The Modulatory Role of Communicated Treatment Rationale on Treatment Expectation Effects in Depression.

NCT04719663 | Completed

• 1 other identifier: CRC 289 Project A16
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Placebo groups in clinical trials on depression show impressive improvements. Yet, there is little research on the mechanism underlying this effect. The aim of this study is to assess how patients' treatment expectations modulate the placebo treatment effects. We expect that patients' treatment expectation determines placebo responses and treatment outcomes, and that this expectation is influenced by the disorder explanations (information about the illness models) typically provided during the initial medical encounters that precede treatment. In the study we aim to manipulate depressed patients' expectations by providing two different clinician-delivered illness and treatment rationales (biological/ psychological). Patients will then receive placebo treatment (pharmacological/ psychological), that is either congruent or incongruent with the previously communicated treatment rationale. Hypotheses:

1. 1.Providing a treatment-congruent treatment rationale leads to a better outcome than providing treatment-incongruent rationales.
2. 2.Treatment-congruent explanations reduce the risk of side effect development, in particular in the medication arm.
3. 3.Inter-individual differences in the effect of provided treatment rationale are associated with pre-treatment experiences and expectations, depression severity and comorbid anxiety.

Conditions

Condition: Major Depressive Disorder (MDD)

Keywords

Placebo effect; Treatment rationale; Depression; Expectations

Outcome Measures

Primary Outcomes (1)

• Change in depression severity scores after 4 weeks of treatment - 'Montgomery Asberg Depression Scale' (MADRS)

  Expert rating to assess depression severity; 10 items; each item is rated on a 7-point scale (0-6); total scores range between 0-60 (higher scores indicate more severe depression)

  Baseline, post-treatment (4 weeks after start of treatment)

Secondary Outcomes (6)

• Change in depressive symptom scores after 4 weeks of treatment- 'Beck Depression Inventory' (BDI-II)

  Baseline, post-treatment (4 weeks after start of treatment), and at follow-up (1 week later)

• Change in subjective disability scores after 4 weeks of treatment - adaptation of 'Pain Disability Index' (PDI)

  Pre-treatment (2-7 days after baseline), post-treatment (4 weeks after start of treatment), and at follow-up (1 week later)

• Change in 'Generic Assessment of Side-Effects' scores (GASE) after 4 weeks of treatment

  Pre-treatment (2-7 days after baseline), post-treatment (4 weeks after start of treatment), and at follow-up (1 week later)

• Change in treatment expectations at the start of treatment - 'Treatment Expectation Questionnaire' (TEX-Q)

  Baseline, pre-treatment (2-7 days after baseline)

• Change in subjective stress scores after 4 weeks of treatment - 'Perceived Stress Scale' (PSS-10)

  pre-treatment (2-7 days after baseline), post-treatment (4 weeks after start of treatment), and at follow-up (1 week later)

Other Outcomes (10)

• Treatment adherence

  Once per week (during the 4-week treatment period)

• Common biological stress markers

  Baseline

• Current treatment effects after 4 weeks of treatment

  post-treatment (4 weeks after start of treatment)

Study Arms (5)

1. Congruent Rationale & Treatment: Biological/Pharmacol.

EXPERIMENTAL

Participants receive a biological illness explanation and treatment rationale. During treatment they receive a placebo pill (Buscopan).

Behavioral: Biological illness and treatment rationale; Drug: Active pharmacological placebo

2. Incongruent Rationale & Treatment: Psychological/Pharmacol.

EXPERIMENTAL

Participants receive a psychological illness explanation and treatment rationale. During treatment they receive a placebo pill (Buscopan).

Behavioral: Psychological illness and treatment rationale; Drug: Active pharmacological placebo

3. Congruent Rationale & Treatment: Psychological/Psychol.

EXPERIMENTAL

Participants receive a psychological illness explanation and treatment rationale. During treatment they receive a placebo psychological treatment (emotional writing).

Behavioral: Psychological illness and treatment rationale; Behavioral: Active psychological placebo

4. Incongruent Rationale & Treatment: Biological/Psychol.

EXPERIMENTAL

Participants receive a biological illness explanation and treatment rationale. During treatment they receive a placebo psychological treatment (emotional writing).

Behavioral: Biological illness and treatment rationale; Behavioral: Active psychological placebo

5. Natural course control

NO INTERVENTION

Participants receive no intervention and remain on the psychotherapy waiting list. Participants who are recruited externally and are not on a waiting list, will be offered the option to join the waiting list.

Interventions

Biological illness and treatment rationale BEHAVIORAL

Depression is described as a brain disorder and the role of monoamine, brain structures, and brain functions are reported as central mechanisms of relevance for its etiology and treatment. Biological processes are illustrated using typical charts and visualizations. Psychological influences are mentioned, but only as a byproduct of the disorder.

1. Congruent Rationale & Treatment: Biological/Pharmacol.; 4. Incongruent Rationale & Treatment: Biological/Psychol.

Psychological illness and treatment rationale BEHAVIORAL

Depression is described as a psychological disorder resulting from emotion regulation deficits. The suppression of emotions receives a special role in explaining depression. The psychological processes are illustrated using charts and visualizations. Biological aspects are mentioned, but only as a byproduct of the disorder.

2. Incongruent Rationale & Treatment: Psychological/Pharmacol.; 3. Congruent Rationale & Treatment: Psychological/Psychol.

Active pharmacological placebo DRUG

The active placebo pill does not have direct effects on the brain. Buscopan (butylscopolamine, 10 mg daily, 1 pill in the morning) does not cross the blood-brain barrier, yet induces some smaller side effects that resemble those of antidepressants (e.g., mouth dryness, fatigue, nausea). Treatment duration is 4 weeks. The rationale is briefly explained to participants as "stimulating the biological balance in humans with depression, using a well-tolerated drug similar to Buscopan, which is well-known from pain treatments.

1. Congruent Rationale & Treatment: Biological/Pharmacol.; 2. Incongruent Rationale & Treatment: Psychological/Pharmacol.

Active psychological placebo BEHAVIORAL

"Emotional writing" consists of writing about emotional experiences (4 sessions, one per week, 30 minutes each). The study instructor will be present displaying standard psychotherapeutic attitudes but will not read the participant's notes. The rationale for this treatment is briefly explained as "improving the dealing" with emotions to achieve a psychological balance in humans with depression.

3. Congruent Rationale & Treatment: Psychological/Psychol.; 4. Incongruent Rationale & Treatment: Biological/Psychol.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of major depression according to the 'Structured Clinical Interview for DSM-V' (SCID)
• Age\>17
• Comorbidity is allowed if major depression is the dominant clinical problem
• Concordant medication is allowed if kept constant for the four weeks before and until the end of the trial (with the exception of benzodiazepines and if not contraindicated together with Buscopan)
• Fluency in German
• Informed consent

You may not qualify if:

• Severe depression (BDI\> 30) or suicidality
• Psychosis
• Significant neurological diseases
• Other mental or physical disorder with substantial influence on disability
• Benzodiazepine intake
• Any intolerance against Buscopan and sucrose or any medical condition/treatment conflicting with Buscopan intake

Sponsors & Collaborators

• Philipps University Marburg: lead
• Psychotherapie-Ambulanz Marburg e.V.: collaborator

Study Sites (1)

Department of Clinical Psychology and Psychotherapy, Philipps-University Marburg

Marburg, 35032, Germany

Location

Related Publications (1)

• Henrich L, Wilhelm M, Lange P, Rief W. The role of the communicated treatment rationale on treatment outcome: study protocol for a randomized controlled trial. Trials. 2023 Aug 17;24(1):540. doi: 10.1186/s13063-023-07557-w.

  PMID: 37592320 DERIVED

MeSH Terms

Conditions

Depression

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Winfried Rief

  Philipps University Marburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants will be blinded to the congruency condition. Outcome assessors (diagnosticians) will be blinded to treatment allocation and the congruency condition (both at the pre-measurement and at the post-measurement). The clinicians (care providers) who deliver the illness explanation and treatment rationale will be blinded to the participants' treatment allocation up to the point at which the respective treatment is delivered. This means that the clinician provides the treatment rationale (biological / psychological) without knowledge of whether a congruent or incongruent treatment will be delivered afterwards. The staff members who deliver the treatment (care providers) will be different to the clinician who delivers the rationales. Thus the treatment will be delivered without knowledge of whether a congruent or incongruent illness explanation was given.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 22, 2021
• Study Start: April 13, 2021
• Primary Completion: September 12, 2023
• Study Completion: September 12, 2023
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

DE (1)