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

Veränderungen Dynamischer Symptom-Netzwerke Unter Pharmakologischer, Psychotherapeutischer Und Kombinierter Behandlung Bei Depression (DYNDET)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression - Major Depressive Disorder
• Intervention / Treatment: Drug: Psychopharmacological treatment; Behavioral: Cognitive-behavioral group treatment (CBGT-D)

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Frankfurt, Germany, 60486
    • Clinical Psychology and Psychotherapy
    • Contact: Ulrich Stangier, Prof. Dr.; Phone Number: +496979823842; Email: stangier@psych.uni-frankfurt.de
    • Contact: Mareike Ebert, M.Sc.; Email: m.ebert@psych.uni-frankfurt.de
  • Frankfurt, Germany, 60528
    • Department of Psychiatry, Psychosomatics and Psychotherapy
    • Contact: Oliver Grimm, PD Dr.; Phone Number: +6906963012224; Email: O.Grimm@med.uni-frankfurt.de
  • Marburg, Germany, 35039
    • Department of Psychiatry and Psychotherapy
    • Contact: Igor Nenadić, Prof. Dr.; Phone Number: +4964215865002; Email: nenadic@uni-marburg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Depressive disorder (mild to moderate symptom severity)
2. 18-65 years
3. must own a smartphone with internet access

Exclusion Criteria:

1. severe depressive episode
2. acute suicidality,
3. bipolar disorder,
4. substance use disorder
5. psychotic depression
6. severe medical or neurological illness
7. insufficient german language skills
8. concurrent psychotherapeutic treatment
9. conditions that may interfere with fMRI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psychopharmacological treatment; Participants receive psychopharmacological treatment according to guideline-based clinical practice.	Drug: Psychopharmacological treatment; 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.
Experimental: Psychotherapeutical group treatment; Participants receive manualized cognitive-behavioral group psychotherapy.	Behavioral: Cognitive-behavioral group treatment (CBGT-D); 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.
Experimental: Combined intervention; Combination of the aforementioned psychopharmacological and cognitive-behavioral group treatment.	Drug: Psychopharmacological treatment; 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.; Behavioral: Cognitive-behavioral group treatment (CBGT-D); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton rating scale for depression (HAM-D)	Observer rated scale of depression severity. Total score ranging from 0 to 51, with lower scores indicating less severity of depressive symptoms.	From Inclusion to immediately Post-Treatment (11 weeks)
Montgomery-Åsberg Depression Rating Scale (MADRS)	Observer rated scale of depression severity. Total score ranging from 0 to 60, with lower scores representing less severity of depressive symptoms.	From Inclusion to immediately Post-Treatment (11 weeks)
The Inventory of Depressive Symptomatology clinician (IDS-C)	Observer rated scale of depression severity. Total score ranging from 0 to 84, with lower scores indicating less severity of depressive symptoms.	From Inclusion to immediately Post-Treatment (11 weeks)
Social and Occupational Functioning Assessment Scale (SOFAS)	Observer rated scale of social and functional impairment. Scores ranging from 0 to 100, with higher scores representing a higher level of functioning.	Immediately at Inclusion
Positive and Negative Affect Schedule - Short Form (PANAS-SF)	Self report scale of positive and negative affect. Scores can range from 10 to 50 for both subscales (positive affect and negative affect). Higher scores indicate a higher level of either positive or negative affect	From Inclusion to immediately Mid-Treatment (7 weeks)
Perseverative Thinking Questionnaire (PTQ)	Self-rating scale for repetitive negative thinking. The score ranges from 0 to 60. Higher scores indicate a higher level of repetitive negative thinking	From Inclusion to immediately Mid-Treatment (7 weeks)
The Acceptance and Action Questionnaire (AAQ-2)	Self-rated measure of psychological flexibility. Score ranging from 7 to 49. Higher total scores indicate less flexibility, while lower total scores indicate more flexibility.	From Inclusion to immediately Mid-Treatment (7 weeks)
Fragebogen zur sozialen Unterstützung (F-SozU)	Self-report scale of social support. A higher score indicates a better outcome.	From Inclusion to immediately Mid-Treatment (7 weeks)
Couples Satisafction Index (CSI-4)	Self-report scale of relationship satisfaction in couples with a score range from 0 to 21. Higher scores are associated with higher levels of relationship satisfaction.	From Inclusion to immediately Mid-Treatment (7 weeks)
Perceived Deficits Questionnaire - Depression (PDQ-D)	Self-rating scale of cognitive dysfunction. Score ranging from 0 to 80. Higher scores representing higher cognitive dysfunction.	From Inclusion to immediately Mid-Treatment (7 weeks)

Collaborators and Investigators

• Sponsor: Goethe University
• Collaborators: Johann Wolfgang Goethe University Hospital; Philipps University Marburg
• Investigators: Principal Investigator: Igor Nenadic, Prof. Dr., Philipps University Marburg

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: February 23, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 23, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2025-2718

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data that underlie reported results will be shared after deidentification.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No