Archive for the ‘Evidence-based Treatments’ Category

Vivitrol Treatment for Opioid-addicted Criminal Justice Offenders

Vivitrol

Naltrexone, an oral opioid blocker, is now available as an extended-release monthly injection, under the brand name Vivitrol. Initially marketed for alcohol addiction, it also treats opioid addiction. This medication is an opioid antagonist, which means that though it attaches to opioid receptors, it does not stimulate the receptor. Since naltrexone has a higher affinity for the receptor than opioid agonists (like oxycodone, heroin, and methadone) it can’t be displaced. This means it blocks opioid effects, including euphoria. Vivitrol is used for alcohol addiction because part of the pleasure from alcohol consumption is thought to be mediated through opioid receptors.

Some patients say Vivitrol blocks opioid cravings. From a purely biological view, that would be surprising, since it does not stimulate the opioid receptor. Yet some studies suggest it reduces opioid cravings, and some patients claim it reduces opioid cravings. It’s hard to know if this is due to a physiologic effect, or a mental process. If a patient who has just been given an opioid blocker believes he then is unable to feel any euphoria from opioids, maybe his cravings diminish.

I haven’t used Vivitrol much. I had one patient who came two months in a row for his injection, then was lost to follow up. I’ve had about three prospective Vivitrol patients scheduled to see me in my office and all three were no-shows for their appointments, very irritating.

This medication is expensive, at over a thousand dollars for one monthly injection.

In short, from the studies I’ve read and my own experience, I’m not convinced naltrexone will ever be as effective as methadone or buprenorphine in the treatment of opioid addiction.

When I saw an article in the New England Journal of Medicine, titled “Extended-release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders,” I read it with interest. This article was in the March 31, 2016 issue, describing a study of 308 subjects, done by Lee et al., at five sites in the Northeast.

The study subjects were recruited from volunteers with histories of opioid dependence who were involved with the criminal justice system, but not incarcerated. These people agreed to be randomized to the treatment with Vivitrol or treatment as usual. Subjects were excluded if they had elevated liver function tests, were pregnant or trying to become pregnant, or had serious physical or mental health problems. They were also excluded if they had a chronic pain diagnosis for which opioids were prescribed, or if they had been hospitalized with a drug overdose within the past 3 years. They were excluded from the study if they preferred addiction treatment with buprenorphine or methadone medications, since obviously naltrexone can’t be given with those two medications.

The test subjects randomized to the Vivitrol group received injections every 4 weeks with counseling around medication side effects. Beyond that, both the Vivitrol group and the treatment as usual group had similar counseling schedules. People in the treatment as usual group were referred to treatment programs in the community, including providers of methadone and buprenorphine. Test subjects were seen every two weeks for 24 weeks, then at week 27, 52, and 78. Urine toxicology was obtained at each visit, as was self-report of drug use. Researchers also collected subject-reported data about criminal activity, re-arrest and incarceration.

The study examined how long it took subjects in each group to relapse to opioid use. The researchers defined relapse as ten or more days of opioid use out of the preceding four weeks. The rate of opioid-free drug screens was also evaluated for each group.

The treatment lasted 24 weeks. During this time, this study found that subjects randomized to receive naltrexone had significantly longer time until relapse to opioids than the group randomized to treatment as usual: 10 weeks for Vivitrol subjects compared to 5 weeks for treatment as usual group. The naltrexone group had higher rates of opioid-negative drug screens, and lower percentage of self-reported days with opioid use.

The groups didn’t differ significantly on rates of other, non-opioid drug use or the rates of re-incarceration.

This study also examined relapses in both groups after treatment ended, at week 52 and week 78, and found both groups had similar rates of opioid-negative urine samples. Surprisingly, in both groups, about half the subjects had negative drug screens for opioids.

In summary, this study showed that extended-release naltrexone by injection helped people addicted to opioids refrain from using opioids for much longer, and helped them have fewer days of opioid use. However, once the medication was stopped, the rate of drug use for these subjects was the same as treatment as usual group.

I have a few thoughts about the study.

  1. This data nicely fits with our present disease model of addiction as a chronic illness. Just as with diseases like high blood pressure and diabetes, when the treatment medication stopped, the disease returned.
  2. Out of the 153 subjects randomized to receive naltrexone, only 91 got all six of the planned injections. Authors state various reasons for the drop-outs, and indicated only five dropped out due to an adverse reaction to Vivitrol.
    Really? This interests me. Naltrexone has significant side effects in some people. Since naltrexone is an opioid blocker, it probably blocks the opioids made by the human body, called endorphins. Yet only one patient dropped out due to side effects?
    The authors said 39% of the Vivitrol group had adverse events related to the drug, and listed injection site reaction as most common, occurring in nearly a third; next most common were headache, and gastrointestinal upset. Is it possible some subjects in the Vivitrol group dropped out due to side effects but didn’t tell the researchers? I don’t know.
  3. Compliance was much better in this study of extended-release injection than with daily oral medication. That makes sense. With oral naltrexone, the person with opioid addiction has to decide to take medication every day, as opposed to once a month with Vivitrol.
  4. None of the naltrexone patients died, either during treatment or after. This is important, since after a period of abstinence from opioids, overdose risk is thought to be increased. But we didn’t see that effect after the medication was stopped. None of the patients died in an attempt to “override” the blockade of Vivitrol either.

Two subjects in the treatment as usual group died. I don’t think those numbers are nearly large enough to draw statistical conclusions, though.

  1. The authors acknowledge the lack of blinding – with a medication like depot naltrexone, it would be hard to give a sham injection to control subjects. This medication is thick and not an easy shot to give. It would feel much different than a placebo shot of sterile saline, for example. Perhaps the idea of getting an active medication helped subjects in that group believe it was helping, giving better results not due to the actual medication. That’s the problem with no placebo control – there’s no way to know.
  2. More study subjects in the treatment-as-usual group sought help from opioid-agonist treatments with buprenorphine and methadone than did the naltrexone group, at 37% versus 11%.

Thirty-sever percent?? That’s over a third. That tidbit is thrown in with little explanation, other than they subjects went to MAT “primarily after resumed illicit opioid use and relapse.”

From the article, I can’t tell if these subjects were counted as having relapsed or not. The number of subjects was likely too small to do any meaningful analysis, but I am very curious about their outcome.

  1. I find the high rate of opioid-negative drug screens in both groups to be surprising. Each had about half the subjects test negative for opioids at one year after treatment and a year and a half after treatment. That’s good…but just a little too good, perhaps.

So, in this study of opioid-addicted people involved with the criminal justice system, extended-release injected naltrexone prolonged the time to first opioid use compared with treatment as usual. Vivitrol also increased the rate of opioid-free days.

Of course, the big question isn’t IF naltrexone works…the question is how well it works, compared with methadone and buprenorphine?

Ongoing studies will hopefully give us that information soon.

 

Addiction Medicine: News Briefs

News Briefs

Following are several short news updates I thought might interest readers:

Heroin Vaccine

In a blog I posted in 2013, I mentioned a new heroin vaccine being developed. Last fall, the researcher got a 1.6 million dollar grant to continue research studies on the vaccine.

Kim Janda, researcher at the Scripps Institute in California, created the vaccine. The idea behind the vaccine is that it tricks the body into making antibodies against a substance, in this case heroin. After the person has formed these antibodies, if heroin is used, antibodies bind to the drug and keep it from attaching to brain receptors. Since heroin can’t bind to the brain’s pleasure receptors, the person has no euphoric effect from heroin.

Every type of opioid needs a specific antibody to be created, so Dr. Janda plans to try to create a vaccine against oxycodone and hydrocodone, too.

Such vaccines could be another tool with which to fight opioid addiction, but would need to be combined with psychosocial counseling for maximum effectiveness. The vaccine prohibits the opioid from attaching to mu opioid receptors, but would not alleviate cravings for opioids. It would have no effect on withdrawal symptoms, either.

Thus far, the vaccine looks promising in rat studies. We have no human data, and researchers in Virginia Commonwealth University will be helping with primate studies. If these are as successful, human trials could then begin, meaning it would take years to come to market, if it is successful.

I wonder if the vaccine can be overridden. In other words, is it possible to inject so much heroin that all the antibodies are used? If so, could extra heroin still cross the blood-brain-barrier to cause euphoria? I don’t know. Stay tuned for more data.

Frontline: Chasing Heroin

Did everyone get a chance to watch the PBS Frontline segment about opioid addiction and its treatment? You can watch the entire show at: http://www.pbs.org/wgbh/frontline/film/chasing-heroin/

I missed this program when it originally aired on 2/23/16, but watched it last weekend, and I’m glad I did. It was very good.

The program started by giving the history of opioid addiction in our country, and the factors that lead to the over-prescribing of opioids starting in the late 1990’s. The program described the inappropriate marketing of OxyContin, the pain management movement, and mistakes about assumed rates of opioid addiction in patients prescribed opioids long-term.

The program showed how many people who were addicted to prescription opioids eventually switched to cheaper and more potent heroin. They described the usual progression from snorting or smoking heroin to injecting it.

Heroin addiction currently disproportionately affects the white middle class, unlike past decades, when heroin was seen as an inner-city, minority problem. Some of the people interviewed rightfully pointed out possible racism of our current focus on the problem of opioid addiction. Since the white middle class got addicted, people are talking about how to fix this epidemic. When minorities were affected, not so much attention was lavished upon the affected population.

The show interviewed key people in this nation who know much about addiction and its treatment. Barry Meier, who wrote the book “Pain Killer” back when it was not considered proper to criticize Purdue Pharma, was interviewed, as was Sam Quinones, who wrote, “Dreamland.” (I reviewed this book recently on my blog, saying it did a great job of explaining how heroin has quietly swept across the U.S.)

Dr. Thomas McLellan, former deputy director of the ONDCP (Office of National Drug Control Policy) spoke about addiction, and Nora Volkow, from NIDA, was interviewed about the disease aspect of addiction. She explained how addicting drugs damage the brain, making it harder to stop using drugs once they’ve been started.

Robert DuPont, our first Drug Czar, was interviewed and he gave some historical perspective.

Facts from experts are helpful, but real stories from affected people have more emotional power. The program followed several opioid-addicted people as they sought help. Their paths through addiction and attempts at treatment illustrate many of the problems of our present treatment system, or rather lack of system.

I was mostly pleased with how the program handled medication-assisted treatment with methadone and buprenorphine (Suboxone/Subutex, etc.). The program showed the story of a community in Washington State, hard hit with heroin addiction, which voted not to allow a methadone clinic to become established, a classic example of the NIMBY attitude. One of the people who objected to the methadone clinic then had a son who became addicted, and the program showed his gradual change of mind about addition treatment programs.

The program said what we in the field know too well: MAT is an evidence-based and proven form of treatment, yet it remains “controversial” to many people working in addiction treatment.

I felt that issue could have been pushed farther and examined in more depth, but of course that’s my bias.

Toward the end of the show, an interviewer asks a doctor something to the effect of, “…so you can prescribe OxyContin to as many patients as you want, but you can only prescribe Suboxone to one hundred people???” The doctor answers yes, that’s what the law says.

Touché.

Also towards the end of the show, they discussed Seattle’s LEAD program. I liked to hear a law enforcement officer say, “We can’t arrest our way out of this problem.” Given that LEAD is based on harm-reduction principles, the program showed that though LEAD helps a great many people, other people don’t choose to participate in drug addiction treatment.

Thank God that law enforcement is starting to admit law enforcement can’t fix addiction.

Addiction Medicine Finally Recognized as a Medical Specialty

Earlier this month, the American Board of Medical Specialties (ABMS) announced that Addiction Medicine achieved specialty status.

It’s hard to explain quite what this means, but I’ll try. Addiction Medicine is now formally recognized as a specialty field of medicine with a distinct arena of clinical knowledge, grounded in evidence-based information. Board certified Addiction Medicine physicians should now be recognized as experts in this field.

It is also hoped that recognition of Addiction Medicine as a specialty will result in medical students and residents getting more training about drug use and abuse, and addiction prevention and treatment. We already have fellowship training programs for Addiction Medicine, and hopefully these will expand, to train more physicians in this specialty.

According to the information sent by the American Board of Addiction Medicine, addiction and risky substance use accounts for about a third of all hospital costs, and is responsible for twenty percent of all deaths in the United States. Slightly fewer than four thousand of us are certified by the American Board of Addiction Medicine, so more doctors are needed in this important field of medicine.

I am so grateful to all of the people who worked so hard to get this recognition of Addiction Medicine. I know this is something the members of the American Society of Addiction Medicine have been striving toward for over a decade. Thanks to all of you!

 

People with Addiction Need Support, Not Judgement

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So I was reading my local newspaper this morning, and was dismayed to read a letter to the editor that criticized our county for paying for transportation for Medicaid patients to get to and from methadone clinics. The author of the letter said, and I am paraphrasing, that we should stop spending money on drug addicts.

I probably started growling without realizing it, because my fiancé asked me, “What?” I told him that I was feeling a desire to write a letter to the editor coming over me.

So I did. I wrote a letter, brief as I could make it while still containing all the facts, outlining my view of the importance of providing addiction treatment. I will send it to the newspaper, but here it is in a slightly edited version for my blog:

“I’m writing in response to an angry letter to the editor in the September 11, 2015 issue of the paper. The author expressed shock and anger that her tax dollars were going to support “drug addicts.”

First of all, who does this person think these “drug addicts” are? I can tell you – They are our friends and neighbors and fellow residents of our county. For some people, the phrase “drug addicts” may still conjure images of depraved street bums, but that’s not accurate. As the medical director of an opioid addiction treatment center, I can tell you that my patients are good people. They didn’t plan to become addicted, and they certainly don’t want the addiction to continue. Anyone can develop addiction, and that’s particularly true with opioids. If the author of that letter to the editor isn’t afflicted by addiction, she should be grateful, and feel compassion towards her neighbors who do have this potentially fatal disease.

Second, all sorts of media outlets tell us repeatedly that this country is in the middle of an opioid addiction epidemic. In the past, our area has been identified as having one of the highest rates of opioid overdose deaths in the country. Due to hard work by many key people, the opioid overdose death rate has fallen. Programs like Project Lazarus in North Carolina have played key roles. Organizations like this realized opioid addiction must be tackled on many fronts: prevention, education, better prescribing, overdose prevention kits, drug take-back days…and treatment. Is the author of the letter suggesting we should ignore patients with this disease, and not use taxpayers’ money to pay for treatment?

My third point is that treatment is essential. Once an addiction has developed, the person has lost control over drug use. Telling the person “just stop,” won’t work. It didn’t work in the 1980’s and it doesn’t work now.

Medication-assisted treatment with methadone or buprenorphine (better known under the brand name Suboxone or Subutex) has the most evidence for success. In fact, this form of treatment has more evidence to support its use than most anything else in medical practice. We now have fifty years of studies that show a patient on medication-assisted treatment is more likely to stop using opioids, have better physical health, better mental health, more likely to become employed, less likely to commit crimes to support drug use, and less likely to die of a drug overdose.

Is it the right treatment for everyone? No, of course not…there are other means of treatment and no one addiction treatment is right for everyone. But many patients get tremendous benefits from methadone treatment (and buprenorphine).

People never hear about methadone patients who are doing well. They aren’t sedated when on a proper dose, and they look like everyone else. Due to stigma against methadone, these patients quietly go about their business, telling no one about their medication. They go to work and do their jobs, they sit behind you at church, and they shop with you at the grocery store. Many of them pay taxes too. They are nice people and good neighbors.

Should taxpayers’ dollars support addiction treatment? I sure hope so! According to studies, every dollar spent on addiction treatment saves taxpayers anywhere from $4 to $8. That’s for drug addiction treatment in general, and methadone treatment saves even more than that. Most of the savings is due to lower costs for incarceration and lower costs of hospitalization. [1]

Think about it: what if one of these patients being transported for methadone treatment stops going to her treatment program? Relapse rates are very high, so it’s likely she’ll return to active addiction. If she contracts endocarditis (an infection of the heart valve seen in IV drug users), she could be in the hospital for six weeks. What’s Medicaid’s cost then? It’s not unrealistic to say the costs could run into the millions, particularly if she needed heart surgery. True, that money may come out of a different budget, but I say we can’t afford NOT to pay for transportation and treatment.”

1. http://www.drugabuse.gov/publications/principles-drug-addiction-treatment-research-based-guide-third-edition/frequently-asked-questions/drug-addiction-treatment-worth-its-cost

New Book About the War on Drugs

aaaaaaaaaaaaaaaaaaaaaaaaChasing-the-Scream

I’ve got a great new book to recommend to anyone interested in the U.S.’s failed war on drugs. It’s “Chasing the Scream: The First and Last Days of the War on Drugs,” by Johann Hari. Published in 2015, I heard about this book at an Addiction Medicine conference when it was highly recommended by one of my colleagues.

As the title implies, the first part of the book describes how the war on drugs was initiated, not by the Reagans, but by Harry Anslinger, our first drug war general, back in the 1930’s. Anslinger is portrayed as an arrogant man, close-minded, filled with hubris, and lacking in compassion. He played on the public’s worst prejudices in order to get draconian drug laws passed, and showed no mercy enforcing them. He fanned the flames of public fears of drug-intoxicated minorities in order to expand his scope of power and prestige. His statements, preposterous from a medical point of view, still echo in the mouths of politicians today.

The author says Anslinger helped to create U.S.’s first drug lord, Arnold Rothstein, who is only the first of many ruthless gangsters to follow. Demand for drugs in the face of strict drug laws creates irresistible opportunities for criminals. The book describes how the war on drugs re-incarnated Anslinger and Rothstein with each generation; the names change but the tactics and destruction remain the same.

It’s an interesting concept.

Part Two of the book describes the lives of drug addicts. The author shows how people with addiction are forced to behave like sociopaths in order to maintain their supply of drugs. For example, many addicts deal drugs on a small scale to help finance their own drug use, an action they would be unlikely to undertake without the strong motivation of their own addiction.

The author goes on to illustrates how police crackdowns on drug dealers actually lead to increased gang violence. When top drug-dealing gang members are jailed, it creates a power vacuum, which leads to increased violence as rival gang members jockey for positions of power. Ultimately, the amount of drug dealing remains the same.

His reasoning does make sense, and is backed by interviews from urban bystanders in the violence of drug wars, both in the U.S. and Mexico.

This section of the book also discusses the inequalities of the drug war. The war on drugs is really a war on people who use drugs, and minorities are much more likely to targets of the drug war. Black drug dealers are more likely to be arrested than white dealers. People with money and influence aren’t targeted, while police go after the downtrodden, less likely to mount legal defenses if treated unfairly. Police do this in order to meet arrest quotas with less trouble from those targeted.

I could believe this, but then in the same section, the author also accuses police of expanding their budgets by confiscating high-dollar cars and homes from the rich people caught in the drug wars. So that was a little contradictory.

The author points out how a youngster who gets arrested for a drug offense is unemployable for the rest of his life, and how he can’t get student loans or public housing. To me that sounded a little overblown, since I know people who have managed to go to school, get their GED, then get a college education and even an advanced degree. I’m sure having a crime in one’s background makes this more difficult, but not impossible. That makes me question the accuracy of the author’s other assertions. For example, I have no idea if a drug charge eliminates all possibility of public housing.

Part three of the book is hard to read. In it, the author describes inhumane treatment of addicts who have been jailed. Arizona is noted for being a particularly brutal state for addicted inmates.
Inmates in general in the U.S. are treated horribly but no one seems to care, since few people have compassion for criminals.

This same section of the book also describes the horrible violence in Mexico brought about by the U.S. demand for illicit drugs. With so much profit to be made, drug cartels become ruthless. The author says in order to make sure other potential rivals stay in fear, dealers must engage in ever-increasing violence and depravity.

The fourth section of the book presents interesting ideas. First of all, the author claims the desire to get high is nearly universal. Far from being a deviant desire, the author advances the theory that the desire for intoxication is found in all humans in all civilizations at all times of human existence. He questions the goal of eliminating all drug use, and says it isn’t realistic.

I agree with him. The desire for euphoria is hard-wired into humans. When that urge runs amok, we may seek to satisfy that desire incessantly with drugs or other destructive behaviors.

The author then describes how life events affect the risk of addiction as if this were something new, but we’ve known for years that stress affects addiction risk. People who have experienced abuse and deprivation as children are more susceptible. But then the book connects our society’s present method of dealing with addiction, which is to shame addicts and cause them more pain. This approach is, predictably, counterproductive.

He says the more drug addicts are stressed, forced to live in poverty, are ostracized and shamed, the less likely they are to be able to find recovery.

Then the book goes into a weird tangent, saying that opioid withdrawal really isn’t all that bad, and the withdrawal is mostly mental in nature. He quotes some scientists who say that people living interesting and productive lives don’t get addicted, because they are happy. The book implies that the biological model has been overblown and scientists ignore the psychosocial components that cause addiction.

He’s wrong. Experts in addiction and its treatment haven’t forgotten the psychosocial components of addiction. But for decades, people have argued addiction is just bad behavior. They say addicts need punishment, rather than coddling in treatment programs. These people completely denied scientific components of the disorder. As a result, scientists interested in treating addiction poured money, time, and energy into proving the scientific portion of the disease. But now the same people who said there was no science to support addiction as a disease complain that scientists ignore the role of psychosocial factors that cause addiction.

In reality, both biologic AND psychosocial factors influence who becomes addicted. It isn’t either/or but both/and. It isn’t productive to argue about which is more important, because both types of causative factors need to be addressed in the disease of addiction.

The fifth part of the book is the most interesting. Chapters in this section describe the changes that occurred when drug addiction was treated more as a public health problem and less like a crime.

In a grass roots organization in Vancouver, Canada, a heroin addict managed to mobilize people to approach heroin addiction in a completely new way. This addict unified addicts and the people who care about them to create political pressure. This group attended town meetings, protested, and organized people who cared about the marginalized addicts of Downtown Eastside of Vancouver. Eventually, this organization managed to create such a stink that the mayor of Vancouver met with this addict-leader, and was so impressed by the insights and arguments that he authorized the establishment of a safe injection house.

Ultimately, Vancouver had one of the most progressive and harm-reduction oriented policies on drug addiction. Their overdose death rate plummeted. Health status of addicted people improved.

Similar harm reduction policies were enacted in Great Britain and in Switzerland, with similar reduction in overdose death rates and in improved health status for drug addicts. In Great Britain, physicians could legally prescribe heroin for opioid addicts for a period of time, from the mid-1980’s until 1995, when this program was ended. All of the health gains – reduced overdose deaths, reduced crime, reduced gang activity, and improved physical health for the addicts – were instantly reversed as soon as the program was stopped.

An entire chapter is dedicated to the changes seen in Portugal, where drugs are now decriminalized, but not legalized. This means thought drug use is not a crime, selling these drugs is still illegal. This chapter describes the changes that happened in Portugal, where harm reduction and public health strategies were enacted beginning in 2001. The nation has one of the lowest rates of illicit drug use in the world, though it’s important to understand that heroin has traditionally been the main drug of this country. Addicts’ lives are more productive and death rates are down. Crime rates dropped, and now the whole country supports these harm reduction strategies to the draconian drug laws that Portugal had in the past.

Near the end of the book is a chapter about what is happening in Uruguay, a small South American country where drugs are now not only decriminalized but legalized.

Anyone interested in the creation of a sound drug policy needs to read this book. It’s extensively researched, and the author spoke with many of the key individuals responsible for changes in drug policy all over the world. I haven’t critically researched all data he quotes in his book about the results of drug decriminalization and legalization, but he gives references for much of what’s contained in the book so that any interested reader can do so.

This book is uniquely interesting because the author combines data and statistics with personal stories of various addicts and their families. This technique combines the power of individual story with the facts of a more objective and detached view.

I don’t agree with all of the authors conclusions. For example, when he tries to say addiction is more about a person’s socioeconomic and emotional status rather than about the drugs…nah. Addiction is not all about the addictive nature of the drug itself, but it is a major factor. When you discount the euphoric attraction of opioids, cocaine, and the like, you risk misunderstanding a huge part of addiction. When a substance produces intense pleasure when ingested, it’s more likely to create addiction. After all, we don’t get addicted to broccoli…

It’s important to know this author has been in hot water in the past, accused of plagiarism. Knowing this made me a little distrustful of his interviews with people throughout the book, but I think the ideas illustrated by the interviews are still valid.

It’s a book filled with food for thought.

Opioid Addiction in Pregnancy: More Information about the Use of Methadone Versus Buprenorphine

aaaaaaaaaaababy

The MOTHER (Maternal Opioid Treatment: Human Experimental Research) trial of 2012 (Jones et al) gave us much-needed information about how buprenorphine compares to methadone when used to treat opioid-addicted pregnant women. This landmark study showed us buprenorphine can be just as effective as methadone. Babies born to moms on buprenorphine had the same incidence of opioid withdrawal (called neonatal abstinence syndrome, or NAS) at 50%, but the withdrawal was significantly less severe, the babies required about half the medication as the babies born to moms on methadone. Also, buprenorphine-exposed babies spent significantly less time in the hospital – about half as long as methadone-exposed infants.

Some doctors point out that more women on buprenorphine dropped out of that study than women on methadone, and say that proves buprenorphine is less effective. However, the majority of those women didn’t leave treatment; they just left the buprenorphine arm of the study.

This week I read another study, by Meyer et al, soon to be published in the Journal of Addiction Medicine. This study also looked at pregnant patients being treated for opioid addiction.

The authors of this new study pointed out that the MOTHER trial was a placebo- controlled, double- blind study comparing buprenorphine with methadone, but in real life, the decision to start an opioid-addicted pregnant woman on buprenorphine versus methadone is more complex, and determined by other factors. So the study by Meyer et al did a retrospective analysis. They looked at cases where the choice of buprenorphine versus methadone was made by the patient and physician, as happens in real life, then studied the outcomes. The authors of the new study believed findings will be more pertinent to what happens in everyday clinical practice.

In this retrospective cohort study, 609 pregnant patients were started on either buprenorphine (361) or methadone (248). This study took place over the years from 2000 to 2012 at a single site, University of Vermont.

The study collected various data about the newborns: their sex, estimate gestational age at delivery, birth weight, head circumference, length of stay in the hospital, whether the baby received breast milk, and if the child was sent home with the mother. The study also looked at if the newborn has NAS and if the baby needed medication, and length NAS treatment.

In the results, first-time mothers were significantly more likely to start buprenorphine than methadone. Mothers positive for Hepatitis C were more likely to be started on methadone. In both groups, more than 80% of the moms were smokers. About 30% of both groups had to have a C-section at delivery.

Both groups had similar prenatal care; more than 65% of the mother in both groups initiated care within the first trimester. However, women in the buprenorphine group were significantly more likely to get what the authors defined as “adequate” prenatal care. Women on buprenorphine were also more likely to already be in treatment when they became pregnant, compared to the women in the methadone group.

Nineteen women switched from buprenorphine to methadone, out of the three-hundred and sixty-one women who started on buprenorphine. Only five of those patients switched because buprenorphine was not strong enough for them, or other medication side effects. Most were switched to methadone because they needed more intensive monitoring at an opioid treatment program due to continued positive urine drug screens. Only three women out of the three-hundred and sixty-one started on buprenorphine dropped out and were lost from treatment.

No women were switched from methadone to buprenorphine, as one would expect. That’s because in order to switch from a full opioid, methadone, to a partial opioid, buprenorphine, the pregnant opioid addict would have to go into at least mild withdrawal, thus putting her at risk for adverse events. That’s not a risk most doctors are willing to consider.

Babies born to moms on buprenorphine, as compared to methadone, were significantly more likely to have longer gestational age. This is a good thing, because it means there were significantly fewer preterm deliveries on buprenorphine compared to methadone. The babies born to moms on buprenorphine were significantly more likely to have higher birth weights and bigger head circumference.

Just like what we saw in the MOTHER trial, this study also showed that the infants born to moms on buprenorphine required significantly less medication to treat neonatal abstinence syndrome. The buprenorphine-exposed babies required medication for a significantly shorter time than methadone-exposed newborns.

More than 95% of the infants were sent home in the care of the mother or family, which makes me think this study was done on women with fairly good stability at the time of delivery.

The authors of the study concluded that this evidence suggests that buprenorphine gives outcomes that are at least as good as with methadone.

I’d take that conclusion one step farther and say we now have several studies that show less neonatal withdrawal in babies exposed prenatally to buprenorphine compared to methadone. I have to ask myself: knowing what I do from these studies, which medication would I want to take during pregnancy? I’d prefer buprenorphine, and if it didn’t work for any reason, I’d switch to methadone.

I explain all of this to pregnant patients with opioid addiction upon admission, though I’m careful to also point out that methadone is still officially the gold standard in many places.

I think that will change soon. We are getting more information that shows outcomes equal to methadone with less severe neonatal withdrawal.

Expanding Access to Buprenorphine

aaaabalance

My last blog post stimulated some lively debate, and I thought this topic deserved further discussion. However, I would like to ask commenters to talk about the issue and please refrain from mentioning specific names of previous commenters. Please and make your points in a thoughtful and respectful manner. Thanks for your cooperation.

Given our present epidemic of opioid addiction and opioid overdose deaths, authorities are considering lifting the 100-patient limit for physicians who prescribe buprenorphine from office-based settings. Some people in the addiction treatment field oppose expanding access to buprenorphine in the office setting, saying some of these patients don’t get the counseling that they need, but only medication. They say there aren’t enough regulations to prevent shady physicians from opening buprenorphine mills.

Experts on both sides of the debate make good points. It’s a tough topic, but let’s explore the issues further.

1. “You don’t provide enough counseling.”

Weirdly, this used to be a main complaint against OTPs, but now OTP personnel are directing the same complaint toward office-based buprenorphine physicians.

Is there any data to help us decide how much counseling is enough for opioid-addicted patients who are started on medication, either buprenorphine or methadone?

The POATS trial gives some information on this topic. (Weiss et al, 2010, http://ctndisseminationlibrary.org/protocols/ctn0030.htm )

POATS showed that opioid-addicted patients maintained on buprenorphine/naloxone were likely to reduce illicit opioid use during treatment with the medication, but most relapsed after being tapered off the medication at twelve weeks. So this part of the study supported keeping patients on medication longer, just like the older data with methadone for heroin users. No surprises so far.

Now comes the interesting part: POATS showed similar outcomes for patients getting standard medical management versus standard medical management plus fairly intense counseling. The group with added counseling didn’t do any better than the standard medical management group.

However, the standard medical management consisted of an hour-long first visit with the doctor, and a fifteen- to twenty- minute visit per week for the first four weeks, then every two weeks.
This may be more than an average buprenorphine doctor provides in real life. It’s a little more than I do for my office-based patients. My first visit with new patients is one hour, and usually I see them back in one week for a twenty-minute visit. But then, if they are doing well, I see them every two weeks, until the patient is established in counseling. After that, if all is going well, I cut down to monthly visits. I conclude that the average buprenorphine doctor may have to increase visit frequency to get the results seen in the POAT study.

The group with enhanced counseling treatment got 45 minutes with a counselor twice per week for the first four weeks, then twice per month. At present, patients of OTPs must have two counseling sessions per month, even at the beginning of treatment. Opioid clinic opponents say twice per month isn’t even close to enough counselling, and use this point as a reason to say opioid treatment programs deliver bad care.

The POAT study was relatively short. Twelve weeks may not be long enough to detect an improvement in patients getting enhanced counseling. We know life changes usually don’t happen quickly. Maybe it is unfair to say the counseling didn’t help, because the patients weren’t followed long enough.

Now let’s look at interim methadone. Interim methadone was proposed as an alternative to long waiting lists for patients to enter an opioid treatment program. People were concerned about the welfare of opioid addicts who wanted help, but had to wait for a treatment slot to open. Interim methadone is a short-term, simplified treatment where methadone medication is started for the opioid addict, until the patient can be admitted to an OTP. With interim methadone, some counseling given, but only for emergency situations. Drug screening is still done, but is more limited than for OTP patients. These interim patients can transition to a traditional opioid treatment program when a slot opens for them.

It appears that starting just methadone, with limited other services, still helps the patients. Studies show these patients are less likely to continue to use heroin, are less likely to commit crimes, and more likely to enter a full-service OTP when admission is offered. [1]

Would “interim buprenorphine” work as well? I don’t think there are any studies to give us data, but it seems logical that it would.

2. “Just apply to be an OTP”

Government officials have said that if office-based physicians wish to see more than one hundred buprenorphine patients, the physician should apply to become an opioid treatment center.

When I first read this suggestion, I laughed, because it sounded so silly to me. Well-intentioned though this statement might be, it starkly exposed a lack of knowledge of the average physician’s economic circumstances.

I don’t know many doctors like me who have the necessary capital to do this. Some professionals in the field estimate it takes starting capital of around a quarter of a million dollars. I’ve seen one OTP fold due to inadequate financial support and management, and another escape closure by a narrow margin. These days, it takes deep pockets to afford the eighteen to twenty-four month process to establish an OTP. Getting the certificate of need alone can take years. (Just look at Crossroad’s struggles to get a CON in Eastern Tennessee, an area with arguably more opioid addiction per capita than most other states!)

OTP sites must be approved by multiple agencies: the DEA, CSAT, SOTA, and local authorities to name a few. The pharmacy has to meet strict regulations, as do personnel. If you want to accept Medicaid, that’s another avalanche of regulation and paperwork.

I’m not saying it’s impossible for a physician to open an OTP, but I am saying that it would cost so much that most doctors who treat opioid addiction wouldn’t consider it. I could be wrong – maybe my colleagues are making a whole lot more than me…

3. “In it for the money.”

Experts in the field who work for opioid treatment programs oppose expansion of office-based treatment, saying doctors charge exorbitant fees for their patients. Sadly, in some cases, they are right. But many office-based doctors charge reasonable fees. If we allowed doctor to treat more than one hundred opioid-addicted patients at one time with buprenorphine, wouldn’t that reduce demand for services? And when demand decreases, shouldn’t cost of treatment drop too?

For example, let’s take a community where one buprenorphine doctor is price gouging, and charging $500 per month for only one doctor’s visit. The second buprenorphine doctor charges $250 per month for the same service plus addiction counseling. Both are at their one- hundred patient limit. If both were allowed to increase the number of their patients, wouldn’t the second, more reasonably-priced doctor get some of the more expensive doctor’s business?

Conversely, some advocates for office-based treatment say that opioid treatment programs are upset because they have lost money in recent years. They accuse organizations like AATOD of wanting to limit further expansion of office-based programs because it cuts into their business. With more access, more patients would abandon OTPs for these less restrictive programs

DATA 2000 changed the landscape of opioid addiction treatment. OTPs aren’t the only option for patients seeking treatment for their opioid addiction.

My point is, both OTPs and buprenorphine doctors can accuse the other group of being in it for the money. But as I pointed out in my last blog…no medical treatment in this country is free.

4. “My medication is better than your medication.”

Patients entering opioid addiction treatment often ask me, “Which is better, buprenorphine or methadone?” I say, “Both.” Each has its advantages, and I’ve discussed this in previous blog entries. Briefly, buprenorphine is safer, since there is a ceiling on its opioid effects, but it’s more expensive. Patients on buprenorphine also seem to leave treatment prematurely more often than methadone patients. This isn’t a good thing, since the majority of these patients relapse back to illicit opioid use.

Methadone, as a full opioid agonist, may be more difficult to taper off of, and maybe fewer patients leave treatment prematurely because of that feature. Methadone has been around for fifty years now, with a proven track record. It works, and it’s dirt cheap. Methadone does have more medication interactions, but those can usually be managed if all the patient’s doctors communicate with each other.

Buprenorphine isn’t strong enough for all opioid addicts. Because it’s a partial agonist, there’s a ceiling on its opioid effect. This property means it’s much safer than methadone, but it doesn’t work for everyone.

Buprenorphine is safer than methadone, which to me is its best quality. I’ve started hundreds of patients on buprenorphine and never had an induction death. Sadly, I cannot say the same of methadone. I am not saying overdose death is impossible with buprenorphine…I’m saying it’s much less likely, and that’s worth a lot to me.

Buprenorphine’s superior safety profile is one reason it was approved for use in an office setting. Methadone is riskier to prescribe from an office, because misuse and diversion is more likely to be fatal with this drug. That’s why buprenorphine has fewer restrictions on it. Neither medication is good or bad; the difference between the medications is pharmacologic, not moral.

Next week, I’ll describe my OTP, where we provide methadone, buprenorphine under the OTP license, and buprenorphine under my office-based license, all on the same premises. I think we’ve created a continuum of care that’s able to meet the needs of patients as their recovery evolves.

At our program, it’s not one program versus another. Difference patients need different things, and the same patient may need different things at different points in recovery.

1. Schwartz et al, “A Randomized Control Trial of Interim Methadone,” Archives of General Psychiatry, 2006

The Benzodiazepine Dilemma: New Guidelines for Opioid Treatment Programs from IRETA

aaabenzos

I’ve written about benzodiazepines before in this blog (See my post of November 3, 2012). I worry about overdose deaths and other complications in patients for whom I prescribe methadone who are also taking benzodiazepines, prescribed or illicit.

Now doctors at OTPs have help from the Institute for Research, Education and Training in Addiction (IRETA). This well-respected organization located in Pittsburgh, Pennsylvania just issued an evidence-based document titled, “Management of Benzodiazepines in Medication-Assisted Treatment.” You can access this document at IRETA’s website: http://ireta.org/

I love IRETA for tackling this subject. There’s much misinformation about the use of benzodiazepines, even for patients without addiction. But for patients with addiction, benzodiazepines can be deadly when combined with opioids including methadone and buprenorphine.

IRETA’s document first describes how and why these guidelines were created. Opioid treatment programs often have patients who also use benzodiazepines, both by prescription and illicitly. Physicians at OTPs have widely varying responses to these patients. Some programs have zero tolerance, meaning they won’t allow anyone on benzodiazepines to be in their opioid treatment program. Other physicians at OTPs actually prescribe benzodiazepines for their patients when they feel it’s clinically indicated. IRETA wanted to delve into actual scientific literature and consult a panel of experts for interpretation of that data. This IRETA document describes in detail how the literature search was done. It also goes into exhaustive detail about how each statement in the set of guidelines was vetted by experts.

This paper’s guidelines fall into seven categories:

General guidelines
Assessment for MAT
Addressing benzodiazepine use
MAT for patients with concurrent benzodiazepine use
Noncompliance with treatment agreement
Risk management/Impairment assessment
Special circumstances

Here are the general guidelines, taken directly from the document:

CNS depressant use is not an absolute contraindication for either methadone or buprenorphine, but is a reason for caution because of potential respiratory depression. Serious overdose and death may occur if MAT is administered in conjunction with benzodiazepines, sedatives, tranquilizers, anti-depressants, or alcohol.
People who use benzodiazepines, even if used as a part of long-term therapy, should be considered at risk for adverse drug reactions including overdose and death.
Many people presenting to services have an extensive history of multiple substance dependence and all substance abuse, including benzodiazepines, should be actively addressed in treatment. MAT should not generally be discontinued for persistent benzodiazepine abuse, but requires the implementation of risk management strategies.
Clinicians should ensure that every step of decision-making is clearly documented.
Clinicians would benefit from the development of a toolkit about the management of benzodiazepines in methadone treatment that includes videos and written materials for individuals in MAT.

Please note that under the third point of the general guidelines, it says patients shouldn’t be taken off MAT because of repeated benzo use, but need “risk management strategies.” That’s a little vague, but IRETA guidelines go into more detail later in the document.

IRETA’s second section of guidelines is about assessment for MAT. The guidelines say all of the usual things; for example, they say a doctor should do a complete evaluation of a patient presenting for treatment, as described in SAMHSA’s TIP (Treatment Improvement Protocol) 40 and 43. The evaluation should include the patient’s history of medical problems and history of all drug use, even over the counter medication. A mental status assessment and a drug screen should also be included.

Also under the assessment section, IRETA suggests adding patient education about the dangers of mixing benzos with methadone or buprenorphine. I like this idea, and I do something similar. When I ask about past drug use, I always warn patients about the potential bad outcome of mixing benzos and alcohol with the medication I’m going to prescribe, and I repeat the warning at the end of our interaction.

IRETA suggest doctors go farther, and give patients information not only about overdose risk, but also about the other problems benzodiazepines can cause. Benzodiazepines are associated with a greater risk of depression and suicide. Having a prescription for benzodiazepines doubles a patient’s risk for an auto accident, and increases the risk for other accidents, like falls. Taking a benzodiazepine prescription is associated with an increased risk for hip fracture.

The IRETA guidelines remind us that there is “Substantial and growing literature that suggests long term use of benzodiazepines (especially in large doses) leads to cognitive decline.” (page 16 of the report) the guidelines also say that benzodiazepines are associated with emotional blunting, and long-term sleep and mood disturbances. Even more relevant, studies show that patients on benzodiazepines have worse outcomes in medication-assisted treatment.

The third section of IRETA’s guidelines is about addressing benzodiazepine use. They say that a patient should be willing to address their benzo addiction. IRETA says that uncontrolled use of benzodiazepines is a contraindication to treatment with methadone or buprenorphine because of the “extremely high risk for adverse drug reaction involving overdose and/or death during the induction process.”

I’m in the “amen” corner for that one! But it’s hard for me to know which patients use benzos occasionally to help opioid withdrawal, and which patients use benzos heavily in an uncontrolled manner. Most patients, seeing me for admission to MAT, minimize their use of benzodiazepines, knowing it’s a big issue. If they’re getting benzodiazepine prescriptions in large amount from multiple doctors, I can see that on our state’s prescription monitoring program. If the patient is taking benzos illicitly, I may not have a way to know this. Information from family members and friends can sometimes help, if the patient will allow. Or family members and friends may be as heavily involved in addiction as the patient presenting for treatment.

The IRETA guidelines remind us that patients on long-term benzodiazepine therapy are at risk for adverse drug reactions which can include overdose and death. The guidelines say that central nervous system depressants are not absolutely contraindicated with methadone, but also put patients at risk for overdose and death. I assume at this point in the document, its authors are referring to other non-benzo central nervous system depressants like carisopradol (Soma), zolpidem (Ambien), and the other “z” sleep medications, and perhaps pregabalin (Lyrica).

IRETA’s benzodiazepine guidelines for OTPs are extensive, so I’m going to split my review of the contents over two blog entries. Stay tuned…or even better, go read them for yourself:
http://ireta.org/sites/ireta.org/files/Best%20Practice%20Guidelines%20for%20BZDs%20in%20MAT%202013_0.pdf

1. Thomas et al, “Benzodiazepine use and motor vehicle accidents. Systematic review of reported association.” Canadian Family Physician, 1998 April;44:799-808.
2. Smink et al, “The relationship between benzodiazepine use and traffic accidents: A systematic literature review.” CNS Drugs, 2010 Aug.24(8)6390653.

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