A small group of drugs accounts for most prescribing in chronic and neuropathic pain. They are familiar, but the questions that come up in clinic are about the details: which of two similar drugs to choose, how to move a patient from one to another, how high a dose is worth trying, and how to stop safely. This article works through those questions one drug class at a time, with a section at the end written for patients.

1. Tricyclics: Amitriptyline and Nortriptyline

Amitriptyline is a tertiary amine tricyclic with balanced serotonin and noradrenaline reuptake inhibition and strong receptor blockade. Nortriptyline is its demethylated active metabolite, a secondary amine that is more noradrenergic and less anticholinergic, sedating and hypotensive. Efficacy in pain is broadly similar. Nortriptyline is usually better tolerated, especially in older adults.

Table 1. Amitriptyline and nortriptyline compared

Which one to choose

• Nortriptyline for older adults, patients sensitive to anticholinergic effects (prostatic symptoms, constipation, cognitive impairment), patients with postural symptoms, or when level monitoring is wanted.
• Amitriptyline when sedation is helpful, such as with poor sleep, and because it has the broader trial evidence in pain and migraine.
• Known CYP2C19 poor or ultrarapid metabolisers: consider nortriptyline or another agent in place of amitriptyline.

Checks before starting

Table 2. Pre-prescribing checklist for tricyclics in chronic pain

Starting and monitoring

• Dose: start at 10 mg at night and increase by 10–25 mg every 1–2 weeks. The usual analgesic range is 25–75 mg.
• Trial length: allow 6–8 weeks at a tolerated dose before judging benefit. Side effects are worst during titration.
• Driving: warn about drowsiness early in treatment.
• Levels: check nortriptyline levels if toxicity is suspected or the patient takes a CYP2D6 inhibitor.
• Evidence: the best evidence is in neuropathic pain. Nortriptyline did not beat placebo in fibromyalgia or knee osteoarthritis, and NICE does not recommend antidepressants for low back pain.

Stopping a Tricyclic

Stopping abruptly can cause a discontinuation syndrome driven mainly by cholinergic rebound: abdominal cramps, diarrhoea, nausea, sweating, headache and flu-like malaise, along with insomnia, vivid dreams and anxiety. Symptoms usually start 2–4 days after the last dose and settle within 1–2 weeks. Unlike gabapentinoid withdrawal, it does not cause seizures. Rebound hypomania is uncommon and should prompt a psychiatric assessment.

• Low-dose analgesic use (50 mg or less): reduce in 10–25 mg steps every few days to a week, stopping over about 1–2 weeks.
• Higher doses or long-term use: taper over at least 2–4 weeks, and sometimes over months.
• If symptoms appear: go back to the previous dose, then taper more slowly.
• Withdrawal or recurrence: withdrawal comes on within days and fades over 1–2 weeks. Pain that persists in the original distribution suggests the underlying condition has returned.
• Intolerance to amitriptyline: switching to nortriptyline at a roughly equivalent dose is reasonable and avoids most of the rebound seen with stopping outright.

2. SNRIs: Duloxetine and Venlafaxine

Duloxetine is generally the preferred SNRI for neuropathic pain. It has the larger evidence base, is licensed for diabetic peripheral neuropathic pain and works at 60 mg once daily. Venlafaxine is analgesic only at 150–225 mg a day, is off-label for pain, and carries more cardiac and discontinuation concerns. There is no direct head-to-head trial.

Table 3. Duloxetine and venlafaxine compared

Which one to choose

• Duloxetine first for most patients, including those with coexisting depression.
• Venlafaxine is reasonable in hepatic disease (with dose reduction), in patients taking CYP2D6 substrates that duloxetine would raise (tamoxifen, metoprolol, tricyclics), with CYP1A2 inhibitors, or when duloxetine is not tolerated. It must be titrated to at least 150 mg to reach an analgesic dose.
• Avoid venlafaxine in uncontrolled hypertension, arrhythmia or QTc risk, and where adherence is poor, since missed doses cause rapid withdrawal symptoms.

Checks before starting

• MAOIs: contraindicated, including linezolid. Allow 14 days after stopping an MAOI. Wait 5 days after duloxetine and 7 days after venlafaxine before starting one.
• Serotonergic drugs: tramadol, tapentadol, fentanyl, methadone, triptans, tricyclics, lithium and St John’s wort. Combination is not forbidden, but counsel the patient and monitor at the start and after each dose increase.
• Mood: ask about personal and family history of bipolar disorder, and monitor patients under 25 closely.
• Sodium: check at baseline in older adults and patients on diuretics, and recheck if confusion, unsteadiness or falls develop.
• Bleeding: risk rises with antiplatelets, anticoagulants and NSAIDs. Consider a PPI in patients at high GI risk.
• Duloxetine: do not prescribe with substantial alcohol use or chronic liver disease. Avoid potent CYP1A2 inhibitors such as fluvoxamine and ciprofloxacin. Postural hypotension and falls are most likely in the first week and after dose increases. Nausea is the most common reason for stopping; starting at 30 mg and taking it with food helps.
• Venlafaxine: measure blood pressure at baseline and during treatment, and control hypertension first. Consider a baseline ECG with cardiac risk or other QT-prolonging drugs. The Cochrane review found little compelling evidence for venlafaxine in neuropathic pain, so reserve it for patients who cannot take first-line agents.

Is there any advantage in 120 mg of duloxetine?

For most patients, no. The pivotal diabetic neuropathy trials did not show 120 mg to be better than 60 mg, and the Cochrane review found the two doses similarly effective: pooled pain reduction against placebo was almost identical (0.96 and 0.93 points on an 11-point scale), with an NNT of 5.2 at 60 mg and 4.9 at 120 mg. Adverse effects are more common at the higher dose.

• A trial of 120 mg may be reasonable in a partial responder who tolerates 60 mg well after at least 4–8 weeks, or when depression or anxiety is not controlled at 60 mg. Increase in 30 mg steps, reassess at 4–6 weeks, and return to 60 mg if there is no meaningful gain.
• Usually better than escalating: add a gabapentinoid or switch class. Combination therapy is supported by more evidence than dose escalation.

Switching from Amitriptyline to Duloxetine

For most patients on low-dose amitriptyline, a short overlapping cross-taper over about 2–4 weeks is reasonable. No trial has compared schedules, so the plan below reflects standard practice. It assumes an adult on a stable dose with adequate renal function, no chronic liver disease or heavy alcohol use, and no MAOI.

Table 4. Cross-taper by starting amitriptyline dose

• CYP2D6 interaction: duloxetine can raise amitriptyline and nortriptyline levels substantially. Watch for sedation, confusion, constipation, urinary retention, postural symptoms and tachycardia, and reduce the amitriptyline dose early.
• Serotonin syndrome: both drugs are serotonergic. Tell the patient to report agitation, tremor, muscle jerks, sweating, fever or diarrhoea. Avoid adding tramadol, triptans, lithium or St John’s wort during the switch.
• QTc: get a baseline ECG in patients with cardiac disease, older patients and those on other QT-prolonging drugs.
• Expected outcome: head-to-head data show similar efficacy (about 59% and 55% achieving a good response with duloxetine and amitriptyline). Allow at least 4–6 weeks at 60 mg before deciding duloxetine has failed.
• Planned combination: some patients do better on both. If so, keep amitriptyline at 25 mg or less and monitor closely.

Stopping an SNRI

Both drugs cause a discontinuation syndrome, and venlafaxine causes it more often and more severely. In placebo-controlled data covering the first two weeks after stopping, dizziness occurred in 17.5% with venlafaxine and 5.1% with duloxetine, and nausea in 7.6% and 2.2%. With venlafaxine, symptoms can appear within 24 hours of a missed dose.

• Onset and course: usually 2–4 days after the last dose, peaking at 1–2 weeks. Most cases resolve, but symptoms can last longer in some patients.
• Symptoms: flu-like symptoms, insomnia, nausea, dizziness, electric-shock sensations, anxiety and irritability. There is no craving.
• General approach: taper over at least 2 weeks. After long-term use, plan for months, making each reduction smaller as the dose falls.
• Duloxetine: 60 mg to 30 mg for at least 1–2 weeks, then stop. The capsule cannot be split.
• Venlafaxine: use the modified-release form and reduce in 37.5 mg steps. The final steps from 75 mg to zero are usually the hardest.
• If symptoms are intolerable: restart the previous dose, then taper more slowly.
• Withdrawal or relapse: withdrawal starts within days. Return of pain or low mood starts later and resembles the original condition. Plan replacement analgesia before stopping.

3. Gabapentinoids: Gabapentin and Pregabalin

Both drugs bind the α2δ subunit of voltage-gated calcium channels, and at equivalent doses they relieve neuropathic pain about equally well. The real differences are pharmacokinetic. Benefit is modest overall, with an NNT of about 7–8 in neuropathic pain, so agree a trial period and a target before starting.

Table 5. Gabapentin and pregabalin compared

Comparative efficacy

• Head-to-head trials are small and short. Most found no difference, and the few that favoured pregabalin generally gave relatively more pregabalin than gabapentin.
• Switching from one to the other is reasonable if the first fails, given the pharmacokinetic differences.
• Limited or no benefit has been shown in non-specific or radicular low back pain and in chemotherapy-induced neuropathy.
• Stop the drug if there is no meaningful response about 4 weeks after reaching an adequate dose.

Checks before starting

• Kidney function: both drugs are cleared only by the kidneys, so dose by creatinine clearance, and calculate it in older adults even when creatinine looks normal. In older adults with an eGFR below 60, starting above 300 mg a day of gabapentin or 75 mg a day of pregabalin was linked to more encephalopathy, falls, fractures and respiratory depression. Give a supplemental dose after dialysis.
• Opioids and sedatives: the combination adds respiratory depression risk. Higher-risk patients include those with COPD or sleep apnoea, older adults, and patients taking opioids, benzodiazepines, Z-drugs or sedating tricyclics.
• Misuse and overdose: in UK primary care data, gabapentinoid users had more substance misuse and overdose, particularly with a history of substance misuse or mental illness and with co-prescribed opioids or benzodiazepines. The overdose association was stronger for pregabalin.
• Common adverse effects (drug compared with placebo): dizziness 26% and 7%, sedation 17% and 5%, weight gain 10% and 3%, peripheral oedema 9% and 4%. Oedema matters in heart failure, and weight gain matters in diabetes.
• Older adults: higher risk of falls, fractures and confusion. Gabapentin at 2400 mg a day or more carries the highest risk.
• Other warnings: low mood and suicidal thoughts, angioedema and hypersensitivity, and impaired driving. Data in pregnancy are limited, with a signal for malformations with pregabalin.

Gabapentin absorption

Gabapentin is absorbed in the proximal small bowel, mainly by the L-amino acid transporter system. That carrier has limited capacity and saturates at higher concentrations, and the absorption window is narrow, so drug that passes the upper intestine unabsorbed is lost. Elimination is linear, with a half-life of 5–7 hours at any dose. The non-linearity comes entirely from absorption.

Table 6. Gabapentin bioavailability by total daily dose (three divided doses)

• Per dose: absorption is already less than proportional above about 300 mg.
• Per day: serum levels rise roughly in line with dose up to about 1800 mg a day, then less than expected.
• Between patients: variability is large, and older patients reach higher levels for a given dose.
• Practical consequence: smaller doses taken more often keep each dose below the point of saturation. Going from 1800 to 3600 mg a day doubles the tablet burden but increases absorbed drug by much less than double.

Is it worth going above 1800 mg of Gabapentin?

In neuropathic pain trials, doses from 1800 to 3600 mg a day were effective, and the effect was similar across that range. A Cochrane review found that these doses give meaningful relief to about 3–4 in 10 patients with postherpetic neuralgia or diabetic neuropathy, compared with 1–2 in 10 on placebo, with no evidence of a dose-response above 1200 mg a day. Adverse effects and falls risk rise with dose.

• Partial response and well tolerated at 1800 mg: a time-limited trial up to 2400–3600 mg a day is reasonable if renal function allows. Set a functional goal beforehand, reassess at about 4 weeks, and return to the lower dose if there is no further gain.
• Little or no benefit at 1800 mg after about 4 weeks: further escalation is unlikely to help. Switch to pregabalin, an SNRI or a tricyclic.
• Before calling it a failure: confirm the patient is taking it three times a day.

Converting Gabapentin to Pregabalin

A 6:1 gabapentin to pregabalin ratio is a reasonable and widely used conversion, especially at higher gabapentin doses. It is a pharmacokinetic convention, not a validated equivalence. Per milligram, pregabalin is only about 2.5 times as potent, but because gabapentin absorption saturates, the effective ratio widens as the dose rises. Use 6:1 as a starting point, round down, and titrate to response.

Table 7. Example conversions (normal renal function)

• Direct switch (simplest): give the last gabapentin dose at bedtime and start pregabalin at the converted dose, divided twice daily, the next morning.
• Cross-taper (older or frail patients, or high doses): give half the gabapentin dose plus half the target pregabalin dose for 4 days, then stop gabapentin and give the full pregabalin dose.
• Low gabapentin doses (900 mg a day or less): absorption is closer to linear, so 6:1 may underdose. Start pregabalin at 150 mg a day and titrate.
• Kidney function: use the renally adjusted pregabalin dose, not a straight conversion.
• After switching: watch for peripheral oedema, and for sedation in the first few days if the patient also takes an opioid or a tricyclic. Reassess about 4 weeks after reaching the target dose.

Stopping a Gabapentinoid

Gabapentin and pregabalin should be tapered over at least a week and never stopped abruptly. Withdrawal usually starts within 48 hours of the last dose, and seizures have been reported even in patients without epilepsy. Most chronic pain patients do better with a slower taper than the one-week minimum.

• Common symptoms: insomnia, nausea, headache, anxiety, sweating, diarrhoea, dizziness and tremor.
• Serious symptoms: seizures, agitation, confusion, psychotic symptoms, depression and suicidal thoughts.
• Rebound pain: the original pain may return or flare, and this needs to be told apart from withdrawal.

Table 8. Suggested gabapentinoid taper by situation

If withdrawal develops, the most effective treatment is to restart the same drug at the last tolerated dose and then taper more slowly. No standardised protocol exists, and the evidence is limited to case reports and expert consensus.

1. Assess severity. Mild symptoms can be managed as an outpatient. Seizures, delirium, psychosis or suicidal thoughts need urgent in-person assessment.
2. Look for other causes: alcohol, benzodiazepine or opioid withdrawal, infection and metabolic causes of delirium.
3. Restart at the last dose tolerated without symptoms, in divided doses. Symptoms usually settle within 1–3 days.
4. Hold that dose for 1–2 weeks, then resume the taper in smaller steps.
5. Treat symptoms with targeted short-term agents and avoid adding further CNS depressants. Benzodiazepines should be limited to short, supervised courses in severe cases.

4. Tramadol and Tapentadol

Both are dual-action opioids. Tramadol is a weak µ-agonist prodrug with prominent serotonin and noradrenaline reuptake inhibition. Tapentadol is a stronger, directly active µ-agonist with mainly noradrenaline reuptake inhibition and no active metabolites. Neither shows clearly better efficacy in chronic pain, and the evidence for both is low quality.

Table 9. Tramadol and Tapentadol compared

Which one to choose

• Tramadol suits mild to moderate pain that does not need a strong opioid component, and it has more real-world safety data.
• Tapentadol is worth considering when serotonergic load, CYP2D6 genotype or CYP-mediated interactions are a problem, or for neuropathic or mixed pain needing a stronger opioid effect. It is not a first-line opioid.

Checks before starting

• Is an opioid justified? Both are for use when non-opioid options have failed or are inadequate. Agree functional goals and an exit plan, and use the lowest effective dose for the shortest time.
• Misuse risk: review the prescribing history and ask about personal or family substance use.
• Respiratory: COPD, untreated sleep apnoea, hypoxia or hypercapnia, and frail or debilitated patients carry a higher risk of respiratory depression, even at recommended doses.
• Sedatives: benzodiazepines, gabapentinoids, alcohol and sedating tricyclics add to CNS depression. Avoid the combination where possible or reduce doses.
• Serotonergic drugs: with an SSRI, SNRI or tricyclic, use tramadol (and to a lesser degree tapentadol) at reduced doses with monitoring. Both are contraindicated with MAOIs and within 14 days of stopping one.
• Seizure risk: higher with tricyclics, bupropion, epilepsy, head injury and alcohol withdrawal. Avoid both drugs in poorly controlled epilepsy.
• Tramadol with a CYP2D6 inhibitor (fluoxetine, paroxetine, bupropion, duloxetine): less active metabolite is made, so analgesia falls, while more parent drug remains, so serotonergic risk rises.
• Other contraindications: significant respiratory depression, acute severe asthma, bowel obstruction or ileus, raised intracranial pressure and pregnancy.

Table 10. Dosing points for Tramadol and Tapentadol

With both drugs, start a bowel regimen with the opioid, reassess benefit, function and harms within 1–4 weeks, and taper when stopping. Withdrawal can last about a week.

5. Carbamazepine and Oxcarbazepine

These are the first-line drugs for trigeminal neuralgia. Oxcarbazepine is the 10-keto analogue of carbamazepine, designed to avoid formation of the toxic epoxide metabolite. Both block voltage-gated sodium channels and work about equally well. Carbamazepine has the stronger evidence, with an NNT of about 2. Oxcarbazepine generally causes fewer CNS side effects and far fewer interactions, but more hyponatraemia. Response varies between individuals, so if one fails it is worth trying the other.

Table 11. Carbamazepine and Oxcarbazepine compared

Which one to choose

• Carbamazepine for the strongest evidence, in younger patients on few other medicines, or when sodium is already low.
• Oxcarbazepine for older adults, patients on several drugs (anticoagulants, statins, antidepressants, opioids such as tramadol or methadone), or after non-allergic side effects with carbamazepine.
• Neither in AV block or conduction disease, or after an allergic reaction to the other drug. Cross-reactivity is about 25–30% between the two, so consider a non-aromatic option such as gabapentin, pregabalin, baclofen or botulinum toxin.

Carbamazepine dose schedule for trigeminal neuralgia

1. Start: 100 mg twice daily. In frail or older patients, consider 100 mg once daily.
2. Titrate: add 200 mg a day no more often than every 3 days, and only as far as needed for pain control. Go slower if side effects appear.
3. Target: most patients need 400–800 mg a day. Modified-release preparations give lower peaks and fewer side effects.
4. Ceiling: 1200 mg a day for most patients.
5. Review: at least every 3 months, try to reduce to the minimum effective dose or stop.
6. Remission taper: reduce by 100 mg every 7–14 days, slowly enough that a recurrence is noticed.

Dizziness, drowsiness, unsteadiness and nausea are most common at the start. Serum levels do not guide efficacy in trigeminal neuralgia and are useful only for suspected toxicity or adherence. About half of patients find the drug stops working or is not tolerated over 5–10 years.

Checks before starting

• Baseline tests for both drugs: ECG, full blood count, liver function, sodium and creatinine.
• HLA-B*15:02: test before starting in patients of Asian ancestry. Do not use carbamazepine if positive, because of the risk of Stevens-Johnson syndrome.
• Allergy history: a serious rash on any aromatic antiepileptic (carbamazepine, oxcarbazepine, lamotrigine, phenytoin) rules out both drugs. Cross-reactivity across the group runs at 40–80%.
• Sodium: recheck at 1 month and then regularly, especially in older adults and patients on diuretics, SSRIs or SNRIs.
• Pregnancy and contraception: both are teratogenic and both lower the effect of oral contraceptives. An intrauterine device or depot injection is preferred.
• Older adults: expect dizziness, ataxia, double vision and falls. Long-term use lowers bone density, so consider calcium and vitamin D.
• Carbamazepine only: contraindicated with previous bone marrow suppression, porphyria or an MAOI in the past 14 days. Repeat blood count and liver function periodically. It lowers levels of warfarin, DOACs, contraceptives, tramadol, methadone and tricyclics, while macrolides, azole antifungals, diltiazem, verapamil and grapefruit juice raise carbamazepine to toxic levels.
• Oxcarbazepine only: be cautious if baseline sodium is already low. Sodium below 125 mmol/L occurred in 2.5% of patients in trials.
• Counselling: tell patients to stop the drug and seek urgent advice for any rash or mouth sores, particularly in the first few months.

Switching from Carbamazepine to Oxcarbazepine

Switch directly at a ratio of 200 mg carbamazepine to 300 mg oxcarbazepine. Carbamazepine’s enzyme induction fades over about 2 weeks, so levels of other medicines rise and any narrow-margin drugs need rechecking. Check sodium at 1–2 weeks and at 1 month.

6. Diclofenac and Naproxen

Diclofenac and naproxen give similar pain relief at standard doses, so the choice rests on safety. Naproxen has the most favourable cardiovascular profile of the traditional NSAIDs. Diclofenac causes fewer gastrointestinal complications but carries more cardiovascular and liver risk.

Table 12. Diclofenac and Naproxen compared

Which one to choose

• Cardiovascular disease or high cardiovascular risk: naproxen is preferred if an NSAID is needed at all. Avoid diclofenac.
• High GI risk (over 65, previous ulcer or bleed, anticoagulant, steroid, SSRI or SNRI): diclofenac is less toxic to the gut than naproxen, but either needs a PPI, and celecoxib with a PPI is usually a better choice.
• Both cardiovascular and GI risk: naproxen with a PPI, or avoid NSAIDs altogether. Topical diclofenac is a good option for knee or hand osteoarthritis because systemic exposure is minimal.
• Liver disease or heavy alcohol use: avoid diclofenac.
• Low-dose aspirin: naproxen can block aspirin’s antiplatelet effect, so give the aspirin first.

Cautions that apply to both

• Kidney: avoid if creatinine clearance is below 30, and avoid the combination with an ACE inhibitor or ARB plus a diuretic. Check creatinine and potassium after starting in at-risk patients.
• Heart failure and blood pressure: both cause fluid retention and raise blood pressure.
• Dose and duration: use the lowest effective dose for the shortest time.
• Long-term use: monitor blood pressure, creatinine and blood count, and liver function with diclofenac.

7. Topiramate in migraine prevention

Topiramate is an antiepileptic used to prevent migraine. Its exact mechanism is unknown, but four actions probably contribute: it blocks voltage-dependent sodium channels, enhances GABA-A activity, antagonises AMPA and kainate glutamate receptors, and inhibits carbonic anhydrase. Together these damp down overexcited neurons in the trigeminocervical complex and may suppress cortical spreading depression.

Table 13. Topiramate titration for migraine prevention

• Target: 100 mg a day for episodic and chronic migraine. Stop titrating once the patient responds or side effects become intolerable. 200 mg a day is no more effective and is tolerated less well.
• Evidence: rated effective (Level A) and comparable to propranolol, valproate and amitriptyline.
• Trial length: judge response after at least 8 weeks at the target dose. Continue for about 6 months, then consider tapering by 25–50 mg a day each week.
• Kidneys: if creatinine clearance is below 70, use half the dose with slower titration. Avoid in severe renal or hepatic impairment.

Checks before starting

• Pregnancy and contraception: topiramate causes fetal harm, including cleft lip and palate. Do not use in pregnancy, and patients who could become pregnant need highly effective contraception. In the UK it is subject to the MHRA Pregnancy Prevention Programme.
• Eyes: acute myopia and secondary angle-closure glaucoma can occur, usually within the first month. Tell patients to seek urgent care for sudden blurred vision or eye pain.
• Kidney stones and acidosis: check bicarbonate and creatinine at baseline, advise a good fluid intake, and avoid other carbonic anhydrase inhibitors.
• Mood and cognition: screen for depression and warn about word-finding difficulty and slowed thinking. About a quarter of patients stop because of side effects.
• Common side effects: tingling (23%), weight loss (16%) and somnolence (13%).
• Interactions: valproate (raised ammonia), lithium, amitriptyline (levels can rise), alcohol and other sedatives.
• Stopping: taper gradually, because abrupt withdrawal can cause seizures.

8. Stopping at a glance

Table 14. Summary of discontinuation across the drug classes

Medication review at Pain Spa

At Pain Spa, a review of current medications is part of every new patient assessment with Dr Murli Krishna, Consultant in Pain Medicine. The aim is to make sure each drug is still earning its place, to simplify regimens where possible, and to plan safe changes alongside other treatments, including image-guided interventions where appropriate.

Key sources

• Derry S, Wiffen PJ, Aldington D, et al. Nortriptyline for neuropathic pain in adults. Cochrane Database of Systematic Reviews, 2015.
• Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database of Systematic Reviews, 2014.
• Waldfogel JM, Nesbit SA, Dy SM, et al. Pharmacotherapy for diabetic peripheral neuropathy pain and quality of life: a systematic review. Neurology, 2017.
• Sokol R, Grossman E, Bourgery R. Nonopioid pharmacologic management of chronic noncancer pain. American Family Physician, 2025.
• Goodman CW, Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Internal Medicine, 2019.
• Williams CD, Al-Jammali Z, Herink MC. Gabapentinoids for pain: a review of published comparative effectiveness trials. Drugs, 2023.
• Bockbrader HN, Budhwani MN, Wesche DL. Gabapentin to pregabalin therapy transition: a pharmacokinetic simulation. American Journal of Therapeutics, 2013.
• Sinclair JMA, Kalk NJ, Kaar SJ, et al. Evidence-based consensus guidelines for the pharmacological management of substance dependence: British Association for Psychopharmacology. Journal of Psychopharmacology, 2026.
• Roulet L, Rollason V, Desmeules J, Piguet V. Tapentadol versus tramadol: a narrative and comparative review. Drugs, 2021.
• Bendtsen L, Zakrzewska JM, Heinskou TB, et al. Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia. Lancet Neurology, 2020.
• Cruccu G, Di Stefano G, Truini A. Trigeminal neuralgia. New England Journal of Medicine, 2020.
• Manufacturers’ product information for the medicines discussed.

This article is intended for healthcare professionals and is for education only. It does not replace clinical judgement, the BNF or the Summary of Product Characteristics. Doses should be checked against current UK prescribing information before use.