SUMMARY TABLE. Trials included in the article review.

Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/investigator

Overall change/patient

Side effects

Total lesions (count) 2, 4, 6, 10

Doxycycline

Fusidin cream

È

Í

Randomized. Specific 

population. 

Patient not blinded. 

Topical fusidin was as 

effective as oral 

doxycycline.

n=110 Mild/mod

female 31

male 79

Age 18.0 y

#1

Wellington, New 

Zealand

Parallel

Adams, 1991

Overall change/patient

Overall change/physician

7

Vehicle

Delta-0.2%-

chlormadione

Delta-5%-chlormadione

È

Í

No losses to followup. 

Not randomized. 

Neither 0.2% delta 

chlormadinone acetate nor 

5% delta chlormadinone 

acetate cream had any 

treatment effect on acne.

n=20 Can't say

female 9

male 11

#2

Palo Alto, USA

Parallel

split face

Adams, 1970

Overall change/physician

Severity (Agrawal)

12

Placebo

Zinc sulfate Í

Arms not comparable. 

Oral zinc sulphate was no 

more effective than placebo 

in mild acne but 

improvement was seen in 

patients with pustules, 

nodules and cysts.

n=42 Can't say

female 11

male 31

#3

Varanasi, India

Parallel

Agrawal, 1985

Severity change (Akamatsu)

8

Roxithromycin (300)

Roxithromycin (150)

È

Í

No losses to followup. 

General population. 

Not randomized. Patient 

not blinded. Enroller not 

blinded. Outcome 

assessor not blinded. 

Arms not comparable. 

Execution not as 

designed. 

A daily dose of 300 mg of 

roxithromycin was more 

effective than a lower dose 

of 150mg in treating severe 

acne.

n=30 Can't say

female 28

male 2

Age 14.0-26 y

#4

Osaka, Japan

Parallel

Akamatsu, 1996

Summary Table: Page 1 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/physician

Side effects

16

Isotretinoin (0.5)

Isotretinoin (0.3)

Isotretinoin (0.1)

È

Í

No losses to followup. 

Referral population. 

Not randomized. Patient 

not blinded. Enroller not 

blinded. Outcome 

assessor not blinded. 

Best clinical response with 

lowest range of side effects 

was achieved with a dosage 

of 0.3 mg/kg.

n=30 Sev

female 16

male 14

Age 23.1 y

#5

Kuwait

Parallel

Al Mishari, 1986

Severity change

Side effects

16

Erythromycin

Tetracycline

È

Í

No losses to followup. 

Not randomized. Patient 

not blinded. Enroller not 

blinded. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. 

Tetracycline and 

erythromycin, at low doses, 

were safe and effective in 

treating acne vulgaris.

n=40 Can't say

female 22

male 18

Age 12.5-26 y

#6

Kuwait

Parallel

Al Mishari, 1987

Severity (Anderson)

Severity change

1, 2, 3, 4, 5, 6, 7, 8

Vehicle (topical) + 

placebo (oral)

Tetracycline (topical) + 

placebo (oral)

Tetracycline (oral) + 

vehicle (topical)

Í

Arms not comparable. 

Execution not as 

designed. 

Oral and topical 

tetracycline were each as 

better than placebo in 

reducing acne severity.

n=60 Mod

female 0

male 60

#10

Cincinnati, USA

Parallel

Anderson, 1976

Overall change/dermatologist

Overall change/generalist

12

Placebo

Vitamin A

È

Í

Data shows outcome 

assessor blinded. Local 

population. 

Arms not comparable. 

No evidence that Vitamin 

A improved acne.

n=80 Can't say

female 34

male 46

#12

Scotland

Parallel

Anonymous, 1963

multicenter

Summary Table: Page 2 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Change (GPRG)

Comedone-free

Comedones (count)

Inter-treatment 

preference/patient

Side effects

2, 4, 8

Tretinoin

Methyl prednisolone + 

neomycin

Í

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. 

No significant difference 

was found between 

tretinoin lotion and 

methylprednisolone lotion.

Mild/mod/se

v

n=68

female 76

male 60

#13

UK

Parallel

split face

Anonymous, 1974

multicenter

Overall change

12

Saline

Fractionated tfd

Unfractionated tfd

È

Í

No losses to followup. 

Arms not comparable. 

Human dialyzable transfer 

factor produced the same 

clinical improvement in 

acne as placebo.

n=39 Sev

female 21

male 18

Age 21.5 y

#15

Tampere, Finland

Parallel

Ashorn, 1985

Cysts change [cystic]

Papules change [papules]

Pustules change [pustular]

Severity change

8

Hydroxyquinoline + 

benzoyl peroxide

Hydroxyquinoline + 

benzoyl peroxide + 

hydrocortisone

È

Data show patient 

blinded. Data shows 

enroller blinded. Data 

shows outcome assessor 

blinded. Referral 

population. 

Quinoderm-hydrocortisone 

was superior to quinoderm 

alone.

#16 n=54 Mild/mod

Manchester, UK

Cross-over

matched

Ashurst, 1964

Severity change (grade)

8

Ocimum basilicum

Tetracycline Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. 

Responses to tetracycline 

and osmium basilicum 

leaves were similar; Leaves 

were much less expensive.

n=51 Can't say

female 18

male 33

Age 11.0-30 y

#17

Madras, India

Parallel

Balambal, 1985

Inflammatory (count)

Non-inflammatory (count)

Unwanted effects

4, 8, 12

Benzoyl peroxide

Tea tree oil

È

Data shows enroller 

blinded. No losses to 

followup. Data shows 

outcome assessor 

blinded. 

Tea tree oil may be a useful 

alternative treatment for 

mild to moderate acne.

n=124 Mod

female 60

male 64

Age 19.7 y

#18

Sydney, Australia

Parallel

Bassett, 1990

Summary Table: Page 3 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Oiliness

Severity change

12

Placebo

16-epiestriol-3-allyl 

ether

Í

Not randomized. Major 

losses to followup. Arms 

not comparable. 

No significant difference in 

acne or in reduction of 

oiliness with respect to 

placebo.

n=134 Can't say

female 87

male 47

#19

Duluth, USA

Parallel

Becker, 1965

multicenter

Diarrhea

Overall change/patient

Papules (count)

Papules change (count)

Pustules (count)

Pustules change (count)

2, 4, 6, 8

Vehicle

Clindamycin 

hydrochloride

Clindamycin phosphate

Topical clindamycin 

hydrochloride and topical 

clindamycin phosphate 

were both effective and 

similar to one another.

n=358 Mod

female 224

male 133

Age 21.5 y

#20

San Diego, USA

Parallel

Becker, 1981

multicenter

Overall change/patient

Overall change/physician

Side effects

6, 12

Phisohex

Triclosan Í

Enroller not blinded. 

Outcome assessor not 

blinded. 

The mixture of triclosan 

and a detergent was as 

effective as Phisohex®.

Mild/mod/se

v

#21 n=34

Middlesex, UK

Cross-over

Bettley, 1976

Abdominal pain

Face severity (Leeds)

Inflammatory (count)

Non-inflammatory (count)

Non-inflammatory 

(count/median)

Total inflammatory (count)

Total lesions (count)

Total lesions (count/median)

Total severity (Leeds)

4, 8, 16, 24

Tetracycline + placebo

Azelaic acid + placebo Í

Not randomized. Major 

losses to followup. 

Topical azelaic acid was as 

effective as systemic 

tetracycline.

n=45 Mod/sev

female 0

male 45

Age 18.5 y

#22

Leeds, UK

Parallel

Bladon, 1986

Severity change (Cook)

Severity change (Cook))

2, 4, 6, 8, 10, 13

Placebo (topical) + 

tetracycline 

hydrochloride (oral)

Placebo (topical) + 

placebo (oral)

Tetracycline 

hydrochloride (topical) 

+ placebo (oral)

È

Randomized. Data 

shows outcome assessor 

blinded. 

Tetracycline reduced acne 

severity more than placebo.

n=75 Mod

female 12

male 63

Age 16.3±2.3 y

#23

Cincinnati, USA

Parallel

Blaney, 1976

Summary Table: Page 4 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Papules (count)

Side effects

2

Erythromycin (stearate)

Erythromycin (base)

È

Randomized. 

Oral erythromycin was 

effective in the treatment of 

acne vulgaris.

n=40 Mod

Age 20.2 y

#24

lidkoping, Sweden

Parallel

Bleeker, 1983

Inflammatory change (%)

Severity (Kligman)

2, 6

Erythromycin stearate 

+ placebo

Doxycycline + placebo

È

Í

Randomized. Data show 

patient blinded. Data 

shows enroller blinded. 

No losses to followup. 

Data shows outcome 

assessor blinded. 

Arms not comparable. 

Both erythromycin and 

doxycycline produced 

improvement after 2 weeks 

and neither had side effects.

n=56 Mod

female 29

male 27

Age 20.3 y

#25

Lidkoping, Sweden

Parallel

Bleeker, 1981

multicountry

Inflammatory (count)

Non-inflammatory (count)

Severity (Leeds)

4, 8, 12

Erythromycin + zinc 

acetate

Erythromycin

È

Í

Randomized. 

Arms not comparable. 

n=45 Mild/mod

female 15

male 30

Age 14.1 y

#28

Leeds, UK

Parallel

Bojar, 1994

Nodules (count)

Papules (count)

Pustules (count)

4, 8

Tetracycline + vehicle

Clindamycin phosphate 

+ placebo

È

Í

No losses to followup. 

Arms not comparable. 

No clinical difference was 

found between topical 

clindamycin and oral 

tetracycline.

n=20 Mod

female 13

male 7

Age 18.0 y

#29

Stockholm, 

Sweden

Parallel

Borglund, 1984

Adverse effects

Comedones (count)

Papules (count)

Pustules (count)

Skin discoloration

6, 10

Meclocycline + benzoyl 

peroxide

Meclocycline

Benzoyl peroxide

È

Í

No losses to followup. 

Outcome assessor not 

blinded. Arms not 

comparable. 

For acne patients 

susceptible to skin 

irritation from benzoyl 

peroxide, combined 

treatment with benzoyl 

peroxide and a topical 

antibiotic was 

advantageous.

n=102 Mod

female 54

male 48

Age 19.0 y

#30

Stockholm, 

Sweden

Parallel

Borglund, 1991

multicountry

Summary Table: Page 5 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Closed comedone change (%)

Overall change/patient

2, 4

Fulguration

Tretinoin

Í

Data shows outcome 

assessor blinded. 

Referral population. 

Patient not blinded. 

Fulguration can offer a 

simple but effective 

treatment for eliminating 

white heads.

n=11 Mild

female 10

male 1

Age 22.0-36 y

#31

Leeds, UK

Parallel

split face

Bottomley, 1993

Large comedone change (%)

Small comedones change (%)

4

Electrocautery

Fulguration

Í

Data shows outcome 

assessor blinded. 

Referral population. 

Patient not blinded. 

Use electrocautery on large 

closed comedones.

n=12 Mild

female 8

male 4

Age 23.0 y

#32

Leeds, UK

Parallel

split face

Bottomley, 1993

Diarrhea

Inflammatory (count)

Overall change/patient

Overall change/physician

8

Vehicle (oral) + vehicle 

(topical)

Tetracycline + vehicle

Clindamycin + vehicle

Both oral tetracycline and 

topical clindamycin 

reduced the number of acne 

lesions.

n=87 Mild

female 44

male 43

Age 20.3 y

#33

Oslo, Norway

Parallel

Braathen, 1984

Response

Side effects

12

Vitamin A

Vehicle

È

Í

No losses to followup. 

Referral population. 

Not randomized. 

Enroller not blinded. 

Outcome assessor not 

blinded. Arms not 

comparable. 

Topical vitamin A was 

more effective than placebo.

n=75 Mild/mod

Age 13.0-30 y

#34

Birmingham, USA

Parallel

Bradford, 1974

Summary Table: Page 6 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones (group count)

Comedones [female] (count)

Comedones [male] (count)

Overall change

Overall change [female]

Overall change [male]

Papules (group count)

Papules [female] (group 

count)

Papules [male] (group count)

Pustules (total count)

Pustules [female] (total 

count)

Pustules [male] (total count)

12

Vehicle

Vitamin A

È

Í

Randomized. No losses 

to followup. 

Outcome assessor not 

blinded. Arms not 

comparable. 

Topical vitamin A was 

more effective than placebo.

n=72 Mild/mod

female 23

male 49

Age 15.6±2.7 y

#35

Birmingham, USA

Parallel

matched

Bradford, 1974

Back severity 

(Harcup/median)

Chest severity 

(Harcup/median)

Face/neck severity 

(Harcup/median)

Side effects

12, 24

Tetracycline

Erythromycin acistrate

È

Local population. 

Erythromycin acistrate was 

a safe, well tolerated 

alternative to tetracycline 

for systemic treatment of 

acne.

n=60 Mod/sev

female 19

male 41

Age 21.0±4.4 y

#36

Helsinki, Finland

Parallel

Brandt, 1994

multicenter

Comedones change (count)

Cysts change (count)

Overall change/patient

Overall change/patient (vas)

Papules change (count)

Pustules change (count)

2, 4, 6, 8, 10, 12

Chloramphenicol + 

hydrocortisone

Tretinoin

È

Í

Randomized. 

Patient not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Chloramphenicol/hydrocort

isone and tretinoin showed 

similar activity over 12 

weeks.

n=56 Mod

Age 18.0-22 y

#37

Lancaster, UK

Parallel

Brookes, 1978

multicenter

Comedones (count)

Overall change/patient

Overall change/physician

Papules (count)

Pustules (count)

Side effects

12

Benzoyl peroxide

Tretinoin Í

Patient not blinded. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Tretinion produced greater 

improvement than benzoyl 

peroxide.

n=97 Mod

female 39

male 58

Age 12.0-36 y

#38

St. Georges, UK

Parallel

Bucknall, 1977

Summary Table: Page 7 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory (count)

Inflammatory (counts)

Non-inflammatory (count)

Severity (Leeds)

Total Lesions (count)

Withdrawal due to side 

effects

4, 8

Placebo

Erythromycin (topical)

Benzoyl peroxide

Í

Not randomized. 

Inconsistent 

ascertainment across 

arms. 

Benzoyl peroxide and 

topical erythromycin are 

equally effective in 

reducing the number of 

superficial inflamed lesions.

Mild/mod/se

v

n=94

female 19

male 70

Age 18.8±18.9 y

#39

Leeds, UK

Parallel

matched

Burke, 1983

Adverse reactions

Adverse-gastrointestinal

Adverse-skin

Overall change/patient, 

investigator

Severity (Cook)

4, 8, 12, 16

Tetracycline (topical) + 

tetracycline (oral)

Placebo + tetracycline 

(oral)

È

Í

No losses to followup. 

Not randomized. 

Topical tetracycline, in 

combination with 8 weeks 

of oral tetracycline was 

well accepted by patients 

and reduced acne severity 

at 16 weeks.

n=85 Can't say

female 44

male 38

Age 20.4±4.9 y

#40

Bristol, UK

Parallel

Burton, 1990

multicenter

Inter-treatment 

preference/physician

5, 10

Placebo

Sulfadimethoxine

È

No losses to followup. 

Sulfadlimethoxine was a 

"useful and safe" agent in 

the treatment of acne 

vulgaris.

n=134 Sev

female 107

male 27

Age 15.0-41 y

#41

Phildelphia, USA

Cross-over

Cahn, 1959

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity (Cook) 2, 4, 8, 12

Tretinoin

Tretinoin + clindamycin

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Combination more 

effective in inflamed acne.

n=40 Mod/sev

Age 14.0-26 y

#42

France

Parallel

Cambazard, 1998

multicenter

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity (Cook) 2, 4, 8, 12

Tretinoin

Tretinoin + clindamycin

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Combination more 

effective than tretinoin 

alone.

n=161 Mod/sev

Age 14.0-26 y

#43

France

Parallel

Cambazard, 1998

multicenter

Summary Table: Page 8 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity (Cook) 2, 4, 8, 12

Tretinoin

Tretinoin + clindamycin

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Combination not 

demonstrated superior to 

tretinoin in Velac gel®.

n=157 Mod/sev

Age 14.0-26 y

#44

France

Parallel

Cambazard, 1998

multicenter

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity (Cook) 2, 4, 8, 12

Clindamycin

Tretinoin + clindamycin

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. 

Combination superior for 

inflammatory acne.

n=209 Mod/sev

Age 14.0-26 y

#45

France

Parallel

Cambazard, 1998

multicenter

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity (Cook) 2, 4, 8, 12

Clindamycin

Tretinoin + clindamycin

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. 

Combination not superior 

to clindamycin.

n=40 Mod/sev

Age 14.0-26 y

#46

France

Parallel

Cambazard, 1998

multicenter

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity (Cook) 2, 4, 8, 12

Clindamycin

Tretinoin + clindamycin

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. 

Combination superior to 

clindamycin for noninflammatory acne.

n=162 Mod/sev

Age 14.0-26 y

#47

France

Parallel

Cambazard, 1998

multicenter

Summary Table: Page 9 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Discontinuation due to side 

effects

Total lesions change

Total lesions change (%)

16, 24

Levonorgestrel + 

ethinyl estradiol (0.030)

Cyproterone + ethinyl 

estradiol (0.035)

Cyproterone + ethinyl 

estradiol (0.05)

È

Data shows enroller 

blinded. 

Lower frequency of side 

effects in the 35 mcg group.

n=133 Can't say

female 133

male 0

Age 15.0- y

#48

Halmstad, Sweden

Parallel

Carlborg, 1986

multicenter

Burning severity (patient)

Desquamation severity 

(investigator)

Edema severity (investigator)

Erythema severity 

(investigator)

Papules severity 

(investigator)

Pruritis severity (patient)

Tightness severity (patient)

Vesicle severity (investigator)

2

Tretinoin

Adapalene

È

Í

No losses to followup. 

Data shows outcome 

assessor blinded. 

Not randomized. Patient 

not blinded. 

Adapalene was better 

tolerated than tretinoin.

n=15 Mild/mod

female 26

male 4

Age 28.4±6.3 y

#49

Sophia Antipoli, 

France

Parallel

split face

Caron, 1997

Good/excellent response (%)

Inflammatory (count)

Inflammatory (count/median)

Local side effects

Overall change/physician (%)

2, 4, 6, 12, 16, 20, 24

Benzoyl peroxide

Azelaic acid Í

Enroller not blinded. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. Execution 

not as designed. 

Treatments showed equal 

benefit. Benzoyl peroxide 

produced a more rapid 

effect on cutaneous lesions; 

azelaic acid applications 

were better tolerated.

#52 n=309 Mild

Milan, Italy

Parallel

Cavicchini, 1989

multicenter

Comedones change (%)

Inflammatory change (%)

Papules change (%)

Pustules change (%)

2, 4, 6, 8, 10

Erythromycin + 

benzoyl peroxide

Benzoyl peroxide

Vehicle

Erythromycin

Í

Inconsistent 

ascertainment across 

arms. 

The combination is more 

effective than vehicle.

n=177 Mod/sev

female 81

male 115

Age 15.0-30 y

#53

NY, USA

Parallel

Chalker, 1983

Summary Table: Page 10 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Erythema score

Inflammatory change (%)

Non-inflammatory change 

(%)

Peeling score

Severity change (Cook %)

2, 5, 8, 11, 14

Vehicle

Isotretinoin

È

Í

Specific population. 

Inconsistent 

ascertainment across 

arms. 

Isotretinoin 0.05% gel is 

useful for mild to 

moderately severe acne.

n=313 Can't say

female 112

male 156

Age 19.5 y

#54

Augusta, USA

Parallel

Chalker, 1987

multicenter

Overall change/patient 

[center a]

Overall change/patient 

[center b]

Severity [center a] 

(Charoenvisal)

Severity [center b] 

(Charoenvisal)

Side effects

4, 12, 24

Desogestrel + ethinyl 

estradiol

Cyproterone + ethinyl 

estradiol (.05)

Í

Patient not blinded. 

Enroller not blinded. 

Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. 

Decreased mean acne score 

occured with both ethinyl 

estradiol-desogestrel and 

ethinyl estradiolcyproterone. No difference 

between groups was 

reported.

n=66 Can't say

female 66

male 0

Age 16.0-30 y

#55

Songkhla, 

Thailand

Parallel

Charoenvisal, 19

Comedones change (%)

Pustules change (%)

Side effects 1, 2, 4, 6, 10, 13

Vehicle

Clindamycin

Clindamycin is effective in 

treating moderate-severe 

acne.

n=98 Mod/sev

female 32

male 49

Age 21.0 y

#56

Salt Lake City, 

USA

Parallel

Christian, 1975

Comedones change

Papules change

Pustules change

Side effects

2, 4, 8

Vitamin A + placebo

Vehicle + 

oxytetracycline

Vitamin A + 

oxytetracycline

È

Í

Data shows enroller 

blinded. 

Major losses to 

followup. 

Vitamin A was better than 

oxytetracycline for 

comedones and, less 

effective for pustules, and 

equally good for papules. 

Vitamin A produced more 

local side effects.

n=238 Can't say

female 135

male 103

Age 11.0-44 y

#57

Copenhagen, 

Denmark

Parallel

Christiansen, 197

multicenter

Comedones (Christiansen)

Comedones severity 

(Christiansen)

Nodes+cysts (score)

Papules severity 

(Christiansen)

Pustules (score)

Side effects

4, 8

Vehicle

Tretinoin (0.05%)

Tretinoin (0.02%)

Í

Major losses to 

followup. 

0.05% tretinoin was more 

effective than 0.02% 

tretinoin and placebo for 

papules and comedones but 

not pustules. Side effects of 

0.05% and 0.02% were 

similar.

#58 n=256 Sev

Copenhagen, 

Denmark

Parallel

Christiansen, 197

multicenter

Summary Table: Page 11 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Burning

Erythema desquamation

Total lesions

Total lesions change 

(count/median)

2, 4, 6, 8

Motretinide

Tretinoin

È

Í

Referral population. 

Major losses to 

followup. 

Motretinide and tretinoin 

0.05% were equivalent but 

authors acknowledge study 

was too small to detect 

differences.

n=37 Mild

female 20

male 11

Age 21.0 y

#59

Arhus, Denmark

Parallel

Christiansen, 197

Overall change/physician

Reduction in application due 

to side effects

Side effects

Total lesions change

2, 4, 8

Vehicle

Tretinoin

Motretinide

Í

Arms not comparable. 

Retinoic acid the most 

potent, but motretinide 

better tolerated.

#60 n=257 Mild/mod

Copenhagen, 

Denmark

Parallel

Christiansen, 197

multicenter

Comedones change (count)

Local reactions

Total lesions change (count)

2, 4, 6, 8

Motretinide

Vehicle Í

Major losses to 

followup. Arms not 

comparable. Execution 

not as designed. 

Motretinide was superior to 

placebo.

n=19 Can't say

female 22

male 7

Age 18.5 y

#61

Aarhus, Denmark

Parallel

Christiansen, 197

multicenter

Adverse effects

Clinical 

assessment/physician (score)

Comedones change (median 

%)

Improved by 50% or more

Inflammatory change 

(count/median)

2, 4, 6, 8, 10

Zinc + erythromycin

Benzoyl peroxide + 

erythromycin

Í

Patient not blinded. 

Benzoyl peroxide 5% + 

erythromycin 3% was 

superior to erythromycin + 

zinc 1.2%.

n=72 Mod

Age 24.0 y

#62

London, UK

Parallel

Chu, 1997

Adverse reaction

Discontinuation due to side 

effects

2, 4, 8, 12

Tretinoin

Adapalene

È

Í

Randomized. Specific 

population. 

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Arms not comparable. 

Adapalene 1% was better 

tolerated than tretinoin 

.025%.

n=591 Mod/sev

female 276

male 317

Age 12.0-30 y

#63

Sophia Antipolis, 

France

Parallel

Clucas, 1997

multicountry

Summary Table: Page 12 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Irritation (score)

Severity (Michaelsson)

3, 6, 9, 12

Vehicle

Zinc Í

Not randomized. Major 

losses to followup. Arms 

not comparable. 

Topical zinc therapy alone 

produced no significant 

benefit.

n=30 Mild/mod

Age 16.0-30 y

#64

Houston, USA

Parallel

Cochran, 1985

Back severity

Chest severity

Face severity

Severity change/patient (vas)

Side effects

8, 12, 24, 36

Cyproterone + ethinyl 

estradiol (0.05)

Cyproterone + ethinyl 

estradiol (0.035)

Í

Not randomized. 

Cyproterone-ethinyl 

estradiol-35 and 

cyproterone-ethinyl 

estradiol-50 were equally 

effective.

n=96 Can't say

female 78

male 0

Age 16.0-35 y

#66

Oxford, UK

Parallel

Colver, 1988

Improvement

Side effects

48-78 (unspecified)

Topical treatment

Tetracycline Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Systemic tetracycline was 

better than topical 

treatment.

n=68 Can't say

female 27

male 41

Age 19.0 y

#69

Chicago, USA

Parallel

Cornbleet, 1961

Overall change/physician

Relapse

Side effects

4-22 (unspecified)

Tetracycline

Demethylchortetracyclin

e

È

Í

Randomized. Data show 

patient blinded. Data 

shows enroller blinded. 

No losses to followup. 

Outcome assessor not 

blinded. 

Demethylchlorotetracycline 

was superior to tetracycline.

n=100 Can't say

female 59

male 41

Age 21.3 y

#70

Chicago, USA

Parallel

Cornbleet, 1964

Severity change

Side effects

4, 8, 12

Tetracycline 

hydrochloride

Demethylchlortetracycli

ne

Vehicle

Antibiotics were not 

superior to vehicle.

n=150 Can't say

female 99

male 51

#71

Miami, USA

Cross-over

matched

Crounse, 1965

Summary Table: Page 13 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones (count)

Cysts (count)

Papules (count)

Pustules (count)

Side effects

19

Tetracycline

Minocycline

È

Data shows enroller 

blinded. Data shows 

outcome assessor 

blinded. 

Minocycline was as 

effective as tetracycline.

n=100 Mod/sev

female 73

male 27

Age 20.0 y

#72

Gainesville, USA

Parallel

Cullen, 1976

Nodules (count)

Non-inflammatory (count)

Overall change/patient (vas)

Papules (count)

Pustules (count)

Severity (Burton)

4, 8, 12

Zinc sulfate/citrate 

complex

Tetracycline

Í

Patient not blinded. 

Enroller not blinded. 

Arms not comparable. 

Execution not as 

designed. 

Tetracycline was superior 

to zinc complex in 

mild/severe acne.

#74 n=48 Mod

Leeds, UK

Parallel

Cunliffe, 1979

Erythema

Inflammatory (count)

Non-inflammatory (count)

Overall assessment/patient 

(vas)

Scaling

Severity (Leeds)

4, 8, 12

Benzoyl peroxide

Chloramphenicol + 

hydrocortisone + sulfur

È

Í

No losses to followup. 

Not randomized. 

Chloramphenicol and 

benzoyl peroxide 5% were 

equally effective.

n=48 Mod

female 24

male 24

Age 15.0-17 y

#75

Leeds, UK

Parallel

matched

Cunliffe, 1980

Erythema

Inflammatory (count)

Non-inflammatory (count)

Overall change/patient (% 

improvement)

Scaling

Severity (Pillsbury)

4, 8

Benzoyl peroxide 

(lotion)

Benzoyl peroxide (gel)

Í

Major losses to 

followup. 

Benzoyl peroxide gel and 

lotion were equally 

effective.

n=48 Mod

female 28

male 20

#76

Leeds, UK

Parallel

matched

Cunliffe, 1981

Inflammatory change (%)

Local side effects

Non-inflammatory change 

(%) 8, 12

Azelaic acid

Placebo

È

Í

Randomized. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

20% azelaic acid can be 

used as monotherapy for 

papulo-pustular acne.

n=40 Can't say

female 14

male 26

#77

Leeds, UK

Parallel

matched

Cunliffe, 1989

Summary Table: Page 14 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory (count)

Non-inflammatory (count)

Severity (Leeds)

Total lesions change (%)

0, 1, 2, 4, 8, 12

Tretinoin

Adapalene (0.03%)

Adapalene (0.1%)

È

Í

Randomized. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

Major losses to 

followup. Arms not 

comparable. 

Adapalene 0.1% and 

tretinoin were equally 

effective; adapalene had 

fewer side effects.

Mild/mod/se

v

n=89

Age 12.0-30 y

#78

Montpellier, 

France

Parallel

Cunliffe, 1997

multicountry

Burning

Dryness

Inflammatory change (%)

Non-inflammatory change 

(%)

Scaling

2, 4, 8, 12

Tretinoin

Adapalene

È

Randomized. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

Adapalene was as effective 

as tretinoin and had 

superior skin safety results.

n=268 Can't say

female 125

male 143

Age 19.5 y

#80

Leeds, UK

Parallel

Cunliffe, 1997

multicountry

Overall change/physician

Skin irritation

2

Benzoyl peroxide + 

sulfur

Sulfur

È

Í

Data show patient 

blinded. Data shows 

enroller blinded. 

Arms not comparable. 

Benzoyl peroxide plus 

sulphur was better than 

sulphur alone.

Mild/mod/se

v

n=113

female 59

male 54

Age 12.0-40 y

#82

Vancover, Canada

Parallel

Danto, 1966

multicenter

Irritation

Overall change/physician

2, 7

Salicylic acid + 

resorcinol + sulfur

Tretinoin (.05%)

Tretinoin (.02%)

Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. Execution 

not as designed. 

Vitamin A acid (tretinoin) 

is no cure-all.

#84 n=60 Can't say

Ghent, Belgium

Parallel

De Bersaques, 19

Summary Table: Page 15 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones (count)

Overall change/patient

Overall change/physician

Severity change (score shift)

4, 8, 12 Side effects

Benzoyl peroxide

Miconazole + benzoyl 

peroxide

È

Randomized. No losses 

to followup. 

Combination of miconazole 

+ benzoyl peroxide was 

more effective therapy 

benzoyl peroxide alone.

n=105 Mod

female 49

male 56

Age 12.0-24 y

#85

Louvain, Belgium

Parallel

Degreef, 1982

Post-therapy overall change

Side effects

Unspecified

Polythionate + 

quaternary ammonia 

complex of polythionate

Polythionate

Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Arms not comparable. 

Two preparations of 

polythionate produced 

benefits in patients with 

mild to severe acne.

n=72 Can't say

female 46

male 26

Age 11.5-35 y

#86

Detriot, USA

Parallel

Delaney, 1959

Comedones change 

(count/median)

Papules change 

(count/median)

Pustules change 

(count/median)

Severity (Leeds)

Severity change 

(Dieben/median)

16

Cyproterone + ethinyl 

estradiol (0.035)

Desogestrel + ethinyl 

estradiol

Í

Major losses to 

followup. 

Cyproterone + ethinyl 

estradiol had a similar 

effect on mild to moderate 

acne.

n=183 Mild

female 183

male 0

Age 18.0-35 y

#87

Oss, The 

Netherlands

Parallel

Dieben, 1994

multicountry

Closed comedones change 

(%)

Open comedones change (%)

Overall change/physician

Papules change (%)

Pustules change (%)

Skin reaction

Total lesions change (%)

Withdrawals

2, 4, 8, 10, 12

Erythromycin

Vehicle Í

Major losses to 

followup. 

Erythromycin base 1.5% 

liquid is effective.

n=253 Mod/sev

female 161

male 93

#89

Buffalo, USA

Parallel

Dobson, 1980

multicenter

Summary Table: Page 16 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones (count)

Inflammatory (count)

Irritation

Stinging, erythema, 

desquamation

2, 4, 8, 12

Tretinoin

Isotretinoin

È

Í

No losses to followup. 

Patient not blinded. 

Enroller not blinded. 

Isotretinoin and tretinoin 

had a similar effect.

n=30 Mod

female 18

male 12

Age 13.0-30 y

#90

Mexico City, 

Mexico

Parallel

Dominguez, 1998

Abdominal pain

Inflammatory severity 

(Dreno)

Nausea

Severity/patient

Severity/photo

4, 8

Zinc

Placebo

È

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Oral zinc gluconate at a 

low dose showed 

significantly better results 

than placebo in the 

treatment of inflammatory 

acne.

n=66 Mod

female 27

male 39

Age 22.0±7.0 y

#91

France

Parallel

Dreno, 1989

multicenter

Dryness (score)

Erythema (score)

2

Adapalene-immediate

Adapalene-delayed Í

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Adapalene 0.1% was well 

tolerated, even when 

applied immediately after 

washing.

n=25 Mild/mod

female 36

male 14

Age 19.4±6.9 y

#92

Tucson, USA

Parallel

split face

Dunlap, 1998

Desquamation

Dryness (score)

Erythema (score)

Inter-treatment preference

Intolerance

Local reactions/Dryness 

(score)

Stinging/burning

Total adverse skin symptom 

(score)

Total adverse skin symptoms 

(score)

1, 2, 3, 4

Adapalene

Tretinoin

È

Í

Randomized. No losses 

to followup. 

Patient not blinded. 

Majority of patients prefer 

0.1% adapalene gel over 

tretinoin 0.025% cream. 

Adapalene causes less skin 

irritation.

n=100 Mild/mod

female 96

male 104

Age 18.5 y

#93

USA

Parallel

split face

Dunlap, 1998

multicenter

Summary Table: Page 17 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Burning

Dryness

Erythema

Inflammatory (count)

Non-inflammatory (count)

Pruritis

Scaling

2, 4, 8, 12

Benzoyl peroxide

Isolutrol Í

Major losses to 

followup. 

Benzoyl peroxide and 

isolutrol were both effective 

at reducing inflamed 

lesions. Isolutrol was not 

effective for non-inflamed 

lesions. Isolutrol produced 

fewer side effects.

n=70 Mild/mod

female 26

male 44

Age 18.6 y

#94

Camperdown, 

Australia

Parallel

Dunlop, 1995

Inflammatory (count)

Non-inflammatory (count)

Overall change/patient 

(scale)

Severity (Leeds)

Total lesions (count)

4, 8, 12

Vehicle

Salicylic acid

2% salicylic acid has a 

significant effect on noninflammatory lesions at 8 

to 12 weeks and on 

inflammatory lesions at 12 

weeks, with few side effects.

n=114 Mild/mod

female 28

male 86

Age 16.0-25 y

#95

Leeds, UK

Parallel

Eady, 1996

Overall change/investigator

Total lesions change (%)

2, 4

Benzoyl peroxide + 

chlorhydroxyquinoline

Benzoyl peroxide + 

chlorhydroxyquinoline 

+ hydrocortisone

Vehicle

Benzoyl peroxide

È

Randomized. No losses 

to followup. 

Benzoyl peroxide alone, in 

combination with 

chlorhydoxyquinoline 

alone or with 

hydrocortisone were all 

clinically superior to 

placebo. Loroxide HC® 

demonstrated the most 

rapid benefit.

n=196 Mild/mod

Age 14.0-24 y

#97

Cincinnati, USA

Parallel

Ede, 1973

Comedones change

Comedones change (%)

Inflammatory change (%)

Total lesions change (%) 2, 4, 8, 12

Isotretinoin

Tretinoin Í

Arms not comparable. 

Tretinoin and isotretinoin 

had similar efficacy.

#98 n=18 Can't say

Stanford, USA

Parallel

Elbaum, 1988

Papules (count)

Pustules (count)

3, 6, 9, 12

Clindamycin 

phosphate (lotion)

Clindamycin phosphate 

(gel)

Placebo

Í

Patient not blinded. 

Enroller not blinded. 

Clindamycin solution and 

gel were effective.

n=135 Mod

Age 13.0-35 y

#99

Ann Arbor, USA

Parallel

Ellis, 1988

Summary Table: Page 18 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones change (count)

Dose regime altered

Inflammatory (count)

Inflammatory change (%)

Non-inflammatory (count)

Non-inflammatory change 

(%)

Severity (Leeds)

Side effects

Total lesions change (%)

2, 4, 8, 12

Tretinoin

Adapalene

È

Í

Specific population. 

Patient not blinded. 

Major losses to 

followup. 

Both adapalene and 

tretinoin were effective. 

Adapalene was more useful 

than tretinoin for treating 

open comedones.Side 

effects were similar.

n=297 Mod

female 145

male 152

#100

USA

Parallel

Ellis, 1998

multicenter

Comedones (count)

Erythema

Papules (count)

Peeling

Pustules (count)

Severity change

2, 4, 7, 10

Vehicle

Sulfurated lime

Sulphurated lime produced 

faster and greater 

improvement with 

significant reduction in 

papule counts compared to 

vehicle. Clay mask system 

eliminates odor and 

staining associated with 

Vleminckx's solution®.

n=59 Mod

Age 13.0-30 y

#101

Los Angeles, USA

Parallel

Elstein, 1981

Overall change

Unspecified

Methyl prednisolone + 

neomycin + sulfur

Vehicle

È

Í

Randomized. Data show 

patient blinded. Data 

shows enroller blinded. 

Major losses to 

followup. Arms not 

comparable. 

Methylprednisolone/neomyc

in/sulphur was effective for 

early and late stages of 

acne vulgaris.

#102 n=134 Can't say

Montreal, Canada

Parallel

Ereaux, 1965

Back improvement

Chest improvement

Complete healing

Face improvement

Side effects

12, 32

Cyproterone + ethinyl 

estradiol (0.035)

Desogestrel + ethinyl 

estradiol

Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Cyproterone produced 

greater improvement for 

facial acne than desogestrel.

n=162 Can't say

female 162

male 0

Age 20.0-40 y

#103

Turku, Finland

Parallel

Erkkola, 1990

multicenter

Summary Table: Page 19 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Cheilitis duration (%)

Cystic change (%)

Cystic change post-treatment 

(%)

Cystic diameter change (%)

Cystic diameter change posttreatment

Desquamation duration 

(week)

Pruritus duration (weeks)

1, 2, 3, 4, 5, 6, 7, 8, 

10, 12; post-therapy:2, 

4, 6, 8

Isotretinoin (1.0)

Isotretinoin (0.1)

Isotretinoin (0.5)

Í

Randomized. Data show 

patient blinded. Data 

shows enroller blinded. 

Arms not comparable. 

No significant difference is 

efficacy were noted 

between the groups.

n=16 Sev

female 0

male 16

Age 16.0-31 y

#106

Iwoa city, USA

Parallel

Farrell, 1980

Medication used (mg/kg)

Papules change (%)

Severity change (Cook %)

Severity change (Cook)

2, 4, 6, 8, 10

Erythromycin + zinc 

(gel) + Placebo (oral)

Erythromycin + zinc 

(liquid) + placebo (oral)

Tetracycline (oral) + 

placebo (topical)

Placebo (topical) + 

placebo (oral)

Randomized. Data show 

patient blinded. Data 

shows outcome assessor 

blinded. Local 

population. 

Erythromycin/zinc gel or 

liquid are as effective as 

oral tetracycline.

Mild/mod/se

v

n=149

female 0

male 149

Age 18.0-26 y

#108

Augusta, USA

Parallel

Feucht, 1980

Severity (Cook)

Total lesions (count)

12

Benzoyl peroxide 

(contingent contract)

Benzoyl peroxide (noncontingent contract)

Benzoyl peroxide (self 

monitoring)

Untreated

Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Arms not 

comparable. 

Methods that monitor 

compliance improve acne 

outcomes.

n=42 Mod

female 34

male 8

#109

Athens, USA

Parallel

Flanders, 1985

Summary Table: Page 20 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/patient

Overall change/physician

Severity/photo 2, 4, 6, 8, 10, 12

Vehicle

Tolbutamide

È

Í

Data shows outcome 

assessor blinded. 

Not randomized. Major 

losses to followup. Arms 

not comparable. 

Tolbutanide was no better 

than placebo.

#110 n=30 Mod/sev

Madison, USA

Parallel

Flinn, 1961

Comedones (count)

Irritation

Irritation [female]

Irritation [females]

Irritation [male]

Papules (count)

Pustules (count)

Total lesions (count)

Total lesions change (%)

Total lesions change 

[female] (%)

Total lesions change [male] 

(%)

4, 8, 12

Benzoyl peroxide + 

miconazole

Benzoyl peroxide

Í

Patient not blinded. 

Major losses to 

followup. 

Benzoyl peroxide and 

benzoyl peroxide + 

miconazole were equally 

effective. Benzoyl peroxide 

+ miconazole was more 

effective in women and was 

better tolerated.

n=52 Mod/sev

female 26

male 26

Age 18.0 y

#111

Basel, Switzerland

Parallel

Fluckiger, 1988

Inflammatory (adjusted 

count)

Inflammatory (count)

Inflammatory (score)

Non-inflammatory (count)

Overall change/patient (vas) -4, 0, 4, 8

Triclosan + propylene 

phenoxetol

Triclosan

Vehicle

Í

Major losses to 

followup. 

Topical triclosan combined 

with topical acne creams 

was more effective than 

acne creams alone.

n=72 Mild/mod

female 0

male 72

Age 18.0-22 y

#114

Hamburg, 

Germany

Parallel

Franz, 1978

Local reactions

Overall change/patient

Overall change/physician

Severity change (Fraser %)

4, 8, 12

Hydrocortisone + sulfur

Chloramphenicol + 

hydrocortisone + sulfur

È

Randomized. 

Both preparations produced 

comparable decreases in 

number of lesions.

n=37 Can't say

female 25

male 12

#115

Aberdeen, UK

Parallel

Fraser, 1980

multicenter

Summary Table: Page 21 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones severity (Cook)

Macules score (Cook)

Papules score (Cook)

Papules time (Cook)

24, 48 Severity (Cook)

Cyproterone + ethinyl 

estradiol (0.035)

Cyproterone + ethinyl 

estradiol (0.05)

Í

Major losses to 

followup. 

Both cyproterone-ethinyl 

estradiol-35 and 

cyproterone-ethinyl 

estradiol-50 produced 

improvement;the lower 

estrogen dose was as 

effective as the higher dose.

n=73 Mod/sev

female 73

male 0

Age 23.0±3.3 y

#117

Montreal, Canada

Parallel

Fugere, 1990

multicenter

Burning

Closed comedones change 

(%)

Cysts change (%)

Erythema (patient)

Erythema (physician)

Open comedones change (%)

Papules change (%)

Pustules change (%)

Scaling (patient)

Scaling (physician)

Stinging

4, 8

Benzoyl peroxide 

(alcohol)

Benzoyl peroxide 

(water)

Water-based benzoyl 

peroxide produced less 

irritation than alcohol 

based benzoyl peroxide.

n=49 Can't say

female 64

male 34

Age 14.0-44 y

#118

Norway

Parallel

split face

Fyrand, 1986

Discontinuation due to side 

effects

Irritation (score)

1-21days (unspecified)

Petrolatum

Tretinoin (0.025% 

cream)

Tretinoin (0.01% gel)

Tretinoin (0.025% gel)

Tretinoin (0.05% 

cream)

Tretinoin (0.1% cream)

Adapalene

È

Í

No losses to followup. 

Patient not blinded. 

Adapalene was better 

tolerated than tretinoin.

n=28 Can't say

female 25

male 3

Age 22.0-72 y

#119

USA

Parallel

split face

Galvin, 1998

Summary Table: Page 22 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Discontinuation due to side 

effects

Irritation (score)

Local reactions/Irritation 

(Cumulative score)

1-21 days (unspecified)

Petrolatum

Tretinoin (0.025% 

cream)

Tretinoin (0.1% gel)

Tretinoin (0.05% 

cream)

Tretinoin (0 .1% cream)

Adapalene

È

Í

No losses to followup. 

Patient not blinded. 

Adapalene produced less 

irritation than any 

concentration of tretinoin.

n=27 Can't say

female 20

male 7

Age 22.0-72 y

#120

USA

Parallel

split face

Galvin, 1998

Overall change/patient

Severity change/photo

6

Benzoyl peroxide + 

metronidazole

Vehicle

È

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Benzoyl peroxide + 

metronidazole was superior 

to placebo.

n=43 Mod/sev

female 24

male 19

Age 19.0 y

#121

Varberg, Sweden

Parallel

Gamborg-Nielsen,

Overall change/patient

Overall change/physician

Severity change/photo

6

Benzoyl peroxide

Benzoyl peroxide + 

metronidazole

È

Í

No losses to followup. 

Patient not blinded. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Benzoyl peroxide + 

metronidazole was superior 

to benzoyl peroxide alone.

n=60 Mod/sev

female 33

male 27

Age 24.0 y

#122

Varberg, Sweden

Parallel

Gamborg-Nielsen,

Overall change/patient

Overall change/physician

Severity change/photo

6

Oxytetracycline + 

vehicle

Benzoyl peroxide + 

metronidazole + placebo

Í

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Benzoyl peroxide + 

metronidazole was 

comparable to 

oxytetracycline.

n=52 Mod/sev

female 30

male 22

Age 26.0 y

#123

Varberg, Sweden

Parallel

Gamborg-Nielsen,

Summary Table: Page 23 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Closed comedones change 

(%)

Open comedones change (%)

Overall change/patient

Papules change (%)

Pustules change (%)

Side effects

2, 4, 8, 12

Tetracycline + placebo

Erythromycin + placebo

È

Randomized. 

Tetracycline and 

erthromycin both reduced 

acne severity, but the 

reduction was faster in the 

tetracycline group for 

closed comedones.

n=178 Mild/mod

female 87

male 91

#125

Chapel Hill, USA

Parallel

Gammon, 1986

multicenter

Comedones change (count)

Desquamation

Erythema

Papules change (count)

Pustules change (count)

Severity change (severity)

2, 3, 4, 5, 6, 7, 8

Placebo + cotrimoxazole

Sulfur-resorcinol + 

cotrimoxazole

Tretinoin + 

cotrimoxazole

È

Í

General population. 

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. 

With each in combination 

with cotrimoxazole, 

retinoic acid was more 

effective than sulphurresorcinol and placebo; 

sulphur-resorcinol was 

more effective than placebo.

n=211 Can't say

female 146

male 65

Age 19.3 y

#126

Como, Italy

Parallel

Gandola, 1976

multicenter

Abdominal pain/diarrhea

Dry eyes/conjunctivitis

Dry mouth

Dry nose

Dry skin

Dryness/cheilitis

Headache

Increased appetite

Pruritis

Red/scaling face

Skin fragility

2, 4

Alitretinoin

Isotretinoin

È

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. 

All subjects had mucocutaneous reactions; other 

side effects were reported 

to a greater extent with 

alitretinoin.

n=26 Can't say

female 0

male 26

Age 17.0-40 y

#127

Geneva, 

Switzerland

Parallel

matched

Geiger, 1996

multicountry

Summary Table: Page 24 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Active papules (sqrt count)

Active pustules (sqrt count)

Back severity (log Leeds)

Chest severity (log Leeds)

Face severity (log Leeds)

Less active papules (sqrt 

count)

Less active pustules (sqrt 

count)

Overall change/patient

Side effects

4, 8

Oxytetracycline

Trimethoprim

È

Í

Randomized. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

Patient not blinded. 

Execution not as 

designed. 

Oxytetracycline and 

trimethoprim were both 

effective.

#128 n=45 Mild

London, UK

Parallel

Gibson, 1982

Mucous membrane side 

effects

Nodulocystic change (%)

Nodulocystic change posttherapy (%)

Nodulocystic change posttreatment/face (%)

Nodulocystic change/face (%)

Skin side effects

Systemic side effects

2, 4, 6, 8;4, 8 posttherapy

Isotretinoin

Etretinate

Í

Data show patient 

blinded. Data shows 

enroller blinded. No 

losses to followup. Data 

shows outcome assessor 

blinded. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Isotretinoin was 

significantly more effective 

than etretinate in reducing 

severe acne.

n=56 Sev

female 0

male 56

Age 23.4 y

#130

Boston, USA

Parallel

Goldstein, 1982

multicenter

Burning

Closed comedones (count)

Diarrhea

Dryness

Erythema

Itching

Open comedones (count)

Overall change/patient

Overall change/physician

Papules (count)

Peeling

Pustules (count)

Severity (Goltz)

6, 12

Clindamycin (lotion)

Clindamycin (solution)

È

Í

Randomized. Data 

shows enroller blinded. 

Patient not blinded. 

Clindamycin lotion was 

less drying than solution 

and was equally effective.

n=70 Mod/sev

Age 22.0 y

#131

Minneapolis, USA

Parallel

Goltz, 1985

Summary Table: Page 25 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change

Overall change/patient

Overall change/photo

12

Placebo

Spironolactone (200)

Spironolactone (150)

Spironolactone (100)

Spironolactone (50)

È

Í

Randomized. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

Major losses to 

followup. Arms not 

comparable. 

The clinical response to 

spironolactone was dose 

dependent and was best at 

a dose of 1250-200mg.

n=36 Sev

female 19

male 17

Age 24.0 y

#132

London, UK

Parallel

Goodfellow, 1984

Comedones change (count)

Overall change/patient

Papules change (count)

Pustules change (count)

Severity change (% 

Michaelsson)

Severity change 

(Michaelsson)

3, 6

Placebo

Zinc sulfur

È

Randomized. Data show 

patient blinded. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

Zinc and placebo showed 

comparable effectiveness.

n=59 Mod

female 22

male 27

Age 20.3 y

#133

Umea, Sweden

Parallel

Goransson, 1978

Overall change/patient

Overall change/physician

Papules (count)

Pustules (count)

Side effects 2, 4, 6, 8

Placebo

Tetracycline + placebo

Clindamycin + placebo

Specific population. 

Both topical clindamycin 

phosphate and oral 

tetracycline hydrochloride 

were effective in moderate 

to severe acne.

n=305 Mod/sev

Age 18.0-35 y

#136

Montreal, Canada

Parallel

Gratton, 1982

Summary Table: Page 26 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Face severity change (Leeds 

%)

Inflammatory change (%)

Non-inflammatory change 

(%)

Post-therapy facial severity 

change (Leeds %)

Post-therapy inflammatory 

change (%)

Post-therapy noninflammatory change (%)

Post-therapy total severity 

change (Leeds %)

Systemic reactions

Total severity change (Leeds 

%)

8, 16, 24, 32 (= 4 posttherapy)

Tetracycline + placebo

Cyproterone + ethinyl 

estradiol + placebo

Cyproterone + ethinyl 

estradiol + tetracycline

È

Í

Data shows outcome 

assessor blinded. 

Major losses to 

followup. Arms not 

comparable. 

Cyproterone + ethinyl 

estradiol was as effective as 

tetracycline

in treating women.

n=92 Can't say

female 92

male 0

Age 16.0-30 y

#137

Leeds, UK

Parallel

Greenwood, 1985

Post-therapy overall 

state/observer

7, 7-11, 12-14, 14-18 

(unspecified)

Sham rays

Grenz rays

È

Í

Randomized. 

Arms not comparable. 

Treatment with Grenz rays 

is not recommended.

n=40 Can't say

female 42

male 38

Age 15.0-25 y

#138

Amsterdam, The 

Netherlands

Parallel

split face

Groot, 1963

Post-therapy overall 

state/observer

7, 7-11, 12-14, 14-18 

(unspecified)

Grenz rays

Sham rays

È

Í

Randomized. 

Major losses to 

followup. Arms not 

comparable. 

Treatment with Grenz rays 

is not recommended.

#139 n=33 Can't say

Amsterdam, The 

Netherlands

Parallel

split face

Groot, 1963

Summary Table: Page 27 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity [intention to treat] 

(Leeds)

Severity [per protocol] 

(Leeds) 

Severity change [intention to 

treat] (Leeds %)

Severity change [per 

protocol] (Leeds %)

Side effects

Withdrawal due to side 

effects

1, 4, 12

Adapalene

Tretinoin

È

Í

Randomized. 

Patient not blinded. 

Adapalene 0.1% gel 

reduced inflammatory and 

total lesions more rapidly 

than tretinoin 0.025% gel 

and was better tolerated.

n=105 Mild/mod

female 39

male 66

Age 20.5 y

#140

Strasburg, France

Parallel

Grosshans, 1998

multicountry

Face severity (Leeds)

Face severity change (Leeds)

Total lesions (count)

Total lesions change (count)

4, 8, 12

Vehicle

Cyproterone (topical)

Cyproterone + ethinyl 

estradiol (0.035)

Í

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Topical cyproterone acetate 

and oral cyproterone + 

ethinyl estradiol were 

equally effective.

n=45 Mild/mod

female 45

male 0

Age 30.3 y

#141

Vienna, Austria

Parallel

Gruber, 1998

Overall change/patient

Overall change/physician

Severity (score)

Total lesions change (%)

2, 4, 8, 12

Chloramphenicol + 

sulfur

Chloramphenicol + 

hydrocortisone + sulfur

Í

Arms not comparable. 

Chloramphenicol/sulphur 

with or without 

hydrocortisone was 

effective for mild to 

moderate acne.

n=50 Mild/mod

female 29

male 15

#142

Northampton, UK

Parallel

Guerrier, 1980

Nodules (count)

Papules (count)

Pustules (count)

2+ (unspecified)

Clindamycin 

hydrochloride

Clindamycin phosphate

È

Í

Data show patient 

blinded. Data shows 

enroller blinded. Data 

shows outcome assessor 

blinded. 

Major losses to 

followup. Arms not 

comparable. 

Clindamycin hydrochloride 

was slightly better than 

clindamycin phosphate.

#143 n=42 Sev

USA

Parallel

split face

Guin, 1979

Summary Table: Page 28 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/physician

Side effects

Vehicle

Clindamycin

Í

No losses to followup. 

Not randomized. 

The study was too small to 

demonstrate a difference.

#144 n=31 Mod/sev

Indianapolis, USA

Parallel

split face

Guin, 1981

Adverse reaction

Efficacy to initial (Spearman)

Inflammatory (count/median)

Inflammatory change (ratio 

to initial)

Non-inflammatory 

(count/median)

Non-inflammatory change 

(ratio to initial)

Non-responders

Overall change/physician 

(score)

Total lesions (count/median)

Total lesions (ratio to initial)

Total lesions change (ratio to 

initial)

2, 4, 8, 12

Retinyl beta-glucuronide

Vehicle

È

No losses to followup. 

RBG reduced both 

inflammatory and noninflammatory lesions.

n=29 Mild/mod

female 0

male 29

Age 20.4 y

#145

Ames, USA

Parallel

Gunning, 1994

Adverse reaction

Inflammatory (count/median)

Inflammatory lesion (ration 

to initial)

Non-inflammatory 

(count/median)

Non-inflammatory change 

(ratio to initial)

Non-responders

Overall change/physician 

(score)

Total lesions (count/median)

Total lesions change (ratio to 

initial)

2, 4, 6, 8, 14, 19, 28

Retinyl beta-glucuronide

Tretinoin

È

Í

No losses to followup. 

Outcome assessor not 

blinded. 

RBG and tretinoin were 

equally effective for mild to 

moderate acne.

n=15 Mild/mod

Age 22.5 y

#146

Ames, USA

Parallel

Gunning, 1994

Summary Table: Page 29 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones change (%)

Comedones change (count)

Inflammatory change (%)

Local side effects

Macules (count)

Nodules (count)

Severity (Cook)

2, 4, 8, 12

Erythromycin

Erythromycin + zinc

È

Data shows enroller 

blinded. 

Erythromycin/zinc lotion 

was more effective than 2% 

erythromycin in reducing 

number of acne lesions and 

severity grade of acne.

#147 n=122 Mod

Rotterdam, The 

Netherlands

Parallel

Habbema, 1989

multicountry

Inflammatory changes 

(Witkowski discretized %)

Non-inflammatory change 

(Witkowski discretized %)

Overall change (Witkowski 

discretized % )

Overall change (Witkowski 

discretized %)

Side effects/Withdrawal

Time to favorable status 

(Mean weeks)

10

Benzoyl peroxide (10%)

Benzoyl peroxide (5%)

Tretinoin

Tretinoin + benzoyl 

peroxide (10%)

Tretinoin + benzoyl 

peroxide (5%)

Í

No losses to followup. 

Patient not blinded. 

Enroller not blinded. 

Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. 

Tretinoin + benzoyl 

peroxide is the treatment of 

choice.

Mild/mod/se

v

n=250

female 202

male 48

Age 11.0-39 y

#149

Surabaya, 

Indonesia

Parallel

Handojo, 1979

Comedones (count)

Inflammatory (count)

Side effects

2, 4, 6

Vehicle

Fusidin Í

Inconsistent 

ascertainment across 

arms. 

Fusidin cream was superior 

to placebo cream in mild to 

moderate acne.

n=79 Mild/mod

female 16

male 54

Age 19.0 y

#151

Copenhagen, 

Denmark

Parallel

Hansted, 1985

Inter-treatment severity 

comparison

Overall change/matched 

(vas)

Severity (Leeds)

Severity change/photo

Side effects

4, 8, 12

Oxytetracycline

Co-trimoxazole

È

No losses to followup. 

Local population. 

 Trimethoprim + 

sulphamethoxazole was 

more effective than 

oxytetracycline.

Mild/mod/se

v

n=16

female 10

male 6

Age 15.5 y

#152

Malvera, UK

Parallel

matched

Harcup, 1980

Summary Table: Page 30 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Cysts change (%)

Nodules change (%)

Papules changes (%)

Pustules change (%)

Severity change (% Wright)

Side effects

Total lesions (%)

12

Minocycline

Doxycycline Í

Patient not blinded. 

Major losses to 

followup. 

Doxycycline is just as 

effective as minocycline.

Mild/mod/se

v

n=43

female 21

male 22

Age 20.0 y

#155

Lancaster, UK

Parallel

Harrison, 1988

Severity (Michaelsson)

12

Spironolactone [women]

Spironolactone [men]

Cimetidine [men]

Cimetidine [women]

Í

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. Arms not 

comparable. 

Acne severity decreased 

with spironolactone and 

cimetidone, but more so 

with spironolactone.

n=50 Mod/sev

female 31

male 19

Age 14.0-25 y

#156

Varanari, India

Parallel

Hatwal, 1988

Overall comparison

Severity change (Plewig)

Unspecified

Vehicle

Erythromycin Data show patient 

blinded. No losses to 

followup. Data shows 

outcome assessor 

blinded. 

n=29 Mod/sev

female 16

male 12

Age 15.0-34 y

#157

Irondheim, 

Norway

Parallel

matched

split face

Hellgren, 1980

Adverse reactions

Comedones (count)

Comedones change (%)

Cysts change (%)

Inflammatory (count)

Inflammatory change (%)

Overall change/investigator

Total lesions change (%)

Total lesions change (count)

2, 4, 8

Erythromycin

Clindamycin phosphate

È

Í

Data shows outcome 

assessor blinded. 

Patient not blinded. 

Enroller not blinded. 

Topical erythromycin was 

more effective than topical 

clindamycin phosphate for 

inflammatory acne. 

Erythromycin pledgets 

were more convenient, 

sanitary, and easier to use 

than clindamycin lotion.

n=120 Mod

female 56

male 49

Age 21.3±1.0 y

#158

Raritan, USA

Parallel

Henderson, 1995

Summary Table: Page 31 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Severity change [phase i] 

(Witkowski %)

Severity change [phase ii] 

(Witkowski %)

5, 10

Co-trimoxazole

Vehicle

È

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

 Trimethoprim + 

sulphamethoxazole was 

superior to vehicle.

n=42 Can't say

female 14

male 70

Age 13.0-30 y

#160

Gothenburg, 

Sweden

Cross-over

matched

Hersle, 1972

Severity (Witkowski)

Severity change [phase ii] 

(group %)

Side effects 5

Placebo

Minocycline

È

Data shows outcome 

assessor blinded. 

Minocycline was superior 

to placebo.

n=43 Can't say

female 14

male 29

Age 14.0-34 y

#161

Gothenburg, 

Sweden

Cross-over

Hersle, 1976

Adverse effects

Severity change

2-18 (unspecified)

Placebo

Demethylchlortetracycli

ne

È

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Demethylchlortetracycline 

was effective. 

Photosensitivity was the 

most common side effect.

#162 n=37 Mod/sev

Miami, USA

Parallel

Hicks, 1962

Overall change/patient

Overall change/physician

Side effects

Withdrawal due to side 

effects

4, 8, 12

Placebo

Zinc sulfate

Zinc treatment was better 

than placebo.

n=112 Mod/sev

Age 18.4 y

#163

Gavle, Sweden

Parallel

Hillstrom, 1977

multicenter

Closed comedones change 

(%)

Cysts change (%)

Open comedones change (%)

Papules change (%)

Pustules change (%)

Total lesions change (%)

4, 8

Meclocycline 

sulfosalicylate + placebo

Tetracycline + vehicle

È

Í

Randomized. No losses 

to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Topical meclocycline 

sulfosalicylate was an 

effective and safe 

alternative to systemic 

tetracycline.

n=60 Mild/mod

female 34

male 26

Age 20.0 y

#164

Rodovre, Denmark

Parallel

Hjorth, 1984

Summary Table: Page 32 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change

2, 4, 8

Vehicle

Aluminum chloride

È

Data show patient 

blinded. 

Topical 6.25% aluminum 

in anhydrous alcohol had a 

good clinical effect.

n=25 Mild/mod

female 36

male 14

Age 23.0 y

#165

Rodovre, Denmark

Parallel

split face

Hjorth, 1985

Overall change/physician

Total lesions (count/median)

12, 20

Azelaic acid + placebo

Tetracycline 

hydrochloride

È

Í

Randomized. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Arms not 

comparable. Execution 

not as designed. 

20% azelaic acid cream 

was an effective topical 

treatment for inflammatory 

acne.

n=333 Mild/mod

female 155

male 178

#166

Copenhagen, 

Denmark

Parallel

Hjorth, 1989

multicenter

Inflammatory (count/median)

Nodes+cysts (count/median)

Overall change/patient

4, 8, 12, 16, 20, 24

Tetracycline 

hydrochloride + placebo

Azelaic acid + placebo

È

Í

Randomized. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Arms not 

comparable. Execution 

not as designed. 

20% azelaic acid cream 

was an effective topical 

treatment for inflammatory 

acne.

n=261 Mod/sev

female 68

male 193

#167

Coppenhagen, 

Denmark

Parallel

Hjorth, 1989

multicenter

Mild/mod local side effects

Mild/mod systemic side 

effects

Persistent severity reduction

Severe side effects

Severity change

Severity reduction 

(cumulative %)

Time to severity reduction 

(days)

3, 6, 9, 12, 15, 18, 21, 

24

Minocycline

Tetracycline Í

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. 

No statistically significant 

difference between the two 

treatments.

n=104 Mod/sev

female 27

male 22

Age 17.4 y

#171

Lackland, USA 

Cross-over

Hubbell, 1982

Summary Table: Page 33 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Post-therapy severity (Cook)

Severity (Cook)

Severity difference/staff, 

patient

Severity/patient (Cook)

4, 8

Relaxation training + 

benzoyl peroxide + 

erythromycin

Group therapy

Benzoyl peroxide + 

erythromycin

È

Data shows enroller 

blinded. No losses to 

followup. Data shows 

outcome assessor 

blinded. 

Biofeedback relaxation 

combined with cognitive 

imagery reduced acne 

severity.

n=30 Mild/mod

female 24

male 6

Age 27.1±6.6 y

#172

Coral Gables, USA

Parallel

matched

Hughes, 1983

Inflammatory (count)

Local reactions I

Local reactions II

Non-inflammatory (count)

Severity (Leeds) 4, 8, 12

Vehicle

Benzoyl peroxide

Isotretinoin

È

Í

Referral population. 

Arms not comparable. 

Both topical benzoyl 

peroxide (5%) and topical 

isotretinoin (5%) were 

effective treatments for 

mild/moderate acne. 

Isotretinoin had a slower 

response rate for resolution 

of inflamed lesions.

n=77 Mild/mod

female 31

male 46

Age 18.7 y

#173

Leeds, UK

Parallel

Hughes, 1992

Inflammatory (count)

Severity change

3

Vehicle

Clobetasol

È

Í

No losses to followup. 

Not randomized. Patient 

not blinded. Enroller not 

blinded. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Execution 

not as designed. 

Clobetasol propionate did 

not significantly reduce the 

number of inflamed acne 

lesions.

n=11 Mod

female 14

male 8

Age 15.0-25 y

#175

Leeds, UK

Parallel

split face

Hull, 1989

Inflammatory change (%)

Local effects

Non-inflammatory change 

(%)

Total lesions change (%)

2, 4, 8, 12

Vehicle

Gluconolactone

Benzoyl peroxide

Í

Arms not comparable. 

Topical gluconolactone as 

effective as benzoyl 

peroxide for inflamed and 

total lesions, and was better 

tolerated.

n=150 Mod/sev

female 65

male 70

Age 20.1 y

#176

Sydney, Australia

Parallel

Hunt, 1992

Summary Table: Page 34 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Clinical assessed facial 

lesions

Clinical assessment back 

lesions

Clinical assessment chest 

lesions

Face severity (Jaffe)

Greasiness

12

Vehicle

Hydroxyquinoline + 

benzoyl peroxide + 

hydrocortisone

Hydroxyquinoline + 

benzoyl peroxide

Benzoyl peroxide

È

Data show patient 

blinded. Data shows 

enroller blinded. Data 

shows outcome assessor 

blinded. 

The combination cream 

better was superior.

#177 n=107 Can't say

UK

Parallel

Jaffe, 1989

multicenter

Adverse reactions/No 

withdrawals

Adverse 

reactions/Withdrawals

Premenstrual change/patient 

[phase ii]

Premenstrual overall 

change/patient [phase ii]

Premenstrual overall 

change/physician [phase i]

Premenstrual overall 

change/physician [phase ii]

4, 8

Hydrochlorthiazide

Vehicle Í

Major losses to 

followup. 

Hydrochlorothiazide was 

ineffective in premenstrual 

acne.

n=42 Can't say

female 42

male 0

#178

New York City, 

USA

Cross-over

Jelinek, 1972

Improvement

16, 24

Sham rays

Grenz rays

È

Í

No losses to followup. 

Not randomized. 

Enroller not blinded. 

#179 n=40 Can't say Grenz rays had no effect.

London, UK

Parallel

matched

split face

Jelliffe, 1969

Severity change (group %)

4, 7

Sham rays

Grenz rays

È

Í

No losses to followup. 

Not randomized. 

Enroller not blinded. 

Grenz rays at 50 kV may 

be beneficial.

#180 n=42 Can't say

London, UK

Parallel

matched

split face

Jelliffe, 1969

Summary Table: Page 35 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Burning-irritation

Dryness

Exudate

Eye irritation

Herpes simplex

Inflammatory (group count)

Oiliness

Overall change/physician

Pruritis

Redness

Scaling

Side effects

3, 6, 9, 12

Vehicle

Erythromycin

È

Data shows outcome 

assessor blinded. 

Specific population. 

2% topical erythromycin 

improved moderate to 

severe acne, but some side 

effects were seen.

n=175 Mod

female 88

male 68

Age 22.6±5.6 y

#184

Indianapolis, USA

Parallel

Jones, 1981

Local reactions/Cheilitis 

severity

Local 

reactions/Conjunctivitis

Local reactions/Dermatitis 

severity

Local 

reactions/Desquamation 

severity

Non-inflammatory change 

(%)

Post-therapy noninflammatory change (%)

Systemic reactions/Arthralgia

Systemic reactions/Epistaxis 

severity

Systemic reactions/Malaise

4, 8, 12, 16, 20, 24, 

28, 32

Isotretinoin (1.0)

Isotretinoin (0.5)

Isotretinoin (0.1)

È

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. Execution not as 

designed. 

Isotretinoin at 0.5 mg/kg 

was recommended over 0.1 

or 1.0 mg/kg for initial 

treatment, balancing 

relapse rate and side effects.

n=76 Mod

female 45

male 31

Age 24.3±6.2 y

#185

Leeds, UK

Parallel

Jones, 1983

Closed comedones (count)

Nodules (count)

Open comedones (count)

Papules (count)

Pustules (count)

Side effects

3, 6, 9, 12

Tetracycline 

hydrochloride + placebo

Clindamycin + placebo

Í

Major losses to 

followup. 

Topical clindamycin was 

effective to treat moderate 

acne vulgaris.

n=44 Mod

female 42

male 2

Age 13.0-30 y

#186

Athens, Greece

Parallel

Katsambas, 1987

Summary Table: Page 36 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Burning

Comedones change (%)

Erythema

Inflammatory (count/median)

Itching

Overall change/physician

Scaling

4, 8, 12

Vehicle

Azelaic acid

È

Í

Randomized. 

Inconsistent 

ascertainment across 

arms. 

Azelaic acid was a 

therapeutically active drug.

n=92 Mod

female 65

male 27

Age 19.0 y

#187

Athens, Greece

Parallel

Katsambas, 1989

Comedones (count)

Comedones (count/median)

Erythema

Overall change/physician

Scaling

20

Tretinoin

Azelaic acid

È

Í

Randomized. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. 

20% azelaic acid cream 

showed the same 

therapeutic benefit in 

comedonal acne as 0.05% 

tretinoin cream but caused 

side effects.

n=289 Can't say

female 152

male 137

Age 17.5 y

#188

Athens, Greece

Parallel

Katsambas, 1989

Overall change/physician

Side effects

6-48 (unspecified)

Placebo

Gamma-globulin Í

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Gamma-globulin every two 

weeks was not useful in the 

management of moderate 

acne.

n=40 Mod/sev

female 21

male 19

Age 15.0-30 y

#189

Providence, USA

Parallel

Kern, 1962

Severity/face (king)

4, 8, 12, 16

Isotretinoin (0.1)

Isotretinoin (1.0)

Isotretinoin (0.5)

Í

Major losses to 

followup. Arms not 

comparable. 

No evidence of dose 

response.

Mild/mod/se

v

n=48

female 24

male 24

Age 25.0 y

#190

Leeds, UK

Parallel

King, 1982

Summary Table: Page 37 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/physician

16, end of study (up to 

36)

Proprietary formula 

(sulfur + salicylic acid 

+ resorcinol)

Placebo

Komed® (sulfur + 

salicylic acid + 

resorcinol)

È

Í

No losses to followup. 

Referral population. 

Arms not comparable. 

Komed was an effective 

treatment.

Mild/mod/se

v

n=51

female 38

male 13

Age 13.0-28 y

#191

UK

Parallel

split face

Kirton, 1967

Overall change/physician

3

Demethylchlortetracycli

ne

Placebo

È

Í

No losses to followup. 

Arms not comparable. 

Systemic 

demethylchlortetracycline 

was effective in treating 

acne vulgaris.

#192 n=74 Can't say

Houston, USA

Parallel

Knox, 1965

Overall change/physician, 

patient

3, 7

Placebo

Demethylchlortetracycli

ne

È

No losses to followup. 

Demethylchlortetracycline 

was better than placebo.

#193 n=74 Can't say

Houston, USA

Cross-over

Knox, 1965

Comedones (count)

Inflammatory change

Inflammatory change 

(median %)

Side effects

2, 4, 8, 11

Vehicle

Meclocycline

Í

No losses to followup. 

Referral population. 

Not randomized. 

Inconsistent 

ascertainment across 

arms. 

Meclocycline is effective 

and safe. Twice daily is as 

effective as once-daily, but 

perhaps achieves effect 

quicker.

#194 n=134 Mod/sev

Sioux Falls, USA

Parallel

Knutson, 1981

multicenter

Adverse effects

Inflammatory change 

(median %)

2, 5

Vehicle

Meclocycline

Í

No losses to followup. 

Referral population. 

Not randomized. 

Inconsistent 

ascertainment across 

arms. 

Meclocycline is safe and 

effective. Once daily 

administration is as 

effective, but longer time to 

reach maximal effect.

#195 n=217 Mod/sev

Sioux Falls, USA

Parallel

Knutson, 1981

multicenter

Summary Table: Page 38 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory (count)

Itching

Non-inflammatory (count)

Redness

Scaling

12

Acidic syndet bar

Soap

È

Í

Randomized. Data 

shows enroller blinded. 

Patient not blinded. 

Outcome assessor not 

blinded. 

Acidic syndet lowerd the 

number of inflammatory 

acne lesions in acne-prone 

patients more than regular 

use of soap.

n=114 Mild

female 47

male 67

Age 20.0±3.3 y

#197

Munich, Germany

Parallel

Korting, 1995

Clinical assessment

Comedones (count)

Papules (count)

Pustules (count)

Severity/patient (vas)

Side effects

12

Vehicle

Tretinoin (0.025%)

Tretinoin (0.05%)

È

Í

Data shows enroller 

blinded. No losses to 

followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Topical tretinoin 0.05% 

and 0.025% were both 

better than placebo and 

about equally effective. 

There were fewer side 

effects with 0.025% 

tretinoin.

n=60 Can't say

Age 18.0-21 y

#198

Liecester, UK

Parallel

Krishnan, 1976

Closed comedones (count)

Dryness, peeling, erythema, 

burning and itching

Nodes+cysts (count)

Open comedones (count)

Overall change/physician

Papules (count)

Pustules (count)

Severe side effects

3, 6, 12

Vehicle

Clindamycin phosphate

È

Í

No losses to followup. 

Inconsistent 

ascertainment across 

arms. 

Topical clindamycin was 

effective for moderate to 

severe acne and was well 

tolerated. [By the 

Combined Acne Severity 

Classification, these 

patients' acne is classified 

as "mild to moderate."]

n=45 Mild/mod

Age 12.0-30 y

#199

Louisville, USA

Parallel

Kuhlman, 1986

Clinical change (grouped)

Clinical change/photo 

(grouped)

Clinical improvement/photo 

(grouped)

Severity change (Pillsbury 

modified)

Side effects

6, 12

Tetracycline

Placebo

È

Í

Randomized. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

Referral population. 

Arms not comparable. 

Tetracycline was better 

than placebo for moderate 

acne. (Note that baseline 

data was not provided to 

document acne severity.)

n=51 Can't say

female 25

male 26

Age 18.0 y

#201

Leeds, UK

Parallel

Lane, 1969

Summary Table: Page 39 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Closed comedones (count)

Papules (count)

Side effects

4, 8, 12

Vehicle

Isotretinoin (0.05%)

Isotretinoin (0.1%)

.01% and 0.05% istretinoin 

reduced acne grade, 

particulary closed 

comedones, more than 

placebo. 0.1% isotretinoin 

was better tolerated.

#202 n=82 Mild/mod

Warsaw, Poland

Parallel

Langner, 1994

Comedones (count)

Cysts (count)

Papules (count)

Pustules (count)

6

Silicic acid

Vehicle

È

Í

No losses to followup. 

Enroller not blinded. 

Silicic acid was more 

effective than placebo.

n=30 Mod

female 19

male 11

Age 19.0 y

#204

Helsinki, Finland

Parallel

Lassus, 1996

Erythema

Inflammatory (count )

Inflammatory (count)

Peeling

Severity (Cook )

Severity change (Cook %)

2, 4, 8, 10, 12

Vehicle

Erythromycin

È

Randomized. 

2% erythromycin was 

better than vehicle.

n=225 Mild/mod

female 76

male 132

Age 18.6 y

#205

Augusta, USA

Parallel

Lesher, 1985

multicenter

Comedones+pustules (count)

Cysts (count)

Cysts diameters (mm)

Integumentary side effects I

Integumentary side effects II

Integumentary side effects III

Post-therapy back total 

lesions change

Post-therapy chest total 

lesion change

Post-therapy 

comedones+pustules (count)

Post-therapy cyst diameters 

(mm)

Post-therapy long term cyst 

(count)

Systemic reactions

Systemic reactions/Special 

senses

2, 4, 8, 12, 16, 20, 24, 

35

Tetracycline 

hydrochloride

Isotretinoin

Í

Enroller not blinded. 

Major losses to 

followup. 

After 16 weeks treatment 

both isotretinoin and 

tetracycline produced 

similar improvement in 

patients with severe 

recalcitrant nodulocystic 

acne. 8 weeks after 

treatment, patients treated 

with isotretinoin continued 

to improve more than those 

treated with tetracycline.

n=30 Sev

female 1

male 29

Age 25.4±6.5 y

#206

Toronto, Canada

Parallel

Lester, 1985

Summary Table: Page 40 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Closed comedones change 

(count)

Inflammatory change (count)

Local tolerability

Non-inflammatory change 

(count)

Open comedones change 

(count)

Overall change/patient

Papules change (count)

Pustules change (count)

Severity change (% response)

4, 8, 12

Erythromycin

Clindamycin phosphate Í

Patient not blinded. 

Topical erythromycin 2% 

gel was as effective as 

topical clindamycin 

phosphate 1% solution in 

reducing number of lesions 

and in improving overall 

acne condition.

n=109 Mild/mod

female 50

male 52

Age 17.8 y

#208

Brooklyn, USA

Parallel

Leyden, 1987

multicenter

Severity change (Pillsbury %)

3, 6

Placebo

Zinc sulfate

Zinc had a weak but 

statistically significant 

effect.

Mild/mod/se

v

n=59

female 22

male 32

Age 20.3 y

#211

Umea, Sweden

Parallel

Liden, 1980

Overall change/physician

Side effects

4, 8, 12

Tetracycline 

hydrochloride

Tetracycline (sustained 

release)

È

Í

Data shows outcome 

assessor blinded. 

Major losses to 

followup. Arms not 

comparable. 

Sustained-release 

tetracycline (at half the 

standard dose of 

tetracycline) was as 

effective as treracycline 

hydrochloride.

n=55 Can't say

female 23

male 16

Age 20.0 y

#212

London, UK

Parallel

Lim, 1974

Comedones (count)

Inflammatory (count)

Local adverse reactions 4, 8, 16

Vehicle

Inocoterone acetate

È

Randomized. 

Topical inocoterone acetate 

produced a modest clinical 

effect.

n=153 Mod

female 0

male 153

#213

Hershey, USA

Parallel

Lookingbill, 1992

multicenter

Summary Table: Page 41 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory change (%)

Local side effects

Non-inflammatory change 

(%)

Overall change/physician

2, 5, 8, 11

Vehicle

Benzoyl peroxide

Clindamycin

Clindamycin + benzoyl 

peroxide

È

Í

Randomized. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

General population. 

Major losses to 

followup. Arms not 

comparable. 

A combination was better 

than either component 

alone.

n=393 Mod

female 202

male 191

Age 18.5 y

#214

Hershey, USA

Parallel

Lookingbill, 1997

multicenter

Inflammatory change

12

Comedone extraction 

(cheeks/forehead)

Comedone extraction 

(forehead)

È

Í

No losses to followup. 

Not randomized. Patient 

not blinded. Enroller not 

blinded. Outcome 

assessor not blinded. 

Comedones extraction was 

effective in superficial, but 

not cystic, acne. It was 

more effective on the 

forehead than the cheeks.

n=20 Can't say

female 4

male 16

Age 15.0-22 y

#215

Philadelphia, USA

Parallel

matched

split face

Lowney, 1964

Inflammatory change

Unspecified

Comedone extraction 

(cheeks/forehead)

Untreated

È

Í

No losses to followup. 

Not randomized. Patient 

not blinded. Enroller not 

blinded. Outcome 

assessor not blinded. 

Comedones extraction was 

effective in superficial, but 

not cystic, acne. It was 

more effective on the 

forehead than the cheeks.

n=12 Can't say

female 3

male 9

Age 14.0-18 y

#216

Philadelphia, USA

Parallel

matched

split face

Lowney, 1964

Closed comedones (count)

Open comedones (count)

Papules (count)

Pustules (count)

Severity (Leeds)

Severity/flash photo (Leeds)

Severity/fluorescent photoface+nose (Leeds)

Severity/fluorescent photonose (Leeds)

Severity/fluorescent 

photography

2, 4, 8, 12

Clindamycin

Vehicle

È

Í

Data shows outcome 

assessor blinded. 

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. 

Clindamycin was more 

effective than placebo in a 

study using fluorescence 

photography.

n=42 Mod

female 19

male 13

Age 13.0-31 y

#217

Boston, USA

Parallel

Lucchina, 1996

Summary Table: Page 42 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Closed comedones change 

(count)

Comedones change (count)

Inflammatory (count)

Nodules change (count)

Open comedones change 

(count)

Overall change/investigator

Overall change/patient

Total lesions change (%)

Total lesions change (count)

4, 8, 12, 16, 20, 24, 

25, 26

Norgestimate + ethinyl 

estradiol + inactive drug

Placebo

È

Í

Randomized. Data 

shows outcome assessor 

blinded. Specific 

population. 

Major losses to 

followup. 

Norgestimate-ethinyl 

estradiol use led to greater 

decreases in acne lesion 

counts and better global 

ratings than placebo in 

women with moderate acne

n=257 Mod

female 231

Age 27.0 y

#218

Cinncinnati, USA

Parallel

Lucky, 1997

multicenter

Inflammatory change (%)

Non-inflammatory change 

(%)

Overall change/physician

Side effects

Total lesions change (%)

2, 4, 8, 12

Polyoprepolymer-2

Tretinoin

Tretinoin + 

polyoprepolymer-2

È

Data show patient 

blinded. Data shows 

enroller blinded. 

Referral population. 

Tretinoin and tretinoin 

with polymer were equally 

efficacious and safe for 

mild-moderate acne.

n=344 Mild/mod

female 135

male 136

Age 20.0±5.8 y

#219

Cincinnati, USA

Parallel

Lucky, 1998

multicenter

Adverse effect

Adverse effects

Any adverse outcome

Dry skin

Eruption

Inflammatory change (%)

Non-inflammatory change 

(%)

Other skin symptoms

Systemic adverse effects

Total lesions change (%)

2, 4, 8, 12

Vehicle

Tretinoin (ethanol)

Tretinoin 

(polyoprepolymer-2)

Í

Arms not comparable. 

Ethanol and 

polyprepolymer-2 gels 

containing 0.025% 

tretinoin had similar 

efficacy but 

polyoprepolymer-2 caused 

less peeling and drying.

n=215 Mild/mod

female 118

male 97

#220

Cincinnati, USA

Parallel

Lucky, 1998

multicenter

Adverse reaction

Comedones (count)

Comedones change (%)

Papules (count)

Papules change (%)

Pustules (count)

Pustules change (%)

Severity change

2, 4, 6, 8

Benzoyl peroxide 

(alcohol)

Benzoyl peroxide 

(acetone)

Tretinoin

Í

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Benzoyl peroxide and 

tretinoin were equally 

effective.

n=147 Mod

female 107

male 40

Age 18.7 y

#221

San Antonio, USA

Parallel

Lyons, 1978

multicenter

Summary Table: Page 43 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Adverse reaction

Overall change/patient

Overall change/physician 

[mild]

Overall change/physician 

[moderate]

Overall change/physician 

[severe]

10, 24

Vehicle

Staphylococcal toxoid

È

No losses to followup. 

Specific population. 

Staphylococcal toxoid 

injection was efficacious in 

management of recalcitrant 

pustular acne.

Mild/mod/se

v

n=66

female 0

male 66

#222

UK

Parallel

Macdonald, 1951

Comedones change [phase 

i+ii] (count)

Dizziness and headaches

Pustules change [phase i+ii] 

(count)

Red macular rash

4

Placebo

Co-trimoxazole

È

Data show patient 

blinded. Data shows 

enroller blinded. Data 

shows outcome assessor 

blinded. 

Trimethoprimsulphamethoxazole was as 

effective as placebo.

n=40 Can't say

Age 18.5 y

#223

Glasgow, UK

Cross-over

matched

Macdonald, 1972

Comedones reduction 

percentage change (%)

Inter-group difference 

papule % change (%)

Inter-group difference 

pustule % change (%)

Side effects

4, 10

Hydrocortisone + 

buttoxethyl nicotinate + 

chloramphenicol

Vehicle

È

Í

Data show patient 

blinded. 

Enroller not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Topical mixture of sulphur 

chloramphenicol 

hydrocortisone and 

buttoxyl ethyl nicotinate 

was better than vehicle.

Mild/mod/se

v

n=120

female 78

male 42

#224

Manchester, UK

Cross-over

Macdonald, 1976

Severity (Pillsbury)

Severity change (Pillsbury)

Severity/arm (Pillsbury)

Systemic adverse effects

12, 24, 36

Gestodene + ethinyl 

estradiol

Desogestrel + ethinyl 

estradiol

Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Ethinyl estradiol 

desogestrel and ethinyl 

estradiol-gestodene were 

effective in reducing acne.

n=24 Mild/mod

female 24

Age 24.0±3.7 y

#225

Rome, Italy

Parallel

Mango, 1996

Summary Table: Page 44 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/physician

4-6 (unspecified)

Neomycin + methyl 

prednisolone

Vehicle

Aluminum 

chlorhydroxide + sulfur

Í

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. Execution 

not as designed. 

Neomycin + 

methylprednisolone was 

effective.

#228 n=776 Can't say

Sussex, UK

Parallel

Mcguiness, 1965

multicenter

Inflammatory change (%)

4, 8, 12

Ionax®

E-solve®

Clindamycin 

hydrochloride (Ionax®)

Clindamycin 

hydrochloride (Esolve®)

Clindamycin phosphate 

(Ionax®)

Clindamycin phosphate 

(E-solve®)

È

Randomized. Local 

population. 

The effectiveness of 

clindamycin compared 

with the hydroalcoholic 

products was not 

significantly greater.

n=88 Mod/sev

female 64

male 20

Age 20.3 y

#229

Gainesville, USA

Parallel

split face

McKenzie, 1981

Comedones change 

(geometric mean)

Exfoliation

Inflammatory change 

(geometric mean)

Overall assessment/patient

Overall assessment/physician

Pustular lesions

Side effects

2, 4, 8

Benzoyl peroxide

Benzoyl peroxide + 

miconazole

È

Randomized. No losses 

to followup. 

Benzoyl peroxide + 

miconazole was better than 

benzoyl peroxide alone, 

particularly for 

inflammatory acne.

Mild/mod/se

v

n=20

Age 17.0±2.4 y

#231

Porto, Portugal

Parallel

Mesquita Guimar

Summary Table: Page 45 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones change (count)

Comedones severity change 

(Michaelsson difference)

Overall change/patient

Overall change/physician

Papules change (count)

Papules severity change 

(Michaelsson difference)

Pustules change (count)

Pustules severity change 

(Michaelsson difference)

Total severity change/photo 

(Michaelsson)

2, 4, 8, 12

Oxytetracycline

Zinc sulfate

È

No losses to followup. 

The effects of oral zinc and 

chlortetracycline were 

comparable in patients 

with moderate to severe 

acne.

n=40 Mod/sev

female 16

male 24

Age 15.0-29 y

#232

Uppsala, Sweden

Parallel

Michaelsson, 197

Severity change 

(Michaelsson %)

Side effects

2, 4, 6, 8, 12

Zinc sulfate + Vitamin 

A palmitate

Zinc sulfate

Vitamin A palmitate

Vehicle

È

Í

No losses to followup. 

Arms not comparable. 

Zinc decreased the number 

of papules, pustules and 

infiltrates. There was no 

significant effect for 

Vitamin A.

n=64 Mod/sev

female 26

male 38

Age 13.0-25 y

#233

Uppsala, Sweden

Parallel

Michaelsson, 197

Itching

Overall change/physician

12-16 (unspecified); 14 

average

Vehicle

Povidone-iodine Í

Major losses to 

followup. Outcome 

assessor not blinded. 

Betadine was an effective 

treatment for mild acne.

#235 n=30 Mild

Columbia, USA

Parallel

Milikan, 1976

Itching

Overall change/physician

12-16 (unspecified)

Tetracycline + vehicle

Povidone-iodine + 

tetracycline

Í

Major losses to 

followup. Outcome 

assessor not blinded. 

Povidone-iodine skin 

cleanser may not penetrate 

deeply enough to produce 

significant improvement in 

moderate acne.

#236 n=30 Mod/sev

Columbia, USA

Parallel

Milikan, 1976

Summary Table: Page 46 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Face severity (Leeds)

Face severity/photo

Macules (count)

Nodules (count)

Papules (count)

Systemic reactions I > once

Systemic reactions I once 

only

Systemic reactions II > once

Systemic reactions II once 

only

Total severity (Leeds)

8, 16, 26

Cyproterone (2 mg) + 

ethinyl estradiol

Cyproterone (.05 mg) + 

ethinyl estradiol

Norethisterone + 

placebo + ethinyl 

estradiol

Cyproterone and 

norethisterone were both 

effective.Cyproterone 

achieved effects faster. Side 

effects rates were 

comparable.

n=90 Mod/sev

female 90

male 0

Age 23.7 y

#237

London, UK

Parallel

Miller, 1986

Overall change/physician

2, 4, 6, 8

Vehicle

Tretinoin

Erythromycin

Erythromycin + 

tretinoin

Í

Not randomized. Patient 

not blinded. Enroller not 

blinded. Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. 

Erythromycin + tretinoin 

was more effective than 

either alone.

n=80 Mod/sev

female 35

male 45

Age 16.5 y

#238

Philadelphia, USA

Parallel

Mills, 1978

Inflammatory change (%)

Non-inflammatory change 

(%)

Total lesion change (%)

8

Polystyrene

Polyethylene

Polyester

Aluminum oxide

Pumice

Í

Not randomized. Patient 

not blinded. Enroller not 

blinded. Major losses to 

followup. Outcome 

assessor not blinded. 

Arms not comparable. 

The beneficial effects of 

these abradants were slight.

#239 n=50 Mod/sev

Philadelphia, USA

Parallel

Mills, 1979

Summary Table: Page 47 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Total lesions change (%)

2, 4, 6, 8

Vehicle

Benzoyl peroxide

È

Í

No losses to followup. 

Not randomized. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

 2.5% benzoyl peroxide 

was more effective than 

vehicle and caused more 

side effects.

#241 n=50 Mild/mod

Philadelphia, USA

Parallel

Mills, 1986

Total lesions change (%)

2, 4, 6, 8

Benzoyl peroxide (5%)

Benzoyl peroxide 

(2.5%)

È

Í

No losses to followup. 

Not randomized. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

There was no difference in 

efficacy or side effects 

between the 2.5% and 

5.0% benzoyl peroxide.

#242 n=52 Mild/mod

Philadelphia, USA

Parallel

Mills, 1986

Burning

Erythema

Peeling

2, 4, 6, 8 Total lesions change (%)

Benzoyl peroxide (10%)

Benzoyl peroxide 

(2.5%)

È

Í

No losses to followup. 

Not randomized. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

 2.5% and 10% benzoyl 

peroxide showed equal 

efficacy.The 10% 

formulation caused more 

frequent and severe 

burning, erythema, and 

peeling.

#243 n=50 Mild/mod

Philadelphia, USA

Parallel

Mills, 1986

Comedones change (%)

Dryness change (score)

Erythema change (score)

Inflammatory change (%)

Papules change (%)

Pustules change (%)

Total lesions change (%)

2, 4, 8

Erythromycin

Clindamycin

È

Í

No losses to followup. 

Enroller not blinded. 

Arms not comparable. 

Erythromycin produced a 

greater reduction in 

pustules, papules, total 

inflamed lesions and total 

lesions, and was preferred 

by patients in terms of 

convenience, ease of 

application, and 

portability. Clindamycin 

was more effective for 

comedones.

n=120 Mild/mod

Age 18.0-30 y

#244

East Brunswick, 

USA

Parallel

Mills, 1992

Summary Table: Page 48 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones (count/max 

range)

Comedones (count/median)

GI+other side effects

Gyn side effects

Overall change/patient

Papules (count/max)

Papules (count/median)

Papules range (count/max)

Pustules (count/max)

Pustules (count/median)

Skin side effects

8, 16, 24

Cyproterone + ethinyl 

estradiol

Minocycline 

hydrochloride

Í

Patient not blinded. 

Enroller not blinded. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. 

Cyproterone-ethinyl 

estradiol and minocin were 

found to be equally 

effective in reduced the 

lesion count for 

comedones, papules and 

pustules and in pts 

subjective assessment of 

their skin.

n=98 Mild/mod

female 98

male 0

Age 23.4±5.1 y

#245

London, UK

Parallel

Monk, 1987

multicenter

Closed comedones (count)

Closed comedones change 

(%)

Open comedones (count)

Open comedones change (%)

Papules (count)

Papules change (%)

Pustules (count)

Pustules change (%)

Withdrawals due to side 

effects

4, 8, 12

Soybean liposome

Glycolic acid + soybean 

liposome

È

No losses to followup. 

Glycolic acid and soybean 

liposome was more 

effective and acted more 

quickly than soybean 

liposome alone.

n=40 Mild/mod

female 20

male 20

Age 16.0±3.0 y

#246

Italy

Parallel

split face

Morganti, 1997

Overall change/physician

4-8 (unspecified)

Oleandomycin

Triacetyl-oleandomycin Í

Not randomized. Major 

losses to followup. 

Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. Execution 

not as designed. 

Triacetyl-oleandomycin is 

effective.

#247 n=142 Can't say

Salt Lake City, 

USA

Parallel

Morginson, 1960

Summary Table: Page 49 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones (count)

Total lesions (count)

8

Quinestradol

Placebo Í

Not randomized. Major 

losses to followup. 

Quinestradol is effective, 

especially for comedones.

n=60 Mild/mod

female 60

male 0

#248

Reggio Emilia, 

Italy

Parallel

Moroni, 1976

Change (count)

Overall change/patient

Positive side effects

Severity/photo

Side effects

Total lesions [phase i+phase 

ii] (count)

12

Placebo

Spironolactone

È

Í

Data shows outcome 

assessor blinded. 

Major losses to 

followup. 

Spironolactone 

significantly improved 

acne.

n=58 Mild/mod

female 58

male 0

#249

London, UK

Cross-over

Muhlemann, 198

Severity change [phase i]

Severity change [phase ii]

Side effects

Unspecified

Placebo

Oxytetracycline Í

Not randomized. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Oxytetracycline in low 

dosage over a prolonged 

period of time was safe and 

effective.

n=76 Mod/sev

female 50

male 26

Age 11.0-33 y

#250

Unknown

Cross-over

Murphy, 1962

Overall change/physician

Papules (count)

Pustules (count)

8

Tretinoin

Motretinide (bid)

Motretinide (qd)

È

No losses to followup. 

Motretinide was an 

effective alternative to 

tretinoin.

n=60 Mod/sev

female 39

male 21

Age 15.0 y

#253

Vasteras, Sweden

Parallel

Nordin, 1981

Back severity (Leeds)

Chest severity (Leeds)

Face severity (Leeds)

Inflammatory (count)

Non-inflammatory (count)

Side effects

8, 12

Oxytetracycline (oral) 

+ vehicle

Benzoyl peroxide + 

placebo (oral)

Tetracycline (topical) + 

placebo (oral)

Í

Inconsistent 

ascertainment across 

arms. 

Topical tetracycline was as 

effective as either 5% 

benzoyl peroxide gel or 

oral tetracycline.

n=69 Mod

female 45

male 24

Age 12.0-33 y

#255

Leeds, UK

Parallel

Norris, 1991

Summary Table: Page 50 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Closed comedones (count)

Open comedones (count)

Papules (count)

Pustules (count)

Total lesions (count)

Withdrawal due to side 

effects

4, 8, 12

Doxycycline + placebo

Minocycline + placebo

Doxycyline and 

minocycline were equally 

effective.

n=79 Mod/sev

female 44

male 35

Age 20.5 y

#257

Reykjavik, Iceland

Parallel

Olafsson, 1989

Closed comedones (count)

Open comedones (count)

Papules (count)

Pustules (count) 4, 6, 8, 10, 12

Vehicle

Zinc sulfate Í

Major losses to 

followup. 

Oral zinc produced no 

benefit in males with 

moderate acne.

n=30 Mild/mod

female 0

male 22

Age 19.1 y

#259

New York City, 

USA

Parallel

Orris, 1978

multicenter

Comedones (count)

Inflammatory (count)

Overall change (score)

Side effects

2, 4, 7, 10

Erythromycin + 

benzoyl peroxide

Clindamycin phosphate

È

Data show patient 

blinded. Data shows 

enroller blinded. No 

losses to followup. Data 

shows outcome assessor 

blinded. 

Topical erythromycin with 

benzoyl peroxide was more 

effective than clindamycin.

n=205 Mild/mod

female 205

male 0

Age 23.0-50 y

#260

Collegeville, USA

Parallel

Packman, 1996

multicenter

Erythema

Itching/burn

Overall improvement 

(discretized %)

Peeling

Side effects

Total lesions (count)

2, 4, 6, 8

Tetracycline 

hydrochloride

Clindamycin

Í

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Topical clindamycin was 

superior to topical 

tetracycline for treatment 

of mild-moderate acne. 

Both produced minimal 

side effects.

n=52 Mild/mod

female 26

male 23

Age 22.3 y

#261

Albuquerque, USA

Parallel

Padilla, 1981

Severity change

Side effects

24

Levonorgestrel + 

ethinyl estradiol

Desogestrel + ethinyl 

estradiol

Í

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. Arms not 

comparable. 

Desogestrel + ethinyl 

estadiol was superior to 

levonorgestrel + ethinyl 

estadiol.

n=54 Can't say

Age 24.0 y

#263

Oulu, Finland

Parallel

Palatsi, 1984

multicenter

Summary Table: Page 51 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Severity (Allen-Smith)

24

Levonorgestrel + 

ethinyl estradiol

Desogestrel + ethinyl 

estradiol

È

Í

No losses to followup. 

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Desogestrel and ethinyl 

estadiol produced more 

improvement than 

levonorgestrel + ethinyl 

estadiol.

n=33 Mild/mod

Age 24.0 y

#264

Oulu, Finland

Parallel

Palatsi, 1986

Comedones (count)

Esophagitis

Mild diarrhea and cramping

Overall change/physician

Overall change/physician 

(rating)

Pustules (count)

Severity (Panzer)

1, 2, 4, 8

Tetracycline

Clindamycin

È

Í

Randomized. Referral 

population. 

Major losses to 

followup. Arms not 

comparable. 

Clindamycin 1% and 

tetracycline showed similar 

efficacy.

n=48 Mod

female 30

male 18

Age 17.5 y

#265

New Orleans, USA

Parallel

Panzer, 1977

Inflammatory (count)

Non-inflammatory (count)

2, 4, 6

Sunder vati

Shankhabhasma vah

Placebo

Thiostanin

Sookshama triphala

È

Data shows outcome 

assessor blinded. 

Sunder vati taken orally 

was effective in the 

treatment of acne vulgaris.

n=82 Mod

female 40

male 42

Age 21.1 y

#266

Pune, India

Parallel

Paranjpe, 1995

Open comedones (count)

Overall change/investigator

Overall change/patient

Pustules (count)

Side effects

3, 6, 9, 12

Clindamycin (solution)

Clindamycin (gel) Í

Patient not blinded. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Topical clindamycin 

phosphate gel and topical 

1% clindamycin phosphate 

solution showed equal 

efficacy for treatment of 

moderately severe acne. 

[By the Combined Acne 

Severity Classification, 

these patients' acne is 

classified as "mild."] Gel 

was less drying than 

solution.

#267 n=60 Mild

Portland, USA

Parallel

Parker, 1987

Summary Table: Page 52 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory (count)

Non-inflammatory (count)

Overall assessment (vas)

Overall change/patient

Side effects

2, 4, 8, 12

Minocycline

Clindamycin

È

Í

Data shows enroller 

blinded. No losses to 

followup. Specific 

population. 

Patient not blinded. 

Minocycline was twice as 

expensive as clindamycin. 

Both treatments were 

effective and there were no 

major differences in 

efficacy or side effects.

n=80 Mod/sev

female 28

male 52

Age 21.0 y

#268

Manchester, UK

Parallel

Peacock, 1990

multicenter

Cysts change (%)

Reduction in application due 

to side effects

4, 8

Isotretinoin

Placebo

È

Randomized. No losses 

to followup. 

Isotretinoin was more 

efficacious than placebo for 

patients with treatmentresistant cystic acne.

#269 n=33 Sev

Bethesda, USA

Parallel

Peck, 1982

Comedones severity

Improvement in papules

Improvement on pustules

Overall change

Side effects

4-12 (unspecified)

Tretinoin

Vehicle Í

Enroller not blinded. 

Arms not comparable. 

Tretinoin was superior to 

placebo.

n=61 Can't say

Age 17.0-21 y

#270

San Diego, USA

Parallel

Pedace, 1971

Overall change/patient with 

physician

12

Serum gonadotrophin

Placebo

È

Í

Data show patient 

blinded. Data shows 

enroller blinded. Data 

shows outcome assessor 

blinded. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Treatment with serum 

gonadotrophin treatment 

did not improve acne.

Mild/mod/se

v

n=40

female 17

male 23

#271

Liverpool, UK

Parallel

Pettit, 1959

Summary Table: Page 53 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Total lesions change (%)

14

Vitamin A

Sulfur + resorcinol

Benzoyl peroxide

Í

Not randomized. Patient 

not blinded. Enroller not 

blinded. Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Outcome assessor 

not blinded. Arms not 

comparable. Execution 

not as designed. 

Vitamin A was superior to 

both benzoyl peroxide and 

sulphur + resorcinol.

#272 n=189 Can't say

Philadelphia, USA

Parallel

Plewig, 1969

Comedones (discretized %)

Cysts

Inflammatory (discretized %)

Papules change

Pustules

Side effects

Total inflammatory [phase i] 

(count)

Total inflammatory [phase 

ii] (count)

4, 8

Doxycycline

Placebo Í

Major losses to 

followup. 

Doxycycline was an 

effective treatment for 

inflammatory acne but not 

for non-inflammatory acne.

n=62 Mild

female 36

male 88

Age 19.0 y

#273

Philadelphia, USA

Cross-over

Plewig, 1970

Closed comedones (count)

Open comedones (count)

Papules (count)

Pustules (count)

4, 8

Vehicle

Erythromycin

È

Í

Randomized. Specific 

population. 

Inconsistent 

ascertainment across 

arms. 

Erythromycin 2% gel 

produced greater 

improvement than vehicle 

in facial acne.

n=187 Mild/mod

female 98

male 89

Age 20.8±6.4 y

#274

Boston, USA

Parallel

Pochi, 1988

multicenter

Diarrhea

Lesions change

Overall change/patient (vas)

8

Tetracycline 

hydrochloride

Clindamycin 

hydrochloride

Í

Not randomized. 

Enroller not blinded. 

Major losses to 

followup. Outcome 

assessor not blinded. 

Arms not comparable. 

Clindamycin and 

tetracycline were 

equivalent.

n=47 Sev

female 19

male 28

Age 13.0-34 y

#275

St. Louis, USA

Parallel

Poulos, 1976

Summary Table: Page 54 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Chest/back total lesions 

(count)

Face/neck total lesions 

(count)

Overall change/patient vas 

(p value)

Overall change/patient vas 

(p-value)

Post-therapy chest/back total 

lesions (count)

Post-therapy face/neck total 

lesions (count)

Post-therapy overall 

change/patient vas (p value)

Post-therapy total 

severity/photo (Leeds)

Side effects

Total severity/photo (Leeds)

4, 8, 16, 20, 28, 36

Isotretinoin

Dapsone Í

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Isotretinoin was better than 

dapsone.

n=40 Sev

female 0

male 40

Age 16.0-31 y

#276

Middlesex, UK

Parallel

Prendiville, 1988

multicenter

Inter-treatment lesion change

Inter-treatment lesion 

change [female]

Inter-treatment lesion 

change difference (count)

Inter-treatment lesions 

change [male]

Lesions change

Lesions change [female]

Lesions change [male]

2, 4, 6, 8

Erythromycin

Vehicle Í

Enroller not blinded. 

Topical erythromycin 

solution showed greater 

reduction in lesion counts 

than placebo solution, but 

differences were not 

clinically significant.

n=73 Mild/mod

female 68

male 70

Age 20.3±2.2 y

#277

Iowa City, USA

Parallel

matched

split face

Prince, 1981

Inflammatory (count)

Inflammatory change

Total lesions (count) 2, 4, 6, 8

Benzoyl peroxide + urea

Benzoyl peroxide

There was no added benefit 

associated with addition of 

urea to benzoyl peroxide in 

treating moderate acne.

n=39 Mod

female 64

male 14

Age 23.0±3.6 y

#278

Iowa city, USA

Parallel

split face

Prince, 1982

Summary Table: Page 55 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Closed comedone change 

(count)

Closed comedones change 

(count)

Closed comedones severity 

change (vas)

Comedones change (count)

Inflammatory change (count)

Open comedone change 

(count)

Open comedones severity 

change (vas)

Overall change/physician, 

patient

Papules change (count)

Papules severity change (vas)

Pustules change (count)

Pustules severity change (vas)

Withdrawals due to side 

effects

2, 4, 8, 12

Tetracycline 

hydrochloride + 

placebo (topical)

Erythromycin + 

placebo (oral)

È

Data show patient 

blinded. Data shows 

outcome assessor 

blinded. 

Topical erythromycin was 

more effective and 

produced fewer side effects 

than oral tetracyline.

n=54 Mod/sev

female 32

male 22

Age 22.9±5.7 y

#279

Los Angeles, USA

Parallel

Rapaport, 1982

Adverse events

Comedones change (count)

Inflammatory change (count)

Overall change/investigator

Overall change/patient

Total lesions change (count)

4, 8, 12, 16, 20, 24, 26

Norgestimate + ethinyl 

estradiol

Placebo

È

Randomized. Data show 

patient blinded. 

Norgestimate + ethinyl 

estradiol was effective.

n=250 Mod

female 231

male 0

Age 28.4 y

#280

USA

Parallel

Redmond, 1997

multicenter

Comedones change (%)

Dryness (severity)

Erythema (severity)

Overall change

Papules change (%)

Pustules change (%)

Severity (Cook)

2, 4, 6, 8

Tretinoin + clindamycin

Tretinoin

Clindamycin Í

No losses to followup. 

Arms not comparable. 

All were similar in efficacy 

and well tolerated.

Mild/mod/se

v

n=64

Age 19.6 y

#283

Atlanta, USA

Parallel

Rietschel, 1983

Summary Table: Page 56 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change

8

Placebo

Hydrochlorthiazide Í

Not randomized. Patient 

not blinded. Enroller not 

blinded. Major losses to 

followup. Outcome 

assessor not blinded. 

Arms not comparable. 

Hydrochlorothiazide was 

no more effective than 

placebo.

n=50 Can't say

female 28

male 22

Age 8.0-29 y

#284

Charleston, USA

Parallel

Riley, 1961

Overall change/physician

Papules change (%)

Pustules change (%)

2, 4, 8, 10, 12

Erythromycin

Vehicle

Í

Data show patient 

blinded. Data shows 

enroller blinded. No 

losses to followup. 

Outcome assessor not 

blinded. Arms not 

comparable. 

Topical erythromycin is 

efficacious for moderately 

severe acne.

n=26 Mod/sev

female 20

male 6

Age 24.9 y

#285

Los Angeles, USA 

Parallel

Rivkin, 1980

Overall change/physician

Side effects

8-24 (unspecified)

Neomycin

Vehicle

Hydrocortisone

Sulfur

Resorcinol + neomycin 

+ hydrocortisone F + 

sulfur

Resorcinol

Í

Not randomized. Major 

losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. Execution 

not as designed. 

Resorcinol, neomycin, and 

sulphur, did not differ from 

base (vehicle) in 

effectiveness.

n=79 Can't say

Age 11.0-30 y

#287

Baltimore, USA

Parallel

Robinson, 1961

Summary Table: Page 57 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/physician

Side effects

Unspecified

Vehicle

Hydrocortisone + sulfur

Neomycin + sulfur

Neomycin + resorcinol 

+ hydrocortisone + 

sulfur

Resorcinol

Hydrocortisone

Neomycin

Sulfur

Í

Not randomized. Major 

losses to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. Execution 

not as designed. 

Sulphur, neomycin, and 

hydrocortisone did not 

differ in effectiveness.

#288 n=188 Can't say

Baltimore, USA

Parallel

Robinson, 1961

Open comedones change 

(count)

Papules change (count)

Pustules change (count )

Pustules change (count)

Severity assessment

Side effects

2, 4, 6, 8

Tetracycline

Clindamycin

È

Í

No losses to followup. 

Referral population. 

Inconsistent 

ascertainment across 

arms. 

Topical clindamycin was 

better at reducing pustules 

than topical tetracycline. 

There was no significant 

difference in reduction of 

comedones or papules.

n=92 Mild

Age 15.0-30 y

#291

Madrid, Spain

Parallel

Robledo, 1988

multicenter

Severity change

Severity change [female]

Severity change [male]

Side effects

Side effects [female]

Side effects [male]

Unspecified

Placebo

Dapsone

È

Í

No losses to followup. 

Not randomized. 

A statistically significant 

number of cases responded 

favorably to dapsone.

Mild/mod/se

v

n=46

female 25

male 19

#293

Pretoria, South 

Africa

Parallel

Ross, 1961

Acne change

Acne change (% face)

Face oiliness change (% face)

Local reactions

Oiliness change

1, 2, 3, 4, 5, 9-10

Salicylic acid

Placebo Í

Not randomized. Patient 

not blinded. Enroller not 

blinded. Major losses to 

followup. Outcome 

assessor not blinded. 

Execution not as 

designed. 

Salicylic acid reduced 

oiliness and improved acne.

n=30 Mild/mod

female 11

male 19

Age 13.0-32 y

#294

Daly City, USA

Parallel

matched

Roth, 1964

Summary Table: Page 58 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inter-treatment severity 

change

Overall change/physician

12

Vehicle

Epiestriol

È

Referral population. 

Epiestriol did not produce 

any significant effect.

#295 n=50 Can't say

Sheffield, UK

Parallel

split face

Rushton, 1962

Overall change/patient

Overall change/physician

Severity (Burton)

Withdrawals due to side 

effects

4, 8

Vehicle

Chloramphenicol + 

hydrocortisone

Í

Arms not comparable. 

Chloranpheniol + 

hydrocortisone was more 

effective.

n=32 Mild/mod

female 22

male 10

#297

Bristol, UK

Parallel

Saihan, 1981

GI symptoms

Severity/investigator 

(Samuelson)

Severity/patient (Samuelson)

Vaginal infection

6, 12

Minocycline

Tetracycline

È

Data shows enroller 

blinded. Data shows 

outcome assessor 

blinded. 

Minocycline was better 

than tetracycline using 

photographic assessment.

n=62 Mod/sev

female 40

male 22

Age 19.0 y

#298

East Stroudsburg, 

USA

Parallel

Samuelson, 1985

Overall change/physician

Side effects

4

Placebo

Tetracycline + sodium 

novobiocin

È

Í

Data show patient 

blinded. Data shows 

enroller blinded. No 

losses to followup. Data 

shows outcome assessor 

blinded. 

Arms not comparable. 

Tetracycline + sodium 

novobiocin was more 

effective than placebo.

n=42 Mod/sev

female 24

male 18

Age 15.0-25 y

#299

New Haven, USA

Parallel

Savin, 1966

Comedones change (%)

Cutaneous

Severity change (Cook %)

Total inflammatory change 

(%)

3, 6, 9, 12

Clindamycin phosphate

Erythromycin + zinc Í

Patient not blinded. 

Enroller not blinded. 

Erythromycin plus zinc 

provided better therapeutic 

benefits, in a shorter time, 

than topical clindamycin. 

Both medications were 

equally tolerated.

n=103 Mod

female 40

male 52

Age 19.1 y

#300

Miami, USA

Parallel

Schachner, 1990

Summary Table: Page 59 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Comedones (count)

Inflammatory (count)

Severity (Cook)

Severity change (Cook)

Side effects

2, 6, 10, 12, 16, 20, 

24, 28, 32, 36, 40, 44, 

48, 52

Vehicle

Erythromycin + zinc Í

Major losses to 

followup. Arms not 

comparable. 

Erythromycin + zinc was 

more effective than vehicle 

after 6 weeks treatment.

n=73 Mod

female 73

male 0

Age 13.0-36 y

#301

Miami, USA

Parallel

Schachner, 1990

Acne flare-up

Burning

Comedones (count)

Comedones (improvement)

Erythema

Inflammatory (count)

Inflammatory (improvement)

Scaling

2, 4, 6, 12

Tretinoin combined

Tretinoin (0.01%)

Tretinoin (0.05%)

Tretinoin (0.025%)

Í

Execution not as 

designed. 

Liposomal tretinoin 

(combined) provided 

comparable efficacy to 

tretinoin 0.025% and 

tretinoin 0.05%, and 

performed slightly better 

for comedones. It was also 

better tolerated.

n=20 Mild

female 14

male 6

Age 24.0 y

#302

Berlin, Germany

Parallel

split face

Schafer Korting, 

multicenter

Inflammatory (count)

Inter-treatment 

preference/patient

Non-inflammatory (count)

Side effects

2, 4, 8, 12

Clindamycin

Erythromycin

Erythromycin and 

clidamycin showed 

comparable effectiveness 

but erythromycin produced 

somewhat more side effects.

n=178 Mod

female 116

male 50

Age 22.6 y

#303

Brooklyn, USA

Parallel

Shalita, 1984

multicenter

Comedones change [phase i] 

(%)

Comedones change [phase 

ii] (%)

2, 4

Salicylic acid

Benzoyl peroxide

È

Í

No losses to followup. 

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Salicylic acid was effective 

in treatment of comedonal 

acne; benzoyl peroxide was 

not.

n=30 Mild

female 15

male 15

Age 13.0-31 y

#304

Brooklyn, USA

Cross-over

Shalita, 1989

Inflammatory change (%)

Local side effects

Overall change/physician

Severity (Allen-Smith)

Severity change (AllenSmith %)

4, 8

Nicotinamide

Clindamycin Í

Major losses to 

followup. Outcome 

assessor not blinded. 

Arms not comparable. 

4% nicotinamide and 1% 

clindamycin gel were 

equivalent in efficacy.

n=76 Mod

female 53

male 23

Age 21.3 y

#305

Brooklyn, USA

Parallel

Shalita, 1995

multicenter

Summary Table: Page 60 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

% Burning grade I

% Dryness grade I

% Erythema grade I

% Scaling grade

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity change

Total lesions change (%)

2, 4, 8, 12

Adapalene

Tretinoin

È

Í

Randomized. General 

population. 

Outcome assessor not 

blinded. Arms not 

comparable. 

Adapalene 0.1% gel bid 

was more effective than 

tretinoin 0.025% gel.

n=288 Mod

Age 12.0-30 y

#306

Brooklyn, USA

Parallel

Shalita, 1996

multicenter

Diarrhea

Facial erythema

Facial stinging

Inflammatory (count)

Non-inflammatory (count)

Severity (Leeds)

4, 8, 12

Clindamycin phosphate 

+ placebo

Minocycline + placebo

È

No losses to followup. 

Referral population. 

Both topical clindamycin 

and oral minocycline were 

effective in the treatment of 

moderate-severe acne.

n=64 Mod/sev

female 24

male 42

Age 14.0-35 y

#307

Leeds, UK

Parallel

matched

Sheehan-Dare, 19

Comedones (count)

Inflammatory (count)

Side effects

Total lesions (count)

1, 2, 4, 8, 12

Placebo

Benzoyl peroxide + 

glycolic acid + zinc 

sulfur

Benzoyl peroxide + 

erythromycin

È

Data show patient 

blinded. Data shows 

enroller blinded. No 

losses to followup. 

Triaz 10% as a special gel 

seems to optimize 

therapeutic power of 

benzoyl peroxide as a 

combo drug rather than by 

itself.

n=92 Mild/mod

Age 16.0-30 y

#310

Dallas, USA

Parallel

Sklar, 1996

Severity change (Smit)

Side effects

12

Minocycline

Doxycycline Í

Arms not comparable. 

Doxycycline and 

minocycline were equally 

effective for severe acne. 

[By the Combined Acne 

Severity Classification, 

these patients' acne is 

classified as "mild."]

#311 n=18 Mild/mod

Wageningen, The 

Netherlands

Parallel

Smit, 1978

Overall change/patient 

(score)

Overall change/physician

Severity change/photo (score)

4

Placebo

Demethylchlortetracycli

ne

Phenethicillin

È

Í

Referral population. 

Patient not blinded. 

There were no significant 

differences, between the 

treatments, including 

placebo.

Mild/mod/se

v

n=66

female 22

male 38

#312

London, UK

Parallel

Smith, 1962

Summary Table: Page 61 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Severity (Cook)

2, 4, 7, 10, 12

Tetracycline 

hydrochloride (oral) + 

placebo

Tetracycline 

hydrochloride (topical) 

+ placebo

Placebo + placebo

È

Local population. 

Topical tetracycline plus 

oral tetracycline and oral 

tetracycline were both more 

effective than placebo.

n=149 Mild/mod

female 80

male 55

Age 19.9 y

#313

Augusta, USA

Parallel

Smith, 1976

Allergic dermatitis

Redness/peeling

Total lesion (count)

Total lesions change 

(descretized %)

8

Vehicle

Benzoyl peroxide (20%) Local population. 

Benzoyl peroxide 20% was 

significantly more effective 

in reducing inflammatory 

acne.

n=59 Mod

female 35

male 16

Age 23.0 y

#314

Albequerque, USA 

Parallel

Smith, 1980

Inflammatory change (%)

Non-inflammatory change 

(%)

Severity change (Leeds)

1, 4, 9, 12

Placebo

Fusidin

Fusidin was no better than 

placebo.

n=56 Can't say

female 15

male 41

Age 18.8±1.1 y

#315

Leeds, UK

Parallel

Sommer, 1997

Dryness (severity)

Erythema (severity)

Inflammatory change (%)

Non-inflammatory change 

(%)

Papules change (%)

Scaling (severity)

Side effects (patient 

assessment)

4, 8, 12

Azelaic acid + glycolic 

acid

Tretinoin + vehicle

Azelaic acid + glycolic acid 

led to a greater reduction in 

papules and inflammatory 

lesions,and caused less 

dryness, scaling and 

erythema than tretinoin.

n=70 Mild

female 53

male 17

Age 24.5 y

#316

San Diego, USA

Parallel

Spellman, 1998

multicenter

Severity change

12

Tetracycline

Tetracycline + 

proteolytic enzymes

È

Í

Data show patient 

blinded. Data shows 

enroller blinded. Data 

shows outcome assessor 

blinded. 

Arms not comparable. 

The combination of 

tetracycline and enzyme 

was better than tetracycline 

alone, but not at a 

statistically significant 

level.

n=51 Sev

female 19

male 32

#317

Aberdeen, UK

Parallel

Stankler, 1976

Summary Table: Page 62 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Overall change/patient 

(Stoughton)

Papules (count)

Side effects

2, 3, 4, 6, 8

Clindamycin (lotion) + 

Placebo (oral)

Tetracycline (oral) + 

Placebo (lotion) Í

No losses to followup. 

Referral population. 

Not randomized. 

Outcome assessor not 

blinded. 

Clindamycin phosphate 1% 

is at least equal to 

tetracycline 500mg/d.

n=50 Mod

Age 18.0-30 y

#318

San Diego, USA 

Parallel

Stoughton, 1980

Inflammatory change post 

therapy/face (%)

Inflammatory change/face 

(%)

Inflammatory change/trunk 

(%)

Inflammatory change/trunk 

post-therapy (%)

Local side effects

Overall assessment/patient 1 

yr. later

Skin side effects

Systemic side effects

4, 8, 12, 16, 20; 4, 8, 

12 post-therapy; 60-90 

post-therapy or 4, 8, 

12, 16, 20;24, 28, 32, 

80-110.

Isotretinoin (1.0)

Isotretinoin (0.1)

Isotretinoin (0.5)

Randomized. Data 

shows outcome assessor 

blinded. Specific 

population. 

The maintenance of the 

clinical improvement was 

much greater when higher 

dosages were used. There 

was no sufficiently 

consistent pattern of side 

effects differences.

n=150 Sev

female 14

male 109

Age 22.9 y

#320

Iowa City, USA

Parallel

Strauss, 1984

multicenter

Inflammatory change (%)

4, 8, 10

Zinc + erythromycin

Vehicle

Í

Randomized. No losses 

to followup. 

Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

Topical erythromycin 4% 

with zinc decreases 

inflammatory lesion counts.

n=22 Mild/mod

Age 13.0-35 y

#321

Iowa City, USA

Parallel

Strauss, 1984

Comedones change (%)

Dryness

Erythema

Inflammatory change (%)

Oiliness

Papules+pustules change (%)

Peeling

Total lesions change (%)

4, 8, 12, 16

Tretinoin + benzoyl 

peroxide + water 

avoidance

Tretinoin + emollient + 

tetracycline

Tetracycline + 

sulfur/salicylic acid + 

polyethylene

È

Í

Randomized. Data 

shows enroller blinded. 

No losses to followup. 

Data shows outcome 

assessor blinded. 

Referral population. 

Patient not blinded. 

A topical program of 

tretinoin, benzoyl peroxide, 

and water avoidance was as 

effective as tetracycline and 

tretinoin and better than 

tetracycline with abrasive 

cleansers.

Mild/mod/se

v

n=122

female 78

male 44

Age 18.2±2.3 y

#323

Salt Lake City, 

USA

Parallel

Swinyer, 1980

Summary Table: Page 63 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory change (%)

Local reactions/Dryness

Local reactions/Erythema

Local reactions/Oiliness

Local reactions/Peeling

Non-inflammatory change 

(%)

Total lesions change (%)

2, 4, 8, 12

Clindamycin phosphate

Benzoyl peroxide

È

Í

No losses to followup. 

Patient not blinded. 

Benzoyl peroxide gel was 

superior to clindamycin 

phosphate.

n=60 Mod

female 34

male 26

Age 19.8 y

#324

Salt Lake City, 

USA

Parallel

Swinyer, 1988

Inflammatory change (%)

Non-inflammatory change 

(%)

Post-therapy relapse

Severity change 

(Michaelsson)

12

Gugulipid

Tetracycline

È

Í

No losses to followup. 

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. Arms not 

comparable. 

There was no statistical 

difference between 

tetracycline and gugulipid. 

Patients with oily skin 

responded better to 

gugulipid suggesting use of 

gugulipid in nodulocystic 

acne.

n=20 Sev

female 5

male 15

Age 16.0-25 y

#325

Bajaj Nagar, India

Parallel

Thappa, 1994

Closed comedones (count)

Nodes+cysts (count)

Non-inflammatory (count)

Open comedones (count)

Overall change/patient

Total inflammatory (count)

Total lesions (count)

2, 4, 8, 12

Erythromycin

Clindamycin

Patients responded equally 

to erythromycin and 

clindamycin.

n=72 Mod/sev

Age 12.0-55 y

#326

Gavelson, USA

Parallel

Thomas, 1982

multicenter

Diarrhea

Erythema

Itching

Nodules (count)

Papules (count)

Peeling

Pustules (count)

Severity/patient

2, 4, 6, 8

Clindamycin 

hydrochloride

Vehicle

Í

Not randomized. 

3 of 9 clindamycin patients 

showed clinical 

improvement.

n=18 Mild/mod

female 11

male 3

Age 22.3 y

#327

Iowa City, USA

Parallel

Thomsen, 1980

Summary Table: Page 64 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Inflammatory (count)

Local irritation

Non-inflammatory (count)

Side effects

4, 8, 12

Metronidazole

Placebo

È

No losses to followup. 

Data shows outcome 

assessor blinded. 

There was no significant 

benefit to using 0.75% 

metronidazole gel over 

placebo in reducing counts 

of inflamed and noninflamed lesions.

n=96 Mild/mod

female 47

male 49

Age 20.7±4.6 y

#328

New South 

Wales/Canperdow

n, Australia

Parallel

Tong, 1994

Comedones (count)

Cysts (count)

Irritancy (score)

Papules (count)

Pustules (count)

Severity change 

(Michaelsson %)

2, 4, 6, 8, 10

Clindamycin

Benzoyl peroxide

Clindamycin + benzoyl 

peroxide

Í

Not randomized. Patient 

not blinded. Enroller not 

blinded. Major losses to 

followup. Outcome 

assessor not blinded. 

Arms not comparable. 

Combination therapy 

consistently demonstrated 

the best overall efficacy as 

regards severity.

n=79 Mod

female 45

male 34

Age 12.0-30 y

#329

Houston, USA

Parallel

Tucker, 1984

Comedones (median)

Infiltrates (median)

Local reaction

Papules (median)

Pustules (median)

Side effects (number)

Withdrawals

4, 8, 12

Isotretinoin (1.0)

Isotretinoin (0.5)

Í

Referral population. 

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Isotretinoin 0.5 mg/kg is 

preferred to 1.0 mg/kg for 

conglobate acne.

Mild/mod/se

v

n=58

female 0

male 58

Age 22.0±6.0 y

#332

Amsterdam, The 

Netherlands

Parallel

van der Meeren, 

multicenter

Closed comedones change 

(count)

Erythema

Mild itching

Open comedones change 

(count)

Open comedones 

change(count)

Papules change (count)

Pustules change (count)

Transient scaling

2, 4, 8

Benzoyl peroxide + 

isoconazole nitrate

Benzoyl peroxide + 

miconazole nitrate

È

Randomized. Data show 

patient blinded. Data 

shows enroller blinded. 

Data shows outcome 

assessor blinded. 

There was no difference 

between benzoyl peroxide 

+ isoconazole nitrate and 

benzoyl peroxide + 

miconazole nitrate.

n=20 Mild/mod

female 26

male 6

Age 13.0-28 y

#335

Brussels, Belgium

Parallel

matched

split face

Van Neste, 1986

Summary Table: Page 65 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Cysts (count)

Infiltrates (count)

Oiliness

Papules (count)

Pustules (count)

Severity change

Side effects

6

Zinc sulfate

Vehicle

È

Í

No losses to followup. 

Data shows outcome 

assessor blinded. 

Not randomized. 

Inconsistent 

ascertainment across 

arms. 

Zinc was better than 

placebo.

n=56 Mod

female 21

male 35

#336

Rohtah, India

Parallel

Verma, 1980

Inflammatory change (%)

Non-inflammatory (count)

Severe erythema

Severity (Leeds)

8, 12

Adapalene (0.1%)

Tretinoin

Adapalene (0.03%)

È

Í

Data shows enroller 

blinded. No losses to 

followup. 

Outcome assessor not 

blinded. Arms not 

comparable. 

0.1% adapalene may be an 

effective and safe treatment 

for mild to moderate acne.

Mild/mod/se

v

#338 n=72

Warsaw, Poland

Parallel

Verschoore, 1991

Inter-treatment severity 

comparison

24-72 (unspecified)

Placebo

Tetracycline-novobiocin

Triacetyl-oleandomycin

Tetracycline-citric acid

Tetracycline phosphate

Erythromycin 

proprionate

Erythromycin stearate

È

Í

Data show patient 

blinded. Data shows 

enroller blinded. Data 

shows outcome assessor 

blinded. 

Major losses to 

followup. Inconsistent 

ascertainment across 

arms. Arms not 

comparable. 

All of the antibiotics were 

more effective than placebo.

n=91 Mod/sev

Age 12.0-36 y

#340

Charlotte, USA

Parallel

Wansker, 1961

Comedones (count)

Cysts (count)

GI distress

Papules (count)

Pustules (count)

Severity (Michaelsson)

2, 4, 6, 8, 12

Placebo

Zinc sulfate

È

Í

Randomized. Local 

population. 

Major losses to 

followup. Arms not 

comparable. 

Zinc had a beneficial effect 

on pustules, but significant 

side effects were observed.

n=52 Mild/mod

female 28

male 24

Age 19.7 y

#341

Iowa city, USA

Parallel

Weimar, 1978

Summary Table: Page 66 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Infiltrates (count)

Papules (count)

Pustules (count)

Side effects 4, 8, 12

Vehicle

Zinc sulfate

È

Í

Randomized. 

Major losses to 

followup. 

Oral zinc sulphate did not 

affect acne.

n=39 Mod

female 9

male 30

Age 17.0-37 y

#342

Copenhagen, 

Denmark

Parallel

Weismann, 1977

Overall change/physician

Severity change/photo

Side effects

2

Fusidin (oral)

Fusidin (topical)

È

Í

Data shows outcome 

assessor blinded. 

Not randomized. Patient 

not blinded. Enroller not 

blinded. Major losses to 

followup. Arms not 

comparable. 

Fusidin orally or in 

ointment was not effective.

Mild/mod/se

v

n=70

female 29

male 41

#344

UK

Parallel

Wethered, 1964

multicenter

Overall change/physician

Patient satisfaction

4

Vehicle

Neomycin + 

methylprednisolone + 

sulfur + aluminum

Í

Randomized. Data 

shows enroller blinded. 

No losses to followup. 

Data shows outcome 

assessor blinded. 

Referral population. 

Arms not comparable. 

A polyvalent approach 

produces the best results.

Mild/mod/se

v

#346 n=48

New York, USA

Parallel

Wexler, 1968

Overall change/physician

Patient satisfaction

4

Sulfur + aluminum 

chlorhydroxide

Neomycin + 

methylprednisolone + 

sulfur + aluminum c

Í

Randomized. Data 

shows enroller blinded. 

No losses to followup. 

Data shows outcome 

assessor blinded. 

Referral population. 

Arms not comparable. 

A polyvalent approach 

produces the best results.

Mild/mod/se

v

#347 n=48

New York, USA

Parallel

Wexler, 1968

Summary Table: Page 67 of 68
Trial information Treatments 

 Time points (wks)

Participants Outcomes Methodological 

Qualifications

 Authors' Bottom Line

Improvement

Side effects overall

Side effects specific

Total change (%)

Total lesion (count) 4, 8

Ibuprofen + placebo

Ibuprofen + tetracycline

Tetracycline + placebo

Placebo Í

Randomized. Data show 

patient blinded. 

Outcome assessor not 

blinded. 

The combination of 

ibuprofen tetracyline is 

effective when 

administered for 2 months.

n=68 Mild/mod

female 12

male 48

Age 20.5 y

#349

Ann Arbor, USA

Parallel

Wong, 1984

Overall change/patient [acne 

conglobata]

Overall change/patient [acne 

vulgaris]

Pigmentation

Severity change/patienttreated side [acne vulgaris]

24

Sham rays + 

hexachlorophene

Grenz rays

Grenz ray + 

hexachlorophene

Untreated

È

Í

No losses to followup. 

Enroller not blinded. 

Outcome assessor not 

blinded. 

Grenz rays were not 

effective in treatment of 

acne.

#350 n=95 Sev

San Francisco, 

USA

Parallel

matched

split face

Wright, 1964

Desquamation

Eczematous reaction

Erythema

Hair discoloration

Itching or burning

Overall change/physician

Pigmentation

Pustular

Side Effects

4-18 (end of therapy)

Benzoyl peroxide (5%)

Benzoyl peroxide(2.5%)

Í

No losses to followup. 

Local population. 

Patient not blinded. 

Enroller not blinded. 

Outcome assessor not 

blinded. Arms not 

comparable. 

No significant difference 

was found either in efficacy 

or severity of side effects.

Mild/mod/se

v

n=200

female 140

male 60

#351

Singapore

Parallel

Yong, 1979

Summary Table: Page 68 of 68