Estimation of Control Before and After Treatment of a Depressive Episode With Serotonin Reuptake Inhibitors

NCT07716982 | Not Yet Recruiting

• 1 other identifier: 2026-A00663-48
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to better understand cognitive and affective processes involved in depression, in particular how individuals estimate their perception of control over events in their environment, as well as related processes such as memory and decision-making. The study also aims to investigate how these processes are affected by antidepressant treatment and how depressive symptoms evolve over time, as well as whether specific peripheral markers (including hormones) are associated with treatment effects.

Conditions

Depression Disorder

Keywords

Depression; controllability; serotonin; SSRI; estimation of control

Outcome Measures

Primary Outcomes (1)

• Controllability Estimation Bias in depressed patients

  normalization of the controllability estimation bias in patients with depression after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). The assessment of controllability is not obtained directly from the participant, but through a computational model inferred from their behavioural data (reaction time (RT), prediction accuracy (percentage of correct responses) and error rate)

  Change between baseline and week 8

Secondary Outcomes (1)

• Controllability Estimation Bias in Depressed Patients vs Healthy Controls

  Baseline

Study Arms (2)

Depression group

EXPERIMENTAL

Patients presenting a depressive episode and receiving serotonergic antidepressant treatment

Drug: Selective Serotonin Reuptake Inhibitors (SSRIs) or serotonergic antidepressants; Other: Experimental tasks

Control group

EXPERIMENTAL

Healthy participants who are not receiving serotonergic antidepressant treatment.

Other: Experimental tasks

Interventions

Experimental tasks OTHER

Experimental tasks assessing cognition, decision-making, and perceived controllability.

Control group; Depression group

Selective Serotonin Reuptake Inhibitors (SSRIs) or serotonergic antidepressants DRUG

Participants are prescribed serotonergic antidepressants such as fluoxetine, sertraline, escitalopram, paroxetine, or serotonin-norepinephrine reuptake inhibitor (SNRI). Dosage, formulation, frequency, and treatment duration are determined by the treating clinician. No experimental manipulation of medication is performed within the study. The intervention is characterized to assess its association with cognitive performance, reaction time (RT), accuracy, and controllability-related decision-making.

Depression group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Affiliated with a social security or national health insurance system, or entitled to such coverage.
• Male or female, aged 18 to 55 years.
• Fluent in spoken and written French.
• Normal or corrected-to-normal vision.
• Access to a computer and an internet connection.
• Available for the 8-week study period following treatment initiation (patients) or the baseline visit (healthy controls).
• Willing to use an effective method of contraception (condom, oral contraceptive pill, abstinence, or intrauterine device).
• Eligible for antidepressant monotherapy with a selective serotonin reuptake inhibitor (SSRI: sertraline, fluoxetine, citalopram, or paroxetine) or a serotonin-norepinephrine reuptake inhibitor (SNRI: venlafaxine or duloxetine), with or without concomitant treatment with a short half-life benzodiazepine (\<12 hours; e.g., oxazepam, lorazepam, or clotiazepam), for which the prescription has been issued but treatment has not yet been initiated.
• Montgomery-Åsberg Depression Rating Scale (MADRS) score \>6 and \<35 (corresponding to mild-to-moderate depression), assessed during the routine clinical visit with the treating physician.
• No evidence of suicidal ideation, high-risk behaviors, history of suicide attempt, or overt psychotic symptoms that could compromise participant safety.
• No severe medical condition or unstable physiological state considered incompatible with study participation by the referring physician, including but not limited to unstable chronic diseases (e.g., hypertension or diabetes), respiratory insufficiency, cardiovascular insufficiency, or renal insufficiency.

You may not qualify if:

• History of a major depressive episode within the past 3 years.
• Use of antidepressants, mood stabilizers, or antipsychotic medication within the past 3 years.
• Diagnosis of a neurological or psychiatric disorder affecting central nervous system function (including bipolar disorder, schizophrenia, or other psychotic disorders according to DSM-5 criteria).
• Pregnancy or breastfeeding (self-reported).
• Individuals under legal protection (guardianship, curatorship, or judicial protection measures).
• Planned initiation during the study of a medication or substance known to interfere with serotonergic activity (including MDMA, LSD, psilocybin, ketamine, cocaine, 5-HT2A receptor antagonist antipsychotics, triptans, or lithium).
• Use of serotonin-acting recreational drugs within the previous 6 months (including cocaine, MDMA, or psychedelic substances).
• Refusal to be informed of the potential discovery of a clinically significant incidental finding.
• Antidepressant treatment already initiated before study enrollment.
• Use of benzodiazepines within the 12 hours preceding an experimental session.
• Treatment with benzodiazepines other than oxazepam, lorazepam, or clotiazepam.
• Current hospitalization.
• Risk of suicidal behavior, defined as a score of ≥2 on the "zest for life" ("élan de vie") item of the Montgomery-Åsberg Depression Rating Scale (MADRS).
• Current treatment considered clinically incompatible with study participation by the physician responsible for recruitment.
• Current or previous diagnosis of a depressive or anxiety disorder.

Sponsors & Collaborators

• Hôpital le Vinatier: lead
• INSERM U1028: collaborator

Study Sites (1)

Centre de Recherche en Neuroscience de Lyon

Bron, 69500, France

Location

MeSH Terms

Conditions

Depression

Interventions

Selective Serotonin Reuptake Inhibitors

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs

Study Officials

• Romain Ligneul, PhD

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Romain Ligneul, PhD

CONTACT

+33 04 72 13 89 00; romain.ligneul@inserm.fr

Méline Devaluez, PhD

CONTACT

+33 04 37 91 55 14

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 21, 2026

Record last verified: 2026-07

Locations

FR (1)