Neuropathic Pain

Clinical Snapshot

Neuropathic pain is pain caused directly by a lesion or disease affecting the somatosensory nervous system, rather than by ongoing tissue injury or inflammation — a fundamentally different mechanism from the nociceptive pain covered in the Acute Pain chapter, and one that acetaminophen and NSAIDs do not reliably treat. It can arise from damage anywhere along the somatosensory pathway: peripheral nerves (diabetic peripheral neuropathy, postherpetic neuralgia, nerve trauma), nerve roots (cervical or lumbar radiculopathy), or the central nervous system itself (pain after stroke or spinal cord injury, multiple sclerosis). Because it responds to a different set of drugs — gabapentinoids, certain antidepressants, and topical agents rather than conventional analgesics — correctly recognizing neuropathic pain, ideally supported by a validated screening tool such as the DN4, is the step that determines everything that follows.

Trigeminal neuralgia and acute nerve root compression are managed differently again: trigeminal neuralgia responds specifically to carbamazepine rather than the usual first-line agents, and acute nerve root pain is treated acutely like other acute pain before neuropathic-specific therapy is considered. This chapter also carries a deliberate opioid-sparing message — opioids, including tramadol, are third-line, reserved for a carefully monitored trial only after adequate first- and second-line therapy has been tried.^[1]

Recognize the Condition

How neuropathic pain typically presents

Pain quality often differs qualitatively from nociceptive pain: spontaneous ongoing pain described as burning or aching, paroxysmal pain described as shooting or electric shock-like, and evoked pain triggered by a stimulus that would not normally be painful. Numbness or reduced sensation frequently coexists with the pain itself in the same distribution — a patient may describe an area as simultaneously numb and painful.

Peripheral vs. central neuropathic pain

Peripheral neuropathic pain

Arises from a lesion or disease of the peripheral nervous system. Includes nerve root pain, peripheral neuropathies (diabetic, HIV-related, chemotherapy-induced), carpal tunnel syndrome, trigeminal neuralgia, postherpetic neuralgia, incisional neuralgia, complex regional pain syndrome (CRPS) types I and II, other nerve trauma (causalgia), and phantom limb pain.

Central neuropathic pain

Arises from a lesion or disease of the central nervous system. Includes central post-stroke pain, spinal cord injury pain, pain following traumatic brain injury, multiple sclerosis-related pain, and syringomyelia. The same general treatment principles used for chronic peripheral neuropathic pain apply, though central pain is often more difficult to control and more often needs combination therapy or a multidisciplinary pain program.

Sensory findings on examination

Term	Definition
Allodynia	Pain from a stimulus that does not normally provoke pain, such as light touch on normal-appearing skin.
Hyperalgesia	An exaggerated painful response to a stimulus that is normally painful, along with a lowered pain threshold.
Hyperesthesia	Increased sensitivity to touch.
Hyperpathia	An abnormally exaggerated, often delayed and prolonged, subjective response to a painful stimulus.
Dysesthesia	An unpleasant, disagreeable sensation produced by touch.
Hypoesthesia	Reduced sensation to a stimulus, reflecting sensory loss in the affected area.

Complex regional pain syndrome (CRPS) type I — historically called reflex sympathetic dystrophy — is a distinct neuropathic pain presentation with neurovascular and dystrophic features: burning pain in a nonanatomical distribution, allodynia, sweating, and skin colour/temperature change, progressing if untreated to glossy skin, altered hair/nail growth, osteoporosis, and contractures. CRPS type II (causalgia) follows a clear nerve injury and is managed the same way as other chronic peripheral neuropathic pain.

Risk Factors

Diabetes mellitus, particularly with longstanding or poorly controlled hyperglycemia (diabetic peripheral neuropathy).
Age over 50 combined with reduced immune competence — the main risk factors for herpes zoster reactivation and subsequent postherpetic neuralgia.
Nerve trauma, including surgical incision, amputation (phantom limb pain), or a penetrating/crush injury.
Chemotherapy exposure, particularly with platinum agents, taxanes, or vinca alkaloids.
HIV infection.
Degenerative spine disease with disc herniation or nerve root compression, most often at C5-C6 or L5-S1.
Stroke or spinal cord injury (central neuropathic pain).
Multiple sclerosis.
Malignancy directly invading or compressing a nerve.
A personal or family history of chemical dependency, or a history of severe psychiatric disorder — relevant to weighing the risk of opioid therapy if that stage is reached, not itself a cause of neuropathic pain.

Red Flags & Refer

Neuropathic pain therapy should never be started presumptively when any of the following are present — investigate and refer instead:

Rapidly progressive neurological deficit — new or worsening weakness, muscle wasting, or a spreading sensory level — needs urgent imaging and surgical/neurology referral rather than a trial of neuropathic pain medication.
New bowel or bladder dysfunction, saddle anesthesia, or bilateral leg symptoms accompanying back or leg pain — possible cauda equina syndrome, a surgical emergency.
Pain accompanied by unexplained weight loss, fever, night pain unrelieved by position change, or a history of malignancy — investigate for an underlying malignant, infectious, or inflammatory cause before treating symptomatically.
Herpes zoster affecting the ophthalmic division of the trigeminal nerve (forehead, tip of the nose) — refer for same-day ophthalmology assessment given the risk of vision loss.
Signs of serotonin syndrome (agitation, hyperreflexia, clonus, tremor, diaphoresis, fever) in a patient on more than one serotonergic agent — for example, an SNRI combined with tramadol, another antidepressant, or a triptan — stop the causative agent(s) and seek urgent assessment.^[2]
Signs of TCA cardiotoxicity — new arrhythmia, syncope, or marked QT prolongation — especially in a patient with pre-existing cardiac disease or on a high TCA dose; obtain an ECG before starting or increasing a TCA in anyone with cardiac risk factors, and stop the drug if toxicity is suspected.
Suspected complex regional pain syndrome with progressive trophic or autonomic changes (skin colour or temperature change, swelling, altered hair/nail growth) — refer for pain-specialist assessment.
Signs of opioid toxicity or respiratory depression, particularly when an opioid is combined with a gabapentinoid or another CNS depressant.^[3]

Assessment & Diagnosis

Distinguishing neuropathic from nociceptive pain

Feature	Neuropathic pain	Nociceptive pain
Underlying mechanism	Lesion or disease directly affecting the somatosensory nervous system (peripheral nerve, root, spinal cord, or brain)	Ongoing activation of normal, intact pain receptors by tissue injury or inflammation
Typical descriptors	Burning, electric shock-like, shooting, stabbing, tingling, numbness	Aching, throbbing, sharp, cramping, tender to pressure
Distribution	Follows a nerve, root, or other neuroanatomical pattern	Localized to the site of tissue injury, or refers in a predictable somatic pattern
Associated sensory findings	Allodynia, hyperalgesia, hypoesthesia, dysesthesia often present on exam	Normal sensation outside the injured area; tenderness reproduces with palpation of the injured tissue
Response to acetaminophen/NSAIDs	Typically poor to absent	Typically effective
Typical causes	Diabetic peripheral neuropathy, postherpetic neuralgia, nerve root compression, post-stroke or spinal cord injury pain, trigeminal neuralgia, chemotherapy-induced neuropathy	Fracture, sprain, surgical incision, arthritis, visceral inflammation
Screening tool	DN4 score of 4 or more out of 10, or painDETECT score of 19 or more, supports a neuropathic component	Not applicable

Many patients have mixed pain — for example, chronic low back pain with a radicular neuropathic component plus mechanical nociceptive pain. Treat each component according to its own mechanism rather than assuming one therapy will cover both.

History

Characterize the pain's temporal profile (constant vs. paroxysmal), quality (burning, shooting, electric shock-like, tingling), and distribution (whether it follows a nerve, root, or dermatomal pattern).
Ask specifically about features suggesting an underlying treatable cause requiring separate workup: new malignant, ischemic, inflammatory, or infectious disease.
Assess functional status, mood, sleep, and quality of life with a validated tool (e.g., Brief Pain Inventory, Hospital Anxiety and Depression Scale) — these guide both the treatment plan and the definition of a successful response.
Review current and previous treatments in detail, including the actual dose and duration tried — many reported "failures" reflect an inadequate trial rather than true non-response.
Ask about a personal or family history of substance use disorder and any history of severe psychiatric illness, particularly before considering opioid therapy.
Apply a validated neuropathic pain screening tool (DN4 or painDETECT, below) when the diagnosis is uncertain.

Physical examination

Map the area of sensory abnormality — hypoesthesia, allodynia, hyperalgesia, hyperesthesia, dysesthesia, or hyperpathia — and confirm it corresponds to a plausible nerve, root, or central distribution.
Perform a focused neurologic exam for motor weakness, reflex changes, or other findings suggesting a progressive lesion needing imaging and possible surgical referral (see Red Flags & Refer).
Look for a concurrent musculoskeletal or psychological contributor to the pain presentation — mixed pain is common, and each component needs its own treatment approach.

Investigations

MRI or CT imaging when a space-occupying or compressive lesion is suspected (progressive neurologic deficit, malignancy risk, or failure of conservative management for nerve root pain) — not needed routinely for typical diabetic peripheral neuropathy or postherpetic neuralgia with a classic history and exam.
Electromyography/nerve conduction studies when the diagnosis or the specific nerve(s) involved is unclear.
Diagnostic sympathetic blockade when complex regional pain syndrome is suspected and the diagnosis is in question.

Neuropathic pain screening questionnaires

The DN4 (Douleur Neuropathique 4) is a 10-item screening tool combining 7 patient-reported items with 3 brief clinician-administered sensory-examination items — 1 point for each item present, out of a maximum of 10.^[4] It is a simple, unambiguous point-sum, structurally similar to other validated scoring tools used elsewhere in this platform, though it still requires a brief hands-on sensory exam rather than being purely self-reported.

Item	Points
Interview — does the pain have any of the following characteristics?
Burning	1
Painful cold	1
Electric shocks	1
Interview — is the pain associated with any of the following symptoms in the same area?
Tingling	1
Pins and needles	1
Numbness	1
Itching	1
Examination of the painful area
Hypoesthesia to touch	1
Hypoesthesia to pinprick	1
Pain caused or increased by brushing (tactile allodynia)	1

A total score of 4 or more out of 10 supports a neuropathic pain component. Use the DN4 to decide whether a neuropathic-specific agent is appropriate — it does not replace clinical judgement or the search for an underlying cause.

painDETECT is an alternative, entirely patient-completed screening questionnaire that needs no hands-on sensory examination, making it useful when a bedside exam is not practical.^[5] A score of 19 or higher suggests a neuropathic component is likely, 13-18 is ambiguous, and 12 or below suggests it is unlikely.

Treatment Targets

Reduce pain from moderate-or-severe to mild — complete resolution is uncommon and should not be the stated goal for most patients.
Balance meaningful pain relief against tolerable, manageable side effects; the right dose is not always the maximum tolerated dose.
Restore function: sleep, mood, activities of daily living, and work/social participation, not just the pain score in isolation.
Minimize opioid exposure — reserve opioids for a monitored, time-limited trial only after non-opioid first- and second-line options have had an adequate trial.
Identify and treat any reversible underlying contributor found on assessment (for example, optimizing glycemic control in diabetic peripheral neuropathy, or addressing a compressive lesion) alongside symptomatic pain therapy.
Engage the patient as an active participant in a multimodal plan that combines pharmacotherapy with the nonpharmacologic measures below, rather than relying on medication alone.

Choose Initial Treatment

Direct treatment rule

Chronic peripheral and central neuropathic pain (excluding trigeminal neuralgia and acute nerve root pain — see below)

1st line start one of gabapentin, pregabalin, duloxetine, venlafaxine, or a TCA (amitriptyline, nortriptyline, or desipramine), chosen by patient factors rather than a fixed order — prefer duloxetine when comorbid depression or generalized anxiety is present; prefer amitriptyline when comorbid insomnia is present and there is no cardiac risk; prefer pregabalin or gabapentin when comorbid generalized anxiety disorder is present or when minimizing CYP-mediated drug interactions matters; avoid a TCA in patients over 65, with cardiac disease, or with glaucoma/urinary retention risk — use nortriptyline or desipramine instead of amitriptyline if a TCA is still the right choice, since both are better tolerated.^[1]

Diabetic peripheral neuropathy specifically gabapentin, pregabalin, duloxetine, and amitriptyline all have the strongest evidence base and are considered equally reasonable initial choices; optimize glycemic control as part of the overall management plan, since this is a modifiable contributor to neuropathy progression independent of pain control itself.^[6]

Central neuropathic pain (post-stroke, spinal cord injury, multiple sclerosis) uses the same first-line agents — amitriptyline, gabapentin, and pregabalin are the most studied — but response is frequently incomplete even at the maximum tolerated dose; set expectations accordingly, involve a multidisciplinary pain or rehabilitation program early, and address other contributing factors (such as spasticity after spinal cord injury) alongside the neuropathic pain regimen itself.^[7]

Titrate every first-line agent using a start-low, go-slow approach, increasing at the intervals shown in Drug Tables until pain relief occurs or intolerable side effects are reached, and continue an adequate trial — at or near the maximum tolerated dose — for at least 2 to 3 months before judging the agent to have failed.

Do not combine a TCA with an SNRI — additive serotonergic and cardiac risk with no established added benefit over either alone.^[2]

Partial response to first-line monotherapy add a second first-line agent from a different class (for example, a gabapentinoid plus a TCA or SNRI) rather than substituting a higher dose of the same drug once its maximum tolerated dose has been reached — combination therapy is a standard, expected next step, not a treatment failure.^[1]

2nd line — for a localized area of peripheral neuropathic pain (such as a well-defined patch of postherpetic neuralgia or focal diabetic neuropathy), or when oral agents are not tolerated add topical lidocaine or topical capsaicin over the painful area, either as monotherapy in older adults who cannot tolerate systemic agents or as an adjunct to a systemic first-line drug.^[1]

3rd line — reserved for pain that remains significant after adequate first- and second-line trials, ideally with specialist input tramadol or another opioid, or referral for botulinum toxin A injections for refractory focal peripheral neuropathic pain. Position opioids as a deliberate, monitored, time-limited trial rather than a default escalation step, applying the same opioid-prescribing safeguards used for any chronic non-cancer pain indication.^[1]^[8]

Do not use cannabinoids as routine therapy current evidence gives a weak recommendation against cannabinoids for neuropathic pain generally; reserve nabiximols for its specific approved indication (multiple sclerosis-related neuropathic pain/spasticity) under specialist direction rather than using cannabinoids as a general-purpose treatment option.^[1]

Trigeminal neuralgia (a distinct pharmacologic pathway)

1st line carbamazepine — the agents above are not first-line for this specific condition and are considerably less effective for the paroxysmal, shock-like pain of trigeminal neuralgia unless it has a similar shock-like quality.^[9]

2nd line, or when carbamazepine causes intolerable side effects switch to oxcarbazepine, or reduce carbamazepine to a tolerable dose and add baclofen.^[9]

Refractory to medical therapy refer for neurosurgical evaluation (microvascular decompression or an ablative procedure) — surgical options have a high success rate in experienced hands and should not be delayed indefinitely in a patient failing an adequate medical trial.^[9]

Acute nerve root compression (cervical or lumbar radiculopathy)

Acute phase manage with a non-opioid analgesic (acetaminophen and/or an NSAID), plus short-term opioids only if needed for severe pain — the neuropathic-specific agents above, particularly gabapentinoids, have not shown benefit for this specific pain generator and are not first-line here.^[1]

Refer for surgical assessment if pain fails to improve over 6 to 12 weeks of conservative management, if a progressive neurologic deficit develops, or if imaging identifies a surgically treatable lesion — see Red Flags & Refer for signs requiring urgent rather than routine referral.

Non-Pharmacologic Treatment

Physiotherapy, supervised exercise, and physical reconditioning — evidence is limited for many modalities, but they are reasonable adjuncts and should be combined with pharmacotherapy rather than used as an alternative to it.
Cognitive behavioural therapy, mindfulness-based approaches, and other psychotherapy — support coping and function, and address the anxiety/depression that commonly accompanies chronic neuropathic pain.
Sleep hygiene counselling and, where relevant, treatment of comorbid insomnia — poor sleep both worsens pain perception and is worsened by it.
Set expectations explicitly at the first visit: the realistic goal is reducing pain from moderate-or-severe to mild, not complete resolution. Most patients achieve partial relief, and a minority achieve near-complete relief. Framing partial response as a genuine treatment success — rather than a failure requiring escalation — reduces unnecessary dose-chasing and inappropriate opioid escalation.
Schedule regular follow-up visits even when a specific new intervention is not planned — ongoing contact provides psychological support and allows early detection of both inadequate response and emerging adverse effects.
For diabetic peripheral neuropathy, reinforce glycemic control as part of the overall plan, alongside pain-specific therapy.
For nerve root compression that fails conservative management, or for trigeminal neuralgia refractory to medical therapy, surgical options exist (nerve decompression, microvascular decompression, ablative procedures) — see Choose Initial Treatment and Treatment Failure & Next Step.
Interventional procedures such as epidural steroid injections and sympathetic blocks are offered by some chronic pain clinics, but current evidence supporting their efficacy specifically for neuropathic pain is limited — they are not a substitute for an adequate pharmacologic trial.

Pharmacologic Treatment Options

Drug / intervention	Role	Dose / use	Important adverse effects	Teaching points
Gabapentin Preferred	1st-line gabapentinoid	Start 300 mg PO QHS; increase by 300 mg/day every 3-7 days in divided doses to a usual effective dose of 1200-3600 mg/day divided TID	Sedation, dizziness, ataxia, peripheral edema, weight gain	Renally cleared — reduce dose if ClCr under 60 mL/min. Additive respiratory depression risk with opioids — counsel on this and use the lowest effective combined doses.
Pregabalin Preferred	1st-line gabapentinoid	Start 50-75 mg PO BID; increase over 3-7 days to a usual effective dose of 300-600 mg/day divided BID	Sedation, dizziness, peripheral edema, weight gain	BID dosing may improve adherence over gabapentin. Renally cleared — reduce dose if ClCr under 60 mL/min. Same opioid-combination caution as gabapentin.
Duloxetine Preferred	1st-line SNRI	Start 30 mg PO daily for 1-2 weeks if needed for tolerability, then 60 mg PO daily as the usual effective dose	Nausea, dry mouth, insomnia, dizziness	Do not use if ClCr is under 30 mL/min or with significant hepatic impairment. Avoid combining with other serotonergic drugs.
Venlafaxine XR Alternative	1st-line SNRI alternative	Start 37.5 mg PO daily; increase weekly by 37.5-75 mg to a usual effective dose of 150-225 mg/day	Hypertension (dose-related), nausea, sweating, sedation, discontinuation symptoms	Duloxetine is generally preferred given more consistent efficacy evidence; venlafaxine is a reasonable alternative or add-on agent.
Amitriptyline Preferred	1st-line TCA	Start 10-25 mg PO QHS; increase by 10-25 mg every 3-7 days to a usual effective dose of 50-75 mg/day	Anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision), sedation, weight gain, orthostatic hypotension, cardiac conduction effects	Avoid in patients over 65, with cardiac disease, glaucoma, or urinary retention risk — obtain an ECG before starting in anyone with cardiac risk factors. Most sedating TCA, useful when insomnia coexists.
Nortriptyline Alternative	1st-line TCA, better tolerated	Same titration approach as amitriptyline; usual effective dose 50-75 mg/day	Same class effects as amitriptyline, generally less pronounced	Preferred over amitriptyline in older adults or when anticholinergic burden is a concern, if a TCA is still the right choice.
Lidocaine 5% (cream/ointment) Alternative	2nd line, localized peripheral neuropathic pain	Apply to the intact painful area up to 3 times daily as needed	Local skin irritation; systemic toxicity is unlikely with appropriate use on intact skin	Do not apply to broken skin or cover with an occlusive dressing. A dedicated lidocaine patch is not marketed in Canada — cream/ointment formulations are used instead.
Capsaicin cream Alternative	2nd line, localized peripheral neuropathic pain	Apply a thin layer to the painful area 3-4 times daily	Burning/stinging on application, usually diminishing with continued regular use	Warn patients about the initial application burning so they do not stop prematurely; wash hands thoroughly after use and avoid contact with eyes/mucous membranes. The high-concentration 8% patch used in some trials is not marketed in Canada.
Carbamazepine Special situation	1st line specifically for trigeminal neuralgia (not other neuropathic pain)	Start 100 mg PO BID-QID; increase by 100-200 mg/day at weekly intervals to a usual effective dose of 400-1200 mg/day divided	Drowsiness, ataxia, dizziness, hyponatremia, rare severe skin reactions or blood dyscrasia	Consider HLA-B*1502 screening in patients of Asian ancestry before starting, given increased Stevens-Johnson syndrome/toxic epidermal necrolysis risk. Baseline and periodic CBC, electrolytes, and liver enzymes, especially in the first 3 months.
Tramadol Special situation	3rd line	Immediate-release: start 50 mg PO Q4-6H PRN, max 400 mg/day (300 mg/day if over 65); or a controlled-release product started once daily per product monograph, titrated to a maximum of 300-400 mg/day	Nausea, dizziness, constipation, sedation, seizure risk at higher doses	Reserve for after adequate first- and second-line trials. Do not use with an MAOI. Additive seizure and serotonin syndrome risk with other serotonergic or seizure-threshold-lowering drugs. Not for children under 12.
Morphine (or another strong opioid) Special situation	3rd line, refractory pain	Individualized opioid-naive starting dose with slow upward titration — see Drug Tables	Sedation, constipation, nausea, respiratory depression, dependence/misuse risk	Use only after other options have failed, following standard chronic non-cancer pain opioid safeguards (risk screening, treatment agreement, regular monitoring). Avoid combining with a gabapentinoid at higher doses of either agent without close monitoring.
OnabotulinumtoxinA Special situation	3rd line, refractory focal peripheral neuropathic pain	Specialist-administered subcutaneous injections into the painful area, repeated approximately every 12 weeks per protocol	Injection-site pain/bruising, rare focal weakness	Reserve for refractory cases under specialist direction — not a primary-care-initiated therapy.
Cannabinoids (nabilone, nabiximols) Avoid	Not routinely recommended	Reserve nabiximols for its specific approved MS-related neuropathic pain/spasticity indication only	Sedation, dizziness, dry mouth, cognitive effects, dependence potential	Current evidence supports a recommendation against cannabinoids as general neuropathic pain therapy — not a substitute for the first-, second-, or third-line agents above.

Special Populations

Pregnancy

Use nonpharmacologic measures preferentially and avoid drug therapy for neuropathic pain in pregnancy whenever possible; if treatment is genuinely needed, weigh the risks and benefits of the specific agent.

Preferred if a drug is needed amitriptyline — TCAs have the most reassuring pregnancy safety data among the agents used for neuropathic pain.

Alternative SNRIs (venlafaxine, duloxetine) are not associated with an increased major-malformation risk but are generally less effective for neuropathic pain than TCAs; venlafaxine exposure late in pregnancy has been associated with transient neonatal neurobehavioural symptoms (agitation, jitteriness, feeding difficulty).

Topical lidocaine is not expected to result in meaningful systemic absorption and is considered safe in pregnancy.

Avoid gabapentin and pregabalin — pregnancy safety data are insufficient to support routine use; avoid unless no other option is appropriate and specialist input supports the decision.

Avoid valproic acid/divalproex sodium — increased neural tube defect risk.

Carbamazepine and oxcarbazepine are associated with an increased risk of major and minor malformations, including neural tube defects. If either is genuinely required (for example, trigeminal neuralgia unresponsive to alternatives), start high-dose folic acid supplementation (1 mg daily) at least 3 months before a planned conception, continuing through 12 weeks' gestation, then continue a standard prenatal multivitamin (0.4-1 mg folic acid) through pregnancy and for 4-6 weeks postpartum or while breastfeeding continues.

Opioid use in the first trimester carries a small absolute increase in congenital heart defect and neural tube defect risk; near-term use can cause neonatal respiratory depression, sedation, and withdrawal. Tramadol use has also been associated with neonatal withdrawal after prolonged maternal use. Reserve opioids in pregnancy for situations where the benefit clearly outweighs these risks, with specialist input.

Breastfeeding

TCAs are not expected to cause adverse effects in the breastfed infant. With SNRIs, monitor the breastfed infant for drowsiness and adequate weight gain/developmental progress. Topical lidocaine is not expected to cause infant adverse effects — keep infant skin away from treated areas. Gabapentin transfers into breast milk at low levels — monitor for infant drowsiness and adequate weight gain; avoid pregabalin while breastfeeding given insufficient safety data. Carbamazepine and oxcarbazepine are considered compatible with breastfeeding. Monitor infants exposed to opioids or tramadol via breast milk for sedation, poor feeding, or respiratory depression.

Older adults / frail elderly

Start at the lowest available dose and titrate more slowly than in younger adults, aiming for the lowest effective dose rather than the usual adult target. Actively minimize the total number of CNS-active drugs (antidepressants, gabapentinoids, opioids, benzodiazepines) in patients with a history of falls or fractures — each of these classes independently increases fall risk in this population.^[10]^[11]

Drug class	Elderly-specific precaution
Antiepileptics (carbamazepine, oxcarbazepine)	Can cause or worsen SIADH — check sodium at baseline and with dose changes. Falls risk from ataxia/impaired psychomotor function.
Gabapentinoids	Dose adjustment required if ClCr is under 60 mL/min. Sedation and falls risk.
SNRIs	Can cause or worsen SIADH — check sodium at baseline and with dose changes. Duloxetine is contraindicated if ClCr is under 30 mL/min; reduce venlafaxine dose if ClCr is under 70 mL/min.
TCAs	Highly anticholinergic, sedating, and cause orthostatic hypotension — avoid with a history of falls/fractures, delirium, dementia, or lower urinary tract symptoms/BPH. Obtain an ECG before use given cardiac conduction risk.
Opioids	Falls risk from ataxia/impaired psychomotor function. Avoid meperidine (neurotoxic metabolite accumulation). Reduce the tramadol dose if ClCr is under 30 mL/min and avoid it in patients with a seizure disorder.

Renal impairment

Gabapentin and pregabalin both require dose reduction based on creatinine clearance (see Drug Tables) — this is the single most common dosing error with these agents in renal impairment. Duloxetine is contraindicated if ClCr is under 30 mL/min. Venlafaxine requires dose reduction if ClCr is under 70 mL/min. Tramadol requires dose reduction if ClCr is under 30 mL/min. TCAs and topical lidocaine/capsaicin do not require renal dose adjustment.

Hepatic impairment

Avoid duloxetine in significant hepatic impairment. TCAs and opioids may need dose reduction and slower titration given hepatic metabolism — use lower starting doses and monitor closely.

Monitoring & Follow-Up

Arrange initial follow-up around 2 weeks after starting or adjusting therapy, then at regular intervals thereafter — sooner if a new drug or dose change carries a specific early risk to monitor (for example, sodium or cardiac conduction).

Track pain intensity with a simple 0-10 numeric rating scale, at rest and with activity, comparing to the pre-treatment baseline at every visit.
Assess function (e.g., Brief Pain Inventory or Pain Disability Index), mood (e.g., Hospital Anxiety and Depression Scale), sleep, and adherence at follow-up — pain relief without functional improvement is an incomplete response.
Check serum sodium at baseline and with dose changes for any antiepileptic or SNRI, given the shared SIADH/hyponatremia risk.
Reassess renal function periodically in patients on gabapentin, pregabalin, duloxetine, venlafaxine, or tramadol, and adjust doses as renal function changes.
Obtain or repeat an ECG when starting or increasing a TCA in anyone with cardiac risk factors.
For carbamazepine specifically: CBC, electrolytes, and liver enzymes roughly every 1-2 weeks for the first 3 months, then periodically, given the risk of blood dyscrasia and hepatotoxicity in the early treatment period.
If an opioid is used at any line of therapy, apply the same monitoring as any chronic non-cancer pain opioid trial — regular visits (monthly or more often initially), a documented treatment agreement, functional and mood assessment at every visit, and screening for misuse behaviour.^[8]
After 1-3 months of stable relief, consider a supervised trial of dose reduction — postherpetic neuralgia in particular can remit spontaneously, and trigeminal neuralgia can enter remission — tapering gradually to avoid withdrawal/rebound symptoms.

Treatment Failure / Next Step

Confirm the trial was actually adequate: the correct dose was reached (or the maximum tolerated dose, if lower) for at least 2-3 months, with real adherence — a "failed" trial that was underdosed or too short is not a true failure.
Re-confirm the diagnosis: re-screen with DN4/painDETECT, reconsider whether an undiagnosed reversible cause (for example, a compressive lesion or an uncontrolled metabolic cause) is driving the pain, and re-examine for a nociceptive or mixed-pain component that would need a different approach.
For partial response to first-line monotherapy: add a second first-line agent from a different class (for example, a gabapentinoid plus a TCA or SNRI) rather than repeatedly increasing the same drug beyond its tolerated dose.
For no response to an adequate first-line trial: switch to a different first-line class rather than trying a second agent from the same class.
For localized pain that persists despite an adequate systemic trial: add topical lidocaine or capsaicin over the specific painful area.
For pain that remains significant despite adequate first- and second-line trials, alone and in combination: refer for specialist input on third-line options — tramadol or another opioid as a monitored trial, or botulinum toxin A injections for refractory focal peripheral neuropathic pain.
For trigeminal neuralgia failing carbamazepine: switch to oxcarbazepine, or reduce the carbamazepine dose to a tolerable level and add baclofen; if medical therapy remains inadequate, refer for neurosurgical evaluation.
Throughout, actively distinguish between "the drug isn't working" and "the drug isn't tolerated" — an intolerable side effect at an inadequate dose calls for a different agent, not abandoning pharmacotherapy altogether.

Common Errors to Avoid

Using acetaminophen or an NSAID as primary therapy for neuropathic pain — evidence does not support their use as an effective standalone treatment, with the exception of the acute phase of nerve root compression, where they are appropriate.
Combining a TCA with an SNRI, given the added serotonergic and cardiac risk with no established additional benefit.^[2]
Declaring a first-line agent a failure before reaching an adequate dose or an adequate 2-3 month trial duration.
Starting tramadol or another opioid as a first- or second-line agent instead of reserving it for after adequate first- and second-line trials.
Missing the additive respiratory depression risk when a gabapentinoid is combined with an opioid — counsel on this specifically and use the lowest effective combined doses.^[3]
Forgetting renal dose adjustment for gabapentin, pregabalin, duloxetine (contraindicated below ClCr 30 mL/min), venlafaxine, or tramadol.
Starting a TCA in an older adult or a patient with cardiac disease without checking for contraindications or obtaining an ECG first.
Using codeine, or tramadol, in a child under 12 years of age.
Not setting realistic expectations up front — patients and prescribers who expect complete pain resolution often see a genuinely successful partial response as a failure, leading to unnecessary drug-switching or dose escalation.
Treating trigeminal neuralgia with the standard first-line neuropathic pain agents instead of carbamazepine or oxcarbazepine — it responds poorly to the usual first-line drugs.
Missing a red flag (progressive neurologic deficit, cauda equina signs, features suggesting malignancy) and treating symptomatically instead of investigating and referring.
Using cannabinoids as a routine, general-purpose neuropathic pain therapy rather than reserving them for their specific approved indication under specialist direction.

Clinical Decision Algorithm

Algorithm A — Initial assessment: confirming neuropathic pain

Chronic pain presentation with descriptors suggesting a possible neuropathic component (burning, shooting, electric shock-like, numbness, tingling)

Screen for red flags: progressive neurologic deficit, cauda equina signs, suspected malignancy/infection, zoster ophthalmicus

Red flags present

Investigate and refer urgently — do not begin neuropathic pain pharmacotherapy presumptively

No red flags

Apply DN4 (clinician-administered) or painDETECT (patient-completed) screening

DN4 4 or more out of 10, or painDETECT 19 or higher

Neuropathic pain component confirmed — proceed to Algorithm B, C, or D depending on the specific presentation

DN4 under 4, or painDETECT 12 or below

Neuropathic component unlikely — reassess for a nociceptive or mixed-pain cause and treat accordingly

Algorithm B — Chronic peripheral and central neuropathic pain (diabetic peripheral neuropathy, postherpetic neuralgia, post-stroke/spinal cord injury pain, and others)

Confirmed neuropathic pain, not trigeminal neuralgia and not acute nerve root compression

Start one 1st-line agent — gabapentin, pregabalin, duloxetine, venlafaxine, or a TCA — selected by comorbidities and tolerability; start low, titrate over weeks to the target or maximum tolerated dose^[1]

Adequate response after a 2-3 month trial at target/maximum tolerated dose

Continue; reassess periodically and consider a supervised taper after 1-3 months of stable relief

Partial or no response

Partial response: add a 2nd 1st-line agent from a different class. No response: switch to a different 1st-line class

Localized pain area

Add topical lidocaine or capsaicin over the painful area

Diffuse pain, or still inadequate after combination

Refer for specialist input: a 3rd-line trial of tramadol/another opioid, or botulinum toxin A for refractory focal peripheral pain

Algorithm C — Trigeminal neuralgia

Paroxysmal, electric shock-like facial pain in a trigeminal distribution, triggered by light touch

Start carbamazepine — 1st line specifically for this condition^[9]

Good response, tolerated

Continue on the sustained-release formulation; consider periodic dose tapering if remission occurs

Intolerable side effects or inadequate response

Switch to oxcarbazepine, or reduce carbamazepine to a tolerable dose and add baclofen

Still inadequate: refer for neurosurgical evaluation — microvascular decompression or an ablative procedure

Algorithm D — Acute neuropathic pain of herpes zoster, and preventing escalation to postherpetic neuralgia

New dermatomal vesicular eruption with neuropathic pain, or strongly suspected zoster sine herpete in a patient over 60

Within 72 hours of rash onset, or new vesicles still forming, ophthalmic involvement, or immunosuppressed

Start an oral antiviral — acyclovir, valacyclovir, or famciclovir — see Drug Tables

Beyond 72 hours, rash resolved, immunocompetent

Antiviral benefit is limited at this point — focus on pain control

Treat the acute neuritic pain with a TCA (e.g., amitriptyline) and/or gabapentin, escalating as needed; consider a short opioid course for severe acute pain

If pain persists beyond the acute phase as postherpetic neuralgia, manage per Algorithm B — topical lidocaine is specifically well suited to this condition

Drug Tables

How to use this table: doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Gabapentinoids (1st line)

Drug	Dosage	Adverse effects	Drug interactions	Comments
Gabapentin	Initial: 300-400 mg/day PO, in 1 dose at bedtime Titration: Increase at weekly intervals to BID then TID dosing as tolerated Usual effective dose: 1200-3600 mg/day in divided doses Maximum: 3600 mg/day	Sedation, ataxia, tremor; less commonly GI upset, peripheral edema, vision changes, weight gain, respiratory depression	Potentiates respiratory depression risk when combined with opioids. Aluminum/magnesium-containing antacids can decrease bioavailability — separate administration.	Renally cleared — reduce dose if ClCr is under 60 mL/min.
Pregabalin	Initial: 50-150 mg/day PO in 2 divided doses Titration: Increase weekly by 50-150 mg/day Usual effective dose: 300-600 mg/day Maximum: 600 mg/day	Sedation, ataxia, peripheral edema, diplopia, weight gain, dry mouth	No major pharmacokinetic interactions; potentiates respiratory depression risk when combined with opioids.	BID dosing is an advantage over gabapentin for adherence. Renally cleared — reduce dose if ClCr is under 60 mL/min. Doses over 300-450 mg/day may add little further pain benefit for some patients.

Tricyclic antidepressants (1st line)

All TCAs: metabolized by cytochrome P450, with potential interactions with other CYP substrates/inhibitors (e.g., erythromycin, fluoxetine, fluvoxamine, paroxetine) or inducers (e.g., carbamazepine, phenytoin, rifampin); increased sedation with other CNS depressants such as alcohol; increased anticholinergic burden with other anticholinergic agents. Avoid in patients with prostatic hypertrophy, angle-closure glaucoma, or significant heart disease because of cardiac conduction/arrhythmia risk.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Amitriptyline	Initial: 10-25 mg PO QHS Titration: Increase by 10-25 mg every 3-7 days until relief or intolerable side effects Usual effective dose: 50-75 mg/day	Dry mouth, constipation, drowsiness, blurred vision, urinary retention, weight gain, orthostatic hypotension, rare cardiac conduction effects	See class note above.	Most sedating TCA — preferable when insomnia is also present. Avoid in patients over 65, with cardiac disease, glaucoma, or urinary retention risk.
Nortriptyline	Initial: 10-25 mg PO QHS Titration: Increase by 10-25 mg every 3-7 days until relief or intolerable side effects Usual effective dose: 50-75 mg/day	Same class effects as amitriptyline, generally less pronounced	See class note above.	A metabolite of amitriptyline; better tolerated — often preferred in older adults if a TCA is still the right choice.
Desipramine	Initial: 10-25 mg PO QHS Titration: Increase by 10-25 mg every 3-7 days until relief or intolerable side effects Usual effective dose: 50-75 mg/day	Same class effects as amitriptyline, generally the least sedating/anticholinergic TCA	See class note above.	A reasonable choice when sedation or anticholinergic burden from amitriptyline is not tolerated.

SNRIs (1st line)

Drug	Dosage	Adverse effects	Drug interactions	Comments
Duloxetine	Initial: 30 mg/day PO if tolerability is a concern, for 1-2 weeks Usual effective dose: 60 mg PO daily	Nausea, drowsiness, insomnia, dizziness, dry mouth	Avoid potent CYP1A2 inhibitors (e.g., fluvoxamine) and MAOIs.	Do not use with severe renal impairment (ClCr under 30 mL/min) or significant hepatic impairment.
Venlafaxine XR	Initial: 37.5 mg PO daily Titration: Increase weekly by 37.5-75 mg/day Usual effective dose: 150-225 mg/day Maximum: 375 mg/day	Hypertension (dose-related), ataxia, sedation, insomnia, nausea, sweating, dry mouth, constipation, anxiety, anorexia	Levels may be increased by CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, quinidine) or CYP3A4 inhibitors (e.g., erythromycin, itraconazole, ketoconazole, grapefruit juice). Contraindicated with MAOIs.	Duloxetine is generally preferred given more consistent efficacy evidence.

Topical agents (2nd line, localized peripheral neuropathic pain)

Drug	Dosage	Adverse effects	Drug interactions	Comments
Lidocaine 5% cream/ointment	Adults: Apply to the painful area up to 3-4 times daily as needed	No significant systemic effects when used appropriately on intact skin; excessive use, application to broken skin, or an occlusive covering may result in systemic effects such as bradycardia or hypotension	No clinically significant drug interactions at recommended topical use.	Do not use with an occlusive dressing. Most effective for postherpetic neuralgia. A dedicated transdermal patch is not marketed in Canada.
Capsaicin cream (low concentration)	Adults: Apply a thin layer to the painful area 3-4 times daily	Burning/stinging on application, usually diminishing with continued regular use	No clinically significant drug interactions at recommended topical use.	Warn patients about the initial application burning so they do not stop prematurely. Wash hands thoroughly after use; avoid contact with eyes/mucous membranes. The high-concentration 8% patch used in trials is not marketed in Canada.

Antiepileptics for trigeminal neuralgia and refractory adjunctive use

Carbamazepine and oxcarbazepine are 1st/2nd line specifically for trigeminal neuralgia. Clonazepam, valproic acid/divalproex sodium, lamotrigine, and topiramate are reserved for refractory cases, as an adjunct, or when carbamazepine/oxcarbazepine cannot be used.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Carbamazepine	Initial: 100 mg PO BID-QID Titration: Increase by 100-200 mg/day at weekly intervals Usual effective dose: 400-1200 mg/day in 2-4 divided doses (sustained-release formulation may improve adherence, given Q8-12H)	Drowsiness, ataxia, dizziness, nausea, hyponatremia; rare allergic rash, hepatitis, or bone marrow suppression	Induces several CYP isoenzymes, increasing clearance of many drugs (e.g., oral contraceptives, warfarin, risperidone, TCAs); its own clearance may be reduced by CYP3A4 inhibitors (e.g., erythromycin, grapefruit juice, itraconazole, ketoconazole).	1st line for trigeminal neuralgia. Consider HLA-B*1502 screening in patients of Asian ancestry given increased severe skin reaction risk. CBC, electrolytes, and liver enzymes roughly every 1-2 weeks for the first 3 months, then periodically.
Oxcarbazepine	Initial: 75-150 mg PO BID Titration: Increase as tolerated Maximum: 1200 mg/day	Drowsiness, ataxia, dizziness, nausea, hyponatremia (may be more common than with carbamazepine, especially in younger patients); rare allergic rash, hepatitis, or bone marrow suppression	Induces CYP isoenzymes, similar to carbamazepine but with a lower propensity for interactions.	Alternative to carbamazepine with similar efficacy and generally fewer drug interactions/side effects, though a higher hyponatremia risk.
Clonazepam	Initial: 0.5 mg PO QHS, increased gradually as tolerated	Sedation	Additive sedation with other CNS depressants (alcohol, opioids); levels may be increased by CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) or reduced by inducers (e.g., carbamazepine, phenytoin).	Adjunct for trigeminal neuralgia. Discontinue gradually to avoid withdrawal symptoms.
Divalproex sodium	Initial: 250 mg PO BID Titration: Increase by 250 mg/day every 3-4 days as needed	Nausea, alopecia, tremor, weight gain, increased hepatic enzymes	Inhibits CYP2C9, potentially reducing clearance of substrates (e.g., fluoxetine, fluvastatin, sertraline, warfarin); avoid combining with ASA or warfarin. Carbamazepine, phenytoin, and phenobarbital can increase its clearance.	Refractory adjunct/alternative for trigeminal neuralgia. Avoid in pregnancy given neural tube defect risk. Baseline and periodic liver function tests, especially in the first 6 months.
Lamotrigine	Initial: 25 mg PO daily Titration: Slow titration per product monograph to a target of 200-400 mg/day	Rash (rare but can be serious — Stevens-Johnson syndrome), dizziness, headache, diplopia	Levels reduced by carbamazepine/phenytoin; levels increased by valproic acid — a much slower titration is required if combined with valproic acid.	Refractory trial-and-error option. Titrate very slowly to minimize serious rash risk.
Topiramate	Initial: 25 mg PO BID Titration: Increase weekly to a target of 100-400 mg/day	Paresthesia, cognitive slowing, weight loss, rare acute angle-closure glaucoma or metabolic acidosis	Additive CNS depressant effects with alcohol/other CNS depressants; may reduce oral contraceptive efficacy at higher doses.	Refractory trial-and-error option.
Baclofen	Initial: 5 mg PO TID Titration: Increase by 5 mg every 3 days as tolerated Usual effective dose: 30-80 mg/day in divided doses	Sedation, muscle weakness, nausea, dizziness	Potential additive CNS depression with benzodiazepines, opioids, TCAs, and some antihypertensives.	Adjunct to carbamazepine in trigeminal neuralgia. Taper gradually when discontinuing to minimize seizure risk.

Opioids (3rd line, including tramadol)

Reserve for after an adequate trial of first- and second-line agents, applying standard chronic non-cancer pain opioid safeguards. Avoid meperidine (accumulation of the excitotoxic metabolite normeperidine can cause myoclonus and seizures). Codeine is a poor choice for moderate-severe pain of any kind given unreliable conversion to morphine across CYP2D6 metabolizer phenotypes, and codeine/tramadol are not recommended under age 12.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Tramadol (controlled-release)	Initial: 100-150 mg PO once daily depending on product Titration: Increase gradually per product monograph Maximum: 300-400 mg/day depending on product	Sedation, ataxia, constipation, nausea, orthostatic hypotension; seizures and respiratory depression at higher doses	Do not use within 14 days of an MAOI. Caution with drugs that lower seizure threshold (SSRIs, TCAs, bupropion). Carbamazepine may decrease its analgesic effect. Increased sedation with other CNS depressants.	3rd line, alongside other opioids, per current evidence.
Morphine (immediate-release)	Initial: 5-10 mg PO Q4-6H PRN, not to exceed 50 mg/day initially	Nausea, constipation, drowsiness, risk of dependence/misuse, allergic reactions	Additive sedation with other CNS depressants such as alcohol; decreased analgesic effect with somatostatin, rifampin.	Convert to an equivalent daily controlled-release dose after 1-2 weeks once the effective dose is established.
Hydromorphone (immediate-release)	Initial: 1-2 mg PO Q4H PRN, not to exceed 10 mg/day initially	Same class effects as morphine	Same class interactions as morphine.	Convert to an equivalent daily controlled-release dose after 1-2 weeks once the effective dose is established.
Oxycodone (immediate-release)	Initial: 5-7.5 mg PO Q4-6H PRN, not to exceed 33 mg/day initially	Same class effects as morphine	Same class interactions as morphine.	Convert to an equivalent daily controlled-release dose after 1-2 weeks once the effective dose is established.
Oxycodone/naloxone (controlled-release)	Initial: 1 tablet (oxycodone 10 mg/naloxone 5 mg) PO Q12H Maximum: Oxycodone 40 mg/naloxone 20 mg Q12H	Same class effects as morphine	Same class interactions as morphine.	Naloxone is added to reduce opioid-induced constipation and deter parenteral misuse. Excipients can cause severe toxicity if the tablet is misused parenterally.
Fentanyl (transdermal)	Initial: 12 mcg/h transdermal patch Q72H	Same class effects as morphine; allergic reactions including rash	Inhibitors of CYP3A4 (e.g., cimetidine, efavirenz, erythromycin, itraconazole, ketoconazole, ritonavir) may potentiate its effects.	For opioid-tolerant patients only — do not use in opioid-naive patients or children given respiratory depression risk. Follow product monograph conversion tables when switching from another opioid.
Tapentadol	Initial: 50 mg PO Q4-6H, per product monograph Titration: Titrate per product monograph to effect	Nausea, dizziness, somnolence, constipation; lower constipation/GI burden than pure mu-agonists at comparable analgesic doses for some patients	Do not use within 14 days of an MAOI; caution with other serotonergic/seizure-threshold-lowering drugs given its added norepinephrine reuptake inhibition.	A dual-mechanism opioid (mu-agonist plus noradrenergic reuptake inhibition) sometimes considered for neuropathic pain given this second mechanism; positioned alongside other opioids as 3rd line.
Methadone	Dosing: Specialist-directed only	Same class effects as morphine, plus QT prolongation risk	Numerous CYP-mediated interactions and unpredictable, highly variable pharmacokinetics.	Specialist-initiated only — requires specific prescribing authorization and experience. Consider specifically when refractory neuropathic pain coexists with opioid use disorder.

Botulinum toxin (3rd line, refractory focal peripheral neuropathic pain)

Drug	Dosage	Adverse effects	Drug interactions	Comments
OnabotulinumtoxinA	Dosing: Per specialist injection protocol	Injection-site pain/bruising; rare focal muscle weakness	No clinically significant systemic drug interactions at doses used for focal injection.	Specialist-administered subcutaneous injections into the painful area, typically repeated approximately every 12 weeks.

Cannabinoids (not routinely recommended)

Current evidence gives a weak recommendation against cannabinoids as general neuropathic pain therapy. Nabiximols retains a specific Health Canada-approved indication for multiple sclerosis-related neuropathic pain and spasticity and should be reserved for that context under specialist direction.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Nabiximols (delta-9-THC/cannabidiol)	Dosing: Oromucosal spray, individually titrated per product monograph up to a maximum of 12 sprays/day	Dizziness, sedation, dry mouth, nausea, cognitive effects, dependence potential	Additive CNS depression with other sedating drugs; caution with other serotonergic/hepatically metabolized drugs.	Reserve for its specific approved MS-related neuropathic pain/spasticity indication, under specialist direction.
Nabilone	Initial: 0.5 mg PO QHS or BID Titration: Titrate cautiously per product monograph	Sedation, dizziness, dry mouth, mood changes	Additive CNS depression with other sedating drugs.	A synthetic cannabinoid without a neuropathic-pain-specific approved indication; use only under specialist direction if trialled for refractory pain.

Antivirals for acute herpes zoster

Most effective when started within 72 hours of rash onset; also reasonable in a patient over 60 with new severe unilateral neuropathic pain in a dermatomal distribution even before a rash appears, since these agents are safe and well tolerated. Reduces the severity of the acute rash/pain; evidence that antivirals reliably prevent postherpetic neuralgia is limited.

Drug	Dosage	Adverse effects	Drug interactions	Comments
Acyclovir	Adults: 800 mg PO 5 times daily for 7 days	Nausea, headache; rare nephrotoxicity, especially if inadequately hydrated	Additive nephrotoxicity with other nephrotoxic drugs.	Requires the most frequent daily dosing of the three antivirals.
Valacyclovir	Adults: 1000 mg PO TID for 7 days	Nausea, headache; rare nephrotoxicity/thrombotic microangiopathy at high doses	Additive nephrotoxicity with other nephrotoxic drugs.	A prodrug of acyclovir with improved bioavailability, allowing less frequent dosing.
Famciclovir	Adults: 500 mg PO TID for 7 days	Nausea, headache	Additive nephrotoxicity with other nephrotoxic drugs.	Comparable efficacy to valacyclovir with TID dosing.

Evidence note: drug inventory, dosing, adverse effects, and comments reflect standard Canadian practice, cross-checked against current NeuPSIG, Diabetes Canada, CanPain SCI, and European Academy of Neurology guidance.^[12]

References

Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis — The Lancet Neurology, NeuPSIG Review Update Study Group (Soliman N, Moisset X, Ferraro MC, et al.). Lancet Neurol 2025;24(5):413-428
The serotonin syndrome — New England Journal of Medicine (Boyer EW, Shannon M). N Engl J Med 2005;352(11):1112-1120
Gabapentin, opioids, and the risk of opioid-related death: a population-based nested case-control study — PLOS Medicine (Gomes T, Juurlink DN, Antoniou T, et al.). PLoS Med 2017;14(10):e1002396
Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4) — Pain (Bouhassira D, Attal N, Alchaar H, et al.). Pain 2005;114(1-2):29-36
painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain — Current Medical Research and Opinion (Freynhagen R, Baron R, Gockel U, Tölle TR). Curr Med Res Opin 2006;22(10):1911-1920
Neuropathy — Canadian Journal of Diabetes, Diabetes Canada Clinical Practice Guidelines Expert Committee (Bril V, Breiner A, Perkins BA, Zochodne D). Can J Diabetes 2018;42(Suppl 1):S217-S221
The CanPain SCI clinical practice guidelines for rehabilitation management of neuropathic pain after spinal cord injury: 2021 update — Spinal Cord (Loh E, Mirkowski M, Roa Agudelo A, et al.). Spinal Cord 2022;60(6):548-566
Guideline for opioid therapy and chronic noncancer pain — Canadian Medical Association Journal (Busse JW, Craigie S, Juurlink DN, et al.). CMAJ 2017;189(18):E659-E666
European Academy of Neurology guideline on trigeminal neuralgia — European Journal of Neurology (Bendtsen L, Zakrzewska JM, Abbott J, et al.). Eur J Neurol 2019;26(6):831-849
Treatment considerations for elderly and frail patients with neuropathic pain — Mayo Clinic Proceedings (Schmader KE, Baron R, Haanpää ML, et al.). Mayo Clin Proc 2010;85(3 Suppl):S26-S32
American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults — Journal of the American Geriatrics Society, 2023 AGS Beers Criteria Update Expert Panel. J Am Geriatr Soc 2023;71(7):2052-2081
Antiviral treatment for preventing postherpetic neuralgia — Cochrane Database of Systematic Reviews (Chen N, Li Q, Yang J, et al.). Cochrane Database Syst Rev 2014;(2):CD006866

Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.