Opioid analgesics: the same, but different

Challenges in using opioids for chronic pain

Opioids for chronic pain – a flawed concept

The benefits to patients of increasing opioid use for cancer-related pain in the 1990s led to suggestions that these benefits could be achieved for patients with chronic noncancer pain (CNCP).¹ This thought led to a significant increase in opioid use for CNCP in the US, Canada and Australia.^2-4 However, as described below, the simple transmission of practices for cancer pain treatment to the treatment of CNCP was misguided.⁵

Poor outcomes for opioids in chronic noncancer pain

Managing the complexity of the biopsychosocial experience of CNCP with opioids did not benefit many patients, especially with long-term opioid use.^6,7 In some patients with CNCP, long-term opioid treatment of CNCP can limit pain relief and delay improvement in function and quality of life.^7,8 These poor outcomes have been confirmed across many studies.^9,10

Opioid-induced hyperalgesia can increase central sensitisation, which worsens pain in many patients with CNCP, especially those on high doses of opioids.¹¹ Further, adverse outcomes caused by opioid-induced androgen deficiency (OPIAD) leading to hypogonadotropic hypogonadism with low testosterone levels and conditions such as weight gain, decreased muscle mass, fatigue and depression, further worsen the quality of life of patients with CNCP.¹²

Limitations of conventional mu-agonist opioids

Conventional mu-agonist opioids suppress immune function, which can increase infection risk.¹³ The potential risk of opioid-induced ventilatory impairment (OIVI), increasing mortality in users of opioids, is dose-dependent, and increases when attempts to manage CNCP lead to excessive dosing.¹⁴ Physical dependence, misuse, abuse, and the development of addiction in vulnerable patients is a challenge in countries with high opioid prescribing for CNCP.¹⁵

Harmful consequences on society of extreme opioid use

The practice of prescribing opioids for people with CNCP has harmed society.¹⁶ Increased diversion of prescription opioids into the black market and an increase in deaths are linked with prescription opioid misuse and abuse.^17,18Similar trends have been observed in France, Canada, US and Australia.^2-4,19

The same, but different

It has been suggested that the “categorisation of all analgesics that have any component of opioid mechanism of action into the same class is anachronistic.”²⁰

There is a distinction between conventional (or classical) opioids, with their mechanism of action based on mu-opioid receptor agonism, from non-conventional opioids, which have multiple mechanisms of action (opioid and non-opioid).²¹The molecules buprenorphine, tramadol and tapentadol satisfy this characterisation of non-conventional opioids.²²

Buprenorphine, tramadol, tapentadol

Three non-conventional opioids, buprenorphine, tramadol and tapentadol, are approved for CNCP.^23-25 Compared with conventional opioids in the CNCP setting, buprenorphine, tramadol and tapentadol have achieved:

• Better function and quality of life^26-28
• Fewer serious adverse effects on immune and endocrine function, lower rates of adverse gastrointestinal effects, a reduced risk of OIVI, in high doses^29-31
• A lower abuse potential and a lower risk of misuse, abuse, and diversion into black markets^32-34

Non-conventional opioids offer additional options for managing chronic pain^23-25 

References

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