NEUROPATHIC PAIN EVIDENCE SUMMARY

Amitriptyline

  • Studied Dose Range: 12.5 mg to 150 mg/day
  • Duration of Studies: 4 to 9 weeks
  • Things to Consider:
    • Available preparations: oral tablets
    • Typically taken at bedtime due to sleepiness effect
OUTCOME RELATIVE BENEFIT/RISK TREATMENT
EVENT RATE (%) 		PLACEBO
EVENT RATE (%) 		NNT/NNH
Moderate pain improvement or better 2.0
(1.5, 2.8) 		2.0(0.25) = 50% 25% 4
Dry mouth * 12/35 = 34.3% 5.66
(1.37, 23.39) 		2/33 = 6.1% 4
Sleepiness 3.77
(1.17, 12.18) 		12/35 = 34.3% 3/33 = 9.1% 4
Loss of balance 6.60
(0.86, 50.79) 		7/35 = 20% 1/33 = 3% NSS
Stopped due to side effects 2.23
(1.11, 4.45) 		25/159 = 15.7% 10/144 = 6.9% 12
Cost Amitriptyline 10 mg once daily: $1.50 to $2.00 (CAN)
Amitriptyline 25 mg once daily: $2.50 to $3.50 (CAN)
(Canadian medication cost for 30 days supply without pharmacy dispensing fees included)
* Confidence intervals were not provided in the article used for summary therefore we calculated the interval using MedCalc
  • Adverse Event

Cannabinoids

  • Agents Studied: Nabiximols, nabilone and medical marijuana
  • Duration of Studies: 0.25 to 98 days
  • Things to Consider:
    • Available preparations for nabilone and nabiximols: oral capsules, oral sprays
    • Side effects are likely more common (many studies included people with proven tolerance to cannabinoids)
    • Oral capsules: Can be taken once or twice daily
    • Oral spray: Can be used multiple times per day
OUTCOME RELATIVE BENEFIT/RISK TREATMENT
EVENT RATE (%) 		PLACEBO
EVENT RATE (%) 		NNT/NNH
Greater than 30% improvement in pain 1.37
(1.14, 1.64) 		1.37(0.25) = 34.3% 25% 11
Adverse Event - Sleepiness 1.66
(1.46, 1.89) 		320/636 = 50% 224/737 = 30% 5
Adverse Event - "Feeling High" 10.6
(6.86, 16.50) 		162/470 = 35% 17/562 = 3% 4
Adverse Event - Speech disorders 2.91
(1.28, 6.64) 		42/132 = 32% 5/68 = 7% 5
Adverse Event - Dizziness 2.87
(2.02, 4.08) 		116/363 = 32% 33/303 = 11% 5
Adverse Event - Stopped due to side effects Due to combination of studies, unable to obtain accurate value 90/849 + 108/1003 + 40/363 = 11% 38/725 + 18/1108 + 11/303 = 3% 14
Cost Nabilone 2 to 6 mg/day: $94 to $305 (CAN) Nabiximols 4-12 sprays/day: $226 to $903 (CAN) Medical marijuana 1-3 gm/day: $250 to $750 (CAN)
(Canadian medication cost for 30 days supply without pharmacy dispensing fees included)
  • Adverse Event

Duloxetine

  • Studied Dose Range: 60 mg/day
  • Duration of Studies: 8 to 12 weeks
  • Things to Consider:
    • Available preparations: oral capsules
OUTCOME RELATIVE BENEFIT/RISK TREATMENT
EVENT RATE (%) 		PLACEBO
EVENT RATE (%) 		NNT/NNH
Greater than 30% improvement in pain 1.53
(1.33, 1.75) 		1.53(0.25) = 38.3% 25% 8
Adverse Event - Nausea 2.61
(2.14, 3.18) 		424/1816 = 23.3% 156/1826 = 8.5% 7
Adverse Event - Dry mouth 2.63
(1.89, 3.67) 		125/1036 = 12.1% 44/968 = 4.5% 14
Adverse Event - Sleepiness 2.94
(2.17, 3.97) 		149/1335 = 11.2% 55/1343 = 4.1% 15
Adverse Event - Dizziness 1.84
(1.35, 2.51) 		109/1131 = 9.6% 56/1126 = 5.0% 22
Adverse Event - Stopped due to side effects 1.95 (1.60, 2.37) 257/2372 = 10.8% 137/2465 = 5.6% 19
Cost Duloxetine 60 mg once daily: $29 to $32 (CAN)
(Canadian medication cost for 30 days supply without pharmacy dispensing fees included)
  • Adverse Event

Gabapentin

  • Studied Dose Range: 600 to 3600 mg/day
  • Duration of Studies: 2 to 15 weeks
  • Things to Consider:
    • Available preparations: oral capsules
    • High doses requires administration multiple times per day
    • Can cause gait abnormalities which increases fall risk for elderly patients
OUTCOME RELATIVE BENEFIT/RISK TREATMENT
EVENT RATE (%) 		PLACEBO
EVENT RATE (%) 		NNT/NNH
At least a moderate improvement in pain 1.73
(1.47, 2.03) 		1.73(0.25) = 43.3% 25% 6
Adverse Event - Dizziness 2.87
(2.40, 3.44) 		525/2755 = 19.1% 130/1984 = 6.6% 6
Adverse Event - Problems with balance 5.53
(2.49, 12.28) 		39/279 = 14% 5/231 = 2.2% 9
Adverse Event - Sleepiness 2.82
(2.27, 3.50) 		358/2531 = 14.1% 92/1757 = 5.2% 12
Adverse Event - Swelling (especially in ankles) 4.12
(2.66, 6.39) 		132/2003 = 6.6% 20/1322 = 1.5% 20
Adverse Event - Stopped due to side effects 1.38
(1.14, 1.67) 		291/2557 = 11.4% 144/1789 = 8.0% 31
Cost Gabapentin 300 mg once daily: $5.50 to $6.00 (CAN)
(Canadian medication cost for 30 days supply without pharmacy dispensing fees included)
  • Adverse Event

High-Dose Opioids

  • Agents Studied: Morphine and oxycodone
  • Studied Dose Range: 90 mg to 180 mg morphine equivalents/day (typically 60-110 mg/day)
  • Duration of Studies: 1 day to 12 weeks
  • Things to Consider:
    • Available preparations: oral capsules, oral tablets, oral liquid
    • Last option due to risk of dependence, side-effects, and long-term serious harms
    • If absolutely needed, doses should be kept ≤ 90 mg/day of morphine equivalents
    • Should be used short-term
    • Risk of addiction with long term use
    • Side effects are more common in older patients and may lead to falls
OUTCOME RELATIVE BENEFIT/RISK TREATMENT
EVENT RATE (%) 		PLACEBO
EVENT RATE (%) 		NNT/NNH
Benefit (at least 33% pain relief) 1.71
(1.33, 2.21) 		1.71(0.25) = 42.8% 25% 6
Adverse Event - Constipation 3.89
(2.91, 5.20) 		192/566 = 33.9% 48/548 = 8.8% 4
Adverse Event - Sleepiness 1.93
(1.07, 3.49) 		110/376 = 29.3% 49/362 = 13.5% 7
Adverse Event - Nausea 2.95
(2.22, 3.94) 		154/566 = 27.2% 51/548 = 9.3% 6
Adverse Event - Dizziness 2.60
(1.57, 4.32) 		122/566 = 21.6% 45/548 = 8.2% 8
Adverse Event - Stopped due to side effects 2.92
(1.77, 4.83) 		55/435 = 12.6% 18/432 = 4.2% 12
Cost Morphine 60 mg SR Once Daily: $14 - $30 (CAN)
(Canadian medication cost for 30 days supply without pharmacy dispensing fees included)
  • Adverse Event

Pregabalin

  • Studied Dose Range: 300 mg/day
  • Duration of Studies: 4 to 24 weeks
  • Things to Consider:
    • Available preparations: oral capsules
    • Recommended to be taken during nighttime due to possible sleepiness
    • Can cause gait abnormalities which increases fall risk for elderly patients
OUTCOME RELATIVE BENEFIT/RISK TREATMENT
EVENT RATE (%) 		PLACEBO
EVENT RATE (%) 		NNT/NNH
Greater than 30% improvement in pain 1.65
(1.34, 2.04) 		1.65(0.25) = 41.3% 25% 7
Adverse Event - Dizziness 3.39
(2.82, 4.08) 		422/1445 = 29.2% 126/1465 = 8.6% 5
Adverse Event - Sleepiness 3.96
(3.08, 5.09) 		271/1445 = 18.8% 70/1465 = 4.8% 8
Adverse Event - Stopped due to side effects 1.92
(1.55, 2.37) 		218/1445 = 15.1% 115/1465 = 7.8% 14
Cost Pregabalin 300 mg once daily: $17 to $52 (CAN)
(Canadian medication cost for 30 days supply without pharmacy dispensing fees included)
  • Adverse Event

Other Neuropathic Pain Interventions

Below are potential treatment options that were not included in the comparison tool due to limited evidence for these agents. Systematic reviews including less than 200 patients and/or meta-analyses of nonspecific or unclear outcomes were excluded. This was done in order to reduce risk of bias and a potential overestimation of benefit.

Healthcare professionals may want to see the evidence for these agents and therefore, a summary of what was found in the literature for reference is provided along with some clinical limitations for the agents and typical dosing.

INTERVENTION PRIMARY CONDITION OUTCOME POSSIBLE BENEFIT PLACEBO CLINICAL LIMITATIONS
Capsaicin (Low Concentration) * Applied topically 3x/day to area Peripheral Neuropathy >50% pain relief ~29% ~13%
  • Can lead to significant burning/stinging of the skin
  • This tends to be reduced with repeated use
  • Do not use on damaged or broken skin and avoid sensitive areas
Tramadol 100 to 200 mg daily Chronic Neuropathic Pain >30% pain relief over baseline ~57% ~19%
  • Can lead to drowsiness
  • May cause opioid dependence
Botox
50 to 200 IU to area every three months 		Peripheral Neuropathy 30%, 50% or moderate pain relief (pooled) ~60% ~6%
  • Requires repeated injections
Carbamazepine
100 to 2400 mg daily
  • Trigeminal Neuralgia
  • Post-herpetic Neuralgia
  • Post-Stroke/Central
 		Any pain improvement ~61% ~9%
  • Can lead to drowsiness
  • Need to monitor CBC with differential and platelets prior to and during therapy
Venlafaxine * 75 to 150 mg daily
  • Diabetic Neuropathy
  • Atypical facial pain
 		Moderate pain relief or better ~47% ~22%
  • Can cause sleep disturbances and headaches
  • Can cause withdrawal effects if stopped abruptly

Neuropathic Pain

Why doesn’t this calculator cover all treatment options available?

This online calculator does not cover all treatment options available for neuropathic pain. We only included the medication treatments that had the highest quality evidence. A healthcare provider may consider other options not listed in this calculator to manage symptoms, depending on specific needs.

Where can I find the evidence used to create this calculator?

The data used for this calculator can be found within the Neuropathic Pain Systematic Review

Additional tools created with this data can be found at Neuropathic Pain Decision Aid

What is neuropathic pain?1

1. Taylor D. Neuropathic Pain. https://www.emedicinehealth.com/neuropathic_pain_nerve_pain/page2_em.htm. Updated November 2017. Accessed January 13, 2018.

,2

2. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Jul 6;(7):CD008242.

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3. Watson P. Neuropathic Pain. https://www-e-therapeutics-ca.login.ezproxy.library.ualberta.ca/search. Updated May 2017. Accessed January 13, 2018.

Neuropathic pain is a type of pain generally caused by damaged nerves in the body. This damage may have resulted from a medical condition like diabetes, exposure to a toxin, alcohol, or previous surgery. Because the nerves are damaged, pain is not felt the same way as other types of pain.

Unlike pain from an injury, neuropathic pain can happen from normal, light touch, such as from clothing brushing against skin. This leads to feelings of pain that can be described as “burning”, “shooting” or “tingling”. Every person experiences neuropathic pain differently. Neuropathic pain can feel constant, come and go, or it can change in intensity.

Can neuropathic pain be treated or cured?3

3. Watson P. Neuropathic Pain. https://www-e-therapeutics-ca.login.ezproxy.library.ualberta.ca/search. Updated May 2017. Accessed January 13, 2018.

In most cases, neuropathic pain cannot be cured. However, the pain can be managed.

The main goal of treating neuropathic pain is reducing pain to a realistic level that allows a patient to live comfortably. We are rarely able to eliminate the pain entirely.