Combined N-of-1 Trials to Assess Open-Label Placebo Treatment for Antidepressant Discontinuation Symptoms [FAB-study]

Overview
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It has been widely recognized that the placebo effect has a profound impact on treatment outcome in many different conditions. Recent studies imply that this effect appears even if placebos are openly administered; so called "open-label placebos" (OLP). Compelling evidence suggests the efficacy of OLP in the treatment of pain disorders, neuropsychological syndromes, menopausal hot flushes, depression and allergic rhinitis. Research on the underlying mechanisms of OLP is scarce, yet studies indicate that psychological mechanisms as well as neurobiological processes related to expectation- and prediction mechanisms may play a role. While these effects have been linked to OLP as additional treatment, to date, it has not been examined whether OLP could support discontinuation of drug treatments.Antidepressant discontinuation has been frequently associated with negative side effects, interfering with the discontinuation process and generally discouraging discontinuation. Patients frequently report negative expectations towards the discontinuation process, such as fear of experiencing a relapse and negative side effects. Interestingly, OLP may support antidepressant discontinuation, not only through the generation of (positive) expectations, but also mechanisms related to habituation (i.e. taking pills). The objective of this study is to investigate whether OLP is efficacious in reducing negative side effects caused by discontinuation of antidepressant medication.This preregistration is part of the collaborative research center (CRC) SFB/ TRR289 which aims to characterize the psychological and neurobiological effects of treatment expectations on health outcome (https://treatment-expectation.de) and is funded by the Deutsche Forschungsgemeinschaft (DFG).

Sponsor: Universitätsklinikum Hamburg-Eppendorf

SEEK ID: https://ldh.hpi.imise.uni-leipzig.de/projects/4

Funding codes:

CRC 289 Project A15

Public web page: http://phea-studie.de/fab

NFDI4Health PIs: No PIs for this Trial Project

Trial Project start date: 17th Feb 2022

Trial Project end date: 15th May 2024

Extended Metadata (Nfdi4Health MDS 3.3)

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Resource classification(*)

Type of the resource(*) : Study

Title(s)/name(s) of the Project

Title/name(*) : Combined N-of-1 Trials to Assess Open-Label Placebo Treatment for Antidepressant Discontinuation Symptoms [FAB-study]
Language of the title/name(*) : English

Acronym(s) of the Project

Acronym(*) : FAB
Language of the acronym(*) : English

Description(s) of the Project

Description(*) : It has been widely recognized that the placebo effect has a profound impact on treatment outcome in many different conditions. Recent studies imply that this effect appears even if placebos are openly administered; so called "open-label placebos" (OLP). Compelling evidence suggests the efficacy of OLP in the treatment of pain disorders, neuropsychological syndromes, menopausal hot flushes, depression and allergic rhinitis. Research on the underlying mechanisms of OLP is scarce, yet studies indicate that psychological mechanisms as well as neurobiological processes related to expectation- and prediction mechanisms may play a role. While these effects have been linked to OLP as additional treatment, to date, it has not been examined whether OLP could support discontinuation of drug treatments.Antidepressant discontinuation has been frequently associated with negative side effects, interfering with the discontinuation process and generally discouraging discontinuation. Patients frequently report negative expectations towards the discontinuation process, such as fear of experiencing a relapse and negative side effects. Interestingly, OLP may support antidepressant discontinuation, not only through the generation of (positive) expectations, but also mechanisms related to habituation (i.e. taking pills). The objective of this study is to investigate whether OLP is efficacious in reducing negative side effects caused by discontinuation of antidepressant medication.This preregistration is part of the collaborative research center (CRC) SFB/ TRR289 which aims to characterize the psychological and neurobiological effects of treatment expectations on health outcome (https://treatment-expectation.de) and is funded by the Deutsche Forschungsgemeinschaft (DFG).
Language of the description(*) : English

Keyword(s) describing the Project

Keyword(*) : N-of-1 trials, open-label placebo, discontinuation symptoms, antidepressant medication, expectation effects

Language(s) of the project : German

Web page of the project : https://phea-studie.de/fab

Contributor(s) of the Project

Is it a personal or organisational contribution?(*) : Organisational
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Sponsor (primary)
Funding identifier(s) : CRC 289 Project A15
Name of the organisation/institution/group(*) : Universitätsklinikum Hamburg-Eppendorf
Details about the contributing person(s)
Contributor type(*) : Principal investigator
Given name(*) : Yvonne
Family name(s)(*) : Nestoriuc
Digital identifier(s)
Identifier(*) : 0000-0003-2191-0495
Scheme(*) : ORCID
Email address : y.nestoriuc@hsu-hh.de
Phone number : 0406541-2911
Organisation(s) associated with the contributor
Name(*) : Universitätsklinikum Hamburg-Eppendorf
Address : Martinistraße 52, 20251 Hamburg
Web page : https://www.uke.de/
Digital identifier(s)
Identifier(*) : 01zgy1s35
Scheme(*) : ROR

Is it a personal or organisational contribution?(*) : Personal
Details about the contributing organisation(s)/institution(s)/group(s)
Contributor type(*) : Contact
Funding identifier(s) : Not specified
Name of the organisation/institution/group(*) : Philipps University Marburg Medical Center
Details about the contributing person(s)
Contributor type(*) : Contact
Given name(*) : Tilo
Family name(s)(*) : Kircher
Digital identifier(s)
Identifier(*) : 0000-0002-2514-2625
Scheme(*) : ORCID
Identifier(*) : Not specified
Scheme(*) : Not specified
Email address : Not specified
Phone number : Not specified
Organisation(s) associated with the contributor
Name(*) : Philipps University Marburg Medical Center
Address : Not specified
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified
Name(*) : Not specified
Address : Not specified
Web page : Not specified
Digital identifier(s)
Identifier(*) : Not specified
Scheme(*) : Not specified
Identifier(*) : Not specified
Scheme(*) : Not specified

Alternative identifiers

Type of the registry(*) : NCT (ClinicalTrials.gov)
Identifier(*) : NCT05051995

Includes chronic diseases? : true

Characteristics of the Project

Is it an interventional or non-interventional Project? : Interventional
Specification of the type of the Project
Interventional Project type : Crossover
Non-interventional Project type : []
Primary health condition(s) or disease(s) considered in the Project
Primary health condition or disease name(*) : Depressive Symptoms
Terminology/classification(*) : ICD-11
Code of the health condition or disease : F32.9
Groups of diseases or conditions(*)
Which groups of diseases or conditions were the data collected on? : Mental and behavioural disorders (V)
On which diseases or conditions were the data collected? : Lower level ICD-10 (https://icd.who.int/browse10/2019/en), with autocomplete
Collects mortality data? : No
Administrative information about the Project
Status of the ethics committee approval : Request for approval submitted, approval granted
Overall Project status : Completed: Recruitment, data collection, and data quality management completed normally
Participants enrolled by invitation? : No
Start date : 17 February 2022
End date : 15 May 2024
Mono- or multicentric? : Multicentric
Number of centers : 2
One or more data providers? : Several data providers
Number of data providers : 2
Primary subject(*) : Person
Eligibility criteria for Project participants
Eligibility criteria: Minimum age
Minimum eligible age(*) : 18
Unit of age(*) : Years
Eligibility criteria: Maximum age
Maximum eligible age(*) : Not specified
Unit of age(*) : Not specified
Eligible gender : Male, Female, Diverse
Inclusion criteria : Adult participants (18+years) with a former diagnoses of major depressive disorder (MDD), single or recurrent as main diagnosis confirmed by prescribing physician and currently remitted Intake of selective serotonin reuptake inhibitors (SSRI)/ serotonin-norepinephrine reuptake inhibitors (SNRI) (citalopram 20-40mg, duloxetine 60-100mg, escitalopram 10-20mg, paroxetine 20-40mg, sertraline 50-150mg, venlafaxine 75-150mg) or noradrenergic and specific serotonergic antidepressants (NaSSA) (mirtazapine 30-45mg) Discontinuation wish by patient supported by prescribing physician Fulfils the criteria of the S3 national guideline recommendations "Depression" to discontinue antidepressant medication: a) response to antidepressant; b) symptom remission for at least 4 months (first episode) or for 2 years (2 or more episodes with significant functional impairment), constant intake of antidepressant medication (at least 4 weeks on a steady dose) Informed consent
Exclusion criteria : Current moderate or severe psychopathological symptoms or psycho-social impairments Acute or chronic somatic illness which might interfere with depressive disorder, antidepressant or proposed study Acute suicidality, psychotic symptoms, substance abuse, or addiction, current mania, or hypomania confirmed by SCID-5 or other psychopathology which might interfere with depressive disorder, antidepressant or proposed study Any history of bipolar disorder or psychosis confirmed by SCID-5 Severe stressful life events (e.g., death of a family member) within six months prior to study participation Current pregnancy Insufficient German language proficiency.
Population of the Project(*)
Coverage : National
Country(ies) : Germany
Region(s) and/or city(ies) : Hamburg, Marburg, Essen
Interventions of the Project
Name of the intervention(*) : Open-label placebo
Type of the intervention : Other
Additional information about the intervention : Patients receive placebo tablets with the instruction to take 2 pills daily for 2 weeks.
Name(s) of the arm(s) associated with the given intervention : Open-label placebo ABAB Sequence
Exposures of the Project
Name of the exposure : Not specified
Type of the exposure : Not specified
Additional information about the exposure : Not specified
Name(s) of the group(s) associated with the given exposure : Not specified
Outcome measures in the Project
Name of the outcome measure(*) : Change in antidepressant discontinuation symptoms assessed by the 'Generic rating scale for treatment effects' (GEEE_ACT)
Description of the outcome measure : The generic rating scale for treatment effects item 3 assesses the current treatment effect concerning side effects (i.e. antidepressant discontinuation side-effects) on a numeric analogue scale, ranging from 0-10; higher scores indicating higher antidepressant discontinuation symptoms.
Type of the outcome measure : Primary
Time point(s) of assessment : Continuous measurement (2xdaily) for 8 weeks
Name of the outcome measure(*) : Change in treatment expectations assessed by 'Generic rating scale for treatment expectations' (GEEE_EXP)
Description of the outcome measure : The generic rating scale for treatment expectations item 3 assesses treatment expectations regarding side effects (i.e. antidepressant discontinuation side-effects) on a numeric rating scale, ranging from 0-10; higher scores indicating higher treatment expectations.
Type of the outcome measure : Secondary
Time point(s) of assessment : Continuous measurement (2xdaily) for 8 weeks
Name of the outcome measure(*) : Change in (depressed) mood assessed by the 'Patient-Healthcare-Questionnaire' (PHQ-2)
Description of the outcome measure : Self-report comprising 2 items, inquiring the degree to which an individual experiences the core symptoms of depression (i.e. anhedonia and depressed mood); items are scored on a four level Likert scale ranging from 0 (not at all) - 3 (almost constant); total score range from 0-6 (higher scores indicate a higher degree of depressed mood).
Type of the outcome measure : Secondary
Time point(s) of assessment : Continuous measurement (2xdaily) for 8 weeks
Name of the outcome measure(*) : Discontinuation symptoms - 'Discontinuation Related Signs and Symptoms Scale' (DESS)
Description of the outcome measure : The discontinuation related signs and symptoms scale is a self-report questionnaire to assess discontinuation symptoms, incorporating 43 discontinuation symptoms of antidepressant with intensity ratings ranging from 0 (not present) - 3 (severe); total score range from 0-129 with higher scores indicating more severe discontinuation symptoms.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Current treatment effects - 'Generic rating scale for treatment effects' (GEEE_ACT)
Description of the outcome measure : The generic rating scale for treatment effects assesses the current treatment effects (i.e. antidepressant discontinuation) regarding side effects as well as positive and negative aspects on 3 numeric rating scales with eleven response options (0-10); total score range from 0-30 with higher scores indicating higher antidepressant discontinuation effects.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Subjective depressive symptomatology - 'Beck Depression Inventory' (BDI-II)
Description of the outcome measure : Self-report measure to assess depressive symptoms, including 21 items with 4 response options (0-3); total scores range from 0 - 63 (higher scores indicating higher depression severity).
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Expert-rated depression severity scores - 'Montgomery-Åsberg Depression Scale' (MADRS)
Description of the outcome measure : Expert-rated interview to assess the severity of depression by 10 items with up to 7 rating categories (0-6) for each item; total scores range between 0-60 with higher scores indicating more severe depression severity.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Recurrence
Description of the outcome measure : New-onset depressive episode following a period of recovery. Recurrence will be determined by BDI-II sumscore (>19) or MADRS sumscore (>21) over a period of two weeks, confirmed by SCID-5-CV section for MDD.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Mental well-being - 'Short Warwick-Edinburgh Mental Wellbeing Scale' (SWEMWBS)
Description of the outcome measure : Self-report questionnaire to assess mental well-being by 7 statements about thoughts and feelings using 5 response options; total score range from 7-35 with higher sum scores reflecting a higher level of mental well-being.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Adherence - single item
Description of the outcome measure : Treatment adherence assessed by a single item in the clinical interview about adherence to medication or placebo (i.e. experimental phase) intake.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks)
Name of the outcome measure(*) : Treatment expectations - 'Treatment Expectation Questionnaire' (TEX-Q)
Description of the outcome measure : Self-reported measure to assess patients' treatment expectations, consisting of 15 items with 11 response options, total score range from 0-150 (higher scores implying more positive treatment expectations).
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Current treatment expectations - 'Generic rating scale for treatment expectations' (GEEE_EXP)
Description of the outcome measure : The generic rating scale for treatment expectations assesses treatment expectations (i.e. antidepressant discontinuation expectations) regarding positive and negative aspects as well as side effects on 3 numeric rating scales (ranging from 0-10); total score range from 0-30 with higher scores indicating higher treatment expectations.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Pre-experiences with antidepressant discontinuation - 'Generic rating scale for previous treatment experiences' (GEEE_PRE)
Description of the outcome measure : Self-reported previous experiences with antidepressant discontinuation. If experience with antidepressant discontinuation is indicated, the following 3 items rate the experiences regarding side effects as well as positive and negative aspects on 3 numeric analogue scales (ranging from 0-10); total score range from 0-30; higher scores indicate more pre-experiences with antidepressant discontinuation effects.
Type of the outcome measure : Other
Time point(s) of assessment : Baseline
Name of the outcome measure(*) : Subjective Stress - 'Perceived Stress Scale' (PSS-10)
Description of the outcome measure : Self-reported measure of subjective stress, including 10 items with 5 rating categories, total scores range between 0-40; higher scores are suggestive of more subjective stress.
Type of the outcome measure : Other
Time point(s) of assessment : Baseline
Name of the outcome measure(*) : Anxiety vs Depression - 'State-Trait-Anxiety-Depression-Inventory' (STADI)
Description of the outcome measure : Self-report questionnaire as indicator of state and trait anxiety and depression, divided in 2 sections (state vs. trait) consisting of 20 statements with 4 response options, respectively. Total scores per scale range between 20 and 80 with higher sum scores indicating higher state/trait anxiety or depression.
Type of the outcome measure : Other
Time point(s) of assessment : Baseline
Name of the outcome measure(*) : Side effects of SSRIs - 'Generic Assessment of Side Effects' (GASE)
Description of the outcome measure : Self-report measure to assess side effects of antidepressant medication, including 36 items (symptom descriptions) with 4 response options. Items are additionally evaluated on their relation to antidepressant medication (Yes/ No questions). Total scores range from 0-108 (higher scores are reflective of stronger experiences of side effects).
Type of the outcome measure : Other
Time point(s) of assessment : Baseline, post-antidepressant discontinuation (8 weeks after baseline)
Name of the outcome measure(*) : Adverse events - single safety items
Description of the outcome measure : Interview-based measure assessing adverse events by 3 questions (Yes/ No questions), followed by an expert-rating of the intensity of the adverse events (1-5) and relation to treatment (1-5). Higher scores indicate more and/or a higher intensity of adverse events.
Type of the outcome measure : Other
Time point(s) of assessment : Weekly during discontinuation phase (4 weeks); biweekly during experimental phase (8 weeks); follow-up (6 months later)
Name of the outcome measure(*) : Psychopathology - 'Structured Clinical Interview for DSM-5, Clinician Version' (SCID-5-CV)
Description of the outcome measure : Expert-rated semi-structured interview to assess DSM-5 diagnoses.
Type of the outcome measure : Other
Time point(s) of assessment : Screening
Name of the outcome measure(*) : SSRI/SNRI blood serum level
Description of the outcome measure : Blood analysis assessing the blood serum level.
Type of the outcome measure : Other
Time point(s) of assessment : Pre-antidepressant discontinuation (1 week after baseline); post-antidepressant discontinuation (5 weeks after baseline)
Additional information about the Project : This study is part of a collaborative research center (CRC; TRR 289 Treatment Expectation: treatment-expectation.de/en/).
Additional assessments/measurements in the Project : Sociodemographic information
Data sharing strategy of the Project(*)
Is it planned to share the data?(*) : Yes, there is a plan to make data available
Supporting documents available in addition to the data : Study protocol, Statistical analysis plan, Informed consent form
When and for how long will the data be available? : Not specified
Criteria for data access : Not specified
Additional information about data sharing : The FAB-study is a pilotproject within a special research area funded by the DFG: TRR-SFB 289 Treatment Expectation. After deidentification, individual participant data will be shared with the TRR-SFB 289 study team and will be available for other researchers upon reasonable request. Only anonymized data in agglomerated form is used for publications. No personal data of participants will be shared.
DataSHIELD/Opal infrastructure available? : No
Link to data request application : Not specified
Web page with additional information about data sharing : Not specified
Record linkage possible? : false
Non-interventional aspects of the Project
Temporal design : Prospective
Target follow-up duration of the Project
Target follow-up duration(*) : 6
Unit of time(*) : Months
Number of follow-ups conducted : 1
Biosamples retained in a biorepository : None retained
Specific types of retained biosamples : Not specified
Interventional aspects of the Project
Numerical phase : Not applicable
Masking of intervention(s) assignment
Masking implemented? : true
Who is masked? : Outcomes assessor
Additional information about masking : The person performing the data collection (assessor) will be blind to the randomization of the participant for the entire duration of the experimental phase.
Type of allocation of participants to an arm : Randomized
Off-label use of a drug product : No

Annotated Properties

Topic annotations

Psychiatry, Preclinical and clinical studies

Combined N-of-1 Trials to Assess Open-Label Placebo Treatment for Antidepressant Discontinuation Symptoms [FAB-study]

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