THE
EFFECT
OF A CENTRAL
NERVOUS
SYSTEM
STIMULANT
(DEANOL)
ON
BEHAVIOR
Robert B. Kugel, M.D., and Theron Alexander, Ph.D.
Department of Pediatrics, State University of Iowa, Iowa City, Iowa
(Submitted August 13; accepted for publication November 6, 1962.)
ADDRESS: (R.B.K.) Department of Pediatrics, University Hospitals, Iowa City, Iowa.
PEDIA-riucs, April 196:3
651
D
UBING the past decade increasingnum-bers of drugs have been used in
coIl-junction with various types of mental
dis-orders. Most of tilese compounds, accord-mg to Cole and Gerard,’ have yet to
re-ceive full and controlled evaluation of their
usefulness . Precise experimental evaluation
has not been obtained, and accordingly
the value of many of the drugs at the
present time rests largely upon clinical
im-pressions.
Difficulties of research in
psychopharma-cology, as Irwin’ has pointed out, stem
from two main problems : suggestion and
measurement. The highly suggestive
possi-bilities for patients receiving certain kinds
of treatment are well known and are an
important part of the problem of the study
of psychoactive drugs. Problems of
meas-uring human behavior and assaying the
precise effect of intervening variables in
experimentation are also well known. And
further, although the task of testing and
appraising tile vast numbers of compounds
1TlOV on the market seems enormous, the
demand by the public for drugs which will
alleviate emotional stress and have direct
effects on the functioning of the central
nervous system is great. While many
clini-cians believe the whole problem of
in-fluencing the functioning of the central
nervous system should be viewed with
con-siderable caution, it is nevertheless not without possibility that there will be some
drugs that will have an ameliorative effect
On the detrimental results of psychological
stress. There may even be the possibility
that some drug will cause the central
ner-vous system to function in a more efficient
way and thereby increase the effectiveness
of impaired individuals in meeting the
re-quirements of society and in coping with the environment. For example, consider
the success of drugs in the treatment of convulsions when contemplating the prob-lems of psychopharmacology. Our
under-standing of the pathogenesis of the con-vulsive disorders is still incomplete, yet means are at hand for satisfactory symp-tomatic treatment. To expect further suc-cess in treatment of other central nervous
system disorders seems reasonable.
Cole and Cam’ have suggested four ma-jor drug groups, classified as follows: (1)
the major tranquilizers, (2) the minor tran-quilizers, (3) the nonbarbiturate sedatives
and calmatives, and (4) the antidepressive agents. The antidepressive agents are
con-sidered to be central nervous system stim-ulants. These latter are reported to affect the sensory areas in the brain, to increase
alertness, and to alleviate mental fatigue. In this class are such drugs as caffeine,
amphetamine, methylphenidate, pipradrol, iproniazid, and orphenadrine.
The drug, 2-dimethylaminoethanol
(de-anol), used in this study, would be
classi-fled as a central nervous system stimulant. It is held to be of value for treatment of
chronic fatigue states on depression and has been used as an antidepressive agent with children. The drug has been given the generic term “deanol,” and it is a
para-acetamidobenzoic acid salt.
Some studies of the drug’s effectiveness have been published. Clausen et al.
TABLE I
SUBJECTS IN DIAGNOSTIC CATEGORIES
652
behavior although they did see some im-pnovement in the motor test scores. Gellen5 used the drug with children who were considered to be hyperactive and aggres-sive and reported appreciable symptomat-ic improvement and better integrative abil-ity. He relied mainly on interview data,
but puzzles were used to indicate time spent in concentration on a task. La Veck
and Buckley,6 using a number of
psycho-pharmacological agents, including deanol,
with disturbed and mentally retarded
children in an institution, found on the basis of observation and reaction time test that deanol had no significant effect on
behavior.
The purpose of the present study was to make further effort to appraise the ef-fects of deanol in two groups of children:
those with some form of encephalopathy and those with behavior disorder only. The specific goal was to investigate the effect
of the drug on problem solving, integra-live, and emotional behavior.
Subjects
METHOD
For this study, the drug was adminis-tered as a single daily dose of one capsule
containing 100 mg of deanol. The subjects were 42 children in the age range of 6 to
13 years. The mean age was approximate-ly 8 years. Thirty-five of the children had some form of encephalopathy, and seven were given a diagnosis of behavior disorder only. The mean IQ of the entire group of 42 children was 78; such a mean falls
at the lower bonder of the normal range of intelligence test scores.
Initial Appraisal
Medical study included a history of the
prenatal, peninatal, and postnatal periods; growth and development; diseases, acci-dents, and operations; and a systemic re-view. In addition, a physical examination emphasizing neurological study was done. Special attention was given to tests of fine drug did not produce marked changes in
Category Subjects
(no.)
CNS disorder (eneephalopathy) due to
Infection (postnatal) 4
Intoxication
Toxemia of pregiacy Trauma
Prenatal injury 2
Anoxemia at birth 9
Postnatal injury 3
Cerebral defect, congenital 2
Unknown cause (structural evidence of
disorder) 18
Behavior disorder
Aggressive behavior 2
Over-inhibited behavior 4
Negativistic behavior 1
Total, all subjects 42
and gross motor coordination, alternate motion reactions, and reflexes.
Electro-encephalograms were also obtained on all subjects. The diagnostic categories of the subjects used in the study are shown in
Table I.
At the time of the 3-month and 7-month visits, information was gathered about any possible untoward effects of the drug. The
examination of the children at these times included a search for any disorder which might appear as a possible side-effect of the drug. Complete blood counts were made and no toxicity to the drug was noted.
As part of the initial appraisal, the sub-jects were also studied psychologically
through the use of the Stanfond-Binet In-telligence Scale, the Goodenough Intelli-gence Test, the Behavioral Complexity Test,79 and the Vineland Social Maturity Scale. As part of the study the parents
stim-TABLE II
MEASUREMENT ORDER AND MEDICATION SCHEDULE FOR TIlE STUDY
653
nh. Categories are enumeration,
enumera-tion and description, causation, supplanta-tion, and outcome. A response consisting of a description of the stimulus, a reason
for its existence, and a prediction as to
what vill take place next receives the
high-est score; a naming only of the stimulus
receives the lowest score. Emotional
pen-ceptions were measured by Part III of the
BCT, which consists of five cards contain-ing pictures of children and adults. The number of emotional expressions
attnib-uted to the figures in the cards were counted, and the sum provided the “emo-tional perception” score.
Experimental Design
The design for this study is shown in Table II. Medical and psychological
ap-praisais were made of the subjects when
they came into the study, after 3 months
in the study, and at the conclusion of the
study (7 months). Identities of subjects
be-ginning on either drug or placebo were not known by the investigators until after the conclusion of the study.
Data from this study were analyzed via
a Latin square on cross-over analysis of
van-iance design. One random half of the sub-jects (the A group) in the CNS and be-havior disorder groups were given the drug during the first 3 months of the expeni-ment and then given the placebo for the last 3 months. The second random half of the subjects (the B group) were given
the placebo for the first 3 months and then were given the drug for the last 3 months
of tile study.
A Latin square design, as shown in Table III, provides several advantages,
since practice effects associated with
re-testing can be separately assessed and
con-trolled in comparison of experimental and control treatment. The main comparison of drug and placebo thus becomes a
“within” subjects comparison, since each
subject serves as his own control. The
ex-penimental precision surpasses that of an experiment with independent groups of comparable size under such treatment
con-Group Procedure
A Measurement
Drug, 3 months Measurement
Nothing, I month Placebo, 3 months Measurement
B Measurement
Placebo, 3 months Measurement Nothing, 1 month Drug, 3 months Measurement
ditions. The behavioral measurements were analyzed separately.
The criteria measures after the first ap-praisal are described in terms of a gain
(or loss) between initial appraisal and the second appraisal; criteria measures for the second type of treatment are defined as a
gain (or loss) between initial appraisal and the third or concluding appraisal. The data obtained, accordingly, should reflect any change occurring between the initial ap-praisal and each of the subsequent
ap-praisals.
RESULTS
The results, shown in Table IV, indicate the mean gains or losses obtained on
meas-ures used in the study. In general, the data obtained as a result of the appraisal
methodology indicated that there was no demonstrable influence of deanol over the
TABLE III
STATISTICAL DESIGN FOil TREATMENT
OF STUDY DATA
Deanol Placebo
First Treatment
Group A
(;roup B
Second Treatment
Group B
* Gains, or losses, are statistically nonsignificant. placebo in bringing about better scores on the psychological tests. None of the
av-erage deanol gains exceeded the average placebo gains by an amount that was
sta-tistically significant at the 5% level. This
finding was also in evidence upon dividing
the subjects according to weight, with all children weighing less than 63 lb (28.6 kg)
being compared to those over 63 lb. That
is, the drug did not affect the performance significantly more than the placebo even when smaller children were compared with larger ones.
In interviewing the parents of the chil-dren who were in Group A, that is, those who were first given the drug and subse-quently the placebo, it was found that the
parents of 15 children said that while their child was on the drug therapy, they considered his behavior improved; 17 of
the parents, however, saw the child as improved after being given the placebo. In the group who started first on the placebo, 9 were said to have improved while being given the placebo, and 13 were said to have shown improvement while being given deanol. The parents
de-scribed their feelings about improvement in terms of general behavior at home, in
school, in matters of aggressiveness, anx-iety, apathy, emotional instability, nervous-ness, restlessness, and tantrums.
COM MENT
The effectiveness of the drug deanol in this study on the basis of the parameters
used and in the amount of the drug ad-ministered indicates no significant influence upon behavior over the placebo. It should be emphasized that there was a range of various data provided : there were the tasks of the Stanford-Binet Intelligence Scale,
the task of drawing the human figure (Goodenough Intelligence Test), and the
tasks comprising the Behavioral Complex-ity Test. In addition, the Vineland Social
Maturity Scale indicated parents’ view of development. It is obvious, therefore, that a varied number of behavioral
observa-tions and measures were obtained, and one might realistically expect that the effec-tiveness of the drug would be revealed in such a wide range of behavior. From the standpoint of this study it must be
con-cluded that the clinical usefulness of this drug for the dosage used has not been demonstrated.
It is possible that tile drug would
in-fluence behavior if it were administered in a greater amount than used in this study. There is also the possibility that the drug might produce change in other types of disorders than those studied here.
There were few, if any, adverse effects of the drug noted, although in three
in-stances the parents seemed to find the drug upsetting and discontinued the medication. In one instance, the mother felt that after having been on the drug therapy for 6 weeks, the boy had become much worse in his behavior. He attacked people and was
more difficult to manage. Distressed by
TABLE IV
MEAN GAINS, OR LossES, ON CRITERIA MEASURES FROM INITIAL MEASUREMENT*
Deanol
Measure Behavior CNS Combined
Disorder Disorder Groups
Plaecbo
Behavior Disorder
CNS Combined Disorder
\
GroupsStanford-Binet Intelligence Scale Goodenough Intelligence Test
VinelandSocialMaturityScale
Behavioral Complexity Test (BCT)
Emotional Perception Scores (from BCT)
.. -0 . 12
+7 .50 - 1 .76
-0.67 -0.73
+4 .67 +3 .27
+3 .33 +0 . 41
-0 .12 -0.03 -0.72
+3 .50 +0 . 87
..
+7 .83 +1.00 +4 .76
+2 .67
- 1 . 54 -‘2 .23
-0.17 +4 .27
+1 .53
- I .54
-0.34
this, the parents discontinued the drug. In another case the parents reported on
the first return visit that there was a
de-terioration in the boy’s performance, which
came to a climax when he threatened his
stepfather with a knife. In the third
in-stance, a case of muscular dystrophy, the
mother discontinued the drug as she felt it was not useful. These subjects were not included in the study. No evidence of
tox-icity was reported by parents. It is our conclusion, consequently, that the drug had no known adverse effects in the dosage
used; on the other hand, the drug did not cause significant changes beyond those of the placebo in either the test
measure-ments or in reports from parents.
SUMMARY
The effect of deanol on the problem
solving and emotional behavior of 42
chil-dren between the ages of 6 and 13 years was investigated. Both medical and
psy-chological appraisals were made of the
sub-jects, leading to diagnosis of either central
nervous system or behavior disorder. A
cross-over, double-blind experimental
de-sign was used, with the drug being ad-ministered in a dosage of 100 mg daily. The drug did not produce significantly
different scores, on the measures em-ployed, over the scores obtained while the
subjects were given the placebo. No im-portant side-effects of the drug were
oh-served during the experimental period.
REFERENCES
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D.C., National Academy of
Sciences-Na-tional Research Council, 1959.
2. Irwin, S. : Drug screening and evaluative
pro-cedures. Science, 136: 123, 1962.
3. Cole, J. 0., and Carr, C. J.: A synoptic
re-view of psychoactive drugs, in Child
Re-search in Psychopharmacology, edited by S.
Fisher. Springfield, Illinois, Thomas, 1959.
4. Clausen, J., et a!.: The effect of deaner
(2-dimethylaminoethanol) on mentally retarded
subjects. Train. Sch. Bull., 57:3, 1960.
5. Geller, S. J.: Comparison of a tranquilizer and
a psychic energizer used in treatment of
chil-dren with behavioral disorders. J.A.M.A.,
174:481, 1960.
6. La Veck, G. D., and Buckley, P. : The use of
psychopharmacologic agents in retarded
chil-dren with behavior disorders. J. Chron. I)is.,
13:174, 1961.
7. Alexander, T. : Behavioral complexity test. State
University of Iowa, 1961.
8. Alexander, T. : The influence of central nervous
system and behavior disorder upon
com-plexity of response. Amer. Psychologist, 16:
351, 1961.
9. Alexander, T. : Psychological and physiological
pathology of intellection. Child Develop., 31:
238, 1960.
Acknowledgment
\Ve are grateful to the Riker Company for
sup-plying the medicaments and placebos used in this
study. We also appreciate the aid of Prof.
