Neuropathic pain in adults: pharmacological management in non-specialist settings

This guideline covers managing neuropathic pain (nerve pain) with pharmacological treatments (drugs) in adults in non-specialist settings. It aims to improve quality of life for people with conditions such as neuralgia, shingles and diabetic neuropathy by reducing pain and promoting increased participation in all aspects of daily living. The guideline sets out how drug treatments for neuropathic pain differ from traditional pain management.

# Introduction
Pain is an unpleasant sensory and emotional experience that can have a significant impact on a person's quality of life, general health, psychological health, and social and economic wellbeing. The International Association for the Study of Pain (IASP 2011) defines neuropathic pain as 'pain caused by a lesion or disease of the somatosensory nervous system'. Central neuropathic pain is defined as 'pain caused by a lesion or disease of the central somatosensory nervous system', and peripheral neuropathic pain is defined as 'pain caused by a lesion or disease of the peripheral somatosensory nervous system'.
Neuropathic pain is very challenging to manage because of the heterogeneity of its aetiologies, symptoms and underlying mechanisms (Beniczky et al. 2005). There is often uncertainty regarding the nature and exact location of a lesion or health condition associated with neuropathic pain, particularly in non-specialist settings. Examples of common conditions that have peripheral neuropathic pain as a symptom are painful diabetic neuropathy, post-herpetic neuralgia, trigeminal neuralgia, post-surgical chronic neuropathic pain, and neuropathic cancer pain (such as, chemotherapy-induced neuropathy, neuropathy secondary to tumour antigens, or caused by direct invasion or compression of neural structures). Examples of conditions that can cause central neuropathic pain include stroke, spinal cord injury and multiple sclerosis. Neuropathic pain can be intermittent or constant, and spontaneous or provoked. Typical descriptions of the pain include terms such as shooting, stabbing, like an electric shock, burning, tingling, tight, numb, prickling, itching and a sensation of pins and needles. People may also describe symptoms of allodynia (pain caused by a stimulus that does not normally provoke pain), hyperalgesia (an increased response to a stimulus that is normally painful), anaesthesia dolorosa (pain felt in an anaesthetic  area or region), and sensory gain or loss (IASP 2011).
A review of the epidemiology of chronic pain found that there is still no accurate estimate available for the population prevalence of neuropathic pain (Smith et al. 2012). For example, the prevalence of neuropathic pain overall has been estimated to be between 6% and 8%, from postal surveys in France (Bouhassira 2008) and the UK (Torrance 2006). However, these estimates came from studies using different questionnaires. Other condition-specific studies have also mirrored the heterogeneous nature of neuropathic pain. For example, painful diabetic neuropathy is estimated to affect between 16% and 26% of people with diabetes (Jensen et al. 2006; Ziegler 2008). Prevalence estimates for postherpetic neuralgia range from 8% to 19% of people with herpes zoster when defined as pain at 1 month after rash onset, and 8% when defined as pain at 3 months after rash onset (Schmader 2002).
The development of chronic pain after surgery is also fairly common, with estimates of prevalence ranging from 10% to 50% after many common operations (Shipton 2008). This pain is severe in between 2% and 10% of this subgroup of patients, and many of the clinical features closely resemble those of neuropathic pain (Jung et al. 2004; Mikkelsen et al. 2004; Kehlet et al. 2006). Furthermore, a study of 362,693 computerised records in primary care from the Netherlands estimated the annual incidence of neuropathic pain in the general population to be almost 1% (Dieleman et al. 2008). This considerable variability in estimates of the prevalence and incidence of neuropathic pain and similar conditions from general population studies is likely to be because of differences in the definitions of neuropathic pain, methods of assessment and patient selection (Smith and Torrance 2010, Smith et al. 2012).
A number of pharmacological treatments can be used to manage neuropathic pain outside of specialist pain management services. However, there is considerable variation in how treatment is initiated, the dosages used and the order in which drugs are introduced, whether therapeutic doses are achieved and whether there is correct sequencing of therapeutic classes. A further issue is that a number of commonly used treatments are unlicensed for treating neuropathic pain, which may limit their use. These factors may lead to inadequate pain control, with considerable morbidity.
Commonly used pharmacological treatments include antidepressants (tricyclic antidepressants , selective serotonin reuptake inhibitors  and serotoninnorepinephrine reuptake inhibitors ), antiepileptic (anticonvulsant) drugs, topical treatments and opioid analgesics. In addition to their potential benefits, all of these drug classes are associated with various adverse effects.
This short clinical guideline aims to improve the care of adults with neuropathic pain by making evidence-based recommendations on the pharmacological management of neuropathic pain outside of specialist pain management services. A further aim is to ensure that people who require specialist assessment and interventions are referred appropriately and in a timely fashion to a specialist pain management service and/or other conditionspecific services.

# Drug recommendations
For all drugs, recommendations are based on evidence of clinical and cost effectiveness and reflect whether their use for the management of neuropathic pain is a good use of NHS resources. This guideline should be used in conjunction with clinical judgement and decision-making appropriate for the individual patient.
The guideline will assume that prescribers will use a drug's summary of product characteristics (SPC) and the British National Formulary (BNF) to inform decisions made with individual patients (this includes obtaining information on special warnings, precautions for use, contraindications and adverse effects of pharmacological treatments).
This guideline recommends some drugs for indications for which they do not have a UK marketing authorisation at the date of publication, if there is good evidence to support that use. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. The patient (or those with authority to give consent on their behalf) should provide informed consent, which should be documented. See the General Medical Council's Good practice in prescribing and managing medicines and devices (2013). Where recommendations have been made for the use of drugs outside their licensed indications (off-label use), these drugs are marked with a footnote in the recommendations.

# Healthcare setting for this guideline
The recommendations in this clinical guideline are for the pharmacological management of neuropathic pain in non-specialist settings only. The Guideline Development Group acknowledged that there are other pharmacological and non-pharmacological treatments that will be of benefit to people with neuropathic pain, within different care pathways in different settings.

# Terms used in this guideline

## Condition-specific service
A condition-specific service is a specialist service that provides treatment for the underlying health condition that is causing neuropathic pain. Examples include neurology, diabetology and oncology services.

## Non-specialist settings
These are primary and secondary care services that do not provide specialist pain services. Non-specialist settings include general practice, general community care and hospital care.

## Participation
The World Health Organization ICF (International Classification of Functioning, Disability and Health, 2001) defines participation as 'A person's involvement in a life situation.' It includes the following domains: learning and applying knowledge, general tasks and demands, mobility, self-care, domestic life, interpersonal interactions and relationships, major life areas, community, and social and civil life.

## Specialist pain services
These are those that that provide comprehensive assessment and multi-modal management of all types of pain, including neuropathic pain.# Recommendations
People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.
Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including offlabel use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.
The following guidance is based on the best available evidence. The full guideline gives details of the methods and the evidence used to develop the guidance.

# List of all recommendations

## Key principles of care
For guidance on safe prescribing and managing withdrawal of antidepressants and dependence-forming medicines, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.
When agreeing a treatment plan with the person, take into account their concerns and expectations, and discuss:
the severity of the pain, and its impact on lifestyle, daily activities (including sleep disturbance) and participation
the underlying cause of the pain and whether this condition has deteriorated
why a particular pharmacological treatment is being offered
the benefits and possible adverse effects of pharmacological treatments, taking into account any physical or psychological problems, and concurrent medications
the importance of dosage titration and the titration process, providing the person with individualised information and advice
coping strategies for pain and for possible adverse effects of treatment
non-pharmacological treatments, for example, physical and psychological therapies (which may be offered through a rehabilitation service) and surgery (which may be offered through specialist services).For more information about involving people in decisions and supporting adherence, see the NICE guideline on medicines adherence.
Consider referring the person to a specialist pain service and/or a condition-specific service at any stage, including at initial presentation and at the regular clinical reviews (see recommendation 1.1.6), if:
they have severe pain or
their pain significantly limits their lifestyle, daily activities (including sleep disturbance) and participation or
their underlying health condition has deteriorated.
Continue existing treatments for people whose neuropathic pain is already effectively managed, taking into account the need for regular clinical reviews (see recommendation 1.1.6).
When introducing a new treatment, take into account any overlap with the old treatments to avoid deterioration in pain control.
After starting or changing a treatment, carry out an early clinical review of dosage titration, tolerability and adverse effects to assess the suitability of the chosen treatment.
Carry out regular clinical reviews to assess and monitor the effectiveness of the treatment. Each review should include an assessment of:
pain control
impact on lifestyle, daily activities (including sleep disturbance) and participation
physical and psychological wellbeing
adverse effects
continued need for treatment.
When withdrawing or switching treatment, taper the withdrawal regimen to take account of dosage and any discontinuation symptoms.

## Treatment
For guidance on safe prescribing and managing withdrawal of antidepressants and dependence-forming medicines, see NICE's guideline on medicines associated with dependence or withdrawal symptoms.
For advice on treating sciatica, see the NICE guideline on low back pain and sciatica and the September 2020 update information.
Offer a choice of amitriptyline, duloxetine, gabapentin or pregabalin as initial treatment for neuropathic pain (except trigeminal neuralgia). See additional information for more on duloxetine, gabapentin and pregabalin.
If the initial treatment is not effective or is not tolerated, offer one of the remaining 3 drugs, and consider switching again if the second and third drugs tried are also not effective or not tolerated.
Consider tramadol only if acute rescue therapy is needed (see recommendation 1.1.12 about longterm use).
Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments. See additional information for more on capsaicin cream.
Do not start the following to treat neuropathic pain in non-specialist settings, unless advised by a specialist to do so:
cannabis sativa extract
capsaicin patch
lacosamide
lamotrigine
levetiracetam
morphine
-xcarbazepine
topiramate
tramadol (this is referring to long-term use; see recommendation 1.1.10 for short-term use)
venlafaxinesodium valproate (follow the MHRA safety advice on valproate use by women and girls and antiepileptic drugs in pregnancy). December 2022: The MHRA has issued new safety advice on risks associated with valproate for anyone under 55.
Offer carbamazepine as initial treatment for trigeminal neuralgia. Follow the MHRA safety advice on antiepileptic drugs in pregnancy. 
If initial treatment with carbamazepine is not effective, is not tolerated or is contraindicated, consider seeking expert advice from a specialist and consider early referral to a specialist pain service or a condition-specific service.# Additional information

# Recommendation 1.1.8
In November 2013, duloxetine was licensed for diabetic peripheral neuropathic pain only, and gabapentin was licensed for peripheral neuropathic pain only, so use for other conditions was off label. See NICE's information on prescribing medicines.
Pregabalin and gabapentin are Class C controlled substances (under the Misuse of Drugs Act 1971) and Schedule 3 under the Misuse of Drugs Regulations 2001. Evaluate patients carefully for a history of drug abuse before prescribing and observe patients for development of signs of abuse and dependence (MHRA, Drug Safety Update April 2019).
Follow the MHRA safety advice on pregabalin in pregnancy.
Return to recommendation 1.1.8

# Recommendation 1.1.11
In November 2013), capsaicin cream (Axsain) was licensed for post-herpetic neuralgia and painful diabetic peripheral polyneuropathy only, so use for other conditions was off label. The SPC states that this should only be used for painful diabetic peripheral polyneuropathy 'under the direct supervision of a hospital consultant who has access to specialist resources'. See NICE's information on prescribing medicines.
Return to recommendation 1.1.11# Research recommendations
The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future.

# Monotherapy versus combination therapy for treating neuropathic pain
What is the clinical effectiveness, cost effectiveness and tolerability of pharmacological monotherapy compared with combination therapy for treating neuropathic pain?

## Why this is important
Combination therapy is commonly prescribed for neuropathic pain. It may also be a helpful option as a stepwise approach if initially used drugs are insufficient at reducing pain. Combination therapy may also result in better tolerability because smaller doses of individual drugs are often used when combined with other drugs. However, there is a lack of trial evidence comparing the clinical and cost effectiveness and tolerability of different drug combinations. Further research should be conducted as described in table 1 below.
Criterion
Explanation
Population
Adults with a diagnosis of neuropathic pain. Neuropathic pain conditions include:
Central neuropathic pain/central pain
Complex regional pain syndromes
Compression neuropathies/nerve compression syndromes
Facial neuralgia
HIV-related neuropathy
Mixed neuropathic pain
Multiple sclerosis
Neurogenic pain
Neuropathic cancer pain/cancer pain
Neuropathic pain
Painful diabetic neuropathy/diabetic neuropathy
Peripheral nerve injury
Peripheral nervous system disease/neuropathies
Phantom limb pain
Polyneuropathies
Post-amputation pain
Post-herpetic neuralgia
Post-stroke pain
Post-treatment/post-surgery/post-operative pain
Radiculopathies/radicular pain
Spinal cord diseases
Spinal cord injury
Trigeminal neuralgia
Intervention(s)
Pharmacological agents as monotherapy or combination therapy. The pharmacological agents include:
Amitriptyline
Clomipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Nortriptyline
Trimipramine
Citalopram
Escitalopram
Fluoxetine
Paroxetine
Sertraline
Duloxetine
Mirtazapine
Reboxetine
Trazodone
Venlafaxine
Carbamazepine
Gabapentin
Lacosamide
Lamotrigine
Levetiracetam
Oxcarbazepine
Phenytoin
Pregabalin
Valproate
Topiramate
Buprenorphine
Co-codamol
Co-dydramol
Dihydrocodeine
Fentanyl
Morphine
Oxycodone
Oxycodone with naloxone
Tapentadol
Tramadol
Cannabis sativa extract
Flecainide
-HT1-receptor agonists
Topical capsaicin
Topical lidocaine
Comparator(s)
Any of the above listed pharmacological agents as monotherapy compared with any combinations of the above listed pharmacological agents as combination therapy.
Outcome(s)
Patient-reported global improvement (on a 7-point scale)
Patient-reported improvement in daily physical and emotional functioning including sleep (on a 9-point scale)
At least 30% and 50% pain reduction (on a 11-point Numerical rating scale  scale)
Mean change from baseline pain scores (on a 11-NRS scale)
Withdrawal due to adverse effects of the pharmacological agents Adverse effects of the pharmacological agents
HRQoL (for example, EQ-5D, WHOQoL- BREF and London Handicap Scale)
Study design
Parallel triple-blinded randomised controlled trial of at least 12weeks' study period (they should not have enriched enrolment).
All participants should have a 'wash-out' period after assessment for inclusion in the study and before randomisation.
Baseline pain scores between arms should be equal and clearly documented.
Concomitant medications should not be allowed or should be restricted and maintained at a stable dose in the study. Difference in concomitant pain medication usage at baseline should be clearly described in each trial arm, including details of the number of patients on different drugs.
Rescue pain medications should either not be allowed or, if used, their use should be accurately documented.

# Relationship between symptoms, cause of neuropathic pain and its treatment
Is response to pharmacological treatment predicted more reliably by underlying aetiology or by symptom characteristics?

## Why this is important
There is little evidence about whether certain symptoms that present in healthcare settings, or whether different neuropathic pain conditions with different aetiologies, respond differently to different treatments. Current evidence is typically focused on particular conditions and is limited to particular drugs. Further research should be conducted as described in table 2 below.
Criterion
Explanation
Population
Adults with a diagnosis of neuropathic pain. Neuropathic pain conditions include:
Central neuropathic pain/central pain
Complex regional pain syndromes
Compression neuropathies/nerve compression syndromes
Facial neuralgia
HIV-related neuropathy
Mixed neuropathic pain
Multiple sclerosis
Neurogenic pain
Neuropathic cancer pain/cancer pain
Neuropathic pain
Painful diabetic neuropathy/diabetic neuropathy
Peripheral nerve injury
Peripheral nervous system disease/neuropathies
Phantom limb pain
Polyneuropathies
Post-amputation pain
Post-herpetic neuralgia
Post-stroke pain
Post-treatment/post-surgery/post-operative pain
Radiculopathies/radicular pain
Spinal cord diseases
Spinal cord injury
Trigeminal neuralgia
Intervention(s)
Any pharmacological agents as monotherapy or combination therapy (see research recommendation B1).
Comparator(s)
Same pharmacological agents chosen as the main treatments of interest but compare the treatment response across different groups of participants with different neuropathic pain conditions or underlying aetiology.
Outcome(s)
Patient-reported global improvement (on a 7-point scale)
Patient-reported improvement in daily physical and emotional functioning including sleep (on a 9-point scale)
At least 30% and 50% pain reduction (on a 11-NRS scale)
Mean change from baseline pain scores (on a 11-NRS scale)
Withdrawal due to adverse effects of the pharmacological agents Adverse effects of the pharmacological agents
HRQoL (for example, EQ-5D, WHOQoL- BREF and London Handicap Scale)
Study design
Prospective cohort study
All participants should have a 'wash-out' period before assessment for inclusion in the study.
Baseline pain scores between arms should be equal and clearly documented.
Concomitant medications should not be allowed, or should be restricted and maintained at stable dose during the study. Difference in concomitant pain medication usage at baseline should be clearly described in each trial arm, including details of the number of patients on different drugs.
Rescue pain medications either not be allowed or, if used, their use should be accurately documented.

# Carbamazepine for treating trigeminal neuralgia
What is the clinical and cost effectiveness of carbamazepine as initial treatment for trigeminal neuralgia compared with other pharmacological treatments?

## Why this is important
Carbamazepine has been the standard treatment for trigeminal neuralgia since the 1960s. Despite the lack of trial evidence, it is perceived by clinicians to be efficacious. Further research should be conducted as described in table 3 below.
Criterion
Explanation
Population
Adults with a diagnosis of trigeminal neuralgia.
Intervention(s)
Carbamazepine as monotherapy.
Comparator(s)
Any of the below listed pharmacological agents as monotherapy or combinations. The pharmacological agents include:
Amitriptyline
Clomipramine
Dosulepin (dothiepin)
Doxepin
Imipramine
Lofepramine
Nortriptyline
Trimipramine
Citalopram
Escitalopram
Fluoxetine
Paroxetine
Sertraline
Duloxetine
Mirtazapine
Reboxetine
Trazodone
Venlafaxine
Carbamazepine
Gabapentin
Lacosamide
Lamotrigine
Levetiracetam
Oxcarbazepine
Phenytoin
Pregabalin
Valproate
Topiramate
Buprenorphine
Co-codamol
Co-dydramol
Dihydrocodeine
Fentanyl
Morphine
Oxycodone
Oxycodone with naloxone
Tapentadol
Tramadol
Cannabis sativa extract
Flecainide
-HT1-receptor agonists
Topical capsaicin
Topical lidocaine
Outcome(s)
Patient-reported global improvement (on a 7-point scale)
Patient-reported improvement in daily physical and emotional functioning including sleep (on a 9-point scale)
At least 30% and 50% pain reduction (on a 11-NRS scale)
Mean change from baseline pain scores (on a 11-NRS scale)
Withdrawal due to adverse effects of the pharmacological agents Adverse effects of the pharmacological agents
HRQoL (for example, EQ-5D, WHOQoL- BREF and London Handicap Scale)
Study design
Parallel triple-blinded randomised controlled trial of at least 12 weeks' study period (they should not have enriched enrolment).
All participants should have a 'wash-out' period after assessment for inclusion in the study and before randomisation.
Baseline pain scores between arms should be equal and clearly documented.
Concomitant medications should not be allowed or should be restricted and maintained at a stable dose during the study. Difference in concomitant pain medication usage at baseline should be clearly described in each trial arm, including details of the number of patients on different drugs.
Rescue pain medications either not be allowed or, if used, their use should be accurately documented.

# Factors affecting participation and quality of life
What are the key factors, including additional care and support, that influence participation and quality of life in people with neuropathic pain?

## Why this is important
There is evidence suggesting that people with neuropathic pain experience poorer physical and mental health than people with other forms of pain, even when adjusted for pain intensity. The discrepancy between pain intensity and quality of life implies that other, unrecognisable factors are important for people with neuropathic pain and that these factors may influence their daily activities and participation. Further research should be conducted as described in table 4 below.
Criterion
Explanation
Population
Adults with a diagnosis of neuropathic pain. Neuropathic pain conditions include:
Central neuropathic pain/central pain
Complex regional pain syndromes
Compression neuropathies/nerve compression syndromes
Facial neuralgia
HIV-related neuropathy
Mixed neuropathic pain
Multiple sclerosis
Neurogenic pain
Neuropathic cancer pain/cancer pain
Neuropathic pain
Painful diabetic neuropathy/diabetic neuropathy
Peripheral nerve injury
Peripheral nervous system disease/neuropathies
Phantom limb pain
Polyneuropathies
Post-amputation pain
Post-herpetic neuralgia
Post-stroke pain
Post-treatment/post-surgery/post-operative pain
Radiculopathies/radicular pain*
Spinal cord diseases
Spinal cord injury
Trigeminal neuralgia
Note: radiculopathies/radicular pain is now within the NICE guideline on low back pain and sciatica.
Intervention(s)
Any important factors, including elements of additional care and support that are perceived as important by adults with neuropathic pain to improve their daily participation.
Comparator(s)
Non-applicable.
Outcome(s)
HRQoL (for example, EQ-5D, WHOQoL- BREF)
Measurements of participation (for example, the London Handicap Scale)
Satisfaction
Patient experiences
Study design
Qualitative research or structured/semi-structured survey questionnaire.

# Impact of drug-related adverse effects on cost effectiveness and quality of life
What is the impact of drug-related adverse effects on health economics and quality of life in neuropathic pain?

## Why this is important
Pharmacological agents for neuropathic pain are associated with various adverse effects. However, there is little evidence about how this affects cost of the quality of life of patients receiving treatment. Further research should be conducted as described in table 5 below.
Criterion
Explanation
Population
Adults with a diagnosis of neuropathic pain. Neuropathic pain conditions include:
Central neuropathic pain/central pain
Complex regional pain syndromes
Compression neuropathies/nerve compression syndromes
Facial neuralgia
HIV-related neuropathy
Mixed neuropathic pain
Multiple sclerosis
Neurogenic pain
Neuropathic cancer pain/cancer pain
Neuropathic pain
Painful diabetic neuropathy/diabetic neuropathy
Peripheral nerve injury
Peripheral nervous system disease/neuropathies
Phantom limb pain
Polyneuropathies
Post-amputation pain
Post-herpetic neuralgia
Post-stroke pain
Post-treatment/post-surgery/post-operative pain
Radiculopathies/radicular pain*
Spinal cord diseases
Spinal cord injury
Trigeminal neuralgia
Note: radiculopathies/radicular pain is now within the NICE guideline on low back pain and sciatica.
Intervention(s)
Any pharmacological treatment for neuropathic pain, alone or in combination (see research recommendation B1)
Comparator(s)
N/A
Outcome(s)
HRQoL (EQ-5D as well as any condition-specific instruments) in people experiencing adverse effects and people experiencing none
Resource-use and costs in people experiencing adverse effects and people experiencing none
Study design
Casecontrol study
This research should be performed in a cohort of people receiving a variety of pharmacological treatments for neuropathic pain. Those experiencing adverse effects should be matched with those experiencing none, and their HRQoL and resource-use/costs compared. Matching should be performed using as many modifiers of HRQoL as possible, including age, sex and underlying diagnosis.
Analysis of single, named adverse events and also of people experiencing any serious adverse effect (those leading to discontinuation of the medication in question) would be valuable.

# Potential for dependence associated with pharmacological drugs for neuropathic pain
Is there a potential for dependence associated with pharmacological agents for neuropathic pain?

## Why this is important
There has been some suggestion that some pharmacological agents for neuropathic pain are associated with increased potential for misuse. However, there had not been enough high-quality evidence to adequately explore this issue. Further research should be conducted as described in table 6 below.
Criterion
Explanation
Population
Adults with a diagnosis of neuropathic pain. Neuropathic pain conditions include:
Central neuropathic pain/central pain
Complex regional pain syndromes
Compression neuropathies/nerve compression syndromes
Facial neuralgia
HIV-related neuropathy
Mixed neuropathic pain
Multiple sclerosis
Neurogenic pain
Neuropathic cancer pain/cancer pain
Neuropathic pain
Painful diabetic neuropathy/diabetic neuropathy
Peripheral nerve injury
Peripheral nervous system disease/neuropathies
Phantom limb pain
Polyneuropathies
Post-amputation pain
Post-herpetic neuralgia
Post-stroke pain
Post-treatment/post-surgery/post-operative pain
Radiculopathies/radicular pain
Spinal cord diseases
Spinal cord injury
Trigeminal neuralgia
Intervention(s)
Any pharmacological treatment for neuropathic pain, alone or in combination (see research recommendation B1)
Comparator(s)
Any other pharmacological treatment for neuropathic pain, alone or in combination (see research recommendation B1)
Outcome(s)
Drug dependence (including withdrawal symptoms)
Drug abuse or drug misuse
Study design
Long-term follow-up from a randomised controlled trial (minimum 6 months) or community-based observational studies.
For trials:
Intention to observe dependency and misuse should be made in the study protocol and monitored throughout the study period.
All participants should have a 'wash-out' period after assessment for inclusion in the study and before randomisation.
Baseline pain scores between arms should be equal and clearly documented.
Concomitant medications should not be allowed or should be restricted and maintained at a stable dose in the study. Difference in concomitant pain medication usage at baseline should be clearly described in each trial arm, including details of the number of patients on different drugs.
Rescue pain medications should either not be allowed or, if used, their use should be accurately documented.