Medicines used in the treatment of opioid dependence

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Hi, and welcome to this Australian Prescriber podcast on opioid dependence and the drugs used to treat them. And we are basing this on an article in Australian Prescriber, ‘Medicines used in the treatment of opioid dependence’. It's a great little summary and we'll run through some of the salient points here. With us, we have the 2 authors of that article, Dr Hester Wilson, who's a GP and the Chief Addiction Medicine Specialist for New South Wales. Welcome, Hester.

HW: Thank you so much, Justin. It's great to be here.

Lovely. And with you, I have your co-author, Jill Kanck, and Jill is a pharmacist who works for the Murrumbidgee Local Health District in New South Wales. Welcome, Jill.

JK: Thanks for having me. It's great to be here and to be able to talk about treatment options.

Treatment options, of course, for opioid dependence. Opioid dependence, as you both point out in your article, is a chronic condition that can lead to significant harm if left untreated. And it's interesting, I think for GPs, there's a real advantage in thinking of it as a chronic condition. Obviously, it has lots of overlays and interactions with mental health and poverty and socioeconomic conditions, lots of different things, but in the end, I think there are a lot of advantages of thinking about it as a chronic condition in the same way as so many others we are used to treating. It's a relapsing condition, it's a treatable condition. We tend to aim towards maintenance of treatment rather than cure and sending them away for life. And part of that thinking has been encouraged by you over the years, Hester. Tell us about where general practice fits in with the management of opioid dependence.

HW: General practice has a really important place in the management of this condition, just like any other chronic illness. And the way I always think about it is it's a chronic condition just like asthma, just like diabetes, and we have effective treatments and different people will need different input. Some people's asthma is mild and settles. Some people can manage their diabetes with diet. Some need insulin and it's just like this with opioid dependence, this chronic relapsing medical condition.

Unfortunately, it has a bit of a history of being treated as a moral problem or a failing of individuals, when in fact it is, it's a legitimate medical condition that has real harms and we're so fortunate that we have very effective treatments for it.

Before we get onto the treatments, could we start with the diagnosis of it? I notice there are 3 factors which are part of the diagnosis of opioid dependence. The first is loss of control?

HW: Yeah, that's correct. So that sense of loss of control. So unsuccessful attempts to try and cut down or stop or change your use, using for longer than you intended or for higher doses that you intended. And another really important one is continuing to use it even when you don't want to, even when you know it's not helping, even when it's causing you harm.

And that factor would be called salience, which is where the substance becomes dominant. Obtaining that opioid substance starts to take priority over other things you should be doing. And the third one then is tolerance and withdrawal. How are they defined?

HW: So tolerance and withdrawal are signs that there has been neuroadaptation. With tolerance, what people find is that they need a higher dose to get the same effect. And withdrawal is specific experience that happens when you cut down or stop. And for opioids, some of them are kind of general, but some of them are pretty specific for opioids. And it will include things like pupillary dilatation, sweating, eyes streaming, runny nose, nausea, vomiting, diarrhoea, abdominal pain, deep bone muscle joint aches, goose pimples, anxiety, insomnia, yawning. Not everybody will have all of those, but putting them together, and we have some good validated scales to look at withdrawal, give us an idea that somebody is having withdrawal.

Justin, one of the things I would really want our audience to think about is that to have this diagnosis of opioid dependence, you need 2 of the 3, and there is some confusion out there on the part of GPs, they think, ‘Oh, this person's on prescribed opioids, their dose has gone up. When they try and stop it, they've got withdrawals. They must have opioid dependence.’ They actually don't. Unless you've got these other behaviours of the loss of control and the salience, those behavioural parts to it, it actually doesn't fulfil the criteria for opioid dependence. It may be that if you look for it, you'll find those and it's a spectrum of effects that opioids can have. But just because people have tolerance and have withdrawal symptoms when they try and stop does not mean that they have an opioid dependence.

Before we get onto the actual medications, just looking at the system to support the use of these medications, which is really the GP or increasingly nurse prescribers who prescribe them, and then the pharmacists who dispense them, I gather in Australia about three-quarters of opioid dependence treatment is provided in primary care, Hester?

HW: Yeah, that's correct. It's higher in Victoria than it is in New South Wales, and there are some systems factors that play into that. But despite the fact that the majority of people who have opioid dependence who are in treatment are prescribed by GPs or nurse practitioners in primary care, only about 10% of GPs countrywide prescribe. And it depends which area you're looking at, but we only have access to treatment for somewhere between 40%, 50% of people who would benefit from accessing this treatment actually are not able to access it.

I guess one of the things about listening to this podcast is encouraging GPs who perhaps don't feel they have particular expertise in this, that it really is getting easier. And certainly, I was a prescriber 25 years ago in Victoria and it was complex starting people and keeping them on. And I think as we'll find out, the situation really has got easier to fit into your normal skills and timetable in general practice than it perhaps was a couple of decades ago.

HW: Look, Justin, like yourself, I first started prescribing in 1999 and there was methadone at that time and the sublingual buprenorphine came in really for me in general practice around 2004. So I was managing people on methadone, but there's no doubt, it was a more complex treatment. It is a more complex treatment because it is a highly potent opioid agonist. And certainly, one of the dynamics that has happened for myself and for a number of my colleagues in general practice is that we've ended up taking on people who have really complex needs, unstable housing, unstable mental health, other issues going on in their lives that makes them really quite complex to manage.

And to my mind, there's been a mismatch because I, as a GP, I might have all the addiction skills in the world, but if I'm there 2 days a week and it's me and a receptionist, I can't provide the level of care that that individual needs. They do need the specialist setting, the multidisciplinary teams, to support them. And I have to flag that myself and many of my colleagues have managed and do continue to manage people of high complexity in general practice. It's a lot of work and the way that I see it is that we need to treatment match. So for us in general practice, people who are working, can attend appointments, are stable on their dose, do not have risky use of other medications, we might well be managing their mental health, their anxiety, depression, their other health issues, which is what we're good at as GPs-

Yes.

HW: ...but we're not trying to manage someone that needs a lot of welfare support, psychological support, support to get them to appointments, and nursing support as well. That group needs to be seen in the specialist setting. The great thing about these treatments is that they're so effective that the vast majority of people actually settle and could be seen in the general practice setting. And my experience as a prescriber in the general practice setting is incredibly rewarding to see the impact that the treatment and my role in it as well as the pharmacists and other people involved in care can have on allowing people to get on with their lives and to recover.

Jill, I might bring you in now. In particular, let's start with what I think has been a great innovation, less than 10 years old, I think the long-acting injectable buprenorphine. Tell us about that.

JK: So long-acting injectable buprenorphine became available in around 2018 in Australia. It's injected subcutaneously under the skin. So it's a really good option for people who can't get to the pharmacy each day to get their dose of methadone or the sublingual buprenorphine.

So Jill, it sounds particularly useful for the person whose life is a bit chaotic and they're going to miss doses if we ask them to turn up every day, and that certainly was my experience with the methadone. And also, I guess those who have to travel into town from a rural or remote setting to get the buprenorphine. How often do these injections occur?

JK: It can vary. So at the moment, we've got 2 formulations of long-acting injectable buprenorphine. We've got Buvidal, that comes in a weekly and a monthly injection. When we start out with a Buvidal, people usually start with a weekly injection that can be given 2 days before or 2 days after the 7-day mark. So from day 5 to 9. Once we get the client stable on the weekly injection, then there is an option to move them to the monthly injection. And with the monthly, that can be flexible as well. So that can be given from week 3 to week 5. So we do have a window and that does allow greater flexibility for people who want to go back to work or study or look after families.

And what's the second brand?

JK: The second formulation is called Sublocade. That comes in 2 different strengths. Usually people are initiated on the higher strength, the 300 mg, and that's given monthly for 2 doses, and then the client's assessed and the maintenance dose is then usually given at the 100 mg once a month.

Is there any particular reason why the prescriber should choose one over the other? I guess obviously, the number of times it has to be injected would be one.

JK: Possibly. Buvidal does have greater flexibility. So we've got the weeklies and the monthlies, but I guess it just comes down to prescribers, what they're comfortable using, what they've used in the past.

HW: One thing I would add with Sublocade is that it lasts longer. So it's up to 60 days. They're both very effective medications. They're not interchangeable. They are quite different and Sublocade, it's like a loading dose, whereas with Buvidal, it's a buildup dose, but they're both terrific. There's a few differences with it, but bottom line, they just allow people so much flexibility. So yes, you people that find it difficult to get in for appointments or you have to travel to get to their dosing point or their pharmacy, but also people that are working or want to go on holidays or are doing FIFO [fly-in-fly-out] work or just actually don't want to go to a pharmacy all that often. Not that there's a reason why you wouldn't want to go and visit your friendly pharmacist, but it makes life more normal.

We have a friendly pharmacist right here. So I'll ask you, Jill. Oral buprenorphine still is produced and has a place. Tell us about that.

JK: It does. So what we need to think about when we're starting people and treatment is to listen to them. Have they used opioid treatment in the past? What's worked for them? Sublingual buprenorphine could be an option for some of these clients. They prefer to be going into the pharmacy each day to see the pharmacist. So with the sublingual buprenorphine, it's usually a daily dose. Once clients become stable, there is options for them to receive takeaways, and that means they're not having to go to the pharmacy each day to get their dose. Other option is they can have second-daily dosing. So that's quite a safe option for clients that can't get to the pharmacy each day.

To get a little pharmacological about it all, the sublingual dose is combined with naloxone as well as the buprenorphine, is that right? And why is that?

JK: Correct. So the naloxone isn't absorbed sublingually. It's there to deter people from injecting the films. Naloxone is an antagonist. So if it was to be injected, then people can experience quite bad withdrawal symptoms. It can be an option for clients if they prefer to go to the pharmacy each day.

HW: The other advantage with the sublingual buprenorphine is some people actually become needle phobic or are needle phobic. And sometimes people will say, ‘Well, they injected drugs.’ Not everybody that has opioid dependence actually did inject drugs. But people will say, ‘It reminds me of that. I don't want to go back there.’ And look, it is different in different jurisdictions, but the ability to pick up your medication just like you do with any other medication from a pharmacist and take it home and dispense it to yourself at home is certainly an option.

The other thing about the Suboxone, which is the buprenorphine and naloxone combination, is it's a film rather than a tablet, and you put it and it sticks to the side of inside your mouth. The problem with the tablets is that you have to hold them in your mouth while they dissolve and it takes about 5 to 10 minutes and people will find that they swallow it. And when you swallow it, it doesn't work. So the film is actually much easier to take as well.

Jill, before I finish on the medications, back when I started, it wasn't called the opioid dependence treatment. It was called the methadone program. Let's go back to where it started. What role does methadone still have in this?

JK: Methadone can be an option for clients wishing to have an oral form of treatment. Methadone is a full opioid agonist. So when we start out, we need to have a lower dose. There can be some side effects such as CNS [central nervous system] depression, respiratory depression, constipation, and those clients starting on methadone do need to be monitored relatively closely to when they're beginning treatment and the dose increases need to be done slowly.

Hester, do you find many GPs are still using methadone and should we be?

HW: Yeah, the GPs that have been doing this work for a period of time, many of them are not actually using the long-acting injectable. They've had patients for a long time who are very stable on methadone. It works for them. It's very effective treatment. It works very well. I think we are increasingly moving towards the long-acting injectable, and I think that's great because it offers people such flexibility. And for us as prescribers, it's basically a set and forget and people don't have to go into the pharmacy. We don't have to worry about them losing doses.

The way that I approach it is these are the options, these are the good things and the not-so-good things about each of them. It's your choice. There are a few people where I'd go, ‘Oh, I'm not going to give you methadone,’ but that would be for a specific medical reason. And there aren't many of those. But I think probably the ones that would worry me most are people that are struggling with benzodiazepine or other sedatives that just increase their risk of overdose. I'd be very keen for them to be started on buprenorphine and whatever form suits them because of the risk of overdose, and we see this in the overdose stats, is that that combination of opiates and benzodiazepines is a killer.

Yeah. So Jill, as a prescriber, what should we be aware of when it comes to adverse effects and precautions for these medications?

JK: With precautions, we need to look at the client as a whole. So with the medications used for opioid dependence, most of them can cause sedation, they can cause respiratory depression, they can cause constipation. We also need to be aware other medications that a client's taking, so getting a full detailed list of what they're using at home because sometimes these medications can interfere with the opioid treatment medications that we're using.

Thanks, Jill. And could you expand a little on the role of the pharmacist and the heroes who supply this stuff on the ground?

JK: Sure. So our pharmacists are a really important part of the multidisciplinary team. They're not only dispensing and dosing these clients each day, they're really seeing them and listening to what's happening with their lives. They're able to communicate with prescribers and other team members such as social workers and nurses in the team to really get the most out of these treatments for their clients. And the scope for pharmacists is always changing. So we are not just dispensing and dosing methadone anymore. We're actually being able to administer the long-acting injectable buprenorphine in-store, which I think is really important. It gets clients away from hospitals and EDs [emergency departments] back to their communities to be able to continue on with treatment.

So Hester, we're soon to complete this podcast, but before we do, I'd like you to mention completing treatment. Now, you mentioned that it's a chronic relapsing condition, which I guess technically can go on for life, although as with most other medical conditions, eventually at some point, other things tend to take over as being the number one issue a bit later on in life. Can you talk to me about when to stop and if to stop?

HW: Yeah, you're absolutely right. There are some people that will need this treatment lifelong and they will continue on their treatment when they move into aged care, into palliative care. And it's important that people can access that and continue to access it if they need it. But there's another group of people who can complete, who can cut down and stop their treatment. There is a risk that they may relapse and they might need to come back into treatment for a period of time, but we can't know when we first start seeing someone what that trajectory is going to look like. And it may well be that they work on their other health issues, their mental health issues, they get married, have kids, work, and that over time you gently slowly cut this dose down to stop.

And having said that, the long-acting injectable is really looking like a great option to help people complete treatment because you have the injection. Yes, we're saying it lasts 4 to 6 weeks per injection, but it doesn't suddenly switch off at that time. The dose slowly drops down and it's a really effective way with limited withdrawal symptoms that can help people to actually complete treatment.

So to my mind, what I'm doing with the people that I see is I'm always checking in with them, ‘How's this dose working? Do we need to rethink this dose?’ We've got to think about the fact that our patients are ageing and the pharmacokinetics and pharmacodynamics of how human bodies interact with medicines changes as you age. You also pick up other medications along the way that you need, so you've got polypharmacy. So we do need to be thinking all the time, ‘Is this the right dose?’ And are you thinking about maybe it's going to be time to complete treatment soon and let's put a plan in place for that? I've had a number of people over the time that I've been prescribing who have very successfully, slowly over time, cut their dose down and stopped and not needed treatment again.

So it's a very variable story, but I think the bottom line is people need to be in a good place, a good place emotionally, psychologically, they need to be housed, good supports and the focus of their life needs to be not on their drug use. We'll have people saying, ‘I'm just hanging out. I'm just hanging out. I'm going to have a life when I actually get off this stuff.’ And I go, ‘No, you need life now.’ And in fact, sometimes people will do really well when they say to me, ‘Don't tell me what dose I'm on.’ This is methadone and sublingual buprenorphine. ‘Don't tell me what dose I'm on. Just give it to me. I don't want to fixate on the dose. I just want to get on with my life.’ So it's really that focus and the ability to manage your life in other ways, to manage your physical, your mental, social and spiritual life in other ways.

Thank you, Hester. Now, you're obviously very au fait with what's happening in New South Wales. You're the Chief Addiction Medicine Specialist for that state. In your and Jill's article, you have a handy little guide to various state and territory programs. Obviously, we won't go through state by state on this podcast, but it is one of those medications that does tend to have different jurisdictions, different rules, and if someone was looking at becoming a prescriber or a dispenser, I gather they contact their own local state?

HW: Absolutely. So each state and territory has its own guidelines and standards, both for prescribing and for pharmacists doing this dispensing. There are details in the article, but you just go online and look at your jurisdiction's website and there's training available. There's different accreditation standards and there's slightly different programs depending on the jurisdiction that you are working in and that your patients living in. And so do flag those cross-border kind of issues that come up, particularly for us down in Murrumbidgee. We're on the border with Victoria where the rules are slightly different, but the information is there. There is free training. Go and have a look and find out what you need to know for your area.

Wonderful. And I do encourage any listeners who are thinking of dipping their toe in the water to do so. I think it's a great community service. I think it's an essential part of primary care and its genuine community care for a needy group.

Hester Wilson and Jillian Kanck, thank you both so much for coming on our podcast and sharing your wisdom.

HW: Thank you.

JK: Thank you, Justin.

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My guests' views are their own and don't represent Australian Prescriber, and my views are certainly all mine.