The problem with opioids

From a distance, Australia has seemingly avoided the opioid crisis that has spread across North America, but upon closer inspection there are parallels between what is happening in our backyard and what is reported from the other side of the world.

In the past 20 years, Australia has experienced an increase in opioid use disorders and the related harms and unintentional deaths that ensues, which coincides with an upsurge in the long-term prescribing of opioids for chronic non-cancer pain (CNCP).

Opioids were not always seen as the go-to treatment for CNCP, rather they were reserved for terminal cancer patients and post-surgical acute care. This changed in 1996 when the American Pain Society suggested pain was the “fifth vital sign” alongside body temperature, blood pressure, heart rate and breathing. This led the medical community to look at pain as something to be treated.

At the same time, pharmaceutical companies began marketing a range of opioid analgesics to clinicians in the US as ‘safer’ alternatives to drugs such as morphine, in the context of potential patient dependency.

In the early 2000s, the same opioid analgesics were classified on the Pharmaceutical Benefits Scheme (PBS) for the treatment of CNCP.

The data also tells a story. Opioid prescriptions in Australia have increased fourfold since the 1990s, along with significant increases in the prevalence of opioid use disorders and unintentional drug-induced deaths.

Between 2016-2017, 3.1 million opioid prescriptions were dispensed in Australia. In 2018, 3 people died per day on average, due to opioid overdose, with pharmaceutical opioids present in 70% of these cases.

The appropriateness of opioids is now being questioned for functional restoration of patients with CNCP – opioids block the pain without treating the source – with research suggesting non-opioid interventions are more effective for the treatment of CNCP.

In August last year, the Penington Institute released its latest Australia’s Annual Overdose Report and with it came some uncomfortable reading: unintentional drug-induced deaths between 2001 to 2017 increased by 64.3%, while, in 2017, opioids accounted for 56.1% of all unintentional drug-induced deaths.

Statistical significance

“We’ve had a massive increase in opioid prescribing to alleviate pain for patients, but I don’t think it’s been front and centre for clinicians in that process to manage people’s risk of addiction or manage people’s risk of misuse. We’ve got a growing illicit overdose problem, but also a very significant pharmaceutical overdose problem,” Mr John Ryan, CEO of the Penington Institute, said.

Mr John Ryan, CEO of the Pennington Institute
Mr John Ryan, CEO of the Penington Institute

According to Mr Ryan, the prescribing of opioids is not necessarily the problem, it’s the controls around the use of them.

“We live in a society where we expect pharmaceutical solutions to our problems. And that’s perfectly reasonable. But the kind of risk management in relation to those pharmaceuticals has been proven to be inadequate considering the overdose [rates].”

Education on the risks of opioids, along with awareness of potential for problematic behaviour, was needed.

“I don’t think the health sector, of which I’m a part, has adequately focused on those broader issues, including addressing this growing relationship to addiction. It’s a difficult area, there’s no doubt about that, but it’s so prevalent in the community, it’s got to be faced,” he said.

Although the report is not part of a policy initiative, Mr Ryan says the numbers should be persuasive enough to encourage change.

“You have to acknowledge, after seeing the numbers, that we do need policy changes and an increased community awareness of the overdose problem. That’s actually a big step forward if we can improve the level of understanding in the community.”

“Better overdose response would be part of that because we need families of people who are on high-dose pharmaceutical opioids to know the signs of an overdose and how to respond. We also need more access to naloxone and to other drug treatments. Not enough medicos are prescribing opioid substitution treatment and there is not enough psychosocial support for people who are on opioid substitution treatment.”

“[The solution] can be summed up by needing to improve our health approach to drug problems, whether they’re pharmaceutical or illegal drugs. It’s about ramping up a health approach.”

Stigmatisation of drug abuse is a barrier that is holding Australia back from fully realising the magnitude of the situation at our doorstep, according to Mr Ryan.

“It’s extraordinary that so many people are dying from overdose and yet we’re not talking about it. The stigma that has come from illicit drug use is now impacting on people who are on prescribed pharmaceuticals as well.”

“There’s no evidence that stigma is protective but there is evidence to suggest that that it is hurting people, and it’s hurting the families of people affected by drug use as well. People are actually dying for lack of knowledge, which, in 2020 Australia, should no longer be the case.”

Perilous pathway

Ultimately, the narrative belongs to the Australian patients who have first-hand experience of opioid overuse. The journey of drug dependency can begin innocuously, without any forewarning of the perils that lie ahead.

“Peer pressure, probably a splash of depression, and the availability of drugs,” is how Warren, a 36-year-old from the northern suburbs of Perth, describes his first encounter with illicit drugs. “Before I knew it, I was using on the weekends, then during the week.”

Warren spoke of experimenting with cigarettes, cannabis and alcohol in his teens before using methamphetamine in his early 20s before progressing to heroin then codeine.

“I was a habitual codeine user. We used to get it from a chemist. I was using cold water filtration to extract the codeine from the paracetamol. That was a relatively easy process,” he said.

At this point, Warren’s story converges with that of many non-illicit drug abusers, as his drug dependency transitioned from illicit drugs to pharmaceutical medications, with long-term prescriptions for Tramadol being provided by his GP and Xanax and Klonopin from his psychiatrist.

Warren, said it was easy to obtain these scripts concurrently, as long as he stuck to his script.

“As long as I went in, well presented and said, ‘everything’s going fine, I’m working’ etcetera, I tick the box and I get the script. But underneath, I wasn’t well at all.”

Normalising naloxone

While the widespread opioid problem can be traced back to the United States years before it came to Australia, we have the opportunity to learn from responses implemented there, such as recognising the need for a practical intervention for the unintentional deaths due to opioids, for instance naloxone co-prescribing.

“In the US, following recommendations by the Centre for Disease Control and Prevention (CDC) and the American Medical Association, there has been a recognition of the importance of prescribing practices for pharmaceutical opioids and the co-prescribing of naloxone, said Professor Simon Lenton, Director, National Drug Research Institute, Curtin University.

Professor Simon Lenton, Director, National Drug Research Institute, Curtin University
Professor Simon Lenton, Director, National Drug Research Institute, Curtin University

“Their recommendations apply to patients who have been prescribed large doses of opioids, greater than 50 milligrams (opiate oral morphine equivalent), or people who have other risk factors such as substance abuse disorder or concurrent benzodiazepine use.

According to Prof Lenton, practitioners should be encouraged to discuss the risks of opioid use and, “raise the issue of naloxone as a potential medicine that could aid in the event of a family member, for example, witnessing someone going into respiratory decline and potentially at risk of overdose.”

“Providing [naloxone] as part of the treatment is something that should definitely be happening in Australia. Prescribers should be thinking about the patients they are prescribing to and who might be at an increased risk of overdose and the role of naloxone. And now that an intra-nasal product is available in Australia, which can be easily administered, this is now viable as a part of routine practice.”

However, Prof Lenton questions the appropriateness of the terms surrounding opioid use, such as ‘overdose’ and ‘abuse,’ for patients on prescribed opioids.

“The language that’s been used is more appropriate for people who inject drugs and really doesn’t translate well to people who are on pain medication and who clearly don’t have a history of drug injection,” He said.

“Even the use of the term ‘overdose’, most people on chronic pain medication wouldn’t think that applied to them. But there is an opportunity as part of a conversation about the potential side effects of this medication to raise the issue.

“Explaining that, particularly when people inadvertently take too much it, opioids can suppress breathing to the point where people can be at risk of dying. This seems to be doable. And this could provide a context to raise the issue that there is medicine available [Naloxone] that can help reverse that in the rare occasions it happens.”

“It’s about using appropriate language and not alarming people, but being upfront with them about what the real risks of these very strong medicines are. This isn’t to say that prescribing of opioids is inappropriate. Clearly, opioids have a very important role in pain management, but it’s about recognising what the potential risks are and mitigating those risks.”

Another aspect that’s critically important, says Prof Lenton, is for patients who have an opioid dependency to be referred to an “appropriate evidence-based opioid substitution treatment, such as buprenorphine or methadone, which we know reduces the risk of overdose.”

Although opioid overdoses and unintentional deaths are increasing at a community level, Prof Lenton says that interventions, such as naloxone, are not yet scaled-up to a level where they are likely to have an impact on reducing these statistics, which is why engagement of the general medical community on this issue is so important.

Naloxone is free in WA under the Commonwealth Government’s Take Home Naloxone pilot scheme.

Risk mitigation

Substance dependencies can present with a plethora of biological, psychological and social-environmental factors influencing the aberrant behaviour, whilst opioid dependencies from long-term treatment of CNCP adds further complexity to treatment modalities.

Often the foundations of opioid dependencies feature an array of predisposing, perpetuating, precipitating and protecting components requiring a long-term holistic treatment plan.

Dr Richard O’Regan, Clinical Director, Next Step Drug and Alcohol Services
Dr Richard O’Regan, Clinical Director, Next Step Drug and Alcohol Services

Pharmacotherapy is just one aspect of the treatment, says Dr Richard O’Regan, Clinical Director, Next Step Drug and Alcohol Services. Dr O’Regan explained to Medical Forum how his clinic accessed and treated clients with opioid use disorders: an assessment should be undertaken to first identify the features of substance use problems, then a recommendation of staged dispensing of prescriptions.

Dr O’Regan said that although there might be patient push back, ultimately it could save their life.

“It’s the balance between doing what’s in their best interests versus ‘I know this is a pain in your backside and I apologise for that, but in my hierarchy of needs, you being alive is much, much higher than you being a bit miffed’.”

“Some doctors won’t do it or dislike the idea. A patient might say ‘you’re treating me like a drug addict.’ Yeah, well, what I’m trying to do is to keep you alive, keep you safe.”

Dr O’Regan suggests doctors not fall into the trap of a customer satisfaction type relationship with their patient by avoiding pointed questions when opioid prescriptions are broached, such as a basic history of past substance use, such as amphetamines, heroin, injected drugs, alcohol.

“A lot of doctors struggle with patients on high-dose opioids over a long period of time. It’s very, very hard, particularly if they’ve known you for a long time. And over many years, we’ve got to a stage where they’re on benzodiazepines, maybe one or two S8s. The doses creep up and up and up. It’s quite challenging for the doctor then to stop and think, well, hang on, something’s going on here.”

“A lot of the folks that we see have had hard experiences and hard lives, without robust coping mechanisms. You’ve got to be gentle, but firm. Sometimes the caring nature of being a doctor takes precedence with doctors being too permissive, however, I have to do things that patients are not so keen on because I’m looking out for their health.”

Convincing patients on long-term opioid prescriptions to reduce their dosage and ultimately cease taking the drugs is no short conversation.

“It’s not a palatable answer from a patient’s perspective. To have a conversation about the pros and cons of opioid prescribing and the non-medication therapies. It’s a long conversation,” Dr O’Regan said.

The difficulty is in battling the preconceived notions of five or 10 years of opioid treatments and he urges clinicians to reflect on how they address opioids with their patients.

“For a lot of practitioners, I think it’s really hard. Do they have the time? Definitely not. Do they have the inclination? That’s another question, of course, too. ‘Maybe I’d like to. But I’ve got this business to run here and I’ve got 10 patients in the waiting room…’”

Pharmacotherapy paradigms

Conventional pharmacotherapy treatments for opioid use disorders tend to use opioid agonists that activate opioid receptors such as buprenorphine or methadone. While there are less conventional, opioid antagonists (which will be explored later) that block the receptors, such as naltrexone.

Next Step uses injectable buprenorphine (Suboxone) to treat opioid dependencies, which according to Dr O’Regan, “has been a real game changer for us and for our clients.”

Dr O’Regan says that agonists, which stimulate opioid receptors, are a much better treatment becaase completely cutting off the opioid receptors, as with antagonists, leaves individuals vulnerable.

“It’s never as simple as your opioid receptors; it’s you, it’s your partner, your children, your colleagues, it’s your mental health, it’s your other health factors as well,” he said.

“What we find with substance use disorders is a whole lot of chaos in a whole lot of areas. I think of the agonist therapy as ‘time out’. Clients don’t have to go hunting and gathering and committing crime. They can actually take time out because they feel a lot better. [They are able] to study, to address legal issues, to address mental health issues, housing, education, relationships, etc.

“If I remove a client’s capacity to deal with all the problems in their life, instantly, they are going to fall over, and their dependency is going to pop up some other place. We’re dealing with a complex system that’s a long-term treatment.”

Another approach

With two disparate pharmacotherapy approaches, Dr George O’Neil has championed the antagonist approach and has been administering naltrexone to patients with opioid use disorder at his not-for-profit, Fresh Start,  since the 1990s. Dr O’Neil’s approach is unique as he uses Naltrexone implants for the treatment of opioid use disorder (OUD).

Dr George O’Neil
Dr George O’Neil

Naltrexone implants are not listed on the Australian Register of Therapeutic Goods and not approved by the PBS for opioid dependency treatments, therefore each patient who comes to his clinic for implants must be approved by the Therapeutic Goods Administration’s Special Access Scheme. Oral naltrexone is scheduled on the PBS but only for alcohol dependency treatment purposes.

Dr O’Neil estimates each naltrexone implant costs the clinic up-to $7000 but the majority of the clients that walk through the door pay a miniscule proportion or nothing at all.

The status of his treatments is point of contention for Dr O’Neil, who believes Naltrexone implants, along with the holistic approach from Fresh Start (housing, relationships, education and employment) is the most effective way of weening patients off opioids. According to Dr O’Neil, First Start has seen up-to 12,000 clients since it opened its doors and has successfully treated thousands of patients for opioid dependencies with naltrexone implants.

Dr O’Neil’s commercial venture, Go Medical, supplies the O’Neil Long Acting Naltrexone Implant (OLANI) to Fresh Start patients. The OLANI – designed and manufactured by Go Medical – is a slow-realise biodegradable implant that delivers pharmaceuticals, such as naltrexone to patients with OUD.

A criticism of naltrexone implants and the OLANI device is the limited evidence of the treatments’ efficacy, something Dr O’Neil says will soon be established with the National Institute of Drug Abuse (NIDA), in the US, providing a $US6m grant to Go Medical, Columbia University and the New York State Psychiatric Institute to establish the effectiveness of the OLANI for detoxification of patients with OUD and measure the relapse rate as compared with treatments such as opioid receptor agonists.

However, Dr O’Neil is keen to stress there are studies demonstrating the efficacy of naltrexone implants compared to oral naltrexone with regards to post-treatment mortality rates due to overdoses.

Dr O’Neil’s first heard of naltrexone in relation to treating opioid use disorder was in the mid-1990s when he was speaking at a conference on pain management in China.

When he returned to Perth, Dr O’Neil encountered a patient for which methadone was not effective. He approached the TGA for permission to trial oral naltrexone on the patient and after the successful intervention, more patients followed.

“I realised there wasn’t another doctor in Australia helping people to use medicines to get off opiates. And from then on, I was, accidentally, the only doctor in the country doing so,” Dr O’Neil told Medical Forum.

Dr O’Neil, believes the issues faced by patients are as a result of a broken system of pain management and suggests the prescribers are the part of the problem.

“Doctors around the world are starting to wake up and realise, gosh, we’re using opioids for treating pain. Now we have patients addicted to opioids and we’re treating them with more opioids. There’s still a total reliance on treating people with opioids. It’s not good medicine,” he said.

Parlance of pain

What once was the ideal treatment of CNCP is now being recognised as anything but. However, for the general public the association of opioids and chronic pain is synonymous, according to Associate Professor Suzanne Nielsen, Deputy Director of the Monash Addiction Research Centre, in Melbourne.

Associate Professor Suzanne Nielsen, Deputy Director of the Monash Addiction Research Centre
Associate Professor Suzanne Nielsen, Deputy Director of the Monash Addiction Research Centre

“Patients might expect to receive something strong for pain, expecting that [opioids are the best outcome], and perhaps not aware of some of the downsides, particularly of using these drugs in the long-term. And similarly, for medical professionals.

“I trained as a pharmacist about 20 years ago and at that time we were told that if people had genuine pain, it was almost impossible for them to develop addictions to opioids. We now know that that’s absolutely not true. Many health professionals were trained with that understanding.”

A lot of the harms from pharmaceutical opioids were being experienced by people who have been prescribed opioids for pain.

“When we’re trying to reduce opioid-related harm, we need to be thinking about the many different populations. We need different strategies for those who might get pushed off opioids through prescription monitoring versus those that might be on opioids for chronic pain and might have other risk factors,” she said.

“For example, being prescribed multiple central nervous system depressant medicines, or also having some of those co-morbidities such as COPD, which increase the risk of mortality with opioid use. There’s a broad spectrum of patients with a range of issues we need to consider.”

The specific language used in doctor-patient conversations is particularly important, A/Prof Nielsen told Medical Forum.

“When having conversations with patients about opioids, the term overdose is often used. And you see information around naloxone and reducing opioid-related harm using the term overdose. And that just isn’t salient for our patients who are prescribed opioids for chronic pain.

“Often, patients interpret overdoses as something that applies to people who take too many opioids intentionally or associate that with illicit drug use, and it isn’t necessarily something that patients prescribed opioids for chronic pain feel like might happen to them.

“Obviously, our mortality data says otherwise, but we do need to have language to try and bridge that gap and let patients know that there are risks with opioids even when they are used as prescribed interventions such as naloxone, which might be appropriate for a really broad range of people.

“For patients with chronic pain, it’s important not to use the word overdose because it is such a value-laden term and it’s often stigmatised.”

A/Prof Nielsen suggests that explaining symptoms explicitly is more effective, not only for the patient but also encourage them to discuss these symptoms with their families.

“Alerting them to the fact that opioids can affect respiration and when it’s severe, it can cause people to stop breathing altogether. And, in that case, why that person should have naloxone in their home. We need to educate not only patients and their family members around these signs and symptoms and what to look out for.

“Tragically we hear in coroners’ reports of people who died in their sleep when there was someone in the home who heard them with laboured breathing and just didn’t identify that as a sign of respiratory depression, and therefore they didn’t respond.

“Education for family members who may see these signs and symptoms is vital so they can intervene by either administering naloxone on the spot or calling an ambulance and thereby reducing those preventable deaths.”