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Clinical refresher: Recognising red and yellow flags in patients on opioids

Humanity has used opioids for millennia – Sumerian clay tablets from about 3000 BC mention the opium poppy. It’s telling that we are still trying to find the most effective way to use them, says Mark Greener.

Opioid analgesics can be life-changing but people using them should be regularly reviewed, says Dr Emma Davies, advanced pharmacist practitioner in pain management at Cwm Taf Morgannwg University Health Board. 

Despite the well-publicised risks, opioids remain among the most popular medicines – and not just the plethora of POM products. OTC opioid-containing formulations include kaolin and morphine, co-codamol, codeine plus ibuprofen, and codeine-containing cough and cold remedies.

A 2020 estimate suggested that sales of codeine-containing OTC products in the UK reached 26 million units: that is about 7.8 per cent of the total market for oral analgesics in adults.1  

Opioids’ popularity isn’t surprising. After all, pain may be “the most common contemporary medical problem” and even “the greatest health problem of our age”.2 Pain, however, isn’t a simple consequence of tissue damage.

“Pain … always involves our beliefs and emotions as they combine with the biology of neurotransmission to produce complex experiences,” comments David Morris in his thought-provoking book Illness and Culture in the Postmodern Age. Opioid analgesics offer simple answers to complex clinical conundra. 

However, “if opioid analgesics no longer help or cause side-effects, the dose should be reduced and, ideally, stopped,” says pharmacist and pain specialist, Emma Davies.

She helped write the All Wales Pharmacological Management of Pain Guidance,1 which suggests that pharmacists should be vigilant for red and yellow flags. Red flags indicate that the patient may have a serious underlying condition1 and should seek medical advice. Table 1 summarises red flags for people with acute low back pain.

Table 1: Red flags in acute low back pain
Differential diagnosis Patient history Examination
Possible fracture Major trauma Evidence of neurological deficit (e.g. in the legs or perineum in people with low back pain) 
Minor trauma in an elderly person or patient with osteoporosis
Possible tumour or infection Younger than 20 years or older than 50 years of age
History of cancer
Constitutional symptoms (e.g. fever, chills, weight loss)
Recent bacterial infection
Intravenous drug use
Pain worse at night or while supine
Possible significant neurological deficit Severe or progressive sensory alteration of weakness
Bladder or bowel dysfunction

Adapted from All Wales Pharmacological Management of Pain Guidance1

Yellow flags suggest that the patient is vulnerable to progressing to long-term distress, disability and pain. In principle, yellow flags assess the likelihood of persistent problems from any acute pain presentation. Pharmacists can remember these as the 4Ds: Distress, Disability, Dependence and Drugs.2 

“Yellow flags are psychosocial factors that can influence a person’s ability to live with or manage pain and which can indicate a person’s likelihood of acute or longer-term pain becoming problematic,” Dr Davies says. 

“Pharmacists should gain confidence in recognising these signs as early referral to multi-disciplinary support can make a big difference to outcomes, including reducing reliance on opioid analgesics.”

Table 2: Yellow flags in people taking opioids 
Attitudes and beliefs The patient believes that pain is harmful or severely disabling
The patient expects that passive treatment, rather than active participation, will help
The patient feels that "no-one believes the pain is real". This may reflect previous encounters with health professionals
Emotions and behaviour Fear-avoidance behaviour: i.e. patients avoid activity because of the fear of pain
Low mood and social withdrawal
Other psychosocial factors Poor family relationships or history of abusvie relationships
Financial concerns, particularly if related to ill health or ongoing pain
Work-related factors (e.g. conflict over sick leave, ability to perform current job tasks)
Ongoing litigation relating to the chronic pain condition

Adapted from All Wales Pharmacological Management of Pain Guidance1

In addition to helping ensure appropriate use of OTC and POM opioid analgesics, many community pharmacists oversee opioid substitution therapy. And there’s the potential for expanded roles for pharmacists here as well.

The New England Journal of Medicine recently reported results of a pilot study at six pharmacies in Rhode Island that trained 21 pharmacists to implement facilitated unobserved (“take-home”) buprenorphine induction and provide follow-up care.4 

Pharmacists used checklists to assess patients’ histories and withdrawal symptoms and then agreed a buprenorphine regimen with the addiction medicine physician. After patients reached a stable buprenorphine dose, they received either pharmacy-based follow-up or usual care.4 

Pharmacists screened 171 people. Of these, 100 agreed to take part and 58 attained a stable buprenorphine dose. Of the latter, 28 received pharmacy-based follow-up.

Keeping opioid users engaged with care is often difficult. But in the Rhode Island study, 89 per cent of those receiving pharmacy-based care continued to attend visits a month after randomisation compared with just 17 per cent in the usual care group.  

During the first month, there were three non-fatal overdoses and three non-overdose-related opioid emergency department visits. One and two of these respectively were in the pharmacy group.4

“Longer and larger comparative-effectiveness trials are required in order to determine the risks and benefits of induction with patient-centered buprenorphine regimens through pharmacy-based care as compared with conventional and other care models for the treatment of opioid use disorder in the community,” the authors conclude.4 


  1. All Wales Pharmacological Management of Pain Guidance
  2. Over-The-Counter Codeine: Can Community Pharmacy Staff Nudge Customers into Its Safe and Appropriate Use?

  3. Available at

  4. New England Journal of Medicine 2023; 388:185-186 

  5. Archaeometry 2022;DOI:10.1111/arcm.12806

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