All of this new information and all of the research on addiction would be unnecessary if current treatments resulted in recovery for everyone who entered treatment or attended AA meetings. Unfortunately, current treatments can't claim 100 percent success. There are many individuals who try repeatedly, but still can't get sober. Others can manage periods of abstinence, but slide back into relapse. More help, added tools and new methods are needed to add to, but not replace existing treatments. Where do we stand in developing alcoholism/addiction pharmacotherapies?

Pharmacotherapies For Alcoholism

For many years, there was considerable resistance to the use of medications to help alcoholics through alcohol withdrawal. Some thought that if withdrawal were made too easy and comfortable, there would be no deterrent to returning to alcohol use. However, in the past 50 years, this 'let them suffer, it's good for them' attitude has been deemed medically unsafe, ethically barbaric and grounds for malpractice. It is likely that as science continues to produce medications that have clearly demonstrated efficacy in reducing relapse to alcohol use, these medications will gain increasing application. One hopes that this change will not take decades to occur as the advocates for the 'no medication for any purpose' die off and are replaced by more enlightened staff. It would be a great help to alcoholics if we could speed the process, by dropping old beliefs and using the new tools that can help.

Disulfiram:

The 1990s brought revolutionary change to alcoholism treatment. As the decade began, one medication; disulfiram (Antabuse) was approved for the treatment of alcoholism. Disulfiram interferes with the metabolism of alcohol. If a person is taking a therapeutic dose of disulfiram (250-500 mgs per day), and consumes alcohol, in almost any amount, that person will almost immediately experience severe nausea, flushing and other unpleasant symptoms. Although some individuals are able to drink 'on top of' disulfiram without a reaction, most people have a severe negative reaction to alcohol, and about 5 percent experience psychosis and potentially dangerous hypertension with the combination.

The rationale for using disulfiram in treatment is not to make people sick or to conduct aversion therapy. It is a treatment based upon deterrent. If a person wants to stay abstinent from alcohol, swallowing one tablet of disulfiram in the morning is a way to create a powerful deterrent to drinking. When most people are told about the nature of the reaction to disulfiram, they don't need to 'test it' to benefit from the deterrent effect.

For some alcohol users the addition of this deterrent can help them prevent relapse. Disulfiram is not to be used as an unaccompanied treatment, but as a potentially useful adjunct to a more comprehensive plan.

Naltrexone:

Marketed as ReVia by Dupont-Merck, naltrexone has a former life as Trexan, also marketed by Dupont. It is the first medication, since the development of disulfiram in the 1950s, to be approved specifically for the treatment of alcoholism.

There are great expectations for the use of naltrexone. The medication is taken daily in pill form (50 mg. per day), it is safe, cannot be abused, does not produce any dependence and has few side effects. By any scientific efficacy/medical safety measure, naltrexone appears to be a nearly perfect medication for the treatment of alcoholism.

However, according to information from sales records and surveys by several groups (including the authors), most alcoholism-treatment practitioners in the United States use naltrexone infrequently due to its cost and their lack of knowledge about the medication. Naltrexone treatment can add $150 to the cost of a month's treatment. Many physicians and nonphysicians in treatment programs are unaware of the usefulness of naltrexone or how to use it. In other areas of medicine, it is highly probable that the development of such an efficacious medication would prompt physicians to use it readily.

The biggest obstacle to using naltrexone for the treatment of alcoholism is the 'pharmacophobia' of many alcoholism-treatment professionals. This near-hysterical resistance to medication for treating alcoholism (or other substance-abuse disorders) has deep and tangled roots. Many recovering professionals learned in their recoveries that MDs and their prescription pads were evil purveyors of pharmacological lies and temptations. This attitude is often accompanied by a deeply rooted and strongly held belief that recovery has only one successful formula (usually the 12-step program) and that any modification to that approach is unethical. Scientific evidence is irrelevant to these individuals. They believe they have the 'truth' about recovery and don't want to be bothered with other points of view.

Naltrexone is a pharmacotherapy that is pushing the system to change. NIAAA is conducting a number of large studies to gain a better understanding of how to use naltrexone and who can benefit from this medication. The value of naltrexone for the treatment of alcoholism will incorporate substantial amounts of psychological and counseling treatments. No one believes naltrexone to be a penicillin-type cure for alcoholism. Alcoholism recovery will still require lots of work, professional help and peer support. There is no conflict between the use of naltrexone and participation in the spiritual, personal recovery journey supported by 12-step involvement.

Acamprosate:

Acamprosate works by stimulating the production of the brain chemical, gaba. The irritability and dysphoria that often occurs in early recovery is partially the result of gaba depletion. Since one of the factors that contributes to alcohol relapse in early recovery is negative mood states, it is believed that acamprosate will reduce the severity of these relapse triggers and will contribute to achievement and maintenance of alcohol abstinence in the early weeks and months of recovery. Acamprosate, produced by Lipha Pharmaceuticals, is approved for the treatment of alcoholism in many European countries. A major study on the safety and efficacy of acamprosate was recently concluded in the United States. The data to support the approval of acamprosate are under review by the FDA, and it is likely that the FDA will soon approve acamprosate. Its cost and parameters for use are still unknown.

Pharmacotherapies for opiate addiction
Methadone:

Since the work of Dole and Nyswander in the 1960s, methadone treatment has been a source of intense controversy. After more than 30 years of use, two major American political figures, U.S. Senator John McCain and New York Mayor Rudolph Gullianni, have discussed eliminating or severely restricting the use of methadone treatment. Yet even with such powerful political enemies methadone treatment continues to expand. Currently about 180,000 individuals in America are in methadone treatment. Why is methadone treatment so controversial?

The rationale for methadone treatment is simple and the research evidence to support the value of methadone treatment is overwhelming. Methadone is a long acting (24-hour half-life), orally effective medicine that reduces opiate craving and blocks the effect of illicit opiates. When used in adequate doses, in conjunction with necessary counseling services, methadone treatment reduces or eliminates heroin use and associated high-risk behavior and criminal activities. Reviews by numerous blue-ribbon panels show that methadone treatment plays a vitally important role in reducing the morbidity and mortality associated with heroin use. From a public-health perspective, methadone treatment is arguably the most important and effective measure used in substance-abuse treatment.

 
Although methadone produces tremendous benefits, it is far from a perfect medication. Methadone treatment is not synonymous with 'recovery.' Some individuals in treatment continue to use illicit drugs, commit crimes and engage in behaviors that spread communicable diseases. Methadone treatment is restrictive, since it requires frequent visits to a limited network of clinics. When given as 'take home' medication, methadone can be diverted to use by nonpatients. Since withdrawal from methadone is difficult and many individuals appear to need to remain in treatment for many years, there is dissatisfaction with this 'incomplete, medication-supported abstinence.' While the shortcomings of methadone treatment are evident, the availability of methadone has saved tens of thousands of lives.

A current legislative and regulatory process is underway to change the way methadone treatment is regulated and monitored. A transfer of authority from the FDA to several licensing/certification organizations (JCAHO and CARF) will hopefully move methadone treatment toward integration with the mainstream healthcare system. New initiatives are underway to evaluate the feasibility of moving methadone treatment into MD offices and pharmacies to increase access to treatment. Even as new medications are developed to improve the available choices in treatment, methadone will remain a necessary and important option for the treatment of opiate addiction.

LAAM:

Levo-alpha-acetylmethadol (LAAM) has many of the same benefits and restrictions that are associated with methadone. LAAM is a 'pro-drug' which means that the primary effect of the medication only occurs after it is metabolized in the liver. After the liver converts LAAM into dinor-LAAM individuals experience an opioid effect similar to that produced by methadone. Furthermore, nor-LAAM is converted into dinor-LAAM, which extends the opioid effect for another 48 hours. Hence, individuals treated with LAAM need only to take the medication every 2-3 days to maintain a therapeutic blood level. As with methadone, patients treated with LAAM are physically dependent upon the medication, and withdrawal from the medication is difficult. Currently it is only possible to receive LAAM treatment in narcotic treatment program (NTP) clinics licensed to use methadone. The importance of supportive counseling and other services are equally as significant with LAAM as with methadone.

Naltrexone:

Naltrexone is a long-acting narcotic antagonist approved for the treatment of alcoholism. Ten years before its approval for alcoholism treatment, naltrexone was approved by the FDA for the treatment of opiate dependence. From a theoretical perspective, naltrexone appears to be the perfect medication for treating opiate addiction. It is nonaddicting, it produces no euphoria and it has few side effects. When a detoxified opiate addict takes a 50-mg. tablet of naltrexone, his/her opiate receptors are blocked for 24 hours (a 150-mg. dose will produce a 72-hour blockade). Because of this action, if heroin, morphine or any other opiate is taken during this 24-hour period, nothing happens. The normal effect of the opiate is completely blocked; no high; no readdiction.

Unfortunately, after more than 20 years of research and treatment experience with naltrexone, there are two serious limitations to using it. First, an opiate addict can be treated with naltrexone only after they have been detoxified from all opiates for at least 5-7 days. This is frequently a challenge and a significant obstacle to initiation of naltrexone therapy.

Of even greater significance is the problem of retention in treatment. There is a high drop-out rate from naltrexone treatment. When naltrexone use is discontinued for more than 24 hours, (or 72 hours if the dose is 150 mgs.) it is possible to again experience opiate effects and readdiction.

The majority of clinical research studies have reported that under conditions of voluntary treatment admission, success with naltrexone for heroin treatment has been limited.

There are circumstances in which naltrexone appears to apply. Several studies have indicated that opiate-addicted individuals who are under legal or professional licensing pressure to take naltrexone show substantial clinical benefit from treatment. Naltrexone treatment appears to have promise with opiate-addicted physicians, nurses, dentists, psychologists, lawyers and other professionals who can be required to take naltrexone as a condition of maintaining their professional licenses.

Similarly, individuals with histories of opiate addiction who are under legal supervision (parole, probation, drug-court supervision) can be required to take naltrexone as a condition of their legal status. With this group, naltrexone appears to have significant value in reducing opiate relapse and readdiction. As coerced treatment and prison treatment aftercare are increased as options to incarceration, naltrexone may play an increasing role in improving the outcomes with this large and growing group of addicts.

Buprenorphine/Naloxone:

One of the most important changes in the U.S. substance-abuse treatment system since the introduction of methadone more than 30 years ago, will occur in 2000.

The FDA approval of buprenorphine/-naloxone for the treatment of opiate dependency will be a true watershed event. If, as anticipated, the medication is approved for use outside the narcotic treatment program setting (NTP, i.e., methadone clinics), the access for opiate pharmacotherapy treatment will greatly expand. For the first time, opiate dependent individuals will be able to receive highly effective pharmacotherapy in a mainstream medical setting

Buprenorphine/naloxone (Bup/Nx) is a pharmacotherapy that combines two medications (buprenorphine and naloxone) in a single tablet. Buprenorphine is approved in America, in liquid form for the treatment of pain (Buprenex).

Buprenorphine is a partial opiate agonist. A partial agonist has many of the properties of full agonists (e.g. methadone or LAAM), along with some antagonist properties, similar to full antagonists, (e.g. naltrexone). Buprenorphine produces powerful agonist effects (e.g. relieves pain, eliminates opiate withdrawal symptoms, and reduces drug craving and drug seeking).

These properties make it an acceptable medication to opiate addicts. Another advantage is that discontinuation of the medication results in a far less severe withdrawal syndrome than is seen with full agonists.

The 'partial agonist' properties of buprenorphine, mean that it has a 'ceiling effect' for its agonist properties. The opiate effects of buprenorphine increase with increased doses up to a 'ceiling dose'; going above that dose actually results in a reduced opiate effect. This ceiling effect of the medication makes it much safer than a pure agonist.

Overdose fatalities with buprenorphine are unlikely since increasing the dose, increases the medication effect to a point, followed by a reduced effect. Furthermore, this partial agonist has narcotic antagonist properties, which interfere with, or block the effects of other opiates. Hence, buprenorphine has the positive benefits of an opiate that attract patients into treatment (with a better safety profile and milder withdrawal syndrome), plus antagonist effects that discourage the self-administration of other opiates (e.g., heroin).

The decision to combine buprenorphine with naloxone into a combination product, buprenorphine/naloxone (Sub-oxone) is an important step to discourage the illicit injection of buprenorphine. Alone, buprenorphine can be injected and could potentially be abused, if diverted to the street and injected. As a combination product, if injected by an opiate- dependent individual, the naloxone will precipitate an unpleasant withdrawal syndrome. The addition of naloxone to the buprenorphine will produce a powerful deterrent to illicit injection of the medication.

The current hope of addiction professional groups (ASAM) and federal substance-abuse agencies (NIDA and CSAT) is that bup/nx will be approved for physician use outside of the limited and restrictive NTP system. This would allow physicians (probably with special training and/or certification) to treat opiate-dependent patients in their office practices (as is the case for virtually all other medical conditions). This expansion of an effective opiate pharmacotherapy into the broader healthcare system will tremendously expand access to treatment. For the many opiate users who find methadone or LAAM unavailable, unacceptable or ineffective, bup/nx will provide a potentially life-saving option. The introduction of this new medication is a major step toward moving substance-abuse treatment into the mainstream of the healthcare system. Any treatment that has the potential to dramatically change a treatment system raises many questions and creates controversy. This is true with bup/nx. How expensive will bup/nx be? Will third-party payers, including Medicaid, pay for bup/nx? If used in a physician's office, will adequate attention be given to the necessary counseling and support services? If bup/nx is not effective for some patients, will there be a linkage with other forms of treatment including methadone and LAAM? The answers to these questions are not immediately evident.

There will likely be a period of debate and research required to ensure that this medication is used in the most appropriate manner. However, there is little doubt that the introduction of bup/nx into the treatment system will substantially change addiction treatment in the United States. Bup/nx will save thousands of lives by reducing heroin overdose and slowing the spread of injection-related diseases (e.g., HIV and hepatitis). The challenge will be to successfully and positively integrate this important new tool into a system of care that delivers the necessary nonpharmacological treatment elements to promote meaningful recovery from addiction.

The 20th century will certainly be regarded as the period when substance-abuse treatment was pioneered. Self-help programs, therapeutic communities, 'Minnesota model programs', behavioral strategies and mixed models all have been accepted as formats for providing help for individuals with substance-use disorders. The current century will be a time that this field matures and solidifies the scientific foundation for treatments. It is inevitable that pharmacotherapy tolls will play an increasingly important role in this area, as they have in virtually all areas of medicine and psychiatry.

Nonphysician treatment professionals who hope to begin or sustain careers in substance-abuse treatment have a clear choice for their futures. They can resist the use of medication treatments based upon their personal beliefs about the nature of substance-abuse recovery and become dinosaurs, who will be rapidly left behind in the profession; or, they can learn to recognize the potential value that these new tools have to help individuals struggling to find recovery. Building bridges between the medical-care professionals who will manage the access to pharmacotherapies and the counseling professionals who deliver all of the essential nonpharmacological treatment tools is where the 'action' will be in the next several decades. Learning the nature of the medications, how they work, whom they can help and how they can contribute to recovery will be valuable new areas of study for all addiction professionals.