The aim of this study is to increase understanding of the effectiveness and efficiency of psychological treatment for adult patients with posttraumatic stress disorder -PTSD- and to make it more personalized.

Key questions:

1. Which predictors of treatment success influence treatment outcome of patients with PTSD who receive the three psychotherapeutic treatments investigated in this study?
2. Which specific moderators can be identified with regard to the different psychotherapies (Eye Movement Desensitization and Reprocessing -EMDR-; Prolonged Exposure -PE-; and Interpersonal Psychotherapy -IPT- in the second phase)?
3. In patients with PTSD, does offering another proven effective form of trauma-focused psychotherapy (PE after EMDR, or EMDR after PE) improve symptoms following insufficient response to a first 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. Are there differences in treatment tolerance and differences in dropout rates between PE, 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.

Participants receive treatment and will complete questionnaires. The study is conducted in two phases. Its aim is to compare two different trauma-focused treatments (EMDR and PE) for patients with PTSD to one another and with a nontrauma-focused psychotherapy (IPT) and to investigate possible predictors and moderators for treatment success. Patients will first be randomized to PE or EMDR in the first treatment phase. After this first phase, 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. In phase 1 researchers will compare the PE and EMDR group to see which treatment is most effective for whom. In phase 2 researchers will compare the trauma-focused treatments (PE and EMDR group) with the nontrauma-focused treatment (IPT group) to see which treatment is most effective for whom.

Background of the study:

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 Prolonged Exposure (PE; 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. 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. PE). Little scientific knowledge exists about optimal follow-up treatment when patients insufficiently benefit from their initial treatment. 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-traumafocused treatment is Interpersonal Psychotherapy. 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.

Study population:

Subjects are recruited from Dimence, a mental health institution in the Netherlands. Subjects are recruited from patients who register for outpatient treatment within the Dimence division "Specialistic Diagnostics and Treatment" with a primary diagnosis of PTSD. It concerns adults between 18 and 65 years old, both men and women.

Intervention:

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 Prolonged Exposure 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. 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 Prolonged Exposure, patients directly confront traumatic memories and cues and learn to expose themselves to terrifying but not 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.
• 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.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable):

Major adverse events are not expected as these have not been documented in previous studies. 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. The prescription of patients taking medication must be stable prior to the study, and then not changed during the study, 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 two weekly sessions. 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.

Inclusion Criteria:

• Adults between the ages of 18 and 65 who were classified with a primary diagnosis of PTSD (based on the DSM-5 criteria).
• Adults who are willing to participate in the study (informed consent)

Exclusion Criteria:

• Insufficient proficiency in the Dutch language.
• Patients who cannot follow the treatment protocol (for example due to prolonged absence) are excluded from the study.
• Patients who use medication that is not stable. If properly set to the last prescribed medication by the doctor there will be advised to continue and referably not change the medication and its dose during treatment, unless necessary in connection with side effects, crisis, etc.
• Patients that already received an evidence-based form of trauma-oriented treatment for PTSD in the past year and for sufficient treatment duration, in accordance to the Dutch professional practice guidelines (reference: Akwa GGZ (2020, December 1). GGZ Standaarden. Psychotrauma- en stressorgerelateerde stoornissen. Retrieved September 29, 2022, from https://www.ggzstandaarden.nl/zorgstandaarden/psychotrauma-en-stressorgerelateerde-stoornissen/introductie).
• Patients with serious suicidality that requires acute intervention and structural addition of additional treatment interventions.
• Patients with an intellectual disability.
• Patients with a serious addiction as a comorbid problem.
• Patients with an acute mania or a psychotic state.