its ! courses for executives. Newsweek asserts that our executives are addicted to perks and a psychiatrist confesses to being addicted , to computerized literature searches. Now, some of these are obviously and deliberately metaphorical uses of the term. But is it any wonder that we do not seem surprised when psychologists ~ and psychiatrists begin to assert that sex is addicting, and to do so in a serious, non-metaphorical way? This concept, by the way, was given the ultimate stamp of approval in American culture t.D ~ ' when Dear Abbey told her readers, Yes there is sexual addiction, ~: and Dear Abbey supported her position by indicating that there is ~ already a treatment: "Sexoholics Anonymous." Now there are ~ advertisements for hospital-based treatments for sexual addiction ~ Co 3 ~ t~? i `~

~ ' and the topic was included on the scientific program Finall rogram of this m y, one author has concluded that alh of us are ' addicts: "All people are addicts and addictions to alcohol and other drugs are simply the more obvious and tragic attachments. To be alive is be addicted, and to be alive and addicted is to I stand in need of grace." Well, this gives some hint as to the way in which morality , and the scientific issues are continually interacting and remain intertwined. But surely science requires concepts that are somewhat more circumscribed and a process of accepting new clinical syndromes as somewhat more deliberative, Kendler has , argued the changes in scientific nosology should be based on the  accumulation of research findings rather than on expert opinion which can be more mercurial than we wish to believe. He says ' that such a process such as scientifically-based nosology would keep us honest, clarifying what we know and what we don't know, and it should increase our credibility -- the credibility of our „ nosology in the eyes of other mental health groups and of society , at large. And this is a point that I will return to because I think the issue of credibility is worth emphasizing. It was brought up by one of the questioners at the early session and / it's something, as I said, that I'll return to. Because while -, . the media and the laity have every right to use words like "addiction" and "dependence," metaphorically, when these terms ~ are used by helping professions to designate a variety of. problematic behaviors with the implication that they are valid and reliable diagnostic entities that ought to be treated by medical professionals using scientifically validated methods, ' they cease to be metaphors. We run the risk that all of our efforts at diagnosis in this area will be seen as self-serving maneuvers designed to medicalize undesirable behaviors. ~ Accusations of such self-serving behavior are made periodically with varying degrees of cogency. The views of Thomas Saaze and Stanton Peale or only two examples, and I'll return to these ' criticisms momentarily. Now, models definitions and diagnostic criteria are intended to serve different functions. Let me try to illustrate: DSM , III-R and ICD-10 are systems of categorizing problems. As most of you knov, they were originally designed to handle mortality statistics. These compendia of problems are supposedly i atheoretical but in the case of drug dependence both of these , systems of categorization have built their definitions in criteria.for diagnosis around the same conceptual model that was ~ articulated in 1976 in an article on the alcohol dependence syndrome by Edwards and Gross. In 1980, shortly after DSM-III and ICD-9 were issued, a WHO working group was convened to i_.D further develop concepts and definitions that could be used in c; , DSM III-R and ICD-10. The content and postulates of that model a~  are probably familiar to almost all of the people in this ~ audiencR, and several members of this organization were actually ~ ~ - ~ 4 ~ , U~

I I I I I I I I I I I I I I I I participants at that meeting and Jack Durell, our treasurer, was the key government official who was instrumental in-seeing that that meeting took place. Let me therefore review just a few of the assumptions and postulates that were incorporated into that working group's paper. First, some drugs are reinforcing; they induce euphoria or they•attenuate dysphoria. Because repeated use has multiple consequences, they may be aversive or reinforcing, and they may influence habit strength. The drugs are biologically active, inducing neural adaptation. Now, tolerance may influence both reinforcing and aversive effects by permitting or requiring higher doses. Physical dependence may influence reinforcing effects by creating a new motive for repeated use. Another postulate is drugs differ in the mechanisms by which they exert the reinforcing and toxic effects and this is another issue that I'll get back to shortly. The third is that individuals differ in their response to drugs -- their vulnerability -- and that, in turn, is influenced by genetics experience and psychopathology, and environmental cues and internal cues come to be linked to positive effects and- to negative effects through learning. And I think you have heard this from Dr. Chiltris, Dr. McAuliff -- and the urge to use a drug waxes and wanes and is influenced by availability and mood. Environmental cues and internal cues, priming effects, withdrawal, memories of drug effects and, again, these are things that have been reviewed by Chiltris and McAuliff and, in fact, these particular postulates about the model have led to specific interventions that turn out to have some import and have been demonstrated to have some efficacy. Weighing the cost of drug use involves cognition. It's influenced by mood and experience, and by cognitive capacity, and this, too, is an important postulate that has led to specific interventions. Now, the urge to use a drug does not always result in drug use. It's influenced by the perceived costs and consequences, and personality and mood. Now the last of these slides, but certainly not the last of the postulates ...(this, by the way is the figure . . . I want to tell you that this figure is so complex, I've never been able to develop a slide that would be readable at more than ten feet, so it's not important that you pay too much attention to it; it shows . . . if this thing were working, it would show . . . well, in the middle there's drug use leading to neuradaptation, but I'm not gonna go into that) but take my word for it, no place in this complex cartoon that the WHO made, will you find the word, "drug dependence" or "addiction," and so it's . . . so it's logical to ask, "Where in this model does addiction or dependence reside?" The WHO group argued that dependence is located within the system. In the relationship among the elements of the system, 5 I

I I I I I I I I I I I I I I I I I I and while it might be convenient for clinicians and others to see dependence as something going on within the individual, (and, by the way, DSM III-R requires that we entertain that perspective that dependence is in the individual) any interpretation that puts too much emphasis on one part of the system, whether the social influences, the family dynamics, the behavior or the biology of the individual, is probably missing part of the nature of dependence. Now, I should mention that drug abuse is not always a prodromal state. It does not always lead to dependence, nor is it always a transient phase that is followed by nonuse or socially acceptable behavior. It may indeed persist as abuse without other manifestations of dependence. Now, neither the diagram nor the postulate speak to the primacy of any single process. It is not asserted in the model that relief of withdrawal is . . . (Oh, I should get that off. It's simply too hard to read.) but drug dependence (I'll leave that on 'cause it's easy to read.) The essential feature is that drug controls behavior and there's loss of flexibility. But, I want to get back to this issue of primacy of motives. The model doesn't speak to the idea that withdrawal is more important than positive reinforcement. A11 of these factors contribute to the behavior, but this is an area of considerable - interest to researchers and perhaps the clinicians as well, and this question of primacy is a controversy that has persisted for more than a century, and the question is: Do people continue to take drugs to alleviate withdrawal, or do they take them because they continue to experience some of the initial reinforcing effects? Now several developments have rekindled the issue. For example, animals with electrodes planted in the brain will work very hard to get an electrical current. Most of the drugs that are found to be reinforcing tend to lower the threshold for that reinforcing electrical current, and tolerance does not seem to develop to that particular property of the drugs. Another observation is animals can be trained to press a lever to get a number of reinforcing drugs and they'll do so with great enthusiasm even under conditions that are so arranged that the animals never become physically dependent. So the observation that reinforcement is possible and repetitive drug- taking behavior is possible even in the absence of physical dependence, took on even greater significance when it was shown that the.neural substrate, particularly for opiate withdrawal, was distinct from the neural substrate for reinforcement. Now if drug use is interrupted, animals like humans will resume heroin or cocaine use long after there's any reasonable likelihood that the drug-using behavior is related to any effort to alleviate withdrawal. Thus to some researchers it seemed unnecessary to postulate that withdrawal was even necessary as an 6 I

I I I I I I I I I I I I I element iri explaining drug dependence. Roy Weiss is spokesman for the primacy of positive reinforcement =- and he believes it can produce compulsive drug self-administration in the absence of any withdrawal distress, or obvious source of pain or discomfort, and it's sufficient to account for both the initial development and for relapse and rapid re-addiction after patients have been detoxified. Further, he believes it has a distinct neural basis as does withdrawal and physical dependence. Now, it's his belief and that of a number of others, that craving is more often linked to the primary memory of positive reinforcement and that these cravings, which may be evoked by drug-associated stimuli in the environment, persist long beyond the time associated with measurable withdrawal symptoms. And, again, you heard from Dr. Chiltris, that long after people have no evidence of withdrawal, they are still bothered by environmental stimuli that evoke craving which is linked to a memory of positive reinforcement. And it's the emphasis on the memory of positive reinforcement in the form of euphoria that distinguishes this view from those of Ludwig and Wickler who viewed craving as an evocation of conditioned withdrawal that had taken place during active use of the drug. But, in any event, the idea that environmental and internal cues become linked through learning to drug effects -- positive or negative -- is deeply imbedded in the current WHO model on which DSM-III and ICD-10 are based. Now; I don't want to leave anyone with the idea that withdrawal is not important, having just outlined to you the case for positive reinforcement. The regular reoccurrence of withdrawal and its relief by further drug use does produce repeated reinforcement of drug-taking behavior, and because they occur regularly, there's ample opportunity for environmental stimuli and internal mood states to become linked to withdrawal through learning. Subsequently, long after there's any measurable withdrawal, the mood or environmental condition may evoke components of withdrawal syndrome associated with urges to use the drug again.  But perhaps the most important argument that withdrawal can be a major motive in some cases, is that the spectrum of drug- dependent dependent people encompasses many for whom some form of negative reinforcement is the dominant mechanism underlying the development and persistence of dependence. An obvious example is seen in most people who become dependent on benzodiazepines taken ' in the course of treating anxiety symptoms. Many people who have been taking benzodiazepines find difficulty in stopping. In some cases the difficulty is because the original symptoms return; in t"D ~ others, it's because there are new distressing symptoms C~ indicative of withdrawal. The use of benzodiazepines suppresses A;;Ib both kinds of aversive states. In either case, the drug is C_~ , w ~ 7 C~o ' tZi

I I I I I I I I I I I I I I I I I I acting as a negative reinforcer in perpetuating drug-using behavior. There are instances in which benzodiazepi-nes induce euphoria in non-dependent, non-anxious individuals, but they're infrequent.relative to the number of individuals who experience only relief of anxiety. Now, the net conclusion supports the general proposition that drugs can gain control over behavior and produce decreased flexibility by more than one mechanism and the same drug can act in different ways in different individuals. Now as complicated as it is, that WHO cartoon was still oversimplified. The next few slides represent an attempt to add a few elements that I believe deserve a bit more emphasis. Now Tamerin said, and I want to repeat, that the models we use help to determine how we approach treatment and which hypotheses we will choose to test, and I want to . . . that's by way of trying to justify producing efforts at models. (This is just a little bigger and allows me, if I can sharpen it up, but, is there a dot at all? Yes. Can I be heard if I walk over this way? Let me walk over this way. Can you hear me?) This is the urge to use . . . [indistinguishable]. . .. This box shows cognitive risk/benefit assessment. In the original WHO model, it said, - "This leads to drug use." In the real world that's not the way it is. You decide to use either Drug A or Drug B or you decide to use non drug use and non drug use itself can either have positive Qr negative consequences, and so that leads to the idea that maybe you have increased the positive reinforcement aspect of the decision for non drug use. Now that just shows that drug use leaves the most positive consequences or negative consequences and, at the same time, maybe the tolerance and physical dependence and positive and negative consequences feed back to aversive learning and approach learning to alter both the urges to use and the risk/benefit assessment. This slide is an attempt to put in a few of the things that research has indicated tend to increase the likelihood of drug use. Some of the things that are aversive and, obviously, contact of active users is something that we all know increased the urge to use drugs -- available drugs -- increase the urge to use drugs. Uh, there's something over here called "Hassles and Losses" which was the major subject of a paper out of the Yale group. Addicts, particularly those who use illicit drugs, don't lead lives of tranquility; they have more than their share of losses and problems, and all of those have the tendency to increase the urge and, in this case, produce aversive mood states, and aversive mood states always lead to urges to use and to get relief of those and they include not just withdrawal states which are seen here, but anger and depression and anxiety. Now over here we show just the beginning of some of the things that can ameliorate that which includes coping skills. You learn how to cope with feels,ngs other than by using drugs but some 8

I I things interfere with coping skills -- like anti-s9cial i i t ~ personal es and depression and limited intelligence which is something that is too often overlooked. Now, I want to show one more here which are some of the , things that may be ameliorated and they're shown in green, and ' here you see how many places coping skills can intervene in this system. It can affect urges, it can increase one's cognitive ~ risk assessment capacities, but you also see here something called fear. We don't talk about it much, but you have to understand that it does alter the system: people fear the law; . they fear their employer; they can fear various kinds of things; , they can fear AIDS. Let's recognize that what makes the treatment of physicians so uniformly successful is not the ~, efficacy of the psychotherapy we use, it's the contingency ,/ contracts that say if you don't get better when we test you, you're going to lose your medical license. So fear figures in here -- there's fear of the probation officers -- and there are a ~ few other things here which are a little harder perhaps to see. This is really the reason I put up the slides, because some of the things that deal with reducing aversive mood states, include ~, things like hope and faith, and this model is not incompatible _ ' with the kind of view that AA puts together because hope and faith still have a major impact on aversive mood states. ~ And the last slide of this series shows where treatment works and-, as you see, treatment can inte~vene in many places. It can alter the aversive effects of physical dependence. It can ~ work on the negative consequences of drug use. It can offer coping skills. It can induce contingency contracts, if that's what's necessary. It can also be the hope that people have for _ recovery, it can induce self-esteem, we can work directly on I aversive mood states and, as you're gonna hear from Tom McClellan, what we're finding is the more points in the system that treatment is asked to intervene, the more effective is the / treatment. Comprehensive treatment works better than treatment i directed at any one of these multiple factors in the system. ~ Now the purpose of the model, which I have so cursorily presented here, was to conceptualize the relationships among the factors. It was not intended to yield criteria that could be used to decide if an individual was drug dependent. That's the ~ distinction between a model and a definition. The definitions are for people who have to put people into boxes, either to admit them or to put up statistics for national purposes. And r definitions that can classify and identify are necessary both for ~ . epidemiology and clinical work. ~ ~ The classical typologies such as those used by DSM III-R may ~ , be of two types: they can be monothetic or they can be ~ polythetic. Those which require an individual to meat each of ~ several criteria to be assigned to a category are called pa  9 O I

I I I I ~ I I I I I I I I I I I monothetic: you must meet every single one of the items. It's a unique set of criteria and it's both necessary and sufficient. The current DSM III-R classification is polythetic: no one diagnostic.criterion is either necessary or sufficient. Polythetic categories are quantitative by implying that a syndrome may be present in greater or lesser degree, and as I indicated to you in a previous slide, drug dependence is one of those syndromes which we believe exists in degrees of severity. There's no sharp line even though we may have to set up arbitrary criteria as to where we will say it exists. DSM III is also a composite in that individuals are considered dependent if they meet three but once assigned, severity is inferred from the number of individual criteria met. I mention these technical points because the current proposal for DSM IV includes options to make the system more of a hybrid. Under one set of suggestions, changes in physical dependence and tolerance would again become required criteria for drug dependence diagnosis provided several other criteria are met. As in DSM III-R, severity would be judged from the number of additional criteria, but under one option, without physical dependence and tolerance, the diagnosis of dependence could not be made no matter how many other criteria were met. It may be that some of these individuals are responding to the tendency of the concept of addiction to proliferate to a variety of nonchemical dependencies. I really don't know what t:he motive is, but the significance of the change is two-fold: it would obviously inf luence the diagnosis of drug dependence, but it will also influence our response to other repetitive behaviors as well. The restoration of tolerance and physical dependence as required elements would tend to exclude many of these non- chemical repetitive behaviors from some super-category of addictive disorders. Now, I have a few minutes left, and I want to touch on Manifestos, Metaphors, and Credibility. Let me return to this issue of credibility and remind us that many of the behaviors described in the popular media of addictions seem to the average citizen and to most scientists to be voluntary behaviors carried out because they have utility or provide some satisfaction to those involved. About 200 years ago, for most of Western society, the use of alcohol, opiates and tobacco also seemed like voluntary behaviors although, admittedly, like any behaviors so often repeated, they became powerful habits. The attitude was essentially libertarian. If the behaviors, particularly when present excess elicited any attention, they were seen as vices -- moral failings -- or, put in more clearly religious terms, as sin. Then physicians began to assert that some patterns of drug- taking were more like diseases than immoral behavior. But the physicians went further. According to Griffith Edwards, 10