Drugs for Neuropathic Pain

Class/Drug	Dose*	Comments
Antiseizure drugs†
	200–400 mg twice a day	Monitor CBC and liver function during treatment May decrease efficacy of oral contraceptives First-line treatment for trigeminal neuralgia
	300–1200 mg 3 times a day	Starting dose usually 300 mg once a day Dosing goal: 600–1200 mg 3 times a day Adjust dose in patients with renal insufficiency
	600–1200 mg twice a day	Starting dose usually 300 mg once a day May cause hyponatremia or decrease efficacy of oral contraceptives
	300 mg once a day	Limited data; 2nd-line drug
	150–300 mg twice a day Starting dose usually 75 mg twice a day, increased by the same dosage weekly as necessary to a maximum of 300 mg orally twice a day	Adjust dose in patients with renal insufficiency
Valproate	250–500 mg twice a day	Limited data, but strong support for treatment of migraine
Antidepressants
	10–25 mg at bedtime (starting dose), increased weekly by the same dose to a maximum of 150 mg at bedtime	Dosing goal: About 100 mg/day (dosing for pain unlikely to be adequate for relieving depression or anxiety) Not recommended for older patients or patients with a heart disorder because it has strong anticholinergic effects May increase dose to 150 mg or sometimes higher
	10–25 mg at bedtime (starting dose), increased weekly by the same dose to maximum of 150 mg at bedtime	Dosing goal: About 100 mg/day (dosing for pain unlikely to be adequate for relieving depression or anxiety) Not recommended for older patients or patients with a heart disorder because it has strong anticholinergic effects May increase dose to 150 mg or sometimes higher
	20–60 mg once a day (starting dose) Starting at 20–30 mg once a day and increasing by the same dosage weekly to a goal of 60 mg/day; in some cases, increasing to 60 mg twice a day (especially in patients with concomitant depression or anxiety)	Better tolerated than tricyclic antidepressants Dosing goal for pain (60 mg/day) usually sufficient to treat concomitant depression or anxiety
	12.5 mg once a day on day 1, then increased to 12.5 mg twice a day on days 2 and 3, increased further to 25 mg twice a day on days 4 to 7, then 25 mg up to 4 times a day, not to exceed 200 mg/day	Effective for fibromyalgia; not used for neuropathic pain states
	Extended-release (easiest to use): 37.5–75 mg once a day, increased to a target dose of 150–225 mg once a day	More norepinephrine reuptake inhibition at higher doses (≥ 150 mg/day); lower dosages ineffective for neuropathic pain Effective for pain, depression, and anxiety at this dose
Central alpha-2 adrenergic agonists
	0.1 mg once a day	Also can be used transdermally or intrathecally
	2 mg every 6–8 hours (maximum 3 doses a day), increased by 2–4 mg every 1–4 days as needed (maximum: 36 mg a day)
Corticosteroids
	0.5–4 mg 4 times a day	Used only for pain with an inflammatory component
	5–60 mg once a day	Used only for pain with an inflammatory component
NMDA-receptor antagonists
	10–30 mg once a day	Limited evidence of efficacy
	30–120 mg 4 times a day	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 whites, rapid metabolism via hepatic cytochrome P-450 2D6, reducing the therapeutic effect
Oral sodium channel blockers
	150 mg once a day to 300 mg every 8 hours	Used only for neuropathic pain For patients with a significant heart disorder, cardiac evaluation recommended before the drug is started
Topical
	Apply 3 times a day	Some evidence of efficacy in neuropathic pain and arthritis
	Up to 4 at one time†	Meaningful pain relief for 3 months after a single application
EMLA	Apply 3 times a day, under occlusive dressing if possible
	Daily	Available as patch
Other
	Initially 5–10 mg 3 times a day; titrated to 60–120 mg in 3 divided doses	May act via GABA-B receptor Helpful in trigeminal neuralgia; used in other types of neuropathic pain
	60–90 mg/month IV	Evidence of efficacy in complex regional pain syndrome
* Route is oral unless otherwise indicated.

CBC = complete blood count; EMLA = eutectic mixture of local anesthetics; GABA = gamma-aminobutyric acid; NMDA = N-methyl-d-aspartate; WBCs = white blood cells.

Class/Drug

Dose*

Comments

Antiseizure drugs†

200–400 mg twice a day

Monitor CBC and liver function during treatment

May decrease efficacy of oral contraceptives

First-line treatment for trigeminal neuralgia

300–1200 mg 3 times a day

Starting dose usually 300 mg once a day

Dosing goal: 600–1200 mg 3 times a day

Adjust dose in patients with renal insufficiency

600–1200 mg twice a day

Starting dose usually 300 mg once a day

May cause hyponatremia or decrease efficacy of oral contraceptives

300 mg once a day

Limited data; 2nd-line drug

150–300 mg twice a day

Starting dose usually 75 mg twice a day, increased by the same dosage weekly as necessary to a maximum of 300 mg orally twice a day

Adjust dose in patients with renal insufficiency

Valproate

250–500 mg twice a day

Limited data, but strong support for treatment of migraine

Antidepressants

10–25 mg at bedtime (starting dose), increased weekly by the same dose to a maximum of 150 mg at bedtime

Dosing goal: About 100 mg/day (dosing for pain unlikely to be adequate for relieving depression or anxiety)

Not recommended for older patients or patients with a heart disorder because it has strong anticholinergic effects

May increase dose to 150 mg or sometimes higher

10–25 mg at bedtime (starting dose), increased weekly by the same dose to maximum of 150 mg at bedtime

Dosing goal: About 100 mg/day (dosing for pain unlikely to be adequate for relieving depression or anxiety)

Not recommended for older patients or patients with a heart disorder because it has strong anticholinergic effects

May increase dose to 150 mg or sometimes higher

20–60 mg once a day (starting dose)

Starting at 20–30 mg once a day and increasing by the same dosage weekly to a goal of 60 mg/day; in some cases, increasing to 60 mg twice a day (especially in patients with concomitant depression or anxiety)

Better tolerated than tricyclic antidepressants

Dosing goal for pain (60 mg/day) usually sufficient to treat concomitant depression or anxiety

12.5 mg once a day on day 1, then increased to 12.5 mg twice a day on days 2 and 3, increased further to 25 mg twice a day on days 4 to 7, then 25 mg up to 4 times a day, not to exceed 200 mg/day

Effective for fibromyalgia; not used for neuropathic pain states

Extended-release (easiest to use): 37.5–75 mg once a day, increased to a target dose of 150–225 mg once a day

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

Effective for pain, depression, and anxiety at this dose

Central alpha-2 adrenergic agonists

0.1 mg once a day

Also can be used transdermally or intrathecally

2 mg every 6–8 hours (maximum 3 doses a day), increased by 2–4 mg every 1–4 days as needed (maximum: 36 mg a day)

Corticosteroids

0.5–4 mg 4 times a day

Used only for pain with an inflammatory component

5–60 mg once a day

Used only for pain with an inflammatory component

NMDA-receptor antagonists

10–30 mg once a day

Limited evidence of efficacy

30–120 mg 4 times a day

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 whites, rapid metabolism via hepatic cytochrome P-450 2D6, reducing the therapeutic effect

Oral sodium channel blockers

150 mg once a day to 300 mg every 8 hours

Used only for neuropathic pain

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

Topical

Apply 3 times a day

Some evidence of efficacy in neuropathic pain and arthritis

Up to 4 at one time†

Meaningful pain relief for 3 months after a single application

EMLA

Apply 3 times a day, under occlusive dressing if possible

Daily

Available as patch

Other

Initially 5–10 mg 3 times a day; titrated to 60–120 mg in 3 divided doses

May act via GABA-B receptor

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

60–90 mg/month IV

Evidence of efficacy in complex regional pain syndrome

* Route is oral unless otherwise indicated.

CBC = complete blood count; EMLA = eutectic mixture of local anesthetics; GABA = gamma-aminobutyric acid; NMDA = N-methyl-d-aspartate; WBCs = white blood cells.

In these topics

Neuropathic Pain