PT-STRESS study: a two-phase randomized study aimed at predicting and coping with non-response in the treatment of PTSD; the latter by alternating recommended trauma-focused treatments (EMDR/T-CBT), or by switching to interpersonal therapy (IPT).

The symptoms of posttraumatic stress disorder (PTSD) follow exposure to a
traumatic event and are accompanied by significant functional limitations. PTSD
is very common: a multinational study shows a lifetime prevalence of 3.9%.
Effective treatment options exist for people with PTSD, with Eye Movement
Desensitization and Reprocessing (EMDR) and (imaginary) Exposure (a specific
form of trauma-focused Cognitive Behavioral Therapy, T-CBT) both listed as
first-choice interventions in the Dutch standard of care for psychotrauma and
stressor related disorders. Our impression is that of the various proven
effective forms of treatment, these specific forms of trauma-focused treatment
are also used in the Netherlands. About 40% of patients with PTSD do not
benefit sufficiently from either of the aforementioned guideline treatments and
about 18% of patients do not complete a trauma-focused treatment (treatment
dropout). Knowledge about general predictors of treatment success in
psychotherapy is limited, making it currently impossible to predict which
patient will or will not benefit from which specific psychotherapeutic
treatment (i.e., EMDR vs. Trauma-oriented CBT). Little scientific knowledge
exists about optimal follow-up treatment when patients insufficiently benefit
from their initial treatment. Nevertheless, based on the experiences of the
consulted expert group, the national standard of care for psychotrauma and
stress-related disorders recommends that a switch be considered in that case
between EMDR and T-CBT as trauma-oriented forms of psychotherapy. For patients
who drop out (e.g. from inability to tolerate exposure to traumatic memories)
or do not benefit from exposure therapies, an alternative is to switch not to
another proven effective trauma-focused intervention, but to a
non-trauma-focused intervention. A suitable non-trauma-focused treatment is
Interpersonal Psychotherapy (IPT; Markowitz, 2021). Previous research suggests
that IPT can be an effective first-line treatment option, but the effectiveness
of IPT as a second treatment step for people with PTSD who have not responded
to a trauma-focused psychotherapy has never been investigated. We hypothesize
that IPT will yield greater symptom reduction and less dropout for patients
with PTSD who do not respond to a course of trauma-focused psychotherapy
compared to switching to another trauma-focused therapy.

The aim of the current study is to increase understanding of the effectiveness
and efficiency of psychological treatment for patients with PTSD and to better
personalize differential therapeutics.

Key questions:
1. Which generic predictors of treatment success influence treatment outcome of
patients with PTSD who receive the three psychotherapeutic treatments
investigated in this study (regardless of the type of treatment)?
2. Which specific moderators can be identified among the different
psychotherapies (EMDR, CBT; and IPT in the second phase)?
3. In patients with PTSD, does offering another proven effective form of
trauma-focused psychotherapy (T-CBT after EMDR, or EMDR after T-CBT) improve
PTSD symptoms following insufficient response to a first proven trauma-focused
treatment?
4. Is switching from a trauma-focused therapy to a non-trauma-focused treatment
(IPT) a more effective strategy for dealing with non-response to a first proven
effective psychotherapeutic treatment compared to switching to another
trauma-focused therapy?
5. When treating patients with PTSD, are there differences in tolerance of the
method (looking at patient experiences of undesirable effects and negative
events as a result of the treatment) and differences in dropout rate among
T-CBT, EMDR and IPT?

Secondary goals:
- Investigating the extent to which therapist allegiance to a specific therapy
method affects outcomes;
- Investigating whether the quality of therapy implementation or the treatment
integrity (*adherence/ competence*) affects treatment outcomes;
- Investigating how much the quality of the therapeutic alliance influences
outcomes.

The study is a randomized controlled trial (RCT) conducted in two phases. Its
aim is to compare two different proven effective trauma-focused,
guideline-recommended treatments (EMDR and T-CBT) for patients with PTSD to one
another and with a non-trauma-focused psychotherapy (IPT) and to investigate
possible predictors and moderators for treatment success. Patients with PTSD
will first be randomized to T-CBT or EMDR in the first treatment phase. After
this first phase of treatment, non-responders are re-randomized for a second
phase of treatment. They receive either the alternative phase 1 trauma-focused
psychotherapy or IPT as non-trauma-focused therapy for PTSD.

Half of initially non-responsive patients will be treated with the
non-trauma-focused intervention interpersonal therapy (IPT) in phase 2 of the
study. The first and second phases will offer the
trauma-focused treatments Exposure (a specific form of T-CBT) and EMDR.
- Interpersonal Psychotherapy (IPT) does not target the memories of a
traumatic event but the interpersonal consequences of trauma, seeking to
improve affective and interpersonal functioning that PTSD symptoms have
disrupted (Bleiberg & Markowitz, 2019). PTSD following a traumatic life event
produces social withdrawal and a blunted, inhibited emotional life, disrupting
interpersonal functioning. IPT helps benumbed patients recognize and tolerate
their feelings so they can use them to handle their social environment,
determine who is trustworthy, and mobilize protective social supports. IPT
addresses patient emotions and their relationship to interpersonal
interactions. As patients recognize their feelings, the therapist helps
patients to name, normalize, and use their feelings rather than seeing them as
an additional threat.
- In exposure, as a specific form of trauma-focused CBT, patients directly
confront traumatic memories and cues and learn to expose themselves to
terrifying but not in fact dangerous stimuli to achieve habituation or
extinction. The current study will use a protocol-based treatment of Cognitive
Behavioral Therapy for PTSD that includes imaginal and in vivo exposure (Van
Minnen & Arntz, 2017).
- In EMDR, patients are distracted from the traumatic memories by a dual
attention task, usually using eye movements. This study will use a protocolled
EMDR treatment for PTSD (De Jongh & Ten Broeke, 2019).

Major adverse events are not expected as these have not been documented in
previous studies (Hoppen, Lindemann, & Morina, 2022). The greatest burden on
subjects is completing the questionnaires necessary to answer the primary
research questions. In phase 1, this totals approximately 10.5 hours (with
baseline measurement the most extensive and subsequent weekly measurements);
for patients treated for an additional 8 weeks in phase 2, completing the
questionnaires takes approximately another 6 hours. A patient participating in
both treatment phases therefore spends a total of approximately 16.5 hours
completing assessments. Patients taking medication must be stably prescribed
prior to the study, then continued during the study as advised by the doctor
and preferably not changed, unless necessary due to a crisis or serious side
effects. Patients receive treatment sessions twice a week, which is relatively
frequent compared to usual treatment, but research shows that dropout is lower
with twice weekly sessions (Levinson et al., 2022). Study participation further
assures patients that the treatments they receive are performed as intended by
the therapy developer because therapists receive supervision and checks are
made to ensure treatment integrity.