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

0721-20

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).

2022-02-17

2024-06-01

2024-09-01

Recruiting

20

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'CROSSOVER', 'interventionModelDescription': '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).\n\nFor 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).', 'primaryPurpose': 'SUPPORTIVE_CARE', 'maskingInfo': {'masking': 'SINGLE', 'maskingDescription': 'The person performing the data collection (assessor) will be blind to the randomization of the participant for the entire duration of the experimental phase.', 'whoMasked': ['OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2024-01-17