Dynamic Networks in Depression Treatment: Mechanisms of Change in Pharmacological, Psychological and Combined Treatment of Depression

NCT07488910 | Not Yet Recruiting Phase 4

• 1 other identifier: 2025-2718
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief Summary

This study investigates how antidepressant pharmacotherapy, cognitive-behavioral therapy, or their combination modulate the temporal dynamics and connectivity of depressive symptom networks. Using intensive longitudinal ecological momentary assessment data, the trial examines treatment-specific changes in symptom interactions. By applying network-based analytic approaches, the study aims to elucidate differential and potentially complementary mechanisms of change across treatment modalities. Findings may contribute to more informed and individualized treatment strategies for major depressive disorder.

Conditions

Depression - Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Structure of symptom networks via multilevel vector autoregressive modeling (mlVAR)

  Planned network intervention analyses will focus on intervention-specific effects at the symptom-network level. We will describe whether each of the three interventions shows differential direct associations with specific depressive symptoms or processes, operationalized as edges between intervention indicators and symptom/process nodes. We will also examine whether the interventions differ in their pattern of indirect associations within the network, that is, whether changes in some symptoms appear to be associated with downstream changes in other symptoms or processes. In addition, we will compare centrality metrics of depressive symptoms across interventions and over time.

  From Baseline (2 weeks) to immediately Post-Treatment (11 weeks)

Secondary Outcomes (10)

• Hamilton rating scale for depression (HAM-D)

  From Inclusion to immediately Post-Treatment (11 weeks)

• Montgomery-Åsberg Depression Rating Scale (MADRS)

  From Inclusion to immediately Post-Treatment (11 weeks)

• The Inventory of Depressive Symptomatology clinician (IDS-C)

  From Inclusion to immediately Post-Treatment (11 weeks)

• Social and Occupational Functioning Assessment Scale (SOFAS)

  Immediately at Inclusion

• Positive and Negative Affect Schedule - Short Form (PANAS-SF)

  From Inclusion to immediately Mid-Treatment (7 weeks)

Study Arms (3)

Psychopharmacological treatment

EXPERIMENTAL

Participants receive psychopharmacological treatment according to guideline-based clinical practice.

Drug: Psychopharmacological treatment

Psychotherapeutical group treatment

EXPERIMENTAL

Participants receive manualized cognitive-behavioral group psychotherapy.

Behavioral: Cognitive-behavioral group treatment (CBGT-D)

Combined intervention

EXPERIMENTAL

Combination of the aforementioned psychopharmacological and cognitive-behavioral group treatment.

Drug: Psychopharmacological treatment; Behavioral: Cognitive-behavioral group treatment (CBGT-D)

Interventions

Psychopharmacological treatment DRUG

Participants will receive outpatient treatment with escitalopram. Treatment will be initiated at 5 mg/day for three days and increased to a target dose of 10 mg/day. Clinical re-evaluations will take place after two and four weeks. In case of insufficient clinical response, the dose may be increased to 15 mg/day in accordance with guideline recommendations.

Combined intervention; Psychopharmacological treatment

Cognitive-behavioral group treatment (CBGT-D) BEHAVIORAL

Consisting of a group treatment of the same time frame as the psychopharmacological treatment and includes the following components: psychoeducation, behavioral activation, cognitive restructuring, social problem-solving, homework assignments and relapse prevention.

Combined intervention; Psychotherapeutical group treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Depressive disorder (mild to moderate symptom severity)
• years
• must own a smartphone with internet access

You may not qualify if:

• severe depressive episode
• acute suicidality,
• bipolar disorder,
• substance use disorder
• psychotic depression
• severe medical or neurological illness
• insufficient german language skills
• concurrent psychotherapeutic treatment
• conditions that may interfere with fMRI

Sponsors & Collaborators

• Goethe University: lead
• Johann Wolfgang Goethe University Hospital: collaborator
• Philipps University Marburg: collaborator

Study Sites (3)

Clinical Psychology and Psychotherapy

Frankfurt, 60486, Germany

Location

Department of Psychiatry, Psychosomatics and Psychotherapy

Frankfurt, 60528, Germany

Location

Department of Psychiatry and Psychotherapy

Marburg, 35039, Germany

Location

Study Officials

• Igor Nenadic, Prof. Dr.

  Philipps University Marburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the interventions, full blinding is not feasible. Participants are aware of their assigned treatment condition, as the interventions differ in format (e.g., pharmacotherapy versus group CBT). Similarly, therapists and prescribing physicians are not blinded. However, clinical outcome assessments, specifically structured interviews such as the HAM-D, are conducted by trained raters who remain blinded to group allocation wherever possible. To reduce analytical bias, data analysis will be conducted on pseudonymized datasets, with group identifiers masked during preprocessing and statistical modeling stages (Schulz et al., 2010).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Goethe Research Professorship

Model Details: The study employs a parallel-group design with three arms: selective serotonin reuptake inhibitor (SSRI) pharmacotherapy, cognitive behavioral therapy (CBT) delivered in a group format, and a combination of both interventions. The study is multicentred across two locations encompassing three study centres.

Study Record Dates

• First Submitted: February 23, 2026
• First Posted: March 23, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

DE (3)