Tag Archive: National Institute on Drug Abuse (NIDA)

I was driving up the Massachusetts Turnpike one evening last February when I knocked over a bottle of water. I grabbed for it, swerved inadvertently–and a few seconds later found myself blinking into the flashlight beam of a state trooper. „How much have you had to drink tonight, sir?“ he demanded. Before I could help myself, I blurted out an answer that was surely a new one to him. „I haven’t had a drink,“ I said indignantly, „since 1981.“

It was both perfectly true and very pertinent to the trip I was making. By the time I reached my late 20s, I’d poured down as much alcohol as normal people consume in a lifetime and plenty of drugs–mostly pot–as well. I was, by any reasonable measure, an active alcoholic. Fortunately, with a lot of help, I was able to stop. And now I was on my way to McLean Hospital in Belmont, Mass., to have my brain scanned in a functional magnetic-resonance imager (fMRI). The idea was to see what the inside of my head looked like after more than a quarter-century on the wagon.

Back when I stopped drinking, such an experiment would have been unimaginable. At the time, the medical establishment had come to accept the idea that alcoholism was a disease rather than a moral failing; the American Medical Association (AMA) had said so in 1950. But while it had all the hallmarks of other diseases, including specific symptoms and a predictable course, leading to disability or even death, alcoholism was different. Its physical basis was a complete mystery–and since nobody forced alcoholics to drink, it was still seen, no matter what the AMA said, as somehow voluntary. Treatment consisted mostly of talk therapy, maybe some vitamins and usually a strong recommendation to join Alcoholics Anonymous. Although it’s a totally nonprofessional organization, founded in 1935 by an ex-drunk and an active drinker, AA has managed to get millions of people off the bottle, using group support and a program of accumulated folk wisdom.

While AA is astonishingly effective for some people, it doesn’t work for everyone; studies suggest it succeeds about 20% of the time, and other forms of treatment, including various types of behavioral therapy, do no better. The rate is much the same with drug addiction, which experts see as the same disorder triggered by a different chemical. „The sad part is that if you look at where addiction treatment was 10 years ago, it hasn’t gotten much better,“ says Dr. Martin Paulus, a professor of psychiatry at the University of California at San Diego. „You have a better chance to do well after many types of cancer than you have of recovering from methamphetamine dependence.“

That could all be about to change. During those same 10 years, researchers have made extraordinary progress in understanding the physical basis of addiction. They know now, for example, that the 20% success rate can shoot up to 40% if treatment is ongoing (very much the AA model, which is most effective when members continue to attend meetings long after their last drink). Armed with an array of increasingly sophisticated technology, including fMRIs and PET scans, investigators have begun to figure out exactly what goes wrong in the brain of an addict–which neurotransmitting chemicals are out of balance and what regions of the brain are affected. They are developing a more detailed understanding of how deeply and completely addiction can affect the brain, by hijacking memory-making processes and by exploiting emotions. Using that knowledge, they’ve begun to design new drugs that are showing promise in cutting off the craving that drives an addict irresistibly toward relapse–the greatest risk facing even the most dedicated abstainer.

„Addictions,“ says Joseph Frascella, director of the division of clinical neuroscience at the National Institute on Drug Abuse (NIDA), „are repetitive behaviors in the face of negative consequences, the desire to continue something you know is bad for you.“

Addiction is such a harmful behavior, in fact, that evolution should have long ago weeded it out of the population: if it’s hard to drive safely under the influence, imagine trying to run from a saber-toothed tiger or catch a squirrel for lunch. And yet, says Dr. Nora Volkow, director of NIDA and a pioneer in the use of imaging to understand addiction, „the use of drugs has been recorded since the beginning of civilization. Humans in my view will always want to experiment with things to make them feel good.“

That’s because drugs of abuse co-opt the very brain functions that allowed our distant ancestors to survive in a hostile world. Our minds are programmed to pay extra attention to what neurologists call salience–that is, special relevance. Threats, for example, are highly salient, which is why we instinctively try to get away from them. But so are food and sex because they help the individual and the species survive. Drugs of abuse capitalize on this ready-made programming. When exposed to drugs, our memory systems, reward circuits, decision-making skills and conditioning kick in–salience in overdrive–to create an all consuming pattern of uncontrollable craving. „Some people have a genetic predisposition to addiction,“ says Volkow. „But because it involves these basic brain functions, everyone will become an addict if sufficiently exposed to drugs or alcohol.“

That can go for nonchemical addictions as well. Behaviors, from gambling to shopping to sex, may start out as habits but slide into addictions. Sometimes there might be a behavior-specific root of the problem. Volkow’s research group, for example, has shown that pathologically obese people who are compulsive eaters exhibit hyperactivity in the areas of the brain that process food stimuli–including the mouth, lips and tongue. For them, activating these regions is like opening the floodgates to the pleasure center. Almost anything deeply enjoyable can turn into an addiction, though.

Of course, not everyone becomes an addict. That’s because we have other, more analytical regions that can evaluate consequences and override mere pleasure seeking. Brain imaging is showing exactly how that happens.Paulus, for example, looked at methamphetamine addicts enrolled in a VA hospital’s intensive four-week rehabilitation program. Those who were more likely to relapse in the first year after completing the program were also less able to complete tasks involving cognitive skills and less able to adjust to new rules quickly. This suggested that those patients might also be less adept at using analytical areas of the brain while performing decision-making tasks. Sure enough, brain scans showed that there were reduced levels of activation in the prefrontal cortex, where rational thought can override impulsive behavior. It’s impossible to say if the drugs might have damaged these abilities in the relapsers–an effect rather than a cause of the chemical abuse–but the fact that the cognitive deficit existed in only some of the meth users suggests that there was something innate that was unique to them. To his surprise, Paulus found that 80% to 90% of the time, he could accurately predict who would relapse within a year simply by examining the scans.

Another area of focus for researchers involves the brain’s reward system, powered largely by the neurotransmitter dopamine. Investigators are looking specifically at the family of dopamine receptors that populate nerve cells and bind to the compound. The hope is that if you can dampen the effect of the brain chemical that carries the pleasurable signal, you can loosen the drug’s hold.

One particular group of dopamine receptors, for example, called D3, seems to multiply in the presence of cocaine, methamphetamine and nicotine, making it possible for more of the drug to enter and activate nerve cells. „Receptor density is thought to be an amplifier,“ says Frank Vocci, director of pharmacotherapies at NIDA. „[Chemically] blocking D3 interrupts an awful lot of the drugs‘ effects. It is probably the hottest target in modulating the reward system.“

But just as there are two ways to stop a speeding car–by easing off the gas or hitting the brake pedal–there are two different possibilities for muting addiction. If dopamine receptors are the gas, the brain’s own inhibitory systems act as the brakes. In addicts, this natural damping circuit, called GABA (gamma-aminobutyric acid), appears to be faulty. Without a proper chemical check on excitatory messages set off by drugs, the brain never appreciates that it’s been satiated.

As it turns out, vigabatrin, an antiepilepsy treatment that is marketed in 60 countries (but not yet in the U.S.), is an effective GABA booster. In epileptics, vigabatrin suppresses overactivated motor neurons that cause muscles to contract and go into spasm. Hoping that enhancing GABA in the brains of addicts could help them control their drug cravings, two biotech companies in the U.S., Ovation Pharmaceuticals and Catalyst

Pharmaceuticals, are studying the drug’s effect on methamphetamine and cocaine use. So far, in animals, vigabatrin prevents the breakdown of GABA so that more of the inhibitory compound can be stored in whole form in nerve cells. That way, more of it could be released when those cells are activated by a hit from a drug. Says Vocci, optimistically: „If it works, it will probably work on all addictions.“

Another fundamental target for addiction treatments is the stress network. Animal studies have long shown that stress can increase the desire for drugs. In rats trained to self-administer a substance, stressors such as a new environment, an unfamiliar cage mate or a change in daily routine push the animals to depend on the substance even more.

Among higher creatures like us, stress can also alter the way the brain thinks, particularly the way it contemplates the consequences of actions. Recall the last time you found yourself in a stressful situation–when you were scared, nervous or threatened. Your brain tuned out everything besides whatever it was that was frightening you–the familiar fight-or-flight mode. „The part of the prefrontal cortex that is involved in deliberative cognition is shut down by stress,“ says Vocci. „It’s supposed to be, but it’s even more inhibited in substance abusers.“ A less responsive prefrontal cortex sets up addicts to be more impulsive as well.

Hormones–of the male-female kind–may play a role in how people become addicted as well. Studies have shown, for instance, that women may be more vulnerable to cravings for nicotine during the latter part of the menstrual cycle, when the egg emerges from the follicle and the hormones progesterone and estrogen are released. „The reward systems of the brain have different sensitivities at different points in the cycle,“ notes Volkow. „There is way greater craving during the later phase.“

That led researchers to wonder about other biological differences in the way men and women become addicted and, significantly, respond to treatments. Alcohol dependence is one very promising area. For years, researchers had documented the way female alcoholics tend to progress more rapidly to alcoholism than men. This telescoping effect, they now know, has a lot to do with the way women metabolize alcohol. Females are endowed with less alcohol dehydrogenase–the first enzyme in the stomach lining that starts to break down the ethanol in liquor–and less total body water than men. Together with estrogen, these factors have a net concentrating effect on the alcohol in the blood, giving women a more intense hit with each drink. The pleasure from that extreme high may be enough for some women to feel satisfied and therefore drink less. For others, the intense intoxication is so enjoyable that they try to duplicate the experience over and over.

But it’s the brain, not the gut, that continues to get most of the attention, and one of the biggest reasons is technology. It was in 1985 that Volkow first began using PET scans to record trademark characteristics in the brains and nerve cells of chronic drug abusers, including blood flow, dopamine levels and glucose metabolism–a measure of how much energy is being used and where (and therefore a stand-in for figuring out which cells are at work). After the subjects had been abstinent a year, Volkow rescanned their brains and found that they had begun to return to their predrug state. Good news, certainly, but only as far as it goes.

„The changes induced by addiction do not just involve one system,“ says Volkow. „There are some areas in which the changes persist even after two years.“ One area of delayed rebound involves learning. Somehow in methamphetamine abusers, the ability to learn some new things remained affected after 14 months of abstinence. „Does treatment push the brain back to normal,“ asks NIDA’s Frascella, „or does it push it back in different ways?“If the kind of damage that lingers in an addict’s learning abilities also hangs on in behavioral areas, this could explain why rehabilitation programs that rely on cognitive therapy–teaching new ways to think about the need for a substance and the consequences of using it–may not always be effective, especially in the first weeks and months after getting clean. „Therapy is a learning process,“ notes Vocci. „We are trying to get [addicts] to change cognition and behavior at a time when they are least able to do so.“

One important discovery: evidence is building to support the 90-day rehabilitation model, which was stumbled upon by AA (new members are advised to attend a meeting a day for the first 90 days) and is the duration of a typical stint in a drug-treatment program. It turns out that this is just about how long it takes for the brain to reset itself and shake off the immediate influence of a drug. Researchers at Yale University have documented what they call the sleeper effect–a gradual re-engaging of proper decision making and analytical functions in the brain’s prefrontal cortex–after an addict has abstained for at least 90 days.

This work has led to research on cognitive enhancers, or compounds that may amplify connections in the prefrontal cortex to speed up the natural reversal. Such enhancement would give the higher regions of the brain a fighting chance against the amygdala, a more basal region that plays a role in priming the dopamine-reward system when certain cues suggest imminent pleasure–anything from the sight of white powder that looks like cocaine to spending time with friends you used to drink with. It’s that conditioned reflex–identical to the one that caused Ivan Pavlov’s famed dog to salivate at the ringing of a bell after it learned to associate the sound with food–that unleashes a craving. And it’s that phenomenon that was the purpose of my brain scans at McLean, one of the world’s premier centers for addiction research.

In my heyday, I would often drink even when I knew it was a terrible idea–and the urge was hardest to resist when I was with my drinking buddies, hearing the clink of glasses and bottles, seeing others imbibe and smelling the aroma of wine or beer. The researchers at McLean have invented a machine that wafts such odors directly into the nostrils of a subject undergoing an fMRI scan in order to see how the brain reacts. The reward circuitry in the brain of a newly recovering alcoholic should light up like a Christmas tree when stimulated by one of these alluring smells.

I chose dark beer, my absolute favorite, from their impressive stock. But I haven’t gotten high for more than a quarter-century; it was an open question whether I would react that way. So after an interview with a staff psychiatrist to make sure I would be able to handle it if I experienced a craving, I was fitted with a tube that carried beer aroma from a vaporizer into my nose. I was then slid into the machine to inhale that still familiar odor while the fMRI did its work.

Even if the smells triggered a strong desire to drink, I had long since learned ways to talk myself out of it–or find someone to help me do so. Like the 90-day drying-out period that turns out to parallel the brain’s recovery cycle, such a strategy is in line with other new theories of addiction. Scientists say extinguishing urges is not a matter of getting the feelings to fade but of helping the addict learn a new form of conditioning, one that allows the brain’s cognitive power to shout down the amygdala and other lower regions. „What has to happen for that cue to extinguish is not for the amygdala to become weaker but for the frontal cortex to become stronger,“ says Vocci.

While such relearning has not been studied formally in humans, Vocci believes it will work, on the basis of studies involving, of all things, phobias. It turns out that phobias and drugs exploit the same struggle between high and low circuits in the brain. People placed in a virtual-reality glass elevator and treated with the antibiotic D-cycloserine were better able to overcome their fear of heights than those without benefit of the drug. Says Vocci: „I never thought we would have drugs that affect cognition in such a specific way.“

Such surprises have even allowed experts to speculate whether addiction can ever be cured. That notion goes firmly against current beliefs. A rehabilitated addict is always in recovery because cured suggests that resuming drinking or smoking or shooting up is a safe possibility–whose downside could be devastating. But there are hints that a cure might not in principle be impossible. A recent study showed that tobacco smokers who suffered a stroke that damaged the insula (a region of the brain involved in emotional, gut-instinct perceptions) no longer felt a desire for nicotine.

That’s exciting, but because the insula is so critical to other brain functions–perceiving danger, anticipating threats–damaging this area isn’t something you would ever want to do intentionally. With so many of the brain’s systems entangled with one another, it could prove impossible to adjust just one without throwing the others into imbalance.

Nevertheless, says Volkow, „addiction is a medical condition. We have to recognize that medications can reverse the pathology of the disease. We have to force ourselves to think about a cure because if we don’t, it will never happen.“ Still, she is quick to admit that just contemplating new ideas doesn’t make them so. The brain functions that addiction commandeers may simply be so complex that sufferers, as 12-step recovery programs have emphasized for decades, never lose their vulnerability to their drug of choice, no matter how healthy their brains might eventually look.

I’m probably a case in point. My brain barely lit up in response to the smell of beer inside the fMRI at McLean. „This is actually valuable information for you as an individual,“ said Scott Lukas, director of the hospital’s behavioral psychopharmacology research laboratory and a professor at Harvard Medical School who ran the tests. „It means that your brain’s sensitivity to beer cues has long passed.“

That’s in keeping with my real-world experience; if someone has a beer at dinner, I don’t feel a compulsion to leap across the table and grab it or even to order one for myself. Does that mean I’m cured? Maybe. But it may also mean simply that it would take a much stronger trigger for me to fall prey to addiction again–like, for example, downing a glass of beer. But the last thing I intend to do is put it to the test. I’ve seen too many others try it–with horrifying results.

SOUTH SAN FRANCISCO, Calif., Sept. 22 /PRNewswire-FirstCall/ — Titan Pharmaceuticals, Inc. (OTC Bulletin Board: TTNP) today announced that patient enrollment is now complete in the confirmatory, Phase 3 clinical study of Probuphine for the treatment of opioid addiction.  This placebo and active controlled Phase 3 study is being conducted at 20 sites in the United States and the results are expected in the second quarter of 2011, about three months ahead of the original schedule. This study is part of a registration-directed program intended to obtain marketing approval of Probuphine for the treatment of opioid addiction in the United States and Europe.

„We are very encouraged by the excellent response to recruitment for this trial.  Thanks to the ongoing dedication of the Probuphine Consortium of clinical investigators and their staff, we expect to report the results of this important trial significantly ahead of schedule, in the second quarter of next year,“ said Dr. Katherine L. Beebe, Senior Vice President, Clinical Development and Medical Affairs and Principal Investigator of the study.

This study is partially supported by a two-year $7.6 million, Research and Research Infrastructure Grand Opportunities grant through the American Reinvestment and Recovery Act of 2009 (ARRA),  and the second year allocation of approximately $2 million has recently been approved by the National Institutes of Health (NIH). The grant is administered by the National Institute on Drug Abuse (NIDA).

Initial safety and effectiveness of treatment for opioid addiction with Probuphine has been demonstrated in a series of clinical studies. Probuphine also has the potential to reduce limitations currently associated with daily oral buprenorphine therapy, including poor compliance, withdrawal and craving symptoms associated with variable blood levels and diversion and non-medical use of the drug. Results of the Probuphine development program to date will be presented during a symposium titled „Buprenorphine Implant for the Long-Term Treatment of Opioid Dependence,“ on October 6, 2010 in Milan, Italy at the 2010 International Society of Addiction Medicine (ISAM) conference.  The 90-minute symposium is co-chaired by Dr. Beebe of Titan and Dr. Ivan Montoya of NIDA, Division of Pharmacotherapies and Medical Consequences of Drug Abuse (DPMCDA),  and will cover all aspects of the Probuphine development program from early non-clinical studies to pharmacokinetic and clinical studies demonstrating the safety and effectiveness of Probuphine.  Further information about the scientific program may be found on the ISAM website at http://www.isam2010.medicina.unimib.it/scientific_program/day6/

The World Health Organization estimates that 2.8 million individuals in the U.S. and Europe are addicted to illicit opiates such as heroin, and more than 2.0 million individuals in the U.S. alone are addicted to prescription opioid medications.  It is estimated that about twenty percent of this population are currently receiving pharmacological treatment.

About Probuphine

Probuphine is designed to deliver six months of continuous round-the-clock, long-term therapeutic levels of the drug buprenorphine following a single subcutaneous treatment. Buprenorphine, an approved agent for the treatment of opioid addiction, is currently available mainly in the form of a sublingual tablet formulation. The safety and effectiveness of treatment with Probuphine has been initially established in the three Phase 3 studies conducted to date, specifically, a 163 patient placebo controlled study which demonstrated clinically meaningful and statistically significant treatment with Probuphine over a 24 week period, an open label 24 week retreatment study in 62 patients who had successfully completed six months of treatment in the controlled study, and a relative bioavailability study in 9 patients treated with Suboxone® and then switched to Probuphine treatment for 60 days.

Probuphine was developed using ProNeura, Titan’s continuous drug delivery system that consists of a small, solid rod made from a mixture of ethylene-vinyl acetate (EVA) and a drug substance. The resulting product is a solid matrix that is placed subcutaneously, normally in the upper arm in a simple office procedure, and is removed in a similar manner at the end of the treatment period. The drug substance is released slowly, at continuous levels, through the process of diffusion. This results in a constant rate of release similar to intravenous administration.

Research and Research Infrastructure Grand Opportunities Program

The purpose of the Research and Research Infrastructure Grand Opportunities program is to support high impact ideas and large-scale research projects that accelerate critical breakthroughs, early and applied research on cutting-edge technologies, and new approaches to improve the synergy and interactions among multi and interdisciplinary research teams.

This initiative is being offered to help fulfill the goals of the American Recovery and Reinvestment Act to help stimulate the economy through support of biomedical and behavioral research. The ARRA will provide economic stimulus to the nation while furthering the NIH mission to uncover new knowledge that will lead to better health for everyone.

For more information on ARRA funding, visit grants.nih.gov/recovery. To track the progress of Health and Human Services activities funded through the recovery act, visit www.hhs.gov/recovery. To track all federal funds provided through the recovery act, visit http://www.recovery.gov/.

About Titan Pharmaceuticals

For information concerning Titan Pharmaceuticals, Inc., please visit the Company’s website at www.titanpharm.com.

The press release may contain „forward-looking statements“ within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements include, but are not limited to, any statements relating to the Company’s development program and any other statements that are not historical facts. Such statements involve risks and uncertainties, including, but not limited to, those risks and uncertainties relating to difficulties or delays in development, testing, regulatory approval, production and marketing of the Company’s drug candidates, adverse side effects or inadequate therapeutic efficacy of the Company’s drug candidates that could slow or prevent product development or commercialization, the uncertainty of patent protection for the Company’s intellectual property or trade secrets, and the Company’s ability to obtain additional financing. Such statements are based on management’s current expectations, but actual results may differ materially due to various factors, including those risks and uncertainties mentioned or referred to in this press release.

Patients who stay in methadone treatment for 12 months or longer have better therapeutic outcomes — yet most drop out within the critical first year. According to a recent study funded by the National Institute on Drug Abuse (NIDA), a major factor is a clinic’s views of its patients.

Clinics perceiving methadone patients as „consumers“ who spend time and often money on treatment for opioid addiction generally try to attract patients by providing services such as child care, flexible hours, and help with housing and transportation. Clinics with the classic view of patients as „beneficiaries,“ for whom treatment is considered a privilege, may offer patients fewer options and focus on the needs of the program rather than those of the patient. The authors suggest that by viewing patients as consumers of services, rather than beneficiaries, methadone clinics can retain patients in treatment longer and improve therapeutic outcomes.

Participants in the study were 42 patients prematurely discharged from six methadone programs in metropolitan Baltimore, Maryland. The study spanned 18 months, ending in June 2006, and was based on in-depth, semi-structured interviews. About 64 percent of participants were black, the remainder white. Average age of participants was 40 years. About 60 percent were men. Approximately 74 percent of participants reported injecting heroin. The average length of treatment was 124 days, and the group had an average of three prior drug-treatment episodes.

Reasons for Premature Discharge

Of the 42 patients, 17 left early for program-related reasons, 16 because of incarceration, 5 in order to become free of all addictions, and 4 because of life events or logistics. As discussed below, the somewhat rigid „beneficiary“ thread ran through patients‘ dissatisfaction and departure.

Conflicting Views of Reasons for Discharge

Counselors had to select a reason for discharge from eight categories. „Left before completing treatment“ was the counselors‘ most common reason, even for incarcerated patients. According to the authors, this suggested unawareness of the true reasons, but an alternate explanation could be that staff do not necessarily consider paperwork to be related to treatment. Yet the discharge summary report can be important, because ideally it accompanies the patient to any subsequent programs, possibly influencing the patient’s later attempts at recovery.

Specific Program-Related Factors

  • Disagreement with program rules. Some participants were frustrated with program policies and procedures that they believed were applied inconsistently or continuously changed, hindering their ability to improve their lives. For example, a homeless patient had a specific plan for regaining a construction job, but his counselor put other projects in his way, then complained he lacked stable housing. „So I was really bummed.“ He left the program.
  • Conflicts with staff. Some conflicts with counselors led to confrontations and discharge from the program. Program directors sometimes refused patients‘ requests for a different counselor. Some patients saw counselors as disrespecting patients‘ „street“ education. A patient complained that he didn’t need anyone, because he was „a grown man.“
  • „Feetox.“ Rapid detoxification and discharge because of late payment or nonpayment of fees evoked strong reactions. „It’s all about money,“ said an exasperated patient who was feetoxed after falling less than a week behind during the first month of treatment.
  • Scheduling conflicts. Many patients tried to cope with schedules, public transportation problems, family obligations, and job-seeking. A „beneficiary“ working a 12-hour shift couldn’t get to the clinic while it was open. Another found a good job, but the commute was an hour and a half. Both chose work over treatment. The authors did not comment on the possibility that without treatment, relapse and possible job loss might occur

Desire to be Free of Addiction

Despite a generally positive view of methadone, more than 10 percent of discharged patients left treatment primarily to be free of all medication. Some were „scared of becoming dependent“ on methadone. A patient said that trying to work and get to the clinic during the time the clinic was open „became like a schedule,“ letting yet another drug — methadone — control his life.



The authors note that while studies indicate that the clinic director sets clinic policies, the counselor usually has to interpret and enforce the rules, which can create a conflict with their role as therapists. The authors believe that rules regarding take-home doses, missed doses, hours of operation, and children’s presence at the clinic may be critical factors in patient satisfaction and retention.

The authors identify several current problems:

  • A short supply of methadone treatment in the Baltimore area, limiting patients‘ choices and putting some in a dependent relationship with a program.
  • Inability of some patients to negotiate clinic rules.
  • Decreased funding for methadone programs for the past several decades, increasing counselors‘ case loads, making individualized attention difficult, and decreasing the variety of patient services.
  • Financial pressures may lead to „feetoxing“ patients. The authors note that data appear to refute the idea that contributing fees is „therapeutic,“ even for indigent patients. Heroin-addicted individuals given free treatment are more likely to enter and remain in therapy than those required to pay.

Suggestions for Staff to Increase Retention

  • Clearly explain program rules to patients
  • Have an appeal system offering a patient advocate
  • Allow patients to switch counselors if conflicts cannot be resolved
  • Consider having clinical experts review each patient’s case before discharge
  • Instruct counselors to document patients‘ reasons for leaving treatment
  • Separate counselors‘ rule-enforcement and counseling functions

Study Limitations

Because of social desirability, or lack of insight, reasons patients gave may not be accurate. Moreover, elapsed time may have altered patients‘ memory of events. Nevertheless, the data may help programs improve their approaches and their outcomes.


Reisinger HS, Schwartz RP, Mitchell SG, et al. Premature discharge from methadone treatment: Patient perspectives. J Psychoactive Drugs. 2009; 41(3):285-296

The hepatitis C virus (HCV) is one of the leading known causes of liver disease in the
United States. It is a common cause of cirrhosis and hepatocellular carcinoma (HCC) as well as
the most common reason for liver transplantation. At least 4 million people in this country are
believed to have been infected with HCV. Following the identification of hepatitis A and
hepatitis B, this disorder was categorized in 1974 as “non-A, non-B hepatitis.” In 1989, the
hepatitis C virus was identified and found to account for the majority of those patients with non-
A, non-B hepatitis. In March 1997, the National Institutes of Health (NIH) held a Consensus
Development Conference regarding management and treatment of HCV.

This led to an important, widely distributed NIH Consensus Statement that, for several years, defined the
standard of care. Now 5 years later, knowledge of hepatitis C has increased dramatically, leading
to the need to reexamine the approaches to management and treatment. This conference was
convened with the aim of reviewing the most recent developments regarding management,
treatment options, and the widening spectrum of potential candidates for treatment and of
updating the 1997 Consensus Statement.
This NIH Consensus Development Conference on Management of Hepatitis C: 2002 was
held June 10–12, 2002. The primary sponsors of this meeting were the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) and the Office of Medical Applications
of Research (OMAR) of the NIH. The cosponsors were the National Institute of Child Health
and Human Development (NICHD); the National Cancer Institute (NCI); the National Center for
Complementary and Alternative Medicine (NCCAM); the National Institute on Alcohol Abuse
and Alcoholism (NIAAA); the National Institute on Drug Abuse (NIDA); the National Institute
of Allergy and Infectious Diseases (NIAID); the National Heart, Lung, and Blood Institute
(NHLBI); the Centers for Medicare & Medicaid Services (CMS); the Centers for Disease
Control and Prevention (CDC); the U.S. Food and Drug Administration (FDA); and the
U.S. Department of Veterans Affairs (VA).

The Agency for Healthcare Research and Quality (AHRQ) provided support to the NIH
Consensus Development Conference on Management of Hepatitis C: 2002 through its Evidencebased
Practice Center program. Under contract to the AHRQ, the Johns Hopkins University
Evidence-based Practice Center developed the systematic review and analysis that served as a
reference for discussion at the Conference.

This two-and-a-half-day conference examined the current state of knowledge regarding
the management of hepatitis C and identified directions for future research. During the first dayand-
a-half of the conference, experts presented the latest hepatitis C research findings to an
3 independent non-Federal Consensus Development Panel. After weighing this scientific evidence,
the panel drafted a statement, addressing the following key questions:
• What is the natural history of hepatitis C?
• What is the most appropriate approach to diagnose and monitor patients?
• What is the most effective therapy for hepatitis C?
• Which patients with hepatitis C should be treated?
• What recommendations can be made to patients to prevent transmission of
hepatitis C?
• What are the most important areas for future research?

Read the full statement: