How does stockpiling, dependence and diversion relate to dose?

A study across patients recruited from Australian community pharmacies has looked at the link between prescribed opioid dose and problematic behaviours

Many people stay on opioids for years to treat chronic non-cancer pain, despite there being no long-term studies of their effectiveness, a researcher said in presenting the results of a large prospective cohort study this week.

Meanwhile the team from the National Drug and Alcohol Research Centre (NDARC) at UNSW Sydney found a dose-response association between oral morphine equivalents (OME) and patient concerns about their own opioid use as well as opioid dependence, potential extra-medical use, and harmful use.

Dr Gabrielle Campbell, who coordinates the Pain and Opioids IN Treatment (POINT) study, shared results across a national sample of people who have been living in chronic pain for three months or more, and who had been prescribed opioids for a period of six weeks or more.

Of 93% of community pharmacies contacted across Australia, 33% agreed to assist with recruitment, and 1514 people were recruited, she told delegates at the NDARC Symposium this week.

Among the sample, current moderate-to-severe depression and anxiety were relatively high, and about 50% reported childhood abuse or neglect.

At cohort entry, participants had been in pain for a median time of 10 years, and had been on strong pain opioids for a median of four years.

Eighty five percent reported more than one pain condition.

By the end of the five-year study, only 14% of the sample had come off opioids at all, said Dr Campbell.

“So that’s 85% of the sample had now been on them for a median of nine years,” she said.

“One of the main drivers has been chronic pain, but the important thing to realise is that there are actually no long-term studies of their effectiveness in chronic non-cancer pain.

“The longest study looking at effectiveness has been a maximum of 12 months.”

Patient concerns about their opioid use, such as having difficulty remembering, loss of interest, feeling depressed, feeling dependent and problems in work and social settings, showed a dose response where “the higher opioids, the more likely they are to report those problems,” explained Dr Campbell.

Additionally, opioid dependence as measured by the ICD-10 including symptoms such as craving, impaired control, withdrawal, tolerance and preoccupation, showed a dose-response relationship, where the high OME categories were more likely to be dependent.

After adjusting for risk factors such as younger age, male gender, mental health and substance use histories, there were still “significant” results, she said.

Patient concerns with opioid use decreased from about 60% to about 52% over the five years, with OME independently associated with that, revealing a “clear dose response”.

Indicators of potential extra-medical use such as ‘doctor shopping’, stockpiling, diversion, asking for an increase in dose and early script renewal also decreased over the course of the study from 38% at baseline down to 25%.

Only the >=90-199 OME group that was independently associated with it after adjusting.

“With the exception of patient concerns, problematic behaviours were experienced by a significant minority, so dependence and harmful use weren’t experienced by the vast majority of people,” Dr Campbell concluded.

“About 9% were dependent consistently across the cohort, and the highest dose [200+ OME] was associated with that… so once you start getting things like Centers for Disease Control and Prevention guidelines [in the US] coming in saying people shouldn’t be on these doses, but they may not be experiencing problems, you need to be careful about taking people off them, especially on high doses, the abrupt tapering that was going on,” she said.

“It’s not really up to one risk factor, it’s not dose only, there are patient characteristics that need to be taken into consideration. I guess this goes back to the whole holistic [thing], taking into account the whole person, look at how they’re going, monitor them specifically, checking with them often, and the need for continual monitoring.”

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