CYP2D6-dependent opioids should not be prescribed to patients on these common antidepressants.
Taking codeine, oxycodone or tramadol with some common antidepressants leads to worsening pain in older people, a new US study has concluded.
The study was conducted on over 30,000 nursing home residents aged 65-85 taking a combination of antidepressants and opioid painkillers. Over three quarters were female, and 82% were taking CYP2D6 neutral antidepressants.
These opioids are metabolised by the enzyme CYP2D6, and antidepressants such as fluoxetine, paroxetine, duloxetine, doxepin and bupropion are CYP2D6-inhibiting products.
Participants taking these antidepressants had an average 13% higher rate of worsening pain than those on neutral antidepressants (not CYP2D6-dependent). They also had a 37% higher rate of pain-related hospitalisation, 49% higher rate of pain-related emergency department visits, and 93% higher rate of opioid use disorder.
Of the CYP2D6-inhibiting antidepressant group, over 35% reported worsening pain over a one-year period at their quarterly medical assessments.
There was no significant impact on physical function, opioid overdose, or depression noted in the study.
Associate Professor Michael Vagg, pain specialist and director of Pain Matrix, told The Medical Republic that this study was strong evidence such combinations led to increased rates of poor pain control and some increased harm to patients.
“In terms of prescribing guidelines for older nursing home residents, this probably should drive a bit of practice change,” he said.
“This is a big enough study with robust enough findings that we probably actually can stop worrying about whether it is a clinically relevant risk or not; it definitely is. So, I think we have enough evidence that really solidifies the fact that in older patients, we should be avoiding CYP2D6-dependent opioids.”
Codeine is a weak opioid with a lot of potential for side effects, he said, and pain specialists try to avoid prescribing them as they are unreliable and unpredictable due to the genetic variability of CYP2D6 enzyme.
“Around 60% of the Australian population are good metabolisers, and around 10% experience no pain-relieving effects but may still experience the side effects of opioids,” he said.
Professor Vagg said well-known antidepressants like fluoxetine and duloxetine were often used for chronic pain but could turn a good metaboliser into a poor one, meaning they don’t get a good result from codeine or tramadol.
“Things like buprenorphine and tapentadol are not particularly dependent on CYP2D6 and are much more reliable, safer opioids, particularly for the study population of nursing home residents, who are a particularly vulnerable group to medication interactions as they tend to be on multiple medications,” he said.
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In this older group who require care, there are significant rates of low-dose opioid prescription. Options such as NORSPAN patches, buprenorphine and tapentadol lack the anticholinergic side effects of codeine.
“They’re less sedating and make the patient less confused, which are really important in the nursing home population,” he said.
“The takeaway for Australian GPs from this [study] would be it’s yet another reason not to bother with codeine in older people, because they’re more likely to have problems with interactions and poor analgesia.”
He said there were other products that interfered with the efficacy of these opioids, due to the complexity of the metabolic pathway. These included turmeric products and herbal teas containing lotus, which were often used in this population.
