Medication Treatment of OUD, including Use of Evidence-based Treatment Guidelines for OUD

Medication Treatment of OUD, including Use of Evidence-based Treatment Guidelines for OUD


NARRATOR:
Okay, so, as you know these are fairly short talks. So I’m gonna move kind of quickly, but we’ll
have some time for questions at the end. I’m gonna talk about the medications that
are approved for treatment of opioid use disorder, and I have no financial conflicts of interest
to disclose. So, as you probably know by now opioids bind
to several different types of receptors that are widely distributed throughout the body. So, we’re really aware of the ones that are
in the brain and spinal cord, but opioids also have a big impact on the GI tract and
several other body systems and that’s responsible for things such as opioid associated constipation. There are a number of different types of opioid
receptors that are named with Greek letters. The mu opioid receptor is the main one that
we’re interested in because it causes both the euphoria or high associated with opioids
and also is responsible for slowing down breathing, and you know, ultimately causing overdose
if too high doses are taken. There’s also kappa, delta, a number of other
opiod receptors that have various different effects. A few other areas that are controlled by opiod
receptors include obviously pain, some aspects of heart rate, and blood pressure as well. This slide is meant to demonstrate some of
what goes on in addiction to opioids and then what happens when someone gets onto medication
treatment. So, initially when someone is using opioids
for purposes of becoming intoxicated they’re in a cycle, a rapid cycle cycling in between
feeling normal and feeling intoxicated, and most people in this phase of addiction are
trying to recreate the way they felt the first few times they used opioids, but tolerance
is developing as they continue to use it. So they need higher and higher doses in order
to achieve the same or close to the same feeling of intoxication. As people continue using and full fledged
addiction starts to take hold then they get into another phase of opioid use disorder
in which they report that they feel much less pleasure or euphoria if I’m using the opioids
and instead are using largely to try to avoid withdrawal. So, they’re cycling between feeling normal
and feeling bad. So quite a different set of motivators there
to avoid feeling sick, and you may well have had a patient who has said to you, doc, I
don’t use to get high anymore, I don’t feel high, I just use in order to not get sick,
and that’s a really common experience among people with opioid use disorder. When someone goes on medication treatment
one of the big benefits is they stop going through these intense cycles of up and down
or high and normal or normal and withdrawal and instead they have a steady level of opioids
in their system and in their brain so that their moods can stabilize and their whole
experience of life can stabilize and in that situation they’re able to go back to participating
in normal activities, working on understanding the issues that may be triggering them, or
setting them up for relapse, et cetera. So, the idea is to stabilize those new opioid
receptors with a steady, low, non intoxicating dose of the opioid agonist and help the person
return to more normal life. The goals of medications for opioid use disorder
are certainly first to alleviate physical withdrawal and craving, and also to blunt
the euphoric effect of other opioids. So, if someone does slip up and use they don’t
have nearly as reinforcing and positive an effect. Another goal is to reduce or eliminate risky
substance use and to normalize the brain physiology, and the only three medications that are approved
for treatment of opioid use disorder are methadone, which fully activates the mu opioid receptor,
buprenorphine, which partially activates the mu opioid receptor, and naltrexone, which
blocks the mu opioid receptor and prevents other opioids from attaching to it. Substance use disorder is incredibly costly
and study after study has shown that paying for treatment yields tremendous returns for
society in terms of reduced crime and criminal justice costs as well as many dollars saved
in healthcare and not to mention many lives saved. For instance, the average cost of one year
of methadone treatment is $4700 per person, whereas one year of incarceration is at least
$24,000 per person. So how about methadone? Methadone is a full activator of the mu opioid
receptor and it’s very long acting. This means that you don’t change the dose
every day, that if the patient comes in after a couple of days of a steady dose and says,
doc, I’m still not feeling well, you might have the urge to increase that dose, but the
problem is that they don’t reach a steady state with that methadone until about five
days out. So you don’t wanna be titrating very frequently
or you’ll end up with an overdose situation. One of the most important things to understand
about methadone for treatment of opioid use disorder is that the federal government says
it can only be dispensed in a federally operated opioid treatment program. It is illegal to prescribe methadone for addiction
in general practice, and this is really important to note. So, it’s legal to prescribe for pain, but
illegal to prescribe for treatment of opioid use disorder in the office setting. Some of the benefits of methadone treatment
are that people are taking their medication in a daily, observed dose. This means we know exactly how much they’re
getting into their body and we know that they’re taking it every day. It’s a very structured environment and it’s
required by federal regulations to be multidisciplinary. So, patients in an OTP are assigned a counselor
and are required to attend some number of counseling sessions per month. Methadone is also high potency. So people who have been using very large amounts
of opioids can still have their disease controlled with methadone. It’s been super well studied. We’ve been using methadone for more than 60
years at this point. So, we know that methadone has been proven
to improve survival, increase employment. It decreases infection with hepatitis and
HIV, decreases crime in communities where methadone OTPs are implemented, and it’s highly
cost effective. So, in spite of the bad rap that methadone
gets in a lot of settings it is extremely effective. And in studies of treatment for opioid use
disorder methadone typically shows the best treatment retention compared with the other
medications that are available. Limitations are that it still carries a risk
of overdose and it has lots of interactions with other medications. So, if you’re in outpatient practice and you
know that your patient is being treated with methadone you’ll want to look up interactions
for pretty much any medication that you prescribe to make sure that you’re not gonna either
be causing that patient to experience methadone withdrawal or methadone overdose, as well
as to assess whether you need to change the dose of the other medication that you’re prescribing. You have to titrate up slowly in order to
stabilize the dose, and opioid treatment programs are not available in all parts of the country. Particularly in rural areas patients may not
have access. Methadone has traditionally been thought to
have a significant risk of heart rhythm abnormality, something called Torsades de Pointes, which
can cause a fatal arrhythmia. A recent study has called that into question
and says that actually methadone doesn’t cause any more of that than other opioids including
buprenorphine. But several other studies in the past have
found an increased risk. So it’s prudent to keep an eye on that. Stigma is also a big issue, that methadone
is still highly stigmatized. So, if you put all this together and think
about whether methadone is a good bet for your patient it helps to recognize that methadone
is so effective and so important that the WHO lists it as one of the 100 essential medications
that should be available worldwide. It has all of these proven benefits shown
in the upper half of this graph, and the things that are in the lower part of the slide are
myths to one extent or another and most important to point out is that methadone clearly improves
pregnancy outcomes for women who have opioid use disorder. So, occasionally I still hear a healthcare
provider or a counselor urging a pregnant mom to just stop using opioids and that could
be a fatal mistake. So, a much, much more evidence based recommendation
would be to encourage that mom and help that mom to get on medication treatment for her
opioid use disorder. How about buprenorphine? So, this is probably the medication we talk
about the most in this Echo series, and that’s because it’s a highly effective medication
for treatment of opioid use disorder that can be used in the outpatient setting. Unlike methadone, it’s only a partial activator
of the mu opioid receptor, and this probably explains why it is vastly more difficult to
overdose with buprenorphine than with methadone. However, even though it only partly turns
on that receptor it holds onto it like crazy and that’s called receptor affinity. So buprenorphine will hold on and not let
other drugs like heroin come along and knock it off of that mu opioid receptor and that
helps to have a blocking effect to discourage the use of opioids because people don’t feel
as intoxicated if they use them while they’re on buprenorphine. Buprenorphine is typically combined with naloxone
such as the brand name Suboxone and the reason for that is because when naloxone is taken
under the tongue it’s not absorbed and essentially it just disappears without having an impact. But if it’s injected or snorted it causes
withdrawal which is unpleasant, and so this discourages people from using it for purposes
of becoming intoxicated when it’s typically injected or snorted. Buprenorphine’s been available since about
2003 in the form of sublingual tablets and then dissolvable films that are taken under
the tongue. More recently an implant was released, and
quite recently there’s a new long acting injectable, brand name Sublocade, that last for a month
or more after injection and really offers some pretty exciting opportunities for using
this medication in a way that avoids diversion we think, and hopefully will increase adherence. There are some restrictions on who can prescribe
buprenorphine as you probably all know. Physicians who have a DATA-2000 waiver are
allowed to and that requires an eight hour training course and then as of 2017 nurse
practitioners and physician assistants who have completed 24 hours of approved training
are eligible for the buprenorphine waiver. Some of the benefits of buprenorphine are
the much lower risk of overdose and sedation and minimal if any effects on the heart rhythm. There are also very minimal interactions with
other medications, but a couple that we do worry about are benzodiazepines and the substance
alcohol. When combined with those or other strong sedatives
overdose can occur. Another nice thing about buprenorphine is
because it can be prescribed in the primary care setting or the outpatient mental health
setting that reduces stigma and allows for the treatment to be integrated into primary
care. That’s really desirable because we would like
our patients to have access to medical and behavioral care as well as prevention. Buprenorphine is also a super useful tool
when a patient’s being treated with opioids for chronic pain and runs into problems with
that, starts developing an opioid use disorder. We also know that home induction is safe and
effective. It used to be kind of scary to have to have
patients come into the office in withdrawal. Turns out that people with opioid use disorder
are better at starting themselves on buprenorphine than we are, and so home induction works great. Buprenorphine is also highly effective for
pain. It’s an excellent analgesic, but if you’re
using it for pain you wanna give the same total dose but divide it up three or four
times a day so that the person’s not taking it as a daily or twice a day dose, but instead
they’re taking the same amount but divided up typically four times a day because the
analgesic effect of buprenorphine is much shorter than the duration of the withdrawal
prevention properties of the buprenorphine. What are the limitations of buprenorphine? Risk of diversion, possibly lower retention
rates in some studies compared to methadone, and limited access due to reluctance to prescribe. Studies still show that most counties in the
United States don’t have a supply of buprenorphine waivered providers or providers who are willing
to prescribe buprenorphine that meets the need. A couple of other barriers in primary care
include the urgency of scheduling, the need for that induction visit and frequent early
follow up, although as I mentioned home induction is increasingly becoming the standard of care,
and then urine testing and the logistics of prescribing, as well as the need to link patients
to psychosocial services. We used to worry quite a bit about DEA regulators
visiting. They have cut way back on that and having
survived a couple of those myself they’re not as bad as we thought anyway, and nobody
gets handcuffed and taken to prison. It’s more just they wanna look at your records
and they pat you on the back and off they go. So, overall this type of treatment is really
a highly gratifying thing to engage in in primary care practice and is a huge service
for the communities that we live in. Why is overdose potential low with buprenorphine? It probably has to do with this partial activator
effect that there’s a ceiling to the amount of respiratory suppression that occurs with
buprenorphine. Once you get up above a dose of about 32 milligrams
there’s no increase in that respiratory suppression. So whether you take 32 milligrams or 64 milligrams
there’s no increase in the slowing of breathing. So, people don’t die from respiratory suppression. Many studies have looked at the benefits of
buprenorphine. This one I still think is really powerful
from the Lancet in 2003 in Sweden where these researchers randomized a small group of young
people addicted to heroin to get intensive counseling, individual counseling and group
therapy several times a week by master’s level trained therapists and then half the group
got buprenorphine 16 milligrams every day for a year and the other half got tablets
that contained a brief taper of buprenorphine followed by a placebo. At the end of 50 days you can see in that
right hand column all of the patients who were on the placebo had dropped out, and as
compared with the buprenorphine group of whom 70% were still retained at one year. Most of them had urine drug screens that were
negative for all other substances. Notably, 20% of the group who received placebo
died in that single year that they were being studied, really emphasizing the lethal nature
of this disease. This slide shows a number of studies that
have come out since then, showing typical retention rates in treatment. These are mostly outpatient primary care practices. The second one on there by Alford and Labelle
was remarkable in that half the patients in that study were homeless and they still achieved
a rate of retention of 81% at one year out. So it’s clear that with really good support
in the practice, support for the patients you can achieve pretty outstanding results
with this medication. But it’s also important to note that if you
do this treatment there are gonna be some patients who are gonna disappear and drop
out of treatment, no matter how good you are at offering the treatment and it’s important
not to take that personally. This study shows overdose rates in Baltimore. The red line showing overdose rates falling
as that dotted line along the bottom started to rise and that dotted line along the bottom
shows availability of buprenorphine in Baltimore. So, they had a big public health campaign
to increase access to buprenorphine treatment and they saw a really remarkable fall in overdose
deaths. This same pattern has been seen in other municipalities
that introduced buprenorphine in a big way, including in Paris years ago when France made
buprenorphine widely available. They went from having 560 overdose deaths
to a few years later having less than 50 when they introduced widespread access to buprenorphine. What about the new long acting buprenorphine? So, this medication called Sublocade has to
be obtained through a specialty pharmacy who delivers it to your practice for that patient. The patient has to be stabilized for seven
days on sublingual buprenorphine and then it’s recommended that you start with a 300
milligram injection dose. This is injected subcutaneously and you do
the injection in the office. You don’t give it to the patient to take home
because it would be very dangerous if the patient injected it intravenously as it causes
an immediate kind of clot, lump to form, and they could have an embolism or other really
bad consequence. So, it’s dangerous to send a patient home
with it, but if it’s injected subcutaneously in the office it’s quite safe. We’re still gathering data about this. A study was published last week actually showing
that it’s at least equally effective to sublingual buprenorphine but this study was interesting
from a couple of years ago where they started people on Sublocade and then they gave them
hydromorphone doses. So a very potent opioid, and they gave them
increasing doses of hydromorphone to see how much the person liked the hydromorphone. These were non-treatment seeking adults who
had opioid use disorder and they were trying to see how well does the Sublocade do at blocking
the effects of other opioids, and it was quite interesting that after they had had two total
doses of Sublocade they had very minimal response even to the very high doses of hydromorphone. So, this shows they got the injection at number
one on that X axis and another dose at number four and then they didn’t get any subsequent
doses of the Sublocade for the next eight weeks and yet the effect of the Sublocade
persisted in blocking the pleasurable effect of hydromorphone all the way out to 12 weeks. So, this suggests that even when patients
don’t return for an injection on time they still have a blocking dose of that hydromorphone
in their body. We’re hopeful that this may help to decrease
diversion of Suboxone which has been as you all know a significant issue. How about naltrexone? So, naltrexone is the newer kid on the block
for treatment of opioid use disorder. It is an antagonist. It binds very tightly to that mu opioid receptor
and won’t let anything else attach. If you give it to somebody who is opioid dependent
they will have spectacular withdrawal and will no longer be your friend. It’s very important to avoid giving it to
someone who has opioids in their body. It was available and still is available as
a pill, an oral dose, but that is basically completely ineffective for treatment of opioid
use disorder. So, we don’t recommend that. However, the extended release injectable form
Vivitrol given as a 380 milligram intramuscular monthly injection is effective and we’ve been
getting increasing amounts of data recently showing how effective it is. One nice thing about it is you don’t have
to have any special setup or license to prescribe it other than a regular medical license. There are some issues around insurance coverage
for it. It’s not 100% covered yet and there’s a special
injection technique that the injector has to learn in order to inject it safely. A couple of studies published this last year
gave us a lot more confidence in this medication being effective. A study in Scandinavia by Tanum randomized
patients with opioid use disorder who had gone through detox. They then randomized them to start on injectable
naltrexone and they found that naltrexone was non inferior to buprenorphine in terms
of retention, urine drug screen results, and use of heroin. A study that was done here in which actually
our colleagues here at the University of New Mexico were one of the study sites that was
led by Lee and published in the Lancet shortly after that other study last year was larger
and here they actually randomized patients at the time of admission into a detox setting
but they were either going to use buprenorphine or they were gonna get the naltrexone injection
and here what they found was many more patients assigned to naltrexone were likely to leave
during the first couple of weeks of treatment. This was because the patients who were going
onto naltrexone had to go through withdrawal before they started the naltrexone and they
were uncomfortable and decided to leave, whereas the buprenorphine treated patients didn’t
really have to withdraw, were started on buprenorphine, and were doing well. So, 94% of the patients assigned to buprenorphine
were successfully inducted and stabilized versus 74% of the naltrexone patients. However, once patients got started on naltrexone
they did as well as the buprenorphine treated group. All of this underlines the fact that it’s
a whole lot easier to start people on naltrexone if they are already detoxed, quote unquote. So, if they’re in a setting of inpatient,
of rehab, or of incarceration as long as you’re fairly confident they haven’t had access to
opioids that’s where people can effectively be started on naltrexone. Some people do this in the office setting
but it’s pretty hard to convince patients who are opioid dependent to stay off of opioids
for long enough to do this induction. You would wanna start with an oral test dose
with such a patient to make sure, absolutely sure, that they don’t have any opioid in their
body. Special caution, methadone only shows up in
the urine drug screen for about three days after it’s been taken but its effect is much
longer. So, a patient who took methadone last week
will have a negative urine drug screen but will still get very sick if you start them
on naltrexone. So that’s a super important question to ask
and ask again with a patient if you’re considering inducing them on naltrexone. Benefits of naltrexone are that it does not
create opioid dependence, so someone can stop it and not develop withdrawal. It’s also effective for treatment of alcohol
use disorder as you know, so it’s particularly nice to use in the setting of opioid and alcohol
use disorder combined. It does not cause any respiratory depression
or sedation and it’s not a controlled substance, so there are no restrictions on prescribing. Retention appears to be similar to buprenorphine
if successful initiation is achieved. We still don’t have anything like the same
kind of long term outcome studies for naltrexone that we had for buprenorphine or certainly
for methadone, but what we’re learning is encouraging in terms of the benefits. Notably one limitation of naltrexone is that
if someone’s taking naltrexone opioids are ineffective for pain. So, someone who is in a, you know, a crash
injury trauma kind of situation, it’s really hard to control their pain. So other approaches like regional anesthesia
plus non opioid medications are what you definitely need to turn to. Always important to mention overdose prevention
when we’re talking about medications and opioid use disorder. Naloxone which is a short acting cousin of
naltrexone is our friend Narcan which reverses opioid overdose and overdose education and
naloxone dispensing are effective harm reduction strategies and are really effective at keeping
your patient alive while you work with them. So, they should be widely distributed and
used in all kinds of settings where people may be at higher risk of opioid use disorder
but there’s also a pretty good argument to be made for dispensing naltrexone to anybody
who’s being prescribed opioids for any length of time. There are some emerging models of treatment
for medication, medication treatment for opioid use disorder. The Massachusetts Nurse Care Model we’ll hear
about later in this series, but here nurses are actually the main actors in treatment
of opioid use disorder. They manage the care of patients with OUD
and the prescribers are in a more limited role where they’re largely just reviewing
what the nurse is doing and signing the prescriptions. This allows more patients to be followed and
followed effectively. This is the model that was used in that Alford
paper that I showed you that had such excellent retention rates. And then the Vermont Hub and Spoke model is
one in which addiction specialists actually start patients on buprenorphine and then refer
them out to primary care practices as they’re stabilized. So, in summary maintenance medications are
an essential, very important component of evidence based treatment for opioid use disorder
and the strongest long term data at this point support methadone and buprenorphine, but naltrexone
is also highly effective. Important to note that it’s easiest to initiate
in an inpatient setting and can only be initiated in patients who are not currently physically
dependent on opioids. Primary care teams play an incredibly important
role in treatment of opioid use disorder and prevention of overdose and we’re really grateful
for the great work that you all are doing. So, tons of references if you care to peruse
any of those and my email address in case you wanna get in touch with me to–

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