Medications for Neuropathic Pain

Antiseizure medications

CarbamazepineCarbamazepine

Monitor CBC, sodium, and liver function during treatment

CYP3A4 inducers that may decrease efficacy of hormonal contraceptives and induce their own metabolism, requiring higher doses after initiation of therapy

First-line treatment for trigeminal neuralgia

Can cause Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN); consider genetic testing for HLA*B 1502 in higher risk populations

GabapentinGabapentin

Adjust dose in patients with renal insufficiency

LacosamideLacosamide

Monitor ECG for PR interval prolongation

Limited evidence for trigeminal neuralgia, used off-label for neuropathic pain

LamotrigineLamotrigine

Can cause SJS and TEN; consider genetic testing for HLA*B 1502 in higher risk populations

Drug interactions with hormonal contraceptives

OxcarbazepineOxcarbazepine

Considered as efficacious as carbamazepine for trigeminal neuralgia and useful for other paroxysmal neuropathic painConsidered as efficacious as carbamazepine for trigeminal neuralgia and useful for other paroxysmal neuropathic pain

May cause hyponatremia or decrease efficacy of oral contraceptives

Can cause SJS and TEN; consider genetic testing for HLA*B 1502 in higher risk populations.

PhenytoinPhenytoin

Limited data; second-line medication

PregabalinPregabalin

Mechanism similar to gabapentin but more stable pharmacokineticsMechanism similar to gabapentin but more stable pharmacokinetics

Adjust dose in patients with renal insufficiency

TopiramateTopiramate

Monitor for renal function; can cause kidney stones

Monitor for cognitive side effects

Can cause weight loss

May cause metabolic acidosis, requiring periodic serum bicarbonate monitoring

Approved for migraine prevention, used off-label for neuropathic pain

Valproate

Limited data, but strong support for treatment of migraine

ZonisamideZonisamide

Monitor for hypersensitivity reactions, as it is a sulfonamide derivative

Used off-label for migraine and neuropathic pain

Monitor for metabolic acidosis, cognitive impairment, and hyperthermia (can impair sweating)

Antidepressants

AmitriptylineAmitriptyline

Not recommended for older patients or patients with a cardiac condition because it has strong anticholinergic effects

Higher doses needed to relieve concomitant depression than those effective for pain

Desipramine or nortriptylineDesipramine or nortriptyline

Better tolerated than amitriptyline; adverse effect profile better with desipramine than nortriptylineBetter tolerated than amitriptyline; adverse effect profile better with desipramine than nortriptyline

Higher doses needed to relieve concomitant depression than those effective for pain

Not recommended for older patients or patients with a cardiac condition because it has strong anticholinergic effects

DuloxetineDuloxetine

Better tolerated than tricyclic antidepressants

Dosing goal for pain usually sufficient to treat concomitant depression or anxiety

MilnacipranMilnacipran

Effective for fibromyalgia; not used for neuropathic pain states

VenlafaxineVenlafaxine

More norepinephrine reuptake inhibition at higher doses (≥ 150 mg/day); lower dosages ineffective for neuropathic pain

Similar mechanism of action as duloxetineSimilar mechanism of action as duloxetine

Effective for pain, depression, and anxiety at this dose

Central alpha-2 adrenergic agonists

ClonidineClonidine

Also can be used transdermally or intrathecally

TizanidineTizanidine

Less likely to cause hypotension than clonidineLess likely to cause hypotension than clonidine

Corticosteroids

DexamethasoneDexamethasone

Used only for pain with an inflammatory component

PrednisonePrednisone

Used only for pain with an inflammatory component

NMDA-receptor antagonists

MemantineMemantine

Limited evidence of efficacy

DextromethorphanDextromethorphan

May have a role in neuropathic pain in patients who have developed tolerance or a lower pain threshold due to central sensitization

In > 90% of White people, rapid metabolism via hepatic cytochrome P-450 2D6, reduces the therapeutic effect

Metabolism of dextromethorphan blocked by quinidineMetabolism of dextromethorphan blocked by quinidine

Combination dextromethorphan/quinidine available for pseudobulbar affect in patients with amyotrophic lateral sclerosis Combination dextromethorphan/quinidine available for pseudobulbar affect in patients with amyotrophic lateral sclerosis

Oral sodium channel blockers

MexiletineMexiletine

Used only for neuropathic pain

For patients with a significant heart disorder, cardiac evaluation recommended before the medication is started

Topical

Capsaicin 0.025–0.075% (eg, cream, lotion)Capsaicin 0.025–0.075% (eg, cream, lotion)

Some evidence of efficacy in neuropathic pain and arthritis

Topical lidocaine 4–5% applied 1 hour before applying capsaicin can help limit irritationTopical lidocaine 4–5% applied 1 hour before applying capsaicin can help limit irritation

Capsaicin 8% patchCapsaicin 8% patch

Causes a severe sunburn-like skin reaction; oral opioids often required for up to 1 week after application of capsaicin 8% to manage the worsening cutaneous painCauses a severe sunburn-like skin reaction; oral opioids often required for up to 1 week after application of capsaicin 8% to manage the worsening cutaneous pain

Meaningful pain relief for 3 months after a single application

Topical lidocaine 4–5% applied 1 hour before applying capsaicin can help limit irritation.Topical lidocaine 4–5% applied 1 hour before applying capsaicin can help limit irritation.

EMLA

Usually considered for a trial if a lidocaine patch is ineffective; expensiveUsually considered for a trial if a lidocaine patch is ineffective; expensive

Lidocaine 5%Lidocaine 5%

Available as patch

Other

BaclofenBaclofen

May act via GABA-B receptor

Helpful in trigeminal neuralgia; used in other types of neuropathic pain

KetamineKetamine

Used for neuropathic pain; most evidence for complex regional pain syndrome

Various protocols used

Monitor liver function and ECG during treatment

Can cause hypertension, dysphoria/hallucinations, and with chronic use, cystitis