- Email: [email protected]
Deanol in the Treatment of Hyperkinetic Children
Deanol in the Treatment of Hyperkinetic Children NATHAN COLEMAN, M.D., PATRIC DEXHEIMER, ALBERTO DIMASCIO, Ph.D., WILLIAM REDMAN, M.D., RICHARD FINNERTY, M.A.
Previous investigations of deanol acetamidobenzoate have produced some contradictory results as to its usefulness in the treatment of children exhibiting a hyperkinetic syndrome. Studies by Oettinger1-2 indicate that deanol decreases (Deane~)
hyperactivity, increases the capacity to learn, and decreases irritability. KnobeP after studying deanol concluded that deanol is efficacious in the treatment of behavior problems of children, and above all in those hyperkinetic children with moderate unhappiness and isolation. Geller4 drew the conclusion that deanol (at 100 mg/day) was effective in increasing the functional capacity of children with behavior problems. He found that in such children, deanol increased attention span, decreased hyperactivity, allowed the children to perform more organized activity, and to be more efficient in certain objective tests such as solving puzzles and problems. Udabe 5 examined deanol in doses up to 400 in 27 hyperkinetic children and reported "spectacular" results in 22 of them. Fleming and Orland06 studied the effects of deanol in institutional retardates and noted an increase in reaction time. On the other hand, other studies, mainly in mental retardates7.8 or children with encephalopathy,9 have not found deanol to be statistically more effective than placebo. Connors,10 in an excellent review of the literature on deanol, concluded that the "better controlled studies tend to show little or no drug effect". However, he also concluded that most of these studies used a very wide age range, a heterogeneous sample, and a rather low dosage. Connors noted that "the most promising use of the drug (deanol) would be in the acting out behavior problems, especially hyperkinetic impulse disorders and cases with poor classroom behavior and impaired attention". Connors further recommended that doses in the range of 150 to 300 mg be used and the drug studied in children between the ages of 6-12 for a period of at least 3 months. Nathan Coleman, M.D. is Psychiatrist, Fuller Memorial Hospital, South Attleboro, Mass. 02703. Patric Dexheimer, A.B. is Psychologist, Attleboro School Department, Attleboro, Mass. 02703. Alberto DiMascio, Ph.D. is Director of Psychopharmacology, Commonwealth of Massachusetts. William Redmon, M.D. is Director, Attleboro Mental Health Clinic. Richard Finnerty. M.A. is Psychologist, Boston State Hospital. 68
The purpose of the study herein described, accordingly, was to carry out a double-blind, placebo-controlled, evaluation of the efficacy of deanol acetamidobenzoate, when given to school children diagnosed as hyperkinetic, in: (a) modifying the clinical symptomatology they present as behavior problems in school, (b) modifying the concomitant symptoms, behavior and relationships extant in the homes, (c) improving their academic performance and achievement in the schools, and (d) improving their basic 1.0. test performance level and various subtest scores. METHOD
The main study* consisted of a double-blind comparison of the active medication (deanol) with an inactive medication (placebo) when administered for a 12 week period, in a parallel group design.
Subject Selection Criteria The study population consisted of fifty (50) children, ages 6-12, referred from local physicians, mental health centers, pupil adjustment counselors. or teachers. The bases for initial referrals were that the children had exhibited, for a considerable period of time, behavioral problems-consistent with the hyperkinetic syndrome-at school or at home to the extent that it had interfered with their school performance and / or their interpersonal relationship with parents, sibs or peers. Children, whose parents-after having been completely informed of the total treatment study aims, methods, and evaluation procedures-requested inclusion of their child in the program, were given a pediatric, psychiatric, and psychological evaluation. Furthermore, the child's teacher was asked to fill out Connors Teachers Rating Scale and the parents asked to fill out Connors Parents Rating Scale. To aid in assuring that the child's problems were of sufficient magnitude to warrent psychopharmacological treatment, only those children who were rated as exhibiting 3 or more behavioral disturbances or symptoms at the "very much" level; or as exhibiting 5 or more behavioral disturbances or symptoms, on the Connors' Teachers Rating Scale were included.
* an anciUary study tacked on to the end of this study consisted of an open-crossover examination of treatment failures: plabeco-failures were administered deanol and deanol failures were administered methylphenidate. Volume XVII
DEANOL IN HYPERKINETIC CHILDREN-COLEMAN, ET AL.
These criteria had to be substaintiated by parental affirmation that disturbances were of long-term duration (6 or more months and confirmed by a psychiatric diagnosis of hyperkinesis. Excluded from study was any child with signs of (or history of) definite organic brain damage, I.Q. below 80 as measured by the WISC, psychosis, physical contraindications, or any child under treatment by other physicians.
Medication and Dosage Regimen Patients selected as being appropriate for treatment study were assigned on a randomized basis to one of two groups. One group (25 patients) received an inactive medication (placebo) and the other group (25 patients) received the active medication (deanol). Both medications were prepared as similar appearing pink tablets containing either 100 mg of deanol of the placebo. A coded bottle was prepared-labelled with each child's name-containing the assigned treatment medication. A study nurse was responsible for administering the prescribed amount of medication during each of the five school days. During the first week each child was prescribed two (2) tablets on arrival at school and one (1) tablet after lunch (for a total of 300 mg). Parents were given a sufficient number of tablets to continue the same dosage regimen at home over the weekend. During the second week each child was given three (3) tablets on arrival in the morning and one (1) at lunch time (total daily dose of 400 mg). During the third week-and all subsequent weeks until the end of the 12 week main study--each child was given three (3) tablets in the morning and two (2) tablets at lunch time, either by the study nurse during the weekdays or by the parents on weekends (a total of 500 mg daily). This dosage schedule could have been adjusted or discontinued if adverse reactions necessitated it: such was never required. Measures of Drug Effects To assess drug response the following procedures and measurements were completed for each child prior to treatment and at the end of the 12 week treatment period. 1. Psychiatric Examination: the child psychiatrist interviewed the students with the aims of determining whether a diagnosis of hyperkinesis of moderate degree was appropriate and of excluding those with psychotic manifestations or obvious brain damage. The psychiatrist filled out the Rutter and Graham Scale and made a global evaluation on each child. 2. Pediatric Examination: each child was given a standard physical examination (induding a complete CBC, urinalysis, alkaline phosphatase, HCT and HGB. 3. Psychological Examination: the psychologist tested April/May/June, 1976
all children on the WISC, the Wide Range Achievement Test (WRAT) and on the Porteus Maze Test. 4. Teacher's Ratings: for each child the present teacher (who had the child in class for a minimum of 3 months) filled out Connor's Teacher's Rating Scale (40 items). The Scale includes Global Evaluations. 5. Parents' Ratings: for each child the parents filled out Connor's Parents' Rating Scale (93 items). The Scale also includes Global Evaluations. RESULTS
The data analyses of pre-treatment information documented that the children were moderately disturbed children who exhibited hyperactivity and impulsivity, were seen by both parents and teachers as having conduct problems and learning or inattention problems. I. Q. level revealed average intelligence = 100.1 with a range from 82 to 125), but the teachers rated their overall scholastic performance as = 3.6 on a 1 to 4 scale). "very much" impaired Parents rated the children mid-point on a 1 to 4 severity scale = 2.5 between "little" and "much" disturbed. Statistical assessments were made of data obtained prior to treatment to determine whether any bias occurred as a result of the randomization procedure. The two treatment groups did not differ in male/female proportion, age, grade, height, weight, severity of illness, on any subtest of the WISC or the WRAT, on the Porteus Maze Test, on any factor of the Teacher's Questionnaire, nor on any factor of the Parent's Questionnaire.
ex
ex
ex
Global Ratings Analyses Analysis of drug effects for the Global Clinical Change ratings made by the psychiatrist at the end of 12 weeks revealed that greater improvement was noted for the deanol patients than for the placebo (X 2 3df = 7.73, p. = .05). Similarly, the Teachers Global Improvement Ratings of Classroom Behavior at the end of 12 weeks showed that deanol produced the greater degree of overall improvement (X 2 2df = 5.34, p. = .06). When the teacher was asked to make a global evaluation of how much the child's Group Participation had changed, there was no statistically significant difference between deanol and placebo treated groups. The teachers did rate deanol-treated children as improving more than placebo-treated children with regard to Attitude Towards Authority (X 2 2df = 5.18, p. = .07). In their Global Ratings at the end of 12 weeks, the parents described their children as being a "little" disturbed (rating them 2.1 on a 1 to 4 scale, compared to 2.5 pre-treatment) but no statistically significant differ69
PSYCHOSOMATICS
ence was noted between the two treatment groups. However, when parents were asked to compare their child with other children the same age, more placebotreated children were rated as comparatively worse: the deanol-treated children were rated comparatively favorable to their peers (X2 2df = 6.4, p. = .05).
Rating Scales Factor Score Analyses Analysis were carried out on the Teachers' Rating Scale using the Factors derived by Connors. l1 The 40 items were given their assigned weights and 4 Factor scores were computed (Conduct Problems, Inattentive,
Anxiety Tension and Hyperactivity). The pre-post Factor Scores were compared (matched t-tested) for both drug groups and the pre-post differences contrasted by drug groups. Children treated either by placebo or deanol showed a statistically significant increase in attention and a reduction in hyperactivity. The two treatment groups did not, however, differ statistically on any factor, although the deanol patients tended (p. = .10) to show a greater reduction in hyperactivity. The Parents' Rating Scale items were similarly assigned the weights derived by Connors l l and his 8 Factors computed. Pre-post analyses revealed that both treatment groups showed a statistically significant im-
TABLE I PSYCHIATRISTS GLOBAL IMPROVEMENT RATING AT 12 WEEKS DEANOL
PLACEBO
6 10 2 5
14 5 5
No Change Slight Improvement Moderate Improvement Marked Improvement
x:!
TABLE III
= 7.73 p.
1
TEACHER'S GLOBAL RATING OF ATTITUDE TO AUTHORITY
Worse Same Better
DEANOL
PLACEBO
2 9 11
7 11 4
.05
3dl
X'
5.18 p.
.07
2df
Data available only on 46 patients. (3 patients moved and one dropped early in the study for non-treatment involved reasons).
Data available for 45 patients only. (3 patients moved, one dropped early in the study, and one patient assigned to different classroom).
TABLE II TEACHER'S GLOBAL CLASS BEHAVIOR CHANGE RATINGS
Worse Same Better
DEANOL
PLACEBO
4
10 7 6
5 13
x:! = 5.34 p.
TABLE IV PARENTS RATINGS OF COMPARISON WITH OTHER CHILDREN
Worse Same Better
DEANOL
PLACEBO
4
10 10
14 3
o
.06
2df
x:! =
6.4 p.
.05
201f
Data available only for 45 patients. (3 patients moved, one dropped early in study, and one patient assigned to different classroom) .
70
Data available on only 41 patients.
Volume XVII
DEANOL IN HYPERKINETIC CHILDREN-COLEMAN, ET AL.
TABLE V CONNORS TEACHER'S FACTORS
PLACEBO
BETWEEN GROUP DIFF SIGNIFICANCE
DEANER
FACTOR
Pre
Post
Diff
Pre
Post
Diff
Conduct Problem Inattentive Anxiety Tension Hyperactivity
2.26 2.79 2.37 3.23
2.26 2.38 2.24 3.00
.41 *** .13 .23** *
2.32 2.78 2.24 3.27
2.13 2.37 2.17 2.69
.18 .41 *** .07 .58
***
=
statistically significant (p
<
n.s. n.s. n.s. .10
.01) pre-post change (matched t-test)
provement in only one Factor (Impulsive Hyperactive). The two groups did not show differential treatment effects on any Factor.
peers, rated the placebo-treated patients as worse, but the deanol-treated patients about the same as a normal peer cohort.
Psychometric Test Analyses
In the Factor Scores derived from the Teacher's or Parent's Rating Scales the only factor tending to show a differential drug effect was the Teacher's Hyperactive Factor-
Statistical analyses made for all WISC subtest scores, Verbal I.Q. scores, Performance I.Q. scores, and full scale I.Q. scores revealed no statistically significant differential treatment effects. Analyses of the spelling, arithmetic, and reading scores on the WRAT and of the Porteus Maze performance also revealed no differential drug treatment. Both treatment groups showed statistically significant improvement on the Porteus Maze in their 12 week testing. While the placebo treated patients improved to a statistically significant degree on their arithmetic and reading performance on the WRAT, the deanol treated patients also showed some improvement-so that the difference between groups was not statistically significant. CONCLUSIONS AND SUMMARY
The data presented lend themselves to the interpretation that deanol acetamidobenzoate, when administered at doses of 300-500mg per day for 12 weeks to moderately disturbed hyperkinetic children (6 to 12 years of age), as seen by a psychiatrist, by teachers, and by parents to produce greater overall improvement in comparison to patients similarly treated with a placebo. While it is true that in three instances of the Global Ratings (Psychiatrists' Clinical Change, Teachers' Global Improvement, and Teachers' Rating of Attitude towards Authority) the differences did not always achieve a .05 level of significance (p = .05, .06, .07, respectively), in each instance it was the deanol patients who had shown the greater beneficial change. Parents, when asked after the 12 week treatment period to compare the children to a group of normal April/May/June, 1976
That no differential drug effects were found on the various WISC subscale scores or on the Verbal Performance or Full Scale I.Q. levels should not be surprising in a study lasting only 12 weeks. Similarly, achievement on the three scholastic components of the WRAT also requires a greater than 12 week period to show appreciable drug effects. Selection of these tests to show short-term drug effects was in retrospect not a wise choice. Special thanks are due to Ruth Boivin, R.N., and Catherine Memory, A.B., for their diligent efforts in carrying out this project. BIBLIOGRAPHY 1. Oettinger, L.: The use of deanol in the treatment of disorders of behavior in children. J. Pediat. 53(6) :671-675, 1958. 2. Oettinger, L.: Meratran: Preliminary report on a new drug for the treatment of behavior disorders in children. Dis. Nerv. Sys. 16,299-302, 1955. 3. Knobel, M.: Two-dimethylaminoethanol in behavior problems of children. Sem. Med. (B. Air.), 119(24):939-944, 196\. 4. Geller, S.J.: Comparison of a tranquilizer and a psychic energizer. lAMA, 174:481-484, 1960. 5. Udabe, R.L.: Clinical experience with 2-dimethylaminoethanol in the psychopharmacology of children. Read at the Third Latin American Congress of Psychiatry, Lima, Peru, October 25-31, 1964.
71
PSYCHOSOMATICS 6. Fleming, J.W. and Orlando, R.: Effect of deanol on attention in the mentally retarded: A reaction time method. J. New Drugs, 2:239-244, 1962. 7. Clausen, J.: The effect of Deaner (2-dimethylaminoethanol) on mentally retarded subjects. Train. Sch. Bull., 57(1):3-12,1960. 8. Jacobs, J.: A controlled trial of Deaner and a placebo in mentally defective children. Brit. J. Clill. Pract., 19(2): 77-86, 1965.
9. Kugel, R.B. and Alexander, T.: The effect of a central nervous system stimulant (deanol) on behavior. Pediatrics, 31 :651-655, 1963. 10. Conners, C.K.: Deanol and behavior disorders in children: a critical review of the literature and recommended future studies for determining efficacy. Psychopharm. Bull. (Special Issue) pp. 188-195, 1973. II. Connors, C.K.: Rating Scales for use in drug studies with children. Psychopharm. B/I/I. (Special Issue) pp. 24-84, 1973.
Proposed Amendments to the Constitution (1976) The following amendments to the constitution were reviewed and approved by the Executive Council, May 14-15, 1976 to be published for review by the membership according to constitutional procedure. The membership will be asked to pass on these amendments at the Annual Meeting of the Academy in November 1976 at Charleston, South Carolina. ARTICLE VI-Section I-Governing Body of the Academy-Executive Council 3. Nine (9) elected active Fellows--representative of regional continental areas whenever possible. 4. Four (4) past presidents (not counting the immediate past president) shall be members with vote for a period of four (4) years. This term commences at the completion of immediate past president year. ARTICLE VI-Section 2-Executive Council-Duties 8. Prescribe additional rules as necessary for the legal functioning of the Academy in any business matters or activities not otherwise provided for by the by-laws but in accordance with the constitution. 9. All executive council members must attend at least one meeting (interim or annual) per year, otherwise their elected position on the executive council for the following year may be forfeited at the discretion of the council. ARTICLE VI-Section 6-Executive Director I. There shall be an executive director who is appointed by the Executive Council of the Academy for two (2) years with stipend to be fixed by the same. ARTICLE VII-Editor of Psychosomatics I. There shall be an Editor for Psychosomatics who is elected by the Executive Council of the Academy for a period of five (5) years with stipend to be fixed by the same.
72
Volume XVII
Previous investigations of deanol acetamidobenzoate have produced some contradictory results as to its usefulness in the treatment of children exhibiting a hyperkinetic syndrome. Studies by Oettinger1-2 indicate that deanol decreases (Deane~)
hyperactivity, increases the capacity to learn, and decreases irritability. KnobeP after studying deanol concluded that deanol is efficacious in the treatment of behavior problems of children, and above all in those hyperkinetic children with moderate unhappiness and isolation. Geller4 drew the conclusion that deanol (at 100 mg/day) was effective in increasing the functional capacity of children with behavior problems. He found that in such children, deanol increased attention span, decreased hyperactivity, allowed the children to perform more organized activity, and to be more efficient in certain objective tests such as solving puzzles and problems. Udabe 5 examined deanol in doses up to 400 in 27 hyperkinetic children and reported "spectacular" results in 22 of them. Fleming and Orland06 studied the effects of deanol in institutional retardates and noted an increase in reaction time. On the other hand, other studies, mainly in mental retardates7.8 or children with encephalopathy,9 have not found deanol to be statistically more effective than placebo. Connors,10 in an excellent review of the literature on deanol, concluded that the "better controlled studies tend to show little or no drug effect". However, he also concluded that most of these studies used a very wide age range, a heterogeneous sample, and a rather low dosage. Connors noted that "the most promising use of the drug (deanol) would be in the acting out behavior problems, especially hyperkinetic impulse disorders and cases with poor classroom behavior and impaired attention". Connors further recommended that doses in the range of 150 to 300 mg be used and the drug studied in children between the ages of 6-12 for a period of at least 3 months. Nathan Coleman, M.D. is Psychiatrist, Fuller Memorial Hospital, South Attleboro, Mass. 02703. Patric Dexheimer, A.B. is Psychologist, Attleboro School Department, Attleboro, Mass. 02703. Alberto DiMascio, Ph.D. is Director of Psychopharmacology, Commonwealth of Massachusetts. William Redmon, M.D. is Director, Attleboro Mental Health Clinic. Richard Finnerty. M.A. is Psychologist, Boston State Hospital. 68
The purpose of the study herein described, accordingly, was to carry out a double-blind, placebo-controlled, evaluation of the efficacy of deanol acetamidobenzoate, when given to school children diagnosed as hyperkinetic, in: (a) modifying the clinical symptomatology they present as behavior problems in school, (b) modifying the concomitant symptoms, behavior and relationships extant in the homes, (c) improving their academic performance and achievement in the schools, and (d) improving their basic 1.0. test performance level and various subtest scores. METHOD
The main study* consisted of a double-blind comparison of the active medication (deanol) with an inactive medication (placebo) when administered for a 12 week period, in a parallel group design.
Subject Selection Criteria The study population consisted of fifty (50) children, ages 6-12, referred from local physicians, mental health centers, pupil adjustment counselors. or teachers. The bases for initial referrals were that the children had exhibited, for a considerable period of time, behavioral problems-consistent with the hyperkinetic syndrome-at school or at home to the extent that it had interfered with their school performance and / or their interpersonal relationship with parents, sibs or peers. Children, whose parents-after having been completely informed of the total treatment study aims, methods, and evaluation procedures-requested inclusion of their child in the program, were given a pediatric, psychiatric, and psychological evaluation. Furthermore, the child's teacher was asked to fill out Connors Teachers Rating Scale and the parents asked to fill out Connors Parents Rating Scale. To aid in assuring that the child's problems were of sufficient magnitude to warrent psychopharmacological treatment, only those children who were rated as exhibiting 3 or more behavioral disturbances or symptoms at the "very much" level; or as exhibiting 5 or more behavioral disturbances or symptoms, on the Connors' Teachers Rating Scale were included.
* an anciUary study tacked on to the end of this study consisted of an open-crossover examination of treatment failures: plabeco-failures were administered deanol and deanol failures were administered methylphenidate. Volume XVII
DEANOL IN HYPERKINETIC CHILDREN-COLEMAN, ET AL.
These criteria had to be substaintiated by parental affirmation that disturbances were of long-term duration (6 or more months and confirmed by a psychiatric diagnosis of hyperkinesis. Excluded from study was any child with signs of (or history of) definite organic brain damage, I.Q. below 80 as measured by the WISC, psychosis, physical contraindications, or any child under treatment by other physicians.
Medication and Dosage Regimen Patients selected as being appropriate for treatment study were assigned on a randomized basis to one of two groups. One group (25 patients) received an inactive medication (placebo) and the other group (25 patients) received the active medication (deanol). Both medications were prepared as similar appearing pink tablets containing either 100 mg of deanol of the placebo. A coded bottle was prepared-labelled with each child's name-containing the assigned treatment medication. A study nurse was responsible for administering the prescribed amount of medication during each of the five school days. During the first week each child was prescribed two (2) tablets on arrival at school and one (1) tablet after lunch (for a total of 300 mg). Parents were given a sufficient number of tablets to continue the same dosage regimen at home over the weekend. During the second week each child was given three (3) tablets on arrival in the morning and one (1) at lunch time (total daily dose of 400 mg). During the third week-and all subsequent weeks until the end of the 12 week main study--each child was given three (3) tablets in the morning and two (2) tablets at lunch time, either by the study nurse during the weekdays or by the parents on weekends (a total of 500 mg daily). This dosage schedule could have been adjusted or discontinued if adverse reactions necessitated it: such was never required. Measures of Drug Effects To assess drug response the following procedures and measurements were completed for each child prior to treatment and at the end of the 12 week treatment period. 1. Psychiatric Examination: the child psychiatrist interviewed the students with the aims of determining whether a diagnosis of hyperkinesis of moderate degree was appropriate and of excluding those with psychotic manifestations or obvious brain damage. The psychiatrist filled out the Rutter and Graham Scale and made a global evaluation on each child. 2. Pediatric Examination: each child was given a standard physical examination (induding a complete CBC, urinalysis, alkaline phosphatase, HCT and HGB. 3. Psychological Examination: the psychologist tested April/May/June, 1976
all children on the WISC, the Wide Range Achievement Test (WRAT) and on the Porteus Maze Test. 4. Teacher's Ratings: for each child the present teacher (who had the child in class for a minimum of 3 months) filled out Connor's Teacher's Rating Scale (40 items). The Scale includes Global Evaluations. 5. Parents' Ratings: for each child the parents filled out Connor's Parents' Rating Scale (93 items). The Scale also includes Global Evaluations. RESULTS
The data analyses of pre-treatment information documented that the children were moderately disturbed children who exhibited hyperactivity and impulsivity, were seen by both parents and teachers as having conduct problems and learning or inattention problems. I. Q. level revealed average intelligence = 100.1 with a range from 82 to 125), but the teachers rated their overall scholastic performance as = 3.6 on a 1 to 4 scale). "very much" impaired Parents rated the children mid-point on a 1 to 4 severity scale = 2.5 between "little" and "much" disturbed. Statistical assessments were made of data obtained prior to treatment to determine whether any bias occurred as a result of the randomization procedure. The two treatment groups did not differ in male/female proportion, age, grade, height, weight, severity of illness, on any subtest of the WISC or the WRAT, on the Porteus Maze Test, on any factor of the Teacher's Questionnaire, nor on any factor of the Parent's Questionnaire.
ex
ex
ex
Global Ratings Analyses Analysis of drug effects for the Global Clinical Change ratings made by the psychiatrist at the end of 12 weeks revealed that greater improvement was noted for the deanol patients than for the placebo (X 2 3df = 7.73, p. = .05). Similarly, the Teachers Global Improvement Ratings of Classroom Behavior at the end of 12 weeks showed that deanol produced the greater degree of overall improvement (X 2 2df = 5.34, p. = .06). When the teacher was asked to make a global evaluation of how much the child's Group Participation had changed, there was no statistically significant difference between deanol and placebo treated groups. The teachers did rate deanol-treated children as improving more than placebo-treated children with regard to Attitude Towards Authority (X 2 2df = 5.18, p. = .07). In their Global Ratings at the end of 12 weeks, the parents described their children as being a "little" disturbed (rating them 2.1 on a 1 to 4 scale, compared to 2.5 pre-treatment) but no statistically significant differ69
PSYCHOSOMATICS
ence was noted between the two treatment groups. However, when parents were asked to compare their child with other children the same age, more placebotreated children were rated as comparatively worse: the deanol-treated children were rated comparatively favorable to their peers (X2 2df = 6.4, p. = .05).
Rating Scales Factor Score Analyses Analysis were carried out on the Teachers' Rating Scale using the Factors derived by Connors. l1 The 40 items were given their assigned weights and 4 Factor scores were computed (Conduct Problems, Inattentive,
Anxiety Tension and Hyperactivity). The pre-post Factor Scores were compared (matched t-tested) for both drug groups and the pre-post differences contrasted by drug groups. Children treated either by placebo or deanol showed a statistically significant increase in attention and a reduction in hyperactivity. The two treatment groups did not, however, differ statistically on any factor, although the deanol patients tended (p. = .10) to show a greater reduction in hyperactivity. The Parents' Rating Scale items were similarly assigned the weights derived by Connors l l and his 8 Factors computed. Pre-post analyses revealed that both treatment groups showed a statistically significant im-
TABLE I PSYCHIATRISTS GLOBAL IMPROVEMENT RATING AT 12 WEEKS DEANOL
PLACEBO
6 10 2 5
14 5 5
No Change Slight Improvement Moderate Improvement Marked Improvement
x:!
TABLE III
= 7.73 p.
1
TEACHER'S GLOBAL RATING OF ATTITUDE TO AUTHORITY
Worse Same Better
DEANOL
PLACEBO
2 9 11
7 11 4
.05
3dl
X'
5.18 p.
.07
2df
Data available only on 46 patients. (3 patients moved and one dropped early in the study for non-treatment involved reasons).
Data available for 45 patients only. (3 patients moved, one dropped early in the study, and one patient assigned to different classroom).
TABLE II TEACHER'S GLOBAL CLASS BEHAVIOR CHANGE RATINGS
Worse Same Better
DEANOL
PLACEBO
4
10 7 6
5 13
x:! = 5.34 p.
TABLE IV PARENTS RATINGS OF COMPARISON WITH OTHER CHILDREN
Worse Same Better
DEANOL
PLACEBO
4
10 10
14 3
o
.06
2df
x:! =
6.4 p.
.05
201f
Data available only for 45 patients. (3 patients moved, one dropped early in study, and one patient assigned to different classroom) .
70
Data available on only 41 patients.
Volume XVII
DEANOL IN HYPERKINETIC CHILDREN-COLEMAN, ET AL.
TABLE V CONNORS TEACHER'S FACTORS
PLACEBO
BETWEEN GROUP DIFF SIGNIFICANCE
DEANER
FACTOR
Pre
Post
Diff
Pre
Post
Diff
Conduct Problem Inattentive Anxiety Tension Hyperactivity
2.26 2.79 2.37 3.23
2.26 2.38 2.24 3.00
.41 *** .13 .23** *
2.32 2.78 2.24 3.27
2.13 2.37 2.17 2.69
.18 .41 *** .07 .58
***
=
statistically significant (p
<
n.s. n.s. n.s. .10
.01) pre-post change (matched t-test)
provement in only one Factor (Impulsive Hyperactive). The two groups did not show differential treatment effects on any Factor.
peers, rated the placebo-treated patients as worse, but the deanol-treated patients about the same as a normal peer cohort.
Psychometric Test Analyses
In the Factor Scores derived from the Teacher's or Parent's Rating Scales the only factor tending to show a differential drug effect was the Teacher's Hyperactive Factor-
Statistical analyses made for all WISC subtest scores, Verbal I.Q. scores, Performance I.Q. scores, and full scale I.Q. scores revealed no statistically significant differential treatment effects. Analyses of the spelling, arithmetic, and reading scores on the WRAT and of the Porteus Maze performance also revealed no differential drug treatment. Both treatment groups showed statistically significant improvement on the Porteus Maze in their 12 week testing. While the placebo treated patients improved to a statistically significant degree on their arithmetic and reading performance on the WRAT, the deanol treated patients also showed some improvement-so that the difference between groups was not statistically significant. CONCLUSIONS AND SUMMARY
The data presented lend themselves to the interpretation that deanol acetamidobenzoate, when administered at doses of 300-500mg per day for 12 weeks to moderately disturbed hyperkinetic children (6 to 12 years of age), as seen by a psychiatrist, by teachers, and by parents to produce greater overall improvement in comparison to patients similarly treated with a placebo. While it is true that in three instances of the Global Ratings (Psychiatrists' Clinical Change, Teachers' Global Improvement, and Teachers' Rating of Attitude towards Authority) the differences did not always achieve a .05 level of significance (p = .05, .06, .07, respectively), in each instance it was the deanol patients who had shown the greater beneficial change. Parents, when asked after the 12 week treatment period to compare the children to a group of normal April/May/June, 1976
That no differential drug effects were found on the various WISC subscale scores or on the Verbal Performance or Full Scale I.Q. levels should not be surprising in a study lasting only 12 weeks. Similarly, achievement on the three scholastic components of the WRAT also requires a greater than 12 week period to show appreciable drug effects. Selection of these tests to show short-term drug effects was in retrospect not a wise choice. Special thanks are due to Ruth Boivin, R.N., and Catherine Memory, A.B., for their diligent efforts in carrying out this project. BIBLIOGRAPHY 1. Oettinger, L.: The use of deanol in the treatment of disorders of behavior in children. J. Pediat. 53(6) :671-675, 1958. 2. Oettinger, L.: Meratran: Preliminary report on a new drug for the treatment of behavior disorders in children. Dis. Nerv. Sys. 16,299-302, 1955. 3. Knobel, M.: Two-dimethylaminoethanol in behavior problems of children. Sem. Med. (B. Air.), 119(24):939-944, 196\. 4. Geller, S.J.: Comparison of a tranquilizer and a psychic energizer. lAMA, 174:481-484, 1960. 5. Udabe, R.L.: Clinical experience with 2-dimethylaminoethanol in the psychopharmacology of children. Read at the Third Latin American Congress of Psychiatry, Lima, Peru, October 25-31, 1964.
71
PSYCHOSOMATICS 6. Fleming, J.W. and Orlando, R.: Effect of deanol on attention in the mentally retarded: A reaction time method. J. New Drugs, 2:239-244, 1962. 7. Clausen, J.: The effect of Deaner (2-dimethylaminoethanol) on mentally retarded subjects. Train. Sch. Bull., 57(1):3-12,1960. 8. Jacobs, J.: A controlled trial of Deaner and a placebo in mentally defective children. Brit. J. Clill. Pract., 19(2): 77-86, 1965.
9. Kugel, R.B. and Alexander, T.: The effect of a central nervous system stimulant (deanol) on behavior. Pediatrics, 31 :651-655, 1963. 10. Conners, C.K.: Deanol and behavior disorders in children: a critical review of the literature and recommended future studies for determining efficacy. Psychopharm. Bull. (Special Issue) pp. 188-195, 1973. II. Connors, C.K.: Rating Scales for use in drug studies with children. Psychopharm. B/I/I. (Special Issue) pp. 24-84, 1973.
Proposed Amendments to the Constitution (1976) The following amendments to the constitution were reviewed and approved by the Executive Council, May 14-15, 1976 to be published for review by the membership according to constitutional procedure. The membership will be asked to pass on these amendments at the Annual Meeting of the Academy in November 1976 at Charleston, South Carolina. ARTICLE VI-Section I-Governing Body of the Academy-Executive Council 3. Nine (9) elected active Fellows--representative of regional continental areas whenever possible. 4. Four (4) past presidents (not counting the immediate past president) shall be members with vote for a period of four (4) years. This term commences at the completion of immediate past president year. ARTICLE VI-Section 2-Executive Council-Duties 8. Prescribe additional rules as necessary for the legal functioning of the Academy in any business matters or activities not otherwise provided for by the by-laws but in accordance with the constitution. 9. All executive council members must attend at least one meeting (interim or annual) per year, otherwise their elected position on the executive council for the following year may be forfeited at the discretion of the council. ARTICLE VI-Section 6-Executive Director I. There shall be an executive director who is appointed by the Executive Council of the Academy for two (2) years with stipend to be fixed by the same. ARTICLE VII-Editor of Psychosomatics I. There shall be an Editor for Psychosomatics who is elected by the Executive Council of the Academy for a period of five (5) years with stipend to be fixed by the same.
72
Volume XVII