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Pediatric Anxiety Underrecognized and Undertreated

Graham J. Emslie, M.D.
Generalized anxiety disorder, separation anxiety
disorder, and social phobia are relatively prevalent disorders that affect 6 to 20% of children
and adolescents.1 However, these disorders frequently go unrecognized by medical professionals. This is a critical problem, since a younger
age of onset and severity of illness result in poor
outcomes in adolescents and adults. Furthermore,
the failure to identify these disorders early in life
leads to increased rates of anxiety disorders, depression, and substance abuse later in life, as
well as to educational underachievement.2 In
this issue of the Journal, the report by Walkup et
al. on the ChildAdolescent Anxiety Multimodal
Study (CAMS)3 addresses the need of early treatment for these disorders.
It is important to understand that clinicians
did not always consider anxiety disorders among
children to be related to adult anxiety disorders.
Once similar diagnostic criteria for anxiety disorders were developed for children and adults
with the publication of the Diagnostic and Statistical
Manual of Mental Disorders, fourth edition (DSM-IV),4
it was recognized that adult anxiety disorders
often have their origins in childhood. For example, overanxious disorder of childhood, once
considered an age-bound condition, was then
understood as part of a continuum of generalized anxiety disorder that began in childhood.
After generalized anxiety disorder and social
phobia were labeled with DSM-IV criteria consistent across the life span, it was clear that early
onset, particularly in preadolescents, was an indicator of poor prognosis. In all, the changes in
diagnostic categories that stemmed from the
DSM-IV criteria have led to increasing awareness
of the longitudinal effect of anxiety disorders and
have permitted extrapolation of treatments from
research in adults to children.

Anxiety disorders may go unrecognized in the

pediatric population for several reasons. For one
thing, fears and worries are common in healthy
children. Normal, developmentally appropriate
worries, fears, and shyness can be difficult to
distinguish from anxiety disorders. For diagnosis, worries and fears must persist and must lead
to impaired functioning. However, even distressing and dysfunctional symptoms are frequently
unrecognized because children with anxiety disorders often report only physical symptoms (e.g.,
headache and stomachache) and are unable to
verbalize their internalized symptoms of worry
or fear. Furthermore, such reported symptoms
are often accommodated by family or school,
and the affected child may simply avoid anxietyprovoking situations (avoidant coping). Such overaccommodation strategies may minimize the
immediate symptoms yet often lead to increased
difficulty in coping with these anxieties later.
For example, a child with marked social anxiety
may well have substantial difficulties transitioning from elementary school to junior high school
if the problem is not addressed. Furthermore, a
child with severe social anxiety may have less
opportunity to develop the necessary social skills
for success later in life because of avoidant coping. Thus, recognizing anxiety disorders in children is the necessary first step in providing treatment that would facilitate learning healthier
coping skills.
These issues are central to the CAMS study.
Although early randomized, controlled trials demonstrated the effectiveness of the individual treatments (antidepressant medications and cognitive
behavioral therapy) used in this study, CAMS
compares the two monotherapies, examines their
combination, and reveals several interesting findings. First, the two monotherapies were equally

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effective. The effect of cognitive behavioral therapy, as compared with placebo, appeared to be
more evident later in the treatment course (after
8 weeks), whereas improvement with medication
appeared earlier in the study. Either cognitive
behavioral therapy or antidepressants equally improved symptoms by 12 weeks, but cognitive behavioral therapy took slightly longer (8 to 12
weeks), whereas the use of an antidepressant resulted in rapid initial improvement, which then
plateaued with little further improvement after
8 weeks. However, if monotherapy is to be used,
the optimal sequencing of treatments (i.e., which
to initiate first) is not answered by this study.
Combination treatment, on the other hand,
appeared clearly superior to each of the monotherapies alone, and the absolute difference between combination therapy and placebo was a
striking 57 percentage points. Although the
high response rate with combination treatment
is encouraging, the goal of treatment is remission of symptoms. Specific remission criteria
were not provided in the study, but the data suggest that a high proportion of children in the
combination-therapy group had no or minimal
symptoms by the end of treatment, based on the
very low mean score on the Clinical Global ImpressionSeverity scale.
Another noteworthy point about CAMS is that
it is primarily a study of prepubertal children
(mean age, 10.72.8 years). Yet, despite the young
age of the patients, the placebo response rate
was only 24%, and the severity of illness in the
placebo group (as rated on the Pediatric Anxiety
Rating Scale) at the end of the study (a score of
12.8) was just below the cutoff for study entry
(13.0, with scores above 13.0 on a scale of
0 to 30.0 indicating clinically meaningful anxiety). These outcomes demonstrate that even in
quite young children, anxiety disorders are persistent.
Large multicenter trials such as this one have
necessary limitations. Such studies do not answer questions about which treatment should be
initiated first, and the dose of medication is constricted by the study design. There have been no
fixed-dose studies of antidepressants in anxiety
disorders, so whether lower doses would be equal
ly effective is not clear. In addition, although the
evaluators were unaware of study-group assignments, the patients in the combination-therapy
group and in the group receiving cognitive behavioral therapy alone were obviously aware of
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their assignments. However, without the addition

of more study groups, this trial answers the most
compelling question about treatment of anxiety
disorders: treatment is indicated.
It appears unlikely that the majority of children with severe and persistent anxiety disorders
are receiving optimal evidence-based care in the
community. The dissemination of clinical research to clinical practice (both psychotherapy
and psychopharmacology) remains a challenge
and should be a national priority. Evidence from
clinical trials such as CAMS needs to be integrated into treatment guidelines. One hopes that
future studies from the CAMS group will provide additional insight concerning matching the
treatment with individual patients. Particularly
important for clinicians and families to understand is that partial treatment of anxiety disorders is not adequate treatment. Residual symptoms
increase the likelihood of relapse.5,6 Furthermore,
children with anxiety disorders may self-limit
their exposure to age-appropriate developmental
milestones if their disorder is insufficiently
treated. From a public health perspective, it is
crucial that effective treatments be available for
children who need them. The identification of
improved methods for bridging research to clinical practice remains an important next step.
Dr. Emslie reports receiving research support from Biobehav
ioral Diagnostics, Eli Lilly, Forest Laboratories, Shire, and Somerset,
consulting fees from Eli Lilly, Pfizer, Shire, Biobehavioral Diag
nostics, Forest Laboratories, Validus Pharmaceuticals, and Wyeth
Pharmaceuticals, and lecture fees from McNeil Consumer and
Specialty Pharmaceuticals. No other potential conflict of interest
relevant to this article was reported.
From the Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas.
1. Costello EJ, Egger HL, Angold A. Developmental epidemiol-

ogy of anxiety disorders. In: Ollendick TH, March JS, eds. Phobic
and anxiety disorders in children and adolescents. New York:
Oxford University Press, 2004:61-91.
2. Woodward LJ, Fergusson DM. Life course outcomes of young
people with anxiety disorders in adolescence. J Am Acad Child
Adolesc Psychiatry 2001;40:1086-93.
3. Walkup JT, Albano AM, Piacentini J, et al. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety.
N Engl J Med 2008;359:2753-66.
4. Diagnostic and statistical manual of mental disorders, 4th
ed.: DSM-IV. Washington, DC: American Psychiatric Association,
1994.
5. Birmaher B, Axelson DA, Monk K, et al. Fluoxetine for the
treatment of childhood anxiety disorders. J Am Acad Child Adolesc Psychiatry 2003;42:415-23.
6. Dadds MR, Holland DE, Laurens KP, Mullins M, Barrett PM,
Spence SH. Early intervention and prevention of anxiety disorders in children: results at two-year follow-up. J Consult Clin
Psychol 1999;67:145-50.
Copyright 2008 Massachusetts Medical Society.

n engl j med 359;26 www.nejm.org december 25, 2008

The New England Journal of Medicine

Downloaded from nejm.org on November 9, 2011. For personal use only. No other uses without permission.
Copyright 2008 Massachusetts Medical Society. All rights reserved.