Table A Excluded Studies in capsaicin systematic review

Table B Included studies: neuropathic pain

Table C Included studies: musculoskeletal conditions

Forrest plots of efficacy data
 
 
 

Search strategy for RCTs of capsaicin [as supplied by author]

#1 randomised control trial (MeSH term)

#2 random* OR blind OR double-blind OR double-masked OR masked OR trial

#3 #1 OR #2

#4 administration, topical (MeSH term)

#5 topical* OR cutaneous OR dermal OR transcutaneous OR transdermal OR percutaneous OR skin OR massage OR embrocation OR gel OR ointment OR aerosol OR cream OR crème OR lotion OR mouse{??} OR foam OR liniment OR spray OR rub OR balm OR salve OR emulsion OR oil OR patch OR plaster

#6 #4 OR #5

#7 musculoskeletal diseases (MeSH) OR diabetic neuropathies (MeSH) OR polyneuropathies (MeSH) OR neuralgia (MeSH)

#8 neuropath* OR diabet* post-herpetic OR neuralgia OR mastectomy OR arthrit* OR rheumat* or osteoarth* OR tend?nitis OR sciatica OR lumbago OR fibrositis

#9 #7 OR #8

#10 vagin* OR cervix OR cervical OR tubal OR ligation OR thrombophlebitis OR rectal OR suppository OR intra-articular OR intra-muscular OR intra-venous OR morphine OR warfarin OR nebuliz* OR PCA OR foetal OR endoscop* OR laporoscop*

#11 #9 NOT #10

#12 capsaicin (MeSH)

#13 capsaicin OR capsaicine OR capsici OR axsain OR capsidol OR capsig OR capsin OR capsina OR capsiplast OR capzasin-P OR dolorac OR gelcen OR katrum OR "No pain-HP" OR priltam OR "R-gel" OR zacin OR zostrix OR capsicum

#14 #12 OR #13

#15 #3 AND #6 AND #11 AND #14
 
 

Hierarchy of outcomes was used to extract information on efficacy, in preferential order:

Number of patients with a 50% or more reduction in pain

Patient reported global assessment of treatment

Pain on movement

Pain on rest or spontaneous pain

Physician or investigator global assessment of treatment
 
 

Table A [as supplied by authors] Excluded Studies in capsaicin systematic review
 

Reference	Reason for exclusion
Basha KM, Whitehouse FW. Capsaicin: a therapeutic option for painful diabetic neuropathy. Henry Ford Hos Med J 1991;39:138-40.	Single centre arm of multicentre study (duplicate of Capsaicin study group included trial)
Dailey GEI, Muchmore DP, Springer JW, Donofrio PD, Walker FO, Hunt VP et al. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabetes Care 1992;15:159-165.	Single centre arm of multicentre study (duplicate of Capsaicin study group included trial)
Dini D, Bertelli G, Gozza A, Forno GG. Treatment of the post-mastectomy pain syndrome with topical capsaicin. Pain 1993;54:223-6.	Not randomised controlled trial
Donofrio P, Walker F Hunt V Tandan R Fries T Lewis G et al. Treatment of painful diabetic neuropathy with topical capsaicin: A multicenter, double-blind, vehicle-controlled study. Arch Int Med 1991;151:2225-29.	Single centre arm of multicentre study (duplicate of Capsaicin study group included trial)
Drake HF, Harries AJ, Gamester RE, Justins D. Randomised double-blind study of topical capsaicin for treatment of post-herpetic neuralgia. Pain 1990; S58.	Abstract only - insufficient information
Ellison N, Loprinzi CL, Kugler J, Hatfield A, Miser A, Sloan J et al. Evaluation of a capsaicin cream for the treatment of postoperative neuropathic pain. Proc Annu Meet Am Soc Clin Oncol 1996;15:543 Abs.	Abstract only & duplicate of included study (reference Ellison 1997)
Epstein JB, Marcoe JH. Topical application of capsaicin for treatment of oral neuropathic pain and trigeminal neuralgia. Oral Surg Oral Med Oral Pathol 1994;77:135-40.	Not randomised controlled trial
Fusco BM, Alessandri M. Analgesic effect of capsaicin in idiopathic trigeminal neuralgia. Anesth Analg 1992;74:375-7.	Too few patients (12 total)
Mathias BJ, Dillingham TR, Zeigler DN, Chang AS, Belandres PV. Topical capsaicin for chronic neck pain. A pilot study. Am-J-Phys-Med-Rehabil 1995;74:39-44.	Not randomised controlled trial
McCarthy GM, McCarty DJ. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumat 1992;19:604-7.	No usable information
McCarty DJ, Csuka M, McCarthy G, Trotter D. Treatment of pain due to fibromyalgia with topical capsaicin: A pilot study. Sem Arth Rheumat 1994;23Supp 3:41-7.	No usable information
McCleane G. The analgesic efficacy of topical capsaicin is enhanced by glyceryl trinitrate in painful osteoarthritis: a randomized, double blind, placebo controlled study. Eur J Pain 2000;4:355-60.	No dichotomous efficacy outcomes & no usable adverse event/withdrawals data
Peikert A, Hentrich M, Ochs G. Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course. J Neurol 1991;238:452-6.	Not randomised controlled trial
Pfeifer MA, Ross DR Schrage JP Gelber DA Schumer MP Crain GM et al. A highly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy. Diabetes Care 1993;16:1103-15.	Not randomised controlled trial
Robbins WR, Staats PS, Levine J, Fields HL, Allen RW, Campbell JN et al. Treatment of intractable pain with topical large-dose capsaicin: preliminary report. Anesth Analg 1998;86:579-83.	Too few patients (10 total)
Scheffler NM, Sheitel PL Lipton MN. Treatment of painful diabetic neuropathy with capsaicin 0.075%. J Am Pod Med Assoc 1991;81:288-93.	Single centre arm of multicentre study (duplicate of Capsaicin study group included trial)
Schnitzer TJ, Morton C, Coker S, Flynn P. Effectiveness of reduced applications of topical capsaicin (0.025%) in osteoarthritis. Arthritis and Rheumatism 1992;35:S132.	Abstract only. Insufficient information
Stam C, Bonnet MS van Haselen RA. The efficacy and safety of a homeopathic gel in the treatment of acute low back pain: a multi-centre, randomised, double-blind comparative clinical trial. Brit Homeopathic J 2001;90:21-8.	Capsaicin present at low dose in a cream containing rubefacients
Tandan R, Lewis GA, Krusinski PB, Badger GB, Fries TJ. Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up. Diabetes Care 1992;15:8-14.	Single centre arm of multicentre study (duplicate of Capsaicin study group included trial)
Vickers ER, Cousins MJ, Walker S, Chisholm K. Analysis of 50 patients with atypical odontalgia. A preliminary report on pharmacological procedures for diagnosis and treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:24-32.	Patients not randomised to treatment groups
Watson CP, Evans RJ, Watt VR. Post-herpetic neuralgia and topical capsaicin. Pain 1988;33:333-40.	Not randomised controlled trial
Watson CP, Evans RJ, Watt VR. The post-mastectomy pain syndrome and the effect of topical capsaicin. Pain 1989;38:177-86.	Not randomised controlled trial

 
 

Table B [As supplied by authors] Included studies: neuropathic pain
 

efficacy at 8* weeks: successful outcomes/total

local adverse events

AE related withdrawals

Ref

participants & condition

control

QS

OPVS

outcome

capsaicin

control

capsaicin

control

capsaicin

control

16

DN, n=277 mean age 60

placebo

R=1 D=1  W=1 QS=3

12

Improvement

96(-)/138

74(-)/139

unclear

unclear

18/138

5/139

17

DN, n=58  18-85 yrs

placebo

R=1 D=1  W=1 QS=3

12

Improvement

(17/29)

(11/29)

DNS

DNS

DNS

DNS

19

PHN, n=32  mean age 72

placebo

R=1+1 D=1+1 W=0 QS=4

14

physician global

12^(12)/16

5^(5)/16

5/16

2/16

0/16

0/16

20

PHN, n=143 mean age 70

placebo

R=1+1 D=1  W=0 QS=3

13

Improvement

48^(41)/74

23^(26)/69

45/74

23/69

16/74

1/69

23

N, n=99 mean age 63

placebo

R=1 D=1+1  W=0 QS=3

14

75% pain reduction

10(-)/49

5(-)/50

DNS

unclear

unclear

unclear

24

PN, n=40† mean age 59

placebo

R=1 D=1+1  W=0 QS=3

14

Improvement

23(21)/40

26(22)/40

unclear

unclear

DNS

DNS

25

PM, n=25  mean age 57

placebo

R=1 D=1  W=1 QS=3

11

50% pain reduction

8^(-)/14

3^(-)/11

12/14

1/11

1/14

0/11

26

DN, n=235,  mean age 60

amitriptyline

R=1+1 D=1+1 W=0 QS=4

14

physician global

35(34)/118

41(35)/117

52/118

DNS

DNS

DNS

30

N, n=100 mean age 40

placebo

R=1+1 D=1+1 W=0 QS=4

14

pain at rest

no dichotomous data

27/50

0/50 placebo

DNS

DNS

31

HIV assoc N n=26,  mean age 40

placebo

R=1 D=1  W=1 QS=3

9

pain at rest

no dichotomous data

DNS

DNS

5/11

0/15

* numbers in parenthesis are efficacy at 4 weeks, if reported

† within patient trial, with treatment and control randomly assigned to either left or right side

^ outcome at 6 weeks

All 0.075% capsaicin apart from ref 36 (0.025%)

AE = adverse event, DN = diabetic neuropathy, PN = polyneuropathy, PHN = post herpetic neuralgia, PM = post mastectomy pain, N = neuropatic pain

QS (quality score): R=randomisation, D=double blinding, W=withdrawals

OPVS (Oxford Pain Validity Score): maximum 16 points
 
 
 

Table C [As supplied by authors] Included studies: musculoskeletal conditions
 

efficacy at 4 weeks (successful outcome/total)

local adverse events

AE related withdrawals

Ref

participants & condition

control

QS

OPVS

outcome

capsaicin

control

capsaicin

control

capsaicin

control

18

OA & RA  n=101  mean age 58

placebo

R=1 D=1 W=1 QS=3

13

pain on rest (CAT scale)

22/52

18/49

23/52

1/49

2/52

0/49

21

OA  n=113  mean age 62

placebo

R=1 D=1 W=1 QS=3

13

patient global

22/57

15/56

26/57

DNS

5/57

0/56

22

back pain n=154 18-75 yrs

placebo

R=1 D=1+1 W=0  QS=3

14

50% reduction

26/77*

13/77*

unclear

unclear

10/77

6/77

27

OA n=64  40-85 yrs

0.25% capsaicin

R=1 D=0 W=1 QS=2

12

50% reduction

19/32

24/32

unclear

unclear

2/32

1/32

28

OA  n=59  mean age 68

placebo

R=1 D=1 W=0 QS=2

10

pain on rest (CAT scale)

no dichotomous data

12/29

6/30

DNS

DNS

29

jaw pain n=30  mean age 36

placebo

R=1 D=1+1 W=1 QS=4

12

pain on rest (VAS scale)

no dichotomous data

13/17

2/13

2/17

0/13

* 3 weeks

All 0.025% capsaicin apart from ref 30 (capsicum plaster: 11 mg capsinoids)

AE = adverse event, OA=osteoarthritis, RA=rheumatoid arthritis

QS (Quality Score): R=randomisation, D=double blinding, W=withdrawals

OPVS (Oxford Pain Validity Score): maximum 16 points
 
 
 

Forrest plots of efficacy data [as supplied by authors]

Neuropathic pain

Musculoskeletal pain