This week, NICE published a clinical guideline on the pharmacological management of neuropathic pain in adults to amalgamate current evidence on the effectiveness, cost-effectiveness and adverse reactions of the drugs currently used.
The recommendations will help GPs determine the best treatments for adults with this difficult and distressing condition. The guideline also raises awareness of the diagnosis and the capacity in which neuropathic pain can be successfully treated in non-specialist healthcare settings.
What is neuropathic pain?
Neuropathic pain is defined as 'pain arising as a direct consequence of a lesion or disease affecting the somatosensory system'.1
Unlike nociceptive pain, neuropathy is associated with 'shooting' or 'burning' pains, sensations similar to electric shocks, and abnormal responses to touch, heat or cold.
It also tends to be more severe, can be associated with poorer general health and is usually resistant to standard analgesic management.
Common causes of peripheral neuropathic pain encountered in primary and community care include peripheral diabetic neuropathy (PDN), postherpetic neuralgia and lumbar radiculopathy. Central neuropathic pain can be associated with stroke and multiple sclerosis, among other common conditions.
There is increasing evidence that the split between nociceptive and neuropathic pain is not entirely clear, and many pains are actually caused by a combination of these mechanisms; for example, back pain and post-surgical pain.
Why are these guidelines needed?
Although there are different causes of neuropathic pain, generally they can be treated using the same drug classes; however, the drugs used are generally not the same as those used successfully as first-line treatments for other types of pain.
However, evidence from literature and patient groups indicates that neuropathic pain is often treated away from primary care.
For example, it has been estimated that around 8 per cent of the adult population may have some pain with neuropathic features,2 and may therefore benefit from specific treatment; however, few GPs will have prescribed this proportion of their practice population drugs used for neuropathic pain (including tricyclic antidepressants and anticonvulsants).
This may be due to the diagnosis being overlooked, or partly through fear or risk of side- effects of these drugs.
There is a consensus regarding how neuropathic pain can be effectively assessed in primary care3 and we must share the best ways that patients should be treated for this, while minimising any adverse reactions.
Moreover, there will be a wide range of cost implications for the potentially effective drugs, so a comparison of their cost effectiveness is also important.
What do the guidelines cover?
The clinical guideline explicitly examines the drugs that should be used in non-specialist NHS healthcare settings - primary and community care settings, or a hospital clinic that does not specialise in pain or neurology.
Although recognising their importance, non-pharmacological treatments were not considered in the scope of this guideline and the drug treatments recommended are only for neuropathic pain in adult patients.
Antidepressants, anticonvulsants and opioids were included in the literature search, as were topical treatments (capsaicin and lidocaine).
The guideline only considered RCTs and effective treatment was judged in the event of a 30 per cent or a 50 per cent reported reduction in a pain scale score (depending on the study); improved quality of life was also considered.
Adverse reactions assessed included treatment withdrawal because of side-effects; specific side-effects were also assessed.
Additionally, a health technology assessment report describing a detailed cost-effectiveness study of drugs used in neuropathic pain was critically appraised and applied to the review.
What are the main recommendations?
As with all robust systematic reviews, the RCTs identified were rigorously assessed for their quality in the development of this guideline.
As a result, the bulk of RCTs included relate to more recently developed drugs. There was a relative paucity of good trials relating to some of the drugs more commonly used in primary care, such as carbamazepine and amitriptyline. The recommendations reflect this, but nonetheless are valid and of immediate practical help.
The main recommendations for drug treatment of neuro-pathic pain in non-specialist settings are (see the NICE guideline for further details):
1. First line: amitriptyline pregabalin (duloxetine in PDN, amitriptyline if contraindicated).
2. Second line: if first line was amitriptyline switch to or combine with pregabalin. If first line was pregabalin switch to or combine with amitriptyline (or other tricyclic antidepressant).
For PDN, if first line was duloxetine, switch to amitriptyline or pregabalin, or combine with pregabalin. If first line was with amitriptyline switch to or combine with pregabalin.
3. Third line: consider a referral to pain or condition-specific specialist. Consider adding tramadol alone or in combination with second-line treatment in the interim.
Consider topical lidocaine if the patient is unable to take medication orally.
Patients currently on effective treatment for neuropathic pain that falls outside of these recommendations should not have their treatment changed.
Neuropathic pain is a complex condition whereby the causes and treatments are the subject of much ongoing research.
The NICE clinical guideline provides GPs and other relevant healthcare professionals with a useful and clearly defined evidence-based approach, setting out the drug treatments which have been proven to work the best on patients.
The absence of specific recommendations relating to carbamazepine may be surprising, but this reflects a lack of recent or relevant high quality RCTs available at the time.
Furthermore, the recommendation that strong opiates should be offered without specialist involvement may create some discussion, but again this is due to a lack of available evidence to support their use in non-specialist settings, as well as the considerable risk of dependency.
GPs can still manage the use of opioids once they have been prescribed by a specialist, and tramadol is recommended as a third-line treatment option, while specialist referral is being sought.
Although more expensive than its counterpart gabapentin, pregabalin was associated with fewer side-effects and was deemed to be more cost-effective as it is easier to administer.
There was insufficient evidence available for meaningful head-to-head comparison of drugs.
As with all guidance, the recommendations of NICE are not definitive and much more research is needed regarding the pharmacological management of neuropathic pain; these areas have been highlighted for researchers to consider.
However, if implemented, the guideline has the potential to really improve the treatment and management of an important, distressing and very often unrecognised condition in primary and community healthcare settings.
- Professor Smith is professor of primary care medicine at the Centre of Academic Primary Care, University of Aberdeen and a member of the guideline development group for this NICE guideline.
NICE. Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings
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1. Loeser JD, Treede RD. The Kyoto protocol of IASP Basic Pain Terminology. Pain 2008; 137(3): 473-7.
2. Torrance N, Smith BH, Bennett MI, Lee AJ. The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey. J Pain 2006; 7(4): 281-9.
3. Haanpaa M, Backonja M-M, Bennett M, et al. Assessment of neuropathic pain in primary care. Am J Med 2009; 122: S13 - S31.
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Item Code: MINT/PPR-12008
Date of Preparation: May 2012