SUPPLEMENT
Treatment of Alcohol and Other Drug
Dependence
Richard Saitz
Departments of Medicine and Epidemiology, Youth Alcohol Prevention Center, Clinical Addiction
Research and Education Unit, Section of General Internal Medicine, Boston University and Boston Medical Center, Boston, MA
KEY CONCEPTS
Addiction (e.g., alcohol or drugs) is a chronic disease. Specific behavioral and pharmacological treatments have proven efficacy.
Addressing addiction includes intervention for risky and problem use.
Clinicians who are not addiction specialists can play important roles in addressing addiction. Liver Transpl
13:S59-S64, 2007.©2007 AASLD.
Unhealthy alcohol and drug use are associated with substantial morbidity, disability, mortality, and costs.1,2 They are among the leading preventable
causes of death and disability. Most cases of esopha-geal cancer, 60% of chronic pancreatitis, 50% of cirrho-sis and chronic hepatitis, 42% of acute pancreatitis, and substantial proportions of other medical illnesses including human immunodeficiency virus (HIV) and in-juries are attributable to alcohol and other drugs. More than 100,000 people in the United States die each year as a result of alcohol and illicit drugs. In the United States, substance (alcohol and drug) use cost far more than other common medical illnesses— over $400 bil-lion a year, compared with approximately a quarter of that sum for coronary heart disease and an eighth of that sum for obstructive lung disease and asthma.
Despite these consequences and costs, and despite the fact that over a third of hospital admissions are related to unhealthy alcohol and other drug use, most such patients do not receive addiction treatment. But efficacious treatments exist. Tobacco addiction is more common and causes more deaths than alcohol or other drug use. It can be treated effectively with brief advice, individual and group counseling, and several medica-tions (nicotine replacement, bupropion, varenicline).
But this review of addiction treatment focuses on alco-hol and other drug use, excluding tobacco, a topic wor-thy of separate focus. For alcohol and other drug dis-orders, behavioral and pharmacological treatments have proven efficacy. A number of these treatments have been proven effective relatively recently, have not yet been widely disseminated into practice, and can be implemented outside of addiction specialty treatment settings.3,4
Finally, unhealthy use of substances by people who have not yet met diagnostic criteria for a substance use disorder can also be effectively treated with brief inter-ventions. These interventions are of particular impor-tance to clinicians who are not addiction specialists because they are brief and can be done by nonspecial-ists. These clinicians also have critical roles in facilitat-ing receipt of addiction treatment by their patients.
But before discussing specific treatments, it is impor-tant to consider the fact that addiction is a chronic disease, so that expectations of treatment outcome are appropriate.5 Treating addiction is perhaps more like
treating and managing asthma and diabetes than it is like curing a bacterial infection.
ADDICTION IS A CHRONIC DISEASE
Alcohol and drug (substance) dependence share a num-ber of features in common with other common chronic illnesses.6These include the following: physiologic
ba-sis; diagnoba-sis; definable risk factors; heritability; poor adherence to treatment; no cure; relapse common; lon-gitudinal care required; and denial.
Substance dependence has a physiologic basis. For example, people with alcohol dependence, even during abstinence, have reduced gamma-aminobutyric acid
Abbreviations:HIV, human immunodeficiency virus; GABA, gamma-aminobutyric acid; AA, Alcoholics Anonymous.
Address reprint requests to: Richard Saitz, Departments of Medicine and Epidemiology, Youth Alcohol Prevention Center, Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Boston University and Boston Medical Center, 91 East Concord Street 200, Boston, MA 02118-2644. Telephone: 617-414-7399; Fax: 617-414-4676; E-mail: rsaitz@bu.edu
DOI 10.1002/lt.21339
Published online in Wiley InterScience (www.interscience.wiley.com).
(GABA) receptors in the brain, as measured by single positron emission tomography, than do people without alcohol dependence. Alcohol potentiates inhibitory GABA transmission in the central nervous system. These decreases in central GABA receptors may there-fore be related to the uncontrollable desire to drink seen in people with dependence. Whether these changes are a cause or effect of heavy drinking is not known. Phys-iologic characteristics that do appear to have causal roles are enzymatic activities that lead to higher levels of serum acetaldehyde after drinking (e.g., aldehyde dehydrogenase deficiency). These higher amounts of acetaldehyde that are unpleasant (e.g., nausea) are as-sociated with a lower risk for alcohol dependence.
Substance dependence can be reliably diagnosed. Al-though there is no laboratory test, structured inter-views (and expert clinicians) yield diagnoses with con-sistency. These diagnoses have prognostic value in terms of natural history and treatment response.
Substance dependence has definable risk factors, and like other common chronic illnesses has a substan-tial genetic etiology—although also similarly, there is no single gene responsible for the risk. Just over 50% of alcohol dependence is related to nonshared environ-mental influences (e.g., peers, bad childhood experi-ences). The remainder is related to genetics. In adoption studies, having a parent with alcohol dependence dou-bles the risk. About one-third of identical twins will have alcohol dependence if their twin has it. Epidemi-ologic studies have identified specific genes that in-crease risk. For example, genes involved in dopamine synthesis, which is critical for the reward pathway where all substances of abuse have action, increase the risk. And the gene that includes the locus that codes for alcohol dehydrogenase has been identified as a risk factor for alcohol dependence.
As with other chronic medical illnesses, treatments are effective but are often not adhered to, there are no cures, and relapse is common. Similarly, substance dependence affects physical, social, and emotional well-being, and requires longitudinal health care. After alcohol-dependence treatment, 40-60% of patients are abstinent 1 year later, and an additional 15-30% have not returned to dependent drinking. In comparison, adherence to medication regimens in diabetes, hyper-tension, and asthma are 30-50% and are generally even worse for nonpharmacological treatments. Relapse, or recurrence of symptoms requiring additional medical care to establish remission of symptoms of these dis-eases, is actually similar to that seen in substance dependence (up to 70%). And these observations are true despite that fact that in practice, substance depen-dence treatment is often short term. Despite this, re-lapse rates are not 100%, as would be the case for diabetes treated only in the short term.
Last, even one of the classic characteristics of alco-holism, denial, is a common feature among patients with other chronic illnesses like diabetes and hyperten-sion. Denial is a common response to being “accused” of (or diagnosed with) having an undesirable characteris-tic.
In the United States, although there are addiction medicine specialists, most addiction treatment is deliv-ered in specialty treatment programs by substance abuse counselors. The view from outside this system is often that patients should go to “detox.” Detoxification is useful when patients are beginning to cut down or abstain, and it is valuable as a first step in treatment. Physical and emotional symptoms of withdrawal can be ameliorated by using medications cross-tolerant to the substance being used (e.g., benzodiazepines for alcohol withdrawal). But detoxification alone (most often done in ambulatory settings) is not addiction treatment, in that it does not prevent relapse. For example,⬍20% of patients with opioid dependence are abstinent 1 year after detoxification alone. Unfortunately, most patients who undergo detoxification in the United States do not receive further addiction treatment. Addiction treat-ment is aimed at decreasing the chronic consequences of uncontrolled substance use, including physical and interpersonal consequences, and social, psychological, legal, and employment problems. In addition, treat-ment aims to reduce substance use, including lapses (usually defined as use on one occasion) and relapses (usually defined as more than one occasion of heavy use).
TREATMENT
What Is Addiction Treatment?
Alcohol treatment includes access to psychological, medical, employment, legal, and social services, some-times removal from a drinking or otherwise harmful environment, use of mutual (self)-help groups, pharma-cotherapy, and counseling by both specialists and non-specialists.
This counseling includes brief counseling by physi-cians in medical settings.7,8 Of note, as would be the
case for heart disease or gastrointestinal disease, a single lecture or review article such as this one cannot even briefly mention all known efficacious addiction treatments, and certainly cannot provide detailed indi-cations, prescribing information, and counseling ingre-dients. As a result, this article focuses on principles and the best proven treatments, particularly those of rele-vance to those who are not addiction physicians or counselors.
How Effective Is Treatment?
At 1 year, two-thirds of patients have a reduction in alcohol consequences (injury, unemployment) and con-sumption (by 50%).9One-third are abstinent or
drink-ing moderately without consequences. Monetary bene-fits of alcohol and drug treatment to society outweigh costs 4-12-fold (depending on drug and treatment type). For opioid dependence, pharmacotherapy and counseling can achieve abstinence rates of 60-80%.
Principles of Treatment
The National Institute on Drug Abuse has published 13 principles of effective treatment.10These are:
1. No single treatment is appropriate for all individu-als. Treatments should be individualized according to patient needs.
2. Treatment needs to be readily available. Patients ready for treatment can be lost if treatment is not immediately accessible.
3. Effective treatment attends to multiple needs of the individual, not just his or her drug use. These needs include addressing substance use and any associated medical, psychological, social, voca-tional, and legal problems.
4. As with any chronic illness, an individual’s treat-ment and services plan must be assessed continu-ally and modified as necessary to ensure that the plan meets the person’s changing needs.
5. Remaining in treatment for an adequate period of time is critical for treatment effectiveness. The ap-propriate duration for an individual depends on the problems and needs but is usually at least 3 months. Treatment should include strategies to keep patients in treatment.
6. Counseling (individual and/or group) and other be-havioral therapies are critical components of effec-tive treatment for addiction. These therapies ad-dress motivation, problem solving, relationships, social functioning, and skills useful for avoiding drug use.
7. Medications are an important element of treatment for many patients, especially when combined with counseling and other behavioral therapies.
8. Addicted or drug-abusing individuals with coexist-ing mental disorders should have both disorders treated in an integrated way.
9. Medical detoxification is only the first stage of ad-diction treatment and by itself does little to change long-term drug use.
10. Treatment does not need to be voluntary to be ef-fective. Mandated treatment can increase treat-ment entry and retention.
11. Possible drug use during treatment must be mon-itored continuously, with results presented to pa-tients. Monitoring helps patients resist urges to use substances, and positive results can signal a need to intensify treatment.
12. Treatment programs should provide assessment for HIV–acquired immunodeficiency syndrome, hepatitis B and C, tuberculosis, and other infec-tious diseases, and counseling to help patients modify or change behaviors that place themselves or others at risk of infection.
13. Recovery from drug addiction can be a long-term process and frequently requires multiple episodes of treatment, or long-term treatment.
Behavioral Treatments
Behavioral treatments for addiction with proven effi-cacy are not simply generic counseling sessions. A number of therapies with specific content and doses, often clearly laid out in manuals, have been proven effective in well-designed studies. Motivational
inter-viewing (or manualized 4-session motivational en-hancement therapy) is a client-centered, directive method for enhancing intrinsic motivation to change by exploring and resolving ambivalence. Cognitive behav-ioral therapies emphasize skills to cope with situations that might precipitate substance use. Twelve-step facil-itation emphasizes the disease model of addiction and encourages and facilitates full participation in 12-step groups like Alcoholics Anonymous. Contingency man-agement (sometimes referred to as involving motiva-tional incentives) provides rewards for treatment adher-ence or negative drug testing results. Marital and family therapy can also be effective treatments for addiction. In the context of medication prescription for alcohol dependence, “medical management” by patients’ physi-cians, physician assistants, or nurses, a relatively brief form of repeated counseling similar to what medical physicians routinely do for other medications, appears to effective.3 Medical management involves asking
about medication side effects and adherence, and en-couraging abstinence.
A number of other behavioral treatments have proven efficacy. These include but are not limited to the follow-ing: relapse prevention counseling, supportive-expres-sive psychotherapy, individualized drug counseling, be-havioral therapy for adolescents, multidimensional family therapy for adolescents, multisystemic therapy, community reinforcement approach plus vouchers, voucher-based reinforcement therapy in methadone maintenance treatment, day treatment with abstinence contingencies and vouchers, and the Matrix model. The details of these and other treatments are beyond the scope of this article.
Pharmacological Treatments
Pharmacological treatments for opioid dependence in-clude methadone maintenance, buprenorphine, and naltrexone.11 As with other pharmacotherapies, drug
use should be monitored, and patients should partici-pate in counseling and obtain any needed social sup-port.
Naltrexone is a synthetic opioid antagonist that blocks the euphoria associated with opioid use. To avoid precipitating withdrawal, it is given after an opi-ate-free period, and it is given daily or 3 times a week. It does not prevent craving, and nonadherence is com-mon. This medication is best used in patients who are highly motivated to maintain abstinence (such as im-paired physicians or people on parole) who receive counseling and careful monitoring.
Methadone is a long-acting opioid agonist taken or-ally.12,13 To be effective, it must be given over a long
period of time at a dose sufficient to prevent with-drawal, block effects of illicit use, and decrease craving (generally ⱖ60 mg once a day). Patients stabilized on doses of methadone do not experience any euphoria from taking the drug; they feel normal and can function normally (or as normal as someone not receiving psy-choactive medication can feel). In the United States, methadone can only be prescribed as a treatment for
opioid dependence by physicians in licensed metha-done maintenance programs or by physicians with spe-cific permission to prescribe it as office-based opioid therapy, currently an unusual exception. In these pro-grams, to which access is limited, patients tend to be subject to stigma and to inconvenient and even punitive rules, such as needing to present daily at a particular time for dosing. Nonetheless, as part of a comprehen-sive drug treatment program, methadone treatment in-creases survival, inin-creases treatment retention, de-creases illicit opioid use, dede-creases hepatitis and HIV seroconversion, decreases criminal activity, increases employment, and improves birth outcomes. As with detoxification, ⬎80% of patients who undergo treat-ment will relapse to illicit opioid use in a year.
Of note, methadone is also an excellent choice for short-term prevention of withdrawal in general hospital settings. The goal of methadone treatment in those set-tings is to allow the treatment of the underlying medical or surgical condition. In these cases, the dose is 20-40 mg in 24 hours, usually initially provided as 15-20 mg followed by an additional 5-10 mg after 2-3 hours, until symptoms of withdrawal abate.
Buprenorphine is a partial opioid agonist provided sublingually for maintenance.14With the exception of
pregnant women, patients should be treated with a combination tablet of buprenorphine and naloxone. Naloxone is a short-acting opioid antagonist that is not absorbed sublingually but that prevents the tablets from being abused intravenously because it would pre-cipitate withdrawal. Buprenorphine itself can precipi-tate withdrawal, so induction involves waiting for marked withdrawal symptoms (from the abused opioid) to appear, after which buprenorphine can be initiated at a low dose, then titrated higher to the usual mainte-nance doses of 8-16 mg once daily. Buprenorphine is quite safe, in part because the opioid effect has a ceil-ing: after a certain dose, no additional effect accrues. Although experience with buprenorphine is more lim-ited than that with methadone, clinical trials have found that buprenorphine increases abstinence from illicit opioids, increases retention in treatment, and de-creases opioid craving and even mortality. Some pa-tients maintained on methadone can be switched to buprenorphine. Those less likely to succeed on bu-prenorphine are those requiring higher doses of meth-adone or requiring more structured treatment pro-grams.
Pharmacological treatments for alcohol dependence include disulfiram, acamprosate, naltrexone, and long-acting injectable naltrexone. These medications reduce heavy drinking and increase abstinence.
Disulfiram, an inhibitor of aldehyde dehydrogenase, re-sults in increased levels of acetaldehyde and an unpleas-ant reaction after consumption of ethanol. The usual oral daily dose is 500 mg. In one of the largest studies of this medication, disulfiram was no better than placebo in achieving abstinence. But it is not clear whether a place-bo-controlled trial is the best way to test a drug whose efficacy depends largely on the patient knowing that they may experience a very unpleasant reaction. Of note, in
post hoc analyses, the drug was more effective in those who were adherent to it. In at least 5 controlled studies, disulfiram was associated with marked increases in ab-stinence when administration of the drug was supervised by a concerned other. Disulfiram has numerous contra-indications, and the risk-benefit ratio for people at risk of complications should they experience the ethanol reac-tion (e.g., those with esophageal varices) needs to be con-sidered. High doses can lead to an idiosyncratic fulminant hepatitis and neuropathy.
Acamprosate increases continuous abstinence at 1 year by 8%, from 15% to 23%, and increases abstinent days by 27 days.15The mechanism of action is unclear,
but the drug appears to work by affecting the glutamate system. The usual oral dose is 666 mg 3 times daily. The main side effect is diarrhea, which subsides with continued use, and the medication needs adjustment for renal insufficiency (and is contraindicated in pa-tients with renal failure).
Naltrexone decreases relapse to heavy drinking by approximately 11% (decrease in absolute risk from 48% to 37%).15Naltrexone is a long-acting opioid antagonist
that is absorbed when taken orally. The usual dose is 50 mg daily. The medication blocks endogenous opi-oids, thus decreasing the reinforcing pleasurable ef-fects of drinking. The main side efef-fects, nausea and dizziness, subside with continued use. Naltrexone can-not be given to patients with opioid dependence or a need for opioids. In the event of an acute need for opioids to treat pain, naltrexone should be discontin-ued, and in the short term, very high doses of opioids will be required under close monitoring. Monthly injec-tions of naltrexone (380 mg intramuscularly), as estab-lished by a placebo-controlled trial, also decreases heavy drinking, and may address the problems with adherence that occur with oral pharmacotherapies that need to be provided daily or more frequently.4The
man-ufacturer has a program that coordinates product delivery for all patients being treated and provides in-formation regarding appropriate storage and adminis-tration.
Most studies of pharmacotherapies have been in pa-tients who have completed detoxification first, but nal-trexone appears to be efficacious even in patients who have a short duration of abstinence before beginning treatment. Of course, abstinence must be achieved be-fore beginning disulfiram to avoid the disulfiram-etha-nol reaction. During naltrexone or disulfiram treat-ment, liver enzymes should be monitored periodically. Although the drugs can cause increases in liver en-zymes, most studies of alcohol dependence pharmaco-therapy find decreases or no difference in levels in treated patients compared with control patients. All alcohol-dependence pharmacotherapies are category C; they should only be prescribed during pregnancy if risks will clearly outweigh benefits. Combinations of naltrexone and acamprosate do not appear to offer clear additional efficacy compared with either drug alone.
For dependence on drugs other than alcohol, to-bacco, and opioids, there are no well-established phar-macotherapies, although many are under investigation.
CO-OCCURRING MENTAL HEALTH
CONDITIONS
Diagnosis of co-occurring mental health problems can be challenging in people with addictions because there is substantial overlap in symptoms, and sometimes the temporal relations are difficult to sort out. Nonetheless, patients with co-occurring mental health conditions should have the conditions treated, regardless of whether the condition preceded the addiction or not. Psychiatric illness can interfere with adherence to and participation in addiction treatment, and it can trigger relapse. Psychiatric treatment can decrease these ef-fects. For example, for those with anxiety disorders, buspirone can decrease heavy alcohol consumption. Fluoxetine is similarly effective in those with alcohol dependence and major depression.
ADDRESSING ADDICTION
What Is Risky and Problem Use?
Excessive use of alcohol (e.g.,⬎14 standard drinks per week or 4 drinks per occasion by men, 7 and 3 for women and the elderly) and use of drugs by people who do not meet criteria for substance dependence is more common than addiction. Problem use describes people who are using substances (or drinking heavily) and experiencing consequences of that use but who do not meet dependence criteria. People with risky use have not yet experienced consequences but are at risk (e.g., excessive alcohol use, any illicit drug use).
How Can Risky and Problem Use Be
Identified?
Risky and problem use should be identified because brief intervention has efficacy (proven for alcohol, some evi-dence for efficacy for drug use), and because the preva-lence is higher than that of dependence. Brief intervention can prevent future use and can likely decrease conse-quences. Screening tests can identify risky and problem use, and all adults should be screened. A single question can identify risky alcohol use: “How many times in the past year have you had 5 (4 for women) or more drinks in a day?” (a positive test is one or more times). Although screening tests are less well validated for drug use, several questionnaires have been developed, and a consensus panel recommended the following single question as a screening test: “Have you ever used street drugs more than 5 times in your life?” Longer screening question-naires include the Alcohol Use Disorders Identification Test, a 2-item conjoint (drug and alcohol) screening test, the World Health Organization Alcohol Smoking and Sub-stance Involvement Screening Test. Laboratory tests are generally insensitive and nonspecific when used for screening for unhealthy alcohol use. Laboratory testing for drug use is similarly not very useful for screening patients because of short half-lives and the need to test for many drugs of abuse.
Brief Intervention
“Brief intervention” generally refers to 10-15 minutes of counseling, with feedback about use, advice, and goal setting, and follow-up contact with a clinician. The ad-vice should be appropriate to the patient’s readiness to change. Randomized trials in diverse clinical settings have found that brief interventions can reduce risky drinking amounts by 11%. Decreased heroin and co-caine use may result from brief intervention.16
Al-though not consistently found in controlled studies, brief intervention may also decrease consequences of alcohol and other drug use, including serum gamma-glutamyltransferase levels, hospitalization, and death.
Most People With Addictions Do Not Receive
Treatment
Most people with addictions do not receive effective treatment. Most are not identified in medical settings. Even when patients with addictions are identified in medical settings, they often do not receive any effica-cious interventions. And even when patients enter ad-diction care via detoxification, the initial steps are most often not followed by efficacious addiction treatment. For example, 80% of people with opioid addiction do not receive medication-assisted treatment.
Screening and Brief Intervention
Clinicians who are not addiction specialists can play critical roles in improving identification and manage-ment of patients with addictions. Universal screening can identify patients with addictions. Brief interven-tions can reduce substance use and/or recommend linkage to addictions care. Follow-up and support of specialty addiction treatment plans can contribute to relapse prevention efforts.1
Referral to Mutual Help Groups
Mutual or self-help groups such as Alcoholics Anony-mous (AA) provide social support and an alcohol- and drug-free social network. Observational studies suggest that AA can increase abstinence for people with alcohol dependence who participate. Clinicians can refer pa-tients to these groups, and they can help by suggesting that patients try groups until they find one they are comfortable with, and by asking about meeting atten-dance and participation.1
Pharmacotherapy for Alcohol Dependence
Clinicians who are not addiction specialists can become familiar with prescribing pharmacotherapies for alco-hol dependence, and can then do so while having ad-diction specialists manage the many other interven-tions needed for successful addiction treatment (e.g., counseling, assistance with employment or housing).Buprenorphine
Clinicians who are not addiction specialists can also be-come familiar with prescribing buprenorphine for opioid
dependence and prescribe this treatment. In the United States, a waiver is required from the Drug Enforcement Administration.17,18Obtaining the waiver requires
certi-fication in addiction medicine or psychiatry, or evidence of training (at least 8 hours) specifically acceptable for this purpose. Then, as with pharmacotherapy for alcohol de-pendence, the clinician can prescribe, knowing that other aspects of addiction treatment are addressed either in their practice or by addiction specialty clinicians or pro-grams. Prescribing this effective opioid treatment in a medical office represents a dramatic contrast with the requirement to attend a program to receive methadone. Buprenorphine has the potential to be more accessible to patients than methadone because it can be prescribed in a doctor’s office. Access is currently limited in the United States by the numbers of physicians prescribing this treatment and by a regulatory limit of 30 patients per physician, which can be increased to 100 after the first year.
Integrating Care
Clinicians who are not addiction specialists can help pa-tients receive the care that they need over time. Papa-tients with addictions often require coordinated, integrated care for addiction, mental health, and medical problems. These services are often delivered in different places by different clinicians, in short-term programs, leading to fragmented, uncoordinated care, and increasing the risk of errors and suboptimal care. Attention to the whole clinical picture and monitoring of all of the care received (e.g., case management) can improve care. Systems that integrate medical, addiction, and psychiatric care have the potential to improve patient outcomes.
CONCLUSIONS
To manage addictions appropriately, one must recog-nize that alcohol and other drug dependence are chronic illnesses. As such, the focus should be on long-term management with the goal of relapse prevention. Continued treatment is associated with better outcome than short-term treatment. Behavioral treatments with proven efficacy include motivational enhancement and cognitive behavioral therapy, contingency manage-ment, less intense and less specialized medication management, and brief counseling interventions that have efficacy specifically for nondependent unhealthy alcohol use, and perhaps for initiating referral for care. Pharmacological treatments, usually in the context of counseling, also have proven efficacy. The best proven of these include acamprosate, naltrexone (oral and long-acting injectable), and disulfiram for alcohol de-pendence, and methadone and buprenorphine for opi-oid dependence. To avopi-oid addressing only the most se-verely affected patients, attention needs to be directed to the larger proportion of patients with risky use to whom the largest number of health problems can be attributed. Care for addictions should include attention to psychiatric comorbidity. Clinicians who are not diction specialists can play very important roles in
ad-dressing addiction by identifying patients with risky, problem, or dependent use; by providing brief counsel-ing and prescribcounsel-ing efficacious medications; by ad-dressing common comorbidities; and by referring to specialists when needed.
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