Effectiveness and cost effectiveness of a Cognitive Behavioral Therapy (CBT) program in clinically depressed adolescents; individual CBT versus care as usual.

Title of the study
Effectiveness and cost effectiveness of a Cognitive Behavioral Therapy (CBT)
program in clinically depressed adolescents; individual CBT versus care as
usual.

Background of the study
Depressive disorders in adolescents is an important health problem and are
(combined with anxiety disorders) one of the most prevalent disorders in
adolescence. The year prevalence of depressive episodes among youngsters
between 13 and 17 years of age is 2,8% (Verhulst et al., 1997). Before entering
adulthood, 14 to 25% of the adolescents has experienced one episode of a
depressive disorder (Ryan, 2005). Besides the high prevalence, 40 to 90% of the
depressed adolescents has a co morbid disorder such as anxiety (25%), OCD
(15%), and ADHD or behavioural disorders (25-40%) (Depressie richtlijn, 2009).
Even more, there is a heightened risk of developing social problems, juridical
problems, learning problems, substance abuse, negative life events, physical
problems, teen pregnancies en suicide (Ryan, 2005; Portzky & van Heeringen,
2009). Depressive disorders in 15 to 24 year olds are in the top-3 of diseases
with the highest burden of disease expressed in DALY*s (Hoeymans et al., 2006).
Depressive disorders are usually chronic disorders with a high risk of
recidivism. Therefore it is important that depression is treated in an early
stage with an effective treatment (Ryan, 2005).
In the international literature, there is no consensus on the degree of
effectiveness of psychotherapeutic interventions in depressed adolescents. In a
meta-analysis, only a modest effect size of 0.34 was found (Weisz et al.,
2006). Partially this can be explained by the large diversity of the
investigated interventions (prevention to intervention) and the differences in
the severity of the depression at pre-treatment (symptom level to diagnosis).
Other meta-analyses focussed on psychotherapeutic interventions found effect
sizes of respectively 0.72 (Michael & Crowley, 2002) and 1.27 (Lewinsohn &
Clarke, 1999). In a meta-analysis solely directed at Cognitive Behavioural
Therapy (CBT) an effect size of 0.53 was found (Klein et al., 2007).
Until recently there is no evidence based intervention available for depressive
disorders in adolescents in the Netherlands. In the past few years, the focus
has been directed at prevention of depressive symptoms with programs like *Grip
op je dip* en *Head Up*. Both programs are not (yet) evidence based and not
suitable for clinically depressed adolescents. A CBT program that is indeed
suitable for this study population is the *D(o)epressiecursus* (translation;
D(o)epression course)* (Stikkelbroek, Bouman, & Cuijpers, 2005). This
intervention is frequently used in clinical practice. The *D(o)epressiecursus*
is a revision of the *Coping with depression course for Adolescents
(CWD-A)* (Clarke et al., 1990). The CWD-A is often investigated by means of
RCT*s in an American population and results repeatedly show that the CWD-A is
more effective than care as usual (Clarke et al., 1995; Clarke et al., 2001;
Clarke et al., 2002). Because the CWD-A was only investigated by one research
Group, it is regarded as probably efficacious (David-Ferdon & Kaslow, 2008).
The effectiveness of the *D(o)epressiecursus* has not been investigated yet.
However the databank effective interventions by the Dutch Youth Institute (NJI)
has labelled the *D(o)epressiecursus* as theoretically well founded. Besides
the guideline depression in youth (Depressie Richtlijn, 2009) recommends the
*D(o)epressiecursus* as psychotherapeutic intervention of choice in depressed
adolescents. In this study the effectiveness of the individual CBT program the
*D(o)epressiecursus* will be investigated by comparing it to care as usual.
The costs of depression in adolescents have not been studied before. A recent
cost-of-illness study on children with anxiety disorders shows that both the
costs of school absence as productivity loss of the parents are substantial
(Bodden et al., 2008). Given the high degree of comorbidity of anxiety and
depression and the fact that both disorders are among the internalising
disorders, the same high costs are expected in adolescents with depression.
Lynch and colleagues (2005) investigated the cost-effectiveness of a group
based prevention course *Coping with Stress* in adolescents with a subclinical
depression. It was concluded that group CBT was more cost effective in
comparison to care as usual. However, intervention related costs like
productivity costs expressed as school absence were not taken into account.
These costs will be included in this study.
Within intervention research in depressed adolescents, little is known about
possible moderators and mediators of treatment. A lot of authors mention the
necessity to investigate these variables (David-Ferdon & Kaslow, 2008; Weisz et
al. 2006). Therefore, moderators and mediators will be investigated in this
research.

The aim of this study is to investigate the effectiveness and the
cost-effectiveness of the individual CBT program the *D(o)epressie cursus* by
means of the following hypotheses;
1. Is the individual CBT program the *D(o)epressie cursus* more effective than
care as usual (without CBT)?
2. Is the individual CBT program the *D(o)epressie cursus* more cost-effective
than care as usual (without CBT)?
3. What is the cost-of-illness of clinical depression in adolescents?
4. Which moderators (comorbidity, severity of depression, age, ethnicity,
gender, suicidal thoughts and psychopathology in parents) influence the
effectiveness of CBT?
5. Which mediators (negative automatic thoughts, cognitive emotion regulation
and attribution style) influence the effectiveness of CBT?
6. Do non-specific treatment variables such as therapeutic alliance, client
expectancy, client satisfaction and treatment adherence influence effectiveness
of CBT?

This research includes a multi-center and randomized clinical trial. Within the
participating institutions, adolescents with a clinical depression will be
assigned at random into either treatment group (D(o)epressie cursus) or control
group (care as usual without CBT). Clients will be recruited via First and
second order Mental health care institutions. An intake procedure and a
diagnostic procedure are executed for each client. If the adolescent meets the
inclusion and exclusion criteria and thus is diagnosed with a primary
depression diagnosis, he or she will receive oral and written information
about the research project. Also the parents are the legal authorised persons
will receive information. If the adolescent is 18 years or older, parents will
only be approached to participate in this research if the adolescent gives his
or her permission (also in informed consent). If both the adolescent and the
parents are willing to participate, they are asked to confirm their
participation by signing an informed consent form; both the adolescent and the
parents sign this form. If the adolescent is 18 years or older, he or she can
also particpate withouth his or her parents. Random assignment per client will
be executed using computer generated block randomisation so an equal number of
adolescents is assigned to the treatment group and the control group. The
content or the kind of treatment the adolescent receives in the control group
will be decided within the institution. Four assessments will be executed
namely prior to the beginning of treatment (pre-test assessment), immediately
after treatment (post-test assessment or after 15 sessions), 6 months after the
end of treatment (6 month follow-up) and 1 year after treatment (1 year
follow-up).
Measurements will consist of a diagnostic interview with the parent and the
adolescent, questionnaires (adolescent and parent) and reviews by the
therapist. The diagnostic interviews will be assessed by independent
researchers that are blinded to condition. Also temporary assessments will take
place to investigate possible mediators. This mediator assessment consists of a
small questionnaire each 5 sessions. To calculate the cost-effectiveness,
quality of life and cost diaries will be assessed. For each completed
assessment, the family will receive a gift cheque of 10 euro*s. To obtain a
high treatment integrity in both conditions, a few treatment sessions will be
chosen ad random that are videotaped or audio taped.

Adolescents are randomly assigned to the CBT program the *D(o)epressie cursus*
or care as usual (without CBT).

Adolescents assigned to the experimental condition, the D(o)epressie cursus,
will receive a individual CBT program. This program is a protocolised
individual version of CBT and consists of 15 weekly sessions that last 45
minutes and two parent sessions after 3 and 9 weeks. The D(o)epressie cursus is
based on the social learning theory about the aetiology of depressions by
Lewinsohn (Lewinsohn, Antonuccio, Steinmetz, & Teri, 1984). According to this
theory, there is a connection between the number of positive interactions
between a person and his environment on one hand, and depression on the other.
A triggering event such as a radical life event, causes a person to have less
positive interactions with his environment. Because of this a negative spiral
of negative thoughts, even less positive interactions with the environment and
a deteriorating depressed mood emerges. The D(o)epressiecursus is a CBT program
that aims to reduce depressive complaints in adolescents with a depressive
disorder. Because depressive episodes are multi-factorial determined and
because of the interaction between biological, social, cognitive and
environmental factors, the focus of the intervention is broad. The intervention
contains the following components; psycho-education (information about
depression and the rationale for the aetiology of the complaints and the
treatment of them), setting attainable goals (translate large goals into
realistic short term goals), self monitoring (registration of the mood,
activities and thoughts), activation (planning frequent, joyful activities),
improving social skills and communication skills (improvement and stimulation
of social behaviour), relaxation techniques, cognitive restructuring
(identifying and changing unrealistic negative thoughts about the self, others
and events), role play and problem solution skills (teaching the creation of
solutions for problems via brainstorm, choosing, trying and evaluating) and
relapse prevention. The exercises will be executed within the sessions and will
be generalised into real life by means of homework assignments. In the parent
sessions, parents will receive psycho education and information on CBT.

The control treatment consists of care as usual for clinical depression like it
is now offered within the participating institutions. Care as usual will
consist of elements of Interpersonal Therapy (IPT), family therapy, parent
counselling, medication, mindfulness, acceptance commitment therapy (ACT),
psychodynamic therapy (short duration), (non-directive) conversation therapy,
creative therapy and running therapy, except for CBT. As far as possible, the
control condition will be a reflection of care as usual as it is currently
offered. Within the control condition no CBT will be offered.
Until now, the content of care as usual for depressed adolescents in the
Netherlands is unknown. One of the sub aims of this study is to direct the
question of; Which treatments are executed in clinical practice and to which
degree are these treatments executed in accordance to the basic treatment
principles? We conducted a survey by Phone among the participating
institutions. This inventory showed that the current care as usual in clinical
practice consists of a large scale of protocolised and non-protocolised
treatments such as Interpersonal Therapy (IPT), family therapy, parent
counselling, medication, mindfulness, ACT, psychodynamic therapy (short
duration), (non-directive) conversation therapy, creative therapy and running
therapy. It appears that in clinical practice, the recent guidelines of the
guide depression in youth (Depressie Richtlijn, 2009) are not applied yet. The
guideline recommend CBT, IPT and medication as treatment of choice. Besides, an
eclectic method of working is utilised in clinical practice, in which elements
of different treatments are combined based on the clinician*s view as was also
shown in a American study (Weersing & Weisz, 2002). Therefore, it is important
to register the content of care as usual per session. This will be obtained by
using the Therapy Procedures Checklist (TPC; Weersing, Weisz & Donenberg,
2002). The therapist will fill in the TPC to monitor the treatment techniques
he or she uses in each session. In such a way, care as usual in adolescents
with a clinical depression can be surveyed.

In this research a structured clinical interview and questionnaires will be
assessed which are frequently used in clinical practice and research worldwide.
The structured interview with the adolescent and the parent (K-SADS) and a
couple of questionnaires (CBCL and YSR) are part of the routine diagnostic
cycle within mental health care (duration 2 hours for the adolescent and 2
hours for the parent). These interviews and questionnaires will also be
assessed if someone doesn*t participate in research. In clinical practice, the
K-SADS and a couple of questionnaires are also assessed at post treatment to
monitor if the depression diagnosis is still present (2 hours adolescent and 2
hours parent), so this also is a part of the routine in clinical practice. At
the 2 follow-up measurements, the K-SADS and questionnaires will be assessed as
well (2x 2 hours adolescent and 2x2 hours parent), this is not routine. The
time investment for filling in the extra questionnaires (not the routine
questionnaires) is therefore limited, namely at pre-treatment 1,5 hour for the
adolescent and 1,5 hour for the parent. At post treatment, follow-up1 and
follow-up2, the time investment will be somewhat lower namely 1 hour and 20
minutes for the adolescent and 1 hour for the parent. Even more, adolescents
and parent have to fill in a questionnaire twice to monitor the mediator
variables. This short questionnaire takes two times 15 minutes. In total, the
time investment will be 14 hours for the adolescent (inclusive the 4 hours
routine measurements) and 13 hours for the parent (inclusive 4 hours routine
measurements). Besides, no burden and no risks are associated with the
assessment of the measurements. In contrary, filling in some of these
questionnaires can give more awareness of the risks that are present in
adolescents with a depression (and thus reduces risk). For example, a suicide
taxation list is assessed through which suicide thoughts and attempts ill be
identified faster and therefore can be handled faster. The adolescent is in
treatment so if parents or the adolescent have a supplementary question or
treatment goal based on filling in the questionnaire, they have direct access
to their therapist. Some of these measurements were also assessed in previous
studies of Clarke.
The intervention in the experimental condition is based on CBT. According to
the guideline depression (Depressierichtlijn, 2009), CBT is recommendend as
tretament of chouice for adolescent with a clinical depression. Therefore, no
harmful effects are expected of the d(o)epressie cursus. Besides, therapists
are trained and supervised. The control condition consists of care as usual
that the institution offers to adolescents with a depression. In this
condition, the adolescent isn*t denied care that is offered in regular
treatment except CBT.
To investigate the treatment integrity, two treatment sessions will be selected
that will be sound- or videotaped. Videotaping or sound taping sessions is very
common and almost routine within the mental health care setting and is used for
intervision and training purposes. Adolescents aged 12 to 18 years and their
parents have to give their formal permission before the session is taped. They
are given information on the purpose (treatment integrity) and that two
sessions with the adolescent will be taped. Both the adolescent and the parent
have to sign an Informed consent and are free to refuse the taping. If they
refuse to cooperate with taping two sessions, this will have no consequences
for the treatment. If the adolescent is 18 years or older, than only the
permission of the adolescent is sufficient to tape two treatment sessions. The
adolescent has to sign an Informed consent.
The investment of the therapists is also limited in time. The therapist fills
in characteristics of the depression and the treatment by means of
questionnaires. A part of this, such as filling in the treatment record is part
of the routine method of working. The assessment of additional questionnaires
and the interview will be done by a research assistant. The contribution of the
therapists is not a burden and does not pose any risks.
The above mentioned burden and risks are very small and do not outweigh the
advantage that, based on this research, information about the effectiveness of
treatment for adolescents with a depression will be available.