S T U D I E S I N T H E PSYCHOLOGICAL E F F E C T S O F A NEW D R U G (DIETHYLPROPION)

Subjective effects in the natural environment

C.-0. JONSSON, L. SJOBERG and S. VALLBO

Psychological LaboratoTy, University of Stockholm, and Beckomberga Hospital, Bromma, Sweden

JONSSON, C.-O., SJ~BRRG, L. & VALLBO, S. Studies in the psychological effects of a new drug (diethylpropion). Subjective effects in the natural environ- ment. Scand. J . Psychol., 1965, 6,52,-58.-Two doses diethylpropion, one dose pipradrol, one dose amobarbital and placebo were administered to I 16 subjects, who rated their state on twenty variables. The variables were intercorrelated under pipradrol and pentymal. The correlation matrices were subjected to factor analysis. Four factors were found in both studies: Happiness, Alertness, Relaxation, and Flight of thoughts. There is some agreement between the two factor analyses. There were few significant effects of the drugs on factor scores, but the structure is quite unambiguous: pipradrol and diethylpropion are stimulating, and amobarbital tranquilizing.

In connection with preliminary studies in the effects of diethylpropion on perceptual and psychomotor performance (Jonsson, Sjoberg & Vallbo, 1964), we also made some observa- tions on subjective variables. These observations were the point of departure for this study.

As pointed out earlier (Jonsson et al., 1964), laboratory experiments offer smaller fewer possibilities for generalisation to the ‘natural’ environment in which a drug is consumed than do investigations taking place directly in the environment itself. On the other hand the degree of experimental control and precision is decreased by leaving the laboratory setting. We feel therefore that it is necessary to work along both lines if fairly broad knowledge about a drug is to be obtained. In this investigation we have chosen to study subjects in their natural environment, at home or at work. We have investigated the effects of the drugs on the subjective states of the subjects only.

In addition to diethylpropion in two doses, 25 mg and 50 mg, and two placebo tablets with lactose, the subjects were given 2 mg pipradrol and IOO mg amobarbital. Pipradrol is regarded as a weakly stimulating drug and amobarbital as tranquilizing. We did not dare to use amphetamine and phenmetrazine in this non-laboratory study, as we had earlier seen some dangerous side-effects of these drugs.

Administration of the drugs At the beginning of the experiment the subjects received six envelopes with 2 tablets each,

containing the different drugs. All tablets were the same colour, size and form. The subjects consumed two tablets every second day at nine o’clock in the morning.

Subjects The participants were IOI women and 15 men. The average age of the women was 28.0

years, S.D. 7.3 years, and their average weight 59.4 kg, S.D. 8.1 kg. The average age of the men was 26.9 years, S.D. 5.9 years, and average weight 73.6 kg, S.D. 6.3 kg. Some of the subjects hospital attendant trainees, received a small payment for their participation.

52 Scand. J. PJychol., Vol. 6, I965

PSYCHOLOGICAL EFFECTS OF A NEW DRUG (DIETHYLPROPION) 53

Design of the experiment The subjects took the drugs in their ‘natural’ environment, i.e., housewives at home and

others at their place of work. The experiment was conducted during a two-week period with sessions Monday, Wednesday, and Friday. The female subjects were instructed to refrain from participating if they expected a menstruation period during that time. The drug was taken about nine o’clock in the morning; the ratings were made at about 1 1 o’clock. The subjects were instructed ta refrain from discussing the investigation. The order of rotation was the following: A placebc and a dose of diethylpropion were given each week. Half of the subjects received the smaller dose of diethylpropion the first week and the larger the second week. In addition, half of the subjects received pipradrol the first week and half amobarbital. The order of tablets within each week was taken from a table of random numbers.

Subjective ratings Two hours after taking the tablets the subjects judged their status on a rating schedule.

They had eight categories to choose amongst for the first 19 variables and six categories for the 20th. Responses indicating no change from the normal conditions were not allowed in order to maximize information about change. The categories were verbally defined and included a reference to the subject’s normal state (except for variable no. 20 which is a preference variable, not a descriptive one).

I . Alert 2. Calm and relaxed 3. Happy 4. Working capacity 5. Flight of thoughts 6. Hungry 7. Irritated 8. Clarity of thought 9. Freedom from worry

10. Ability to concentrate I I . Distance to surroundings 12. Restless I 3. Talkative 14. Intruding thoughts I 5 . Self-confidence 16. Tired 17. Friendly 18. Dizzy 19. Sleepy

higher rating: more alert more relaxed, calmer happier better able to work ‘more’ flight of thoughts hungrier more irritated clearer freer from worry better able to concentrate surroundings are nearer than usual less restless more talkative thoughts intrude more greater self-confidence less tired friendlier dizzier sleepier gladly 20. Would you like to fee- as you LJ now often?

We have tried to reduce the number of variables by the method of factor analysis (see below). A similar schedule has been used by Lasagna, von Felsinger & Beecher (1955) and Di-

mascio & Buie (1964) but without systematic analyses of the dimensions.

FACTOR ANALYSIS

In order to obtain greater reliability in our data before the statistical testing of effects, and to be better able to survey the data, we decided to subject our schedule to factor analysis. The complications with such an approach are of course many. It is, for example, conceivable

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54 c.-0. JONSSON, L. SJOBERG AND s. VALLBO

TABLE I . Tetrachoric correlations between the 20 rating variables; Amobarbital data above and Pipradrol data below the diagonal.

- ~~

Rating variable number I 2 3 4 5 6 7 8 9 10 1 1 12 13 14 15 16 17 18 19 20

I 47 86 79 12 23 -14 77 80 2 22 36 34 04 -09 26 52 71 3 70 51 72 -06 I I -27 62 60 4 68 30 89 -10 07 -28 85 43 5 21 -21 25 29 16 51 -13 -03 6 -03 -10 03 08 33 27 I5 -03 7 -18 -56 04 01 53 34 -22 -07 8 28 49 43 50 -15 06 - 1 5 60 9 53 17 64 61 22 -06 08 38

10 17 39 27 42 -13 22 -20 80 41 XI 19 13 47 38 10 28 -01 90 25 12 06 81 28 17 -30 -09 -35 66 11

13 22 12 50 63 35 21 -04 39 52 14 22 -28 og 26 58 38 5 5 -06 30 15 43 -07 35 27 10 24 25 37 69 16 35 23 31 40 -02 00 -40 65 27

18 -01 -31 11 10 48 33 41 -31 02

19 18 15 34 36 -26 -06 -10 82 30 20 52 47 46 40 03 00 -14 58 28

17 60 22 66 73 37 03 17 55 69

59

5 0 75

- 23

36

22

- I 2

83 49

75 60 33

28 75 45

- 39 71 67

I1

71 50 68 26 21 47 58 49 55 73 50 60

-04 -38 24

-24 -61 13

82 64 56 51 36 42 64 71 18

63 52 48 12

48 05

02 -04 18

11 -71 5.5 10 05 24 11 31 36 35 21 57

-01 -22 13

56 41 35 56 5 s 43

32 60 98 62 -22 76 77 45 41 36 40 12 22 30 16 57 78 64 -40 76 76 34 75 87 73 -41 84 78 67 -09 05 - 0 5 59 - 1 5 -14 21 04 16 -12 22 02 -02

that the factor structure radically changes at different levels of effect as well as with different kinds of effects. On the other hand, there is perhaps reason to expect a considerable amount of invariance in the factor space, since this should chiefly be an expression of the subjects’ semantic habits, which can perhaps be assumed to be ‘robust’. We have chosen to test empirically, to some extent, the reasonableness of such an expectation of invariance by analysing the intercorrelations with both pentymal and pipradrol. The intercorrelations (tetrachoric, cut as near the median as possible) are found in Table I . Before the analysis we propounded set up the hypothesis that four factors would be found, and specified which variables we assumed to be loaded with these factors. An attempt was then made to rotate to the confirmation of the hypothesis (subjective rotation). The rotated factor loadings are given in Tables z and 3. The results are summarized in Table 4. There were no clear indi- cations of further meaningful factors beyond the expected four. Our final choice of scales for the operational definitions of our factors appears in Table 5 . Data processing is hereafter limited to the four factors.

That our hypotheses were on the whole confirmed is evident in Table 4. Variable 11, distance to surroundings, was an exception and entered into factor I, alertness. It was also surprising that the factor ‘happy’ is so poorly represented in amobarbital, and that the factor ‘relaxed‘ has low loadings in pipradrol data. This may have been because the drugs produce greater variation in those variables in which the effects are greater. That this is not

S c a d . I. Psychol., Vol. 6,1965

PSYCHOLOGICAL EFFECTS OF A NEW DRUG (DIETHYLPROPION)

TABLE 2. Rotated factor matrix, Pipradrol.

I" 11' 111' IV" V' VI'

I

2

3 4 5 6 7 8 9

I 0

I1

I2

I3 14 15 16 I7 18 19 20

16 45 26 29

- 33 - 02

- 36 86 23 88 68 68 28

- I4 20

84 33

- 49 88 55

49 - 09

60 69 51 37 37 52 64 54 60 04 70

54 50 71 17 50 39

58

60 68 72 57

- 27 - 33

16 37 0 5

- 05 34 16

- I 8 04 02

41

- 0 1

01

- I 2 36

06 - 25 19 29

- 23 01

- 08 - I 4 I1 0 8 I2 34

- 28 26 - 1.5 16

00 - 08 15 16

- 07 21

ox 49 26 - 06 36 0 5

- 07 01

06 - 43 - 13 - 09 - 13 27 - 24 - 25

17 20

I 1

- 03 - 07 - I 4

- 07 07 0 5 39

- 33 - 07 - I9

- 21

02

00

67 - 06

0 1

- 26 07

- 23

TABLE 3. Rotated factor loadings, Amobarbital.

I

2

3 4 5 6 7 8 9

I 0

11

I2

I3 I4 1.5

16 17 18 I9 20

88 23 85 78 01

0 1

- 32 66 42 38 67 43 64 23 56 88 66

- 41 91 73

22

41 - 01 - 01

73 27 76

25

00

- 12 - 01

- 43 49 81

- 0.5

- 09 69

- 15

I1

00

29 70 24

- 25 - 17 - 14

40 77 40 24 41

07 49 08 37

- 04

20

I1

02

21

I9 04 06 44

- 04 31 09 53 00

76 44 40 06 17 35 43 28

- 04 36 41

09

14 33 23

- 21

- 30 1 5

02

- 01

02

31 28 28 18 47 28 61 06 34 23

55

Scand. I. Psychol., Vol. 6, 1965

c.-0. JONSSON, L. SJOBERG AND s. VALLBO

TABLE 4. Summary of findings.

Pipradrol Amobarbital

Name of factor items items and strength and strength Predicted Additonal loadings loadings

Happy

Alert

Relaxed

Flight of thoughts

I

8 16 19

.60 .i4

.64 .o I

.70 .28

.54 4 7 -7 1 .61

I 0 .54 .02

14 .58 19

4 69 -33

Strong Weak

.r6

.86 3 4 .88

3 .26 4 .29

1 0 .88 I 1 .68 I2 .68

.88

.66

.88 -9 I

.85

.78 -38 .67 -43

17 -33 .66 Strong Strong

2 -29 a70

5 14

I 2 .49 .41

15 .Ol .49 9 - .08 *77

16 - .43 .08 Weak Medium

.XI .73

.36 .8 I

7 - .28 .76 I 8 - .13 5 9

Weak Strong

TABLE 5. Variables chosen to memure factors.

Factor Variables no.

Happy 3, 13, 1 5 9 17 Alert Relaxed 2, I2

Flight of thoughts 5 , I 4

I , 8, 16, 19, I I

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57 PSYCHOLOGICAL EFFECTS OF A NEW DRUG (DIETHYLPROPION)

TABLE 6. Arithmetic nteans and standard deviations.

5.0 mg 2.5 mg Factor Pipradrol Amobarb. Dietylpr. Dietylpr. Placebo

Happy M = 5.06 s = 0.83

Alert M = 4.79 s = 0.98

Relaxed M-4.85 s= 1.16

M = 4.67 s = 0.95

Flight of thoughts

M = 4.79 S = 0.97

M = 4.42 s = 1.28

M = 5.02

s= 1.00

M = 4.47 s = 0.94

M = 4.93 s=1 .28

M = 477

M = 4.55 s= 1.54

M = 4.80 s= 1.24

S=I.43

M=5.06 S = 0.99

M = 4.85

M = 4.74

s = 1.12

s= I . 2 5

M=4.65 s = 0.98

M = 4.84 S = 0.79

M = 4.66 s = 0.84

M=4.91 s = 0.89

M=4.58 S = 0.79

the case, however, is seen in Table 6. It should be pointed out that similarity between the two sets of rotated factors is not very large. I t might be improved by objective rotation.

RESULTS

In the processing of the data we have combined the two placebo values so that differences are tested between only five 'drugs' in four factors. Significant differences (at the 5 yo level) were only obtained between pipradrol and amobarbital in factor 'alert' and between placebo and pipradrol in factor 'relaxed'. Wilcoxon's matched pairs signed rank test (Siegel, 1956) was used. The means and the standard deviations for the five drugs are given in Table 6 for each of the four factors; the means appear also in Fig. I . I t is evident that the trend is very clear (although not statistically significant); pipradrol and amobarbital give opposite results relative to the placebo, and the two doses of diethylpropion give results in the same direction as pipradrol.

I t might be argued that an over-all test of significance should be used to give an evaluation of the differences in Table 6. We regard this as superfluous, however, in view of the fact that all the differences between the drugs and placebo are consistent with the hypothesis that diethylpropion and pipradrol are stimulant drugs, while amobarbital is a sedative.

0 5

o c

Ln 03

0 0.2 a.

o i

0 0

.w C .-

- 0 t

FIG. I . Mean effects of the 4 active drugs and placebo, calculated as deviations from the theoretical mean (4.5) of the category scale used.

S c a d . J . Psychol., Vol. 6,1965

58 c.-0. JONSSON, L. SJOBERG AND s. VALLBO

With two exceptions, then, we were not able to obtain any significant effects. However, we do not refrain from interpreting Table 6 and Fig. I as convincing signs that diethyl- propion should, in the first place, be referred to the stimulating drugs. Taken in the doses used in the experiment it is apparently not a powerfully stimulating drug (on the average), but neither is z mg pipradrol.

The study was made possible through research grants from A/B Kabi, and from the Swedish Council of Social Research, Stockholm.

REFERENCES

DIMASCIO, A. & BUIE JR, D. H. (1964). Psycho- LASAGNA, L., VON FELSINGER, J. M. & BEECHER, pharmacology of chlorpentermine and d- H. K. (1955). Drug-induced mood changes amphetamine. Clin. Pharmacol. F9 Therap., in man. I. Observations on healthy subjects, 5, 174-184. chronically ill patients, and ‘postaddicts’.

Studies in the psychological effects of a new SIEGEL, S. (1956). Nonparamehic statistics for drug (Diethylpropion). I. Perceptual and the behavioral sciences. New York: McGraw- psychomotor performance. [Rep. Psychol. Hill. Lab., Univ. Stockholm No. 174.1

JONSSON, C.-O., SJOBERG, L. &VALLBO, S. (1964). J. Amer. Med. Ass., 157, 1006-1020.

Scad. 1. Psychol., Vol. 6,1965