Disentangling Pharmacological and Expectation Effects in Antidepressant Discontinuation

Summary

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).

Conditions

• Depressive Symptoms
• Expectations
• Antidepressants

Interventions

DRUG

Treatment 'discontinuation of antidepressant medication'

Pharmacological intervention: Participants will discontinue their antidepressant medication.

DRUG

Treatment 'continuation of antidepressant medication'

Pharmacological intervention: Participants will remain on their antidepressant medication.

BEHAVIORAL

Expectation 'high'

Psychological intervention: Participants' expectations will 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). expectation).

BEHAVIORAL

Expectation 'moderate'

Psychological intervention: Participants' expectations will be manipulated by varying verbal instructions using the open-hidden paradigm. 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).

Sponsors & Collaborators

• Philipps University Marburg

  collaborator OTHER

• Helmut Schmidt University

  collaborator OTHER

• University Hospital, Essen

  collaborator OTHER

• Universitätsklinikum Hamburg-Eppendorf

  lead OTHER

Principal Investigators

• Yvonne Nestoriuc, Prof. Dr. · Universitätsklinikum Hamburg-Eppendorf

• Tilo Kircher, Prof. Dr. · Philipps University Marburg

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-08-01

Primary Completion

2025-02-26

Completion

2025-11-26

Countries

• Germany

Study Locations