Unanswered questions over codeine scheduling change

Codeine dependence is becoming increasingly common. So what are the treatment options for at-risk patients?

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GPs may be hit with an influx of patients seeking codeine prescriptions or help with their dependence issues if fears around the February rescheduling of the drug are realised.

Codeine is the most widely used opioid in Australia, with an estimated 15 million or more packets of over-the-counter medication sold every year, and another 12 million or so prescribed by clinicians.

While it’s difficult to determine how many people are using codeine occasionally, compared with how many have dependence or misuse problems, the snapshots of data we do have are concerning.

Codeine-related deaths more than doubled in the 10 years between 2000 and 2009, according to one Australian study, rising from 3.5 to 8.7 deaths per million.

Of those deaths, two out of five were people known to have taken over-the-counter codeine, and it’s these alarming figures that have helped create the groundswell of support behind the move to up-schedule the opioid in a bid to curb its use.

But the measures, due to take force in just a few months, have been controversial.

Submissions to the Therapeutic Goods Administration’s July meeting alone spanned 700 pages across many hundreds of individual arguments. And now the debate has been reignited over the issue of whether it’s in the patient’s best interests to cut off a convenient supply of the painkiller.

The Pharmacy Guild, which has been pushing for a partial reversal of the scheduling change to allow pharmacy dispensing for patients with acute pain, argue the move will increase costs and create unfair barriers for patients in rural and regional Australia who need temporary pain relief for ailments such as toothache and migraine.

According to Pharmacy Guild figures, four out of five people who use codeine, do so to treat occasional, acute pain. However, this still leaves one in five who are chronic users and potentially at risk of developing dependence issues.

In addition, switching to prescription-only opioids may not be the silver bullet for the dependency issue.

Research from the Penington Institute found that between 2006 and 2014, prescription opioid deaths increased 87% across Australia and 148% in rural and regional Australia. When it comes to total drug-related deaths in the country, more than two in three are from prescription-drug abuse, according to the Australian Bureau of Statistics.

According to the Pharmacy Guild, without a real-time monitoring system GPs will have little-to-no idea whether the patient asking for the medication is a doctor shopper, meaning the move to prescription-only may do little to stem the tide of codeine dependence.

So more than ever, GPs will bear the burden of identifying and treating patients misusing codeine.

Outlining the extent of the codeine problem in Australia at a recent National Drug and Alcohol Research Centre symposium, senior researcher Dr Suzanne Nielsen described several key questions.

Firstly, how many people need treatment, and do we have the capacity to treat them all?

One of the challenges was that we did not necessarily have a good sense of the scale of the problem. That is, how many people were dependent and might be affected by the up-scheduling, Dr Nielsen said.

The recent trends across a number of different datasets indicated there had been an increase in codeine-related harms and deaths, she said.

Figures from the National Drug and Alcohol Research Centre show an increase in those seeking treatment. One in 20 people seeking opioid-substitution treatment now list codeine as their primary drug of concern, up from one in 37 in 2014.

“For me … the fact that one in 20 people who [are being treated] with either methadone or buprenorphine report that codeine is their drug of concern when entering treatment, I find is a really striking statistic,” Dr Nielsen said.

People often began by using over-the-counter codeine for a pain condition, usually an acute one, but the ongoing use and escalation was often in the context of psychosocial stress and mental-health problems, Dr Nielsen told the audience at the University of NSW.

It’s these mental-health concerns that can often drive the very high and ongoing use, in addition to the fact that they will experience withdrawal if they stop.

It’s not uncommon for people to be taking as many as 100 tablets a day, putting themselves as risk of the severe physical effects of the paracetamol or anti-inflammatory that accompanies the over-the-counter opioid.

“[But] this is something people typically self-manage and don’t necessarily come forward to seek help, or they don’t necessarily know how to seek help,” she said.

“So this is something very hidden.”

Which begs the question, how and when are we going to identify the people who need help? Is it going to be before codeine becomes unavailable, or will it only be after the rescheduling when their supply has been cut off and the patient is going through withdrawal?

Reports suggested many Australians were identified for the first time in hospital systems with not only dependence, but also severe organ damage and gastrointestinal damage, Dr Nielsen said. This included cases of gastrointestinal bleeds and ulcers, anaemia, renal problems and life-threatening complications, such as hypokalaemia.

One recent study of South Australian hospitalisations for codeine misuse put the estimated bill at over $1 million for 99 patients in that state alone. It’s clear that identifying patients much earlier in the dependency journey could prevent the most severe physical effects of the drug use.

Which raises the next questions: Who is going to identify these patients and what training is needed to be able to effectively do this? What tools and treatments are available once at-risk patients are identified and where can dependent patients be referred?

Dr Nielsen and her team recently undertook a systematic review to understand what literature could be used to guide GPs and others in identifying people with codeine dependence, but found little in the way of validated tools or a clearly defined process to help clinicians.

At the moment, codeine users tended to turn to treatment because they were concerned about their own use, rather than any difficulty accessing opioids.  Of course, the February rescheduling could change that, Dr Nielsen said.

In general, people who had become dependent to codeine preferred to try to help themselves and not necessarily seek treatment, and her research has shown strategies such as support groups are common.

And when they did seek professional help, codeine users also tended to prefer treatment within primary care.

“We know that a lot of these patients are already under the care of primary-care providers, but that those providers might not be confident with using some of the treatments that we have available,” Dr Nielsen said.

As necessary as it might be to resource specialist services, it was critical that primary care became upskilled to respond to patients in treatment, she added.

“It makes it challenging when we’re used to saying ‘here are the opiate services, come and get it’, and that’s not necessarily what is going to work in this patient group.”

While the systematic review highlighted the dearth of information guiding clinicians to identify problem codeine users, the TGA has issued an online tip sheet for clinicians. It stresses that codeine is not indicated for chronic pain, and that doses of 30mg or higher are only indicated for acute, mild to moderate pain.

Hitting back at the Pharmacy Guild’s claim that codeine should be available OTC for acute pain, AMA president Dr Michael Gannon backed another of the TGA’s points, that low-dose codeine/paracetamol combinations were no more effective than paracetamol alone and combinations with ibuprofen, and no more effective than ibuprofen alone.

“This evidence shows that codeine is not that good an analgesic and doctors should be prescribing superior alternatives for acute pain, and codeine has no role in the management of chronic pain,” he said in an interview with
ABC Radio.

At low doses it was no better than paracetamol or ibuprofen alone, and at high doses it was increasingly a drug of abuse, he said.

“So, there’s no argument here. I’m not interested in GPs, other specialists, prescribing yet more and more codeine. The more we know about this drug, the more we realise that we should be looking for more effective and safer alternatives.”

Instead, if codeine were invented next week it would “struggle to get listed”, Dr Gannon said.

“This is a harmful drug. It’s hurting people, it’s killing people.”

But if it became apparent that a patient was codeine dependent, there were effective treatments for them, Dr Nielsen emphasised. It was important that people in the community and healthcare providers were aware of that fact in the lead up to the rescheduling.

There was evidence that opioid agonist treatment and psychological treatments were effective for these patients, although there was limited data from randomised controlled trials, Dr Nielsen said.

Dr Nielsen’s systematic review, which has been submitted for publication, was accompanied by a cohort study of around 100 codeine-dependent patients. Among opioid substitution therapies, buprenorphine treatment was one of the most common treatment approaches identified.

Interestingly, the study showed around a quarter of participants continued to occasionally use over-the-counter codeine, but sporadically rather than persistently.

What was positive about the study was that there was high retention across the two-year follow up, which was different from previous studies of the treatment in patients dependent on illicit opioids.

Buprenorphine and other opioid substitution therapies appear to work well.

Despite codeine being seen as a fairly weak opiate and associated with a “mild” drug dependence, studies overwhelmingly described needing fairly standard opioid-addiction doses of buprenorphine for treating these patients, of around 12 to 16mg per day and often up to 32mg per day, Dr Nielsen said.

In general, patients with codeine problems were more likely to be employed, have lower depression scores, less likely to have injected and less likely to use heroin than those dependent on other prescribed opioids, which might bode well for their recovery.

But they were at an increased risk of overdose, Dr Nielsen said. “This is not a group without risk factors.”

Research suggested psychosocial treatment might also be important in addressing the mental-health problems underlying or exacerbating the dependence. Group therapy, or telemedicine for regional and rural patients, could be an option for reaching financially or geographically challenged patients.

A major barrier was lack of knowledge among the community and healthcare professionals about the treatments available and just how effective they might be, she said.

In addition, some patients also reported their health professional did not appear to consider their codeine dependence a serious problem.

Dr Nielsen said the message was that opioid dependence was common in the community across a range of opioids, including codeine, and Australia needed to acknowledge and destigmatise the condition to make it easier for people to seek help.

“This is really a problem with opioids,” Dr Nielsen said. “This isn’t a problem with people.”