The MOP II study examines how to improve therapy for people struggling with a depressive disorder. Cognitive Behavioral Therapy (CBT) and Short-Term Psychodynamic Psychotherapy (STPP) are two evidence-based treatments for depression that are widely used. Meta-analyses indicate that CBT and STPP are one average equally effective and superior to no treatment. However, many patients do not respond sufficiently and relapse rates after acute phase treatment are high.

Earlier research and theoretical insights suggest three promising strategies to enhance the effectiveness of psychotherapy. First, we want to examine whether increasing the frequency of the sessions will increase the effect of therapy. We want to compare once-weekly and twice-weekly sessions in both CBT and STPP to see whether more frequent sessions lead to better and more lasting reductions in depressive symptoms with the same total number of sessions.

Second, the study aims to answer what works for whom in two different psychotherapeutic approaches. People with depression differ in personality, life experiences, relationship styles, and how they understand the causes of their depression. Previous findings suggest that patients do better when the therapy approach matches how they see their problems. The MOP II study wants to replicate this finding.

Third, the study wants to examine how therapy leads to change. In CBT, improvement is thought to happen through changes in thinking patterns, such as fewer negative automatic thoughts and less rumination. In STPP, change is expected to come from better self-understanding, greater emotional awareness, and healthier ways of relating to others.

Consequently, the goal of the MOP II study is to find out whether more frequent therapy, better matching of patients to treatment type, and a clearer understanding of how therapy works can lead to faster improvement of depressive symptoms.

Major depressive disorder (MDD) leads to significant disability, mortality, and economic strain. It ranks fourth globally in terms of disease burden and is expected to rank first in high-income countries by 2030, highlighting an urgent need for effective treatments. Evidence-based psychotherapy methods and antidepressant medications are equally effective treatments. Cognitive Behavioral Therapy (CBT) and Short-Term Psychodynamic Psychotherapy (STPP) are two evidence-based treatments for depression that are widely used. Meta-analyses indicate that CBT and STPP are one average equally effective and superior to no treatment. However, many patients do not respond sufficiently and relapse rates after acute phase treatment are high, estimated at up to 40%.

The guidelines from the UK National Institute for Health and Care Excellence (NICE) underscore the importance of personalized care. They recommend various therapies, including CBT and STPP, tailored to individual needs and preferences of patients with both mild and severe depression. However, the empirical evidence supporting personalized care is limited and insufficient.

Earlier research and theoretical insights suggest two promising strategies to enhance the effectiveness of psychotherapy. First, increasing the frequency of therapy sessions may lead to better treatment outcomes. Second, conducting experimental studies that explore "what works for whom and how" may provide knowledge that can improve efficacy, raise the proportion of responders, and reduce relapse risk. Based on such research, tailoring interventions to individual needs can further optimize treatment success.

2. Background 2.1 Once versus twice weekly sessions of psychotherapy A meta-regression analysis by Cuijpers et al. found a strong association between session frequency and treatment effect size. Specifically, increasing the frequency from one to two sessions per week-while keeping the total number of sessions constant-led to a substantial increase in effect size (g = 0.45). These findings suggest that concentrating psychotherapy sessions within a shorter time frame may enhance treatment efficacy. However, as Cuijpers et al. (2013) concluded, more research is necessary to validate the robustness of these results. The optimal duration and intensity of psychotherapy remain unclear, and most previous studies have lacked controlled designs.

To our knowledge, only one randomized controlled trial (RCT) has directly compared the effects of once-weekly versus twice-weekly psychotherapy sessions. Bruijniks et al. conducted an RCT investigating whether patients with depression receiving twice-weekly sessions of cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) showed greater symptom improvement than those receiving once-weekly sessions of the same therapies. The study found an effect size of 0.55 in favor of twice-weekly sessions. However, in a two-year follow-up study, Bruijniks et al. reported that while the differences persisted for up to nine months, no significant differences remained at the 24-month follow-up.

The long-term effects of increasing session frequency in patients with MDD remain uncertain. It is likely that different trajectories of improvement emerge between those receiving once versus twice-weekly therapy. A deeper understanding of these trajectories has the potential to refine treatment strategies for MDD, ultimately benefiting patients, clinicians, psychotherapy trainers, healthcare managers, and policymakers. Different trajectories of improvement are likely for patients receiving one session per week compared to those receiving two sessions per week. Understanding these differences has the potential to improve outcome for the treatment of MDD.

2.2 What works for whom? (Moderators/Specific markers) Patients with MDD differ in symptom severity and characteristics regarding comorbidity, personality traits, and interpersonal functioning. The present project is a pre-planned follow-up of the Mechanisms Of change in Psychotherapy - I (MOP I) study. Further knowledge into how specific markers (e.g. various sociodemographic; age, gender, education level, comorbidities, personality traits, and relational competence) impact the treatment outcomes of CBT versus STPP are needed. Further we, aim to replicate the preliminary findings from MOP I, which indicated that by evaluating patients' narratives regarding the perceived causes of their depression and the conditions necessary for recovery, a meaningful match could be established. Specifically, when the scoring of a patient's narrative aligned with the therapeutic approach they received-either psychodynamic therapy (PDT) or cognitive behavioral therapy (CBT)-the likelihood of significant improvement in their depressive symptoms was substantially higher. The results may aid in selecting the optimal treatment modality of choice for patients with a depressive disorder.

2.3 How does psychotherapy work? (Mediators) A mediator of treatment outcome is a specific mechanism of change for a particular form of psychotherapy suggesting how or why symptom change occurs. Psychotherapy is likely to involve multiple mechanisms of change.

The theoretical framework for CBT assumes that changes in cognitive processes and underlying schemas are followed by reduced symptoms and improved functioning and quality of life. Thus, negative automatic thoughts, dysfunctional attitudes, different attributional styles, and cognitive schemas, are all potential mediators of change in CBT. Evidence from research into mechanisms of change specific to CBT suggests that rumination, worry, dysfunctional attitudes and cognitive schemas could be specific mediators (Lemmens et al., 2016).

In STPP, theoretically assumed mediators of change are improved self-understanding, improved emotional awareness, more mature defence mechanisms, and reflective functioning.

However, there is limited empirical evidence supporting the role of these theoretical constructs as mediators in psychotherapy. More research is needed to determine whether these variables mediate the effects of psychotherapy and to what extent they are specific to CBT or STPP.

3. Aims The primary aim of this project is to investigate whether patients receiving twice-weekly sessions of CBT and STPP experience faster, greater, and sustained improvement in depressive symptoms compared to those receiving weekly sessions. Secondly, we want to examine potential moderators and mediators of change in CBT and STPP.

Session frequency We hypothesize that patients receiving therapy twice weekly, regardless of the therapeutic approach, will show greater improvement in depressive symptoms compared to those receiving therapy once weekly.

Further, we also want to examine if there are differences in each of the two treatment approaches.

With regards to once versus twice-weekly sessions we hypothesize that:

1. Patients receiving twice weekly sessions in CBT will improve more in depressive symptoms than patients receiving one weekly session.
2. Patients receiving twice weekly sessions in STPP will improve more in depressive symptoms than patients receiving one weekly session.

The second set of hypotheses pertains to the analysis of potential moderators and mediators of treatment. More specifically we want to examine the following research question:

Moderators of outcome 3. Can the findings from MOP I be replicated with respect to a questionnaire that demonstrated the ability to match patients to CBT and PDT, resulting in significantly improved treatment outcomes? 4. Are there certain patient characteristics that moderate the outcome of CBT and/or STPP respectively? 5. Are there certain patient characteristics that moderate the outcome of once vs twice weekly session of CBT and/or STPP respectively? 6. If so, which patient characteristic differentially influence outcome in the four treatment conditions? Mediators of change 6. Does improvement occur through different or similar change processes in the two treatment modalities and in once vs twice weekly sessions?

We will test the following theoretically based hypotheses:

In CBT, symptom and functional improvement are mediated by changes in negative automatic thoughts, rumination, dysfunctional attitudes, and cognitive schemas.

In STPP, symptom and functional improvement are mediated by improved self-understanding/insight, emotional awareness, tolerance for emotional distress, and more mature defence mechanisms.

4. Study design Randomized Controlled study. This is a randomized clinical study. Patients will be randomized to either CBT (once or twice weekly) or STPP (once or twice weekly). Clinical assessments will be conducted at baseline, during therapy, at the end of therapy, and at follow-up investigations 1 and 3 years after treatment termination. The design is single blind, i.e. outcome assessors at treatment termination and further follow-up evaluations will not be aware of assigned study condition.

5. Materials and methods 5.1. Participants Patients referred to outpatient psychiatric clinic at Nydalen Psychiatric Outpatient Clinic, Oslo University Hospital (OUS) and Vinderen Psychiatric Outpatient Clinic, Diakonhjemmet Hospital due to symptoms of depression are candidates for the MOP-study. A total of 200 patients will be included.

5.2. Inclusion criteria Patients aged between 18-65 years, with MDD according to clinical assessment and a Hamilton Depression Rating Scale (HDRS) > 14.

Written consent will be obtained from all patients. The participants must be able to speak and understand a Scandinavian language and have the willingness and ability to give informed consent.

5.3. Exclusion criteria Exclusion criteria are a current or past neurological illness, traumatic brain injury, current alcohol and/or substance dependency disorders, psychotic disorders, bipolar disorders, developmental disorders, and IQ <70.

6.0. Treatment conditions 6.1 Cognitive behavioral therapy In condition 1 the treatment consists of 16 weekly CBT sessions followed by three booster sessions at monthly intervals. The treatment is thus offered within a time frame of 28 weeks. In condition 2, the treatment consists of 8 biweekly CBT sessions followed by three booster sessions at 2-week intervals. The treatment is thus offered within a time frame of 14 weeks. Treatment principles are based on "Cognitive Therapy of Depression" by Aaron Beck (Beck et al., 2024) and "Cognitive Behavior Therapy. Basic and Beyond" by Judith S. Beck (Beck, 2020).

Sessions are structured yet flexible, with active therapist involvement. Patients' complete homework and behavioral experiments. Each session starts with a mood score, reviews previous assignments, sets an agenda, and ends with a summary and new homework.

Therapists use interventions like Socratic questioning, the ABC and Diamond models, challenging automatic thoughts, behavioral activation, and identifying thinking traps. These techniques help patients examine beliefs, modify unhelpful thoughts, and engage in positive activities to break cycles of avoidance and negativity.

Early sessions focus on goal setting, case formulation, and building a therapeutic alliance. Later sessions target symptom reduction, while booster sessions reinforce progress and prevent relapse.

6.2 Short-Term Psychodynamic Psychotherapy (STPP) For patients randomized to STPP, condition 3 consists of 28 weekly sessions (Cregeen, 2018). The treatment is thus offered within a time frame of 28 weeks. Condition 4 consists of 28 biweekly sessions. The treatment is thus offered within a time frame of 14 weeks. The treatment principles are based on "Long-term psychodynamic psychotherapy" by Glen O. Gabbard (Gabbard, 2017), which according to the author also can be applied to shorter and / or time-limited therapies. This basic text outlines central principles of psychodynamic psychotherapy such as the significance of unconscious mental functioning, the importance of childhood experiences in concert with genetic factors in shaping adult mental life, and how the phenomena of transference, countertransference, and the patient's defenses and resistance may affect the therapy process.

Therapists explore sensitive topics, interpersonal relationships, and transference with moderate intensity, adapting interventions to each patient's needs. In STPP therapists aim to alleviate depressive symptoms by providing new insights into the connections between past and present experiences, focusing on relational challenges, difficult emotions, defense mechanisms and other unconscious material.

Treatment guidelines, including session structure and therapist-patient roles, are co-developed by therapists and researchers.

7. User involvement A service user is involved in the current project, its background, methodology, and research question, and has had valuable input to all aspects of the study thus far. This service user has experience with both CBT and STPP. Furthermore, she represents two service user organizations (The Service Users' Council at the Oslo University Hospital and The Norwegian Association of Youth Mental Health). She has expressed her enthusiasm for this project and will contribute to developing further relevant research questions, interpreting analyses, and disseminating the results. It is important for us that MOP II is relevant from a service user's perspective. We plan for 2 meetings each year with payments according to set rates by the Norwegian Directorate of Health. We strive to engage additional service users with experience of depression, comorbid disorders, and therapy, preferably differing in age and gender.

8. Plan for implementation The project is a clinically and patient-oriented research study that includes a heterogenous group of patients with MDD and addresses questions that clinicians seek answers to. Through close collaboration with clinicians and management at the outpatient clinics, along with our representative patient sample, there will be a quick path from results to clinical implementation.

9. Reliability and validity The baseline clinical examination will be conducted by a group of experienced clinicians who will complete a training and reliability program at the Division of Psychiatric Treatment Research. In addition, the raters will receive supervision on a regular basis by an experienced rater and clinician. Consensus meetings will be held to assure the reliability of assessments.

The psychotherapy with CBT and STPP will be conducted by therapists from Nydalen and Vinderen psychiatric outpatient clinic, who have completed/started the two-year training in CBT and STPP. In addition, all therapists will receive specific training in the CBT and STPP study manuals. The treatment sessions will be videotaped, and independent and experienced researchers will carry out an assessment of treatment fidelity on a selection of random tapes.

The post-intervention assessments will be conducted by experienced clinicians with training in the protocol.

10. Time schedule The patients will be included from March 2026. The estimated time in treatment is between 4 (conditions 1 and 3) and 9 (conditions 2 and 4) months. With 6-8 therapists in each treatment modality treating 3 patients each at any point of time, our goal is that approximately 45 patients may be treated each year and that all patients will have ended their therapy by December 2030. The last patients will be assessed three years after the end of treatment in December 2033.

Inclusion criteria:

• age 18-65 years
• Major Depressive Disorder Hamilton Depression Rating Scale (HDRS) > 14.
• Speak and understand a Scandinavian language
• Willingness and ability to give informed consent.

Exclusion Criteria:

• Current or past neurological illness
• Traumatic brain injury
• Current alcohol and/or substance dependency disorders
• Psychotic disorders
• Bipolar disorders
• Developmental disorders
• IQ <70.