Dangerous drug combinations a concern for patients with chronic pain


By Sunalie Silva

7 Oct 2021

The overuse of opioids for the treatment of chronic non cancer pain (CNCP) has again been called out after a large Australian study shows they are commonly prescribed long-term and in dangerous combinations with other drugs – with those without private health insurance being most exposed to the harmful practice.

The longitudinal study led by Dr Natasa Gisev, clinical pharmacist and senior lecturer at the National Drug and Alcohol Research Centre in Sydney, investigated pharmacological and non-pharmacological patterns of treatment use in 1334 adults receiving opioids for CNCP over four years.

Back pain (79.2%) and arthritis (66.6%) represented the most common conditions reported among the cohort many of who had been living with pain for 10 years or more.

Many participants used analgesics including paracetamol and NSAIDs in addition to opioids. Of concern, say investigators, NSAIDs were commonly used consistently, suggesting ongoing prescribing, despite guidelines recommending short-term use of these medicines due to the risk of adverse effects like gastrointestinal bleeding.

Psychotropic medicine use was also common, reflecting increased prescribing of these medicines for CNCP. The most common antidepressants used were amitriptyline, duloxetine, and venlafaxine – medicines that have evidence of effectiveness for CNCP and recommended in treatment guidelines note investigators adding that mental health comorbidities including depression occurred in 47% of the cohort at baseline.

Alarmingly, nearly half of the cohort received a gabapentinoid, indicated only for neuropathic pain, at some point over the study period while nearly a third of participants were using pregabalin for non-neuropathic pain.

“The concomitant use of pregabalin or gabapentin with opioids has been shown to increase the odds of opioid-related death by 68% and 60%, respectively say the researchers who stressed that reports of increasing harms from the combination of these medicines highlight a need for caution in prescribing gabapentinoids for non-neuropathic conditions.

Meanwhile sedative-hypnotic use was reported by half of the cohort, including across multiple waves, despite limited evidence of effective analgesia and recommendations against use of these medicines with opioids due to the increased risk of ADEs including sedation.

While the combinations of medicines used by participants was not the focus of the study investigators add that associations have previously been shown between use of antidepressants or pregabalin and other psychotropic medicines, raising concerns about the risks associated with polypharmacy in CNCP.

Opioid dependence

Talking to the limbic about the findings, rheumatologist Professor Rachelle Buchbinder, who was not involved in the study, said much more needs to be done to stem the growing tide of opioid dependent people.

“With better ways of deprescribing, educating patients about the long term harms of opioids and evidence of lack of effect for long term use, and using alternatives to opioids in the first place so they are not started.”

On dangerous polypharmacy combinations Professor Buchbinder said the study highlights the importance of providing education around deprescribing.

“I will always flag dangerous combinations such as gabapentin and opioids and get patients off the gabapentin as first step. In fact for back pain and radicular pain gabapentin has been proven not to work any better than placebo but has many harms so I am still shocked by how many patients continue to be prescribed it for these indications.

It is also well known that the combination of gabapentin and opioids is dangerous especially if in high doses. So we need to raise awareness and educate the large number of people continuing to prescribe this drug inappropriately. Unfortunately having the evidence and guidelines are not enough on their own. There needs to be better implementation of this evidence translated into practice. We also need to regulate against pharma who push these drugs and educate doctors and the public on understanding the evidence,” she said.

And despite the use of pharmacotherapy long term, most participants continued to report moderate pain severity and interference scores throughout the four-year period, which researchers say highlights the ‘ongoing complexity of CNCP management and that many individuals continue to live with pain despite engaging with treatment.’

It’s a finding that Professor Buchbinder has also observed.

“We have also found this in our data in rheumatoid arthritis patients in the Australian Rheumatology Association Database – a large proportion of patients still taking opioids despite having no active disease. It probably indicates that these drugs are probably not helping or might be prolonging the problem. There is some evidence to suggest that being on opioids actually delays recovery.”

Non-drug treatments

Reporting on the use of non-pharmacological treatments like consultations with medical specialists and physiotherapists in the preceding 12-months, investigators said participation ranged between 61.2-75.0%.

And despite evidence of the effectiveness of specialised pain management programs, less than one quarter of the cohort reported accessing these services at any point.

In a single year, 12-month use of pain programs ranged from 5.8-10.3%.

“Given the stronger evidence of long-term benefits and improved functional outcomes compared with medicines, it is suggested that expanding multidisciplinary pain management may be an important strategy to reducing over reliance on medicines which expose individuals to ADEs,” the investigator team said.

But the study also highlights a divide between those who hold private health insurance and those without with the cohort analysis revealing an association between private health insurance and greater use of physical and specialised non-pharmacological treatments.

While some specialist, mental health, and allied health services are subsidised in Australia for chronic conditions out-of-pocket costs vary, and the annual number of subsidised allied health visits is capped at five.

And while some public pain programs exist, wait lists are unbearably long, according to 2016-18 data showing median waiting periods of 110 days compared with 14.5 days for private services

Investigators also say their analysis, which adjusted for health cover status, suggests that ability to pay for services is a greater driver of this treatment use than health status and, potentially, clinical need.

“These findings suggest that current models are insufficient and access to effective pain management strategies remains a significant problem for many people with CNCP, even within the context of a universal healthcare scheme.”

The study is published in Pain.

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