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

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

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

Conditions
-----------------
Condition: Major Depressive Disorder (MDD)

Intervention / Treatment
-----------------
* Behavioral: Biological illness and treatment rationale
* Behavioral: Psychological illness and treatment rationale
* Drug: Active pharmacological placebo
* Behavioral: Active psychological placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. Congruent Rationale & Treatment: Biological/Pharmacol.<br>Participants receive a biological illness explanation and treatment rationale. During treatment they receive a placebo pill (Buscopan). | Behavioral: Biological illness and treatment rationale<br>* 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.<br>Drug: Active pharmacological placebo<br>* 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.<br>|
| Experimental: 2. Incongruent Rationale & Treatment: Psychological/Pharmacol.<br>Participants receive a psychological illness explanation and treatment rationale. During treatment they receive a placebo pill (Buscopan). | Behavioral: Psychological illness and treatment rationale<br>* 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.<br>Drug: Active pharmacological placebo<br>* 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.<br>|
| Experimental: 3. Congruent Rationale & Treatment: Psychological/Psychol.<br>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<br>* 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.<br>Behavioral: Active psychological placebo<br>* 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.<br>|
| Experimental: 4. Incongruent Rationale & Treatment: Biological/Psychol.<br>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<br>* 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.<br>Behavioral: Active psychological placebo<br>* 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.<br>|
| No Intervention: 5. Natural course control<br>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. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in depressive symptom scores after 4 weeks of treatment- 'Beck Depression Inventory' (BDI-II) | Self-report questionnaire to assess subjective depression symptomatology; 21 items (each item response is scored 0-3); total scores range from 0 - 63 (higher scores indicate more depressiveness) | 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) | Self-report questionnaire to assess illness burden; 7 items; each item rated on a 0 (no disability)-10(maximum disability) standardized numerical analogue scale; total scores range from 0-70 (higher scores indicate more disability) | 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 | Self-report questionnaire to assess experience of side effects; 36 items; each item describes a side-effect symptom which is rated on a 4-point scale from 0 (not present)-3 (strong experience); total scores range from 0-108 (higher scores indicate stronger experience of side effects) | 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) | Self-report questionnaire to assess expectations about treatment outcomes; 15 items; each rated on a 0 (no expectation of improvement)- 10(most improvement imaginable) numeric scale; total scores range from 0-150 (higher scores indicate better treatment expectations) | Baseline, pre-treatment (2-7 days after baseline) | 
| Change in subjective stress scores after 4 weeks of treatment - 'Perceived Stress Scale' (PSS-10) | Self-report questionnaire to assess subjective stress experience; 10 items; each item is rated on a 5-point scale from 0(never) to 4(very often); total scores range between 0 and 40 (higher scores indicate more subjective stress) | pre-treatment (2-7 days after baseline), post-treatment (4 weeks after start of treatment), and at follow-up (1 week later) | 
| Change in anxiety scores after 4 weeks of treatment - 'State-Trait-Anxiety- Depression-Inventory' (STADI) | Self-report questionnaire to assess state and trait anxiety and depression; 40 (20 state scale; 20 trait scale) items; each item is rated on a 4-point scale from 1(not at all) to 4(very much); total scores per scale range between 20 and 80 (higher scores indicate more anxiety) | State scale: Baseline; pre-treatment (2-7 days after baseline), post-treatment (4 weeks after start of treatment) and at follow-up (1 week later); Trait scale only measured at baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Placebo effect, Treatment rationale, Depression, Expectations