Aust. paediat. J. (1975) 11:190-194
Overdosage - The rise and fall of tricyclic antidepressants by T.C.K. BROWN* from the Royal Children’s Hospital, Melbourne.
Brown, T.C.K. (1975). Aust. paediut. J., 11,190-194. Overdosage - The rise and fall of tricyclic antidepressants. The incidence of tricyclic antidepressant overdosage increased dramatically when these drugs were added to the N.H.S. Pharmaceutical Benefit List. The incidence has declined since the advent of safety packaging, despite an increase in the prescription rate. Most patients ingested tablets prescribed for their mothers or themselves - an alarming number of the latter being prescribed for enuresis in children under 5 years old. 7 7 % of patients were under 5 years of age.
In 1970-71 there was a dramatic increase in the number of children admitted to the Royal Children’s Hospital following overdosage of tricyclic antidepressants. Several of these children exhibited signs of serious overdosage including convulsions, coma, respiratory depression, cardiac arrhythmias and hypotension. A 13 kg child who ingested 1,000 mg of imipramine survived following intensive medical treatment, but 2 other children died. The sudden increase in the number of overdosages in children fonowed the addition of tricyclic antidepressant drugs to the general Pharmaceutical Benefit list in August, 1970 (Fig. 1). These drugs have also been increasingly taken in overdoses by adults in Melbourne (Burrows and Harari, 1974). The paper discusses briefly (1) whose tablets were taken, (2) the age of children most affected, (3) method of safety packaging, (4) subsequent events leading to a decline in the number of children with overdosage since safety packaging was introduced, and concludes with a summary of steps which can be taken to reduce the consequences of these ingestions.
Received 1 July, 1975 *Director of Anaesthesia.
1. Source of Tablets Table I summarizes whose tablets have been taken by 126 patients admitted to the Intensive Care Unit with tricyclic antidepressant overdosage. 36 children (28%) ingested their own tablets. A number of these were children in the older group who were being treated for psychiatric disturbances, but there were at least 20 who had been receiving the drug for enuresis and it is alarming that 9 of these were under 4 years of age. It is unnecessary to begin treatment of enuresis with these drugs before the age of 5 or 6 years, since enuresis ceases spontaneously in most children before this age. TABLE 1. Source of Tablets Resulting in Overdosage
Number of Patients 1966-8 1969-71 1972-74 7 12 17 2 23 15 1 6 4 Siblings 1 11 7 Grandparents 5 2 Other relatives 2 3 Neighbours, Friends 3 2 1 Rubbish bins 2
Own Mother Father
Total 36 40 11 19 7 5 5 3
- 62 51 126 13
- - - -
Overdosage 191
T.C.K. Brown
recommended that unused tablets should be flushed down the toilet or returned to a chemist. 2. Age Incidence Fig. 1. summarizes the age incidence of the children affected and indicates where serious overdosage occurred. The majority (77%) were under 5 years of age, with a preponderance aged 1 to 2 years (53%). This is a typical age distribution for childhood overdosage, e.g. 70% of accidental ingestions reported by the U.S. National Clearing House of Poison Control Centres were in children less than 5 years of age (Done et al., 1971). This is the particularly dangerous age, when small children pick things up and frequently put them in their mouth. They are too young to appreciate labels on bottles indicating that the tablets are dangerous for children. It is also difficult to teach very young children not to eat attractive tablets, especially when they see their relatives taking them o r have them prescribed for themselves. Young children are more likely to develop serious complications because fewer tablets will cause a serious overdosage.
The largest number of patients had taken their mothers’ tablets (32%), but the proportion who obtained their tablets from this source compared with those taking their own tablets has decreased from almost 2 : l in the years 1969-1971 to about 1 : l in 1972-1974. Bain and Turner (1971) reported 15 out of 20 deaths in children under 10 years of age in the U.K. between 1965-1969 had taken their mothers’ tablets, while Goel and Shanks (1974) found 60% of a series (Jan, 1972 July, 1973) had taken tablets prescribed for enuresis. 18 patients took their siblings’ tablets, which were mostly prescribed for enuresis. In the remaining cases the tablets belonged to the father, a grandparent, relatives, and in a few cases neighbours or friends. In one case a girl was given tablets by her boyfriend at school, obviously hoping for a ‘trip’. Another dangerous source of tablets was rubbish bins ( 3 cases); in 2 of these children the overdosage was serious, and one of them died. The danger of this means of disposal of old tablets is not adequately appreciated, and it is
L
40
NUMBER OF PATIENTS
TRICYCLIC ANTIDEPRFSSANT OVERDOSAGE
-
R. C . H.
-
1967
-
1974
AGE DISTRIBUTION
30Serious overdosage
20 =
4
1
2
3
4
5
AGE
6
7
- YEARS
Fig. 1
8
91011
1213
192
AUSTRALIAN PAEDIATRIC JOURNAL
3. Safety Packaging In 197 1 the incidence of tricyclic antidepressant overdosage suddenly increased when these drugs became available as an N.H.S. Phamaceutical Benefit (Brown, Dwyer and Stocks, 1971). The National Health and Medical Research Council had recognized the problems of accidental overdosage and a recommendation in 1970 stressed the need for increased education, storage of poisonous substances in places inaccessible to children, and the use of safety containers (N.H.M.R.C., 1970). A study was conducted in an inner suburban creche to compare the accessibility to children aged 2 t o 5 years of tablets in various types of containers and wrappings. There were 6 children in each age group - 2, 3, 4 and 5 year olds. 16 were Australian born and 8 were migrants. Each group of 6 were seated around a large table and instructed to obtain the ‘ Smarties’ or tablets as quickly as possible. a) Each child was presented, one at a time, with a small bottle and later a larger bottle of the type commonly dispensed by chemists; each bottle contained a ‘Smartie’. They were timed from receiving the bottle until the sweet was put into the mouth. b ) ‘Palm n’ Turn’ containers each containing 2 ‘Smarties’ were given to all the children in each age group at the same time, and the time taken until they got the ‘Smarties’ out or gave up trying. c) Four tablets in cellophane wrapping (Amphojel), and four in foil wrapping (Aspalgin), were given to each group, and the time taken until the children either unwrapped them or gave up trying.
d) The 5 year olds were also given 4 small tablets (Stelazine) wrapped in cellophane. The incentive to obtain the tablets was a ‘Smartie’ exchanged for each unwrapped tablet. The results are summarized in Table I1 which indicates the number of children in each group who succeeded in obtaining the tablets and the average time taken by these children to gain access to them. The individual times taken to unwrap 4 or 3 (circled dot or square) tablets is graphically displayed against age in Fig. 2. All but 1 child obtained the tablets in the bottles. One 2 year old would not try to get them out. The only children to gain access to the ‘Palm n’ Turn’ containers did so forcibly, using their teeth. The 4 year olds in particular were frustrated by not getting access easily. The majority gave up; the 2 year olds did not try for more than 30 seconds, while the 4 years olds tried for at least 3 minutes. Cellophane wrapping posed little difficulty, except to 4 of the 2 year olds. Foil wrapping proved more difficult, and it can be seen from Fig. 2 that most of the younger children were not able to get all the tablets out; 3 of the 2 year olds gave up within 1 minute. The findings in this study are similar to those reported in a previous study on Palm n’Turn and foil wrapping (Hosking and Williamson, 1969) which showed that Palm n’Turn containers are effective in preventing access to tablets. Breault (1974) in Windsor, Ontario, reported considerable success with Palm n’Turn child-resistant containers in that community, and this was the result of a cooperative effort by the County Medical Society, the Poison Control Centre and the local pharmacists. The objection which has been raised -
SAFETY PACKAGING
7
TABLE 2. Number Succerrful ond Average Ttme t o Gain Access t o Tablets of Those Who Were Successful ( 6 in Each Group) AGE
3 years
2 year3
4 years
5 years Agein
Av. No. Succcrs- Timc
No.
Av. Succcss- Time
ful Small bofflc Large bofflc Palm “‘Turn Cellophane Foil Cc11ophanc
55 5
fd
OCCI.
15 2
6 0
6
0
-
2
2 1
100 420
6
-
-
4
-
SCCL
I8 8 206 132 446
-
No. Av. Succcrr Time SCCS. f“l 6 6 3 6 6
~-
5 8
104 210
Au.
Av.
Succcss-
Time
f“l
$eC%
6
6 2 6 5 6
9% 9% 235 85 250 95
Year3
5t ... ‘“1 4 [
ACCESS TO WRAPPED TABLETS
.Or’
=
. 2
C
9
. 7
L
Cellophane. Foil
Cellophane -sni(lll lablei Gore updlerunwrapping
r
.1
3 Tobletr n
T.C.K. Brown
against Palm n'Turn containers is that elderly and manually incapacitated adults cannot open them, and instances have been reported where the tops were left off such containers because of difficulty in opening and closing them, and that children had consequently gained access to the tablets. Containers with safety tops of this and other similar types tend to prevent a significant proportion of children from gaining access to the tablets they contain, but children who do gain access can get to all the tablets (Done et al., 1971). Foil wrapping has the advantage over cellophane that the tablets cannot be seen, and a child's attention is therefore not drawn to them. The foil has also proved to be much more difficult for children to open in this study and the majority of the younger children gave up before getting even 4 tablets. On the basis of this and other studies, it was concluded that foil wrapping could prevent young children from gaining access to a dangerous number of tablets, especially in the age group most at risk. 4. Subsequent Action and Results In October, 1971, a dramatic increase in cases of overdosage with tricyclic antidepressant in children (Brown, Dwyer, Stocks, 1971), led the authors to recommend to the Director General of Health and the Minister of Health that all tablets of tricyclic antidepressants should be wrapped in foil. Although the Government did not issue an instruction insisting on safety packaging, it encouraged pharmaceutical manufacturers to do so, and soon afterwards tricyclic antidepressants were safety packaged. One company even suggested that their product was safer because i t was foil wrapped. Another company chose 'blister' packaging rather than foil wrapping, on the grounds that the pharmacist could check pressure of the tablet, but it also had the disadvantage that the tablets were visible to a child, and thus more likely to be attractive than when invisible in foil. All the other local manufacturers now wrap antidepressant tablets in foil strips. The result has been a marked decrease in the number of admissions with tricyclic antidepressant overdosage to the Royal Children's Hospital, despite a nearly 50% increase in the number of NHS prescriptions for these drugs in Victoria during the same time. This is dramatically demonstrated in Fig. 3. It is concluded that foil wrapping has been effective in reducing accidental overdosage in children.
Overdosage TRICYCLIC
193
ANTIDEPRESSANT OVERDOSAGE
ADMISSIONS R C H and N H S PRESCRIPTIONS IN VICTORIA
/
19(1w7 6768
\ r#
~900000
m e ewomi 71.12 72-73 73-74 1 7 5 "Ems
Fig. 3
The Standards Association of Australia is currently drawing up standard methods for testing the effectiveness of child-resistant 'closures' for therapeutic substances. Coincident with the decline in number of overdosages with tricyclic antidepressants in children, there has been decrease in the seuerity of the intoxication. Several other factors have contributed to this, including the increased use of the emetic syrup of ipecacuahna, which has been distributed to general practitioners throughout the Melbourne area. Gastric lavage and the instillation of activated charcoal to adsorb any drug remaining in the gastrointestinal tract have also been increasingly used when the evidence indicated that a significant number of tablets has been ingested. The adsorption activity is affected by the charcoal: drug ratio, and is considerably increased by using a 10: 1 rather than a 5: 1 ratio. It is important to appreciate that there is Considerable variation in adsorptive activity of different brands of charcoal; some preparations such as Merck Aktivkohle @ (Merck. Sharp & Dohme) are very effective in adsorbing tricyclic antidepressants, while some others are relatively ineffective (Oppenheim and Stewart, 1975; Dozzi, Leversha, Stewart, 1974). The clinical manifestations of severe overdosage can be effectively treated with intravenous diazepam or physostigmine for convulsions (Burks et al., 1974), intravenous sodium bicarbonate (Brown et al., 1973; Brown, 1975), physostigmine for cardiac arrhythmias (Slovis e t aL, 1971), and artificial ventilation when indicated. In conclusion, safety packaging, reduced absorption and more effective treatment of complications when they occur, have all helped to counteract what was, in 1971, 'a new menace': tricyclic antidepressant overdosage.
194 AUSTRALIAN PAEDIATRIC JOURNAL REFERENCES Bain, D.J.G., Turner, T. (1971). Imipramme Poisoning. Arch. Dis. Childh 46 : 887. Breault, HJ. (1974). Five years with five million child resistant containers. Clin Tovical. 7 : 91-96. Brown, T.C.K., Dwyer, M.E., Stocks, J.G. (1971). Antidepressant overdosage in children - a new menace. Med J. Aust. 2 : 848-851. Brown, T.C.K., Barker, G.A., Dunlop, M.E., Loughnan, P.M. (1973). The use of Sodium bicarbonate in the treatment of tricyclic antidepressant arrhythmias. Anaes. Intens. Care. 1 : 203-210. Brown, T.C.K. (1976). Tricyclic Antidepressant Overdosage: Experimedtal Studies on the Management of circulatory complications.Clin. Toxicology - in press. Burks, J.S., Walker, J.E., Rumack, B.H., Ott, J.E. (1974). Tricyclic Antidepressant Poisoning. J. Amer. Med ASSOC. 230 : 1405-1407. Burrows, G.D., Harari, E. (1974). Psychiatric aspects of drug overdosage in adults. Anaes. Intens. Care 2 : 310. Dozzi, A.M., Leversha, A., Stewart, N.F. (1974). Comparisons of Activated charcoal. Australian J. Hosp. Pharrn 4 : 40-41. Done, A.K., Jung, A.L., Wood, C., Klauber,M.R. (1971). Evaluation of Safety Packaging for the protection of children. Pediatrics. 48 : 613-628. Hosking, C.S., Williamson, A.M. (1969). The Ability of Children to obtain tablets from different containers. Med J. Aust. 2 : 793-794 Goel, K.M., Shanks, R.A. (1974). Amitriptyline and Imipramine Poisoning in Children. Brit. Med J. 1 : 261-263.
N.H.M.R.C. (1970). Report of Seventieth Session, April 1970 p. 11. Oppenheim, R.C., Stewart, N.F. (1975). Adsorption of tricyclic antidepressants by Activated Charcoal. Aust. J. Pharm. S c i 4 :-79. Slovis, T.L., Ott, J.E., Teitelbaum, D.T., Lipscomb, W. (197 1). Physostigmine therapy in acute tricyclic antidepressant poisoning. Clin Toxicol. 4 : 451457.
Acknowledgements The late Dr. John Stocks, a quiet but astute Director of Anaesthesia and Intensive Care, was a catalyst in activating the author’s work on antidepressant overdosage and supported the representations to the Government regarding safety packaging. The author would also like to thank Miss J. Van Valen for her help with the study on safety packaging, Mrs. V. James and the Photographic Department for the preparation of the illustrations and Mrs. E. Saccardo for typing the manuscript.
Correspondence to: Dr. T.C.K. Brown, Director of Anaesthesia, Royal Children’s Hospital, Flemington Road, Parkville, Victoria. 3052..
Overdosage - The rise and fall of tricyclic antidepressants by T.C.K. BROWN* from the Royal Children’s Hospital, Melbourne.
Brown, T.C.K. (1975). Aust. paediut. J., 11,190-194. Overdosage - The rise and fall of tricyclic antidepressants. The incidence of tricyclic antidepressant overdosage increased dramatically when these drugs were added to the N.H.S. Pharmaceutical Benefit List. The incidence has declined since the advent of safety packaging, despite an increase in the prescription rate. Most patients ingested tablets prescribed for their mothers or themselves - an alarming number of the latter being prescribed for enuresis in children under 5 years old. 7 7 % of patients were under 5 years of age.
In 1970-71 there was a dramatic increase in the number of children admitted to the Royal Children’s Hospital following overdosage of tricyclic antidepressants. Several of these children exhibited signs of serious overdosage including convulsions, coma, respiratory depression, cardiac arrhythmias and hypotension. A 13 kg child who ingested 1,000 mg of imipramine survived following intensive medical treatment, but 2 other children died. The sudden increase in the number of overdosages in children fonowed the addition of tricyclic antidepressant drugs to the general Pharmaceutical Benefit list in August, 1970 (Fig. 1). These drugs have also been increasingly taken in overdoses by adults in Melbourne (Burrows and Harari, 1974). The paper discusses briefly (1) whose tablets were taken, (2) the age of children most affected, (3) method of safety packaging, (4) subsequent events leading to a decline in the number of children with overdosage since safety packaging was introduced, and concludes with a summary of steps which can be taken to reduce the consequences of these ingestions.
Received 1 July, 1975 *Director of Anaesthesia.
1. Source of Tablets Table I summarizes whose tablets have been taken by 126 patients admitted to the Intensive Care Unit with tricyclic antidepressant overdosage. 36 children (28%) ingested their own tablets. A number of these were children in the older group who were being treated for psychiatric disturbances, but there were at least 20 who had been receiving the drug for enuresis and it is alarming that 9 of these were under 4 years of age. It is unnecessary to begin treatment of enuresis with these drugs before the age of 5 or 6 years, since enuresis ceases spontaneously in most children before this age. TABLE 1. Source of Tablets Resulting in Overdosage
Number of Patients 1966-8 1969-71 1972-74 7 12 17 2 23 15 1 6 4 Siblings 1 11 7 Grandparents 5 2 Other relatives 2 3 Neighbours, Friends 3 2 1 Rubbish bins 2
Own Mother Father
Total 36 40 11 19 7 5 5 3
- 62 51 126 13
- - - -
Overdosage 191
T.C.K. Brown
recommended that unused tablets should be flushed down the toilet or returned to a chemist. 2. Age Incidence Fig. 1. summarizes the age incidence of the children affected and indicates where serious overdosage occurred. The majority (77%) were under 5 years of age, with a preponderance aged 1 to 2 years (53%). This is a typical age distribution for childhood overdosage, e.g. 70% of accidental ingestions reported by the U.S. National Clearing House of Poison Control Centres were in children less than 5 years of age (Done et al., 1971). This is the particularly dangerous age, when small children pick things up and frequently put them in their mouth. They are too young to appreciate labels on bottles indicating that the tablets are dangerous for children. It is also difficult to teach very young children not to eat attractive tablets, especially when they see their relatives taking them o r have them prescribed for themselves. Young children are more likely to develop serious complications because fewer tablets will cause a serious overdosage.
The largest number of patients had taken their mothers’ tablets (32%), but the proportion who obtained their tablets from this source compared with those taking their own tablets has decreased from almost 2 : l in the years 1969-1971 to about 1 : l in 1972-1974. Bain and Turner (1971) reported 15 out of 20 deaths in children under 10 years of age in the U.K. between 1965-1969 had taken their mothers’ tablets, while Goel and Shanks (1974) found 60% of a series (Jan, 1972 July, 1973) had taken tablets prescribed for enuresis. 18 patients took their siblings’ tablets, which were mostly prescribed for enuresis. In the remaining cases the tablets belonged to the father, a grandparent, relatives, and in a few cases neighbours or friends. In one case a girl was given tablets by her boyfriend at school, obviously hoping for a ‘trip’. Another dangerous source of tablets was rubbish bins ( 3 cases); in 2 of these children the overdosage was serious, and one of them died. The danger of this means of disposal of old tablets is not adequately appreciated, and it is
L
40
NUMBER OF PATIENTS
TRICYCLIC ANTIDEPRFSSANT OVERDOSAGE
-
R. C . H.
-
1967
-
1974
AGE DISTRIBUTION
30Serious overdosage
20 =
4
1
2
3
4
5
AGE
6
7
- YEARS
Fig. 1
8
91011
1213
192
AUSTRALIAN PAEDIATRIC JOURNAL
3. Safety Packaging In 197 1 the incidence of tricyclic antidepressant overdosage suddenly increased when these drugs became available as an N.H.S. Phamaceutical Benefit (Brown, Dwyer and Stocks, 1971). The National Health and Medical Research Council had recognized the problems of accidental overdosage and a recommendation in 1970 stressed the need for increased education, storage of poisonous substances in places inaccessible to children, and the use of safety containers (N.H.M.R.C., 1970). A study was conducted in an inner suburban creche to compare the accessibility to children aged 2 t o 5 years of tablets in various types of containers and wrappings. There were 6 children in each age group - 2, 3, 4 and 5 year olds. 16 were Australian born and 8 were migrants. Each group of 6 were seated around a large table and instructed to obtain the ‘ Smarties’ or tablets as quickly as possible. a) Each child was presented, one at a time, with a small bottle and later a larger bottle of the type commonly dispensed by chemists; each bottle contained a ‘Smartie’. They were timed from receiving the bottle until the sweet was put into the mouth. b ) ‘Palm n’ Turn’ containers each containing 2 ‘Smarties’ were given to all the children in each age group at the same time, and the time taken until they got the ‘Smarties’ out or gave up trying. c) Four tablets in cellophane wrapping (Amphojel), and four in foil wrapping (Aspalgin), were given to each group, and the time taken until the children either unwrapped them or gave up trying.
d) The 5 year olds were also given 4 small tablets (Stelazine) wrapped in cellophane. The incentive to obtain the tablets was a ‘Smartie’ exchanged for each unwrapped tablet. The results are summarized in Table I1 which indicates the number of children in each group who succeeded in obtaining the tablets and the average time taken by these children to gain access to them. The individual times taken to unwrap 4 or 3 (circled dot or square) tablets is graphically displayed against age in Fig. 2. All but 1 child obtained the tablets in the bottles. One 2 year old would not try to get them out. The only children to gain access to the ‘Palm n’ Turn’ containers did so forcibly, using their teeth. The 4 year olds in particular were frustrated by not getting access easily. The majority gave up; the 2 year olds did not try for more than 30 seconds, while the 4 years olds tried for at least 3 minutes. Cellophane wrapping posed little difficulty, except to 4 of the 2 year olds. Foil wrapping proved more difficult, and it can be seen from Fig. 2 that most of the younger children were not able to get all the tablets out; 3 of the 2 year olds gave up within 1 minute. The findings in this study are similar to those reported in a previous study on Palm n’Turn and foil wrapping (Hosking and Williamson, 1969) which showed that Palm n’Turn containers are effective in preventing access to tablets. Breault (1974) in Windsor, Ontario, reported considerable success with Palm n’Turn child-resistant containers in that community, and this was the result of a cooperative effort by the County Medical Society, the Poison Control Centre and the local pharmacists. The objection which has been raised -
SAFETY PACKAGING
7
TABLE 2. Number Succerrful ond Average Ttme t o Gain Access t o Tablets of Those Who Were Successful ( 6 in Each Group) AGE
3 years
2 year3
4 years
5 years Agein
Av. No. Succcrs- Timc
No.
Av. Succcss- Time
ful Small bofflc Large bofflc Palm “‘Turn Cellophane Foil Cc11ophanc
55 5
fd
OCCI.
15 2
6 0
6
0
-
2
2 1
100 420
6
-
-
4
-
SCCL
I8 8 206 132 446
-
No. Av. Succcrr Time SCCS. f“l 6 6 3 6 6
~-
5 8
104 210
Au.
Av.
Succcss-
Time
f“l
$eC%
6
6 2 6 5 6
9% 9% 235 85 250 95
Year3
5t ... ‘“1 4 [
ACCESS TO WRAPPED TABLETS
.Or’
=
. 2
C
9
. 7
L
Cellophane. Foil
Cellophane -sni(lll lablei Gore updlerunwrapping
r
.1
3 Tobletr n
T.C.K. Brown
against Palm n'Turn containers is that elderly and manually incapacitated adults cannot open them, and instances have been reported where the tops were left off such containers because of difficulty in opening and closing them, and that children had consequently gained access to the tablets. Containers with safety tops of this and other similar types tend to prevent a significant proportion of children from gaining access to the tablets they contain, but children who do gain access can get to all the tablets (Done et al., 1971). Foil wrapping has the advantage over cellophane that the tablets cannot be seen, and a child's attention is therefore not drawn to them. The foil has also proved to be much more difficult for children to open in this study and the majority of the younger children gave up before getting even 4 tablets. On the basis of this and other studies, it was concluded that foil wrapping could prevent young children from gaining access to a dangerous number of tablets, especially in the age group most at risk. 4. Subsequent Action and Results In October, 1971, a dramatic increase in cases of overdosage with tricyclic antidepressant in children (Brown, Dwyer, Stocks, 1971), led the authors to recommend to the Director General of Health and the Minister of Health that all tablets of tricyclic antidepressants should be wrapped in foil. Although the Government did not issue an instruction insisting on safety packaging, it encouraged pharmaceutical manufacturers to do so, and soon afterwards tricyclic antidepressants were safety packaged. One company even suggested that their product was safer because i t was foil wrapped. Another company chose 'blister' packaging rather than foil wrapping, on the grounds that the pharmacist could check pressure of the tablet, but it also had the disadvantage that the tablets were visible to a child, and thus more likely to be attractive than when invisible in foil. All the other local manufacturers now wrap antidepressant tablets in foil strips. The result has been a marked decrease in the number of admissions with tricyclic antidepressant overdosage to the Royal Children's Hospital, despite a nearly 50% increase in the number of NHS prescriptions for these drugs in Victoria during the same time. This is dramatically demonstrated in Fig. 3. It is concluded that foil wrapping has been effective in reducing accidental overdosage in children.
Overdosage TRICYCLIC
193
ANTIDEPRESSANT OVERDOSAGE
ADMISSIONS R C H and N H S PRESCRIPTIONS IN VICTORIA
/
19(1w7 6768
\ r#
~900000
m e ewomi 71.12 72-73 73-74 1 7 5 "Ems
Fig. 3
The Standards Association of Australia is currently drawing up standard methods for testing the effectiveness of child-resistant 'closures' for therapeutic substances. Coincident with the decline in number of overdosages with tricyclic antidepressants in children, there has been decrease in the seuerity of the intoxication. Several other factors have contributed to this, including the increased use of the emetic syrup of ipecacuahna, which has been distributed to general practitioners throughout the Melbourne area. Gastric lavage and the instillation of activated charcoal to adsorb any drug remaining in the gastrointestinal tract have also been increasingly used when the evidence indicated that a significant number of tablets has been ingested. The adsorption activity is affected by the charcoal: drug ratio, and is considerably increased by using a 10: 1 rather than a 5: 1 ratio. It is important to appreciate that there is Considerable variation in adsorptive activity of different brands of charcoal; some preparations such as Merck Aktivkohle @ (Merck. Sharp & Dohme) are very effective in adsorbing tricyclic antidepressants, while some others are relatively ineffective (Oppenheim and Stewart, 1975; Dozzi, Leversha, Stewart, 1974). The clinical manifestations of severe overdosage can be effectively treated with intravenous diazepam or physostigmine for convulsions (Burks et al., 1974), intravenous sodium bicarbonate (Brown et al., 1973; Brown, 1975), physostigmine for cardiac arrhythmias (Slovis e t aL, 1971), and artificial ventilation when indicated. In conclusion, safety packaging, reduced absorption and more effective treatment of complications when they occur, have all helped to counteract what was, in 1971, 'a new menace': tricyclic antidepressant overdosage.
194 AUSTRALIAN PAEDIATRIC JOURNAL REFERENCES Bain, D.J.G., Turner, T. (1971). Imipramme Poisoning. Arch. Dis. Childh 46 : 887. Breault, HJ. (1974). Five years with five million child resistant containers. Clin Tovical. 7 : 91-96. Brown, T.C.K., Dwyer, M.E., Stocks, J.G. (1971). Antidepressant overdosage in children - a new menace. Med J. Aust. 2 : 848-851. Brown, T.C.K., Barker, G.A., Dunlop, M.E., Loughnan, P.M. (1973). The use of Sodium bicarbonate in the treatment of tricyclic antidepressant arrhythmias. Anaes. Intens. Care. 1 : 203-210. Brown, T.C.K. (1976). Tricyclic Antidepressant Overdosage: Experimedtal Studies on the Management of circulatory complications.Clin. Toxicology - in press. Burks, J.S., Walker, J.E., Rumack, B.H., Ott, J.E. (1974). Tricyclic Antidepressant Poisoning. J. Amer. Med ASSOC. 230 : 1405-1407. Burrows, G.D., Harari, E. (1974). Psychiatric aspects of drug overdosage in adults. Anaes. Intens. Care 2 : 310. Dozzi, A.M., Leversha, A., Stewart, N.F. (1974). Comparisons of Activated charcoal. Australian J. Hosp. Pharrn 4 : 40-41. Done, A.K., Jung, A.L., Wood, C., Klauber,M.R. (1971). Evaluation of Safety Packaging for the protection of children. Pediatrics. 48 : 613-628. Hosking, C.S., Williamson, A.M. (1969). The Ability of Children to obtain tablets from different containers. Med J. Aust. 2 : 793-794 Goel, K.M., Shanks, R.A. (1974). Amitriptyline and Imipramine Poisoning in Children. Brit. Med J. 1 : 261-263.
N.H.M.R.C. (1970). Report of Seventieth Session, April 1970 p. 11. Oppenheim, R.C., Stewart, N.F. (1975). Adsorption of tricyclic antidepressants by Activated Charcoal. Aust. J. Pharm. S c i 4 :-79. Slovis, T.L., Ott, J.E., Teitelbaum, D.T., Lipscomb, W. (197 1). Physostigmine therapy in acute tricyclic antidepressant poisoning. Clin Toxicol. 4 : 451457.
Acknowledgements The late Dr. John Stocks, a quiet but astute Director of Anaesthesia and Intensive Care, was a catalyst in activating the author’s work on antidepressant overdosage and supported the representations to the Government regarding safety packaging. The author would also like to thank Miss J. Van Valen for her help with the study on safety packaging, Mrs. V. James and the Photographic Department for the preparation of the illustrations and Mrs. E. Saccardo for typing the manuscript.
Correspondence to: Dr. T.C.K. Brown, Director of Anaesthesia, Royal Children’s Hospital, Flemington Road, Parkville, Victoria. 3052..
