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Articles - Addiction
Written by Thomas Mclellan   
Wednesday, 04 October 2000 00:00

Drug Dependence, a Chronic Medical Illness

Implications for Treatment, Insurance and Outcomes Evaluation

Thomas McLellan, PhD, David C. Lewis, MD, Charles P. O'Brien, MD, PhD Herbert D. Kleber, MD

Author Affiliations: The Treatment Research Insti­tute, Philadelphia, Pa (DrMcLellan); The Penn/VA cen­ter for Studies of Addiction at the Veterans Affairs Medical Center and the University of Pennsylvania, Philadelphia (Drs McLellan and O'Brien); The Brown University Center for Alcohol and Addiction Studies, Providence, RI (Dr Lewis); and The National Center on Addiction and Substance Abuse at Columbia Uni­versity, New York, NY (Dr Kieffer).

Corresponding Author: A. Thomas McLellan, PhD, The Treatment Research Institute,150 S Independence Mall W, Suite 600, Philadelphia, PA 19106-3475

(e-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it )

Many expensive and disturbing social problems can be traced directly to drug dependence. Re-cent studies(1-4) estimated that drug de­pendence costs the United States ap­proximately $67 billion annually in crime, lost work productivity, foster care, and other social problems.(2-4) These expensive effects of drugs on all social systems have been important in shap­ing the public view that drug depen­dence is primarily a social problem that requires interdiction and law enforcement rather than a health problem that requires prevention and treatment.

This view is apparently shared by many physicians. Few medical schools or residency programs have an ad-equate required course in addiction. Most physicians fail to screen for alco­hol or drug dependence during rou­tine examinations.(5) Many health pro­fessionals view such screening efforts as a waste of time. A survey (6) of general practice physicians and nurses indi­cated that most believed no available medical or health care interventions would be "appropriate or effective in treating addiction." In fact, 40% to 60% of patients treated for alcohol or other drug dependencies return to active substance use within a year following treatment discharge.(7-9) One implication is that these disappointing results con-firm the suspicion that drug depen­dence is not a medical illness and thus is not significantly affected by health care interventions. Another possibil­ity is that current treatment strategies and outcome expectations view drug dependence as a curable, acute condi­tion. If drug dependence is more like a chronic illness, the appropriate stan­dards for treatment and outcome expectations would be found among other chronic illnesses.

To explore this possibility, we un­dertook a literature review comparing drug dependence with 3 chronic ill­nesses: type 2 diabetes mellitus, hyper-tension, and asthma. These examples were selected because they have been well studied and are widely believed to have effective treatments, although they are not yet curable. Our review searched all English-language medical and health journals in MEDLINE from 1980 to the present using the following key words: heritability, pathophysiology, diagno­sis, course, treatment, compliance, adherence, relapse, and reoccurrence. Im­portantly, our definition of drug and our review criteria included all over-the-counter (alcohol and nicotine), pre­scription (benzodiazepines, amphet­amines, opiates), and illegal (heroin, marijuana, cocaine) drugs.

The review is presented in 2 parts. The first part considers some charac­teristic aspects of chronic illness, such as diagnosis, heritability, etiology, and pathophysiology. The second part re-views recent advances in the medical treatment of drug dependence and con­siders treatment response, particu­larly medication adherence and re-lapse or recurrence. Although we are aware that arguments by analogy are limited, we believe this comparative analysis of drug dependence with other chronic illnesses offers some instruc­tive and provocative implications.



Most adults have used alcohol and/or other drugs, sometimes heavily to the point of abuse but rarely to the point where that use could reasonably be called an illness. There is no labora­tory test for dependence, but the diag­nostic differentiation of use, abuse, and dependence has been operationally re-fined and repeatedly shown to be reli­able and valid.(10,11)

Dependence or what is commonly called addiction is operationally defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(10) as a pathologic condition manifested by 3 or more of 7 criteria. Two of these cri­teria, tolerance and withdrawal, indi­cate neurologic adaptation or so-called physiologic dependence. However, as has been pointed out,(12) physiologic adaptation (tolerance or withdrawal) by itself is neither neces­sary nor sufficient for a diagnosis of sub-stance dependence. Indeed, those receiving a dependence diagnosis are required to show a "compulsive desire for and use of the drug(s) despite seri­ous adverse consequences" such as "use instead of or while performing impor­tant responsibilities"(10,11)

There are several short (<5 min­utes of patient or practitioner time) questionnaires that can screen for al­cohol and other drug dependence disorders with high rates of sensitivity and specificity.(13) Following a positive screening result, standardized diagnos­tic checklists can be applied during the medical evaluation. Diagnoses that result from these standardized and eas­ily applied criteria have been reliable and valid across a range of clinical and nonclinical populations.(11)

Genetic Heritability

One of the best methods for estimat­ing the level of genetic contribution is to compare the rates of a disorder in monozygotic and dizygotic twins. Heri­tability estimates from twin studies(14,15) of hypertension range from 0.25 to 0.50, depending on the sample and the diagnostic criteria used. Twin stud­ies of diabetes offer heritability esti­mates of approximately 0.80 for type 2(16) and 0.30 to 0.55 for type 1 diabetes mellitus." Finally, twin studies(18,19) of adult-onset asthma have produced a somewhat broader range of heritabil­ity estimates, ranging from 0.36 to 0.70.

Several twin studies(20-23) have been published in the substance depen­dence field, all showing significantly higher rates of dependence among twins than among nontwin siblings and higher rates among monozygotic than dizygotic twins. Published heritability estimates include 0.34 for males de-pendent on heroin, 0.55 for males de-pendent on alcohol, 0.52 for females dependent on marijuana, and 0.61 for cigarette-dependent twins of both sexes.(20-23) More studies of heritability are needed across drug types and sexes, but the evidence suggests significant ge­netic contribution to the risk of addic­tion comparable to that seen in other chronic illnesses.

Role of Personal Responsibility

Since the use of any drug is a volun­tary action, behavioral control or will-power is important in the onset of dependence. Thus, at some level an addicted individual is at fault for initi­ating the behaviors that lead to a de­pendence disorder. Doesn't this volun­tary initiation of the disease process set drug dependence apart, etiologically, from other medical illnesses?

There are many illnesses in which voluntary choice affects initiation and maintenance, especially when these vol­untary behaviors interact with genetic and cultural factors. For example, among males, salt sensitivity is a ge­netically transmitted risk factor for the eventual development of one form of hypertension.(24,25) However, not all of those who inherit salt sensitivity de­velop hypertension. This is because the use of salt is determined by familial salt use patterns and individual choice. Similarly, risk factors such as obesity, stress level, and inactivity are prod­ucts of familial, cultural, and personal choice factors.(24,25) Thus, even among those with demonstrated genetic risk, a significant part of the total risk for de­veloping hypertension can be traced to individual behaviors.

There are also involuntary compo­nents embedded within seemingly vo­litional choices. For example, al-though the choice to try a drug may be voluntary, the effects of the drug can be influenced profoundly by genetic fac­tors. Those whose initial, involuntary physiologic responses to alcohol or other drugs are extremely pleasurable will be more likely to repeat the drug taking than those whose reaction is neu­tral or negative. Work by Schuckit(26) and Schuckit and Smith(27) has shown that sons of alcohol-dependent fathers in­herit more tolerance to alcohol's ef­fects and are less likely to experience hangovers than sons of non–alcohol-dependent fathers. In contrast, the in­herited presence of an aldehyde dehy­drogenase genotype (associated with alcohol metabolism) causes an invol­untary skin "flushing" response to alcohol.(28-30) Individuals who are homo­zygous for this allele (approximately 35% of the Chinese population, and 20% of Jewish males in Israel) have an especially unpleasant initial reaction to voluntary alcohol use to the point where there are virtually no alcoholics found with this genotype.(28-30)


The acute effects of alcohol and other drugs have been well characterized. However, even a complete understand­ing of these acute effects cannot ex-plain how repeated doses of alcohol and other drugs produce paradoxically in-creasing tolerance to the effects of those drugs concurrent with decreasing vo­litional ability to forgo the drug. As sug­gested by Koob and Blooms(31) the chal­lenge is to find an internally consistent sequence by which molecular events modify cellular events and in turn pro-duce profound and lasting changes in cognition, motivation, and behavior. Research on the neurochemical,neu­roendocrine, and cellular changes as­sociated with drug dependence has led to remarkable findings during the past decade, as summarized in the recent lit­erature.(32-35) Herein, we summarize just 3 areas of investigation.

Addictive drugs have well-specified ef­fects on the brain circuitry involved in the control of motivated and learned behaviors.(31-36) Anatomically, the brain cir­cuitry involved in most of the actions of addictive drugs is the ventral tegmental area connecting the limbic cortex through the midbrain to the nucleus accumbens.(35-36) Neurochemically, alco­hol, opiates, cocaine, and nicotine have significant effects on the dopamine sys­tem, although through different mecha­nisms. Cocaine increases synaptic do­pamine by blocking reuptake into presynaptic neurons; amphetamine produces increased presynaptic release of dopamine, whereas opiates and alco­holdisinhibit dopamine neurons, pro­ducing increased firing rates. Opiates and alcohol also have direct effects on the en­dogenous opioid and possibly the y-ami­nobutyric acid systems.(31-36)

Significantly, the ventral tegmental area and the dopamine system have been associated with feelings of euphoria,(31-36) Animals that receive mild elec­trical stimulation of the dopamine sys­tem contingent on a lever press will rapidly learn to press that lever thou-sands of times, ignoring normal needs for water, food, or rest.(36) Cocaine, opi­ates, and several other addictive drugs produce supranormal stimulation of this reward circuitry.(31-36)

Given the fundamental neuro-anatomy and neuropharmacology of this system, it is understandable that ad­dictive drugs could produce immedi­ate and profound desire for their read-ministration. Less clear is why simply preventing the administration of these drugs for some period would not cor­rect the situation, return the system to normal, and lead to a "sadder but wiser" individual who would be less instead of more likely to reuse those drugs.

It is known that use of these drugs at some dose, frequency, and chronic­ity will reliably produce enduring and possibly permanent pathophysiologic changes in the reward circuitry, in the normal levels of many neurochemi­cals, and in the stress response system.(31,35,37-41) Volkow et al (37-42) found impairments in the dopamine system of abstinent former cocaine users 3 months after their last use. Otherstudies(39,40) have documented sustained changes in the stress response system following abstinence from opiate or co­caine dependence. Researchers do not know how much drug use is required to create these changes or whether these effects ever return to normal. Somatic signs of withdrawal last several days, motivational and cognitive impair­ments may last several months(33) but the learned aspects of tolerance to the drug may never return to normal.(35,36,41)

A second explanation for the endur­ing pathology seen among drug-dependent persons and their ten­dency to relapse lies in the integration of the reward circuitry with the moti­vational, emotional, and memory cen­ters that are colocated within the lim­bic system. These interconnected regions allow the organism not only to experience the pleasure of rewards but also to learn the signals for them and to respond in an anticipatory manner.(36,41,43) Repeated pairing of a person (drug-using friend), place (corner bar), thing (paycheck), or even an emo­tional state (anger, depression) with drug use can lead to rapid and en-trenched learning or conditioning. Thus, previously drug-dependent in­dividuals who have been abstinent for long periods may encounter a person, place, or thing that previously was as­sociated with their drug use, produc­ing significant, conditioned physi­ologic reactions, such as withdrawal-like symptoms and profound subjective desire or craving for the drug.(43,44) These responses can combine to fuel the "loss of control" that is considered a hall-mark of drug dependence.(10)

These conditioned physiologic responses have been shown in labora­tory studies(41,45,46) of currently abstinent former opiate, cocaine, and alcohol—dependent individuals. Childress et al,(43) using positron emission tomography, examined limbic and control brain regions of detoxified, male, cocaine-dependent subjects and cocaine-naive controls during videos of cocaine-related scenes. During the video, these currently abstinent former cocaine-dependent subjects experienced in-creased craving and showed a pattern of limbic increases and basal ganglia decreases in regional cerebral blood flow that mimicked the effects of the drug itself. This pattern did not occur in cocaine-naive controls or among the for­merly cocaine-dependent patients in response to a neutral video.(43) Thus, even artificial video scenes of cocaine-related stimuli, presented in the sterile context of a positron emission tomog­raphy laboratory, produced excitation of brain reward regions and triggered drug craving.


A central question in the comparison of drug dependence with other ill­nesses is whether dependence will de-crease without treatment and whether it will respond to medications and other interventions. There is a large re-search literature on drug dependence treatment outcomes.(7-9,34,35,47-49) The treatment of addiction has been de-scribed in a manual(50) and 2 detailed volumes (51,52) Space permits only a few ex­amples from that literature, addressing questions of particular import to phy­sicians.

Untreated Persons

Examinations of untreated, dependent persons offer some indication of the natural course of addiction. For example, Metzger et al(53) measured drug use, needle-sharing practices, and human immunodeficiency virus (HIV) infec­tion rates of 2 large samples of opiate-dependent persons in Philadelphia, Pa. The in-treatment (IT) group included 152 patients randomly selected at admis­sion to a methadone maintenance pro-gram. Out-of-treatment (OT) subjects were also heroin-dependent individuals matched to the IT group by age, race, sex, neighborhood, and other relevant background factors, although none of the 103 OT subjects had received treatment. Both groups were interviewed and tested for HIV status every 6 months for 7 years. At the initial assessment, 13% of the IT sample and 21% of the OT sample were HIV positive. By 7 years, 51% of the OT group but only 21% of the IT group tested HIV positive.53 Of course, even this substantial between-group difference does not prove that treatment participation was the causal agent. It is likely that the OT subjects lacked the motivation for change found among the treated patients. Thus, lack of desire for personal change, rather than the effects of the treatment itself, could have produced the differences seen.

One way to separate the effects of drug dependence treatment from the effects of motivation is to compare treated and untreated substance-dependent indi­viduals who were explicitly not inter­ested in treatment. Booth and col­leagues50 studied 4000 intravenous drug users seeking HIV testing as part of a multisite acquired immunodeficiency syndrome initiative in 15 cities. Sub­jects were randomly assigned to either standard HIV testing alone or to stan­dard testing plus 3 sessions of motiva­tional counseling from a health educa­tor. At 6-month follow-up, those who received additional counseling showed half the rate of drug injection (20% vs 45%), 4 times the likelihood of absti­nence (confirmed by urinalysis), and sig­nificantly lower arrest rates (14% vs 24%) than those randomly assigned to receive just HIV testing.(54) Studies of other illnesses show that screening and brief advice from physicians can affect the motivation for change among pa­tients and the longer-term course of their health. The data of Booth et al suggest this is true even for seriously addicted individuals.

Svikis et al(55) studied drug abuse treatment in pregnant, cocaine-dependent women who did not originally apply for treatment. All women had simply ap­plied for prenatal care and were found to be positive for cocaine use on a rou­tine drug screen. They were compared with 46 pregnant, demographically matched women who tested positive for cocaine use and received standard pre-natal care during the year before the op­ening of the experimental treatment program. Drug dependence treatment consisted of 1. week of residential care followed by twice-weekly addiction counseling in the context of the sched­uled prenatal visits.

At delivery, 37% of the treated patients tested positive for cocaine use compared with 63% of the untreated women. Infants of the treated women averaged higher birth weights (2934 vs 2539 g) and longer gestational periods (39 vs 34 weeks) than those of the com­parison group. Following delivery, 10% of infants in the treated group required care in the neonatal intensive care unit (mean, 7 days). In comparison, 26% of infants in the untreated group required intensive care (mean, 39 days). Aver-age costs of care were $14500 for the treated group and $46 700 for the com­parison group. These data indicate that drug-dependent women can be screened and motivated during prenatal care and that drug dependence treatment can be combined with traditional prenatal care in an extremely cost-effective manner.


In addition to medications for nico­tine dependence, such as nicotine gum and patch and bupropion hydrochlo­ride, medications for alcohol and opi­ate addiction have been developed under Food and Drug Administration guidelines, have been researched in ran­domized clinical trials, and have reached the market. Herein, we discuss a few recent developments, but a complete review has been published by the Institute of Medicine.(35)

Opioid Dependence.

Opioid ago­nists, partial agonists, and antagonists are the 3 primary types of medications available for the treatment of opioid de­pendence, all acting directly on opioid receptors, particularly µ-receptors.(35) Agonist medications, such as metha­done hydrochloride, are prescribed in the short-term as part of an opioid de­toxification protocol or in the long-term as a maintenance regimen. Double-blind, placebo-controlled tri­als(56,57) have shown methadone to be ef­fective in both inpatient and outpa­tient detoxification, although the long-term effects of detoxification alone, without continuing treatment, have been uniformly poor. As a mainte­nance medication, methadone's oral route of administration, slow onset of action, and long half-life have been ef­fective in reducing opiate use, crime, and the spread of infectious diseases, as was recently validated by a Na­tional Institutes of Health Consensus Conference.(58)

The partial agonist buprenorphine hydrochloride is administered sublin­gually and is active for approximately 24 to 36 hours.(59) Large double-blind, placebo-controlled trials of buprenorphine have shown reductions in opi­ate use comparable with methadone but with fewer withdrawal symptoms on discontinuation.(60) Importantly, the combination of buprenorphine plus nal­oxone hydrochloride, designed to reduce injection use, will soon be released for prescription in primary care settings.(61)

Opioid antagonists such as naltrex­one block the actions of heroin through competitive binding for 48 to 72 hours, producing neither euphoria nor dys­phoria in abstinent patients (62,63) Naltrexone is used as a maintenance medi­cation, designed as an "insurance policy" in situations where the patient is likely to be confronted with relapse risks. Naltrexone in combination with social or criminal justice sanctions is routinely used in the monitored treatment of physicians, nurses, and other professionals (63) In a recent controlled trial, Cornish and colleagues(64) showed that naltrexone added to standard fed­eral probation produced 70% less opi­ate use and 50% less reincarceration than standard probation alone.

Alcohol Dependence.

Naltrexone has been found effective at 50 mg/d for re­ducing drinking among alcohol-dependent patients (65,66) It works by blocking at least some of the "high" pro­duced by alcohol's effects on µ-opiate receptors. More recently, European re-searchers have found encouraging re­sults using the 'γ-aminobutyric add ago­nist acamprosate to block craving and relapse to alcohol abuse.967) Alcohol-dependent patients prescribed acam­prosate showed 30% higher absti­nence rates at 6-month follow-up than those randomized to placebo. Further-more, those who returned to drinking while receiving acamprosate reported less heavy drinking (≥5 drinks per day) than those receiving placebo."

Stimulant Dependence.

Although there are not yet effective medications for the treatment of cocaine or amphet­amine dependence,(35) there are proven behavioral treatments.(66-71) There also are promising animal studies of a potential vaccine that binds to and inacti­vates metabolites of cocaine,(72) but clini­cal trials will not be scheduled for several years.

Comparing Treatments for Drug Dependence With Treatments for Other Chronic Diseases

There is no reliable cure for drug de­pendence. Dependent patients who comply with the recommended regimen of education, counseling, and medication have favorable outcomes during and usually for at least 6 to 12 months following treatment.(47-50) Fa­vorable outcomes typically continue in patients who remain in methadone maintenance or in abstinence mainte­nance through participation in Alco­holics Anonymous (AA) or other self-help programs.(48,50-52) However, because of insurance restrictions, many pa­tients receive only detoxification or acute stabilization with no continuing care.(3,6,9) Others drop out of rehabilita­tion-oriented treatment and/or they ig­nore physician advice to continue tak­ing medications and participating in AA. Thus, 1-year, postdischarge follow-up studies(47,52,73) have typically shown that only about 40% to 60% of discharged patients are continuously abstinent, al-though an additional 15% to 30% have not resumed dependent use during this period. Problems of low socioeco­nomic status, comorbid psychiatric con­ditions, and lack of family and social supports are among the most impor­tant predictors of poor adherence dur­ing addiction treatment and of relapse following treatment.(47-52.74)

Hypertension, diabetes, and asthma are also chronic disorders, requiring continuing care throughout a patient's life. Treatments for these illnesses are effective but heavily dependent on adherence to the medical regimen for that effectiveness. Unfortunately, stud­ies have shown that less than 60% of adult patients with type 1 diabetes melli­tus fully adhere to with their medica­tion schedule(75) and less than 40% of patients with hypertension or asthma adhere fully to their medication regi­mens(76,77) The problem is even worse for the behavioral and diet changes that are so important for the maintenance of gains in these chronic illnesses. Again, studies indicate that less than 30% of patients with adult-onset asthma, hyper-tension, or diabetes adhere to pre-scribed diet and/or behavioral changes that are designed to increase func­tional status and to reduce risk factors for recurrence of the disorders(75-78) Across all 3 of these chronic medical ill­nesses, adherence and ultimately out-come are poorest among patients with low socioeconomic status, lack of fam­ily and social supports, or significant psychiatric comorbidity.(75-79) Perhaps because of the similarity in treatment adherence, there are also similar relapse rates across these disorders. Outcome studies indicate that 30% to 50% of adult patients with type 1 diabetes and approximately 50% to 70% of adult patients with hyperten­sion or asthma experience recurrence of symptoms each year to the point where they require additional medical care to reestablish symptom remission (75,80)


Few persons who try drugs or regu­larly use drugs become dependent. However, once initiated, there is a pre­dictable pathogenesis to dependence marked by significant and persistent changes in brain chemistry and func­tion. It is not yet possible to explain the physiologic and psychological pro­cesses that transform controlled, vol­untary use of alcohol and other drugs into uncontrolled, involuntary depen­dence. Twin studies indicate a definite role for genetic heritability. Nonethe­less, personal choice and environmen­tal factors are clearly involved in the expression of dependence. In terms of vulnerability, onset, and course, drug dependence is similar to other chronic illnesses, such as type 2 diabetes, hyper-tension, and asthma.

Our review of treatment response found more than 100 randomized controlled trials of addiction treatments, most showing significant reductions in drug use, improved personal health, and reduced social pathology but not cure.(7-9,34,35,47-52,81,82) Recent treatment advances include potent, well-tolerated medications for nicotine, alco­hol, and opioid dependence(35,58,61,65-67) but not marijuana or stimulant depen­dence. There is little evidence of effec­tiveness from detoxification or short-term stabilization alone without maintenance or monitoring such as in methadone maintenance or AA.(47-52.57) However, as in treatments for other chronic disorders, we found major prob­lems of medication adherence, early drop-out, and relapse among drug-dependent patients. In fact, problems of poverty, lack of family support, and psychiatriccomorbidity were major and approximately equal predictors of non-compliance and relapse across all chronic illnesses examined.(74-83)

Thus, our review suggests that drug dependence shares many features with other chronic illnesses. We are aware that arguments by analogy are lim­ited, and even marked similarities to other illnesses are not proof that drug dependence is a chronic illness. None­theless, these similarities in heritabil­ity, course, and particularly response to treatment raise the question of why medical treatments are not seen as ap­propriate or effective when applied to alcohol and drug dependence. One pos­sibility is the way drug dependence treatments have traditionally been delivered and evaluated.

Many drug dependence treatments are delivered in a manner that is more appropriate for acute care disorders. Many patients receive detoxification only.(3-35,48,49) Others are admitted to spe­cialty treatment programs, where the goal has been to rehabilitate and discharge them as one might rehabilitate a surgical patient following a joint re-placement (47)Outcome evaluations are typically conducted 6 to 12 months following treatment discharge. The usual outcome evaluated is whether the pa­tient has been continuously abstinent after leaving treatment.

Imagine this same strategy applied to the treatment of hypertension. Hyper­tensive patients would be admitted to a 28-day hypertension rehabilitation program, where they would receive group and individual counseling regarding be­havioral control of diet, exercise, and life-style. Very few would be prescribed medications, since the prevailing insur­ance restrictions would discourage main­tenance medications. Patients complet­ing the program would be discharged to community resources, typically with-out continued medical monitoring. An evaluation of these patients 6 to 12 months following discharge would count as successes only those who had remained continuously normotensive for the entire postdischarge period. In this regard, it is interesting that relapse among patients with diabetes, hypertension, and asthma following ces­sation of treatment has been consid­ered evidence of the effectiveness of those treatments and the need to retain patients in medical monitoring. In contrast, relapse to drug or alcohol use following discharge from addiction treatment has been considered evidence of treatment failure. The best outcomes from treat­ments of drug dependence have been seen among patients in long-term metha­done maintenance programs(49,50,58,83) and among the many who have continued participating in AA support groups.(84,85)


For primary care physicians, this re-view suggests that addiction screening, diagnosis, brief interventions, medica­tion management, and referral criteria should be taught as part of medical school and residency curricula and rou­tinely incorporated into clinical prac­tice(86.87) For those in health policy, our review offers support for recent insur­ance parity initiatives.(88) Like other chronic illnesses, the effects of drug de­pendence treatment are optimized when patients remain in continuing care and monitoring without limits or restric­tions on the number of days or visits cov­ered. Although it is unknown whether care delivered in a specialty program or coordinated through primary care will provide the maximal benefits for pa­tients and society, it is essential that prac­titioners adapt the care and medical monitoring strategies currently used in the treatment of other chronic illnesses to the treatment of drug dependence.


This review was supported by grants from the Department of Veterans Affairs, the Na­tional Institute on Drug Abuse, the Center for Sub-stance Abuse Treatment, The Robert Wood Johnson Foundation, and the Office of National Drug Control Policy.


The manuscript was reviewed (but not supported financially) by the Physician Leadership for National Drug Policy before submission, and Dr Lewis is a member of that organization.


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JAMA October 4, 2000 vol 284 no 13


Our valuable member Thomas Mclellan has been with us since Sunday, 19 December 2010.