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L'Abbé plot showing response rates in studies using multiple application low dose capsaicin (yellow) and single application high dose capsaicin (blue). Size of circle is proportional to size of study (inset scale).
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Figure 1

L'Abbé plot showing response rates in studies using multiple application low dose capsaicin (yellow) and single application high dose capsaicin (blue). Size of circle is proportional to size of study (inset scale).

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Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
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Figure 2

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

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Forest plot of comparison: 1 0.075% capsaicin versus placebo, outcome: 1.1 Clinical success.
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Figure 3

Forest plot of comparison: 1 0.075% capsaicin versus placebo, outcome: 1.1 Clinical success.

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Forest plot of comparison: 2 8% capsaicin versus placebo (single dose), outcome: 2.1 ≥30% pain relief.
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Figure 4

Forest plot of comparison: 2 8% capsaicin versus placebo (single dose), outcome: 2.1 ≥30% pain relief.

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Forest plot of comparison: 1 0.075% capsaicin versus placebo, outcome: 1.2 Adverse event: burning, stinging, erythema.
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Figure 5

Forest plot of comparison: 1 0.075% capsaicin versus placebo, outcome: 1.2 Adverse event: burning, stinging, erythema.

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Comparison 1 0.075% capsaicin versus placebo, Outcome 1 Clinical improvement.
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Analysis 1.1

Comparison 1 0.075% capsaicin versus placebo, Outcome 1 Clinical improvement.

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Comparison 1 0.075% capsaicin versus placebo, Outcome 2 Adverse event: burning, stinging, erythema.
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Analysis 1.2

Comparison 1 0.075% capsaicin versus placebo, Outcome 2 Adverse event: burning, stinging, erythema.

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Comparison 1 0.075% capsaicin versus placebo, Outcome 3 Adverse event: coughing, sneezing.
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Analysis 1.3

Comparison 1 0.075% capsaicin versus placebo, Outcome 3 Adverse event: coughing, sneezing.

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Comparison 1 0.075% capsaicin versus placebo, Outcome 4 Adverse event withdrawal.
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Analysis 1.4

Comparison 1 0.075% capsaicin versus placebo, Outcome 4 Adverse event withdrawal.

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Comparison 2 8% capsaicin versus placebo (single dose), Outcome 1 ≥30% pain relief.
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Analysis 2.1

Comparison 2 8% capsaicin versus placebo (single dose), Outcome 1 ≥30% pain relief.

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Comparison 2 8% capsaicin versus placebo (single dose), Outcome 2 Adverse event: erythema, pruritus.
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Analysis 2.2

Comparison 2 8% capsaicin versus placebo (single dose), Outcome 2 Adverse event: erythema, pruritus.

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Table 1. Summary of outcomes: successful treatment

Study ID

Treatment

Clinical improvement

Backonja 2008

(1) Capsaicin 8% patch 60 min, n = 206

(2) Placebo patch, n = 196

≥ 30% pain reduction from baseline to weeks 2 to 12:

(1) 91/206

(2) 69/196

Bernstein 1989

(1) Capsaicin 0.075% cream, n = 16

(2) Vehicle cream, n = 16

≥ 40% pain relief at 6 weeks:

(1) 8/16

(2) 1/16

Biesbroeck 1995

(1) Capsaicin 0.075% cream, n = 118

(2) Amitriptyline 25 to 125 mg (oral), n = 117

Mean decrease in pain intensity at 8 weeks:

(1) 42%

(2) 44%

CSG 1992

(1) Capsaicin 0.075% cream, n = 138

(2) Vehicle cream, n = 139

Mean decrease in pain intensity at 8 weeks:

(1) 40.1%

(2) 27.8%

Ellison 1997

(1) Capsaicin 0.075% cream, n = 49

(2) Placebo cream, n = 50

≥75% decrease in pain score:

(1) 10/49

(2) 5/50

Low 1995

(1) Capsaicin 0.075% cream, n = 40

(2) Placebo cream, n = 40

Undefined improvement at 8 weeks:

(1) 22/40

(2) 25/40

Simpson 2008

(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) Placebo patch, n = 82

≥30% pain reduction from baseline to weeks 2 to 12:

(1) 30/72

(2) 19/78

(3) 27/75

(4) 15/82

Capsaicin 1 to 3 combined 76/225

Tandan 1992

(1) Capsaicin 0.075% cream, n = 11

(2) Placebo cream, n = 11

Reduction in pain by at least one category at 8 weeks:

(1) 7/11

(2) 2/11

Watson 1992

(1) Capsaicin 0.075% cream, n = 14

(2) Vehicle cream, n = 11

≥ 50% pain relief at 6 weeks:

(1) 8/14

(2) 3/11

Watson 1993

(1) Capsaicin 0.075% cream, n = 74

(2) Vehicle cream, n = 69

Improvement in pain severity at 6 weeks:

Assuming 12 participants not included in analysis are evenly distributed

(1) 26/68

(2) 13/63
Figuras y tablas -
Table 1. Summary of outcomes: successful treatment
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Table 2. Summary of outcomes: adverse events and withdrawals

Study ID

Treatment

Local AEs

Systemic AEs

Serious AEs

Withdrawals

Backonja 2008

(1) Capsaicin 8% patch, n = 206
(2) Placebo patch, n = 196

Erythema:
(1) 193/205
(2) 128/197

Cough not reported, so <3%

Various, all ≤ 5% in both groups

(1) 10/205
(2) 6/197

(1 in capsaicin group judged related to medication)

AE:
(1) 1/205
(2) 0/197

Other:
(1) 18/205 (10 LoE, 8 other)
(2) 18/198 (9 LoE, 9 other)

Bernstein 1989

(1) Capsaicin 0.075% cream, n = 16
(2) Vehicle cream, n = 16

Burning, stinging, erythema
(1) 5/16
(2) 2/16

None

None

AE: none

Other:
3 lost to follow up ‐ no details of group or time

Biesbroeck 1995

(1) Capsaicin 0.075% cream, n = 118
(2) Amitriptyline 25 to 125mg (oral), n = 117

Total skin AEs:
(1) 68/118 (52 burning)
(2) 2/117 (unspecified)

Cough/sneeze:
(1) 7/118
(2) 1/117

None with capsaicin

Limited therapeutic dose for majority of amitriptyline participants

(1) None

(2) Not reported

AE: none related to capsaicin

Other:

(1) 14 did not contribute any post baseline efficacy data
(2) 9 did not contribute any post baseline efficacy data

Capsaicin study group 1992

(1) Capsaicin 0.075% cream, n = 138

(2) Vehicle cream, n = 139

Burning:

(1) 87/138

(2) 17/139

Cough/sneeze:

(1) 16/138

(2) 2/139

Burning, cough, sneeze, rash, erythema:

(1) 113 events

(2) 29 events

Other AE:

(1) 6/138

(2) 8/139

Increased pain:

(1) 2/138

(2) 5/139

No data

AE:

(1) 18/138

(2) 5/139

Other:

(1) 20/138 (7 non‐compliant, 10 other health problems, 3 other)

(2) 15/139 (6 non‐compliant, 2 lack of efficacy, 5 other health problems, 2 other)

Ellison 1997

(1) Capsaicin 0.075% cream, n = 49

(2) Placebo cream, n = 50

Significantly more burning, redness and coughing with capsaicin than placebo (P <0.0001)

No data

No data

AE: no data from first phase

Other: no data

Low 1995

(1) Capsaicin 0.075% cream, n = 40

(2) Placebo cream, n = 40

Burning:

(1) 29/40

(2) 16/40

Sneezing:

(1) 5/40

(2) 1/40

Itching:

(1) 4/40

(2) 2/40

Rash:

(1) 5/40

(2) 0/40

No data

No data

1 did not complete entire study ‐ no further details

Simpson 2008

(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) Placebo patch, n = 82

Pruritus:

(1‐3) 39/225

(4) 5/82

Burning:

(1‐3) 18/225

Warson 1993

(4) 2/82

Cough:

(1) 5/225

(2) 1/82

Various, ≤ 5% in both groups, except URTI (8%, 6%)

(1‐3) 1/225

(4) 2/82

(all deaths, all judged unrelated to study medication)

AE:

(1‐3) 2/225

(4) 1/82

Other:

(1‐3) 19/225 (1 LoE, 18 other)

(4) 8/82 (2 LoE, 6 other)

Watson 1992

(1) Capsaicin 0.075% cream, n = 14

(2) Vehicle cream, n = 11

Burning:

(1) 13/14

(2) 1/11

Cough:

(1) 1/14

(2) 0/11

No data

No data

AE:

(1) 1/14

(2) 0/11

Other:

(1) 0/14

(2) 1/11 (recurrence of malignancy)

Watson 1993

(1) Capsaicin 0.075% cream, n = 74

(2) Vehicle cream, n = 69

Burning,stinging, erythema:

(1) 45/74

(2) 23/69

Cough:

(1) 4/74

(2) 1/69

No more than 3/group with any systemic AE. No significant difference between groups

None

AE:

(1) 18/74

(1) 2/69

Other:

(1) 2/74

(2) 1/69

Exclusions: 12 participants treated did not meet entrance criteria, further 6 had protocol violations

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Table 2. Summary of outcomes: adverse events and withdrawals
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Comparison 1. 0.075% capsaicin versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Clinical improvement Show forest plot

6

389

Risk Ratio (M‐H, Fixed, 95% CI)

1.59 [1.20, 2.11]

1.1 Unspecified or <50% pain relief

4

265

Risk Ratio (M‐H, Fixed, 95% CI)

1.49 [1.10, 2.03]

1.2 ≥50% pain relief

2

124

Risk Ratio (M‐H, Fixed, 95% CI)

2.06 [0.99, 4.30]

2 Adverse event: burning, stinging, erythema Show forest plot

5

557

Risk Ratio (M‐H, Fixed, 95% CI)

2.64 [2.10, 3.31]

3 Adverse event: coughing, sneezing Show forest plot

5

557

Risk Ratio (M‐H, Fixed, 95% CI)

5.73 [2.15, 15.25]

4 Adverse event withdrawal Show forest plot

4

477

Risk Ratio (M‐H, Fixed, 95% CI)

5.02 [2.28, 11.08]
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Comparison 1. 0.075% capsaicin versus placebo
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Comparison 2. 8% capsaicin versus placebo (single dose)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 ≥30% pain relief Show forest plot

2

709

Risk Ratio (M‐H, Fixed, 95% CI)

1.40 [1.12, 1.74]

2 Adverse event: erythema, pruritus Show forest plot

2

709

Risk Ratio (M‐H, Fixed, 95% CI)

1.52 [1.35, 1.72]
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Comparison 2. 8% capsaicin versus placebo (single dose)
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