Opioids and overdose risk

People who live with ongoing pain face daily challenges in getting on with their lives despite the pain. Among the many pharmaceutical and non-pharmaceutical treatments for persistent pain, opioids raise a lot of controversies because their possible severe side effects can sometimes overweight their benefits.

Opioid medicines – such as morphine, codeine, oxycodone, methadone and others – can affect the brain to make people less aware of pain. But opioids also affect things other than pain levels, and many people taking these drugs long-term experience a lot of unwanted effects, some very serious. 

For example, opioids may slow or even stop the breathing, which is why opioid overdoses are so dangerous.

In a Perspective published in the Medical Journal of Australia that reviews the latest information, Monash University researchers build a case for routine co-prescription of an opioid antagonist, naloxone, and opioids, in the attempt to close the gap between scientific evidence and clinical practice.

According to the scientific literature, routinely prescribing naloxone to be administered in case of opioid overdose could save the vast majority of people who overdose.

“Naloxone has been used to reverse heroin overdose for a long time. It is a relatively new concept to think about using it for reducing prescription opioid-related mortality,” says Associate Professor Suzanne Nielsen, deputy director of the Monash Addiction Research Centre in Melbourne and one of the authors of the literature review.

“We support that,” says Associate Professor Meredith Craigie, a pain management specialist at the Queen Elizabeth Hospital in Adelaide, and member of the Faculty of Pain Medicine. “It’s all about reducing the risk of harm to people.

“We should all be alarmed that anyone is accidentally dying from their prescription medicines that are being used to manage a condition that would not normally kill people.”

Naloxone is an opioid antagonist used to counter the effects of opioid overdose blocking opioid receptors in the brain. Because naloxone acts rapidly, it quickly reverses opioid overdoses.

Currently, naloxone is available in Australia for intramuscular injection or nasal spray but it is not routinely co-prescribed. New South Wales, Western Australia and South Australia are trialling a program that makes naloxone freely available to people using prescription or illicit opioids and at risk of opioid-related death.

There is a common perception that opioid overdose and death is predominantly related to the use of illegal drugs, like heroin. But accidental mortality among people with chronic pain who use opioid medicines is not uncommon.

In Australia, opioid prescriptions have increased from 2.4 million in 1992 to 15 million in 2016. Over the past decade, the rate of opioid deaths has almost doubled, from 3.8 deaths per 100.000 Australians in 2007 to 7.4 per 100,000 in 2019, when 1,865 people died.

According to the Australian Institute of Health and Welfare, the majority of these deaths involved prescription drugs rather than illegal drugs, and the number of deaths with prescription drugs has substantially increased. Among deaths associated with common prescription opioids, half involved people with chronic pain.

In the US, an average of 38 people died each day in 2019 from overdoses involving prescription opioids: that’s 14,000 deaths in one year and 28% of all opioid overdose deaths.

The American Centers for Disease Control and Prevention (CDC) already recommends co-prescribing naloxone for long-term opioid users with chronic pain who are at risk. That includes patients taking an oral high daily morphine dose, have a history of substance use disorder, or have a history of overdose.

In comparison, 78% of Australian patients taking opioids for chronic pain would qualify for take-home naloxone. Yet, only around 4% receive a naloxone prescription.

Nielsen found that the biggest barrier to prescribing naloxone was doctors’ lack of awareness of the risks associated with opioids. “People don’t necessarily recognise the risk with prescription opioids. And that’s surprising because we know that the majority of deaths associated with those are from prescription opioids,” she says.

Australian GPs have reported being hesitant in prescribing opioids to younger patients with chronic pain because they perceive the risk of opioid-related harm to be higher for this age group. In contrast, doctors are more comfortable prescribing opioids for older patients, as they believe these patients’ risk-to-benefit ratio is lower.

But middle-aged and older people are those with the highest risk for accidental overdose, says Craigie. “With aging we start to lose some physiological reserves, and that in itself is an increased risk,” she says.

“There is often the assumption that those deaths are just among people who are misusing their medicine. But we know that a large number of people who are prescribed opioids for chronic pain have some other risk factors such as being on a high dose, or having other morbidities,” says Nielsen.

Another common concern among doctors is that prescribing naloxone might make patients feel judged or offended.

“Language is another barrier,” says Nielsen. She says the term “overdose” is often linked to illicit drug use and suicide, while referring to it as “severe opioid-related side effects” or “life-threatening opioid toxicity” removes the stigma associated with it.

Research shows that when people are informed, they are happy to keep naloxone in their meds cabinet. Nielsen calls on doctors to start conversations that are centred around opioid safety and emergency medicine. She says doctors should talk to patients and their families about potential opioid adverse effects, how to identify overdose symptoms and how to intervene.

“Sometimes recommending [naloxone] does give you the opportunity to have a helpful conversation with patients, because a lot of them don’t realise that they have this increased risk,” agrees Craigie.

People on strong long-term opioids are often prescribed laxatives and antiemetics (drugs hat mitigate against vomiting and nausea) to contrast some common opioid side effects. Neilsen says this concept should be extended to naloxone.

“Just like anyone who has peanut allergy would keep an EpiPen at home, if you take strong opioid, there is a risk you could have a severe adverse reaction, thus it makes sense to have naloxone available,” says Nielsen.

“There is a need to normalise the supply of naloxone as a routinely co-prescribed emergency medication.

“But that will require a shift in community and doctors’ attitudes, increase awareness around naloxone, and reduce the stigma associated with it.”