Effectiveness of EMDR for adolescents with Major Depressive Disorder

Major depressive disorder (MDD) is one of the most common psychiatric disorders
of childhood and adolescence (Mullen, 2018). It has been estimated that 14 to
25% of adolescents experience at least one episode of a depressive disorder
before entering adulthood (Ryan, 2005). MDD is a leading cause of disability in
terms of burden of disease and poor functioning (Smith, 2014; Stikkelbroek,
Bodden, Dekovi* & van Baar, 2013). Furthermore, MDD with adolescent onset has
been found to be associated with a range of physical health problems and other
mental health disorders in adult life (Thapar, Collishaw, Pine & Thapar, 2012;
Weersing, Jeffreys, Do, Schwartz & Bolano, 2017) as well as with social
problems, legal problems, and elevated suicide risk (Stikkelbroek et al.,
2013). Current treatments show limited effectiveness and high drop-out and
relapse rates. For example, the mean effect size of Cognitive behavioural
therapy (CBT), which is recommended as evidence-based psychosocial intervention
for MDD in the NICE guideline (2019), was only 0.29 in a meta-analysis of CBT
for adolescent MDD (Weisz et al., 2017). In a Dutch multicentre study carried
out in specialized mental health institutions Stikkelbroek, 2016) CBT was not
found to be more effective than treatment as usual (TAU). In fact, CBT
performed worse on both drop-out and the number of adverse events during
treatment than TAU. Hence, the development of innovative strategies for
treatment of MDD, especially during adolescence, is of paramount importance in
order to enhance the number of adolescents that profit of treatment.

A developing body of research highlights the role of family relationships and
interactions as being particularly relevant to the onset and maintenance of MDD
in adolescents (Feeny et al., 2009; Schwartz et al., 2012; Stein et al., 2000).
Family functioning is rated as more dysfunctional in families with a depressed
adolescent (e.g. Tamplin, Goodyer & Herbert, 1998) compared to families without
mental disorders. Family functioning predicts onset of adolescent MDD (e.g.
Wang, Tian, Guo, & Huebner, 2020) and possibly treatment outcome (e.g. Feeny et
al 2009, Rengasamy et al., 2013).
Also, the role of distressing experiences that relate to the development and
maintenance of MDD has been recognized for decades (Monroe, Slavich and
Georgiades, 2014, Mandelli, Petrelli & Serretti, 2015). More specifically, it
was found that traumatic interpersonal experiences, like humiliation and
entrapment (Kendler et al., 2003), and different forms of childhood abuse,
primarily emotional abuse and emotional neglect (Hovens et al., 2010, Mandelli
et al., 2015) are related to MDD. Moreover, having a history of childhood
trauma predicts poor efficacy of treatment (Barbe, Bridge, Birmaher, Kolko &
Brent, 2004; Lewis et al. 2010; Nanni, Uher & Danese, 2012), which highlights
the importance of identifying trauma histories and adding trauma focused
interventions when treating depressed adolescents (Lewis, 2010).

Eye movement desensitization and reprocessing (EMDR) therapy (Shapiro, 2017)
appears to be a promising treatment for MDD in adolescents (Paauw, De Roos,
Tummers, De Jongh & Dingemans, 2019). According to the recent treatment
guidelines EMDR therapy (Shapiro, 2017) is one of the recommended treatments
for posttraumatic stress disorder (PTSD; ISTSS Guidelines Committee, 2018;
World Health Organization, 2013). It has been found to be capable of processing
memories of distressing events (Shapiro, 2017). In the past five years several
studies have been conducted demonstrating preliminary evidence for the efficacy
of EMDR therapy in the treatment of MDD in adults. Promising results were
obtained from studies investigating EMDR therapy as an adjacent therapy to CBT
(Hoffman et al., 2014), to pharmacological treatment (Ostacoli et al., 2018,
Minelli et al., 2019) and to inpatient treatment (Hase et al., 2015; 2018).
Three studies, investigating the efficacy of EMDR as a stand-alone treatment,
demonstrated significant reductions of depressive symptoms (Gauhar, 2016), even
for patients with long-term depression (Wood, Ricketts & Parry, 2018) and
treatment-resistant depression (Minelli et al., 2019). Treatment of MDD also
resulted in significant decreases of trauma symptoms (Gauhar, 2016) and anxiety
symptoms (Minelli et al., 2019), improved social functioning (Minelli et al.,
2019) and quality of life (Gauhar, 2016). In addition to the abovementioned
randomized controlled trials (RCTs), various case studies and pilot studies
were also conducted (see Wood & Ricketts (2013) and Carletto et al. (2017).
However, the listed studies were all focused on adult patients. A first larger
effectiveness study with adolescents (apart from a case series by Bae, Kim &
Park; 2008) was recently carried out by our group, where we included 32
adolescents with MDD as a primary diagnosis in an outpatient youth mental
healthcare institution (Paauw, De Roos, Tummers, De Jongh & Dingemans, 2019).
After 6 EMDR sessions, 60.9% of the adolescents who finished treatment, no
longer met DSM-IV criteria of MDD and the severity of comorbid anxiety,
posttraumatic stress symptoms and somatic complaints were significantly
reduced. At follow-up measurement three months after treatment, these results
were maintained. Since these results were very promising more high quality
studies are needed (e.g. with a randomized controlled design, a larger number
of participants and a longer follow-up period).

This study aims to investigate the effectiveness of EMDR (n=32) in comparison
to a waiting list in (n=32) adolescents (12-18 years) with a primary diagnosis
of MDD (DSM-5; American Psychiatric Association, 2013). It is hypothesized that
the application of EMDR therapy is associated with a significant decrease in
severity of depressive symptoms and decrease of percentage of patients meeting
DSM-5 criteria for MDD compared to the waiting list. Furthermore, we
hypothesize that treatment will be associated with a significant decrease in
severity of co-morbid symptoms (i.e., post-traumatic stress symptoms, anxiety,
somatic and overall social-emotional problems) compared to waiting list. In
addition, we will examine whether baseline posttraumatic stress symptoms
severity, family functioning and having experienced emotional abuse or neglect
significantly predicts post-treatment outcome.

In this study patients will be randomly assigned to one of two conditions: (a)
EMDR treatment or (b) waiting list condition.
Randomisation will be done (using SPSS function *random numbers*) by an
independent researcher. Assessments (see figure 1) are scheduled pre-treatment
(T0), post-treatment (T1), at 3-months (T2) and at 6-months (T3) follow-up.
Assessment will be done by a team of independent assessors (i.e., trained
clinicians and master level students) who are blind for the condition.
Participants in the waiting list condition are offered EMDR treatment after T1,
subsequently they are also assessed post-treatment and at 3- and 6-months
follow-up (see Figure 1).
The primary outcome variables are depressive symptoms (as measured by the CDI)
and the presence or absence of a MDD diagnosis, based on the Kiddie-SADS
Interview (K-SADS-PL-5; Kaufman et al., 2016). Secondary outcomes variables are
post-traumatic stress symptoms, anxiety, somatic symptoms and overall
social-emotional problems.
Because perceptual differences on symptoms and family functioning between
adolescents with MDD and their parents (c.f. Chen et al., 2017) exist,
questionnaires will be administered to both adolescents and parents.

The Dutch version of the standard EMDR protocol with age-specific adaptations
for children and adolescents (De Roos, Beer, De Jongh & Ten Broeke, 2020) will
be used. This procedure includes eight phases: history taking, preparation,
assessment, desensitization, installation, body scan, closure and re-evaluation
(Shapiro, 2017). Treatment consists of a maximum of six weekly 60-minute
individual treatment sessions. When all target memories from the case
conceptualisation can be retrieved without emotional disturbance (i.e. SUD
related to the memory is reduced to zero) in less than six session, this will
be classified as early completion of treatment.
Memories are placed in a hierarchy based on the Subjective Units of Disturbance
(SUD), and are treated subsequently from high to low SUD. Each session will be
followed by a 15-minute meeting with the adolescent and one or both parents.
The content of this meeting is discussed beforehand with the adolescent and
comprises any one of the following elements: (1) an outline of the content of
the session (2) parents* view on the course of symptoms in the week before the
session and (3) the need and possibilities for emotional support of the
adolescent after the session.
Therapists have at least completed both Basic and Advanced EMDR training. All
sessions will be videotaped and all therapists participate in monthly two-hour
supervisions by a certified EMDR Europe Child and Adolescent Consultant (CdR).
Additional supervision by email or telephone is provided on request.

Participation in the study is not associated with obvious risks. The burden of
participation in the study is small and temporary. Baseline assessment (T0)
takes up to two hours to complete; time investment for follow-up assessments
(T1-T3) is 1-1.5 hours.

All participants will be offered active treatment, either directly after
inclusion, or after 6 weeks waiting list condition.

For participants in both active and waiting list condition a patient safety
plan will routinely be made as part of the assessment phase. For participants
in the waiting list condition a therapist is available in case of crisis or
sudden worsening of symptoms; a record will be made of such contacts. During
treatment phase, the therapist and multidisciplinary team, and also the 24-our
crisis team, are available in the same way as during care-as-usual.

If depressive symptoms remain after EMDR treatment, additional treatment
interventions can be applied.