Pharmacotherapy and Relapse Prevention
By Kate Jackson
Social Work Today
Vol. 4, No. 7, Page 26

Pharmacotherapy is another effective tool to battle drug and alcohol addiction, but without adjunctive psychological therapy, medications can be little more than a prescription for failure.

In recent years, several new pharmacologic approaches to the treatment of drug and alcohol addiction have emerged and been demonstrated effective. Yet, for various reasons, they’re seldom prescribed. Healthcare providers are often simply not well-informed about these options, while others dismiss pharmacology on ethical grounds, insisting that it’s inappropriate to fight fire with fire. Some, explains G. Alan Marlatt, PhD, professor and director, Addictive Behaviors Research Center, University of Washington, department of psychology, even frown upon pharmacotherapy for individuals with co-occurring disorders such as depression and anxiety.

Many addiction medicine professionals argue that the benefits of therapy with these new agents outweigh or nullify the objections. Mindful that an eventual goal for individuals struggling with addiction is a drug-free existence, Marlatt insists nevertheless that to deny them the opportunity to make use of drugs for relapse prevention is to deprive them of tools that can be highly beneficial. “Because we don’t know—nor does anyone else at this point—what is the most effective treatment for people with addiction problems, the more irons in the fire and the more options that people have, the better,” he maintains.

Pharmaceutical interventions—methadone being the most classic—he says, have reduced problems for many people and lessened the risk for HIV and hepatitis among heroin addicts. He and other experts insist that addiction professionals, including social workers, should be aware of all the options that might improve the lives of their clients and patients and consider all possibilities to devise individualized approaches.

“There needs to be a culture change because we haven’t had the benefits of this pharmaceutical science until now,” agrees David R. Gastfriend, MD, assistant professor of psychiatry, Harvard Medical School, and director of the Addiction Research Program, Massachusetts General Hospital. “The realization is coming that this is a disease of brain chemistry, and if the field learns to use these medicines properly, there will be more effort to build the pharmacological armamentarium.”

Pharmacotherapy for Opiate Addiction
Until very recently, a key treatment for those addicted to heroin and other opiates was replacement therapy with methadone, which is also addictive, but which has a longer half-life than heroin. It doesn’t produce the extreme highs and allows individuals to maintain the addiction in a more controlled fashion so it doesn’t necessarily become a social and health problem, says Wolfgang Sadée, Dr.rer.nat, Felts Mercer professor of medicine and pharmacology; chair, department of pharmacology; director, program in pharmacogenomics; and director, School of Biomedical Sciences at Ohio State University. Because withdrawal results in severe symptoms, this maintenance drug must be taken daily and is a long-term treatment. Individuals taking methadone must travel each day to a clinic where the drug is administered—a requirement that is both highly inconvenient and often stigmatizing.

A new drug is changing all that. Introduced to United States’ pharmacies in January 2003, Suboxone (buprenorphine) is an FDA-approved prescription medication to help individuals who are dependent on opiates such as heroin and prescription painkillers, including OxyContin, Vicodin, and Percocet. Because doctors can administer buprenorphine in their offices and provide prescriptions for maintenance that patients can take as they would any other medication, the drug eliminates the inconvenience and sense of shame often associated with methadone treatment at clinics.

Buprenorphine, an opiate that is a derivative of thebaine, was initially a pain medication anesthesiologists administered intramuscularly. An effective analgesic, the drug stayed in the body for a relatively long period of time, and thus proved to have some of the ideal properties that would make it a good medicine to treat addiction and a viable alternative to methadone. Researchers found that it could be given sublingually rather than intramuscularly, which slows its onset of action.

What makes a drug addictive is the speed and onset of action in addition to the action itself, says Samuel M. Silverman, MD, FAPA, medical director, substance abuse services, Rushford Behavioral Health. Crack cocaine, for example, is more addictive than cocaine because the same substance, when brought into the lung rather than being snorted or taken intravenously, reaches the brain more quickly. Heroin, which can be smoked or injected, is also very addictive.

Because buprenorphine’s onset of action occurs 60 to 90 minutes after sublingual administration, it doesn’t produce euphoria. Furthermore, it sits on the opiate receptor for 24 to 48 hours, says Silverman, and while it’s there it prevents other opiates from working. “If a person takes buprenorphine and continues to use heroin on top of it, the heroin has no place to go because the opiate receptor is blocked and the person can’t get high,” says Silverman. “The drug binds tightly to the receptor and disassociates very slowly off of it.” As a result, it can be used once a day or once every other day and is safe even in cases of overdose. While taking too much heroin or methadone can lead to fatal respiratory depression, he explains, taking too much buprenorphine merely causes the drug to be ineffective, which makes it an ideal drug to treat opiate addiction.

For most patients, treatment is likely to be long-term. Silverman explains that studies have shown that from 70% to 90% of people who have had successful treatment at methadone clinics relapse within one year after stopping the treatment. This new approach may reverse the conventional wisdom that says treatment should end as quickly as possible. “The longer a patient is in treatment, the better the outcome,” he says. “So as a provider, if you find that this medication is correcting some kind of deficiency at the opiate receptor—if it works and it’s allowing people to reclaim their lives—you might want to consider revising the paradigm by which patients are taken off of medication quickly.”

Silverman used to treat patients in detox and get them off opiates very quickly, but he found that these patients typically returned because they were unable to overcome their cravings. He then began to use buprenorphine for maintenance and his patients have had positive outcomes. In light of statistics showing poor outcomes when patients are taken off medications such as methadone, Silverman decided not to rush to take his patients off buprenorphine. It would be akin, he suggests, to telling patients with diabetes to stop using insulin because they’ve used it long enough. Not only is treatment successful, says Silverman, but his patients report no significant side effects. “I have 30 patients on it, and side effects are not an issue—not even sedation or euphoria. I keep looking for them, but I can’t find them.”

Patients getting methadone—the only other drug for opiate addiction—can only receive the drug at methadone clinics, which, says Silverman, means they must come in every day for perhaps the first 90 days and wait in line to receive the methadone. Working parents and others trying to hold down jobs and meet responsibilities are severely hampered by such restrictions, and many are demoralized by the stigma associated with having to go to the clinics. Treatment with buprenorphine, however, doesn’t burden patients in that way and improves their ability to get a grip on life. Millions of ordinary Americans who become dependent on prescription painkillers after being properly treated for pain need this treatment, he says. Silverman has an arrangement with a pharmacy to have buprenorphine delivered to his office, and he gives it to his group therapy patients one week at a time, supervising and monitoring the dosage.

Buprenorphine, like other pharmacotherapies, isn’t intended to work by itself. “If patients ever come off the drug,” says Silverman, “they’re not going to be prepared to deal with the stressors and do the things they need to do to stay in recovery.” People struggling against addiction, he insists, also need to learn how to change their lives. “If we just give the medicines and don’t deal with the addictive tendencies, the outcome won’t be as good.” Buprenorphine, he explains, is a tool for getting patients to come back and keep coming back until they get it right.

Social workers, Silverman adds, are generally encouraged about this new tool. “They see this as a way to stop the revolving door and have patients take hold and remain engaged in treatment. The patients in my group are in treatment for six to 12 months. They form a relationship with the group and with each other, and for the first time people can work with them. Their minds are present and they’re not thinking about getting high. It makes it easier for counselors to do what they wanted to do when they got into this area: to work with people who are motivated.”

As helpful as buprenorphine is, its use has been limited, in part because physicians must have special training to prescribe it and because they’re currently limited to treating only 30 patients at one time. Treatment centers and hospitals that employ physicians, says Silverman, would love to use it, but they’re also limited to 30 patients, regardless of the number of physicians working within them.

New Options for Alcoholism Treatment
For decades, the only medical option for individuals struggling with alcohol addiction has been Antabuse (disulfiram), which works by blocking the metabolism of alcohol and making individuals feel sick if they drink. “The idea is that people get up in the morning, take Antabuse to keep them from drinking during the day,” says Marlatt. The end result, he says, is that alcoholics generally wouldn’t take it. Most were not inclined to continue taking something they’d have to take for a lifetime, and others insisted they didn’t need a pill to tackle their drinking problems. The average number of days alcoholics continued to take Antabuse, he says, was less than one week.

In light of less-than-stellar results with Antabuse, providers have embraced the promise of a new approach. Originally developed to combat opiate addiction, naltrexone is now used in the battle against alcoholism. Unlike Antabuse, it doesn’t produce a negative reaction; rather, it reduces cravings and thus helps reduce relapse rates. Naltrexone itself isn’t new, but a new formulation, Vivitrex, is being studied. A once-monthly dose injection into the buttocks blocks the endorphin system for one month, reducing the excessive reward alcoholics receive when they drink, explains Gastfriend, who, along with other researchers in a multisite study, researched the long-acting preparation as part of a large phase 3 FDA trial. Patients, he says, don’t become dependent on the drug, which is not only nonaddictive but also nonsedating.

It’s not clear how long patients will need to remain on the drug to prevent relapse. But Gastfriend explains that the study extended the offer of the medicine beyond the six months of the initial trial, and there are patients who have continued on the medicine for more than two years because “there was an astounding effect in which the percentage of heavy drinking days dropped dramatically and very significantly.” The drug is being prepared for FDA review, and Gastfriend anticipates that it’s likely to be available to the public within two years. “The experience of 624 patients in the study suggests that it could have a big effect on improving patients’ lives, so counselors and therapists will have to learn a lot about the benefits of medication for alcoholism in order to be able to deliver that promise,” he says.

Acamprosate Calcium
Another new drug for treating those who are alcohol-dependent and helping them stay alcohol-free is acamprosate calcium, marketed as Campral. These delayed-release tablets were approved in July by the FDA for patients who are abstinent at the initiation of treatment. Campral doesn’t work by blocking the effects of alcohol, and its mechanism of action is unclear. Researchers believe it works by restoring the normal balance of neurotransmitter systems. Although research is promising, it’s too soon to predict how Campral will change the way in which alcoholism is treated. The first new medication in nine years approved for the treatment of alcohol dependence, Campral is expected to be available to physicians, pharmacies, and patients at the end of this year.

These new drugs, says Donna Yi, MD, addictions psychiatrist specializing in psychopharmacology and medical care at the Menninger Clinic’s Professionals in Crisis Program treatment team at Baylor College of Medicine, are great advances that give providers more tools with which to individualize treatment.

Not a Panacea
Although pharmacology extends the ability of addiction professionals to offer help, scientists still look forward to a revolution in addiction medicine. “We would like to eventually find something that alleviates or breaks the vicious cycle of addiction in a way that is innocuous and allows patients to live a normal life, but that’s really not the case right now,” explains Sadée.

In the meantime, many believe these pharmaceutical agents are improving lives. They caution, however, that they’re not a complete solution. Without adjunctive psychological therapy, pharmacotherapy can be little more than a prescription for failure. “These drugs can help reduce cravings or provide short-term motivation, but in the long term, people struggling with addiction are going to need more than that,” says Sadée.

Pharmacotherapies, he notes, have a more immediate short-term effect but tend to wear off in the long run or people stop using them for various reasons. Some may feel that after a period of use, they’ve achieved their goals and no longer need the medication, so they stop pharmacotherapy and run an increased risk of relapse. Others are troubled by the fact that they remain dependent on a drug—even if it’s a drug used to treat addiction—and insist on trying to master their addiction on their own.

Instead, says Marlatt, pharmacotherapy must be offered as a tool that can be used as part of a larger program of lifestyle change that includes some form of behavioral therapy and counseling that helps individuals develop coping strategies. Behavioral programs, he’s quick to point out, can be gradual in their effect because people must learn new skills and it takes them some time to become proficient. Treatment, adds Yi, may also encompass 12-step work, relapse prevention skills, dialectical behavior therapy, cognitive-behavioral therapy, family therapy, and couples therapy. By combining these modalities, however, you can double the prospects for success. “With relapse prevention,” says Yi, “it’s a big umbrella.”

Patients, she adds, need to know how to manage the consequences of their illness and work on harm avoidance in an all-encompassing way. Just as you would tell patients with diabetes or cardiovascular disease that they have to manage areas in their lives that have been affected by disease and change their lifestyles, she says, “you can’t just tell patients that taking a pill will rid them of their cravings. If they don’t deal with the stressors at home, with bad relationships, with their inability to cope with stress, with the jobs at which they’re unhappy, then medication is less likely to work.”

What works best in addiction treatment, says Marlatt, is to have a patient working with a counselor who’s committed to monitoring the patient’s progress and providing a variety of tools—whether medication, a 12-step program, cognitive-behavior therapy, mindfulness meditation, family therapy, or a combination of approaches—to see what works best for the individual. The challenge, he says, is in matching the individual to the right program. “The biggest thing right now in the addiction field,” he says, “is consumer choice—making people, both patients and providers, aware that there is more than one way to beat addiction.”

Concludes Gastfriend: “The more we equip providers with effective tools, the more they will realize that this is just another illness, like cancer, which isn’t hopeless any longer, and like schizophrenia, which isn’t the devil’s curse any longer. The era of medication is arriving, and it’s time to learn more about it.”

— Kate Jackson is a staff writer for Social Work Today.

Seizure Drug Holds Promise
The May 17 issue of The Lancet reported the findings of a landmark study by researchers at the University of Texas Health Science Center at San Antonio indicating that Topamax (topiramate), an antiepilepsy drug, is effective in promoting abstinence among alcohol-dependent individuals. One hundred fifty patients were still drinking heavily when they were enrolled in the study, which was conducted by Professor Bankole A. Johnson, MD, PhD, and colleagues. The patients were randomized to receive oral topiramate or placebo for three months along with a minimum intervention behavior treatment. Those who took topiramate were six times more likely than those on the placebo to be abstinent continually for at least one month during the trial. The advantage of topiramate, the researchers observe, is that it can be used on patients who have not yet become abstinent, thus allowing people to be treated earlier.

— Source: University of Texas Health Science Center at San Antonio

For more information, visit the following Web sites:
• www.aapspharmaceutica.com/frontiers
• www.opoiddependence.com
• http://buprenorphine.samhsa.gov
• www.merck.de