Condition: Major Depressive Disorder (MDD)NCT04719663
The Modulatory Role of Communicated Treatment Rationale on Treatment Expectation Effects in Depression.
A study testing Biological illness and treatment rationale and Psychological illness and treatment rationale in people with Condition: Major Depressive Disorder (MDD), run by Philipps University Marburg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Condition: Major Depressive Disorder (MDD)
- What is being tested?
- Biological illness and treatment rationale and Psychological illness and treatment rationale
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteGermany
- Study dates
- 13 Apr 2021to 12 Sep 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Clinical Psychology and Psychotherapy, Philipps-University Marburg
Marburg, 35032
About this study
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.
Read more
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.
- Being tested
- Biological illness and treatment rationale, Psychological illness and treatment rationale, Active pharmacological placebo, Active psychological placebo
- Keywords
- Placebo effect, Treatment rationale, Depression, Expectations
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biological illness and treatment rationaleBehavioural
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.
Psychological illness and treatment rationaleBehavioural
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.
Active pharmacological placeboDrug
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.
Active psychological placeboBehavioural
"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.
| Study group | Role | What they receive |
|---|---|---|
| 1. Congruent Rationale & Treatment: Biological/Pharmacol. | Experimental | Participants receive a biological illness explanation and treatment rationale. During treatment they receive a placebo pill (Buscopan). Receives: 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). Receives: 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). Receives: 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). Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start13 Apr 2021
- Primary completion12 Sep 2023
- Study completion12 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Condition: Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philipps University Marburg
- Sponsor type
- University, hospital or other
- Collaborators
- Psychotherapie-Ambulanz Marburg e.V.
- Responsible party
- Principal investigator, Winfried Rief, Philipps University Marburg
- Investigators
- Winfried Rief, Principal investigator, Philipps University Marburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04719663
- Sponsor's protocol ID
- CRC 289 Project A16
- Status last verified
- Nov 2023
- First submitted
- 6 Jan 2021
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 37592320
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Modulatory Role of Communicated Treatment Rationale on Treatment Expectation Effects in Depression.
- ClinicalTrials.gov ID
- NCT04719663
- Acronym / sponsor ID
- CRC 289 Project A16
- Keywords
- Placebo effect, Treatment rationale, Depression, Expectations
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Philipps University MarburgUniversity, hospital or other
- Collaborators
- Psychotherapie-Ambulanz Marburg e.V.
- Study start
- 13 Apr 2021 (actual)
- Primary completion
- 12 Sep 2023 (actual)
- Study completion
- 12 Sep 2023 (actual)
- First posted
- 22 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 1. Congruent Rationale & Treatment: Biological/Pharmacol. | Experimental | Behavioral: Biological illness and treatment rationale, Drug: Active pharmacological placeboParticipants receive a biological illness explanation and treatment rationale. During treatment they receive a placebo pill (Buscopan). |
| 2. Incongruent Rationale & Treatment: Psychological/Pharmacol. | Experimental | Behavioral: Psychological illness and treatment rationale, Drug: Active pharmacological placeboParticipants receive a psychological illness explanation and treatment rationale. During treatment they receive a placebo pill (Buscopan). |
| 3. Congruent Rationale & Treatment: Psychological/Psychol. | Experimental | Behavioral: Psychological illness and treatment rationale, Behavioral: Active psychological placeboParticipants receive a psychological illness explanation and treatment rationale. During treatment they receive a placebo psychological treatment (emotional writing). |
| 4. Incongruent Rationale & Treatment: Biological/Psychol. | Experimental | Behavioral: Biological illness and treatment rationale, Behavioral: Active psychological placeboParticipants receive a biological illness explanation and treatment rationale. During treatment they receive a placebo psychological treatment (emotional writing). |
| 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- Severe depression (BDI> 30) or suicidality
- Psychosis
- Significant neurological diseases
- Other mental or physical disorder with substantial influence on disability
- Benzodiazepine intake
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Biological illness and treatment rationaleDepression 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. | Behavioural | 1. Congruent Rationale & Treatment: Biological/Pharmacol., 4. Incongruent Rationale & Treatment: Biological/Psychol. |
| Psychological illness and treatment rationaleDepression 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. | Behavioural | 2. Incongruent Rationale & Treatment: Psychological/Pharmacol., 3. Congruent Rationale & Treatment: Psychological/Psychol. |
| Active pharmacological placeboThe 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. | Drug | 1. Congruent Rationale & Treatment: Biological/Pharmacol., 2. Incongruent Rationale & Treatment: Psychological/Pharmacol. |
| Active psychological placebo"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. | Behavioural | 3. Congruent Rationale & Treatment: Psychological/Psychol., 4. Incongruent Rationale & Treatment: Biological/Psychol. |
Primary outcome
Change in depression severity scores after 4 weeks of treatment - 'Montgomery Asberg Depression Scale' (MADRS)
Time frame: Baseline, post-treatment (4 weeks after start of treatment)
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)
6 secondary outcomes
Change in depressive symptom scores after 4 weeks of treatment- 'Beck Depression Inventory' (BDI-II)
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: Baseline, pre-treatment (2-7 days after baseline)
Change in subjective stress scores after 4 weeks of treatment - 'Perceived Stress Scale' (PSS-10)
Time frame: 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)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Derived from this study: PubMed 37592320Henrich 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Winfried Rief principal investigator
Philipps University Marburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Biological illness and treatment rationale and Psychological illness and treatment rationale in people with Condition: Major Depressive Disorder (MDD), run by Philipps University Marburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depression severity scores after 4 weeks of treatment - 'Montgomery Asberg Depression Scale' (MADRS) (time frame: Baseline, post-treatment (4 weeks after start of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04719663, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.