Archive for the ‘Evidence-based Treatments’ Category

News You Can Use

 

 

 

 

 

 

 

 

New ACOG Recommendations:

The American College of Obstetrics and Gynecology (ACOG) just released an updated recommendation about the treatment of opioid use disorder in pregnant women: https://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Obstetric-Practice/Opioid-Use-and-Opioid-Use-Disorder-in-Pregnancy

Their last statement was issued in 2012, in cooperation with the American Society of Addiction Medicine (ASAM). This newer statement was released earlier this month, also in cooperation with ASAM.

By my reading, this update is more direct about recommending medication-assisted treatment for pregnant women with opioid use disorder, and specifically discouraged medically supervised withdrawal from opioids during pregnancy.

This statement was in the update’s conclusions: “For pregnant women with an opioid use disorder, opioid agonist pharmacotherapy is the recommended therapy and is preferable to medically supervised withdrawal because withdrawal is associated with high relapse rates, which lead to worse outcomes. More research is needed to assess the safety (particularly regarding maternal relapse), efficacy, and long-term outcomes of medically supervised withdrawal.”

I suspect this released update may have been prompted by the actions of obstetricians in certain locations (Tennessee, for example), where medically supervised withdrawal is routinely recommended by obstetricians. As you recall in a blog earlier this summer, I showed you a letter written by OBs from TN, recommending “medically supervised withdrawal” for patients on medication-assisted treatment of opioid use disorders.

As the ACOG update emphasizes, there’s scant evidence to show medically supervised withdrawal provides any better outcomes for the baby, but certainly places the mother at risk for relapse.

I am pleased to see this update, and plan to mail it to a few obstetrics practices in my own area. Some OBs may be giving patients recommendations not supported by their own professional organization out of ignorance, in which case more information can help. Other OBs do it for ideological reasons, in which case I doubt any amount of information can help, but at least I’ll know I’ve tried to do something.

Screening for substance use disorders was also strongly emphasized in the new document, with specific recommendations about how this should be done. In other words, asking a pregnant patient, “You don’t take any drugs, do you?” is not considered to be adequate or recommended screening.

Increased Risk for Death in Patients with Opioid Use Disorder who Leave Buprenorphine Treatment

We have multiple studies, dating back decades, showing patients with opioid use disorder who leave treatment with methadone have higher risks of overdose deaths. We believe the same thing is true with buprenorphine treatment, but now we have more data to support that assumption.

A French study of 713 buprenorphine patients showed that being out of buprenorphine treatment was associated with a 30-fold increase in death, compared with patients who stay on buprenorphine treatment.

Now that’s impressive.

This was a study done in France, where most patients with opioid use disorder are treated by general practitioners in private practice. This would be roughly equivalent to what physicians do now in the U.S. in their office-based buprenorphine practices, often called OBOT treatment.

The study was published in the July/August 2017 issue of the Annals of Family Medicine, by Dupouy et al. It looked at new patients admitted onto buprenorphine treatment from early 2007 until the end of 2011, and covered over 3,000 person -years of treatment.

The authors say that the data showed, “…being out of treatment was associated with sharply elevated mortality risk.”

We already knew that people with opioid use disorder have an increased risk of death. Early in this article, the authors state that the accepted mortality rate of untreated heroin use disorder is around 2 people per 100 patient years. This means that if you follow 100 heroin users for a year, it is likely that 2 will be dead at the end of the year. An older study, by Hser et al., followed people with opioid use disorder over time, and found that around 50% were dead at 30 years.

We’ve had other studies that show being in treatment with buprenorphine or methadone decreases risk of death, but this may be the first study showing that getting help in a primary care setting reduces the risk of death so remarkably.

This was a very large study, so the data is more impressive to me All this data supports the conclusion that opioid use disorder is a serious and potentially fatal disease, and that being in medication-assisted treatment markedly reduces the risk of death.

 

What’s a Doctor To Do?

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Above, you will see two documents which illustrate the problem.

The second is a letter sent to North Carolina opioid treatment program (OTP) physicians from the preeminent OB/GYN group at the University of Tennessee. The first is a letter sent last month to obstetrical providers and opioid use disorder treatment providers from the Center for Substance Abuse Treatment, an arm of SAMHSA (Substance Abuse and Mental Health Services Administration).

You will note they recommend polar opposite approaches to the management of opioid use disorder in pregnant women. The obstetricians at University of Tennessee recommend that pregnant women with “chronic narcotic use” be offered the option of taper from opioids, to avoid neonatal abstinence syndrome and to avoid microcephaly.

In contrast, the letter to providers from CSAT division of SAMHSA recommends, “Pregnant women with opioid use disorder should be advised that medically supervised withdrawal from opioids is associated with high rates of relapse and is not the recommended course of treatment during pregnancy.”

That mention of microcephaly in the U of T letter baffles me. The resources cited in their letter referred to one study of head circumference in babies with neonatal abstinence syndrome (NAS). There’s no mention whether the moms are on illicit opioids or MAT. The second study looked at head circumference in babies born to moms with polysubstance use. None of the studies looked at head circumference of infants born to moms on MAT and compared them with controls. Using microcephaly as an argument against MAT is a misuse of data.

Why on earth would Tennessee obstetricians send their letter to NC opioid treatment program providers? Because, as I have ranted about so often in the past, there are no opioid treatment programs in Eastern Tennessee. Because that portion of Tennessee still has no methadone programs, patients are forced to drive across the border to get the gold standard of treatment for opioid use disorder. True, there are some buprenorphine prescribers in that area, and that’s a great thing as far as it goes, but as we know, not all patients do well with buprenorphine, and we have around six decades worth of data about methadone in pregnancy.

So not only does Tennessee refuse to allow the most evidence-based treatment for opioid use disorder to exist in that part of their state, but their physicians seek to control the actions of opioid treatment physicians in North Carolina, and ask us to adopt treatment approaches discouraged by all other expert organizations.

The study touted by Dr. Towers in their above letter was published by Bell, Towers, et al. in September 2016 issue of the American Journal of Obstetrics and Gynecology: http://www.ajog.org/article/S0002-9378(16)00477-4/abstract

After reading this study in some detail, I’m surprised by the authors’ conclusions. I find their conclusions to be based on some very thin evidence.

This study was a retrospective analysis of four groups of pregnant women with opioid use disorder. The first group consisted of incarcerated women, allowed to go through opioid withdrawal without the standard of care, buprenorphine or methadone. How this is even legal is beyond me.

The study says that jail programs in east Tennessee have “no ability to provide opiates to prevent or perform an opiate-assisted withdrawal medical withdrawal.” It went on to say that the jail doctor can treat symptoms with anti-nausea meds, clonidine, and anti-diarrheal meds. They also lack the ability to perform fetal monitoring while incarcerated.

Of the 108 women in group 1, two suffered intrauterine fetal death, one at 34 weeks and one at 18 weeks. The authors don’t say what the expected rate of fetal death would be, and I don’t know either. Apparently the authors didn’t consider these two deaths to be outside the range of normal.

Group 2 consisted of 23 pregnant women with opioid use disorder who were sent to inpatient opioid detoxification followed by long-term follow-up behavioral health programs. These women did well, with only 17% relapsing while in treatment. This group had a 17% rate of neonatal abstinence syndrome in the newborns.

I guess that means all of the four women who relapsed had babies with NAS. That’s 100%, much higher than the 50% rate nationwide. That seems odd to me.

Group 3 did the worst. These 77 women had inpatient detoxification but then did not have the long-term treatment that group 2 were given. Of the infants born to these women, 22% needed admission to the neonatal intensive care unit. Of these 77 women, 74% relapsed, and NAS was present in 70% of those infants. Again, this gives a NAS rate of 95%, which is a great deal higher than most other studies of NAS in babies born to moms using opioids of any kind. Even with methadone, studies give estimates of 50% to 80% at the highest.

Group 4 consisted of 93 women on buprenorphine prescribed by office-based physicians who agreed to taper the women’s doses during pregnancy. The rate of relapse in this group was noted to be 22%, and 17% of all the babies had NAS. Again, this gives a relatively higher NAS rate than has been found in other studies. In this Bell study, NAS occurred in 76% of the women who relapsed, up from 50% of women on buprenorphine in the MOTHER trial who were not tapered.

A little sentence in the articles table of demographics and outcomes gives the clue to why their NAS rates were so high. The way this study determined relapse was by drug screen at the time of admission to the hospital for delivery, or an admission by the pregnant woman, or positive meconium screen, or treatment of NAS in the newborn.

I think relapses could have gone undetected very easily, so that only the women with a relapse close enough to the time of delivery were detected to have used opioids.

Other problems with this study have been pointed out by much smarter people than me. Dr. Hendree Jones, author of the landmark MOTHER trial comparing methadone and buprenorphine during pregnancy, commented in the Journal of Addiction Medicine in the March/April 2017 issue: Her conclusions after a review of the Bell article plus a handful of other similar studies is: “Evidence of fetal safety to support the equivalence of medically assisted withdrawal to opioid agonist pharmacotherapy is insufficient.”

Of course, pregnant patients have one big concern: “What can I do to keep my baby from having withdrawal?” and that’s what they focus on. They are willing to do anything, including coming off methadone or buprenorphine or other opioids, if it will keep their baby from withdrawal. As Doctor Jones cogently points out in the above referenced article, there’s lack of data to show medically-supervised withdrawal from opioids results in less risk of NAS.

In other words, if prevention of NAS is our only goal, there’s not enough evidence to show that reducing opioids during pregnancy will achieve this. In part, that’s due to the high risk of relapse in the mother, and in part due to other factors.

This is the state of the situation right now. Things could change in the future. We do need new studies, done with closer attention to fetal monitoring and drug testing throughout pregnancy to help us determine the ideal treatment of pregnant women with opioid use disorder.

But for right now, maintenance on buprenorphine or methadone is still the treatment of choice.

It’s not only SAMHSA that’s recommending MAT as the treatment of choice for pregnant patients with opioid use disorder. Even the American College of Obstetrics & Gynecology (ACOG), the professional organization of OB/GYNs in the U.S., in a position statement from 2012, says:

  • “The current standard of care for pregnant women with opioid dependence is referral for opioid-assisted therapy with methadone, but emerging evidence suggests that buprenorphine also should be considered.”
  • “Medically supervised tapered doses of opioids during pregnancy often result in relapse to former use.”
  • “The rationale for opioid-assisted therapy during pregnancy is to prevent complications of illicit opioid use and narcotic withdrawal, encourage prenatal care and drug treatment, reduce criminal activity, and avoid risks to the patient of associating with a drug culture.”

The World Health Organization says, in its guidelines from 2014:

  • “Pregnant women dependent on opioids should be encouraged to use opioid maintenance treatment whenever available rather than to attempt opioid detoxification. Opioid maintenance treatment in this context refers to either methadone maintenance treatment or buprenorphine maintenance treatment.”

A new statement from the American Society of Addiction Medicine earlier this year, titled, “Substance Use, Misuse, and Use Disorders During and Following Pregnancy, with an Emphasis on Opioids” said:

  • “For pregnant women with opioid use disorder, opioid agonist pharmacotherapy is the standard of care; the ASAM National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use recommends that pregnant women who are physically dependent on opioids receive treatment using methadone or buprenorphine monoproduct rather than withdrawal management to abstinence.

So the experts agree. Medication-assisted treatment is the gold standard for pregnant women with opioid use disorder.

Why are some OB/GYNs in Tennessee and other areas recommending the opposite, based on evidence that most of us consider preliminary at best, and flimsy at worst?

I don’t know for sure, but I think these physicians suffer from the same biases as other non-medical people. I would like for these physicians to base their actions on the best scientific data, but that’s not happening in some areas. I believe these doctors, with the best of intentions, have been swayed by the political climates of their areas. Rather than challenge long-held beliefs about medication-assisted therapies that have been based on ideology rather than fact, they have stayed inside the comfort zone of believing pregnant women shouldn’t be on methadone or buprenorphine.

This leaves addiction medicine physicians in the middle. We know what the standard of care is, but our patients are told we are wrong, and that they should taper off maintenance medication, or not start it in the first place.

I’ve tried, one OB at a time, to educate gently about what I see as the standard of care. I’ve sent studies and position papers and other data to the OBs with whom I share patients. I’ve blogged about the negative experiences I’ve had. In short, many of these obstetricians say something to the effect of: “Who are you to tell me how to care for this pregnant patient?” After all, I’m not an obstetrician. But I do read, and I do keep my fund of knowledge up to date in the field of addiction medicine, which overlaps with obstetrics at times.

I’m terribly frustrated by the situation, and I know my colleagues at other opioid treatment programs feel the same way. I’m fortunate that there is one group of OBs who are somewhat supportive of my pregnant patients on MAT, and I appreciate that. But often these pregnant ladies using opioids are already going to one of the anti-MAT OBs, and that creates real problems.

If it’s difficult for physicians, just think how the pregnant patients feel. They are given polar opposite recommendations by their OB and their physician at the OTP. They sought help in order to do the best thing for their babies, wanting to be good mothers. In most situations, they have tried desperately to quit opioid on their own, and couldn’t. Now the OB is telling them they must taper off their medication during pregnancy, and the OTP physician is recommending they stay on it, even recommending they increase their dose if needed.

At a difficult time in their lives, these mothers-to-be aren’t sure if they are doing the right thing by being in treatment with MAT or not. They second guess themselves, and their families also recommend, with the best of intentions, that they follow the OB’s directions.

I think this won’t change unless professional organizations like ACOG reach out more directly to obstetricians in the field. Perhaps SAMHSA can organize educational lectures, given by obstetricians who know the data and know the best practice recommendations. Perhaps state medical societies or state medical boards can contact these obstetricians with statements of best practices, if more are needed. With WHO, ACOG, SAMHSA, and ASAM all recommending MAT for opioid-dependent pregnant women, you wouldn’t think further statements of best practice would be needed…yet they are.

All I know is that I don’t seem to be making any headway at all. I need help, and my patients need help.

 

 

 

New Treatment for Neonatal Abstinence Syndrome

 

 

 

 

 

 

 

 

 

 

The June 15, 2017 issue of the New England Journal of Medicine contained an article of great interest. Written by Kraft et al., this article titled, “Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome,” described a study comparing buprenorphine with morphine solution to treat opioid withdrawal in the newborn. This study showed significantly shorter duration of treatment and shorter median length of hospitalization for babies with neonatal abstinence syndrome when treated with sublingual buprenorphine compared to traditional treatment with morphine oral solution.

This study covers a hot topic. Many people are alarmed at the rising rate of NAS in our nation’s hospitals. The incidence of NAS has risen four-fold from 2003 to 2012, and cost $316 million in care for those babies just in 2012. [1] Any new treatment that can reduce the duration of withdrawal in newborns, and thus reduce treatment costs and parental anxiety, is an exciting new development.

The NEJM study described was done at Thomas Jefferson University in Philadelphia, Pennsylvania, with subjects enrolled from late 2011 until mid-2016. To qualify for the study, the babies had to be born full-term, defined as more than 37 weeks of gestation, and had to have been exposed to opioids during the pregnancy. The infants had to have signs and symptoms of neonatal abstinence syndrome (NAS), and parental consent to participate in the study.

The study, abbreviated BBORN, for “blinded buprenorphine or neonatal morphine solution,” excluded babies with low birth weight, exposure to benzodiazepines within 30 days of delivery, or serious other medical conditions. For the first part of patient enrollment, breast fed babies were excluded, but this restriction was lifted by 2013, with the national trend of that encouraged these mothers to breast feed. Nearly all of the mothers were on methadone maintenance, with doses ranging from 25 to 265 in the group assigned to buprenorphine treatment, and 30-260 in the group assigned to morphine oral solution, regarded as treatment as usual.

The design of this study was very strong, since it was doubly blinded, which means the providers caring for these infants didn’t know which were randomized to buprenorphine and which were randomized to morphine.

This double-blind approach is important in general, but especially important when dealing with the evaluation of babies in withdrawal. Sometimes nurses and other medical professionals who are evaluating withdrawal in babies have an emotional reactions. Some of these people can overestimate the degree of withdrawal, leading to longer hospitalization and over-medication.

If you are wondering “How do they get the babies to keep the medication under their tongue?” I wondered the same thing. The study explained that after getting a buprenorphine dose (or placebo, if their active drug was morphine solution), the babies were given a pacifier to extend the time the medication is in contact with the sublingual mucosa.

How clever. When my cat Yoshi was prescribed buprenorphine for urethritis, I had to dose him with buprenorphine, but there’s no way he kept it under his tongue. I thought some had to have gotten absorbed just from the oral mucosa. He definitely had a response to the medication, being opioid-naïve…he fell asleep, which gave him respite from frantic over-grooming of his urethra…

But I digress.

Anyway, this study showed buprenorphine significant decreased the duration of treatment for NAS, by an average of thirteen days, with no increase in adverse events, as compared to treatment as usual with morphine oral solution. The study authors postulate that the long half-life of buprenorphine levels the peaks and troughs seen with the shorter-acting morphine solution.

The study was limited by its small sample size. The authors wanted to get at least 40 subjects in each treatment arm, but had a hard time recruiting parents willing to enter their newborn into a treatment trial. They ended up with 30 patients in the buprenorphine treatment arm, and 28 in the morphine treatment as usual arm.

I can only imagine how hard it was to convince nervous mothers-to-be to enter their babies in this study. They were likely already worried about NAS in their infants, and perhaps feeling guilty about being pregnant while having the disease of opioid use disorder. Asking a mom – or dad – to then enroll in a study using a new medication (new for this use, at least) would be a hard sell.

Thankfully even with fewer test subjects than desired, the data still reached statistical significance. If future studies can replicate these outcomes, we will have a new medication with which to treat NAS, which will reduce the length of stay in the hospital for babies, reduce medical costs, and get these babies home sooner.

  1. Corr et al., “The Economic Burden of Neonatal Abstinence Syndrome in the United States,” Addiction, 6/13/17 http://onlinelibrary.wiley.com/doi/10.1111/add.13842/abstract

Bad Science: “Miracle” Cures for Addiction

snake oil

 

 

Addiction is hard to treat. Like other chronic illnesses, relapses are common, and frustrating to both the patient and the family. Substance use disorders cause considerable disability and even death. Treatments do help many people, especially medication-assisted treatment for opioid use disorder, but still aren’t as successful as we’d like.

Scoundrels looking to make a quick buck often prey on patients with diseases that are difficult to treat, like cancer, multiple sclerosis, substance use disorders, and the like. Sometimes bogus treatments have no basis in science at all. Sometimes minimally helpful treatments are touted as being more successful than science shows that they are. In all these cases, bad science is used to cover questionable, usually financial, motives.

I hate bad science. For the purposes of this blog post, I’m defining bad science as when people attempt to give their treatment, or method, or viewpoint, a sheen of scientific validity by using or misusing data, or by having no relevant data at all.

Some examples are more outrageous than others, and bad science has been used for decades.

Charles B. Towns, together with Dr. Alexander Lambert, declared the Towns-Lambert cure for alcohol and drug addiction to be 90% effective. The Towns-Lambert cure was a mixture of belladonna, hyoscyamine, and herb called prickly ash, castor oil, and mercury. Patients were also given chloral hydrate, a sedative similar to a barbiturate, along with morphine and paraldehyde. It fact, it was while he was a patient in Towns’ New York hospital that Bill Wilson, co-founder of Alcoholics Anonymous, had his vision that lead to his spiritual awakening, which in turn lead to the formulation of the Twelve Step program of AA.

Eventually, the number of repeat patients undermined claims of the cure rates of the Towns-Lambert method. Despite his lack of evidence, Towns’ claims became ever more extravagant, leading Dr. Lambert eventually to disassociate himself from Townes. Eventually, the Towns cure was discredited and disappeared.

This wasn’t the first treatment with better marketing than science, and it certainly wasn’t the last.

I had the displeasure of seeing a product being promoted at a recent conference I attended. This device, and I’m not going to give the name since I don’t want to give the promoter any free publicity, generates electrical pulses to the head. Three electrodes are placed just under the skin, and the device is worn for five days while the patient receives intermittent electrical stimulation. This supposedly gets rid of opioid withdrawal symptoms.

The person peddling this new invention shot himself in the foot in my view as soon as he said this device worked 100% of the time. When I asked for studies which had been published in peer-reviewed journals, he said they had loads of studies. Sadly, none were yet published that had been done in humans. He did have human data, but it wasn’t published yet, since an IRB (internal review board) hadn’t approved the study design before they undertook the study, so they had to find someone to approve the study after it was done.

Huh? No, that’s not the way review boards work. Review boards review studies before they are done, to assure no patient will be put in danger needlessly. I’ve never heard of a post-study review board.

So anyway, their human data hadn’t yet been published.

I hinted (oh OK, I came right out and said it) that perhaps it was a bit unethical to promote and expensive treatment ($500, not covered by insurance) unless they had human data, approved and reviewed by the research community, showing efficacy. The promoter of the item countered by saying it was unethical NOT to provide this device, given the benefit it provides.

He didn’t understand that my objection was to the lack of scientific process that all new treatments should undergo, to show they are of at least some benefit prior to use in clinical practice. This should be done before the treatment is marketed. But he pointed to all the success stories on their website, testimonials by patients of how effective this treatment was at preventing opioid withdrawal.

These testimonials are called anecdotal data in the scientific community. Anecdotal data isn’t nothing. It is a type of information that can suggest a potential effective treatment. But anecdotal data alone isn’t sufficient to claim efficacy. It’s only a potential starting point.

People tend to give testimonial type of anecdotal information more credence than they deserve. Hearing a story of miraculous healing touches our hearts. If we are also desperate for a similar cure, we risk making emotional decisions rather than rational ones.

I wasn’t trying to tell this salesman his product didn’t work. For all I know it will be the greatest breakthrough in addiction medicine in the last one hundred years. What I’m saying is that we don’t yet know if it works, because it hasn’t yet been properly tested. And therefore, I thought it was unethical to sell it before testing it.

Does anyone remember Prometa? It was all the rage ten years ago. News articles asked if it was the big breakthrough in addiction treatment. Anecdotal stories from former methamphetamine addicts were heart-warming. The company that supplies Prometa, Hythiam, was created by a former junk bond salesman, which could have been a red flag. That salesman heavily promoted Prometa with the anecdotal stories from addicts who had lost everything but were now drug free and happy.

The medications that made up Prometa are hydroxyzine (an antihistamine with sedating properties), gabapentin (an anti-seizure medication also used for neuropathy) and flumazenil ( a benzodiazepine antagonist). All three are FDA approved for uses other than addiction, but the proprietary combination of these made up Prometa, and it was sold as an addiction treatment cure without FDA approval. This is perfectly legal, by the way.

One drug treatment court, in Tacoma, Washington, paid $400,000 to buy Prometa for its participants. When it was discovered that several of the people making decisions for the drug court also owned stock in Hythiam, it left some people believing there was a conflict of interest. And after results from that drug treatment court were available, Prometa performed no better than traditional (and much cheaper!) treatments. [1]

Ten years later, I rarely hear the word Prometa. Hythiam changed its name to Catasys. Dr. Walter Ling, a very respected scientist in the addiction treatment world, completed a double-blind placebo-controlled studies showed Prometa to be no more effective than placebo.

But all this happened after that former junk bond trader made up to $15,000 for every Prometa patient treated. All those patients and their families were disappointed by another treatment that promised much and delivered nothing better than placebo.

I think it’s unethical for a company to bring a product to market before there’s adequate science to prove that it works. This rather rigorous process is what makes a product or procedure or methadone evidence-based.

Until you’ve got something that’s evidence-based, please don’t waste my time by trying to sell it to me.

When the marketing of a medication outpaces the research supporting it, watch out. We are in snake oil territory.

If a salesman blathers about how good his product is, but can’t hand you a good study published in a peer-reviewed journal, beware. With science, you’re supposed to do the studies first, then present at a conference of your peers, or in a peer-reviewed journal. The data should be able to be replicated by other facilities before we can see it is an evidence-based treatment. Barring that, it’s only a possible treatment among many possible treatments.

  1. “Prescription for Addiction,” 60 Minutes, CBS News, December 9, 2007 http://www.cbsnews.com/news/prescription-for-addiction/3/
  2. Ling et. al., “Double-blind placebo-controlled evaluation of the PROMETA program,” Addiction, 2012 Feb;107(2):361-9

Art Therapy as Treatment for Substance Use Disorders

 

Mural at our opioid treatment program

Mural at our opioid treatment program

 

 

 

We have a bunch of really creative people enrolled in our opioid addiction treatment program, skilled in arts of all kinds. We have an art therapy group, and I love looking at their creations.

As a special project, a group of patients made a beautiful mural on one wall of our facility, seen above. On the far left, scenery is dark and foreboding, with tombstones and other images of bleakness. Gradually there’s a transition as you look to the right. At the far right, the imagery is more cheerful, with pretty flowering trees and green grass. In the middle, signposts direct the viewer to the left, labeled “addiction,” and to the right, labelled “recovery.”

I started to wonder about whether art therapy was evidence-based, probably because I wanted it to be, because I like the idea of art therapy.

I found studies showing art therapy can decrease denial, reduce opposition to treatment, and give people with substance use disorders a means of communication. (Cox & Price, 1990, Allen et al, 1985, Moore, 1983) Some studies show that art can help lessen shame, and be an aid to group discussions for people with substance use disorders. (Johnson, 1990). Art can also help patients feel more motivated about making changes. (Holt & Kaiser, 2009, Matto et al, 2003)

So it appears there’s some evidence to show that art therapy can be of help to recovering people.

I have two posters framed in my office. They aren’t the usual inspiration posters of “teamwork” and “dream big,” etc. They don’t have any writing at all, and I picked them because they both inspired me personally. It’s interesting how patients interpret them

One is a print of a representational image of a colorful mountain, topped with praying hands, with a river appearing to flow from the mountain.

I’ve had numerous intriguing comments from patients about this print. Most just say “I like it.” Others say it reminds them that prayer can help them, or that prayer can create beautiful things.

I had one patient look at it for a long while, then back at me, and he said, “You’re a lesbian, aren’t you?” I had to laugh. I have no idea how he got that from my picture. When I told him no, I’m not a lesbian, he seemed disappointed. This illustrates how art can be interpreted differently by different people.

My other poster is a print of a painting that is so realistic that it looks like a photo. It shows a mountain goat in mid-leap between two narrow, snow covered peaks. A deep crevasse separates the two mountains. I’m intrigued by how differently patients react to that one. Many say that they like that one too, and I ask them, “Do you think he makes it?” meaning does the goat land safely? Most patients say something like, “I don’t know…” and others say, “No way. That goat falls.” And still others say, “Of course he does. He’s a mountain goat; that’s what he’s made for.”

Again, interesting perspectives from different people.

Do patients’ reactions to my art prints tell me anything useful for patient treatment? I don’t think it’s that easy. I’m tempted to assume the patient who says the mountain goat will fall is a pessimist, and the patient who says the goat will make it is an optimist, but I don’t know about that. For now, it’s just interesting.

Art is like that. It can help us understand the world in subtle, unique ways.

aaaaaaaaaaaaaaaaaaaaaaleapoffaith

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!