-Lisa Freeman

   The subject of psychotropic medication prescriptions for preschool children has
received its fair share of attention in the mass media since last month's publication of
two simultaneous articles on the topic in the Journal of the American Medical
Association.^1,2 The news coverage has primarily focused on the prescription of
methylphenidate (Ritalin) to treat attention-deficit/hyperactivity disorder (ADHD) in
children aged 2-4 years old, a prescribing practice which more than doubled in
frequency from 1991-1995. But there are several aspects of the literature on this
subject which have not been reported in news "sound bites", and which are worthy of
mention.

   Psychotropic drugs other than psychostimulants (like Ritalin) are also being
prescribed to large numbers of toddlers, often in combination with other drugs.
In a sample drawn from Michigan Medicaid data, out of 223 children aged three years
old and younger who were diagnosed with ADHD, about 60% were given a prescription
for psychotropic drugs, and nearly half of those were prescribed two or more drugs.³

   Aside from Ritalin, one of the most frequently prescribed drugs appears to be
clonidine, an anti-hypertension medication initially used on children to alleviate the
insomnia or other sleep disturbances often caused by Ritalin and other ADHD
medications. However, clonidine is now used by many doctors to treat sleep
disturbances alone, or for aggressive or defiant behavior with or without accompanying
ADHD (although its effectiveness for this use is unproven and seems to be in doubt).⁴
The usage of clonidine by preschool children increased more than any other drug
reported in Zito et al., despite the severe side effects that may occur even when used
by adults. Allergic reactions, cardiac abnormalities or failure, drying of membranes
(including eyes), nausea and loss of appetite are some of the side effects listed in the
Physicians' Desk Reference⁵ and reported in medical literature. Withdrawal
symptoms can be extreme, and fatalities have been reported to have resulted from
children missing a single dose.⁶

   Another class of drugs frequently used to treat young children for ADHD, as well as
other disorders, is the tricyclic antidepressent group (TCAs), which includes drugs
such as Elavil. TCAs initially provided a longer-acting agent for ADHD than Ritalin and
reduced the need for repeated dosing (before the introduction of an "extended-release"
form of Ritalin).⁷ The tricyclic category of drugs is also associated with cardiac
problems, as well as tinnitus, seizures, increased ocular pressure, vomiting, diarrhea,
and anorexia. Particularly troubling with this class of drugs is the risk of tardive
dyskinesia, a disabling, irreversable neuromuscular disorder which appears after years
of drug treatment.⁸ If these drugs begin to be administered at preschool ages and
continue to be taken throughout the school years, the risk of tardive dyskinesia is
greatly increased.

   The use of TCAs on children has recently been decreasing, but another class of drugs
appears to have filled the void: selective serotonin reuptake inhibitors (SSRIs), the
class of drugs including Prozac. While these drugs seem to be safer than TCAs, they
can cause many of the same side effects, plus the added risk of sudden, severe allergic
reactions.⁹ Additionally, there is little evidence that this class of drugs is even
effective in treating the problems for which they are prescribed.¹⁰ Yet a review of
information from the Intercontinental Medical Statistics Study revealed a tenfold
increase in SSRI prescriptions to preschoolers in the United States between 1993 and
1997.¹¹

   Many other psychotropic drugs are prescribed for children, but the only other drugs
that appear to be prescribed with frequency are the neuroleptics, the class of drugs
including Haldol and Thorazine. These are generally prescribed for short-term relief
of relief of nausea or temporary control of behavior, or at very low doses to treat
Tourette's Syndrome. Long-term use is commonly limited to autistic children who
display uncontrollable self-destructive behaviour, although long-term use for general
behavior control is often seen in institutional settings. Neuroleptic drugs do cause
Parkinson-type motor disorders and tardive dyskinesia when taken for many years.¹²

   Risks accompany the use of any medication, and physicians are generally trained to
consider the "risk/benefit" ratio in each situation before prescribing or recommending
a drug.¹³ But when an underage patient is brought into the doctor's office by caretakers
seeking treatment for the child's behavioral problems, one must ask, who stands to
benefit from the treatment? For example, in the case of sleeping disorders, it may be
the caretakers who are the sole beneficiaries of the treatment, which prevents child
care responsibilities from interfering with their own schedules. A child may also
benefit indirectly if caretakers are well-rested and free of resentments, but is drugging
a child really the best way to accomplish this?

   Almost all psychotropic drug prescriptions for preschool children are
"off-label", that is, prescribed for populations for which no standards of dosage
have been established, or for conditions for which the product is not indicated
and has not been tested.¹⁴ Ritalin, for example, is not approved by the FDA for use
by children under age six. Elavil is "not recommended ... for patients under 12 years of
age." And neither Prozac nor Clonidine are approved for pediatric use at all.¹⁵ But
doctors are not constrained by these FDA recommendations; in the case of children
below the recommended minimum ages, they may extrapolate the dosage amounts
based on adult dosage and the weight of their patient.¹⁶

   Medications may also be prescribed for conditions not indicated for its usage. Prozac,
for example, is only indicated for treatment of depression and obsessive-compulsive
disorder, and Elavil is only indicated for treating depression. In the most recent edition
of the Physicians' Desk Reference, clonidine is only listed as an anti-hypertension
drug.¹⁷ Yet doctors have experimented with these and many other medications -- not in
clinical trials, but on a patient-by-patient basis -- to treat separation the anxiety, crying,
bedwetting, and sleep disorders that are commonly associated with preschool-age
children.¹⁸

   Some children's behavior that physicians attempt to modify with drug treatment are not
even considered true disorders by the psychiatric community. For example, one study
reported the treatment of 2-4 year olds with imipramine (a TCA indicated for
depression) for their bedwetting problem,¹⁹ but bedwetting is not even considered a
disorder worthy of treatment when it occurs before the age of five.²⁰

   Psychotropic drugs are being prescribed to children even younger than two
years of age. In the study of pharmacy records done by Zito et al., the researchers
were unable to investigate the use of medications on children younger than two
because years of birth in Medicaid records were recorded in two-digit fields, making it
impossible to determine whether a patient was 1 or 100 years old.²¹ However,
according to FDA marketing data, around 3000 prescriptions for Prozac were issued in 1994 for children younger than one year old.²²

   Little else is known about prescribing patterns of psychotropic drugs to infants in
North America, because publications which record such patterns use age groupings,
with ages 0-5 considered a single group. Some studies in Europe, however, have shown
that starting even prolonged psychotropic drug use at age one or earlier is not unheard
of.²³

   While warnings exist against the use of psychotropics by pregnant women to avoid
exposing the unborn child to the chemicals, many of the same agents may be
administered to an infant by doctors practically as soon as it leaves the womb. Aside
from the possibility of occurrence of listed side-effects, giving powerful drugs to
infants is especially worrisome in terms of their effects on the developing brain.
While an infant's ability to metabolize drugs (thus avoiding poisoning and liver
damage) is similar to that of adults, the brain's synaptic structure, on which these drugs
work, does not achieve its maximum density until about the age of three.²⁴ Rodent
studies of the effects of psychotropics given in this stage of development have
indicated the possibility of permanent deficits in brain function,²⁵ but no comparable
studies have been done on human subjects.

   Treatment of young children with psychotropic drugs is, more often than not,
the only treatment provided. Psychiatric guidelines make it clear that drug treatment
does not cure psychological disorders or problems, but only helps to control
symptoms,²⁶ and that psychosocial intervention and therapy are necessary to help
patients understand and manage their own behaviors, thoughts and feelings. However,
the evidence indicates that fewer than half of preschool children receiving drugs for
ADHD, at least in Medicaid populations, were given psychotherapy as well.²⁷

   The extent to which psychological disorders are caused by biological factors has long
been debated, and remains unresolved. One can argue that rebellious, defiant, or
aggressive behavior can be, in many cases, a healthy response to oppressive or
provocative circumstances, and that it may be the environment, not the individual, that
is in need of modification. Even psychiatric professionals who accept biological
determinism as a valid behavioral model generally recognize the influence of a
person's environment on their behavior, and realize that the individual patient may not
be the only one in need of treatment. Family therapy is often recommended to help
families find constructive ways to express their feelings and resolve their differences.
But when children are too young to communicate their experiences, physicians
probably do not generally view psychotherapy, for the patient or other family
members, to be useful. They have no way of investigating the accuracy of the parents'
perceptions, and must simply rely on the assumption that the parents are representing
the best interest of the child.

   The use of psychotropic drugs on preschool (as well as school-age) children
appears to be more prevalent among Medicaid populations -- in which poor and
non-white families, as well as children in foster care, are overrepresented --
than among HMO groups. Zito et al. also found a geographic difference between two
Medicaid groups, which revealed significantly more dispensing of the most common
psychotropics to preschoolers in the Midwest group than in the Mid-Atlantic group.²⁸

   Is there a substantial difference in the children in these three groups that warrants
different levels of drug treatment? It is more likely that policy differences between the
health care groups account for the difference in time and money invested in kids.
Dispensing a drug to satisfy a parent or caretaker is a quick fix, which may be exactly
what is desired by parents, physicians, and funding agencies which lack the resources
to pursue more expensive therapeutic options.

   Virtually no controlled testing of psychotropic drugs has been carried out
which can apply to preschool children.²⁹ Although ethical issues of consent to
receive a drug and potential harm which can be caused by untested agents has been a
barrier to clinical trials involving children, these concerns have apparently not deterred
physicians from prescribing "off-label" to individual pediatric patients. But the major
source of reluctance to conduct clinical trials on children exhibiting symptoms of
psychological disorders seems to be the necessity of a matched placebo group,
consisting of children who will be, for the duration of the trial, deprived of
medications which might have benefitted them.

   With no clinical trials to determine the effectiveness of psychotropic drugs for young
children, doctors rely on case reports in medical journals, as well as results reported
by teachers and caretakers. While one may expect the effectiveness of a drug in
modifying a "problem" behavior to be accurately reported, the total effect of a drug on
a small child's well-being can only be guessed at. Even if the child is able to describe
the effects or side-effects they experience, this report is likely to be conveyed to the
doctor by a caretaker, who (intentionally or unintentionally) may minimize or
exaggerate the effects of the drug.

   Psychotropic drug use on preschoolers is not confined to the United States.
Studies in Canada, England, France and Germany have also shown increases in this
practice. One survey of school children in 609 primary schools around Strasbourg,
France revealed that 12.1% of the children enrolled were receiving at least one
psychotropic drug at the time of school entry, 36% of whom had started receiving the
drugs at the age of one or younger.³⁰

   The use of medications to alter our thoughts, feelings and behaviors is controversial.
Questions can be raised about whether personality differences among individuals, even
when they may cause conflicts or interfere with an individuals own goals and desires,
might have advantages that are not immediately apparent. One can point to famous
scientists, artists, musicians and writers who suffered from psychological disorders,
and wonder whether they would have been as creative or brilliant had they been treated
with modern medicines. On the other hand, there is no denying that many individuals
have found psychotropic drug treatment to be enormously helpful in reducing their
unwanted symptoms. The decision should be up to the individual patient.

   In the case of pediatric medication, the choice is not made by the patient. The initial
complaint to the doctor, the choice of the drug, and the assessment of its effectiveness
are all made by people other than the patient. If a drug is being used on a child for
lifesaving or critical health purposes, the decision is obvious. But when a
mind-altering drug is given to children, without consent, in order to make them behave
the way we would like, it deprives them of the only thing they can truly be said to own:
themselves.

  1.Zito JM, Safer DJ, dosReis S, Gardner JF, Boles M, Lynch F. "Trends in the prescribing of
    psycho-tropic medications to preschoolers." Journal of the American Medical Association v.
    283, no. 8 (Feb. 23, 2000), p.1025-1030.

  2.Coyle JT. "Psychotropic drug use in very young children." Journal of the American Medical
    Association v. 283, no. 8 (Feb. 23, 2000), p.1059-1060.

  3.Coyle, p.1059.

  4.Cantwell DP, Swanson J, Connor DF. "Case study: adverse response to clonidine." Journal of
    the American Academy of Child and Adolescent Psychiatry v. 36, no. 4 (Apr. 1997), p.539.

  5.PDR 2000. 54th ed. (Montvale, N.J. : Medical Economics, 2000), p.794-796.

  6.Cantwell et al., p.539-544.

  7.Geller B, Reising D, Leonard HL, Riddle MA, Walsh BT. "Critical review of tricyclic
    antidepressant use in children and adolescents." Journal of the American Academy of Child and
    Adolescent Psychiatry v. 38, no. 5 (May 1999), p.513.

  8.PDR 2000, p.549-551.

  9.PDR 2000, p.962.966.

  10.Emslie GJ, Walkup JT, Pliszka SR, Ernst ME. "Nontricyclic antidepressants: current trends in
    children and adults." Journal of the American Academy of Child and Adolescent Psychiatry v.
    38, no. 5 (May 1999), p.519.

  11.Coyle, p.1059.

  12.PDR 2000, p.2153-2156.

  13.Schatzberg AF, Cole JO, DeBattista C. Manual of clinical psychopharmacology. 3rd ed.
    (Washington, D.C. : American Psychiatric Association, 1997), p.4.

  14.Greenhill LL. "The use of psychotropic medication in preschoolers: indications, safety, and
    efficacy." Canadian journal of psychiatry v. 43, no. 6 (Aug. 1998), p.576-7.

  15.PDR 2000, p.550, 794, 964, 2041.

  16.Greenhill, p.576.

  17.PDR 2000, p.549, 794, 963.

  18.Minde K. "The use of psychotropic medication in preschoolers: some recent developments."
    Canadian journal of psychiatry v. 43, no. 6 (Aug. 1998), p.572.

  19.Ibid.

  20.DSM-IV:Diagnostic and Statistical Manual of Mental Disorders. 4th ed. (Washington, D.C. :
    American Psychiatric Association, 1994), p. 109.

  21.Zito et al., p.1026.

  22.Zito et al., p.1025.

  23.Minde, p.573.

  24.Vitiello B. "Pediatric psychopharmacology and the interaction between drugs and the developing
    brain." Canadian journal of psychiatry v. 43, no. 6 (Aug. 1998), p.582.

  25.Vitiello, p.583.

  26.Schatzberg et al., p.1-2

  27.Coyle, p.1059.

  28.Zito et al., p.1029.

  29.Jensen PS, Bhatara VS, Vitiello B, Hoagwood K, Feil M, Burke LB. "Psychoactive medication
    prescribing practices for U.S. children: gaps between research and clinical practice." Journal of
    the American Academy of Child and Adolescent Psychiatry v. 38, no. 5 (May 1999), p.557-563.

  30.Minde, p.573.