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

Sheena Derry; Andrew S C Rice; Peter Cole; Toni Tan; R Andrew Moore

doi:10.1002/14651858.CD007393.pub3

Capsaicina tópica (alta concentración) para el dolor neuropático crónico en adultos

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Referencias

References to studies included in this review

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Backonja M, Wallace MS, Blonsky ER, Cutler BJ, Malan P, Rauck R, et al. NGX‐4010 C107 Study Group. NGX‐4010, a high‐concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomised, double‐blind study. Lancet Neurology 2008;7(12):1106‐12. [DOI: 10.1016/S1474‐4422(08)70228‐X]

Clifford DB, Simpson DM, Brown S, Moyle G, Brew BJ, Conway B, et al. NGX‐4010 C119 Study Group. A randomized, double‐blind, controlled study of NGX‐4010, a capsaicin 8% dermal patch, for the treatment of painful HIV‐associated distal sensory polyneuropathy. Journal of Acquired Immune Deficiency Syndromes 2012;589(2):126‐33. [DOI: 10.1097/QAI.0b013e31823e31f7]

Irving GA, Backonja MM, Dunteman E, Blonsky ER, Vanhove GF, Lu SP, et al. NGX‐4010 C117 Study Group. A multicenter, randomized, double‐blind, controlled study of NGX‐4010, a high‐concentration capsaicin patch, for the treatment of postherpetic neuralgia. Pain Medicine 2011;12(1):99‐109. [DOI: 10.1111/j.1526‐4637.2010.01004.x]

Simpson DM, Brown S, Tobias J, NGX‐4010 C107 Study Group. Controlled trial of high‐concentration capsaicin patch for treatment of painful HIV neuropathy. Neurology 2008;70(24):2305‐13. [DOI: 10.1212/01.wnl.0000314647.35825.9]

Webster LR, Tark M, Rauck R, Tobias JK, Vanhove GF. Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter, randomized, controlled study of NGX‐4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia. BMC Neurology 2010;10:92. [DOI: 10.1186/1471‐2377‐10‐92]

Webster LR, Malan TP, Tuchman MM, Mollen MD, Tobias JK, Vanhove GF. A multicenter, randomized, double‐blind, controlled dose finding study of NGX‐4010, a high‐concentration capsaicin patch, for the treatment of postherpetic neuralgia. Journal of Pain 2010;11(10):972‐82. [DOI: 10.1016/j.jpain.2010.01.270]

References to studies excluded from this review

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Backonja MM, Malan TP, Vanhove GF, Tobias JK, C102/106 Study Group. NGX‐4010, a high‐concentration capsaicin patch, for the treatment of postherpetic neuralgia: a randomized, double‐blind, controlled study with an open‐label extension. Pain Medicine 2010;11(4):600‐8. [DOI: 10.1111/j.1526‐4637.2009.00793.x]

References to ongoing studies

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References to other published versions of this review

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Derry S, Lloyd R, Moore RA, McQuay HJ. Topical capsaicin for chronic neuropathic pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD007393.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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Backonja 2008

Methods	RCT, 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
Participants	Postherpetic 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
Outcomes	PI ‐ 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
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described
Allocation concealment (selection bias)	Low risk	Remote treatment assignment, using unique number on printed labels affixed to outside of patch envelope
Blinding (performance bias and detection bias) All outcomes	Low risk	Low concentration of capsaicin in "identically formulated" control patch to mimic local skin reaction of active treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified (no details) LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Low risk	206/196 participants in treatment arms

Clifford 2012

Methods	RCT, 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
Participants	HIV‐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
Outcomes	PI ‐ 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
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "allocation scheme prepared by Fisher Clinical Services"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Not 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 risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Unclear risk	50 to 200 participants per treatment arm

Irving 2011

Methods	RCT, 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
Participants	Postherpetic 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
Outcomes	PI ‐ 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
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "allocation scheme prepared by Fisher Clinical Services"
Allocation concealment (selection bias)	Low risk	Each 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 risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Low risk	> 200 participants per treatment arm

Simpson 2008

Methods	RCT, DB, multicentre, parallel groups, single application, 12‐week duration. Patches applied to both feet, up to maximum 1000 cm^2. 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
Participants	HIV‐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
Outcomes	PI: 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
Notes	Oxford Quality Score: R1, DB1, W1. Total = 3/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Described only as "randomised"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Control 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 risk	BOCF or 'no improvement' imputed for missing values for dichotomous data analyses
Size	Unclear risk	50 to 200 participants per treatment arm

Webster 2010a

Methods	RCT, 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
Participants	Postherpetic 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
Outcomes	PI ‐ 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
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "randomisation scheme prepared by Cardinal Health"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	"identically appearing control patches"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Unclear risk	50 to 200 participants per treatment arm

Webster 2010b

Methods	RCT, 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
Participants	Postherpetic 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
Outcomes	PI ‐ 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
Notes	Oxford Quality Score: R1, DB2, W1. Total = 4/5
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not described; "randomisation scheme prepared by Cardinal Health"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	"identically‐appearing ...... control patch"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Modified LOCF analysis for primary outcome, but no imputation for weekly scores. All participants included for safety analysis
Size	Unclear risk	50 to 200 participants pre treatment arm

AE: adverse event; BOCF: baseline observation carried forward; DB: double‐blind(ing); LOCF: last observation carried forward; PGIC: patient global impression of change; R: randomisation; RCT: randomised controlled trial; W: withdrawals

Characteristics of excluded studies [ordered by study ID]

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estudios en curso

Study	Reason for exclusion
Backonja 2010	Study duration only four weeks

Characteristics of ongoing studies [ordered by study ID]

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NCT01228838

Trial name or title	Study of NGX‐1998 for the treatment of postherpetic neuralgia
Methods	RCT, DB, multicentre, parallel groups, single application, 12‐week duration Treatment applied for 5 minutes
Participants	Postherpetic neuropathy with > 6 months of pain since vesicle crusting Baseline pain 4 to 9/10 Age 18 to 90 years
Interventions	Capsaicin topical liquid 10% Capsaicin topical liquid 20% Placebo Stable pain medications continued unchanged throughout study
Outcomes	Participants 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 date	October 2010
Contact information	Trudy Vanhove, VP Clinical Development, NeurogesX, Inc
Notes

DB: double‐blind; RCT: randomised controlled trial

Data and analyses

Open in table viewer

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

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 PGIC much or very much improved at 8 and 12 weeks Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.1 Comparison 1 8% capsaicin versus control (single dose), Outcome 1 PGIC much or very much improved at 8 and 12 weeks.
1.1 8 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [1.10, 1.84]
1.2 12 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.55 [1.20, 1.99]
2 PHN ‐ at least 50% pain intensity reduction over weeks 2 to 8 Show forest plot	3	870	Risk Ratio (M‐H, Fixed, 95% CI)	1.44 [1.12, 1.86]
Open in figure viewer Analysis 1.2 Comparison 1 8% capsaicin versus control (single dose), Outcome 2 PHN ‐ at least 50% pain intensity reduction over weeks 2 to 8.
2.1 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	2.95 [0.73, 11.88]
2.2 60‐minute application	3	674	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [1.03, 1.75]
2.3 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	2.02 [0.64, 6.33]
3 PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks Show forest plot	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.00, 1.71]
Open in figure viewer Analysis 1.3 Comparison 1 8% capsaicin versus control (single dose), Outcome 3 PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks.
4 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8 Show forest plot	4	1268	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.13, 1.52]
Open in figure viewer Analysis 1.4 Comparison 1 8% capsaicin versus control (single dose), Outcome 4 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8.
4.1 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.67, 2.69]
4.2 60‐minute application	4	1072	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [1.12, 1.52]
4.3 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [0.74, 2.95]
5 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	3	973	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [1.07, 1.45]
Open in figure viewer Analysis 1.5 Comparison 1 8% capsaicin versus control (single dose), Outcome 5 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12.
6 HIVN ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	2	801	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [1.09, 1.68]
Open in figure viewer Analysis 1.6 Comparison 1 8% capsaicin versus control (single dose), Outcome 6 HIVN ‐ at least 30% pain intensity reduction over weeks 2 to 12.
6.1 30‐minute application	2	340	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [1.14, 2.46]
6.2 60‐minute application	2	359	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.84, 1.44]
6.3 90‐minute application	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	1.94 [0.83, 4.53]
7 Local skin reactions ‐ group 1 Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.7 Comparison 1 8% capsaicin versus control (single dose), Outcome 7 Local skin reactions ‐ group 1.
7.1 Erythema	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [1.30, 1.52]
7.2 Pain	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	2.28 [1.99, 2.62]
7.3 Papules	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	3.58 [1.87, 6.85]
7.4 Pruritus	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	1.99 [0.98, 4.03]
7.5 Oedema	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	2.98 [1.44, 6.18]
8 Local skin reactions ‐ group 2 Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.8 Comparison 1 8% capsaicin versus control (single dose), Outcome 8 Local skin reactions ‐ group 2.
8.1 Erythema	1	129	Risk Ratio (M‐H, Fixed, 95% CI)	6.31 [0.35, 114.82]
8.2 Pain	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.85 [0.99, 3.47]
8.3 Papules	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.59, 4.24]
8.4 Pruritus	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.98, 2.50]
8.5 Oedema	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.75, 2.39]
9 Patch tolerability Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.9 Comparison 1 8% capsaicin versus control (single dose), Outcome 9 Patch tolerability.
9.1 < 90% of application time	6	2074	Risk Ratio (M‐H, Fixed, 95% CI)	3.27 [1.17, 9.15]
9.2 Dermal irritation score > 2 at 2 h	3	1065	Risk Ratio (M‐H, Fixed, 95% CI)	11.80 [4.04, 34.48]
9.3 Dermal irritation score > 0 at 2 h	2	606	Risk Ratio (M‐H, Fixed, 95% CI)	2.28 [1.60, 3.26]
9.4 Rescue medication 0 to 5 d	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	2.47 [2.13, 2.87]
10 Serious adverse events Show forest plot	5	1579	Risk Ratio (M‐H, Fixed, 95% CI)	1.41 [0.82, 2.41]
Open in figure viewer Analysis 1.10 Comparison 1 8% capsaicin versus control (single dose), Outcome 10 Serious adverse events.
11 Withdrawals Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 1.11 Comparison 1 8% capsaicin versus control (single dose), Outcome 11 Withdrawals.
11.1 Adverse events	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.37, 2.00]
11.2 Lack of efficacy	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.32, 1.02]

Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Figure 2

Forest plot of comparison: 1 8% capsaicin versus control (single dose), outcome: 1.1 PGIC much or very much improved at 8 and 12 weeks.

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Figure 3

Forest plot of comparison: 1 8% capsaicin versus control (single dose), outcome: 1.2 PHN ‐ at least 50% pain intensity reduction over weeks 2 to 8.

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Figure 4

Forest plot of comparison: 1 8% capsaicin versus control (single dose), outcome: 1.6 HIVN ‐ at least 30% pain intensity reduction over weeks 2 to 12.

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Figure 5

Skin adverse event rates with capsaicin and control. Yellow symbols are studies recording all events (Group 1). Pink symbols are studies specifying that events are not recorded on the first day after treatment (Group 2). The blue symbol did not specify the period over which events were recorded (Group 2). Size of symbol is proportional to the size of the study

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Figure 6

Forest plot of comparison: 1 8% capsaicin versus control (single dose), outcome: 1.10 Serious adverse events.

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Analysis 1.1

Comparison 1 8% capsaicin versus control (single dose), Outcome 1 PGIC much or very much improved at 8 and 12 weeks.

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Analysis 1.2

Comparison 1 8% capsaicin versus control (single dose), Outcome 2 PHN ‐ at least 50% pain intensity reduction over weeks 2 to 8.

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Analysis 1.3

Comparison 1 8% capsaicin versus control (single dose), Outcome 3 PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks.

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Analysis 1.4

Comparison 1 8% capsaicin versus control (single dose), Outcome 4 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8.

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Analysis 1.5

Comparison 1 8% capsaicin versus control (single dose), Outcome 5 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12.

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Analysis 1.6

Comparison 1 8% capsaicin versus control (single dose), Outcome 6 HIVN ‐ at least 30% pain intensity reduction over weeks 2 to 12.

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Analysis 1.7

Comparison 1 8% capsaicin versus control (single dose), Outcome 7 Local skin reactions ‐ group 1.

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Analysis 1.8

Comparison 1 8% capsaicin versus control (single dose), Outcome 8 Local skin reactions ‐ group 2.

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Analysis 1.9

Comparison 1 8% capsaicin versus control (single dose), Outcome 9 Patch tolerability.

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Analysis 1.10

Comparison 1 8% capsaicin versus control (single dose), Outcome 10 Serious adverse events.

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Analysis 1.11

Comparison 1 8% capsaicin versus control (single dose), Outcome 11 Withdrawals.

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

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 PGIC much or very much improved at 8 and 12 weeks Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1 8 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.42 [1.10, 1.84]
1.2 12 weeks	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.55 [1.20, 1.99]
2 PHN ‐ at least 50% pain intensity reduction over weeks 2 to 8 Show forest plot	3	870	Risk Ratio (M‐H, Fixed, 95% CI)	1.44 [1.12, 1.86]

2.1 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	2.95 [0.73, 11.88]
2.2 60‐minute application	3	674	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [1.03, 1.75]
2.3 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	2.02 [0.64, 6.33]
3 PHN ‐ at least 50% pain intensity reduction over 2 to 12 weeks Show forest plot	2	571	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.00, 1.71]

4 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 8 Show forest plot	4	1268	Risk Ratio (M‐H, Fixed, 95% CI)	1.31 [1.13, 1.52]

4.1 30‐minute application	1	97	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.67, 2.69]
4.2 60‐minute application	4	1072	Risk Ratio (M‐H, Fixed, 95% CI)	1.30 [1.12, 1.52]
4.3 90‐minute application	1	99	Risk Ratio (M‐H, Fixed, 95% CI)	1.48 [0.74, 2.95]
5 PHN ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	3	973	Risk Ratio (M‐H, Fixed, 95% CI)	1.25 [1.07, 1.45]

6 HIVN ‐ at least 30% pain intensity reduction over weeks 2 to 12 Show forest plot	2	801	Risk Ratio (M‐H, Fixed, 95% CI)	1.35 [1.09, 1.68]

6.1 30‐minute application	2	340	Risk Ratio (M‐H, Fixed, 95% CI)	1.67 [1.14, 2.46]
6.2 60‐minute application	2	359	Risk Ratio (M‐H, Fixed, 95% CI)	1.10 [0.84, 1.44]
6.3 90‐minute application	1	102	Risk Ratio (M‐H, Fixed, 95% CI)	1.94 [0.83, 4.53]
7 Local skin reactions ‐ group 1 Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

7.1 Erythema	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [1.30, 1.52]
7.2 Pain	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	2.28 [1.99, 2.62]
7.3 Papules	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	3.58 [1.87, 6.85]
7.4 Pruritus	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	1.99 [0.98, 4.03]
7.5 Oedema	3	1312	Risk Ratio (M‐H, Fixed, 95% CI)	2.98 [1.44, 6.18]
8 Local skin reactions ‐ group 2 Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

8.1 Erythema	1	129	Risk Ratio (M‐H, Fixed, 95% CI)	6.31 [0.35, 114.82]
8.2 Pain	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.85 [0.99, 3.47]
8.3 Papules	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.58 [0.59, 4.24]
8.4 Pruritus	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.57 [0.98, 2.50]
8.5 Oedema	3	735	Risk Ratio (M‐H, Fixed, 95% CI)	1.34 [0.75, 2.39]
9 Patch tolerability Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

9.1 < 90% of application time	6	2074	Risk Ratio (M‐H, Fixed, 95% CI)	3.27 [1.17, 9.15]
9.2 Dermal irritation score > 2 at 2 h	3	1065	Risk Ratio (M‐H, Fixed, 95% CI)	11.80 [4.04, 34.48]
9.3 Dermal irritation score > 0 at 2 h	2	606	Risk Ratio (M‐H, Fixed, 95% CI)	2.28 [1.60, 3.26]
9.4 Rescue medication 0 to 5 d	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	2.47 [2.13, 2.87]
10 Serious adverse events Show forest plot	5	1579	Risk Ratio (M‐H, Fixed, 95% CI)	1.41 [0.82, 2.41]

11 Withdrawals Show forest plot	6		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

11.1 Adverse events	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.37, 2.00]
11.2 Lack of efficacy	6	2073	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.32, 1.02]

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

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Referencias

References to studies included in this review

Backonja 2008 {published data only}

Clifford 2012 {published data only}

Irving 2011 {published data only}

Simpson 2008 {published data only}

Webster 2010a {published data only}

Webster 2010b {published data only}

References to studies excluded from this review

Backonja 2010 {published data only}

References to ongoing studies

NCT01228838 {published data only}

Additional references

Anand 2011

AUREF 2012

Bouhassira 2012

Collins 1997

Cook 1995

Derry 2012

Edelsberg 2009

Edwards 1999

EMC 2012

FDA 1999

Gustorff 2008

Gülfe 2010

Hall 2006

Higgins 2011

Hoffman 2010

Ikenberg 2012

Jadad 1996

Jones 2011

L'Abbé 1987

Loke 2001

Mason 2004

McQuay 2007

Moore 1998a

Moore 1998b

Moore 2005

Moore 2008a

Moore 2008b

Moore 2009

Moore 2011a

Moore 2011b

Moore 2012

Morris 1995

Ohayon 2012

Phillips 2010

Sadosky 2008

Straube 2010

Straube 2011

Toth 2009

Wolff 2011

Yawn 2009

References to other published versions of this review

Derry 2009

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Characteristics of ongoing studies [ordered by study ID]

Data and analyses

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