Prescribing analgesics: a step by step approach

The recent amendment to the Misuse of Drugs Act means that non-medical prescribers can now prescribe controlled drugs (CDs) for patients in pain. This does not purport to be a comprehensive guide to CDs but offers some insight into their place on the analgesic ladder

Pain is one of the commonest reasons why individuals consult healthcare practitioners in the UK. Indeed in 2011 primary healthcare was responsible for spending over £440 million on analgesics that are available over the counter, which works out as an average of £8.80 per person.¹ If you include analgesics that are only available on prescription then the cost to the NHS is considerable. After mental health issues, musculoskeletal pain is one of the leading causes of long term absence from work which brings an added financial burden to society.^2-4 Pain is also the commonest presenting complaint of osteoarthritis,⁵ which is becoming an increasingly common condition with the increasing age of our society.

Consider Joan, a 78 year old lady. She is brought to see you by her daughter complaining of pain in both knees. The pain is like a persistent dull ache. This is mainly a problem when she is walking but is also keeping her awake at night. What would you consider?

Osteoarthritis inevitably increases with age so it is likely that Joan is describing pain secondary to degenerative joint disease. As well as being briefed on her full medical history and current medication, it is important to get a clear history of the pain, including its duration, character and any exacerbating or alleviating factors. On examining her it is worth considering not only her knee joints but also her hip joints, as there can often be referred pain from one to another. However, the key area to think about is what effect this pain is having on her life. Lack of sleep may be causing her some emotional distress that will in turn exacerbate the pain. She may also be becoming socially isolated due to her pain if it is restricting her mobility. Sometimes using validated pain scores or orthopaedic scores⁶ can be useful in quantifying the level of her pain and so enable you to make an assessment of how useful any intervention has been. Pain scores are now widely available, including in other languages.⁷

OTC preparations

Joan tells you that she has been taking occasional Panadol Extra for her pain when it is at its worst but she has not been using anything on a regular basis.

Getting a clear history of what strategies Joan has already tried with regard to her pain is obviously important. If you are unfamiliar with the brand that the patient describes then it is worth checking in the OTC Directory⁸ - in this instance Joan is trying a combination of paracetamol and caffeine, which may in fact be contributing to her sleep problems. Joan is also trying a rescue-based approach to her pain management, whereas it is preferable to try and anticipate the pain and so reduce its occurrence.

Anticipating pain before it occurs can often lead to an overall reduction in a patient's need for analgesics as it ensures that the circulating levels of analgesics are always sufficient to suppress the pain signals in the descending nerve pathways. So the first step to recommend to Joan may well be to substitute regular paracetamol for her Panadol Extra, and to take 2 x 500mg tablets four times daily. Joan could buy her paracetamol over the counter at very low cost. However, the maximum that she can buy at any one time is 32 tablets, which will only last her 4 days if she follows your recommendations, so a prescription may well be warranted to ensure that she has sufficient medication to last for a reasonable period of time. Given Joan's age this will also be free of charge to her as an individual.

NON-OPIOIDS

Joan takes 2 x 500mg paracetamol tablets regularly (i.e 4 times a day so that she has 24hr cover) each day for the next three months with good pain relief. However, she then develops further pain, particularly in her right knee and so comes back to see you.

Joan may be experiencing a flare of her osteoarthritis but she may have developed an injury so again a clear history is important to try and establish what has happened. Whenever an individual's pain changes in severity or character it is worth pausing and considering whether this reflects a deterioration in their original presenting condition, or if it is due to some other pathology. For pain in particular it is also important to continue to take a holistic approach to the assessment as psychological and social factors have a significant role to play. For an acute flare of OA it is worth considering short-term treatment with non-steroidal inflammatory drugs (NSAIDs), such as naproxen, assuming that there are no absolute contra-indications to them. These are obviously not without their consequences - Joan is likely to have a degree of renal impairment by virtue of her age and she will be more prone to gastrointestinal side effects. Co-prescribing a proton pump inhibitor (PPI), such as omeprazole, will help to ameliorate this risk but brings with it an increased risk of clostridium difficile infection9 and community acquired pneumonia.¹⁰ It is also worth bearing in mind what other medications Joan is on, as the risk of significant drug interactions goes up with poly-pharmacy. Topical NSAIDs can also be useful and are recommended by NICE,5 although it should be remembered that the GI side effects are centrally mediated, rather than being a direct irritant effect of oral medication. Topical capsaicin can help in some circumstances, particularly for relatively superficial joints such as hands and knees. Joan may also benefit from non-pharmacological approaches to her pain such as heat treatment or physiotherapy.

OPIOID FOR MILD TO MODERATE PAIN

Joan takes regular paracetamol and naproxen 500mgs twice daily and omeprazole 20mgs for two weeks. Her pain settles and she is able to go back to regular paracetamol only. However, her pain then progresses, particularly at night, such that she is being kept awake by her pain and has non-restorative sleep. She also now describes pain in her lower back.

It appears that Joan's osteoarthritis has now progressed, with a resultant increase in her pain. Once again a change in her presentation should cause you to reflect on whether there is an alternative diagnosis (e.g osteoporosis, metastatic disease) that might be contributing to her condition. It is worth revisiting her pain and orthopaedic scores as it may be that a joint replacement would be of benefit to her. However, the advent of back pain suggests there may now be some spinal involvement for which there is little role for surgery. So it is likely that Joan needs to move up a level on the pain ladder. (Figure 1) This was originally devised by the World Health Organization in relation to cancer pain but can be usefully adapted for other situations.¹¹

You consider that Joan now needs to move up the ladder so you add in a mild opioid. For Joan the most convenient preparation would probably be a combination tablet of both paracetamol and codeine, although this gives you less flexibility in the dosing schedule. Given that Joan's pain appears to be predominantly at night, you could consider continuing with regular paracetamol for her daytime pain relief and giving her codeine and paracetamol at night. This would help prevent drowsiness, a recognised side effect of codeine, being a problem in the day whilst helping with her sleep. The other common side effects to be aware of are nausea, which often settles with use, and constipation for which she may need to take laxatives.

Combination preparations for codeine and paracetamol come in various strengths e.g co-codamol 8/500 (ie/8 mg codeine with 500mg paracetamol), co-dydramol 10/500 or co-codamol forte 30/500. It makes sense to start with the lowest effective dose and it is worth bearing in mind that doses of codeine above 30mg there is minimal increase in effectiveness but side effects become more of an issue.¹² The lowest effective dose of codeine has not been established in practice as most trials use doses of 30-60mg codeine, however some patients, particularly older ones, are very sensitive to potential side effects.¹³ Tramadol can also be a useful opioid analgesic although its effect is often limited by nausea in older people. In terms of potency, codeine is 1/20th the strength of morphine, whereas tramadol is 1/10th.

ADJUVANT ANALGESIA

Joan settles on co-dydramol 10/500 at a dose of two tablets four times daily. She has few side effects apart from constipation, which you manage to control with Movicol on alternate days. She then develops an unpleasant burning sensation down her right leg associated with pins and needles in her right foot.

The character of Joan's pain has now changed. Rather than the dull ache that she previously described that is typical of osteoarthritis she now describes burning pain. This is typical of neuropathic pain and, in Joan's case, is likely to be due to the arthritis in her spine causing irritation of her sciatic nerve. It is important to rule out any red flag symptoms for cauda equina syndrome such as bowel or bladder dysfunction and saddle anaesthesia. Assuming that none of these are present then the focus is back to addressing Joan's pain. Again a short-term trial of an NSAID may help to settle down any inflammation. However, for neuropathic pain an adjuvant analgesic is likely to be the most effective treatment. Neuropathic pain is also very uncomfortable so it is worth screening Joan for any underlying depressive illness as this will inevitably increase her perception of pain.

In terms of adjuvant medications there are two main avenues to explore - tricyclic anti-depressants, such as amitriptyline and anti-convulsants, such as gabapentin. Anti-depressants appear to have a faster onset of action, with positive benefits often being seen within one to two weeks, and they are considerably cheaper, so it makes sense to start with a trial of amitriptyline. Side effects can be a problem and some people, particularly the elderly, are very sensitive to them so it is worth starting with a very small dose, even as little as 10-20mg, and titrating upwards after a few days. It is also worth discussing with patients their role as anti-depressants (albeit usually at a higher dose) as otherwise they may well read the patient information leaflet and then decide not to try the medication.

If amitriptyline is not effective then you can try switching to gabapentin, again starting at a low dose of 300mgs daily and actively titrating it upwards. However this can take up to 4 - 6 weeks to have its full effect. The two drugs can also be used in combination with one another to enhance their effectiveness, although inevitably this also increases the side effect profile. Specialist pain clinics often seem to start with pregabalin, which is a precursor of gabapentin. This does appear to have a better side effect profile but is also significantly more expensive so it should probably be reserved for those who have not tolerated gabapentin.

Side effects to be particularly aware of are constipation and drowsiness, particularly in combination with opioids. Postural hypotension can also be an issue and is a significant cause of falls in the elderly.^14,15

Joan starts amitriptyline 10mgs, which she increases to 25mg after three days. She takes it at 9pm each night and continues with her regular co-dydramol. She finds that she needs to increase her Movicol to each day but otherwise has no problems. However her daughter reports that Joan is having increasing difficulty in managing her medications.

Pain regimens can become increasingly complex for older individuals to manage and so need to be reviewed on a regular basis to ensure that concordance is maximised and side effects minimised. It is also worth checking that patients are not continuing to supplement their prescribed medication with OTC preparations as this can contribute to unintentional paracetamol overdose or inappropriate long-term use of NSAIDS. Also, as osteoarthritis can become widespread there may be issues with gaining access to medication if it is dispensed in childproof containers. Visual impairment may also cause difficulties distinguishing between different medications.

BREAKTHROUGH PAIN

You arrange for Joan to have her medication dispensed in a weekly dosette box. This works well until Joan has a fall downstairs and sustains a fractured neck of femur. Joan undergoes a hemi-arthroplasty but continues to complain of widespread pain. On her discharge from hospital she is now on sustained release morphine 30mgs twice daily, amitriptyline 50mgs nocte and Movicol. She also has some oral morphine solution.

While Joan is in hospital it appears that her paracetamol has been discontinued. It is worth considering restarting this as it can have a synergistic effect with morphine and so enables the dose of morphine to be decreased. However, it is also worth encouraging Joan to make use of her oral morphine solution so as to get a clear picture of what dose she actually needs to become pain free, as this can then be converted to a sustained release preparation. Ideally she should be using 1/6th of her daily dose as her breakthrough dose; in this instance that would be 10mg.

NEXT STEPS

Joan restarts her paracetamol and also adds in the oral morphine solution on a prn basis. Over the next three days she uses an additional 20mgs of morphine in each 24 hour period. However, her daughter says that although Joan's pain appears to be well controlled she is not sure that she is managing the tablets properly despite her dosette box. Consequently you discuss Joan's case with one of the GPs as to how best to address Joan's pain needs.

Oral medication is clearly the route of choice for most patients both for its ease of use and also as it is often the most cost effective formulation. However, there can sometimes be a role for other routes of administration. In this instance it may be worth considering changing Joan onto a patch as this is much less dependent upon her remembering to take it. However you need to remember that it is only the opioid that is being converted and Joan will still need to continue oral medication if you feel that the paracetamol or, more likely, the amitriptyline still have a role to play. There are two main choices of patch - fentanyl, which needs to be applied twice weekly and buprenorphine, which is applied either twice weekly or weekly, depending upon the formulation.

After discussion with the GP you conclude together that a buprenorphine patch would suit Joan best as her daughter can apply this when she comes to visit. Given Joan's current morphine dose, the starting dose of the patch should be 52.5 microgram/hour. (Table 1) For the first patch you show her daughter how to apply it at the same time as Joan takes her last sustained morphine preparation. To make it easier for Joan, you both decide to stop the paracetamol but continue the amitriptyline so Joan is just taking one 50mg tablet each evening. This works really well for Joan and she is even able to decrease her laxative usage. You also arrange for a local befriending volunteer to come and visit Joan twice a week.

CONCLUSION

Managing pain is a complex mixture of both pharmacological and non-pharmacological methods. It is likely that in Joan's case the decreased social isolation from the befriending scheme is at least as important as maximising her analgesic therapy. So in any individual with chronic pain, particularly if their analgesic requirements appear to be escalating, it is worth ensuring that you take a holistic approach to their assessment. This means addressing the social and psychological components of their condition as well as just the possible physical causes of pain. In younger patients with chronic pain it is also worth considering formal pain management programmes that will take all these aspects into consideration. Mindfulness also has an increasing role to play.¹⁶

REFERENCES

1. Hughes, D Painkillers cost the NHS in England £442 million a year http://www.bbc.co.uk/news/health-15627365 (accessed 20 March 2012)

2. Arthritis Research UK. Disability and musculoskeletal problems

http://www.arthritisresearchuk.org/arthritis-information/data-and-statistics/musculoskeletal-pain-and-disability/disability-and-musculoskeletal-problems.aspx (accessed 2 April 2012)

3. Jones, J.R., Huxtable, C.S. and Hodgson, J.T. (2006)

Self-reported work-related illness in 2004/05: Results from the Labour Force Survey.

Health and Safety Executive, National Statistics

4. Silverstein, M. (2008). Meeting the challenges of an aging workforce. American Journal of Industrial Medicine, 51, 269-280

5. The Care and Management of Osteoarthritis in Adults http://www.nice.org.uk/CG59 (accessed 20 March 2012)

6. www.orthopaedicscores.com (accessed 20 March 2012)

7. Pain scales in multiple languages http://www.britishpainsociety.org/pub_pain_scales.htm (accessed March 20 2012)

8. OTC Directory PAGB (available on-line at www.medicinechestonline.com)

9. Cunningham R, et al. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. Journal of Hospital Infection 2003 54: 243-245

10. Can the use of proton pump inhibitors increase the risk of community acquired pneumonia infection? http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Medicines-Q--A/Can-the-use-of-proton-pump-inhibitors-increase-the-risk-of-community-acquired-pneumonia-infection/ (accessed 20 March 2012)

11. The Analgesic Ladder http:// www.patient.co.uk/doctor/Pain-and-Pain-Relief-(Analgesics).htm (accessed 20 March 2012)

12. de Craen AJ, Di Giulio G, Lampe-Schoenmaeckers JE, et al. Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review. BMJ 1996 Aug 10;313(7053):321-5.

13. The management of persistent pain in older persons J Am Geriatr Soc 2002 Jun;50(6 Suppl):S205-24.

14. T Kwok, J Liddle, IR Hastie. Postural Hypotension and Falls Postgrad MedJ3 1995; 71: 278-283

15. Recurrent Falls http://www.patient.co.uk/doctor/Recurrent-Falls.htm (accessed April 2 2012)

16. Chronic pain http://www.moodjuice.scot.nhs.uk/chronicpain.asp (accessed March 20 2012)