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The Use of Psychotropic Medication in Preschoolers: Some Recent Developments

K Minde, MD, FRCPC¹

Objective: To provide an overview of the use of psychotropic drugs in preschoolers.

Method: Literature review.

Results: Although controversy persists, the evidence suggests that preschool children are being given an increasing number of psychotropic drugs, especially by general practitioners and pediatricians.

Conclusion: There is an urgent need to formally evaluate the efficacy of psychotropic medication for young children.

(Can J Psychiatry1998;43:571­575)

Key Words: psychotropic drugs, preschooler

The availability and documented efficacy of pharmacological agents in the treatment of an increasing number of psychiatric conditions have contributed significantly to the remedicalization of adult psychiatry during the past 2 decades. The range of new medications has been beneficial to many of our patients and has strengthened our profession.

Child psychiatry has benefited less from these recent developments, since fewer of the new drugs have been helpful to children. In fact, in a review of psychopharmacological treatments for children, Werry stated that, with the exception of drugs for early-onset adult-type psychiatric disorders, there was little evidence that any available psychopharmacological agent was beneficial for the long-term treatment of psychiatric disorders in children (1). However, the introduction of selective serotonin reuptake inhibitors (SSRIs) has made available an entirely new class of medications with potentially important applications for the treatment of major psychiatric disorders for at least some school-age children and adolescents (2,3).

Conversely, there is general agreement that psychotropic drugs are of little proven value in the management of disturbed infants and preschoolers (4), although soothing syrups containing opium have been prescribed for babies who had trouble falling asleep since around 1000 AD in Avicenna (5) and were marketed in the 1870s as Godfrey's Cordial. This has been documented in the past by well-designed double-blind studies in which preschool children who were diagnosed as autistic (6), hyperactive (7), aggressive (8), or sleep-disturbed (9) were given specific psychotropic medications for a brief period. The authors of these studies reported a decrease in isolated symptoms in children on active medication; however, they also noted that changes were either short-lived or associated with so many side effects that the medication was discontinued in virtually all cases as soon as the acute drug trial was terminated.

Despite these data, there is substantial evidence that an increasing number of infants and preschool children are currently given psychotropic medications for a variety of behaviour problems (10,11), necessitating an examination of this development.

This paper is 1 of 4 communications on this issue. It will review the literature on this topic and place the findings into the context of present-day child psychiatric care. The 3 subsequent papers will explore the topic in more detail by identifying the clinical efficacy and safety of contemporary psychotropic drugs in preschoolers (12), examining their possible impact on human brain development (13), and discussing ethical considerations and clinical guidelines for psychopharmacological interventions in young children (14).

Who uses psychotropic drugs in preschool children?

Both physicians and nonphysicians provide psychotropic medications to preschool children. Among physicians, one finds general practitioners (GPs), pediatricians, and psychiatrists to be most frequently involved in this practice.

Adams'study of the prescribing patterns of 100 GPs and 28 consultant child psychiatrists during a 3-month period in a circumscribed area of England provides some interesting data (15). Based on a questionnaire returned by 83% of the GPs and 79% of the consultants, she found that 73% of the GPs and 46% of the consultants stated that they prescribed hypnotics to preschool children. Further, 37% of the GPs and 18% of the consultants prescribed antidepressants, primarily for the treatment of enuresis. Sixty-one of the GPs (73%) and 16 of the 22 child psychiatrists (72%) had prescribed any psychotropic medication for children aged under 18 years during the period covering her investigation.

Trott and colleagues (16) investigated the prescribing habits of all 787 registered GPs, 34 pediatricians, and 35 psychiatrists in a German state. The response rate was 55%. On average, each pediatrician, GP, and psychiatrist treated respectively 27.5, 70.5, and 1.8 children with psychiatric symptomatology every month. This included 0.3% of all children aged under 2 years and 20.4% of those aged 2 to 5 years.

The 5 most common problems in preschoolers which were treated with or without medication by these physicians and the 5 most frequently prescribed drugs are summarized in Table 1.

^aInformation from Trott and others (16).

As Table 1 indicates, there was little difference between the symptoms treated pharmacologically and those managed by advice alone, although possible variations in symptom severity were not specified. Moreover, the types of medications given to these youngsters are somewhat problematic. For example, there is no evidence that enuresis in preschoolers responds to imipramine or that chlorpromazine is helpful for any of the most common disorders described by the authors. Trott and others also state that all the pediatricians but only 66% of the GPs and 54% of the psychiatrists prescribed psychotropic drugs to children, although some may have done so only for older children (16).

The study also provides data on the average duration of the psychotropic drug treatment by specialty. GPs prescribed drug treatment for an average of 8.1 weeks, pediatricians for 9.5 weeks, and psychiatrists for 14.8 weeks. The data do not allow us to distinguish the duration of pharmacotherapy for different conditions, age groups, or pharmacological agents.

There is also evidence that infants and toddlers are supplied with psychotropic medications by nonphysicians. For example, Shannon and colleagues (17) describe how 4.6% of 1680 consecutive urine drug screens in children, performed at the Boston Children's Hospital, were positive for cocaine, while 1% of the screens were positive for ethanol or benzodiazepine of opiates and cocaine. Of greater concern is that 13% of these positive drug screens were in children younger than 7 months of age.

Schwartz and colleagues in a clinical paper (18) described a study of 82 middle-class teenagers (aged 14 to17 years) who took marijuana regularly and also baby-sat at least twice a month. Eleven percent of these adolescents reported that they regularly calmed the infants and toddlers they baby-sat by blowing marijuana smoke into their nostrils, while older toddlers were given beer to stop crying. They claimed that they had done so to approximately 25 toddlers on 1 to 15 occasions and that the parents had never discovered this. While these data need to be confirmed, the fact that these youngsters often baby-sat in pairs and that both partners independently reported the same events gives this behaviour some stark and troublesome reality.

Which drugs are prescribed in preschool children and why?

There are 2 sources of information about these questions: 1) published epidemiological surveys and 2) the therapy patterns of selected groups of physicians, monitored by Intercontinental Medical Statistics (IMS), an international market research service to the global health care industry.

The most detailed epidemiological survey comes from Kopferschmitt and colleagues (19) in France, who reported on the medical examinations of all 11 595 children enrolled in primary school in Strasbourg and its surrounding countryside for the 1989­90 school year. The survey included 609 schools in 440 communities and involved 26 school physicians. The physicians examined 97.2% (N = 11 274) of all newly enrolled children and interviewed 1 parent of each child.

Results indicated that, overall, 12.1% of all children were receiving psychotropic medications at the time of school entry (N = 1367). However, in some communities, 40% to 65% of all school entries were taking medication, while in the suburb of Strasbourg only 5.2% of children took psychotropic medications. Twelve percent (N = 164) of the overall group receiving medications were taking 2 drugs, and 2% (N = 27) were taking 3 or more different drugs.

The age at which these medications were started was as follows: less than 1 year: 2%
1 year: 34%
2 years: 21%
3 years: 5%
4 years: 14%
5 years: 12%
6 years: 2%

The length of time for which the drugs were given every day and the time for which they were given less regularly can be seen in Table 2.

Table 2.  Duration and frequency  medication was taken by childrena
Duration (years)	Daily (%)	Irregular (%)
< 1	20	22
1	27	34
2	12	26
3	4	13
4	3	4
5	2	10

^aInformation from Kopferschmitt and others (19).

Table 2 indicates that most children had received their medication for 2 years or less on a daily basis (total of 59%), while 27% of the children had taken medications for between 3 to 5 years on an irregular basis. This suggests that many children received medication on a daily basis for 2 years and then switched to a less regular dose schedule. Only 2.7% (37 out of 1369) of the children had totally discontinued their medication by the time of school entry. The prescribed medications are detailed on Table 3.

Table 3.  Medications prescribeda
	N
Brome and calcium	26
Magnesium	56
Phenothiazines	634
Promethazine	758
Valium and other benzodiazepines	47

^aInformation from Kopferschmitt and others (19).

Chlorpromazine and its derivatives were most often prescribed, followed by magnesium and benzodiazepines. All these drugs have numerous side effects and are not known to have established clinical relevance in preschoolers.

In Kopferschmitt's study, the parents most often received psychotropic medications to help manage their children or make them sleep better. Yet only 1% of the children were described as having any actual difficulty sleeping at the time of their examination, although they most likely slept poorly when the medications were initially prescribed.

The other source of estimatied drug use comes from IMS (20). The methodology of IMS is to sample 652 office-based physicians in Canada and 5250 in the United States (US) stratified by province or state and specialty. Each selected physician reports on every patient contact and every drug recommendation in a prearranged 2-day period 4 times yearly, and the numbers are then statistically corrected to include all the physicians in the country. It should be noted that this methodology does not allow assessment of whether or not the prescribed medications were actually bought and consumed or how many refills were obtained. In addition, low numbers of recommendations (less than 35 000 per year in Canada and 100 000 per year in the US) are not statistically reliable and are more prone to reflect idiosyncratic practice patterns.

Tables 4 and 5 provide the estimated drug recommendations of some major antidepressants, tranquilizers, and stimulants for children aged under 6 years and 6 to 12 years. It should be noted that a drug recommendation or prescription is always for a certain quantity of pills (85 pills in the case of methylphenidate in Canada in 1997). This implies that the prescriptions of other major drug groupings for which we do not have data on the total number of pills sold for that age-group per year may conservatively have to be multiplied by 20 to 50 to reflect the actual number of pills given to children.

Table 4.  Estimated drug recommendations by office-based physicians in Canadaa
Drug	Age (years)	1993	1996	1997
Methylphenidate
	0 to 5	4 000b	20 000b	12 000b
	6 to 12	146 000b	364 000	434 000
Hydroxyzine
	0 to 5	30 000b	31 000b	39 000
	6 to 12	45 000	48 000	50 000
Fluoxetine and paroxetine
	6 to 12	--	20 000b	34 000b

^aInformation from Intercontinental Medical Statistics (20).
^bThe precision is low for these numbers.

Table 5.  Estimated drug recommendations by office-based physicians in the United Statesa
Drug	Age (years)	1993	1996	1997
Methylphenidate
	0 to 5	168 000	211 000	172 000
	6 to 12	2 631 000	3 369 000	3 521 000
Hydroxyzine
	0 to 5	441 000	358 000	257 000
	6 to 12	403 000	306 000	297 000
Sertraline
	0 to 5	12 000b	--	17 000b
	6 to 12	20 000b	73 000b	155 000
Fluoxetine and paroxetine
	0 to 5	3 000b	12 000b	33 000b
	6 to 12	121 000	202 000	258 000

aInformation from Intercontinental Medical Statistics (20).
^bThe precision is low for these numbers.

As Tables 4 and 5 indicate, the recommended use of methylphenidate by school-age children in Canada has immensely increased (from 146 000 to 434 000 prescriptions in 4 years, that is, a 300% increase). If we consider that in 1993 each drug recommendation was for 70 pills, while in 1997 the number of pills per recommendation was 85 pills, we can see that the actual consumption of methylphenidate tablets increased from 12.2 to 42.0 million tablets in 4 years. If we consider that Canada has about 2.75 million children aged 6 to 12 years, we in fact prescribe about 15 methylphenidate tablets for each Canadian child in that age-group per year. This does not include long-acting preparations. Likewise, using the same formula, approximately 1 million tablets of methylphenidate were given to children aged under 6 years in 1997, although these numbers are less precise. Fluoxetine and paroxetine were given primarily to school-age children and were prescribed as antidepressant and antianxiety drugs. The number of recommendations for these drugs for children aged under 6 years was too low to be statistically meaningful. Other agents prescribed for the under 6 years age-group were imipramine, dextroamphetamine, thioridazine, lorazepam, and loxapine, mostly as a sedative or antidepressant or for unstated reasons. The numbers were small and unreliable.

Data from the US are somewhat different. There was less of an increase in the drug recommendations for methylphenidate between 1993 and 1997 for children aged 6 to 12 years (about 35%) and an actual decrease for preschoolers. Use of fluoxetine and paroxetine more than doubled in the US but showed little change in Canada. However, there was a very large increase in the recommendations for sertraline, a drug which was not mentioned by the IMS in their Canadian statistics.

Discussion

There is no question that psychotropic drug use in young children has increased significantly over the past decade. The reviewed studies indicate a substantial use of major tranquilizers in Europe and of SSRIs and stimulants in North America. It is puzzling that the use of methylphenidate in school-age children has increased much more in Canada than in the US. This is in contrast to the use of SSRIs, which seems to have increased in the US. One possible explanation for this phenomenon is that health care professionals in Canada follow US trends, that is, they still hope to help children by prescribing more methylphenidate, while our US colleagues have already recognized that this is unrealistic. If this suggested explanation is valid, one might expect to see a commensurate increase in drug recommendations for SSRIs in Canada during the upcoming years. A similar phenomenon may occur with the use of hydroxyzine, for which Canadian data show no change in the past 5 years, while far fewer recommendations for these drugs are now given in the US. In addition, there is good evidence that GPs and pediatricians are more likely than child psychiatrists to prescribe psychotropic medication for children, although there is no evidence that these medications are helpful for difficulties commonly seen in this age-group. Sleep problems (9), feeding disorders (21), or common general behaviour problems do not respond to these medications (22). Moreover, these drugs have never been evaluated for their safety in children, and none has been recommended for use in this population by regulating agencies. The available data also do not tell us anything about the dosages given to children.

Finally, there are a few reports indicating some accidental ingestion of psychotropic drugs by young children administered by either drug-addicted parents or thoughtless teenagers. There are few systematic data on this problem, but the evidence suggests that Godfrey's Cordial is alive and well at the end of the twentieth century.

The need for controls is obvious, and some are already in place in the US, where a strong movement exists to have psychotropic drugs formally evaluated for the use of children by the Food and Drug Administration. There is an obvious need to create similar directives in Canada to protect young children from being exposed to useless and potentially harmful medications.

Clinical Implications Psychotropic drugs should be used in preschoolers only as a last resort and for brief periods. Health care professionals should be aware that young children may have been given psychotropic drugs and investigate. Stimulants are the psychotropic drugs most frequently prescribed for preschoolers. Limitations Most publications examining the use of psychotropic drugs in preschoolers are self reports and are based on data of uncertain empirical value. Most articles reviewed in this paper were published 3 or more years ago and may not fully reflect current practice. The actual toxicity to preschoolers of some psychotropic drugs has not yet been established.

References

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17. Shannon M, Lacouture PG, Roa J, Woolf A. Cocaine exposure among children seen at a pediatric hospital. Pediatrics 1989;83:337­42.

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Résumé

Objectif : Offrir un aperçu de l'utilisation des psychotropes chez les enfants d'âge préscolaire.

Méthode : Analyse documentaire.

Résultats : Bien que la controverse demeure, les témoignages suggèrent que surtout les omnipraticiens et les pédiatres administrent un nombre croissant de psychotropes aux enfants d'âge préscolaire.

Conclusion : Il est urgent d'évaluer officiellement l'efficacité d'une médication psychotrope chez de jeunes enfants.