Is pregabalin being prescribed for pain other than neuropathic pain? Is it being used according to guidelines and the best available evidence? Once prescribed, are patients receiving optimal benefit?

Providing health professionals with answers to these questions is essential for ensuring accurate diagnosis, appropriate prescribing of neuropathic pain medicines and improved quality of life of patients with neuropathic pain.

Line chart showing growth in prescribing of pregabalin since PBS listing in 2013, while amitriptyline and duloxetine stay steady, 2006-16

Figure 1: PBS prescription volumes for pregabalin, amitriptyline and duloxetine, July 2006 to Jun 2016.1

The number of pregabalin prescriptions in Australia was turbocharged when it was PBS-listed in March 2013. From fewer than 200,000 prescriptions in 2012–13, it leapt to 3.26 million in 2015–16 and 3.61 million in 2016–17.1

A 2015 Drug Utilisation Sub-committee (DUSC) report on the first 2 years after pregabalin’s PBS listing found that the number of prescriptions was much higher than predicted. It suggested that prescribing for pain other than neuropathic pain may have been a contributing factor.2

Prescribing pregabalin for non-neuropathic low back pain (LBP) has been a standout concern. This may be happening due to misunderstanding of neuropathic pain among prescribers, as well as the effects of advertising.3 It’s also been suggested that pregabalin is being used for many types of acute and chronic non-neuropathic pain, such as osteoarthritis, in a desperate move to get patients off opioids.4

Essential to understand neuropathic pain

When diagnosing and managing pain, it is essential to understand that there are two types of pain: nociceptive and neuropathic. 

  • Nociceptive pain arises from actual or threatened damage to non-neural tissue (eg ligament, muscle) and is due to the activation of nociceptors. 
  • Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system.5
Find out more from the International Association for the Study of Pain’s taxonomy

With LBP, for example, nociceptive pain usually presents as referred pain, where pain is concentrated proximally in the buttock and thigh but may spread below the knee.6 

Hand holding a painful heel of foot, with nerves highlighted.

With neuropathic pain, which affects around 10%–17% of LBP cases presenting to primary care,7-9 pain is concentrated more in the leg10 and is called radicular pain (or radiculopathy when the main symptoms include numbness or muscle weakness).11 

Most importantly, the differential diagnosis of neuropathic pain type is crucial, because it requires a different therapeutic approach from nociceptive pain.12 An accurate diagnosis of neuropathic pain is needed to enable appropriate prescribing of pregabalin and other neuropathic pain medicines.

Need to follow guidelines and evidence

It appears that pregabalin is being inappropriately prescribed first-line in preference to amitriptyline and other neuropathic pain medicines.

In general, pregabalin has become the clear number one medicine since its PBS listing. (see Figure 1).2

More specifically, pregabalin is PBS-restricted to neuropathic pain refractory to other drugs,13 however the 2015 DUSC report found that 45% of patients were initiated on pregabalin without being on a prior drug regimen.2

Therapeutic Guidelines Ltd logo

These patients may have been refractory to over-the-counter (OTC) or PBS-listed paracetamol or NSAIDs, and hence, fulfilled the restriction criteria.2 But if so, initiating on pregabalin goes against the recommendation of amitriptyline as first line and pregabalin as second line in Australian guidelines.14,15

International Association for the Study of Pain logo

International guidelines such as from the International Association for the Study of Pain (IASP)16 and UK National Institute for Health and Care Excellence (NICE)17 do differ from Australian guidelines by including amitriptyline, duloxetine and pregabalin as first-line medicines. 

National Institute for Health and Clinical Excellence (NICE) UK logo

But regardless, no guidelines recommend prescribing pregabalin in preference over the other medicines. In fact, amitriptyline is the only medicine that’s first-line in Australian and international guidelines.14-19

Best practice on the choice of medicine involves the prescriber weighing up multiple factors. These include efficacy, adverse effect profile, potential for drug interactions, comorbidities, ability of the patient to adhere to a potentially complex medicine regimen, risk of medicine abuse and/or intentional or accidental overdose, and cost.14,18,20,21 

Achieve optimal benefit

Another concern with the pharmacological management of neuropathic pain is that the optimal benefits of neuropathic pain medicines are not being achieved. The 2015 DUSC report found, for example, that the discontinuation rate for pregabalin was 44%. This was nearly twice as high as expected.2

Rather than adverse effects being the cause, it suggested that the starting doses being prescribed may not have been adequate, leading to a lack of effect. It also highlighted a knowledge gap among prescribers on reaching maximum effective dose, including the need to up-titrate and allow an adequate trial period.2

What to do? 

NPS MedicineWise has a program titled Neuropathic pain: Touchpoints for effective diagnosis and management that provides a simple approach to diagnosing and treating neuropathic pain with confidence. 

Find out more about our educational visit on neuropathic pain

Thumbnail of the flyer for the NPS MedicineWise Neuropathic pain visits


Access our free accredited CPD activities on neuropathic pain to find what is most suitable for you.

References

  1. Medicare Australia. Requested PBS & RPBS Items processed from July 2012 to June 2017. Canberra: Department of Human Services, 2018, (accessed 16 January 2018).
  2. Drug utilisation sub-committee. Pregabalin: 24 month predicted versus actual analysis (October 2015). Canberra: DUSC, 2015, (accessed 1 September 2017).
  3. Goh S. Asking the wrong questions: another elephant in the room? BMJ. 2015;350.
  4. Goodman C, Brett A. Gabapentin and pregabalin for pain — is increased prescribing a cause for concern? N Engl J Med 2017;377:411-3.
  5. International Association for the Study of Pain. Taxonomy. Washington: IASP, 2012, (accessed 14 August 2017).
  6. International Association for the Study of Pain. Spinal pain, section 1: Spinal and radicular pain. Classification of Chronic Pain. Washington DC, USA: IASP, 2014, (accessed 31 October 2017).
  7. Hush JM, Marcuzzi A. Prevalence of neuropathic features of back pain in clinical populations: implications for the diagnostic triage paradigm. Pain Manag 2012;2:363-72.
  8. Bardin LD, King P, Maher CG. Diagnostic triage for low back pain: a practical approach for primary care. Med J Aust 2017;206:268-73.
  9. Maher C. Re: prevalence of neuropathic back pain. Personal communication. 31 October 2017.
  10. Freynhagen R, Baron R. The evaluation of neuropathic components in low back pain. Curr Pain Headache Rep 2009;13:185-90.
  11. Bogduk N. On the definitions and physiology of back pain, referred pain, and radicular pain. Pain 2009;147:17-9.
  12. Haanpää ML, Backonja MM, Bennett MI, et al. Assessment of neuropathic pain in primary care. Am J Med 2009;122:S13-21.
  13. Pharmaceutical Benefits Scheme. Pregabalin. Canberra: Department of Health Australia, 2017, (accessed 21 September 2017).
  14. Neurology Expert Group. Therapeutic Guidelines: Neuropathic pain version 5. West Melbourne: Therapeutic Guidelines Limited, 2011, (accessed 30 November 2017).
  15. Western Australian Therapeutic Advisory Group. Advisory Note: Neuropathic Pain Guidelines. Perth: Department of Health, 2017, (accessed 17 August 2017).
  16. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015;14:162-73.
  17. National Institute for Health and Care Excellence (NICE). Neuropathic pain in adults: pharmacological management in nonspecialist settings. Clinical guidance (CG) 173. UK: 2013 (updated 2014), (accessed 1 September 2017).
  18. Endocrinology Expert Group. Therapeutic Guidelines: Diabetes complications. West Melbourne: Therapeutic Guidelines Limited, 2013, (accessed 25 August 2017).
  19. Mu A, Weinberg E, Moulin DE, et al. Pharmacologic management of chronic neuropathic pain: Review of the Canadian Pain Society consensus statement. Can Fam Physician 2017;63:844-52.
  20. Veterans’ Medicines Advice and Therapeutics Education Services (MATES). Managing neuropathic pain: a stepwise approach. Australia, 2013, (accessed 1 September 2017).
  21. Dworkin RH, O'Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132:237-51.