J Int Med Res (1981) 9,152

A Randomized, Controlled Clinical Trial of Four Anti-Dandruff Shampoos Marvin Rapaport, MD, School of Medicine, Department of Dermatology, University of

California at Los Angeles (U.CL.A.), Los Angeles, California, U.S.A.

A total of 199 patients were selected for a comparison of the anti-dandruff efficacy of four shampoos. After a 2-week lead-in (all patients used only Johnson's Baby Shampoo twice weekly) the patients were randomly assigned to Selsun Blu~, Head & Shoulderss, Flexe; or Tegrine. The test preparation, which was unknown to the observer, was used twice weeklyfor 4 weeks. Loose and adherent dandruff were each rated on a scale of 0 to 20 (absent to severe) at the end of the lead-in (when a total score of 15 was required), and each week of study. The mean total pre-study score for all subjects was 19·5. At the end ofthe study the mean improvement scores were: 16·2 (Selsun Blue), 14·6 (Head & Shoulders), 13·5 (Flex), and 13·1 (Tegrin). The improvement was significantly greater (p < 0·05) on Selsun Blue than on any of the other shampoos. At the end of the study significantly (p < 0·05) more patients had total scores ofzero on Selsun Blue (15) than on Tegrin or Head & Shoulders. In addition, the rate of improvement was significantly (p < 0·05) faster with Selsun Blue than with any ofthe other test preparations.

Introduction Dandruff is a chronic, non-inflammatory scalp condition characterized by excessive scaling (Ackerman & Kligman 1969). Estimates of its prevalence range up to 70% of the population (Bourne & Jacobs 1956, Roia & Vanderwyk 1969). There is no known cure for dandruff, only control of the condition. Cleaning the hair and scalp frequently, perhaps daily, often is sufficient. Non-prescription anti-dandruff preparations contain specific ingredients to better control the condition with less frequent shampooing. Among the most commonly used ingredients are selenium sulfide, zinc 0300-0605/81/020152-05 $02·00

pyrithione, and coal tar derivatives in combination with allantoin. Although many studies have been conducted to assess the efficacy of these ingredients (Kligman et al 1974, Kligman, McGinley & Leyden 1976, Orentreich et al 1969), none has directly compared commercially available non-prescription products containing these ingredients in a randomized, controlled design. The present study was performed to accomplish that goal. Accordingly, at weekly intervals, the efficacy of selenium sulfide 1% (Selsun Blue, Abbott Laboratories) was compared with two zinc pyrithione preparations (Head &

©Cambridge Medical Publications Limited

Marvin Rapaport

153

Shoulders, Procter and Gamble; and Flex Balsam and Protein Anti-dandruff Shampoo, Revlon), and a coal tar extract - allantoin combination product (Tegrin Medicated Shampoo, Reedco). Materials and Methods Johnson's Baby Shampoo, for use during the lead-in period, was supplied in 7-ounce containers as marketed by the manufacturer. The four test preparations were supplied in identical 12-ounce plastic bottles. Each of these containers was labelled with the patient's number, instructions for use and appropriate precautionary information. In accordance with the provisions of the protocol, 199 patients were selected for study. All of them were in good general health with no skin disorders, other than dandruff. None

had open lesions, crusts or excoriations on the scalp, and none had a history of adverse reactions to the active ingredients of any of the test preparations (i.e., selenium sulfide, zinc pyrithione, coal tar, or allantoin). Female patients taking oral contraceptives had been taking the same preparation for at least 6 weeks, and no change was anticipated during the 6-week course of the study. Each patient agreed not to swim during the course of the study, and each patient voluntarily signed a statement of informed consent prior to admission to the study. The study was separated into two segments. During the first segment, of 2 weeks' duration, each patient used Johnson's Baby Shampoo twice weekly. No other shampoo or hair preparations (e.g., conditioners, colouring products, and sprays) were used during this period. @ At its conclusion each patient was

Table 1 Description of patients

Test preparation Selsun Blue

Head & Shoulders

Flex

Tegrin

Total

Sex: Male Female

16 34

15 34

15 35

15 35

61 138

Age: 16-20 21-30 31-40 41-50 > 51

8 20 12 5 5

4 16 18 8 3

2 22 16 6 4

2 21 16 7 4

16 79 62 26 16

38 7

31 8 9 2

144 26 19 10

Race: White Black Oriental Spanish Scalp condition: Normal Oily Dry Not reported Shampoo frequency:" < 2/week 2/week > 2/week Not reported

I

40 3 5

4

I

35 8 4 3

16 18 16 0

19 18 10 2

20 19 11 0

18 24 8 0

73 79 45 2

8 17 24

5 23 20 1

12 22 15

5 18 24 3

30 80 83 6

I

-Frequency of shampooing prior to study

I

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The Journal ofInternational Medical Research

again seen and the dandruff was evaluated. Loose dandruff was scored on a scale of 0 to 20. Similarly, adherent dandruff was rated on a scale of 0 to 20, and a total score (loose plus adherent) of at least 15 was required for admission to the comparative segment of the study. The second segment was of 4 weeks' duration. On admission each patient was randomly assigned to one of the four test preparations by means of a computergenerated series of random numbers. The test shampoo was used twice weekly, but no other hair preparations were used during this phase of the study. Each patient was seen at weekly intervals (4 days after the preceding shampoo) when the severity of loose and adherent dandruff was scored by the investigator as it had been scored at the end of the lead-in period.

were randomly separated into four treatment groups. These treatment groups are compared in Table 1. There were no clinically significant disproportions among the four groups with randomization resulting in clinically comparable treatment groups. Most of the patients (69%) were female, and most of them (72%) were white. Relatively few patients (29%) were less than 21 or more than 40 years of age. Most patients (76%) had scalp conditions characterized as normal or oily, and most of them (85%) shampooed their hair twice a week or more frequently prior to the study. Five of 199 patients (3%) failed to complete the course of the study. Three of them, randomly assigned to Selsun Blue Shampoo, failed to return for follow-up. Two others, assigned to Head & Shoulders Shampoo, also failed to complete the study. One of them used a hair spray in violation of the protocol, and the other was found to be 16 years of age, less than the minimum (18) specified by the protocol for participation in the study. Both of them were withdrawn from further study.

Results 1. Description ofPatients A total of 199 patients entered the study and

Table 2 Number of patients with ICores ofzero at each visit

Week ofstudy" 1

2

3

4

Selsun: Loose dandruff Adherent dandruff Total dandruff

n =44 0 4 0

n =45 8 15 7

n =44 8 18 6

n =47 16 30 15

Head & Shoulders: Loose dandruff Adherent dandruff Total dandruff

n=45

n =45 2 14 1

n =44 3 13 3

n =47

Flex: Loose dandruff Adherent dandruff Total dandruff

n =46 0 4

n =47 4 12 3

n=47 8 15 7

n =50 16 20 11

Tegrin: Loose dandruff Adherent dandruff Total dandruff

n =48 0 5 0

n =44 3 10

n =49 6 15 4

n =50 7 18 5

0

9 0

0

0

10 21 7

*The number of subjects evaluated at each visit varies because of missed visits by some subjects

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Marvin Rapaport 2. Effects of Treatment

(B) MEAN DANDRUFF SCORES

(A) DANDRUFF SCORES OF ZERO

The mean scores for loose, adherent, and total dandruff at the end of the lead-in period and at each visit during the subsequent study period for each treatment group, are shown in Table 3. The differences between the mean total scores pre-study and at Week 4, which reflect the improvement during treatment, were larger on Selsun Blue (16·2) than with Head & Shoulders (14·6), Flex (13·5) or Tegrin (13·1). The influence of the pre-study scores, age, sex, race, hair length and scalp condition on the response to treatment was examined statistically using the multiple regression procedure. None of these factors except the pre-study score had a significant effect on the response in any of the treatment groups. To test whether or not the improvement from the initial score to the final score was significantly different for any of the products, an analysis of covariance was performed using the initial scores as a covariate. The results of

A loose or adherent dandruff score of zero signified that loose or adherent dandruff was not observed on clinical examination. A total score of zero represented the absence of both loose and adherent dandruff. The number of patients in each treatment group with scores of zero at each visit during the study period is shown in Table 2. It is apparent from these data that adherent dandruff was cleared more promptly, and in more patients, than was loose dandruff. This was true of all four treatment groups. At the conclusion of the study period there was complete clearance of dandruff (i.e., total scores of zero) in a significantly larger proportion of those on Selsun Blue (32%) than among those on Head & Shoulders (15%), or Tegrin (10%). In addition, the proportion of patients with scores of zero was greater on Selsun Blue (32%) than on Flex (22%), but the difference was not statistically significant.

Table 3 Mean dandruff scores at each evaluation Week ofstudy Prestudy"

1

2

3

4

Se1sun: Loose dandruff Adherent dandruff Total dandruff

n =50 11·3 8·2 19·5

n =44 6·5 4·0 10·5

n =45 4·2 2·4 6·6

n =44 3·1 1·9 5·0

n=47 2·1 1·1 3·3··

Head & Shoulders: Loose dandruff Adherent dandruff Total dandruff

n=49 11·1 8·9 20·0

n =45 7·0 4·5 11·5

n =45 5·3 3·5 8·8

n =44 4·3 3·1 7·5"

n=47 3·5 1·9 5·4

Flex: Loose dandruff Adherent dandruff Total dandruff

n=50 10·5 8·1 18·6

n =46 5·7 4·4 10·1

n =47 4·6 2·9 7·5

n =47 3·5 3·2 6·6··

n =50 2·7 2·4 5·1

Tegrin: Loose dandruff Adherent dandruff Total dandruff

n=50 11·2 8·6 19·8

n =48 6·3 5·1 11·4

n =44 5·5 3·6 9·1

n =49 4·3 2·5 6·8

n=50 3·8 2·8 6·7··

•At the end of the 2-week. lead-in period ··These total scores do not equal the sum of the loose and adherent scores because of the 'rounding off of the mean loose and adherent dandruff

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The Journal ofInternational Medical Research

this analysis and of pair-wise comparisons of Selsun Blue with each of the other shampoos indicated that the improvement on Selsun Blue was significantly (p < 0·05) greater than on Head & Shoulders, Flex, and Tegrin.

investigators noted that they had assessed the effectiveness of zinc pyrithione and selenium sulfide on numerous occasions and always found a suppressant effect on dandruff, with selenium sulfide being more potent. On the other hand Orentreich et al (1969) did not find statistically significant differences in the anti-dandruff efficacy of shampoos containing zinc pyrithione 2% and selenium sulfide 2·5%, a preparation available on prescription. The severity of the dandruff was recorded before and after a variable period of use, which was at least 6 weeks in duration. Interim evaluations were not made and the frequency of use of the shampoos was not uniform.

(C) RATE OF IMPROVEMENT

To determine if Selsun Blue produced a faster rate of improvement than the other antidandruff shampoos tested, a natural logarithmic transformation of the total dandruff scores was used to obtain a linear fit over the baseline and 4 weekly scores. Comparability of the estimates for the rate of reduction on each treatment was tested using a one-way analysis of covariance and when found to be significant, pairwise differences were tested using a one-sided t-test (p < 0·05). The pair-wise analysis indicated that the rate of reduction of total dandruff scores was significantly (p < 0·05) faster for Selsun Blue than for each of the other shampoos tested.

Conclusions On the basis of the results of our study we conclude that selenium sulfide 1% is more effective than the other anti-dandruff preparations tested in the management of dandruff.

(D) ADVERSE EFFECTS

Two patients, one in the Head & Shoulders group and one in the Flex group, reported transient scalp irritation during the study period. Both patients completed the course of the study. There were no other complaints. Discussion The results of this study have shown that Selsun Blue produced a significantly (p < 0·05) greater reduction in total dandruff scores (loose plus adherent dandruff) than Head & Shoulders, Flex, or Tegrin. With respect to the Selsun Blue - Head & Shoulders comparison, these results are in agreement with the findings of Kligman et al (1974). They performed corneocyte counts as a measure of anti-dandruff activity and found selenium sulfide 2·5% to be significantly more effective than Head & Shoulders. They found that the response to Selsun was more rapid, but that parity could occur after 6 to 8 weeks of twice weekly shampoos. In a subsequent report (Kligman et al 1976), these

Acknowledgements We acknowledge the assistance of Stephen R Schwartz, PhD, International Research Services, Inc., in the conduct of this study.

REFERENCES Ackerman A B &; KlismBn A M (1969) Some observations on dandruff. Journal of the Society ofCosmetic Chemistry 20, 81 Bourne S &; Jacobs A (1956) Observations on acne, seborrhea and obesity. British Medical Journall, 1268 KUsman A M, Marples R R, Lantis L R &; McGInley K J (1974) Appraisal of efficacy of anti-dandruff formulations. Journal of the Society of Cosmetic Chemistry 25, 73 KUsman A M, McGinley K J &; Leyden J J (1976) The nature of dandruff. Journal of the Society of Cosmetic Chemistry 27, 111 Orentreich N, Taylor E H, Berger R A &; Auerbach R (1969) Comparative study of two anti-dandruff preparations. Journal of Pharmaceutical Sciences 58, 1279 Roia F C &; Vanderwyk R W (1969) Resident microbial ftora of the human skull and its relationship to dandruff. Journal of the Society of Cosmetic Chemistry 20,113