Disentangling Pharmacological and Expectation Effects in Antidepressant Discontinuation - a Randomized, Balanced Open-hidden Trial

PV7151

Antidepressant medication is established as an evidence-based, guideline-recommended treatment for Major Depressive Disorders. In the past decades, prescriptions of antidepressant medication have markedly increased, with a specific surge in maintenance prescriptions and therefore, long-term intake, despite guideline recommendations to discontinue antidepressant medication after maintenance therapy has been completed. Over half of fully remitted patients who attempt to discontinue their antidepressant medication report adverse discontinuation symptoms. For many patients, discontinuation symptoms are so severe, that they do not manage to complete their discontinuation attempt. While discontinuation symptoms, deterioration of depressive symptoms, and recurrence can result from pharmacological effects of antidepressant discontinuation, patients' expectations towards discontinuation are likely to play an essential role in occurrence, too. The aim of the present study is to explore the interplay of expectations and pharmacological effects in antidepressant discontinuation. Participants who fulfill German national S3 guideline recommendations will receive a 1:1 chance to either discontinue their antidepressant medication or remain on their antidepressant medication. In addition, participants' expectations are intended to be manipulated by varying verbal instructions using the open-hidden paradigm. Within the open trial arms, participants will receive full information about their treatment (i.e., high expectation). Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant medication (i.e., moderate expectation). Participants will have a 1:1:1:1 chance of being allocated to 1 of the 4 experimental groups: open discontinuation (OD), hidden discontinuation (HD), open continuation (OC), or hidden continuation (HC) of their 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).

2022-08-01

2025-12-31

2026-06-30

Recruiting

196

Inclusion Criteria: * Adult patients (18 to 75 years) with fully remitted Major Depressive Disorder, single or recurrent, as main diagnosis confirmed by prescribing physician and SCID-5 (American Psychiatric Association, 2013) * Intake of SSRI/SNRI (citalopram: 20-40mg, escitalopram: 10-20mg, sertraline: 50-150mg, venlafaxine: 75-150mg, duloxetine: 60-100mg, paroxetine: 20-40mg) or NaSSA (mirtazapine: 30-45mg) * Discontinuation wish by patient supported by prescribing physician * Fulfils criteria of the German S3 national guideline recommendations for treatment of Major Depressive Disorders to discontinue antidepressant medication: a) response to antidepressant medication, b) symptom remission for at least four months (for a single episode) or two years (for two or more episodes with significant functional impairment) and c) concurrent intake of antidepressant medication (at least 4 weeks on a steady dose) Exclusion Criteria: * Acute or chronic somatic illness and/or intake of medication which might interfere with depressive disorder, antidepressant medication or proposed study * Acute suicidality, psychotic symptoms, substance abuse or addiction, current mania, or hypomania confirmed by SCID-5 (American Psychiatric Association, 2013) or other psychopathology which might interfere with depressive disorder, antidepressant medication or proposed study * Any history of bipolar disorder or psychosis confirmed by SCID-5 (American Psychiatric Association, 2013) * Severe stressful life events (e.g., death of a family member) within six months prior to study participation * Insufficient German language proficiency * No informed consent * Upon optional participation: MRI-specific exclusion criteria (phobic anxiety, claustrophobia, ferromagnetic implants, etc.)

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'The PHEA-study is a randomized, balanced open-hidden discontinuation trial with a 2x2-factorial design (treatment: continuation versus discontinuation; expectation: high versus moderate). A stratified block-randomization will be applied, with participants receiving either open discontinuation (OD), hidden discontinuation (HD), open continuation (OC), or hidden continuation (HC) of their antidepressant medication. Participants will have a 1:1:1:1 chance of being allocated to one of the four experimental groups. With an anticipated dropout rate of 20 % our recruitment target is N=196 (n=49 per group). Randomization will be stratified by i) intake duration of antidepressant medication with 24 months as a marker for long-term intake (\\<24 months intake vs. ≥ 24 months intake, 3:7); and ii) risk of developing discontinuation symptoms associated with the antidepressant medication (moderate vs. higher or unknown risk, 1:1).', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'In case of assignment to one of the hidden arms, both participants and investigators (i.e. physicians, psychologists, and research assistants) will be blinded to group assignment. Accordingly, in case of assignment to one of the open trial arms, participants and investigators will be aware of group assignment. The primary outcome is a self-report measure assessed via an online-survey by the participants; the outcome assessor (= participant) will therefore only be blinded to group assignment in the hidden arms. The person responsible for randomization and preparation of the medication is not blinded, but has no contact with the study participants.', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 196, 'type': 'ESTIMATED'}}

2024-03-22