Depressive SymptomsFABNCT05051995
Combined N-of-1 Trials to Assess Open-Label Placebo Treatment for Antidepressant Discontinuation Symptoms
A study testing No-treatment in people with Depressive Symptoms and Expectations, run by Universitätsklinikum Hamburg-Eppendorf at 2 sites in Germany.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depressive Symptoms, Expectations, Antidepressants
- What is being tested?
- No-treatment
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 2 sitesGermany
- Study dates
- 17 Feb 2022to 15 May 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
University Medical Center Hamburg-Eppendorf
Hamburg, 20251
Philipps University Marburg Medical Center
Marburg, Hesse, 35037
About this study
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).
Read the detailed description
Rationale: A current issue in the frame of antidepressant medication is the rise of long-term antidepressant use associated with noticeable adverse effects such as withdrawal effects, sexual difficulties, weight gain and emotional numbness. A key factor hindering patients in the discontinuation of antidepressant medication is the emergence of discontinuation symptoms, reported by over half of fully remitted patients discontinuing antidepressants. To date, there is no study examining open-label placebo responses on antidepressant discontinuation symptoms. However, several findings imply that open-label placebos may support the discontinuation process in remitted depressed patients. The susceptibility to placebo responses is encouraged by findings indicating substantial placebo effects in antidepressant trials (67-82%). Additionally, evidence suggests the central role of expectation effects influencing the course of antidepressant discontinuation. Open-label placebos have been found to work through the generation of positive expectations, induced by a positive framing (e.g. verbal instructions). A recent meta-analysis suggests a medium to large effect size of open-label placebos. Regarding the treatment of antidepressant discontinuation symptoms, open-label placebos have the potential to reduce symptoms not only by inducing positive expectations, but also by triggering automatic (positive) responses to the intake of a pill (i.e. conditioning).The aim of this study is to investigate the effect of open-label placebos on antidepressant discontinuation symptoms in fully remitted depressed patients.
Methods: In the proposed study, a pilot sample will discontinue their antidepressant intake under extensive medical and psychological supervision, according to the national and international guidelines over a 13-week course. After a run-in week and the baseline assessment, antidepressant medication will be gradually reduced with individualized discontinuation plans over a period of 4 weeks. Weekly measurements serve to monitor the condition of the participants. After discontinuation, patients will be monitored (with biweekly study visits) for another 8 weeks (experimental phase). Finally, a follow-up measurement 6 months after the study start constitutes long-term monitoring and the assessment of relapse after antidepressant discontinuation. During the experimental phase, patients experiencing moderate discontinuation symptoms are allocated to the intervention group, aimed to examine the effect of open-label placebo on antidepressant discontinuation symptoms. For this purpose, N-of-1 trials comprising multiple crossovers (A: open-label placebo; B: no treatment) within each individual, and varying in a biweekly rhythm, are applied. Patients are randomized to different treatment orders (ABAB; BABA). Twice daily smartphone-measurements are implemented to assess discontinuation symptoms, expectations and mood. Additionally, study visits consist of extensive measurements related to discontinuation symptoms, depressive symptomatology, psychological well-being and treatment expectations. These serve as observational measurement of different effects related to antidepressant discontinuation. During the experimental phase, outcome assessors will be blind to the randomization (i.e. treatment order) of the patients.
Objectives: At the end of the study, the investigators will determine whether open-label placebo reduces negative side effects caused by antidepressant discontinuation by aggregating the N-of-1 trials. Underlying mechanisms such as treatment expectations, as well as the relation to depressed mood, will be under explorative investigation. Additionally, the course of discontinuation symptoms, depressive symptoms (self-report and expert-rated) and treatment adherence during the entire study will be explored. Therefore, potential modulators such as psychopathology, demographics, adverse events, expectations, prior experience, subjective stress, side effects of antidepressants and anxiety vs. depression (trait/state) will be taken into account in data analyses.
- Conditions
- Depressive Symptoms, Expectations, Antidepressants
- Being tested
- Open-label placebo, No-treatment
- Keywords
- N-of-1 trials, open-label placebo, discontinuation symptoms, antidepressant medication, expectation effects
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Open-label placeboDrug
Prior to the open-label placebo administration, an explanation why placebos without concealment might be effective is offered. Participants receive placebo pills with the instruction to take 2 pills daily for 2 weeks.
No-treatmentOther
During the no-treatment phase, participants receive no treatment for 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Open-label placebo ABAB Sequence | Placebo comparator | The N-of-1 trial will, on the level of the individual patient, test whether open-label placebo reduces negative side effects caused by discontinuation of antidepressants compared to no treatment. After antidepressant discontinuation, subjects will be randomized to 2 arms differing in the treatment order (ABAB; BABA). Subjects in this arm (ABAB) will start with open-label placebo (A) for 2 weeks; they will then crossover to no treatment (B) for 2 weeks and repeat this sequence once again. Receives: Drug: Open-label placebo; Other: No-treatment |
| Open-label placebo BABA Sequence | Placebo comparator | The N-of-1 trial will, on the level of the individual patient, test whether open-label placebo reduces negative side effects caused by discontinuation of antidepressants compared to no treatment. After antidepressant discontinuation, subjects will be randomized to 2 arms differing in the treatment order (ABAB; BABA). Subjects in this arm (BABA) will start with no treatment (B) for 2 weeks; they will then crossover to open-label placebo (A) for 2 weeks and repeat this sequence once again. Receives: Drug: Open-label placebo; Other: No-treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in antidepressant discontinuation symptoms assessed by the 'Generic rating scale for treatment effects' (GEEE_ACT)
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.
Measured: Continuous measurement (2xdaily) for 8 weeks
Secondary outcomes (2)
Change in treatment expectations assessed by 'Generic rating scale for treatment expectations' (GEEE_EXP)
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.
Measured: Continuous measurement (2xdaily) for 8 weeks
Change in (depressed) mood assessed by the 'Patient-Healthcare-Questionnaire' (PHQ-2)
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).
Measured: Continuous measurement (2xdaily) for 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2021
- Study start17 Feb 2022
- Primary completion21 Feb 2024
- Study completion15 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Depressive SymptomsStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- To investigate the efficacy of open-label placebo in the reduction of antidepressant discontinuation symptoms, patients experiencing moderate discontinuation symptoms after successful discontinuation (4 weeks) receive open-label placebo treatment or no treatment during the experimental phase (8 weeks). For this purpose, a series of N-of-1 trials is implemented, consisting of multiple crossover trials within each participant. The factor treatment (open-label placebo vs. no treatment) varies intra-individually with a biweekly rhythm, to assess the treatment effect on discontinuation symptoms. A block-randomization is applied, with patients either receiving (A) open-label placebo or (B) no treatment in a biweekly rhythm (group 1: ABAB; group 2: BABA).
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Collaborators
- Philipps University Marburg, Helmut Schmidt University, University Hospital, Essen
- Responsible party
- Sponsor
- Investigators
- Yvonne Nestoriuc, Prof. Dr., Principal investigator, Universitätsklinikum Hamburg-EppendorfTilo Kircher, Prof. Dr., Principal investigator, Philipps University Marburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05051995
- Sponsor's protocol ID
- 0721-20
- Other IDs
- CRC 289 Project A15, U1111-1274-2336
- Acronym
- FAB
- Status last verified
- May 2024
- First submitted
- 23 Aug 2021
- Last updated
- 12 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Nestoriuc Y, Pan Y, Kinitz T, Weik E, Shedden-Mora MC. Informing About the Nocebo Effect Affects Patients' Need for Information About Antidepressants-An Experimental Online Study. Front Psychiatry. 2021 Apr 27;12:587122. doi: 10.3389/fpsyt.2021.587122. eCollection 2021.
PubMed 33986697Rief, W., Nestoriuc, Y., Mueller, E. M., Hermann, C., Schmidt, K., & Bingel, U. Generic rating scale for previous treatment experiences, treatment expectations, and treatment effects (GEEE). PsychArchives. 2021 https://doi.org/10.23668/PSYCHARCHIVES.4717
Pan Y, Meister R, Lowe B, Kaptchuk TJ, Buhling KJ, Nestoriuc Y. Open-label placebos for menopausal hot flushes: a randomized controlled trial. Sci Rep. 2020 Nov 18;10(1):20090. doi: 10.1038/s41598-020-77255-z.
PubMed 33208855Bowers HM, Kendrick T, Glowacka M, Williams S, Leydon G, May C, Dowrick C, Moncrieff J, Laine R, Nestoriuc Y, Andersson G, Geraghty AWA. Supporting antidepressant discontinuation: the development and optimisation of a digital intervention for patients in UK primary care using a theory, evidence and person-based approach. BMJ Open. 2020 Mar 8;10(3):e032312. doi: 10.1136/bmjopen-2019-032312.
PubMed 32152159Meister R, Lanio J, Fangmeier T, Harter M, Schramm E, Zobel I, Hautzinger M, Nestoriuc Y, Kriston L. Adverse events during a disorder-specific psychotherapy compared to a nonspecific psychotherapy in patients with chronic depression. J Clin Psychol. 2020 Jan;76(1):7-19. doi: 10.1002/jclp.22869. Epub 2019 Oct 1.
PubMed 31576565Shedden-Mora MC, Pan Y, Heisig SR, von Blanckenburg P, Rief W, Witzel I, Albert US, Nestoriuc Y. Optimizing Expectations About Endocrine Treatment for Breast Cancer: Results of the Randomized Controlled PSY-BREAST Trial. Clin Psychol Eur. 2020 Mar 31;2(1):e2695. doi: 10.32872/cpe.v2i1.2695. eCollection 2020 Mar.
PubMed 36397978Pan Y, Meister R, Lowe B, Winkelmann A, Kaptchuk TJ, Buhling KJ, Nestoriuc Y. Non-concealed placebo treatment for menopausal hot flushes: Study protocol of a randomized-controlled trial. Trials. 2019 Aug 16;20(1):508. doi: 10.1186/s13063-019-3575-1.
PubMed 31420050Pan Y, Kinitz T, Stapic M, Nestoriuc Y. Minimizing Drug Adverse Events by Informing About the Nocebo Effect-An Experimental Study. Front Psychiatry. 2019 Jul 25;10:504. doi: 10.3389/fpsyt.2019.00504. eCollection 2019.
PubMed 31427995Muller A, Konigorski S, Meissner C, Fadai T, Warren CV, Falkenberg I, Kircher T, Nestoriuc Y. Study protocol: combined N-of-1 trials to assess open-label placebo treatment for antidepressant discontinuation symptoms [FAB-study]. BMC Psychiatry. 2023 Oct 13;23(1):749. doi: 10.1186/s12888-023-05184-y.
PubMed 37833651
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined N-of-1 Trials to Assess Open-Label Placebo Treatment for Antidepressant Discontinuation Symptoms
- ClinicalTrials.gov ID
- NCT05051995
- Acronym / sponsor ID
- FAB / 0721-20
- Conditions
- Depressive Symptoms, Expectations, Antidepressants
- Keywords
- N-of-1 trials, open-label placebo, discontinuation symptoms, antidepressant medication, expectation effects
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Collaborators
- Philipps University Marburg, Helmut Schmidt University, University Hospital, Essen
- Study start
- 17 Feb 2022 (actual)
- Primary completion
- 21 Feb 2024 (actual)
- Study completion
- 15 May 2024 (actual)
- First posted
- 21 Sep 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.
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).
Detailed description
Rationale: A current issue in the frame of antidepressant medication is the rise of long-term antidepressant use associated with noticeable adverse effects such as withdrawal effects, sexual difficulties, weight gain and emotional numbness. A key factor hindering patients in the discontinuation of antidepressant medication is the emergence of discontinuation symptoms, reported by over half of fully remitted patients discontinuing antidepressants. To date, there is no study examining open-label placebo responses on antidepressant discontinuation symptoms. However, several findings imply that open-label placebos may support the discontinuation process in remitted depressed patients. The susceptibility to placebo responses is encouraged by findings indicating substantial placebo effects in antidepressant trials (67-82%). Additionally, evidence suggests the central role of expectation effects influencing the course of antidepressant discontinuation. Open-label placebos have been found to work through the generation of positive expectations, induced by a positive framing (e.g. verbal instructions). A recent meta-analysis suggests a medium to large effect size of open-label placebos. Regarding the treatment of antidepressant discontinuation symptoms, open-label placebos have the potential to reduce symptoms not only by inducing positive expectations, but also by triggering automatic (positive) responses to the intake of a pill (i.e. conditioning).The aim of this study is to investigate the effect of open-label placebos on antidepressant discontinuation symptoms in fully remitted depressed patients.
Methods: In the proposed study, a pilot sample will discontinue their antidepressant intake under extensive medical and psychological supervision, according to the national and international guidelines over a 13-week course. After a run-in week and the baseline assessment, antidepressant medication will be gradually reduced with individualized discontinuation plans over a period of 4 weeks. Weekly measurements serve to monitor the condition of the participants. After discontinuation, patients will be monitored (with biweekly study visits) for another 8 weeks (experimental phase). Finally, a follow-up measurement 6 months after the study start constitutes long-term monitoring and the assessment of relapse after antidepressant discontinuation. During the experimental phase, patients experiencing moderate discontinuation symptoms are allocated to the intervention group, aimed to examine the effect of open-label placebo on antidepressant discontinuation symptoms. For this purpose, N-of-1 trials comprising multiple crossovers (A: open-label placebo; B: no treatment) within each individual, and varying in a biweekly rhythm, are applied. Patients are randomized to different treatment orders (ABAB; BABA). Twice daily smartphone-measurements are implemented to assess discontinuation symptoms, expectations and mood. Additionally, study visits consist of extensive measurements related to discontinuation symptoms, depressive symptomatology, psychological well-being and treatment expectations. These serve as observational measurement of different effects related to antidepressant discontinuation. During the experimental phase, outcome assessors will be blind to the randomization (i.e. treatment order) of the patients.
Objectives: At the end of the study, the investigators will determine whether open-label placebo reduces negative side effects caused by antidepressant discontinuation by aggregating the N-of-1 trials. Underlying mechanisms such as treatment expectations, as well as the relation to depressed mood, will be under explorative investigation. Additionally, the course of discontinuation symptoms, depressive symptoms (self-report and expert-rated) and treatment adherence during the entire study will be explored. Therefore, potential modulators such as psychopathology, demographics, adverse events, expectations, prior experience, subjective stress, side effects of antidepressants and anxiety vs. depression (trait/state) will be taken into account in data analyses.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- To investigate the efficacy of open-label placebo in the reduction of antidepressant discontinuation symptoms, patients experiencing moderate discontinuation symptoms after successful discontinuation (4 weeks) receive open-label placebo treatment or no treatment during the experimental phase (8 weeks). For this purpose, a series of N-of-1 trials is implemented, consisting of multiple crossover trials within each participant. The factor treatment (open-label placebo vs. no treatment) varies intra-individually with a biweekly rhythm, to assess the treatment effect on discontinuation symptoms. A block-randomization is applied, with patients either receiving (A) open-label placebo or (B) no treatment in a biweekly rhythm (group 1: ABAB; group 2: BABA).
| Arm | Type | Receives |
|---|---|---|
| Open-label placebo ABAB Sequence | Placebo comparator | Drug: Open-label placebo, Other: No-treatmentThe N-of-1 trial will, on the level of the individual patient, test whether open-label placebo reduces negative side effects caused by discontinuation of antidepressants compared to no treatment. After antidepressant discontinuation, subjects will be randomized to 2 arms differing in the treatment order (ABAB; BABA). Subjects in this arm (ABAB) will start with open-label placebo (A) for 2 weeks; they will then crossover to no treatment (B) for 2 weeks and repeat this sequence once again. |
| Open-label placebo BABA Sequence | Placebo comparator | Drug: Open-label placebo, Other: No-treatmentThe N-of-1 trial will, on the level of the individual patient, test whether open-label placebo reduces negative side effects caused by discontinuation of antidepressants compared to no treatment. After antidepressant discontinuation, subjects will be randomized to 2 arms differing in the treatment order (ABAB; BABA). Subjects in this arm (BABA) will start with no treatment (B) for 2 weeks; they will then crossover to open-label placebo (A) for 2 weeks and repeat this sequence once again. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| Open-label placeboPrior to the open-label placebo administration, an explanation why placebos without concealment might be effective is offered. Participants receive placebo pills with the instruction to take 2 pills daily for 2 weeks. | Drug | Open-label placebo ABAB Sequence, Open-label placebo BABA Sequence |
| No-treatmentDuring the no-treatment phase, participants receive no treatment for 2 weeks. | Other | Open-label placebo ABAB Sequence, Open-label placebo BABA Sequence |
Primary outcome
Change in antidepressant discontinuation symptoms assessed by the 'Generic rating scale for treatment effects' (GEEE_ACT)
Time frame: Continuous measurement (2xdaily) for 8 weeks
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.
2 secondary outcomes
Change in treatment expectations assessed by 'Generic rating scale for treatment expectations' (GEEE_EXP)
Time frame: Continuous measurement (2xdaily) for 8 weeks
Change in (depressed) mood assessed by the 'Patient-Healthcare-Questionnaire' (PHQ-2)
Time frame: Continuous measurement (2xdaily) for 8 weeks
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 12 Jun 2024.
- Background: PubMed 33986697Nestoriuc Y, Pan Y, Kinitz T, Weik E, Shedden-Mora MC. Informing About the Nocebo Effect Affects Patients' Need for Information About Antidepressants-An Experimental Online Study. Front Psychiatry. 2021 Apr 27;12:587122. doi: 10.3389/fpsyt.2021.587122. eCollection 2021.
- BackgroundRief, W., Nestoriuc, Y., Mueller, E. M., Hermann, C., Schmidt, K., & Bingel, U. Generic rating scale for previous treatment experiences, treatment expectations, and treatment effects (GEEE). PsychArchives. 2021 https://doi.org/10.23668/PSYCHARCHIVES.4717
- Background: PubMed 33208855Pan Y, Meister R, Lowe B, Kaptchuk TJ, Buhling KJ, Nestoriuc Y. Open-label placebos for menopausal hot flushes: a randomized controlled trial. Sci Rep. 2020 Nov 18;10(1):20090. doi: 10.1038/s41598-020-77255-z.
- Background: PubMed 32152159Bowers HM, Kendrick T, Glowacka M, Williams S, Leydon G, May C, Dowrick C, Moncrieff J, Laine R, Nestoriuc Y, Andersson G, Geraghty AWA. Supporting antidepressant discontinuation: the development and optimisation of a digital intervention for patients in UK primary care using a theory, evidence and person-based approach. BMJ Open. 2020 Mar 8;10(3):e032312. doi: 10.1136/bmjopen-2019-032312.
- Background: PubMed 31576565Meister R, Lanio J, Fangmeier T, Harter M, Schramm E, Zobel I, Hautzinger M, Nestoriuc Y, Kriston L. Adverse events during a disorder-specific psychotherapy compared to a nonspecific psychotherapy in patients with chronic depression. J Clin Psychol. 2020 Jan;76(1):7-19. doi: 10.1002/jclp.22869. Epub 2019 Oct 1.
- Background: PubMed 36397978Shedden-Mora MC, Pan Y, Heisig SR, von Blanckenburg P, Rief W, Witzel I, Albert US, Nestoriuc Y. Optimizing Expectations About Endocrine Treatment for Breast Cancer: Results of the Randomized Controlled PSY-BREAST Trial. Clin Psychol Eur. 2020 Mar 31;2(1):e2695. doi: 10.32872/cpe.v2i1.2695. eCollection 2020 Mar.
- Background: PubMed 31420050Pan Y, Meister R, Lowe B, Winkelmann A, Kaptchuk TJ, Buhling KJ, Nestoriuc Y. Non-concealed placebo treatment for menopausal hot flushes: Study protocol of a randomized-controlled trial. Trials. 2019 Aug 16;20(1):508. doi: 10.1186/s13063-019-3575-1.
- Background: PubMed 31427995Pan Y, Kinitz T, Stapic M, Nestoriuc Y. Minimizing Drug Adverse Events by Informing About the Nocebo Effect-An Experimental Study. Front Psychiatry. 2019 Jul 25;10:504. doi: 10.3389/fpsyt.2019.00504. eCollection 2019.
- Derived from this study: PubMed 37833651Muller A, Konigorski S, Meissner C, Fadai T, Warren CV, Falkenberg I, Kircher T, Nestoriuc Y. Study protocol: combined N-of-1 trials to assess open-label placebo treatment for antidepressant discontinuation symptoms [FAB-study]. BMC Psychiatry. 2023 Oct 13;23(1):749. doi: 10.1186/s12888-023-05184-y.
- Individual participant dataSharing planned: Yes. 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.
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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.
Yvonne Nestoriuc, Prof. Dr. principal investigator
Universitätsklinikum Hamburg-Eppendorf
Tilo Kircher, Prof. Dr. principal investigator
Philipps University Marburg
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing No-treatment in people with Depressive Symptoms and Expectations, run by Universitätsklinikum Hamburg-Eppendorf at 2 sites 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 5 inclusion and 7 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 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 antidepressant discontinuation symptoms assessed by the 'Generic rating scale for treatment effects' (GEEE_ACT) (time frame: Continuous measurement (2xdaily) for 8 weeks). 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 NCT05051995, which also lists 9 linked publications.
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 12 Jun 2024; AzTrials last refreshed its copy on 8 Nov 2026.