DEPRESSION
AND
ANXIETY 26:650–660 (2009)
Theoretical Review
OUTCOMES FOR TREATED ANXIOUS CHILDREN: A
CRITICAL REVIEW OF LONG-TERM-FOLLOW-UP
STUDIES
Gili Adler Nevo, M.D.,1,3 and Katharina Manassis, M.D.2,3
Background: Anxiety disorders are the most common psychiatric disorders of
childhood, generating significant distress in the individual and an economic burden
to society. They are precursors to diverse psychiatric illnesses and have an impact on
development. Childhood anxiety’s reach into the future accentuates the importance of
studying the long-term effect of treatment. The purpose of this paper is to examine
existing Long-Term-Follow-Up (LTFU) studies’ capacity to inform us on the impact
of anxiety treatment on development. Method: Medline, PsycInfo, SciSearch,
SocScisearch, Cinhal, Embase, and the Cochrane library were searched. Bibliographies of relevant book chapters and review articles and information from
colleagues with expertise in anxiety were also a source of information. The search
produced more than a thousand citations. Only eight studies met inclusion criteria:
follow-up of a cohort of treated anxious youth for more than 2 years. Results: followup ranged from 2 to 7.4 years. The studies were methodologically rigorous and, in
general, showed maintenance of or improvement in acute treatment gains. The
studies reviewed could not outline course of recovery or control for pivotal
confounding variables such as maturation. Seven of the eight studies employed a
Cognitive Behavioral intervention and one employed a manualized, time-limited,
psychodynamic intervention. No LTFU trial for medication was found. Conclusion:
ample evidence exists for the short-term benefit of pediatric anxiety treatment, but
evidence is still lacking for the understanding of treatment’s role in the facilitation of
healthy development into adulthood. Recommendations for future research are
r 2009 Wiley-Liss, Inc.
proposed. Depression and Anxiety 26:650–660, 2009.
Key words: cognitive behavioral therapy; childhood; adolescent; pediatric;
child psychiatry; anxiety disorders; long-term follow-up; treatment outcome;
development; dimensional diagnosis
INTRODUCTION
Clinicians face a dual responsibility in the treatment
of childhood anxiety disorders: alleviating immediate
suffering caused by the disorder as well as facilitating
healthy development into adulthood. Ample evidence
exists for the former: this review examines the evidence
for the latter.
Anxiety is a salient and fundamental psychological
construct inherent to human nature. It has received
attention in the literature both as a driving force
influencing normal development (see below) and as a
psychiatric symptom. This dual construct is understandable when conceptualizing anxiety disorders as
r 2009 Wiley-Liss, Inc.
1
Department of Psychiatry, Sunnybrook Health Sciences
Centre, Toronto, Ontario, Canada
2
Department of Psychiatry, The Hospital for Sick Children,
Toronto, Ontario, Canada
3
Department of Psychiatry, University of Toronto, Ontario, Canada
Contract grant sponsor: Ontario Mental Health Foundation.
Correspondence to: Dr. Gili Adler Nevo, Sunnybrook Health
Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario,
Canada M4N 3M5. E-mail: [email protected]
Received for publication 4 December 2008; Revised 21 April 2009;
Accepted 22 April 2009
DOI 10.1002/da.20584
Published online 3 June 2009 in Wiley InterScience (www.
interscience.wiley.com).
Theoretical Review: Therapy for Pediatric Anxiety: LTFU
dimensional disorders as opposed to the categorical
disorders (e.g., psychosis). By diagnosing a child with
an anxiety disorder we are merely placing him beyond a
certain cutoff point on a continuum, a cutoff point
beyond which anxiety causes significant distress and/or
impairment.[1]
In most developmental theories, only by overcoming
anxiety is the child able to progress from one developmental stage to the next. To give only a few examples: In
psychoanalytic theory, castration anxiety is the force
behind the resolution of the Oedipus complex. Only by
processing anxiety and overcoming it, is the child able to
accept the rules of society and become part of it.[2]
Anxiety also plays a major role in Margaret Mahler’s
central developmental process of separation–individuation: invincible curiosity pushes the toddler away from
his mother while anxiety brings him back to her. Going
back and forth through the process of separation–individuation helps him internalize his mother and achieve a
more realistic, not omnipotent independence.[3] More
recently, Caspi showed in an impressive series of
publications following a birth cohort from age 3 to
26,[4–11] that temperament persists into adult personality. The mechanism in which personality persists may
be attributed to the child’s interaction with the world
around him/her. With respect to anxiety Caspi states
‘‘shy children may not experience many of the role and
rule negotiations important to the growth of social
knowledge and social skillythey may thus become
increasingly unlikely to initiate or respond appropriately
to social overtures, thereby selecting themselves further
to social isolationypassivity may increase the risk of
being ignored or overlookedycontributing to selfderogating cognitive attributions’’. On the other hand,
he states ‘‘shyness is not inherently problematicyfor
example, the shyness of a young child thrust into a novel
situation is not only normal but may be highly
functional for avoiding potential dangers in developmenty shyness may develop in quite nonpathological
ways through interaction of temperamental qualities
with socialization and cognitive factors’’. These are only
a few of many examples, taken from diverse theoretical
frameworks and spanning various historical periods, of
the multifaceted influence anxiety has on development.
Development implies ‘‘systematic and successive
changes over time in an organism.’’[12,13] Continuity
of a specific anxiety diagnosis (e.g., separation anxiety)
over time should not necessarily be expected, it may be
transformed into a different entity.[14] This entity
may take the form of another psychiatric disorder
(e.g., depression), a change in anxiety level (e.g.,
subthreshold anxiety), dependence on others (or drug
dependence), a rigid pattern of thinking, or any
number of other alternatives (i.e., dimensionality).
Thus, Ollendick et al.[13] state that: ‘‘It is our
recommendation that future studies exploring the
continuity or discontinuity of childhood internalizing
disorders use both a diagnostic, categorical, approach
and a quantative, dimensional approachya second
651
major recommendation for future longitudinal studies
is that they use a developmental perspective’’. In this
manuscript we will review the current literature on the
long-term-follow-up (LTFU) of therapy for pediatric
anxiety in light of the recommendations above
(dimensionality and development). The specific aims
of this review are to consider the following:
1. Review of the nature of LTFU studies, including
what duration is considered long-term and what
treatment modalities have been studied?
2. Gain understanding of predictive variables and
outcome measures used in these studies, and note
whether these are sufficient to examine therapy’s
influence on development.
3. Examine methodological strengths and limitations
of LTFU treatment studies for anxious children.
To provide a context for this review, diagnostic and
treatment considerations, unique to pediatric anxiety
and relevant to LTFU will be described, as well as
obstacles to conducting LTFU studies generally,
regardless of disorder.
PEDIATRIC ANXIETY DISORDERS
Diagnosis. Anxiety disorders are the most common psychiatric disorders of childhood, with an
estimated point prevalence of 5–10% and a lifetime
prevalence of approximately 20%.[15–17] These disorders generate significant distress in the child,
interfere with the normal developmental trajectory,
and may lead to unipolar and bipolar mood disorders,
suicide, drug and alcohol abuse, psychosomatic illness
and loss of work days.[18–21] Childhood anxiety
disorders in DSM-IV-TR[22] include those unique to
childhood (Separation Anxiety Disorder; Selective
Mutism) and those common to children and adults
(Generalized Anxiety Disorder, Social Phobia, Specific
Phobia, Obsessive–Compulsive Disorder, Panic
Disorder, and Post-traumatic Stress disorder). The
classification has changed from previous DSM classifications, which included Overanxious Disorder and
Avoidant Disorder. The current classification recognizes the developmental continuity of most children
and adult disorders, and is advantageous for the
longitudinal study of these disorders across the life
span. Although the phenomenological/categorical
approach is currently the most frequently used and
influential model of diagnosis, with the DSM-IV-TR
diagnoses above being the most popular, it is widely
accepted that there is room for other approaches to
categorization.[23] Dimensional approaches encourage
the focus on common factors that cut across the anxiety
disorders, and have the potential to reduce a large
number of categories to a smaller number of dimensions of behavioral and emotional dysfunction,[24]
making these approaches amenable to research.
Because they regard a problem as a range from mild
Depression and Anxiety
652
Adler Nevo and Manassis
to severe rather than disordered versus healthy, these
approaches are beneficial for screening and prevention.
Dimensional approaches have many limitations as well,
mainly problems of communicability, making them a
better model than the categorical for science, but not
for clinical purposes.[24,25]
Treatment. Acute Treatment studies of childhood
anxiety disorders have focused on pharmacological and
psychological interventions. The same medications used
to treat anxiety in adults are generally used in children,
although few have FDA indications for this use.[26]
Psychological interventions studied have included
psychodynamic psychotherapy and manual-based CBT
with a plethora of short-term studies supporting the
latter. Traditional psychodynamic psychotherapy is
more difficult to study and its effectiveness is not as
supported by the literature. Manualized, time-limited,
psychodynamic psychotherapies are therefore now more
prevalent.[20,27,28] Cognitive behavioral therapy (CBT) is
a time-limited, short-term (10–16 sessions) psychotherapy and has been shown to be efficacious in numerous
randomized controlled trials in reducing children’s
anxiety and improving their general functioning.[29–32]
A recent systematic review[33] found the remission rate
in the CBT groups (56.5%) to be higher than that of the
control groups (34.8%). These response rates are based
on efficacy studies, as there are very few data available
on effectiveness, suggesting that CBT has significant
efficacy, but not necessarily effectiveness. Based on this
evidence CBT now appears to be the treatment of
choice for childhood anxiety disorders; however, a
significant minority (40–50%) of anxious children do
not remit with CBT. Finally, although anxiety treatment
may be effective for alleviating immediate suffering,
anxiety disorders may be a chronic illness or a condition
that affects future development, stressing the importance of examining LTFU of therapy outcome.
METHODOLOGICAL ISSUES IN LTFU
STUDIES
LTFU studies are hard to conduct and difficult to
interpret because of many potential confounding
factors and biases.[34] The question ‘‘why embark on
this type of complicated research’’ is addressed by
Toner and Stueve[35] in their compelling chapter. First,
they argue that LTFU studies are necessary for
accurate descriptions of the courses of mental disorders. Such variety of courses is easily missed with
cross-sectional snapshots. Variation in course of illness
also risks being missed in longitudinal studies of short
duration and in follow-up studies that assess outcome
only at one point in time. Second, LTFU studies
inform our understanding of potential types of
psychiatric disorders insofar as disorders (and their
subtypes) are expected to manifest different courses.
A third use of LTFU studies lies in the identification
of prognostic and outcome variables. Finally, LTFU
studies provide a vehicle for chronicling many other
Depression and Anxiety
changes in the lives of psychiatric patients, such as
changes in symptom content, quality of life, and coping
strategies.
Potential hurdles in conducting LTFU studies are
abundant. Obstacles can be divided into research
methodology issues, ethical considerations, and organizational difficulties.
Methodological issues include the problem of the
cohort effect, i.e., the characteristics of a specific
population may change over time; Referral bias, i.e.,
samples of hospitalized or outpatient clinic patients
studied, are not necessarily representative of the overall
patient population; attrition of subjects with particular
characteristics biasing results; and confounding factors,
especially the effects of maturation and life events
during the follow-up interval. There may also be
relevant changes in culture within the scientific community. Scientific interests, theories, diagnoses, and
instrumentation change over time, so that the selection
and measurement of baseline variables may not live up
to standards at the end of follow-up.[36] Ethical
considerations may also impede LTFU studies. For
example, retrospective studies can create a chickenand-egg problem, insofar as records generally considered confidential are needed to relocate subjects, but
subjects cannot grant permission to release records or
even be informed of their use until they are traced.
Asking subjects’ permission for follow-up at research
study entry is now common, but this practice does not
address the need to recruit community or ‘‘treatment
as usual’’ comparison groups. On the other hand, if
an LTFU were undertaken as a prospective study,
randomizing subjects to a wait list control group
for several years when an efficacious treatment exists
would not be ethical by any standard. Without
a control group, attribution of outcome solely to
the independent variable (e.g., therapy) and not to
confounding variables is not possible.
Organizational difficulties are the third group of
obstacles facing researchers who wish to pursue an
LTFU study. Successful LTFU’s require a stable and
dedicated research team and funding that would enable
uninterrupted contact over the long-term. Given the
vagaries of research funding and the high probability
that staff may change over time, LTFU studies may be
plagued by inconsistencies.
LITERATURE REVIEW
SEARCH STRATEGY AND RESULTS
To select studies for the current review, Medline,
PsycInfo, SciSearch, SocScisearch, Cinhal, Embase,
and the Cochrane library were searched for all studies
that examined the LTFU of psychotherapy and
pharmacotherapy of anxious children and adolescents.
We used these key words and medical subject headings:
long-term follow-up or follow-up; anxiety disorder
or anxiety; child or adolescent or pediatric; therapy or
Theoretical Review: Therapy for Pediatric Anxiety: LTFU
psychotherapy or treatment or pharmacotherapy or
medication. Bibliographies of relevant book chapters
and review articles and information from colleagues
with expertise in anxiety were also a source of
information. This search produced more than a
thousand citations, which included the natural history
of anxiety disorders, follow-up of therapy for adult
anxiety, and mainly, 6–12 month follow-up studies of
anxiety treatment. From these articles we selected
studies that conducted an LTFU (defined as 2 years or
more beyond termination of the original intervention)
of treatment for anxiety disordered children and youth.
Eight studies met these criteria and are discussed in the
following section.
LTFU OF THERAPY FOR PEDIATRIC
ANXIETY
To date, only eight studies have examined the longterm effects of therapy for anxious children. Table 1, at
the end of this section, provides a detailed account of
these studies. Six of the studies followed at long-term a
cohort of children referred to their clinic and treated
through a study protocol.[37–42] Two studies[43,44]
followed a nonreferred population of children screened
at their schools for anxiety. Participants were diagnosed, for the most part, using the DSM anxiety
diagnoses. The two older studies[37,39] used the DSMIII childhood anxiety disorders as opposed to DSM IV,
and the studies which looked at screened nonreferred
populations of children[43,44] used cut-off points for the
specific measures used (see Table 1). Seven of the eight
studies followed a Cognitive Behavioral Therapy
protocol, while one[42] followed a short-term, manualized psychodynamic therapy. The latter did not use a
DSM diagnosis but rather, looked at internalizing
disorders as opposed to externalizing disorders. The
method used for LTFU was either a phone or face-toface interview in the participants’ home using a
semistructured interview (see Table 1). In one study[43]
measures were filled by the child participants in class.
In some of the studies an assessment battery was mailed
prior to the interview.[38,39] A methodological difficulty
encountered in all studies researching a referred
population of children was a lack of control group for
the full length of follow-up. Other methodological
difficulties encountered were a change in nosology
from time of initial intervention to follow-up;[37,39]
inability to obtain follow-up information from both
child and parents;[37,43,44] the use of different measures
on initial assessment and LTFU. This is due both to
change in state of the art measures and age of
participants. Kendall et al.[40] were able to overcome
this difficulty by modifying the semistructured interview and measures to fit changing requirements (e.g.,
ADIS based on DSM IV was used at LTFU as opposed
to DSM III based ADIS used in the initial assessment),
and the use of the adult measures (BDI and MAS)
compatible with the child measures used in the original
653
assessment (CDI and RCMAS); Manassis et al.[41] were
not able to use standardized measures and used probe
questions. Outcome was assessed by number of
participants not meeting anxiety diagnosis at LTFU,
and number of participants who did not reach the cutoff for clinical anxiety levels. Each and every study
highlighted unique aspects of LTFU: Kendall et al.[39]
attempted to tease out treatment components significantly influencing outcome at LTFU. They explored
perceived factors as opposed to theoretical treatment
factors and found a significant relationship between
improvement and theoretical, but not perceived
factors. This suggests that improvement is due to
treatment components and not nonspecific supportive
factors. Follow-up of a nonreferred population who
were treated for anxiety prevention was unique to
two of the studies.[43,44] Comparison of outcome
at LTFU between participants treated with individual
child therapy as opposed to individual therapy with
a family component was an interesting aspect scrutinized by Barrett et al.[37] and Manassis et al.[41]
Manassis et al. also compared the effect of group as
compared with individual therapy. Muratori et al.[42]
were the only group to examine a psychodynamic
intervention and follow a control group throughout the
whole follow-up period. This was possible ethically,
due to the relatively short period of LTFU (2 years) and
unavailability of therapy. Kendall et al.[45] and Manassis
et al.[41] analyzed the effect of treatment on possible
anxiety sequelae (e.g., depression and substance abuse)
and found therapy to reduce these at LTFU. GarciaLopez et al.[38] were the only group to look at an ethnoculturally diverse population.
SUMMARY AND DISCUSSION
This review highlights all LTFU studies for the
treatment of pediatric anxiety published, to the best of
our knowledge, to date. These are eight rigorous
studies that generally show the maintenance of treatment gains at LTFU. In the discussion below we first
address our aims—examination of the nature of the
studies reviewed, suitability of predictive variables and
outcome measures, and methodological strengths and
weaknesses—and then continue to examine the studies
in relation to two concepts, crucial to the understanding of pediatric anxiety, which were presented in
the introduction to this manuscript. The first is the
dimensional aspect of anxiety diagnoses, and the
second is anxiety’s role in healthy development.
Through this dual scrutiny of the studies we hope to
answer the question ‘‘does therapy for pediatric anxiety
impact development and long-term outcome?’’
NATURE OF STUDIES
LTFU studies were found to be scarce. Of hundreds
of treatment outcome studies for anxious children and
youth, only eight continued to follow subjects for more
Depression and Anxiety
Depression and Anxiety
Barrett et al.[37]
Dadds and Spence[44]
Kendall and SouthamGerow[39]
Study
79 (67%) (28 male;
24 female; age range
at LTFU 5 13–21;
mean-16)
5.3–7.1 (average 6.2) years
128 (82%)
2 years
44 (81.8%). (20 male;
16 female; age range at
LTFU 5 11.3–18.2;
average: 15.6)
2–5 (average–3.3) years
Length of FU/Sample size
(at initiation of study and
retention rate)
Predictors tested
Measures and interviews
Prospective randomized
controlled trial
Diagnosis
pretreatment
Comorbidity
Severity of initial
problem; poor
parental
adjustment;
gender
ADIS-C
RCMAS
FSSC-R
CDI
CBCL
Initially: Child: RCMAS
Parent: ADIS-P; CBCL;
Stress, Anxiety, and
Depression Schedule
LTFU: parent
only–ADIS-P; child
anxiety severity.
Clinician:GI
Child:RCMAS, CQ-C
Prospective–retrospective Perceived and
NASSQ, CDI, RI
cohort (i.e., the cohort
theoretical factors
of an original study was
remembered from
Parent: CBCL,
reassessed at follow-up)
treatment;
STAIC-P-Trait,
No control
diagnosis
CQ-P, ADIS-C
pretreatment;
comorbidity
Design
CBT (individual child
Prospective–retrospective
focused CBT) or
cohort
CBT1FAM (the
No control
above1family anxiety
management training)
Coping Koala–a group
modification of
coping cat
Coping cat: a
manualized,
individual, primary
child focused CBT
Intervention
TABLE 1. LTFU studies for the treatment of pediatric anxiety
Treatment gains maintained
at LTFU (85.7% no
longer fulfilled diagnostic
criteria for an anxiety
disorder as compared with
79.6% at 12 M follow-up).
Diagnosis pretreatment1
comorbidity do not affect
LT outcome. CBT1FAM
did not appear to be more
effective than CBT alone
as opposed to greater
efficacy of the combined
therapy in the initial study
Superiority of treatment
condition was seen
immediately post
treatment and at LTFU
but not at 12M follow-up
Onset prevention was seen in
the treatment group. The
only predictor found to
effect failure of therapy
was greater severity of
initial disorder
Treatment gains maintained
at LTFU (90% of
participants did not meet
criteria for original DSM
diagnosis, 74% were
below clinical anxiety
levels on CBCL), but 50%
of participants were in
need of further treatment
after original intervention
Diagnosis pretreatment and
comorbidity do not affect
LT outcome. A significant
relationship emerged
between theoretical
treatment factors and
outcome but not
perceived factors
Results
654
Adler Nevo and Manassis
[42]
Garcia-Lopez et al.[38]
Manassis et al.[41]
Kendall et al.[40]
Muratori et al.
Study
44 (57%) (7 male;
18 female, age range at
LTFU 5 20–22)
5 years
(68%) (29 male;
39 female, age range at
LTFU 5 14–19;
mean 16.4)
6–7 years 63
94 (90%) (53 male;
32 female, age range at
LTFU 5 15–22;
mean 19.3)
5.5–9.3 (average 7.4)
years
60 (96%) (35 male; 23
female, age range at
LTFU 5 6.3–10.9;
mean 8.8)
2 years
Length of FU/Sample size
(at initiation of study and
retention rate)
TABLE 1. Continued
Design
Prospective–retrospective
cohort
No control
CBGT-A; SER-Asv;
IAFS
Prospective–retrospective
cohort
No control
Coping bear—a
Prospective–retrospective
manualized CBT
cohort
protocol (parent only, No control
child only, and
parent–child)
Coping cat: a
manualized,
individual, primary
child focused CBT
Time-limited combined Prospective,
individual and parent- Nonrandomized,
focused
Controlled
Psychodynamic
Psychotherapy
Intervention
K-SADS
CBCL
CGAS
Measures and interviews
None
SPAI
SAS-A
ADIS
Gender, type of
Probe questions
anxiety diagnosis, GI
severity, type of
treatment
ADIS-C/P, CASI
Child reported
Child: RCMAS, CQ-C,
anxiety,
APES
pretreatment:
child’s age; family Parent: CBCL, CQ-P,
STAIC
income; number of
diagnoses; measure
scores. Posttreatment: number
of positive and
negative events;
treatment received
post-treatment
None
Predictors tested
Treatment gains were
maintained at LTFU
48% of patients showed total
remission at LTFU as
compared with 43%
immediately post
treatment
Anxious tendencies persisted
at LTFU, but no longer
required clinical attention
in 70% of treated subjects
Possible predictors of less
favorable outcome: Female
gender, non-GAD
diagnosis, greater severity of
symptoms
The only treatment strategy
still in consistent use was
relaxed breathing
Improvement beyond posttreatment gains at LTFU
(51.2% did not meet criteria
for initial diagnosis at posttreatment while 80.5% did
not meet initial diagnosis at
LTFU). Very few
pretreatment variables
predicted outcome (negative
life events by chills report,
externalizing symptoms by
parent report, and
additional treatment after
leaving the clinic by both
child and parent report)
Significant improvement of
both experimental1control
group, but improvement of
experimental group alone at
2Y. Improvement beyond
post-treatment gains at
LTFU
Results
Theoretical Review: Therapy for Pediatric Anxiety: LTFU
655
Depression and Anxiety
Depression and Anxiety
733 (90%) (325 male;
344 female, age range at
LTFU 5 20–22)
ADIS-C/P, anxiety disorders interview schedule for children/parents; APES, adolescent perceived events scale; CASI, comprehensive adolescent severity inventory; CBGT-A, cognitive
behavioral group therapy for adolescents; CDI, children’s depression inventory; CBCL, child behavior checklist; CQ-C/P, coping questionnaire-child/parent; FSSC-R, fear survey schedule for
children, revised; GI, global improvement scale; IAFS, intervención en adolescents con fobia social, treatment for adolescents with social phobia; K-SADS, schedule for affective disorders and
schizophrenia for school age children; NASSQ, children’s negative affectivity self-statement questionnaire; RCMAS, revised children’s manifest anxiety scale; RI, recall interview; SAS-A, social
anxiety scale for adolescents; SCAS, Spence children’s anxiety scale; SET-Asv, social effectiveness therapy for adolescents, Spanish version; SPAI, social phobia and anxiety inventory; STAIC,
state-trait anxiety inventory for children; STAIC-P-Trait, state-trait anxiety inventory for children-modification of trait version for parents.
SCAS
RCMAS
CDI
Elevated scores on
SCAS, CDI;
older age
3 years
Barrett et al.43
FRIENDS (school-based Prospective randomized
CBT anxiety
controlled trial
prevention program)
Measures and interviews
Predictors tested
Design
Study
Intervention
Length of FU/Sample size
(at initiation of study and
retention rate)
TABLE 1. Continued
Positive evidence for the
durability of prevention
effects in grade 6 boys,
grade 6 girls up to 2 years,
but not grade 9 students.
The intervention group
showed significantly lower
scores for anxiety and
depression as compared
with the control condition
Adler Nevo and Manassis
Results
656
than 12 months. The majority of these studies
examined the long-term effect of a CBT protocol.
No LTFU of medication was found. Apart from two,
the studies examined therapy for a referred population
of children diagnosed with anxiety. The Australian
groups Dadds et al.[44] and Barrett et al.[43] examined a
preventive intervention designed for schools. Duration
of follow-up ranged from 2 to 7.4 years. The studies
assessed patients on the following time points: pretreatment, post-treatment, short-term follow-up (6–12
months), and at the point of LTFU. Barrett et al.
assessed patients additionally at 24 months. Gains were
generally maintained, not only at 1 year follow-up, but
up to 7 years post treatment. In several of the studies
subjects were less symptomatic at LTFU as compared
with immediately post treatment.[40,42,44] The explanation suggested by one of the authors, a ‘‘sleeper effect’’
resulting from therapy,[42,46] is a very plausible one but
cannot be fully validated as long as other confounding
variables, especially the possible contribution of
maturation to these outcomes, have not been controlled.
PREDICTIVE VARIABLES AND OUTCOME
MEASURES
Variables tested as predictors and outcome measures
for each study are outlined in Table 1. Variables tested
included severity of illness, comorbidity, family-related
factors, and demographic characteristics (e.g., gender,
pretreatment age). Primary outcome was determined
either categorically, establishing diagnosis using semistructured interviews, or by evaluating degree of
change on clinical outcome measures. Other outcomes
of interest were coping strategies,[39,40] use of the Child
Behavior Checklist (CBCL), level of functioning,[41]
level of improvement as perceived by the patient,[41]
and level of negative self talk.[39] Seeking further
mental health interventions beyond the original intervention was regarded both as predictor,[40] and as an
outcome itself.[41] Regardless, LTFU studies showed
that the majority of participants did not require
additional help beyond the original intervention. Very
few of these variables were found to significantly
predict outcome in the long-term,[40] stressing the need
for evaluation of innovative predictors and outcome
measures in future studies. Although measures which
are considered dimensional were used (e.g., CBCL),
the data extracted from them stressed categorical
outcomes (symptom severity and diagnoses).[37,39,40,42]
The effect of anxiety on additional dimensions of the
child’s life (e.g., interpersonal relations and self
attribution) were not examined.
METHODOLOGICAL STRENGTHS AND
WEAKNESSES
The eight studies reviewed implemented rigorous
methodological procedures, including the use of
Theoretical Review: Therapy for Pediatric Anxiety: LTFU
structured diagnostic interviews, manualized treatments, treatment integrity checks, and systematic
follow-up. Still, all suffered from limitations typical
of LTFU studies. The first methodological difficulty
was referral bias. As stated above, six of the eight
studies recruited patients referred to an outpatient
specialty clinic. Whereas the Australian groups[43,44]
followed a community-based cohort of school-aged
children. The second methodological difficulty was
attrition. Although all studies found no significant
demographic differences between participants who
agreed to participate in the study both initially and at
LTFU and those who did not, ‘‘the only way to ensure
that differential losses to follow-up have not biased
study results is to hold all losses to an absolute
minimum.’’[47] The studies reported in this review
succeeded in the following 57%[38] to 96%[42] (see
Table 1 for a detailed account of all studies) of the
original cohort. Many of the studies accomplished very
good retention rate. Kendall et al.[40] supplied insights
into the effort invested in this achievement: ‘‘ythe
current study retainedyby using intensive tracking
efforts (i.e., ten or more telephone calls, letters,
internet searches using contact information issued at
intake and at posttrreatment) and interviewer flexibility
regarding scheduling (e.g., weekend home visits)ythe
achieved retention rate underscores the necessity of
time and financial investment in tracking and followup.’’ Moreover, the low attrition rate may be a result of
therapeutic rapport and relationship to the clinic,
stressing the assertion that psychotherapy research is
not only a scientific and technical achievement, but
primarily a humanistic undertaking. The third methodological weakness relates to changes in nosology. The
studies that spanned a time period extending from
DSM III to DSM IV encountered a change in
nosology, for instance the change from overanxious
disorder to Generalized Anxiety Disorder. This emphasizes the advantage of assessing outcome through
dimensional constructs (see above), which highlight
common factors that cut across anxiety disorders and
developmental stages.[23] The fourth methodological
weakness relates to the difference in youth and adult
outcome measures in instances where follow-up was
conducted up to adulthood. In two of the studies[37,39]
the measures used at LTFU were identical to the ones
used in the original study but were not normalized for
the use of adolescents at follow-up. In a third study,[40]
an age appropriate version of the original interviews
was used, resulting in questionable validity due to
the differences between versions. Measurement
equivalence must be ensured in any study that assesses
constructs across developmental periods and highlights
the need for the construction of a novel scale
appropriate for LTFU. The fifth methodological
difficulty was in the inability to account for confounders and other threats to the internal validity of the
study. Longer follow-ups have a better chance of
accumulating variables, some of which may be
657
unexpected and unidentified, which could influence
outcome. The most intuitive and notable of these is, of
course, the effects of maturation itself. None of the
studies were designed to address this issue. The sixth
and most important methodological difficulty is the
lack of control group, the universal problem of
outcome studies for any LTFU of an evidence-based
treatment. All treatment studies initially used a wait list
control group, which was eventually treated, and
therefore could no longer function as control. Only
Dadds et al.[44] and Barrett et al.[43] were able to
provide a control condition for the full period of
follow-up. The long-term control condition was
possible in Barrett’s study as it examined prevention
of anxiety in a non-referred population. Without a
control group the question of spontaneous remission
cannot be adequately addressed.
This manuscript has reviewed the nature of anxiety
focused LTFU studies (scarce, the majority examining
a referred population treated with CBT and evaluation
of outcome at only a few points in time), the variables
studied as predictors and outcome measures (severity of
illness, comorbidity, family-related factors, and demographic characteristics) and methodological difficulties
of these studies. Our review has underscored the
difficulty of deducing the impact of therapy on longterm outcome from current LTFU’s. To elucidate this
issue further, we will now examine these studies
through the prism of two further concepts: The
dimensional and developmental aspects of anxiety.
Anxiety as a dimensional construct. Anxiety is a
complex construct: it causes severe, debilitating distress
on the one hand, but on the other hand, takes a place of
honor in the development of moral conscience and the
capacity for empathy.[48,49] Conceptualizing anxiety as
dimensional is helpful in resolving this complexity, and
has important clinical implications. For example,
anxious children below the diagnostic threshold may
not come to clinical attention but may still suffer
distress. Further, treatment of anxiety is now extending
beyond patients referred to a specialty outpatient clinic
to prophylactic treatment for community cohorts.
Should patients be treated only if they qualify for a
DSM anxiety diagnosis? Should they be treated if they
show any sign of distress? Should the general population be given prophylactic treatment? Utilizing a
dimensional approach is the first step towards identifying the broadest spectrum of children who may benefit
from treatment.
Anxiety and development. Anxiety is expressed
differently at different ages. For example, Last et al.[50]
found a hierarchy in the mean age of the onset of
anxiety disorders: separation anxiety disorder (SAD),
7.5 years; avoidant disorder, 8.2 years; simple phobia,
8.4 years; overanxious disorder, 8.8 years; social phobia,
11.3 years; panic disorder, 14.1 years.
As described in the introduction, anxiety also plays a
complex role in development and can both cause
Depression and Anxiety
658
Adler Nevo and Manassis
distress and motivate psychological maturation. The
latter role raises some interesting questions regarding
intervention and further research. For example: should
any child be treated for immediate relief of his/her
distress or would it be beneficial for the child and his/
her family to work through the difficulty? Is it possible
that well-meaning intervention cause harm by labeling
a child? Could pharmacological interventions cause
harm by socializing the child to rely on external
control? Could treatment be so successful in reducing
anxiety, in an immature stage of moral development, so
as to push a child into antisocial behavior? Or on the
contrary, would successful treatment of anxiety enable a
child to fulfill age appropriate roles, increase a sense of
meaning and self esteem, and enable him/her to
continue healthy development into adulthood? Does
anxiety serve a protective function in that the child
avoids situations or content in his/her environment he
is not ready to encounter? What is the role of family in
the treatment of anxious children and youth? Integrating a development of perspective into therapy research
would enable us to answer the wide variety of questions
above and widen the scope of our hypotheses beyond
phenomenology.
CONCLUSION
Considering anxiety as dimensional and understanding its role in development underscores the importance
of widening our view as to what is considered evidence
for the successful treatment of anxiety. The studies
cited above, although rigorous, were interested primarily in diagnosis and severity of illness as outcome.
Dimensions such as self-efficacy, rigidity of social
interaction, or the patient’s role in society (just to
name a few) were not addressed as well as anxiety’s role
in different developmental stages. This review has
delineated what current state of the art LTFU’s can
teach us regarding therapy’s long-term influence. By
considering the two further themes of dimensionality
and development we hope to widen the scope of what
future studies will be able to show. Specifically, we
recommend the following for future therapy outcome
research:
A developmental emphasis could be given by first,
conducting a follow-up that would not stop at shortterm, but continue to follow patients through developmental stages, at multiple time points, to delineate
the course of illness. Critical periods in the course of
the disorder and the best timing for treatment
intervention, as partially revealed by Barrett et al.,[43]
are of special interest in this respect. Second, study the
role of family in therapy as initiated by Dadds et al.,[44]
Barrett et al.[37] Manassis et al.[41] and stressed by
Kendall and Ollendick.[45]Third, and most importantly,
expand the range of predictors and outcome measures.
Examples of additional predictors and outcomes that
take the developmental perspective into consideration
are listed below.
Depression and Anxiety
A dimensional emphasis could be given by the study
of referred populations, as well as nonreferred cohorts
of children as initiated by Barrett et al.[43] and again, by
expanding the range of predictors and outcome
measures. Examples of predictors and outcomes, which
would take the developmental and dimensional aspects
into consideration, are as follows: family support,
parenting style, attachment, child’s coping style,
measures of moral conscience and rigidity of thinking,
use of defense mechanisms, intelligence, level of
functioning, locus of control, self esteem, self efficacy,
measures of well being and contentment, quality of life,
need for additional therapy after initial intervention,
level of involvement in the community, loss of
work days, or socioeconomic mobility. Collaboration
between the specialties of developmental psychology,
clinical psychology, and psychiatry might prove especially fruitful in finding predictors and outcome
measures.[51] An example is utilizing complex measures
of personality integration, or assessing the Eriksonian
perspective on maturation.[52] The range of outcomes
should be expanded not only in content, but implement
statistical methods (equivalency testing, for example)
that would enable us to know whether the child had
returned to a normal developmental curve, as opposed
to absolute data.[45] These, in turn, may delineate
diverse therapeutic goals (e.g., overcoming a specific
phobia as opposed to maturing into a more central
social role), which would necessitate further study of
diverse treatment modalities, including pharmacotherapy and psychodynamic psychotherapy, to address the
different goals.
Utilizing a dimensional approach would address
‘‘Changes in culture within the scientific community’’
(as termed by Toner and Steuve[35]) as well. These
changes, including diagnostic modifications and variation in outcome measures, could be overcome for
research purposes by utilizing the dimensional approach, which focuses on common factors that cut
across the anxiety disorders and developmental
stages.[24]
In general, the most important methodological gap
should be addressed, i.e., the crucial question of control
group. Utilization of a control group is the only way to
rule out the effect other variables, apart from therapy,
have on outcome. Clearly, it is impossible from an
empathic and ethical point of view to prevent treatment
from the wait list control group of the original
intervention. Ways of overcoming this obstacle might
be the use of normative comparisons as described by
Kendall and Grove,[53] utilize a control group in
a community cohort, as in Barrett et al.[43] or employ
a withdrawal design, for instance, in a comparison
between psychotherapy and pharmacotherapy.
An ideal LTFU study should be undertaken, as Toner
and Steuve[35] and Kendall et al.[40] have stressed, as
a prospective, well-planned study, conducted by a
dedicated clinical and research team who would foster
therapeutic rapport and relationship to the clinic,
Theoretical Review: Therapy for Pediatric Anxiety: LTFU
reducing attrition. In the meantime, until such an
undertaking is initiated, clinicians treating anxious
children and youth must take into consideration that
with regards to the benefit of therapy, ample evidence
exists for alleviating immediate distress, but evidence is
still lacking for understanding therapy’s role in the
facilitation of healthy development into adulthood.
Does therapy for pediatric anxiety impact development
and long-term outcome? The studies above have
unlocked the door to a much anticipated[13] answer,
but further study and refinement are required to fully
opening it.
Acknowledgments. We deeply thank Dr. Anthony
Levitt for his guidance and encouragement.
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