Episode 26: Opioids special #3: Tolerance, dependence and overdose

Voiceover:

Welcome to the NPS MedicineWise podcast, helping health professionals stay up to date with the latest news and evidence about medicines and medical tests.

Dr Jill Thistlethwaite:

My name is Jill Thistlethwaite. I'm a GP and medical advisor at NPS MedicineWise. I'm also an education consultant with an interest in communication skills and shared decision-making.

The management of chronic non-cancer pain is a complex area. Long-term management should take a multidisciplinary approach that minimizes use of opioids and encourages self-management strategies. We know that the analgesic effects of opioids attenuate over time due to physiological tolerance, physical dependence, or opioid-induced hyperalgesia. Physical dependence is common and withdrawal symptoms occur if chronic treatment is stopped suddenly. NPS MedicineWise is running an educational program on opioids, the bigger picture, and this is for health professionals and consumers.

Today, I am joined by Leah Dwyer and Hester Wilson. Welcome Leah and Hester. Leah, if you could just tell us a few words about yourself.

Leah Dwyer:

My name's Leah Dwyer and I am a consumer advisor for Pain Australia. I also worked for Pain Revolution on their communications committee. I'm quite passionate about pain education, and I'm a remedial massage therapist who was diagnosed with cervical dystonia 14 years ago. And I used opioids to manage the related pain.

Dr Jill Thistlethwaite:

Thank you, Leah. And Hester, a few words about yourself.

Dr Hester Wilson:

Hi, I'm a GP and an addiction specialist working in Sydney. I have worked overseas, but always in large metropolitan centers. And I do acknowledge that the settings that my colleagues are working in Australia in rural regional and remote areas is very different to the metro situation.

So I've been working in clinical practice for 30 years now, and I'm just in the process of starting to do some research, looking at the GP's experience of people that suffer chronic pain, are using opioids, who may actually be getting into problems with their opioid use and how they might respond to that.

Dr Jill Thistlethwaite:

Thank you, Hester. So Leah, you mentioned that you have experience with using opioids for chronic non-cancer pain, and also that you have had dependence. Can you tell us a little bit more about your story?

Leah Dwyer:

Well, I had a really boring little accident at my son's school, about 14 years ago, and I developed whiplash and got a concussion. I fell backwards in a mother's running race. I lost, by the way. And when I developed a lot of really strong neck pain, I went to a doctor and asked for something to help with the pain. Was given some tramadol. I think it was two weeks' supply of ramadol. That didn't really help with the pain at all. And then I was referred to a neurologist because by that time I had developed a involuntary muscle movement and the neurologist diagnosed me with cervical dystonia, which is a neuromuscular condition. He suggested that the only treatments available were Botox^a and probably antidepressants and painkillers.

So I did Botox^a for a year, but during that time, the pain was so severe actually, that I started looking for something to tackle that. And opioids were really the only thing that made a dent in my pain. So I started taking an, at that time, over-the-counter pill, Mersyndol^b, which was codeine. And I ended up taking that for about eight years. And during that time, I took more and more Mersyndol^b. I started out taking two to four a day. Then it just escalated over time, very, very gradually. But because I'd been told right in the very beginning that my condition would deteriorate, I thought that my condition was getting worse. So I was experiencing more and more pain, which I needed more and more codeine to deal with.

I knew nothing about how opioids worked. I didn't know anything about opioid-induced hyperalgesia. I didn't know anything about tolerance or dependence back then. I thought my condition was getting worse and I needed more of the drug.

Dr Jill Thistlethwaite:

That's a familiar story in many ways, but also very individual as well. And Hester, as prescribers, we are often told about the harms of opioids. You hear about the risk of dependence with opioid use. Is this exaggerated in the media?

Dr Hester Wilson:

Yes, look, I think the media has a particular story to tell, and I think the reality is it's much more complex. Bottom line is opioids are essential medicines, and we have this bizarre situation in our world where a small group of countries overuse opioids, and we use the majority of opioid medicines in the world, and other parts of the world, people can't access them at all. There is no doubt that opioids are terrific medications for severe acute pain.

What is clear now, however, is that they're problematic in the management of severe chronic pain. The issue is that what we know is that there is a risk of developing problems from your opioid use with chronic pain, and Leah's story, it just breaks my heart. You have had severe pain, you were trying to manage that, you started using over-the-counter medications and you had no idea really what it was that was going on.

That really flags to me, the importance for us as doctors to really understand ourselves and to spend some time explaining the nuances of this medicine that is great medicine, but it does have side effects. It does have issues. And all of us as human beings, if we're taking opioids for any period of time, are at risk of developing problems.

Dr Jill Thistlethwaite:

Yes. And those are the things we really do need to be aware of and have conversations about. Leah, you mentioned that you weren't really given that much information about tramadol, other opioids, when you were prescribed them. Can you remember anything about what was said?

Leah Dwyer:

Really honestly, I wasn't given any information about tolerance or dependence. I remember I was given tramadol and told, "I can't give you more than a two-week supply." And that was it. No explanation as to why she couldn't give me a two-week supply. And she was a very brisk doctor that I used to go to at a walk-in clinic. I liked the fact that she was very brisk because I like to get in and out. So when she just said, "I can't give you more than a two-week supply," I thought, okay, that's a doctor-y thing. I don't know anything about that. I'll take my two weeks supply and just run with that.

But I also was prescribed at one point, in the last year of the eight years, I was prescribed liquid morphine. And when I filled it out at the chemist, the chemist said, " Oh, what's this for, because it's really, really strong. And morphine is very addictive." And that was actually the first time somebody said to me, "This is really strong medication." And I know there's a huge leap between tramadol and morphine, but she was the first person to say, "This is really strong stuff. Are you sure you want this?" Which was really interesting and the concern on her face made me think, oh, maybe I should really think about this and research it and be cautious about it.

Dr Jill Thistlethwaite:

So it was the pharmacist who first mentioned addiction to you?

Leah Dwyer:

Yes. She was the first one to say that. And when I took the first dose, I actually took it first thing in the morning, and I was actually sick at work, which led me to conclude that I shouldn't take it first thing in the morning, just at night. So I took one ml at night and that helped me sleep really well, which I needed. The level of concern on her face prompted me to think that maybe I needed to really know what I was putting in my body and that I needed to think about it.

Dr Jill Thistlethwaite:

Hester, we talked about addiction there. What would you say is the difference if any, between addiction and dependence, and can this affect anybody who takes opioids?

Dr Hester Wilson:

Yes. For me, there is very specific differences between dependence and addiction. Addiction is a term that is a little problematic, and the way that we talk about problematic opioid use is having an opioid use disorder. So part of the opioid use disorder is, as Leah described, needing more, escalating the dose. So becoming tolerant to the medicine. So you need more to get the same effect. And that's one of the 11 criteria for having an opioid use disorder.

The other is having withdrawal symptoms. So with opioids, you can, after you've been on them for a while, develop the tolerance, and then when you try and stop them, you have withdrawal symptoms. And they're pretty specific, but it depends on what particular ones. People can have different symptoms that they would have as an individual. It can be things from nausea, vomiting, diarrhea, stomach cramps, anxiety, insomnia, deep leg aches, sweating, pupillary dilation, and goose flesh are the big ones that people notice. It can also send your pulse rate up a little and your blood pressure up a little. It's a very uncomfortable, miserable condition.

And the other really important part of it is your brain saying to you, "You've got to get this medication. We can't deal with these symptoms. You have to get your medication to stop these symptoms.” And so dependence, there can be a psychological dependence, which is the thought of, I can't do without this. And very commonly people will experience some anxiety. "I'm going to run out. I need to have my script with me. I need to make sure that I've got enough to tide me over just in case the doctor is away." And so they might hoard a few and it really is around that worry that they're going to be without.

The next step up from that is the physical dependence, which includes those physical withdrawal symptoms and the tolerance. On top of that, there are other behaviors that people can experience, which can lead to a mild, moderate, or severe opioid use disorder. And that will include things like repeatedly asking for dose increases or taking big dose increases that are not sanctioned by your doctor. Attending multiple doctors to get more medicines. It can be moving towards using more effective delivery modes for your opioids, including injecting. It can mean that you go into other behaviors which are around things that get you into trouble. Things like stealing scripts or forging scripts, and they are a measure of how much impact the opioid use disorder is having on your life.

The other important part of it, which I think is a really good way to look at it is the salience, the importance that it takes in your life. So it becomes bigger and bigger and bigger, a bigger part of your life. So it stops you from going to work. It stops you from parenting. It stops you from going out with mates. It stops you from having your relationships and it takes over more and more of your life.

It's a kind of a spectrum. And we will see people, and Leah, I haven't heard your full story around all the experiences that you had, but what I'm seeing there is someone who has developed a physiological and psychological dependence, but is less likely to perhaps to have those other really tricky behaviors that tell us that this medication is really causing harm to the individual.

Dr Jill Thistlethwaite:

So it can be very distressing and scary, these symptoms that people have, and often they won't understand what's happening to them.

Dr Hester Wilson:

Absolutely.

Dr Jill Thistlethwaite:

Leah, you mentioned the pharmacist said about the medicine being potentially addictive and that you then went off to do some research. So what happened then? How did you think about your medicine and decide to do something about it?

Leah Dwyer:

I think the catalyst actually was one morning when I... I used to keep all my drugs in the fridge. I'm not really sure why. Instead of taking two Mersyndol^b first thing in the morning, I took three tablets. And a little voice inside of me said, "Leah, what the heck are you doing?" And my bigger voice said, "It's okay. It's only for today. It's going to be a rough day. You've got a lot of clients. You've got to see the ex-husband in the middle of the day." And so I was preempting my day because I knew it was going to be a painful day.

But this little voice that said, "What the heck are you doing?" really countered that little decision to take three instead of two. And it really did say, "This is just another excuse to up the amount that you're taking," because over a year-long period, I realised I was taking more than... At that point, I was taking 12 a day, and I had started to sometimes go to 14, and at that point 15. And it really was a mental slap in the face. And it really was the catalyst to me saying, "Is this really the way I want my life to be? Do I really want my life to revolve around this little pill? Do I really want to be having to carry it in every bag and every jacket and always be trying to find another pharmacist that has Mersyndol^b on the shelf or doesn't look at me funny, like, 'Didn't I just see her two weeks ago?'"

All these little things that it started to really pile up, started to really slap me in the face. And very coincidentally, it was just the year before, so a couple of months before codeine was going to be up-scheduled anyway, and I thought I can go to a doctor and get a script for Mersyndol^b. Any doctor will probably give it to me once I tell them I've got dystonia. Or I can change my life. And I decided to change my life. I decided that I didn't want to be attached to this drug anymore. And I'd experienced enough side effects, like constipation and brain fog and sleeplessness, and just that anxious feeling all the time of, do I have the pills? And I really was, to be perfectly honest, really tired of it.

Dr Jill Thistlethwaite:

So you became very motivated to change your life. But how did you go about it? It couldn't have been easy to reduce and then stop.

Leah Dwyer:

It was not easy. Tapering off of an opioid is difficult. I'm not going to sugarcoat it, but I decided to go back to that friendly pharmacist who works a couple of doors down from the clinic that I'm at. And I just point blank said to her, "I'm taking too much Mersyndol^b." And she said, "Yes, I know." And I thought, oh, thank God. Somebody knows, and they're going to help me. And I said, "I need help." And we devised a tapering schedule, and she said, "Any time you need to come in, even if it's just for me to hold your hand for one minute, come in. Don't hesitate because this is going to be difficult, and you're going to go through a lot physically and emotionally and mentally."

And once we'd devised the tapering schedule, I thought, okay, I need to know everything possible about opioids and there's a lot out there. So I just picked a couple of books and read those while I was tapering, because I thought I need scientific reassurance. I'm a real lover of science. And every time I started to feel like, I can't do this, I can't do this, I would pick up the book. The most important thing I learned was that everything I was going through was actually quite normal, in that this is what an opioid does to a human brain, and this is normal when you begin to taper. Things like an increase in my pain, which was really hard to deal with because normally an increase in pain, I would want to reach for the opioid. But I knew enough at that point to know that my brain was saying, "Give me the drug." And I was saying, "No, I am not giving you the drug. We're not doing this anymore."

And sweating and an increase in the tremor that I normally get from the dystonia. It was almost like my brain was throwing every single trick at me. "I'm going to make her shake. I'm going to make her hurt more. I'm going to make her sleepless. I'm going to make her feel sick." All in an effort to get this opioid. So I was very prepared to experience a lot of really crappy things.

But I think that learning about what an opioid does to any brain really helped me feel stronger, because then I didn't think that, I'm not strong enough for this. I can't do this. It really gave me a lot of strength to realize that I'm really normal. I'm reacting very normally to taking this drug slowly away from my brain.

Dr Jill Thistlethwaite:

Yes, that's just so powerful. It does show that people can taper successfully when motivated and also when they have an understanding of what's happening to them. But Hester, for those people who have problems tapering, different effects that happen when they try to taper, what's the role for opioid substitution therapy? Is it available and who should have it?

Dr Hester Wilson:

Yes, absolutely. I just would be careful about, first of all, saying only the motivated people are the ones that are going to be able to taper. And I do acknowledge what Leah was saying about how difficult it is and how much support you need. And it's just so wonderful that you had a practitioner that said, "If you just want to come in and I'll hold your hand for one minute. I'm here. We're going to do this together." And the support and the therapeutic alliance that happened there, that is so important. It's really brilliant to hear.

But the reality is that it's really hard to know, when you start opioids, if you're going to be someone that's going to get into trouble with them and develop a dependence or develop an opioid use disorder. There are groups of people perhaps who are at higher risk, but probably the vast majority of us, if we're on them for long enough, may well have issues with this medication. It's just part and parcel of the way our bodies respond to this medication. We have opioid receptors all over our brain and all over our body, so it's not surprising that we will have this very common side effect. It's always been really interesting to me that you have side effects, things like constipation and so on, and then you have dependence and addiction, as if it's something different. It is a side effect.

When I'm seeing someone who, it's become clear that first of all, opioids aren't assisting them. There are issues around their risk with their opioid use, and it's time to start changing that. It is really important that first of all, you do need to do a safety and risk assessment, but as much as you can, this is a shared decision that you're making to change this.

And what I do know, and what we hear from Leah as well, is that once you get through this, life gets better. Working with the individual to look at how you can decrease risk, and that may be things including supervised dosing or stage supply of the medications, so getting small amounts. Looking at that overall risk, and I know we'll talk in a little while about overdose. But then working with them to slowly cut that dose down at the rate that they can cope with. Some people will find that they just cannot get that dose down. And it's not a matter of them being weak or unmotivated. The fact is that they have developed a significant dependency, and they are the group that do very well with medication-assisted treatment of opioid dependence or opioid... What are we calling it here? Opioid substitution therapy.

And when we're talking about opioid substitution therapy, we're talking about specific programs that are state-based with methadone and buprenorphine, which are opioid replacements. And in this group of patients, this treatment works really well. The treatment outcomes are excellent. There are different rules in different states. In New South Wales here, GPs can commence people on Suboxone, which is buprenorphine. In other states, they can't. South Australia, I think they can. Other states, there are different rules. But doctors in states can seek support for their patients from specialist services, if you can't start it yourself in your state, and can be involved in supporting their patient to begin that therapy, and then actually can continue managing that therapy in their general practice. In their setting, they will need to have an authority from the state-based authority services.

One of my concerns with opioid substitution therapy is that it's not as accessible or as available as it could be. And so there is an unmet need there, both for people who have a history of illicit opioid use and injecting opioid use, and for people that are oral users and have developed it as a result of trying to treat their pain, that people cannot access this very highly evidence-based and safe treatment, as much as they need it, and they should be able to.

So one of my take-homes for anybody listening to this is, check out your state-based sites around what is available in your state for your patients to access that treatment should anyone need it. I should also flag at this point that all of the states have 24/7 numbers for drug and alcohol specialist advice services, which you can look up on the web as well. So if you're in your general practice, you can just give them a call. They will have a chat to you and help you create a plan, which may well involve things like decreasing risk with staged supply. May look at tapering dose down. And if the tapering isn't working, then moving across to opioid substitution therapy is a really great idea.

Dr Jill Thistlethwaite:

I do take your point about motivation. Because we've talked in other educational resources in our program about the cycle of change and the point where you are in that cycle of change. So I will take on board that fact about being careful about motivation, because I can understand that you don't want to blame someone because they're not motivated. But you have mentioned the risk of overdose and what should the prescribers do to reduce the risk of overdose, and can you tell us a little bit more about that?

Dr Hester Wilson:

Yes, so in terms of risk of overdose, what is clear is as the dose increases, so does your risk of overdose. So it's really important to get a sense of what the oral morphine equivalent dose is. The Australian and New Zealand Pain Society or Association^c have a really great app, which helps you to look at the morphine equivalents. So codeine has a particular one, tramadol has a particular one, so on and so forth, so that you can get a bit of sense of what dose your patient is actually on, because we know as the dose goes up, so does the risk.

The other thing to be thinking in your individual patients is do they have other risks because of their individual situation? So for example, do they have respiratory illness? Are they someone that has sleep apnea or severe asthma or CAL^d ? If they are taking opioids and the way that opioids lead to overdose is through a respiratory depression. So if you have someone that's got impaired lung function, they're going to be an increased risk of that. Are they on other medications that are sedating, that are likely to lead to respiratory depression? Are they taking any other substances? Alcohol, benzodiazepines, other sedatives that increase their risk of having respiratory depression? Have they had overdoses in the past? How are they using their opioids? If they're injecting, if they're using more potent opioids, like fentanyl and heroin, your risk is increased as well.

But please remember that a large number of people who are oral users of opioids, do experience hypoxia. And some people will have repeated non-fatal overdoses, which actually really affect their cognition in their brain. And also a group of people do unfortunately die by opioid overdose.

Dr Jill Thistlethwaite:

Thank you. There's so many things to remember around this topic, and hopefully what we've been talking about this evening will be helpful for health professionals out there who wish to improve their skills in these difficult conversations. So Leah, any main messages that you would like listeners to take onboard?

Leah Dwyer:

I would really like people to know that if you live with a chronic condition, and you have a chronic pain with that condition, or you live with chronic non-cancer pain, back pain, neck pain, there is life after opioids. I think that a lot of people think that they have no choice, or that the only choice they have is, is another drug. And I really want people to understand that there are a lot of other things that we can do as chronic pain patients to change our pain.

I'm especially passionate about pain neuroscience education, and multidisciplinary approach such as psychology, CBT. Physio massage is a great one as well. I just really think that lots of times that we get caught in this idea that this is all there is to manage our pain. And it's just not true.

Dr Jill Thistlethwaite:

Thank you. And Hester, any closing remarks you'd like to make?

Dr Hester Wilson:

Just three things I think that are important. First of all is, don't forget about naloxone. So just thinking back to the risk of overdose, that there is now an intra-nasal option called Nyxoid^e that is available for us as prescribers to prescribe for our patients. So anybody that you're treating with opioids, consider the risk of overdose and consider providing them with Nyxoid^e, and also talking to their family and carers and friends who might be around to explain to them what the signs of overdose are and how they can respond by giving Nyxoid^e and calling an ambulance.

The other two are related, and it's about language and about messaging. And I really agree very much with Leah that the experience that my patients can have is this fear, this terror about not having their medication. And I suspect it's something that opioids do to your brain that make you believe that you cannot do without it.

And absolutely, there is a life after these medications. Looking at those other options that you can use to manage your pain are really important. And for us, as prescribers, as doctors, really think about the language that you use. With my patients, I'm aware that what happens for them is that there can be a lot of shame and guilt about the fact that they've ended up in this situation. And the reality is, this is because we have opioid receptors all over our bodies, and it is a really common, normal response to being exposed to these medicines long-term.

I think it is for us as prescribers, it's to be curious, to be respectful, to support our patients with a goal of helping them have the best possible life they can and working together over time. And don't be afraid to seek help from specialist services, from your colleagues. If you're finding that you don't know what to do next, or you're concerned, but you feel like you're out of your depth, seek help. You don't have to do this all on your own.

Dr Jill Thistlethwaite:

Thank you. That was very, very powerful messages from both of you. And I'm sure our listeners will really take those to heart as they continue to work in this area. I'd like to thank Hester and Leah, and I'd just like to remind our listeners that there are many resources around opioids and prescribing for both health professionals and consumers, including about conversations that we can have, and the language to use on our website at www.nps.org.au. Thank you very much and good evening.

For more information about the safe and wise use of medicines, visit the NPS MedicineWise website at nps.org.au.

^a botulinum toxin type A injection, indications include cervical dystonia

^b Mersyndol tablets contain paracetamol, codeine phosphate hemihydrate and doxylamine succinate. In February 2018, codeine-containing medicines were rescheduled to Prescription Only Medicine (Schedule 4).

^C The Faculty of Pain Medicine, Australian and New Zealand College of Anaesthetists (FPM ANZCA) Opioid Calculator

^d chronic airflow limitation is also known as chronic obstructive pulmonary disease (COPD)

^e naloxone nasal spray may be used as part of the emergency treatment for known or suspected opioid overdose in the home or other non-medical setting