Previous changes

January 2026 — reviewed. A literature search was conducted in December 2025 - January 2026 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. Additional information and clarification have been added relating to risks of dependence and prescribing off-label. There has been minor reorganization of the prescribing section. There have been no major changes to the recommendations.

June 2025 — minor update. Added addiction as a potential adverse effect of pregabalin and gabapentin. 

December 2024 — minor update. Added information about monitoring people treated with pregabalin for signs and symptoms of pregabalin misuse, abuse, or dependence, in line with the updated manufacturer's SPC.

August 2024 — minor update. Removed information regarding capsaicin cream as it is currently unavailable. 

February 2024 — minor update. Interaction between gabapentin/pregabalin and morphine sulfate has been added in line with an update to the manufacturer’s SPC.

January 2024 — minor update. Added additional information regarding duloxetine and dosing following publication of a Cochrane review advising that doses of greater than 60 mg provided no additional benefit.

October 2023 — minor update. Revision to the information regarding use of creatinine clearance for dose adjustments for prescribing gabapentin and pregabalin in people with renal impairment. 

August 2023 — minor update. Toxic epidermal necrolysis added as a possible adverse effect of gabapentin, as well as information added on withdrawal reactions in line with the updated manufacturers' summary of product characteristics.

December 2022 — minor update. Toxic epidermal necrolysis added as a possible adverse effect of pregabalin in line with the updated Summary of Product Characteristics. 

August 2022 — minor update. Information that people taking pregabalin should be monitored for suicidal ideation and discontinuation considered in suspected cases has been added to this topic in line with the updated Summary of Product Characteristics. 

July 2022 — minor update. Information that people taking gabapentin should be monitored for suicidal ideation and discontinuation considered in suspected cases has been added to this topic in line with the updated Summary of Product Characteristics. 

April 2022 — minor update. Further information about assessment prior to initiation of medication and risk of dependence added in line with NICE [NG215] 2022 Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults.

March 2022 — minor update. Information about the use of pregabalin in pregnancy has been updated in line with the manufacturer's Summary of Product Characteristics. 

February 2022 — minor update. Parkinsonism added as an adverse effect of pregabalin in line with updated manufacturer's SPC.

December 2020 — minor update. Severe respiratory depression added as an adverse effect of pregabalin in line with updated manufacturer's SPC.

August 2020 — minor update. Broken URL link updated.

February 2020 — reviewed. A literature search was conducted in January 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. There have been no major changes to the recommendations. The scope of the topic has been updated to clarify that it does not cover the treatment of sciatica.  

May 2019 — minor update. Dysphagia added as an adverse effect of gabapentin. 

March 2019 — minor update. Gabapentin and pregabalin have now be rescheduled as Schedule 3 Controlled Drugs.

October 2018 — minor update. References to amitriptyline being off-label removed. 

September 2017 — minor update. Change to adverse effects for gabapentin to reflect changes to the manufacturer's Summary of Product Characteristics regarding respiratory disorders.

July 2017 — minor update. Addition to adverse effects for pregabalin to reflect changes to the manufacturer's Summary of Product Characteristics.

June 2015 — minor update. Based on an update to the manufacturer's Summary of Product Characteristics, hyponatraemia has been included as a possible adverse effect of gabapentin.

April 2015 — minor updates:

• Correction to the prescribing information for tramadol with regards to the legal requirements for handwriting prescriptions.
• The text regarding the use of tramadol in pregnancy and breastfeeding has been removed and a link to the CKS topic on Analgesia has been provided.

June 2014 — minor update. Update to the text to reflect the fact that tramadol has been reclassified to a schedule 3 controlled drug.

January 2014 to February 2014 — reviewed. A literature search was conducted in January 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The following changes were made:

• The management section has been rewritten to reflect the recommendations in the updated NICE guideline: Neuropathic pain — pharmacological management. The pharmacological management of neuropathic pain in adults in non-specialist settings.
• The prescribing information section has been amended in line with the updated NICE guideline referenced above: prescribing information sections for duloxetine and capsaicin cream have been added, and prescribing information sections for drugs no longer recommended by NICE (imipramine, nortriptyline, and lidocaine plasters) have been removed.
• The evidence section has been rewritten to reflect the changes in the updated NICE guideline referenced above.

August 2012 — minor update. Minor typographical error corrected.

May to September 2010 — topic updated. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

January 2009 — minor update. Drug safety advice from the MHRA (Medicines and Healthcare products Regulatory Agency) that all antiepileptic drug treatment (including carbamazepine and gabapentin) is associated with a small risk of suicidal thoughts and behaviour has been added. Issued in February 2009.

September to December 2008 — this is a new CKS topic. The evidence base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 January 2026.

HTAs (Health Technology Assessments)

No new HTAs since 1 January 2026.

Economic appraisals

No new economic appraisals relevant to England since 1 January 2026.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 January 2026.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 January 2026.

New policies

No new national policies or guidelines since 1 January 2026.

New safety alerts

No new safety alerts since 1 January 2026.

Changes in product availability

• New product MISABRI PR (pregabalin prolonged-release tablets), various strengths, are licensed for the treatment of peripheral and central neuropathic pain in adults. See more here.
• Lidocaine Grunenthal 700 mg medicated plaster — licence extension. Following a licence extension, the plaster is now also indicated for localised neuropathic pain in adults, in addition to its existing licence for neuropathic pain associated with previous herpes zoster infection. See more here.

What is the initial management of a person with neuropathic pain?

For a person with trigeminal neuralgia, see the CKS topic on Trigeminal neuralgia. For a person with sciatica, see the CKS topic on Sciatica (lumbar radiculopathy). 

• For a person with any other neuropathic pain condition, including painful diabetic neuropathy, offer a choice of amitriptyline, duloxetine, gabapentin, or pregabalin. 
  • Note that these are all medicines potentially associated with dependence or withdrawal symptoms, so extra care should be taken to prescribe these safely, and steps should be taken to reduce the risk of dependence. See the section Safe prescribing of medicines associated with dependence for further information. Gabapentin and pregabalin are classified as Class C and Schedule 3 substances, and as such are subject to the relevant regulations and prescribing cautions.
  • Note that not all these medicines are licensed for all types of neuropathic pain, even though they are recommended as options in the guideline from the National Institute for Health and Care Excellence (NICE) on pharmacological treatment of neuropathic pain. See the section on Prescribing unlicensed medicines for further information.
  • Titrate the dosage according to response and tolerability.
  • If the initial treatment is not effective or not tolerated, offer one of the remaining three drugs, and consider switching again if the second and third drugs tried are also not effective or not tolerated.
  • Consider capsaicin cream for people with localised neuropathic pain who wish to avoid, or who cannot tolerate oral treatments. Note this may be an unlicensed indication - see the sections on Prescribing unlicensed medicines and Capsaicin cream for further information.
  • Consider tramadol only if acute, short-term rescue therapy is needed (for example, while awaiting specialist review after failure of first-line options). Tramadol should not be started for long-term use.
• Discuss and agree a management plan with the person. Include:
  • What the medicine has been prescribed for, the intended outcomes of treatment and how these might be assessed.
  • The starting dose and intervals between dose adjustments or titration.
  • Who to contact if problems occur.
  • Information about how long the medicine will take to work and how long they might be taking it for.
  • The duration of each prescription that will be issued.
  • The risks of taking more than the prescribed dose.
  • The symptoms and signs of an overdose, and what they should do if this happens.
  • The plans for reviewing the medicine (including where and by whom this will be done) and the date of their next review.
• Discuss with the person the range of doses likely to be safe and effective. Start with a low dose and agree frequent, regular reviews to ensure that timely adjustments can be made to test effectiveness, safety and acceptability and to find the lowest effective dose. Once an effective dose has been established, avoid automatically increasing the dose if the response is not sustained.
•  The duration of each individual prescription should:
  • Reflect the management plan.
  • Comply with best practice in controlled drugs prescribing.
  • Comply with relevant legislation.
• Devise a plan for regular reviews and include these in the management plan. Use regular follow up appointments to ensure that the benefits of the medicine continue to outweigh the potential harms and check whether the dose needs to be adjusted and, if so, how to do this safely.
• Consider referring the person to a specialist pain service and/or a relevant clinical speciality (for example neurology, diabetology, or oncology) if: 
  • They have severe pain. 
  • Their pain significantly limits their participation in daily activities (including self-care, general tasks and demands, interpersonal interactions and relationships, mobility, and sleeping).
  • The underlying health condition that is causing neuropathic pain has deteriorated.
• For people awaiting referral after initial treatments have failed, consider prescribing a short course of tramadol for pain relief.
  • Prescribe tramadol cautiously, bearing in mind the potential for misuse. Do not prescribe long-term.
  • Tramadol is also a Class 3 and Schedule 3 controlled drug.

How should I follow up a person being treated for neuropathic pain?

• Carry out an early review after starting or changing treatment. Assess the progress made with dose titration and the tolerability and effectiveness of the current treatment, including: 
• • Pain control.
  • Impact on lifestyle, daily activities (including sleep disturbance), and participation.
  • Physical and psychological well-being.
  • Adverse effects.
  • Continued need for treatment.
  • The benefits and risks of continuing the current dose, adjusting the dose or stopping the medicine. Base decisions on this discussion, taking into account, for example:
    • The benefits or harms the person is experiencing from continuing the medicine.
    • For people taking gabapentin or pregabalin, any signs that the person is developing problems associated with dependence (such as running out of a medicine early, making frequent requests for dose increases or reporting loss of efficacy of a medicine that was previously working well)
    • The person's preferences.
• Continue existing treatment if neuropathic pain is effectively managed. 
• If the treatment is not effective or is not tolerated:
  • Offer one of the other three remaining drug options (for example, if on amitriptyline, switch to duloxetine, gabapentin, or pregabalin). If the treatment is still not effective or is not tolerated, consider switching again until a suitable treatment is found, or all four drugs have been tried. 
    • Use clinical judgement to decide whether to titrate the dose more slowly upwards instead of switching (especially if adverse effects improve with time following each dose increase).
    • When withdrawing or switching treatment, taper the withdrawal regimen to take account of dosage and any discontinuation symptoms. See Prescribing information for more information on starting and withdrawing drug treatments.
• Consider referring the person to a specialist pain service and/or a relevant clinical speciality (for example, neurology, diabetology, or oncology) if:
  • They have severe pain.
  • Their pain significantly limits their participation in daily activities (including self-care, general tasks and demands, interpersonal interactions and relationships, mobility, and sleeping). 
  • The underlying health condition that is causing neuropathic pain has deteriorated.
• For people awaiting referral after initial treatments have failed, consider prescribing a short course of tramadol for pain relief. Prescribe tramadol cautiously, bearing in mind the potential for misuse.
  • Tramadol is a Schedule 3 controlled drug and as such is subject to the relevant regulations. 
• Agree and update the management plan after each review. Check that the person knows who to contact if they have problems or concerns.

Safe prescribing of medicines associated with dependence

Gabapentin, pregabalin and tramadol are classified as Class C controlled substances under the Misuse of Drugs Act 1971 and Schedule 3 under the Misuse of Drugs Regulations 2001. In addition to these three treatment options, antidepressants are also included in guidance from the National Institute for Health and Care Excellence (NICE) on safe prescribing medicines associated with dependence or withdrawal symptoms, so the information below applies to all the first-line recommended oral treatments for neuropathic pain.

These are all drugs associated with dependence and/or withdrawal symptoms, and although this is not a reason in itself to avoid prescribing, extra steps should be taken to improve the safety of doing so.

• Before starting or continuing treatment with a dependence-forming medicine or antidepressant, ensure all alternative management options have been considered and discussed.
• Evaluate for factors which might increase the risk of developing dependence (although treatment should not be withheld solely on the basis of one of these factors):
  • A comorbid mental health diagnosis.
  • A history of alcohol or drug misuse.
  • Not having a clear, defined diagnosis to support the prescription.
  • Taking an opioid together with a benzodiazepine.
• Give the person verbal and written information and advice to help them balance benefit with risk of long-term consequences. A 2026 drug safety update from the Medicines and Healthcare Regulatory Agency (MHRA) provides updated information for clinicians to provide to patients when prescribing gabapentin or pregabalin, for example,  which may be helpful when prescribing these medicines. Explain:
  • The potential side effects and how long they might last.
  • That dependence is a potential or expected effect but is not in itself a reason to avoid the medication.
  • The symptoms that suggest the development of problems associated with dependence.
  • Additional implications if the person is pregnant or planning a pregnancy.
  • What the options might be if the medicine does not work.
  • How difficult it might be to stop the medicine later and how reducing or ending treatment will be managed safely.
  • That missing doses may lead to withdrawal symptoms.
  • How to store medicines safely.
• Discuss and agree a management plan with the person. Document the plan and give them a copy. The plan should include:
  • What the medicine has been prescribed for, the intended outcomes of treatment and how these might be assessed.
  • The starting dose and intervals between dose titrations.
  • Who to contact if any problems arise.
  • Information about how long the medication will take to work and how long they might be taking it for.
  • The duration of each prescription that will be issued.
  • The risks of taking more than the prescribed dose.
  • The symptoms and signs of an overdose, and what they should do if this happens.
  • The plans for reviewing the medication and the date of the next review.
• Arrange regular review to:
  • Ensure benefit continues to outweigh harm.
  • Whether the dose needs to be adjusted and, if so, how to do this safely.
• Safe prescribing strategies include:
  • Start at a low dose, and pre-agree the range of doses likely to be safe and effective. Review the dose regularly.
  • Avoid increasing the dose if response is not sustained.
  • Duration of each prescription should comply with best practice in controlled drug prescribing and reflect the management plan.
  • Arrange regular review as above, with the interval dependent on the person's preferences and circumstances, the type of medication and dose, the extent to which the medication is being used within its license and the potential for misuse (risk factors and medication being used).
  • Do not stop the medication abruptly.
  • If the person's individual circumstances or the setting (for example, a secure setting) mean that usual prescribing practices are not suitable, adjust the prescription to ensure that the medicine can be administered safely as part of the setting's routine and does not pose a risk to the person or to others living in that setting.
• Make shared decisions about withdrawing medicines. Discuss withdrawing the medication if:
  • The person is not getting any benefit from it.
  • Problems associated with dependence have developed.
  • The condition for which the medication was prescribed has resolved.
  • The harms outweigh the benefits.
  • The person wants to stop the medication.
• Before withdrawing the medication:
  • Give information about the process of withdrawal that is tailored to their situation and medication.
  • Explain how the withdrawal will be carried out.
  • Explain possible withdrawal symptoms.
  • Give information about support available and who to contact if problems arise.
  • Agree on a dose reduction schedule, and arrange regular reviews.

[NICE, 2022; BNF, 2025; NICE, 2025a; MHRA, 2026]

Unlicensed or off-label use of medicines

The guideline from the National Institute for Health and Care Excellence (NICE) for drug treatment of neuropathic pain includes recommendations for the use of some drugs that are not licensed for this use (off-label or unlicensed use).

• Duloxetine is licensed for diabetic neuropathy but not for other types of neuropathic pain.
• Gabapentin is licensed for peripheral neuropathic pain, but NICE recommends it as an option for central or peripheral neuropathic pain.
• Capsaicin 0.075% cream is licensed for the symptomatic relief of post-herpetic neuralgia and diabetic neuropathy, but NICE recommends it as an option for people with localized neuropathic pain who wish to avoid, or who cannot tolerate, oral treatments.
• Tramadol is licensed for the treatment of moderate to severe pain, although not specifically for neuropathic pain.
• Of the other drugs recommended, however, amitriptyline is licensed for the treatment of neuropathic pain, and pregabalin is licensed for peripheral and central neuropathic pain.

When prescribing drugs outside the terms of their UK license, clinicians should follow relevant professional guidance, such as that from NICE, the Medicines and Healthcare products Regulatory Agency (MHRA), and the General Medical Council (GMC), which state that:

• Unlicensed medicines may be prescribed where, on the basis of an assessment of the individual patient, clinicians conclude for medical reasons that it is necessary to do so to meet the specific needs of the patient.
• The prescribing clinician must:
  • Be satisfied that there is sufficient evidence or experience of using the medicine to demonstrate its safety and efficacy (for example, recommended by NICE guidelines for that clinical situation).
  • Prescribe within their own competence, the professional codes of their own statutory body, and the prescribing policies of their employers.
  • Take full responsibility for the decision when prescribing or advising drugs off-label. This includes:
    • Considering the contraindications, warnings, monitoring requirements and other safety recommendations for each medicine.
    • Explaining to the patient that the medication is unlicensed and the reasons why the medicine has been prescribed. Enough information should be provided so that the person can make an informed decision.
    • Documenting the prescribing and the reasons for prescribing an unlicensed medicine, and the discussion with the patient.
    • Taking responsibility for monitoring or follow-up (either personally or ensuring appropriate follow-up arrangements are in place).

[MHRA, 2014; GMC, 2022; BNF, 2025; NICE, 2025b; NICE, 2025a]

Dose

• For neuropathic pain in adults:
  
  • Initially, prescribe amitriptyline at a dose of 10 mg to 25 mg, to be taken in the evening.
  • If necessary, increase the dose by 10 to 25 mg every 3–7 days in one to two divided doses to an effective dose or the person's maximum tolerated dose (no higher than 75 mg a day).
    • If no improvement is seen with 75 mg a day, consider seeking specialist advice or switching to a different drug (see the section on Follow up). 
    • Dosages higher than 75 mg a day could be considered with caution or in consultation with a specialist pain service.
    • A single dose above 75 mg is not recommended.
    • The maintenance dose is the lowest effective dose.
    • Analgesic effect is normally seen after 2–4 weeks. Consider trialling amitriptyline for 6–8 weeks, with at least 2 weeks at the maximum tolerated dose, before deciding it is not effective.
  • In elderly people, initiate at the lower recommended dose range (10 mg).
  • Amitriptyline is licensed for neuropathic pain in adults.
  • When stopping therapy, gradually withdraw over several weeks.

[Dworkin, 2010; Catalisano, 2024; BNF, 2025; EMC, 2025a]

Contraindications and cautions

• Do not prescribe amitriptyline to people with:
  • Arrhythmias.
  • Bipolar disorder (if they are in a manic phase).
  • Heart block.
  • Recent myocardial infarction.
• Prescribe amitriptyline with caution to people with:
  • Cardiovascular disease.
  • Chronic constipation.
  • Diabetes.
  • Epilepsy.
  • History of bipolar disorder or psychosis.
  • Hyperthyroidism or phaeochromocytoma (due to the risk of arrhythmias).
  • Increased intra-ocular pressure or susceptibility to angle-closure glaucoma.
  • A significant suicide risk.
  • Prostatic hypertrophy or urinary retention.
  • Pyloric stenosis.
• See also the section on safe prescribing of medicines associated with dependence.
  • Note that withdrawal symptoms after prolonged use of amitriptyline may include headache, malaise, insomnia and irritability.

 [BNF, 2025; EMC, 2025a]

Adverse effects

• Cardiovascular — palpitations, tachycardia, orthostatic hypotension, atrioventricular block, bundle branch block (common or very common), hypertension, collapse, worsening cardiac failure, arrhythmia, and cardiomyopathies (uncommon or rare).
• Nervous system — somnolence, tremor, dizziness, headache, drowsiness, dysarthria (very common), disturbance in attention, dysgeusia, paraesthesia, ataxia (common), convulsion, akathisia, polyneuropathy, and extrapyramidal disorder (uncommon or rare).
• Psychiatric — aggression, agitation, confusion, reduced libido (very common or common), hypomania, mania, anxiety, insomnia, nightmares (uncommon), delirium, hallucination, and suicidal thoughts (rare).
• Gastrointestinal — dry mouth, constipation, nausea (very common), diarrhoea, vomiting, hepatic impairment (uncommon), salivary gland enlargement, paralytic ileus, and jaundice (rare).
• Urinary — micturition disorders (common) and urinary retention (uncommon).
• Reproductive system and breast disorders — erectile dysfunction (common), galactorrhoea (uncommon), and gynaecomastia (rare).
• Eye disorders — accommodation disorder, mydriasis (very common or common), glaucoma (very rare), and dry eye (not known).
• Other adverse effects include hyponatraemia, hyperhidrosis, fatigue, thirst (common), tinnitus (uncommon), and reduced appetite (rare) and weight changes.
• Withdrawal symptoms after prolonged use of amitriptyline may include headache, malaise, insomnia, and irritability.

For further information and a full list of possible adverse effects, see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[BNF, 2025; EMC, 2025a]

Drug interactions

Drug interactions for amitriptyline include: 

• Antifungals (fluconazole, terbinafine) — increase the concentration of amitriptyline and increase the risk of toxicity.
• Anti-hypertensives (particularly centrally acting anti-hypertensive medication such as methyldopa and clonidine) — the manufacturer recommends reviewing all anti-hypertensive therapy during treatment with amitriptyline, as the effect may be reduced.
• Buprenorphine and opioids — concomitant use may lead to serotonin syndrome. Concomitant use with tramadol may also increase the risk for seizures in addition.
• Central nervous system depressants (e.g. alcohol, barbiturates) — sedative effects enhanced.
• Cytochrome P450 inducers (oral contraceptives, rifampicin, phenytoin, barbiturates, carbamazepine, St John's Wort) — may increase metabolism of amitriptyline and result in lower levels and reduced response.
• Drugs which prolong the QT interval (e.g. quinidine, terfenadine, sotalol, and cisapride) — use with amitriptyline may increase the risk of ventricular arrhythmias. The manufacturer recommends avoiding the combination.
• Furosemide and other diuretics, which may induce hypokalaemia — manufacturer advises caution.
• Serotonergic agents — concomitant use of other serotonergic agents, such as monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs) or other tricyclic antidepressants may lead to serotonin syndrome. (Symptoms include mental state changes, autonomic instability, neuromuscular abnormalities, and gastrointestinal symptoms.)
• Strong CYP2D6 inhibitors (e.g. bupropion, quinidine, fluoxetine, paroxetine) — the manufacturer recommends using a lower dose.
• Sympathomimetic agents (adrenaline, ephedrine, phenylephrine, phenylpropanolamine) — cardiovascular effects may be potentiated. Manufacturer recommends avoiding using in combination with amitriptyline.

For further information and a full list of drug interactions, please see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[BNF, 2025; EMC, 2025a]

Pregnancy and breastfeeding

Pregnancy

• Amitriptyline is not recommended in women who are pregnant unless the benefits outweigh the risks.
  • There is no robust evidence that exposure to amitriptyline in early pregnancy causes infant congenital malformation, but a teratogenic effect cannot be ruled out.
  • There may be neonatal withdrawal symptoms following use in the final weeks of pregnancy.

Breastfeeding

• Amitriptyline and its metabolites are excreted in low levels in breastmilk and this is not expected to cause any adverse effects, especially if the infant is aged over 2 months of age, however, rare sedation has been reported in neonates. 
• However, the manufacturer advises that a decision must be made whether to discontinue breastfeeding or avoid amitriptyline as a risk to the infant cannot be excluded.

[UKTIS, 2023; LactMed, 2024; BNF, 2025; EMC, 2025a]

Dose

• For central or peripheral neuropathic pain in adults:
  • Prescribe an initial dose of 150 mg a day (given in two to three divided doses).
    • A lower starting dose may be appropriate for some people, for example, people who cannot initially tolerate 150 mg a day or people with reduced renal function (see Table 1). Seek specialist advice and consult the manufacturer's Summary of Product Characteristics for use in people undergoing haemodialysis.
  • If necessary, increase the dose after 3–7 days to 300 mg a day (given in two to three divided doses). The dose can be increased further to a maximum dose of 600 mg a day (given in two to three divided doses) after an additional 7-day interval.
  • Consider trialling pregabalin for 4 weeks before deciding it is not effective.
  • Pregabalin is a Class C controlled substance and a Schedule 3 drug, so prescribe in line with prescribing requirements for this group of medicines.
• If pregabalin is not effective or not tolerated, discontinue treatment gradually over a minimum of 1 week.

Table 1. Recommended dosage adjustment for pregabalin in people with renal impairment.

[Dworkin, 2010; BNF, 2025; EMC, 2025b]

Contraindications and cautions

• Pregabalin can cause drug dependence, which may occur at therapeutic doses. People treated with pregabalin should be monitored for signs and symptoms of pregabalin misuse, abuse or dependence, such as development of tolerance, dose escalation and drug-seeking behaviour.
  • Withdrawal symptoms may occur after discontinuation, including insomnia, headache, nausea, anxiety, diarrhoea, flu-like symptoms, nervousness, depression, pain, convulsion, hyperhidrosis and dizziness. Inform the person about this when starting treatment, and when discontinuing pregabalin, do this gradually over at least a week. 
  • See the section on Safe prescribing of medicines associated with dependence for further information.
• Prescribe pregabalin with caution to people with:
  • A history of substance abuse.
  • A higher risk of respiratory depression, including those:
    • With compromised respiratory function, or respiratory or neurological disease.
    • Renal impairment.
    • Aged older than 65 years.
    • Taking other central nervous system depressants, including opioids.
    • (Consider adjustments in dose in patients at higher risk of respiratory depression and advise all patients to seek medical help if they experience any trouble breathing or shallow breathing.)
  • Conditions that may precipitate encephalopathy.
  • Diabetes mellitus. (Some people with diabetes who gain weight on pregabalin may need to adjust their diabetes medication.)
  • Severe congestive heart failure.
  • Renal impairment.
  • Seizures (may be exacerbated).
• Also prescribe pregabalin with caution to people who are:
  • Elderly.  
  • At risk of falls.
  • At risk of suicide.

[BNF, 2025; EMC, 2025b]

Adverse effects

• Cardiac — tachycardia, first-degree atrioventricular block, sinus bradycardia, congestive heart failure (uncommon), QT interval prolongation, sinus tachycardia, and sinus arrhythmia (rare).
• Eye — blurred vision, diplopia (common); peripheral vision loss, visual disturbance, eye swelling, visual acuity reduced, eye pain, asthenopia, photopsia, dry eye, increased lacrimation, eye irritation (uncommon), vision loss, keratitis, oscillopsia, altered visual depth perception, mydriasis, strabismus, and visual brightness (rare).
• Gastrointestinal — vomiting, nausea, constipation, diarrhoea, flatulence, abdominal distension, dry mouth (common), gastroesophageal reflux disease, salivary hypersecretion, oral hypoaesthesia (uncommon), ascites, pancreatitis, swollen tongue, and dysphagia (rare).
• Metabolism and nutrition — increased appetite (common) and weight gain, rarely anorexia and hypoglycaemia. Some people with diabetes mellitus may need to adjust hypoglycaemic medicines. 
• Musculoskeletal and connective tissue — muscle cramp, arthralgia, back pain, limb pain, cervical spasm (common); joint swelling, myalgia, muscle twitching, neck pain, muscle stiffness (uncommon), and rhabdomyolysis (rare).
• Nervous system — dizziness, somnolence, headache (very common), ataxia, abnormal coordination, tremor, dysarthria, amnesia, memory impairment, disturbance in attention, paraesthesia, hypoaesthesia, sedation, balance disorder, lethargy (common), syncope, stupor, myoclonus, psychomotor hyperactivity, dyskinesia, intention tremor, nystagmus, cognitive disorder, speech disorder, hyporeflexia, hyperaesthesia, burning sensation, ageusia, malaise (uncommon), parkinsonism, convulsions, parosmia, hypokinesia, and dysgraphia (rare).
• Psychiatric — pregabalin can cause drug dependence, which may occur at therapeutic doses. Also, euphoria, confusion, irritability, disorientation, insomnia, libido decreased (common), hallucination, panic attack, restlessness, agitation, depressed mood, elevated mood, aggression, depersonalisation, libido increased, and anorgasmia, apathy (uncommon).
  • Suicidal thoughts and behaviour. There is a small increased risk of suicidal thoughts and behaviour associated with antiepileptic drugs (including pregabalin), which may be seen as early as 1 week after starting treatment.
    
    • Advise people taking pregabalin to be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment.
    • People should seek medical advice if they develop such thoughts or behaviour, and they should be referred for appropriate treatment if necessary.
    • Monitor people for suicidal ideation and behaviour and consider discontinuation of pregabalin in suspected cases.
• Other adverse effects include: 
  • Dyspnoea, pulmonary oedema. 
  • Elevated liver enzymes, jaundice, hepatitis.
  • Erectile dysfunction.
  • Fatigue.
  • Hypotension, hypertension, flushing.
  • Nasopharyngitis.
  • Oedema.
  • Rash, urticaria, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis.
  • Severe respiratory depression. See the section on contraindications and cautions for more information about prescribing to people at risk. Advise patients to seek medical help if they experience any trouble breathing or shallow breathing.
  • Urinary incontinence.
• Dizziness and somnolence are the most commonly reported adverse effects. This could increase the risk of falls, particularly in the elderly.

For further information and a full list of possible adverse effects, see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[MHRA, 2019; BNF, 2025; EMC, 2025b]

Drug interactions

• Alcohol — effects may be potentiated if taken concurrently with pregabalin.
• Opioids —increased risk of respiratory failure, coma and death in patients taking pregabalin and opioids and/or other central nervous system (CNS) depressant medicines. Other CNS depressant medications where CNS depression may be potentiated include antidepressants, antipsychotic medication, baclofen, sedative antihistamines, clonidine, and benzodiazepines. 
• Lorazepam — the sedative effect may be potentiated if taken concurrently with pregabalin. 
• Oxycodone — concurrent use may cause an additive impairment in cognitive and gross motor function.

For further information and a full list of drug interactions, please see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[BNF, 2025; EMC, 2025b]

Pregnancy and breastfeeding

Pregnancy

• Pregabalin should be avoided in pregnancy unless clearly necessary and the benefit to the mother outweighs the risk to the fetus — exposure during the first trimester may cause major birth defects, although studies are not yet conclusive.
• The manufacturer advises that women of childbearing potential should use effective contraception during treatment. 
• Advise people taking pregabalin who are planning pregnancy to discuss treatment with their prescriber prior to becoming pregnant.
• There are limited data on the use of pregabalin in women who are pregnant.
  • If it is used, both mother and fetus should be monitored closely.
  • Although there is no known impact of pregabalin on maternal folate status, women on any anti-seizure medication should be prescribed high dose folic acid (5 mg).

Breastfeeding

• Pregabalin is excreted in low amounts in breastmilk. The effects on the newborn or infant is not known.
• The manufacturer advises against using pregabalin when breastfeeding, and recommends a decision is made whether to discontinue breastfeeding or discontinue pregabalin. 

[BNF, 2025; EMC, 2025b; UKTIS, 2025a]

Dose

• Usual titration (usually suitable for otherwise healthy younger adults).
  • Initially, 300 mg once a day on day 1, then 300 mg twice a day on day 2, then 300 mg three times a day on day 3.
  • Alternatively, start with 300 mg three times a day on day 1, then increase according to response in steps of 300 mg (in three divided doses) every 2–3 days up to a maximum of 3600 mg a day (1200 mg three times a day).
    • If the person experiences adverse effects during daily titration, a slower titration may help.
• Slow titration (suitable if the person is elderly, frail, is in poor general health, has low body weight or has experienced adverse effects with higher doses).
  • Start with 100 mg at night, increasing by 100 mg a day until pain is significantly reduced, intolerable adverse effects occur, or a maximum daily dosage of 3600 mg (1200 mg three times a day) is reached.
    • If the person experiences adverse effects during daily titration, a slower titration (for example, increasing the dose every 3–7 days) may help.
• Consider trialling gabapentin for 3–8 weeks, with at least 2 weeks at the maximum tolerated dose, before deciding it is not effective.
  • It may take several weeks to reach an effective dosage (usually 1200 mg to 3600 mg a day). Onset of action may be seen as early as the second week of treatment with rapid titration, but the peak effect usually occurs about 2 weeks after a therapeutic dosage is achieved; therefore, an adequate trial may be 2 months or longer.
• Adjust the dose for people with renal impairment (see Table 2). Consult the manufacturer's Summary of Product Characteristics if the person is undergoing haemodialysis.
• Gabapentin is a Class C controlled substance and a Schedule 3 drug, so prescribe in line with prescribing requirements for this group of medicines.
• If gabapentin is not effective or not tolerated, discontinue treatment gradually over a minimum of 1 week.
• Note that gabapentin is licensed for the treatment of peripheral neuropathic pain, such as painful diabetic neuropathy and postherpetic neuralgia in adults. However, the National Institute for Health and Care Excellence (NICE) recommends gabapentin as a first-line treatment option for adults with all neuropathic pain (except trigeminal neuralgia and sciatica). For more information about prescribing medication off-label, see the section on Prescribing unlicensed medicines.

Table 2. Recommended dosage adjustment for gabapentin in people with renal impairment.

[Dworkin, 2010; BNF, 2025; EMC, 2025c; NICE, 2025a]

Contraindications and cautions

• Gabapentin can cause drug dependence, which may occur at therapeutic doses. People treated with pregabalin should be monitored for signs and symptoms of pregabalin misuse, abuse or dependence, such as development of tolerance, dose escalation and drug-seeking behaviour.
  • Withdrawal symptoms may occur after discontinuation, including anxiety, insomnia, nausea, pains, sweating, tremor, headache, depression, feeling abnormal, dizziness and malaise. Inform the person about this when starting treatment, and when discontinuing pregabalin, do this gradually over at least a week. 
  • See the section on Safe prescribing of medicines associated with dependence for further information.
• Prescribe gabapentin with caution to people with:
  • A history of substance abuse.
  • Risk of respiratory depression (people with compromised respiratory function, respiratory or neurological disease, renal impairment, and concomitant use of central nervous system (CNS) depressants). The manufacturer advises that dose adjustments may be needed.
  • Low body weight (high doses of oral solution).
  • Mixed seizures (including absences). 
  • Diabetes mellitus. 
  • Renal impairment – dose adjustments are necessary.
• Also prescribe gabapentin with caution to people who are:
  • Elderly.  
  • At risk of suicide.
  • Taking opioids or other CNS depressants. The manufacturer advises reducing the dose of gabapentin or the other CNS depressant, and monitoring for signs of CNS depression, such as somnolence, sedation and respiratory depression.

 [BNF, 2025; EMC, 2025c] 

Adverse effects

• Gastrointestinal — vomiting, nausea, constipation, diarrhoea, flatulence, abdominal pain, dry mouth, gingivitis (common); and pancreatitis (frequency unknown).
• Infections and infestations — viral infection (very common); pneumonia, respiratory infection, urinary tract infection, and otitis media (common).
• Metabolism and nutrition — anorexia, increased appetite (common); hyperglycaemia (uncommon); and hyponatraemia (frequency unknown).
• Musculoskeletal and connective tissue — arthralgia, myalgia, back pain, twitching (common); rhabdomyolysis, and myoclonus (frequency unknown).
• Nervous system — dizziness, somnolence, ataxia (very common); headache, convulsions, hyperkinesia, tremor, dysarthria, amnesia, insomnia, paraesthesia, nystagmus (common); hypokinesia, mental impairment (uncommon); and loss of consciousness (rare).
• Psychiatric — addiction, gabapentin can cause drug dependence, which may occur at therapeutic doses. Also, hostility, confusion and emotional lability, depression, anxiety, nervousness (common); agitation (uncommon); and hallucinations (unknown frequency).
  • Suicidal thoughts and behaviour. There is a small increased risk of suicidal thoughts and behaviour associated with antiepileptic drugs (including gabapentin), which may be seen as early as 1 week after starting treatment.
    • Advise people taking gabapentin to be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment.
    • They should seek medical advice if they develop such thoughts or behaviour, and they should be referred for appropriate treatment if necessary.
    • Monitor people for suicidal ideation and behaviour and consider discontinuation of gabapentin in suspected cases.
• Respiratory — dyspnoea, bronchitis, pharyngitis, cough, rhinitis (common); and respiratory depression (rare).
• Skin and subcutaneous tissue — facial oedema, purpura, rash, pruritus, acne (common); Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, alopecia, drug rash with eosinophilia and systemic symptoms (DRESS), and rythema multiforme (frequency unknown).
• Other adverse effects include: 
  • Acute renal failure, incontinence.
  • Allergic reactions. 
  • Fatigue, fever.
  • Impotence. 
  • Hepatitis, jaundice. 
  • Hypertension, vasodilation.
  • Leucopenia, thrombocytopenia. 
  • Palpitations.
  • Pancreatitis.
  • Peripheral oedema.
  • Vertigo.
  • Visual disturbances. 

For further information and a full list of possible adverse effects, see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[BNF, 2025; EMC, 2025c]

Drug interactions

• Antacids — levels of gabapentin are reduced slightly if taken concurrently with antacids containing aluminium/magnesium hydroxide. Gabapentin should be taken 2 hours after the antacid.
• Central nervous system (CNS) depressants, including opioids — the risk of CNS depression may be enhanced if taken concurrently with gabapentin. Monitor for signs of CNS depression (such as somnolence, sedation or respiratory depression) and adjust the dose of gabapentin, or the dose of the CNS depressant or opioid if required.

For further information and a full list of drug interactions, please see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[BNF, 2025; EMC, 2025c] 

Pregnancy and breastfeeding

Pregnancy

• There are limited data on the use of gabapentin in women who are pregnant.
  • Gabapentin crosses the placenta.
  • There is no robust evidence of an increased risk of congenital malformation when gabapentin is used in pregnancy, but evidence is too limited to definitively exclude risk.
  • Neonatal withdrawal symptoms have been reported in newborns exposed in utero to gabapentin.
• Gabapentin should be avoided in pregnancy unless the benefit to the mother outweighs the risk to the fetus.
  • Ideally, treatment with gabapentin should be reviewed in a woman who is planning pregnancy.
  • Gabapentin may impact on maternal folate status, and high dose folic acid (5mg) should be prescribed to women taking any anti-epileptic in pregnancy.

Breastfeeding

• Gabapentin is excreted in low amounts in breast milk. The effect on breast-fed infants is not known.
• The manufacturer advises gabapentin should only be used in women who are breastfeeding if the benefits clearly outweigh the potential risks.

 [BNF, 2025; EMC, 2025c; UKTIS, 2025b]

Dose

• The initial dose is 60 mg once daily. If necessary, increase the dose up to a maximum of 120 mg a day (in two divided doses). 
• Consider trialling duloxetine for up to 8 weeks before deciding it is not effective.
  • Additional response after 8 weeks is unlikely.
  • Reassess treatment at least every 3 months.
  • A Cochrane review in 2023 reported there was no additional benefit on pain relief at doses higher than 60mg, although the manufacturer advises that due to the variability of plasma concentration, some individuals may benefit from the higher dose.
• If duloxetine is not effective or not tolerated, discontinue treatment gradually over a minimum of 1–2 weeks in order to reduce the risk of withdrawal reactions.
• Note that duloxetine is licensed for the treatment of diabetic peripheral neuropathic pain. However, the National Institute for Health and Care Excellence recommends duloxetine as a first-line treatment option for adults with all neuropathic pain (except trigeminal neuralgia or sciatica). See the section on Prescribing unlicensed medicines for further information about prescribing off-label.

[Birkinshaw, 2023; EMC, 2024; BNF, 2025; NICE, 2025a]

Contraindications and cautions

• Do not prescribe duloxetine to people with:
  • Liver disease resulting in hepatic impairment.
  • Severe renal impairment (creatinine clearance under 30 ml/min).
  • Uncontrolled hypertension.
• Prescribe duloxetine with caution to people with:
  • Bleeding disorders.
  • Cardiac disease.
  • A history of bipolar disorder or mania.
  • A history of seizures.
  • Hypertension.
  • Raised intra-ocular pressure or susceptibility to angle-closure glaucoma.
  • A history of suicide-related events or a significant degree of suicidal thoughts.
• In addition, prescribe duloxetine with caution to people who are:
  • Elderly.
  • Less than 25 years old (higher risk of suicidal behaviour as an adverse effect of antidepressants).
• In addition, see the section on Safe prescribing of medicines associated with dependence.
  • Withdrawal symptoms when treatment is discontinued are common, particularly if duloxetine is stopped abruptly.
  • Withdrawal symptoms include dizziness, sensory disturbances (including paraesthesia or electric shock-like sensations particularly in the head), sleep disturbances (including insomnia and intense dreams), fatigue, somnolence, agitation or anxiety, nausea, vomiting, tremor, headache, myalgia, irritability, diarrhoea, hyperhidrosis and vertigo.

 [EMC, 2024; BNF, 2025] 

Adverse effects

• Cardiovascular — palpitations, increase in blood pressure, flushing (common), tachycardia, supraventricular arrhythmia (mainly atrial fibrillation), syncope, hypertension, orthostatic hypotension, peripheral coldness (uncommon), hypertensive crisis (rare), and stress cardiomyopathy (frequency unknown).
• Gastrointestinal — nausea, dry mouth (very common), constipation, diarrhoea, abdominal pain, vomiting, dyspepsia, flatulence (common), gastrointestinal haemorrhage, gastroenteritis, gastritis, dysphagia (uncommon), stomatitis, haematochezia, breath odour, and microscopic colitis (rare)
• Metabolism and nutrition — reduced appetite (common), hyperglycaemia, particularly in diabetic people (uncommon), dehydration, hyponatraemia, and syndrome of inappropriate antidiuretic hormone (SIADH) (rare).
• Musculoskeletal and connective tissue — musculoskeletal pain, muscle spasm (common), muscle tightness or twitching (uncommon), and trismus (rare).
• Nervous system — headache, somnolence (very common), dizziness, lethargy, tremor, paraesthesia (common), myoclonus, akathisia, nervousness, disturbance in attention, dysgeusia, dyskinesia, restless legs syndrome, poor quality sleep (uncommon), serotonin syndrome, convulsion, psychomotor restlessness, and extra-pyramidal symptoms (rare).
• Psychiatric — insomnia, agitation, decreased libido, abnormal orgasm, anxiety, abnormal dreams (common), suicidal ideation, sleep disorder, bruxism, disorientation, apathy (uncommon), suicidal behaviour, mania, hallucinations, and aggression and anger (rare).
• Respiratory — yawning (common), throat tightness, epistaxis (uncommon), interstitial lung disease, and eosinophilic pneumonia (rare).
• Reproductive system and breast disorders — erectile dysfunction, ejaculation disorders (common), menstrual disorders, sexual dysfunction, testicular pain, gynaecological haemorrhage (uncommon), menopausal symptoms, galactorrhoea, hyperprolactinaemia, and post-partum haemorrhage (rare).
• Skin and subcutaneous tissue — increased sweating, rash (common), night sweats, urticaria, contact dermatitis, cold sweat, photosensitivity reactions, increased bruising (uncommon), Stevens-Johnson syndrome, angioneurotic oedema (rare), and cutaneous vasculitis (very rare).
• Other adverse effects include: 
  • Hypothyroidism (rare).
  • Blurred vision (common), visual impairment (uncommon), and glaucoma (rare).
  • Tinnitus (common), vertigo (uncommon).
  • Hepatitis, abnormal liver enzymes (uncommon), hepatic failure, and jaundice (rare).
  • Dysuria (common), urinary retention, and nocturia (uncommon).
  • Falls (common).
  • Fatigue (common).
  • Weight changes (decrease in weight common, increase uncommon).
  • Withdrawal symptoms on discontinuation.

For further information and a full list of possible adverse effects, see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[EMC, 2024; BNF, 2025] 

Drug interactions

Drug interactions for duloxetine include:

• Anticoagulants and anti-platelet agents — potential increased risk of bleeding, manufacturer advises caution.
• Agents affecting the central nervous system (such as alcohol, sedative agents such as benzodiazepines, anti-psychotics, phenobarbital, and sedative antihistamines) — Manufacturer advises caution.
• Fluvoxamine and ciprofloxacin — concomitant use is likely to result in higher concentrations of duloxetine due to inhibition of CYP1A2, manufacturer advises avoiding the combination. 
• Opioids and buprenorphine — increased risk of serotonin syndrome.
• Serotonergic agents — increased risk of serotonin syndrome when used concomitantly with serotonergic agents such as selective serotonin reuptake inhibitors (SSRIs), other serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants or triptans.
• St John's wort — adverse reactions may be more common if used concomitantly with duloxetine.

For further information and a full list of drug interactions, please see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[EMC, 2024; BNF, 2025] 

Pregnancy and breastfeeding

​​​​​​Pregnancy

• Duloxetine should only be used in women who are pregnant if the benefits outweigh the risks.
  • Toxicity has been shown in animal studies; data from studies in humans are inconclusive, but do not suggest an increased risk of major congenital malformation.
  • If taken in late pregnancy, there is a possible risk of neonatal withdrawal symptoms, and persistent pulmonary hypertension in the newborn (PPHN).
  • Evidence also suggests an increased risk of post-partum haemorrhage following duloxetine exposure within the month prior to delivery.
  • Women should be advised to seek medical advice if they become pregnant, or plan to become pregnant, during treatment with duloxetine.

Breastfeeding

• Duloxetine is excreted in breastmilk in small amounts, however, there is little available data on use during breastfeeding.
• The manufacturer advises that as the safety has not been established, use during breastfeeding is not recommended. 

[UKTIS, 2022; EMC, 2024; BNF, 2025] 

Dose

• Advise the person to apply a small amount of cream (pea size) to the affected area 3–4 times a day (not more often than every 4 hours).
  • The cream should only be applied to unbroken skin.
  • Review treatment after 8 weeks.
• Advise the person:
  • That the cream should be gently rubbed in, and there should be no residue left on the surface of the skin.
  • To wash their hands immediately after applying capsaicin cream unless the hands are the treated areas, in which case they should be washed 30 minutes after application.
  • To avoid taking a hot bath or shower just before or after applying the cream, as it can enhance the burning sensation.
  • To avoid contact with eyes and mucous membranes.
  • To avoid inhalation of vapours from the cream, as transient irritation of the mucous membranes of the eyes and respiratory tract (including exacerbation of asthma) has been reported.
  • That tight bandages should not be applied on top of capsaicin cream.
  • That medical advice should be sought if the condition worsens.
• Note that Capsaicin 0.075% cream is licensed for the symptomatic relief of postherpetic neuralgia after open skin lesions have healed, and for the symptomatic relief of painful diabetic neuropathy (only under the direct supervision of a hospital consultant who has access to specialist resources). However, the National Institute for Health and Care Excellence (NICE) recommends capsaicin cream for people with localized neuropathic pain who wish to avoid, or cannot tolerate, oral treatments. See the section on Prescribing unlicensed medicines for more information on prescribing off-label.

[BNF, 2025; EMC, 2025d; NICE, 2025a]

Contraindications and cautions

• Do not prescribe capsaicin cream for use on:
  • Broken skin.
  • Irritated or inflamed skin.
  • Areas under tight bandages.
  • Skin around the eyes or mucous membranes.

[BNF, 2025; EMC, 2025d] 

Adverse effects

• Adverse effects include:
  • Skin irritation or transient burning on application (more common when used more than four times daily, or if too much cream is used or if it is applied just before or after a bath or shower).
  • Irritation of mucous membranes of the eyes and respiratory tract (rare), causing coughing, sneezing, and watering eyes. Dyspnoea, wheezing, and exacerbation of asthma have also been reported rarely.

[BNF, 2025; EMC, 2025d] 

Drug interactions

• There are no known drug interactions with capsaicin cream.

[BNF, 2025; EMC, 2025d] 

Pregnancy and breastfeeding

• According to the manufacturer, although there have been no studies looking at the safety of capsaicin cream during pregnancy and breastfeeding, the small amount absorbed transdermally is considered unlikely to cause any adverse effects in humans.

[EMC, 2025d] 

Dose

• Although not specifically licensed for the neuropathic pain, tramadol is licensed for the treatment of moderate to severe pain. The National Institute for Health and Care Excellence (NICE) recommends tramadol for people with neuropathic pain (except trigeminal neuralgia and chronic sciatica), only if acute rescue therapy is needed. 
• The dose of tramadol is 50 mg to 100 mg, not more often than every 4 hours (up to a maximum of 400 mg a day), titrated according to the pain severity. An initial dose of 100 mg may be necessary for acute pain.
• Consider increasing the dose intervals in people with renal and/or hepatic insufficiency and in people over the age of 75, as elimination may be delayed.
• Tramadol is a Class C controlled drug and Schedule 3 under the Misuse of Drugs Regulations 2001, so clinicians should follow prescribing rules for this category of medication.

 [BNF, 2025; EMC, 2025e; NICE, 2025a]

Contraindications and cautions

• Do not prescribe tramadol to people with:
  • Acute intoxication with alcohol, analgesics, hypnotics, opioids or any other psychotropic medicinal products.
  • Uncontrolled epilepsy.
• Prescribe tramadol with caution to people with:
  • A history of substance use disorder.
  • A history of mental health disorder.
  • A history of epilepsy.
  • Respiratory depression.
  • Excessive bronchial secretions.
  • Impaired consciousness.
  • Central sleep apnoea (There is a dose-dependent increased risk of central sleep apnoea; consider dose reduction).
  • Adrenocortical insufficiency (reduced dose is recommended).
• In addition, note that:
  • Tolerance and physical and psychological dependence may develop with repeated use of tramadol and other opioids. Withdrawal symptoms may occur on abrupt cessation of therapy or dose reduction. Before starting treatment, patients should be informed of the risks and signs of dependence, and treatment goals and a discontinuation plan agreed. See the section on Safe prescribing of medicines associated with dependence for more information.
  • Capacity to metabolise tramadol varies between individuals. Those who are ultra-rapid metabolisers have a higher risk of toxicity, and those who metabolise it slowly may have a poor therapeutic effect.

For further information and a full list of cautions associated with prescribing opioids, see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

 [BNF, 2025; EMC, 2025e] 

Adverse effects

• Cardiovascular — palpitations, tachycardia, postural hypotension, cardiovascular collapse (uncommon), bradycardia, and increased blood pressure (rare).
• Gastrointestinal — nausea (very common), vomiting, constipation, dry mouth (common), retching, bloating, gastrointestinal discomfort, and diarrhoea (uncommon).
• Metabolism and nutrition — changes in appetite (rare) and hypoglycaemia (frequency not known).
• Musculoskeletal and connective tissue — muscular weakness (rare)
• Nervous system — dizziness (very common), headache, somnolence (common), paraesthesia, tremor, convulsions, abnormal coordination, involuntary muscle contractions, syncope, speech disorders (rare), and serotonin syndrome (frequency not known).
• Psychiatric — hallucinations, confusion, sleep disturbance, delirium, anxiety and nightmares, changes in mood, changes in activity, and changes in cognitive and sensorial ability (rare).
  • Drug dependence may occur with repeated use, even at therapeutic doses. Risk may vary depending on dose, duration of treatment, and individual risk factors.
    • Withdrawal effects may include agitation, anxiety, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal symptoms, and rarely panic attacks, hallucinations, paraesthesias, tinnitus, confusion, delusions, depersonalisation, derealisation, and paranoia.
• Respiratory — respiratory depression, dyspnoea (rare), and hiccups (frequency not known).
• Reproductive system and breast disorders.
• Skin and subcutaneous tissue — hyperhidrosis (common) and skin reactions (uncommon).
• Other adverse effects include: 
  • Allergic reactions.
  • Blurred or altered vision.
  • Difficulty passing urine and urinary retention.
  • Fatigue.

For further information and a full list of possible adverse effects, see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[BNF, 2025; EMC, 2025e] 

Drug interactions

• Anticholinergics or medicines with anticholinergic activity (e.g. tricyclic antidepressants, antihistamines, antipsychotics, muscle relaxants, and anti-Parkinson drugs) — increased risk of anticholinergic side effects.
• Carbamazepine — may reduce analgesic effect and duration of action.
• Gabapentin and pregabalin — risk of respiratory depression, hypotension, profound sedation, coma or death.
• Monoamine oxidase inhibitors (MAOIs) — Manufacturer recommends avoiding concomitant use or use in people who have taken MAOIs in the last 14 days.
• Sedative medicinal products (such as benzodiazepines, antipsychotics, barbiturates, sedative anti-histamines) — increased risk of sedation, respiratory depression, coma and death. Avoid combination unless alternative treatments are not possible. If used, use the lowest effective dose for the shortest possible time.
• Seizure threshold lowering products, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, antipsychotics, bupropion, and mirtazapine) — increased risk of convulsions.
• Serotonergic drugs, such as SSRIs, SNRIs, MAOIs, tricyclic antidepressants, and mirtazapine — increased risk of serotonin syndrome.
• Warfarin — risk of increased INR with increased risk of bleeding.

For further information and a full list of drug interactions, see the British National Formulary (BNF) or Electronic Medicines Compendium (EMC). 

[BNF, 2025; EMC, 2025e] 

Pregnancy and breastfeeding

Pregnancy

• The manufacturer recommends tramadol should not be used in pregnancy as there is inadequate evidence of its safety, although the available data do not show convincing evidence of increased risk of congenital malformations.
  • Regular use in pregnancy may cause drug dependence in the unborn child, leading to withdrawal symptoms in the neonate.
  • Use near term may cause neonatal respiratory depression.

Breastfeeding

• Use of tramadol in breastfeeding women is not recommended as it may be secreted in breast milk and may cause respiratory depression in the infant.

 [BNF, 2025; EMC, 2025e; UKTIS, 2025c]