Provided by David Satcher, M.D., Ph.D.
Surgeon General of the United States of America
Chapter 3: Children and Mental Health
Overview of Mental Disorders in Children
Psychopharmacology
Dramatic increases have occurred over the past decade in the
use of pharmacological therapies for children and adolescents with mental
disorders, but research has lagged behind the surge in their use (Jensen et al.,
1999). Our gaps in knowledge span three areas in particular. First, for most
prescribed medications, there are no studies of safety and efficacy for children
and adolescents. This is true for medications for mental disorders as well as
for somatic disorders. Depending on the specific medication, evidence may be
lacking for short-term, or most commonly, for long-term safety and efficacy. The
problem is even more pronounced with newer medications, most of which have been
introduced into the market for adults. Only in the case of psychostimulants for
ADHD is there an adequate body of research on their safety and efficacy in
children and adolescents, albeit short-term information only (Greenhill et al.,
1998) (see later section on ADHD). Second, there is often limited information
about pharmacokinetics, that is, drug concentrations in body fluids and tissues
over time (Clein & Riddle, 1996). Most of what is known about pharmacokinetics
comes from studies of adults. But pediatric pharmacokinetic studies are crucial
to identifying the appropriate dose and dose frequency for children of different
ages and body sizes. Third, the combined effectiveness of pharmacological and
psychosocial treatments, that is, multimodal treatments, is seldom studied.
Multimodal treatments have the potential to yield dose reductions in
pharmacological treatments, thereby improving the side-effect profile, parental
acceptance, and patient compliance.
The dearth of research on children and adolescents has allowed for widespread
“off-label” use of medications. This means that, for this population, physicians
who are prescribing a given drug do not have the benefit of research and drug
labeling information developed by the sponsor and approved by the Food and Drug
Administration (FDA). Under U.S. food and drug law, a drug is approved by the
FDA only for a defined population. Yet after its approval and market
availability, physicians are at liberty to prescribe it for anyone, even though
the sponsor only is allowed to market the drug for the approved population
(which typically is adults) (FDA, 1998). Fortunately, there is a large body of
clinical experience with children and adolescents to guide prescribing
practices, despite few controlled studies (Green, 1996).
There are several reasons for the paucity of research on medications for
children and adolescents. One is greater caution on the part of both the medical
profession and parents to experiment with children or to prescribe drugs with
potentially serious side effects. Another reason is the need for compliance with
dosing requirements of the clinical trial protocol. When children are research
subjects, enforcing compliance is generally perceived to be more difficult.
Researchers must rely on parents to assess the degree of compliance. A final
reason is the cost of research. Once drugs have reached the market for adults,
pharmaceutical companies have fewer financial incentives to conduct expensive
and methodologically demanding studies with children, to whom drugs may be given
through off-label prescribing. The problem has been significant enough to have
galvanized Congress into passing legislation, the FDA Modernization Act of 1997,
to create financial incentives for drug sponsors to conduct research with
pediatric subjects [FDA, 1999 Title 21 USC 505A(g)]. The FDA Modernization Act
may help alleviate this problem, but it is too early to tell.
Despite the relative lack of information concerning safety and efficacy of
psychotropic agents in children, six scientific reviews have been completed
recently; these reviews comprehensively surveyed all available published
research concerning the safety and efficacy of psychotropic medication, focusing
on six general classes of medication: the psychostimulants (Greenhill et al.,
1998), the mood stabilizers and antimanic agents (Ryan et al., 1999), the
selective serotonin reuptake inhibitors (SSRIs) (Emslie et al., 1999),
antidepressants (Geller et al., 1998), antipsychotic agents (Campbell et al.,
1999), and other miscellaneous agents (Riddle et al., 1998).
Review of this comprehensive body of research evidence indicates strong support
for the safety and efficacy of several classes of agents for several conditions,
specifically, SSRIs for childhood/adolescent obsessive-compulsive disorder, and
the psychostimulants for ADHD. For many other disorders and medications,
however, information from rigorously controlled trials is sparse or altogether
absent (see Figure 3-2). Further, only in the area of ADHD is information now
emerging on longer term safety and efficacy, as well as on the merits of
combining psychopharmacologic and psychotherapeutic treatments.
Given the inadequacy of efficacy data for most nonstimulant psychotropics,
studies are needed for the majority of agents. However, efficacy data appear to
be most urgently needed for SSRIs, mood stabilizers, and novel antipsychotics,
since the level of usage of these medications appears to be highest among the
growing list of psychotropic medications used in youth (Fisher & Fisher, 1996).
In contrast to adult psychopharmacology that is focusing on differential
efficacy and speed of onset of these categories of psychotropics, pediatric
psychopharmacology needs basic studies of efficacy.
Additional information on specific medication treatment is presented in the
succeeding sections, providing more detailed discussion of particular disorders.
In-depth information is presented on two disorders where a great deal of
research has been done, namely, ADHD and major depressive disorder, followed by
briefer discussions of other childhood mental disorders.
4 The criteria are listed in Chapter 1.
Figure 3-2. Grading The Level of Evidence for Efficacy of Psychotropic Drugs in Children
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