Stress Systems and Psychotherapy in Depression

NCT03752853 | Completed

• 1 other identifier: Stress_DEP
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis as well as maladaptive activation of the autonomic nervous system (ANS) are discussed as relevant factors in the development of a major depressive episode and as a correlate of its clinical manifestation. Preliminary evidence suggests that the hypercortisolaemic pattern in a subgroup of depressed patients may predict non-responses to psychotherapeutic treatment. At the same time, it is conceivable that disorder-related alterations in HPA axis and ANS regulation change in response to effective treatment, such as cognitive behavioural therapy (CBT), and that those changes could parallel changes in depressive symptoms. Identifying such associations may shed light on biological and psychological mechanisms of action underlying successful treatment. However, so far, no studies have investigated depressed patients with regard to dysregulation in both stress systems, HPA axis and ANS, before psychotherapeutic treatment, nor have changes in functioning of both systems been inspected in response to treatment. Moreover, a detailed investigation of depressive symptom trajectories over the course of treatment and its associations with changes in HPA axis and ANS regulation is lacking. It can be speculated that specific techniques of the treatment, e.g., typical CBT elements, such as behavioural activation or cognitive restructuring, might particularly be associated with changes in HPA axis and ANS regulation. The main aims of this project are to investigate:

1. 1.whether diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations change from pre- to post-intervention in treatment responders compared to non-responders;
2. 2.whether diurnal salivary cortisol and alpha-amylase concentrations change from pre- to mid-intervention and from mid- to post-intervention in treatment responders compared to non-responders;
3. 3.whether changes in diurnal salivary cortisol, alpha-amylase and hair cortisol concentrations are significantly correlated with changes in depressive symptoms;
4. 4.whether concentrations of diurnal salivary cortisol and alpha-amylase as well as hair cortisol at pre-treatment predict future treatment response (i.e., on a psychological level).
5. 5.which elements of a CBT intervention for depression (behavioural activation vs. cognitive restructuring) are associated with changes in diurnal salivary cortisol and alpha-amylase concentrations.
6. 6.that pre- to post-intervention decreases in diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations will be more pronounced in responders compared to non-responders.
7. 7.that pre- to mid-intervention and mid- to post-intervention decreases in diurnal salivary cortisol and alpha-amylase will be more pronounced in responders compared to non-responders.
8. 8.that changes in depressive symptoms will significantly correlate with changes in diurnal cortisol and diurnal alpha-amylase as well as hair cortisol concentrations.
9. 9.that pre-intervention diurnal salivary cortisol and alpha-amylase as well as hair cortisol concentrations will be higher in future non-responders, compared to responders.

Conditions

Major Depressive Episode

Keywords

major depressive episode; cortisol; alpha-amylase; psychotherapy

Outcome Measures

Primary Outcomes (6)

• Changes in salivary cortisol concentration

  Changes in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary cortisol concentration (nmol/l), measured on two consecutive days, at mid-intervention and post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))

  pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)

• Differences in salivary cortisol concentration

  Differences in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of cortisol concentration (nmol/l), measured on two consecutive days, at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)

  pre-intervention

• Changes in salivary alpha-amylase concentration

  Changes in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary alpha-amylase concentration (U/ml), measured on two consecutive days, at mid-intervention and post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))

  pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)

• Differences in salivary alpha-amylase concentration

  Differences in diurnal profiles (six time points: awakening, +30 min., 11am, 2 pm, 6pm, 9pm) of salivary alpha-amylase concentration (U/ml), measured on two consecutive days, at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)

  pre-intervention

• Changes in hair cortisol concentration

  Changes in hair cortisol concentrations (nmol/l) at post-intervention in responders compared to non-responders to the psychological intervention (assessed by Patient Health Questionnaire (PHQ-9))

  pre-intervention, post-intervention (after an average of six weeks)

• Differences in hair cortisol concentration

  Differences in hair cortisol concentrations (nmol/l) at pre-intervention in responders compared to non-responders to the psychological intervention (assessed by PHQ-9)

  pre-intervention

Secondary Outcomes (3)

• Sleep quality (self-report)

  pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)

• Chronic stress (self-report)

  pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)

• Cognitive biases (self-report)

  pre-intervention, mid-intervention (after an average of three weeks), post-intervention (after an average of six weeks)

Study Arms (2)

iCBT for depression - behavioral activation first (BAF)

EXPERIMENTAL

internet-based intervention for mild to moderate depression: patients receive behavioral activation first, followed by cognitive restructuring

Behavioral: internet-based intervention for mild to moderate depression

iCBT for depression - cognitive restructuring first (CRF)

EXPERIMENTAL

internet-based intervention for mild to moderate depression: patients receive cognitive restructuring first, followed by behavioral activation

Behavioral: internet-based intervention for mild to moderate depression

Interventions

internet-based intervention for mild to moderate depression BEHAVIORAL

The six-weeks, therapist-guided, internet-based intervention for depression includes expressive writing tasks and further consists of key elements of cognitive behavioral therapy (CBT) for depression. In seven consecutive modules, patients receive psychoeducation and instructions for weekly tasks, and an individualized feedback letter of their therapist after each module. The intervention is effective in reducing depressive symptoms (Zagorscak et al., 2018). In the current study, patients will be randomly assigned to two different conditions with varying orders of modules: 1. patients will receive two modules (module 3 and 4) of behavioral activation, followed by two modules (modules 5 and 6) of cognitive restructuring; 2. patients will receive two modules (module 3 and 4) of cognitive restructuring, followed by two modules (modules 5 and 6) of behavioral activation. All other modules (1, 2 and 7) will be identical across conditions.

iCBT for depression - behavioral activation first (BAF); iCBT for depression - cognitive restructuring first (CRF)

Eligibility Criteria

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

You may qualify if:

• Current major depressive episode (F32.0, F32.1, F33.0, F33.1)
• Agreement to participate in the study
• At least 18 years of age

You may not qualify if:

• Diagnosis of schizophrenia, schizotypal and delusional disorders (F20-F29)
• Acute suicidal patients
• Acute manic episode
• Substance related abuse or addiction
• Pregnancy or lactation
• Chronic somatic diseases
• Severe somatic diseases (e.g., endocrinological, neurological, autoimmune diseases)
• Glucocorticoid medication intake during the last six months
• Concurrent psychotherapeutic treatment

Sponsors & Collaborators

• Freie Universität Berlin: lead

Study Sites (1)

Freie Universitaet Berlin

Berlin, 14195, Germany

Location

Related Publications (1)

• Zagorscak P, Heinrich M, Sommer D, Wagner B, Knaevelsrud C. Benefits of Individualized Feedback in Internet-Based Interventions for Depression: A Randomized Controlled Trial. Psychother Psychosom. 2018;87(1):32-45. doi: 10.1159/000481515. Epub 2018 Jan 6.

  PMID: 29306945 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 26, 2018
• Study Start: November 20, 2018
• Primary Completion: August 6, 2020
• Study Completion: August 6, 2020
• Last Updated: October 23, 2020

Record last verified: 2020-10

Locations

DE (1)