Psychologic Aspects of Pediatrics T H E T R E A T M E N T OF B E H A V I O R D I S O R D E R S I N C I I I L D R E N W I T H TOLSEROL ALFRED ~i. FREEDMAN, ~V[.D., ~VIALVINAW. I~REMER, M.D., RICHARD C. ROBERTIELL0, M.D., AND ABRAHAlV[S. EFFRON, M.D. NEW YORK, N. Y. N T I L recently, the clinical investigation of drugs in the treatment of psychiatric childhood disorders has received inadequate attention. I n an earlier p a p e r ~ the available data were reviewed, and our p r e l i m i n a r y observations with Benadryl were reported. The screening procedure to quickly evaluate the possible efficacy of other compounds has continued. This p a p e r is the result of p r e l i m i n a r y observation with Elixir Tolserol* (a,fi,dihydroxy-,/(2m e t h y l - p h e n o x y ) propane).
of Tolserol for children has been rep o r t e d in the t h e r a p y of cerebral palsy, 11 but the emphasis in this s t u d y was on the controI of m o t o r difficulties r a t h e r t h a n on behavior.
Tolserol was first i n t r o d u c e d as a muscle-relaxing agent. 2 It was said to produce a specific depressing effect at the internuncial cell2 Other reports f u r t h e r described effective activity on subcortical efferent pathways, basal ganglia, thalamus, hypothalamus, and brain stem. ~ Several investigators ~, 5 noted a sedative effect, and in psychiatric patients Tolserol was said 4' 6 to be effective in relieving a n x i e t y t e n s i o n states. Finally, it has been used 8 to reduce tension during psychologic testing. U n f o r t u n a t e l y , the enthusiasm of m a n y of these investigators is not equally shared b y all. The ability of Tolserol to relieve anxiety has been p a r t i c u l a r l y questioned?, lo The use
their hospital admission, and all were between 6 and 12 years of age. As
U
PROCEDURE The procedure was essentially as r e p o r t e d in the B e n a d r y l study. There were t w e n t y - t w o c h i 1 d r e it. E i g h t were diagnosed as schizophrenia, five organic,* and nine as p r i m a r y be~ havior disorders. All the children were chosen at r a n d o m at the time of
before, each child was u n d e r continuous observation of the staff, i.e., house staff psychiatrist, research staff psychiatrist, nurses, schoolteachers, recreation instructors, and psychologists. D u r i n g the period of administration of Tolserol, additional compounds were being evaluated in other children on the ward. To exclude subjeetive opinions and trends as far as possible, the staff was not informed as to the n a t u r e of the c o m p o u n d being administered to a n y child. Changes were recorded for the following categories : 1. Excessive motor activity. 2. Anxiety.
From the New York University-Bellevue *For a description of what is meant b y a n Medical Center, Department of Psychiatry child, see Bender, L. : The Psychoand Psychiatric Division of Bellevue Hospital. organic logical Problems of Children With Organic Brain Disorders, Am. J. Orthopsychiat. 19: *Supplied through the c o u r t e s y of ~1. 1~. Squibb & Sons. 404, 1949. 369
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3. Relationship problems with other children. 4. Relationship p r o b l e m s with adults. 5. Soft neurological signs. 6. Affect. 7. Pathognomie symptomatology and fantasy life, i.e., introjected bodies and hallucinations. The five-point scale of scoring previous]y noted was also employed: ++ + 0 --
Marked improvement. Moderate improvement. None or s l i g h t change. Moderate aggravation. Marked aggravation.
The dosage schedule of the Elixir Tolserol is as follows : F i r s t w e e k : 500 mg. t w i c e a Second week: 500 rag. three T h i r d w e e k : 1,000 rag. t h r e e F o u r t h week: 1,500 rag. t h r e e
day. t i m e s a day. t i m e s a day. t i m e s a day.
RESULTS
Results are indicated in Tables I, II, and III. '~ As can be seen in Table I, half of the twenty-two eases showed some over-all improvement; nine were unimproved, and in two there was aggravation of symptoms. The most marked improvement was observed in relationships, both to peer and adults. Nine demonstrated a decrease in manifest anxiety. Only seven of the twenty-two children showed an alleviation of their depression, and six a reduction of hyperactivity. None of the children showed significant change in soft neurological signs, pathognomonic symptomatology, or fantasy life. Ten of the eleven children who showed iraprovement d6monstrated the change in three to five categories, while only one child demonstrated improvement in only one or two categories. *Statistical
%Viiliam I-[clme.
analysis
was
done
by
~[r.
PEDIATRICS
In Table H the data are presented according to diagnosis and age groups. It can be seen that all of the organic children showed improvement with Tolserol. However, there was improvemerit in only three of eight schizophrenie children, and three of nine children with the diagnosis of primary behavior disorders. Except for the behavior disorders, age did not seem to be a significant factor. Of the four children diagnosed as behavior disorders above the age of ]0 years, none showed improvement, while three of the five childre~l between 6 and 9 years showed improvement. Table I I I is a breakdown according to intelligence quotient and diagnosis. It would appear from the data that schizophrenic children with IQ's over 78, and children with behavior disorders and IQ's under 78 showed somewhat better response. DISCUSSION
This preliminary study indicates that Elixir Tolserol is useful in the therapy of children with behavior disorders resulting from organic brain disease. It is less satisfactory in the therapy of children with schizophrenia or primary behavior disorders. In fact, in the latter two diagnostic categories tile results are unimpressive. The Elixir Tolserol tended to manifest its effect primarily in improving interpersonal relationships. It was less effective in reducing manifest anxiety. It is of interest to briefly compare the results obtained with Elixir Tolserol and those reported with Elixir Benadryl. The administration of Tolserol produced the most striking results in children with organic behavior disorders, whereas in those children who received Elixir Benadryl
PSYCHOLOGIC
ASPECTS
OF
IMPI~OVEMENTWITI~: TREATMENT BY
TABLE ]i. NUMBER OF CASES IN ]~]ACK CATEG0au SHOWING TOLSEKOL
Hyperactivity Manifest anxiety Relationship problems to peers Relationship problems to adults Depressed affect 9I T h r e e t o five c a t e g o r i e s One to two categories No categories All cases
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PEDIATRICS
NO]%I~s 1M ['ROVED ~[AINTAINED UN[ MPI%OVED -WORSE 6 1 14 1 9 0 12 1 11 0 9 2 ]0 0 11 1 7 0 14 1 IMPROVED WORSE 10 1 1 :1 9 0 IMPROVED i UNIMPI~OVED I SOME WORSE 11 9 2
TABLE I ~ NUMBER OI~ CHILDREN :IMPROVED W I T H TOLSEROL TI~EATMENT BY -~-GE AND DIAGNOSIS AGED 6-9 YEAI~S AGED 10 12 YEARS NOT NOT DIAGNOSIS CASES IMPROVEI) IMPROVED OASES IMPROVED I]Y[PROVEI) Schizophrenic 4 1 3 4 2 2 Organic 2 2 0 3 3 0 Primary b e h a v i o r 5 3 2 4 0 4 disorders MEAN 1NTuMBEI% OF IMPROVED ~ATEGORIES W I T H TOLSEROL TREATMENT AGED 6-9 YEARS MEAN CASES IMPROVEMENT 4 .75
DIAGNOSIS Schizophrenic
Organic Primary
behavior disorders
,
AGED 1 0 - 1 2 YEARS MEAN CASES 1MPROVEM ENT 4 .50
2
3.00
3
4.67
5
2.40
4
.0O
~U1VfBER ~]V[pROVED AND ~ E A N IMPROVE~V[ENT WIT]i[ TOLSEROL Tt~EATMENT DIAGNOSTIC GROUPINGS AI~ONE DIAGNOSIS Schizophrenic Organic P r i m a r y b e h a v i o r disorders
]
CASES 8 5 9
I
NUMBER IMPROVED 3 5 3
I MEAN IMPROVEMENT .62 4.00 1.33
TABLE 1 [ I ~NTUMBEE OF CASES IMPROVED W I T H TOLSEROL TREATMENT BT I . Q . AND DIAGNOSIS 9 DIAGNOSIS Schizophrenic Organic Primary behavior disorders
i.q. UNDER 78 CASES 4 2 4
IMPROVED ] 2 2
I.Q. 78 AND 0VER
. .
NOT IMP]~OVED 3 0 2
CASES 4 3 5
IMPEOVEI) 2 3 7t
NOT IMPROVED 2 0 4
MEAN NUMBER OF IlV[PROVED CATEGORIES W I T H TOLSEROL TREATMENT
DIAGNOSIS Schizophrenic Organic Primary behavior disorders
I.Q. UNDER 78 MEAN IMCASES PROVEMENT 4 .25 2 4.50 4 '2.25
I.Q. 78 AND OVER MEAN IMCASES PROVEMENT 4 1.50 3 3.67 5 .60
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there was improvement in all children diagnosed as primary behavior disorders. More detailed analysis of other differences will be postponed until present investigations arc completed, and all drugs under study can be compared with each other and with controls. No toxic symptoms were evidenced in any of the children with Elixir Tolserol. Many children complained of its unpleasant taste. Recent experience with a new related compound, Tolseram, indicates that it has the same therapeutic effect, but is more palatable. SU1V[MARY
1. Elixir Tolserol has been administered to twenty-two children with a variety of psychiatric disorders. 2. Administration of this drug produced definite improvement in all the children with the diagnosis of organic behavior disorder. 3. The improvement in children with schizophrenia or primary behavior disorder was unimpressive. 4. The principal improvement was in the area of relationships.
5. Diminution in anxiety was noted in nine of twenty-two children. REFERENCES 1. Effrm b A. S , and Freedman, A. M.: The Treatment of Behavior Disorders in Children With Eenadryl, J. PEDIAT. 42: 261, 1953. 2. Berger, F. M., and Bradley, W.: The Pharmacological Properties of a, fi, dihydroxy-7 (2-methylphenoxy) -propane (Myanesin), Brit. J. Pharmacol. 1: 265, 1946. 3. I-Ienneman, E., Kaplan, A., and Unna~ K.: A Neuropharmacological Study on the Effect of 5V[yanesia (Tolserol) on Motor Systems, J. Pharmacol. 97: 331, 1949. 4. Gammon, G. D , and Churchill, J. A.: Effects of Ziyanesin Upon the Central Nervous System, Am. J. 1Vi. St. 217: 143, 1949. 5. Schlesinger, E. B.: Clinical Applications of lYiyanesin, Tr. New York Acad. St. ii: 5, 1948. 6. Schlan, Q. S.~ and Unna, K. R.: Some Effects of Myanesin in Psychiatric Patients, J. A. iV[. A. 140: 672, 1949. 7. Iierman, 1V[., and Effron, A. S.: Tolserol in the Treatment of the PostAlcoholic State, Quart. J. Studies in Alcohol 12: 26], 1951. 8. iVIercer, IV[., and Hecker, A. O.: The Use of TolseroI (1Kyanesin) in Psychological Testing, to be published. 9. Ewing, J. A., and Mendenhall, J. H.: Clinical Evaluation of the Effect of IVIephenesin on Anxiety, J. h~ent. St. 99: 464, 1953. 10. Black, S. Q.: Effect of ~V[ephenesln Upon Anxiety, Arch. Neurol. & Psychiat. 69: 79,7, 1953. 11. Cook, W.: New Concepts in the :~anagement of Cerebral Palsy, J. South Carolina 3r A. 45: 248, 1949.