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Topical capsaicin (high concentration) for chronic neuropathic pain in adults

  1. Sheena Derry1,*,
  2. Andrew S C Rice2,3,
  3. Peter Cole4,
  4. Toni Tan5,
  5. R Andrew Moore1

Editorial Group: Cochrane Pain, Palliative and Supportive Care Group

Published Online: 28 FEB 2013

Assessed as up-to-date: 10 DEC 2012

DOI: 10.1002/14651858.CD007393.pub3


How to Cite

Derry S, Rice ASC, Cole P, Tan T, Moore RA. Topical capsaicin (high concentration) for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD007393. DOI: 10.1002/14651858.CD007393.pub3.

Author Information

  1. 1

    University of Oxford, Pain Research and Nuffield Department of Clinical Neurosciences, Oxford, Oxfordshire, UK

  2. 2

    Imperial College London, Pain Research, Department of Surgery and Cancer, Faculty of Medicine, London, UK

  3. 3

    Chelsea and Westminster Hospital NHS Foundation Trust, Department of Pain Medicine, London, UK

  4. 4

    Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford Pain Relief Unit, Oxford, UK

  5. 5

    National Institute for Health and Clinical Excellence, Centre for Clinical Practice, Manchester, UK

*Sheena Derry, Pain Research and Nuffield Department of Clinical Neurosciences, University of Oxford, Pain Research Unit, Churchill Hospital, Oxford, Oxfordshire, OX3 7LE, UK. sheena.derry@ndcn.ox.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 28 FEB 2013

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Characteristics of included studies [ordered by study ID]
Backonja 2008

MethodsRCT, DB, multicentre, parallel groups, single application, 12-week duration. Patch applied to painful area, up to 1000 cm2.

Oral pain medication continued without change. Transdermal opioids (≤ 60 mg morphine/day equivalent) permitted, but not topical analgesics.

Rescue medication: after application participants allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days

Pain assessed daily (average pain for last 24 hours). PGIC assessed at endpoint. Clinic visits at 4, 8, 12 weeks


ParticipantsPostherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain in/around facial area

N = 402

M = 190, F = 212

Mean age 71 years

Baseline pain 30 to 90 mm (mean 60 mm)


Interventions(1) Capsaicin patch 8%, n = 206

(2) Control patch, n = 196

Topical local anaesthetic applied for 60 min, then patch applied for 60 min

Control patch contained 0.04% capsaicin to mimic AEs


OutcomesPI - 11-point numeric pain rating scale (responder: ≥ 30% and ≥ 2-point reduction from baseline)

PGIC - 7-point scale (responder: much and very much improved)

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4/5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Low riskRemote treatment assignment, using unique number on printed labels affixed to outside of patch envelope

Blinding (performance bias and detection bias)
All outcomes
Low riskLow concentration of capsaicin in "identically formulated" control patch to mimic local skin reaction of active treatment

Incomplete outcome data (attrition bias)
All outcomes
Low riskModified (no details) LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis

SizeLow risk206/196 participants in treatment arms

Clifford 2012

MethodsRCT, DB, parallel groups, single application, 12-week duration. Patches applied to both feet, up to 1120 cm2.

Oral pain medication continued without change. Transdermal opioids (≤ 80 mg morphine/day equivalent) permitted, but not topical analgesics, or implanted medical device for pain relief.

Rescue medication: during application participants allowed oral oxycodone solution (1 mg/ml) and local cooling; after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days, and paracetamol (≤ 3 g/d) throughout

Pain assessed daily (average pain for last 24 hours). PGIC assessed at 12 weeks. Clinic visits at 4, 8, 12 weeks


ParticipantsHIV-associated distal sensory neuropathy for ≥ 2 months

Exclusion: previous use of NGX-4010

N = 494

M = 432, F = 62

Mean age 50 years

Baseline pain 30 to 90 mm (mean 60 mm)


Interventions(1) Capsaicin patch 8% 30 min, n = 167
(2) Capsaicin patch 8% 60 min, n = 165
(3) Placebo patch 30 min, n = 73
(4) Placebo patch 60 min, n = 89

Topical local anaesthetic applied for 60 min, then patch applied for 30 or 60 min

Control patch contained 0.04% capsaicin to mimic AEs


OutcomesPI - 11-point numeric pain rating scale (responder: ≥ 30% reduction from baseline)

PGIC - 7-point scale (reporting: slightly, much and very much improved)

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4/5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described; "allocation scheme prepared by Fisher Clinical Services"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described as identical; "low-dose capsaicin control patches were used instead of placebo to provide effective blinding ....."

Incomplete outcome data (attrition bias)
All outcomes
Low riskModified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis

SizeUnclear risk50 to 200 participants per treatment arm

Irving 2011

MethodsRCT, DB, multicentre, parallel-group, single application, 12-week duration. Patch applied to painful area, up to 1120 cm2.

Oral pain medication continued without change. Transdermal opioids (≤ 60 mg morphine/day equivalent) permitted, but not topical analgesics.
Pain assessed daily (average pain for last 24 hours). PGIC assessed at 4, 8, 12 weeks. Clinic visits at 4, 8, 12 weeks


ParticipantsPostherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain above neck area

N = 416

M = 190, F = 226

Mean age 70 years

Baseline pain 30 to 90 mm (mean 57 mm)


Interventions(1) Capsaicin patch 8%, n = 212
(2) Control patch, n = 204
Topical local anaesthetic applied for 60 mins, then patch applied for 60 mins
Control patch contained 0.04% capsaicin to mimic AEs


OutcomesPI - 11-point numeric pain rating scale (responder: ≥ 30%, ≥ 50%, and ≥ 2-point reduction from baseline)

PGIC - 7-point scale (responder: much and very much improved)

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4/5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described; "allocation scheme prepared by Fisher Clinical Services"

Allocation concealment (selection bias)Low riskEach kit "designated by a unique kit number, which was printed on the investigational drug label affixed to the outer bag enclosure and on each individual patch envelope"

Blinding (performance bias and detection bias)
All outcomes
Low risk"The NGX-4010 and control patches were identical in appearance, as were the blinded study kits"

Incomplete outcome data (attrition bias)
All outcomes
Low riskModified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis

SizeLow risk> 200 participants per treatment arm

Simpson 2008

MethodsRCT, DB, multicentre, parallel groups, single application, 12-week duration. Patches applied to both feet, up to maximum 1000 cm2.

Oral pain medication continued without change. No topical analgesics.

During application participants allowed oral oxycodone solution (1 mg/ml) or equivalent, after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 7 days

Pain assessed daily (average pain for last 24 hours). PGIC assessed at 12 weeks. Clinic visits at 4, 8, 12 weeks


ParticipantsHIV-associated distal sensory polyneuropathy with ≥ 2 months' moderate to severe pain in both feet

N = 307

M = 286, F = 21

Mean age 48 years (29 to 74)

Baseline pain 30 to 90 mm (mean ˜60 mm)


Interventions(1) Capsaicin patch 8% 30 min, n = 72

(2) Capsaicin patch 8% 60 min, n = 78

(3) Capsaicin patch 8% 90 min, n = 75

(4) Control patch, n = 82

Topical local anaesthetic applied for 60 min, then patch applied for 30, 60 or 90 min
Control patch contained 0.04% capsaicin to mimic AEs


OutcomesPI: 11-point numeric pain rating scale (responder: ≥ 30% reduction from baseline)

Patient global: PGIC - 7-point scale (responder: much and very much improved)

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB1, W1. Total = 3/5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskDescribed only as "randomised"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low riskControl patch contained a low concentration of capsaicin to mimic local skin reaction of active treatment. Although it does not say "identical" or use similar wording, this was judged by the authors to be low risk.

Incomplete outcome data (attrition bias)
All outcomes
Low riskBOCF or 'no improvement' imputed for missing values for dichotomous data analyses

SizeUnclear risk50 to 200 participants per treatment arm

Webster 2010a

MethodsRCT, DB, multicentre, parallel-group, single application, 12-week duration. Patch applied to painful area, up to 1120 cm2.

Oral pain medication continued without change. Transdermal opioids (≤ 60 mg morphine/day equivalent) permitted, but not topical analgesics.

Rescue medication: during application participants allowed oral oxycodone solution (1 mg/ml) and local cooling; after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days, and paracetamol (≤ 2 g/d) throughout.
Pain assessed daily (average pain for last 24 hours). PGIC assessed at 4, 8, 12 weeks. Clinic visits at 4, 8, 12 weeks


ParticipantsPostherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain in/around facial area

N = 299

M = 150, F = 149

Mean age 71 years

Baseline pain 30 to 90 mm (mean 55 mm)


Interventions(1) Capsaicin patch 8% 30 min, n = 72
(2) Capsaicin patch 8% 60 min, n = 77
(3) Capsaicin patch 8% 90 min, n = 73
(4) Control patch, 30, 60, 90 min pooled for analysis n = 77
Topical local anaesthetic applied for 60 mins, then patch applied for 30, 60 or 90 mins
Control patch contained 0.04% capsaicin to mimic AEs


OutcomesPI - 11-point numeric pain rating scale (responder: ≥ 30%, ≥ 50%, and ≥ 2-point reduction from baseline)

PGIC - 7-point scale (reporting: slightly, much and very much improved)

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4/5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described; "randomisation scheme prepared by Cardinal Health"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low risk"identically appearing control patches"

Incomplete outcome data (attrition bias)
All outcomes
Low riskModified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis

SizeUnclear risk50 to 200 participants per treatment arm

Webster 2010b

MethodsRCT, DB, multicentre, parallel-group, single application, 12-week duration. Patch applied to painful area, up to 1000 cm2.

Oral pain medication continued without change. Transdermal opioids (≤ 60 mg morphine/day equivalent) permitted, but not topical analgesics.

Rescue medication: during application participants allowed oral oxycodone solution (1 mg/ml) and local cooling; after application allowed hydrocodone/paracetamol (5/500 mg) for ≤ 5 days, and paracetamol (≤ 2 g/d) throughout.
Pain assessed daily (average pain for last 24 hours). PGIC assessed at 4, 8, 12 weeks. Clinic visits at 4, 8, 12 weeks


ParticipantsPostherpetic neuropathy with at least moderate pain, ≥ 6 months since vesicle crusting. Exclusion: pain in/around facial area

N = 155

M = 72, F = 83

Mean age 70 years

Baseline pain 30 to 90 mm (mean 53 mm)


Interventions(1) Capsaicin patch 8%, n = 102
(2) Control patch, n = 53
Topical local anaesthetic applied for 60 mins, then patch applied for 60 mins
Control patch contained 0.04% capsaicin to mimic AEs


OutcomesPI - 11-point numeric pain rating scale (responder: ≥ 30%, ≥ 50% and ≥ 2-point reduction from baseline)

PGIC - 7-point scale (responder: much and very much improved)

Adverse events

Withdrawals


NotesOxford Quality Score: R1, DB2, W1. Total = 4/5


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described; "randomisation scheme prepared by Cardinal Health"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low risk"identically-appearing ...... control patch"

Incomplete outcome data (attrition bias)
All outcomes
Low riskModified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis

SizeUnclear risk50 to 200 participants pre treatment arm

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Backonja 2010Study duration only four weeks

 
Characteristics of ongoing studies [ordered by study ID]
NCT01228838

Trial name or titleStudy of NGX-1998 for the treatment of postherpetic neuralgia

MethodsRCT, DB, multicentre, parallel groups, single application, 12-week duration

Treatment applied for 5 minutes

ParticipantsPostherpetic neuropathy with > 6 months of pain since vesicle crusting
Baseline pain 4 to 9/10
Age 18 to 90 years

InterventionsCapsaicin topical liquid 10%

Capsaicin topical liquid 20%

Placebo

Stable pain medications continued unchanged throughout study

OutcomesParticipants with ≥ 30% decrease in pain from baseline at weeks 8 and 12

Participants with ≥ 2 unit decrease in pain from baseline at weeks 8 and 12

Starting dateOctober 2010

Contact informationTrudy Vanhove, VP Clinical Development, NeurogesX, Inc

Notes

 
Comparison 1. 8% capsaicin versus control (single dose)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PGIC much or very much improved at 8 and 12 weeks2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 8 weeks
2571Risk Ratio (M-H, Fixed, 95% CI)1.42 [1.10, 1.84]

    1.2 12 weeks
2571Risk Ratio (M-H, Fixed, 95% CI)1.55 [1.20, 1.99]

 2 PHN - at least 50% pain intensity reduction over weeks 2 to 83870Risk Ratio (M-H, Fixed, 95% CI)1.44 [1.12, 1.86]

    2.1 30-minute application
197Risk Ratio (M-H, Fixed, 95% CI)2.95 [0.73, 11.88]

    2.2 60-minute application
3674Risk Ratio (M-H, Fixed, 95% CI)1.34 [1.03, 1.75]

    2.3 90-minute application
199Risk Ratio (M-H, Fixed, 95% CI)2.02 [0.64, 6.33]

 3 PHN - at least 50% pain intensity reduction over 2 to 12 weeks2571Risk Ratio (M-H, Fixed, 95% CI)1.31 [1.00, 1.71]

 4 PHN - at least 30% pain intensity reduction over weeks 2 to 841268Risk Ratio (M-H, Fixed, 95% CI)1.31 [1.13, 1.52]

    4.1 30-minute application
197Risk Ratio (M-H, Fixed, 95% CI)1.34 [0.67, 2.69]

    4.2 60-minute application
41072Risk Ratio (M-H, Fixed, 95% CI)1.30 [1.12, 1.52]

    4.3 90-minute application
199Risk Ratio (M-H, Fixed, 95% CI)1.48 [0.74, 2.95]

 5 PHN - at least 30% pain intensity reduction over weeks 2 to 123973Risk Ratio (M-H, Fixed, 95% CI)1.25 [1.07, 1.45]

 6 HIVN - at least 30% pain intensity reduction over weeks 2 to 122801Risk Ratio (M-H, Fixed, 95% CI)1.35 [1.09, 1.68]

    6.1 30-minute application
2340Risk Ratio (M-H, Fixed, 95% CI)1.67 [1.14, 2.46]

    6.2 60-minute application
2359Risk Ratio (M-H, Fixed, 95% CI)1.10 [0.84, 1.44]

    6.3 90-minute application
1102Risk Ratio (M-H, Fixed, 95% CI)1.94 [0.83, 4.53]

 7 Local skin reactions - group 13Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    7.1 Erythema
31312Risk Ratio (M-H, Fixed, 95% CI)1.40 [1.30, 1.52]

    7.2 Pain
31312Risk Ratio (M-H, Fixed, 95% CI)2.28 [1.99, 2.62]

    7.3 Papules
31312Risk Ratio (M-H, Fixed, 95% CI)3.58 [1.87, 6.85]

    7.4 Pruritus
31312Risk Ratio (M-H, Fixed, 95% CI)1.99 [0.98, 4.03]

    7.5 Oedema
31312Risk Ratio (M-H, Fixed, 95% CI)2.98 [1.44, 6.18]

 8 Local skin reactions - group 23Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    8.1 Erythema
1129Risk Ratio (M-H, Fixed, 95% CI)6.31 [0.35, 114.82]

    8.2 Pain
3735Risk Ratio (M-H, Fixed, 95% CI)1.85 [0.99, 3.47]

    8.3 Papules
3735Risk Ratio (M-H, Fixed, 95% CI)1.58 [0.59, 4.24]

    8.4 Pruritus
3735Risk Ratio (M-H, Fixed, 95% CI)1.57 [0.98, 2.50]

    8.5 Oedema
3735Risk Ratio (M-H, Fixed, 95% CI)1.34 [0.75, 2.39]

 9 Patch tolerability6Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    9.1 < 90% of application time
62074Risk Ratio (M-H, Fixed, 95% CI)3.27 [1.17, 9.15]

    9.2 Dermal irritation score > 2 at 2 h
31065Risk Ratio (M-H, Fixed, 95% CI)11.80 [4.04, 34.48]

    9.3 Dermal irritation score > 0 at 2 h
2606Risk Ratio (M-H, Fixed, 95% CI)2.28 [1.60, 3.26]

    9.4 Rescue medication 0 to 5 d
62073Risk Ratio (M-H, Fixed, 95% CI)2.47 [2.13, 2.87]

 10 Serious adverse events51579Risk Ratio (M-H, Fixed, 95% CI)1.41 [0.82, 2.41]

 11 Withdrawals6Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    11.1 Adverse events
62073Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.37, 2.00]

    11.2 Lack of efficacy
62073Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.32, 1.02]