Study of Electrophysiological Markers of Antidepressants in Major Depressive Disorder (MESANTIDEP)

Major depressive disorder (MDD) is a frequent and particularly disabling disorder. The efficacy of current antidepressants is limited, with 50-60% of patients not achieving a sufficient response to treatment. Indeed, to date, clinicians are unable to predict the therapeutic response a patient will obtain to a given molecule. This often results in several trials of a molecule until clinical efficacy is achieved, with a delay of several months of untreated disease. Achieving faster efficacy by targeting the right molecule for each patient in the 1st line of treatment would limit the morbidity and mortality induced by MDD, and its impact on quality of life. To achieve this goal rapidly, there is a need to identify markers for predicting and monitoring therapeutic response to antidepressants.

This is why the MESANTIDEP study aims to propose electroretinographic (ERG) biomarkers for predicting therapeutic response at 12 weeks for the two main therapeutic classes of antidepressants prescribed as 1st-line treatment for major depressive disorder: Selective Serotonin Reuptake Inhibitors (SSRIs) and alpha-2 adrenergic receptor antagonists (alpha-2 antagonists). Secondly, investigators will look for ERG biomarkers of therapeutic response at 6 weeks, and 12 weeks, for these two therapeutic classes of antidepressants.

For this purpose, patients diagnosed with MDD and requiring the initiation of an antidepressant - of the SSRI or alpha-2-antagonist class - will be included. At their inclusion visit, patients will not yet have started their antidepressant treatment and will undergo various tests. These include clinical questionnaires, sleep assessment questionnaires and three ERG tests (fERG, PERG and mfERG). Antidepressant treatment can be started by the patient the day after the inclusion visit. 6 and 12 weeks later, the patient undergoes the same tests as at the inclusion visit to monitor their therapeutic response to the prescribed antidepressant. The identification of electrophysiological markers predictive of therapeutic response to antidepressants is intended to help clinicians in the treatment of MDD patients. More rapid therapeutic intervention tailored to each patient will limit the functional impact, improve quality of life and reduce the morbidity and mortality associated with the disease. These electrophysiological ERG measurements are easy to perform. They are therefore accessible to all, and can be used, through a multimodal approach, in routine clinical practice.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: Electroretinography (ERG)

• Study Type: Interventional
• Enrollment (Estimated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: De DEUS MARIE; Phone Number: 03 83 92 67 01; Email: Marie.DEDEUS@cpn-laxou.com
• Study Contact Backup: Name: Naoual MELLOUKI, PhD; Phone Number: 0383925267; Email: unic@cpn-laxou.com

Study Locations

• France
  • Nancy
    • Laxou, Nancy, France, 54520
      • Centre Psychothérapique de Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of a current unipolar depressive episode according to DSM-V criteria
• Prescription of antidepressant treatment - SSRI or alpha-2 antagonist - by the psychiatrist or referring physician for the current depressive episode
• Age 18 or more
• Affiliation with a welfare scheme and native French speakers
• Complete information on the study received and written informed consent signed

Exclusion Criteria:

• Diagnosis of a progressive psychiatric disorder (except MDD and anxiety disorder) according to DSM-V criteria
• Seasonal character of the depression
• Current antidepressant treatment
• Recommended antidepressant treatment other than SSRI or alpha-2 antagonist
• High suicide risk
• Retinal or ophtalmologic pathology affecting visual acuity as assessed by the Monoyer scale.
• History of head trauma, epilepsy or other neurological disorders
• Participation in another interventional study (including exclusion period)
• Intellectual disability leading to difficulty participating or impossibility or inability to understand the information provided on the study.
• Persons cited in Articles L. 1121-5 to L. 1121-8 of the French Public Health Code: pregnant women, parturient or breastfeeding mothers, persons deprived of their liberty by a judicial or administrative decision, persons under psychiatric care under duress, persons admitted to a health or social establishment for other goals than research, minors, adults subject to a legal protection, adults who are unable to express their consent and who are not subject to a legal protection measure.
• Criteria incompatible with the use of the ERG device: open wound in an area covered or enveloped by the device; implantable medical device (e.g. pacemaker); user at high risk of contagion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSRI treated patients; MDD patients treated with Selective Serotonin Reuptake Inhibitors (SSRIs) the day after the inclusion visit.	Device: Electroretinography (ERG); ERG are specifically carried out for research. They are performed in Nancy with the MonPackOne device developed by Metrovision for participants at center n°1, and in Paris with the RETeval device developed by LKS Technologie for participants at center n°2. Both devices comply with ISCEV standard and are CE marked. They enable the reccord of Pattern ERG, Flash ERG and Multifocal ERG using corneal and skin electrodes, or Sensor Strip skin electrodes only, for the Nancy and Paris centers respectively.; Other Names: MonPackOneⓇ (Métrovision); RETevalⓇ (LKS technologie)
Experimental: Alpha-2 antagonists treated patients; MDD patients treated with alpha-2 adrenergic receptor antagonists (alpha-2 antagonists) the day after the inclusion visit.	Device: Electroretinography (ERG); ERG are specifically carried out for research. They are performed in Nancy with the MonPackOne device developed by Metrovision for participants at center n°1, and in Paris with the RETeval device developed by LKS Technologie for participants at center n°2. Both devices comply with ISCEV standard and are CE marked. They enable the reccord of Pattern ERG, Flash ERG and Multifocal ERG using corneal and skin electrodes, or Sensor Strip skin electrodes only, for the Nancy and Paris centers respectively.; Other Names: MonPackOneⓇ (Métrovision); RETevalⓇ (LKS technologie)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ERG amplitudes at baseline	Modification of amplitude measured with flash, pattern and multifocal electroretinogram amplitude in microvolt	Baseline (D0)
ERG implicit times at baseline	Modification of implicit time measured with flash, pattern and multifocal electroretinogram implicit time in millisecond	Baseline (D0)
Montgomery Asberg Depression Rating Scale score differences between D0 and W12	A subject will be declared responder (decrease greater than or equal to 8 points between D0 and W12) or non-responder (score difference less than 8 points or increase between D0 and W12). We obtain binary data (responder/non-responder).	Baseline (D0) and 12 weeks after baseline (W12)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ERG amplitudes	Modification of amplitude measured with flash, pattern and multifocal electroretinogram amplitude in microvolt	Baseline (D0)
ERG amplitudes	Modification of amplitude measured with flash, pattern and multifocal electroretinogram amplitude in microvolt	6 weeks after baseline (W6)
ERG amplitudes	Modification of amplitude measured with flash, pattern and multifocal electroretinogram amplitude in microvolt	12 weeks after baseline (W12)
ERG implicit time	Modification of implicit time measured with flash, pattern and multifocal electroretinogram implicit time in millisecond	Baseline (D0)
ERG implicit time	Modification of implicit time measured with flash, pattern and multifocal electroretinogram implicit time in millisecond	6 weeks after baseline (W6)
ERG implicit time	Modification of implicit time measured with flash, pattern and multifocal electroretinogram implicit time in millisecond	12 weeks after baseline (W12)
Montgomery Asberg Depression Rating Scale (MADRS) score differences	A subject will be declared responder (decrease greater than or equal to 8 points between D0 and W12) or non-responder (score difference less than 8 points or increase between D0 and W12). We obtain binary data (responder/non-responder).	Baseline (D0) and 12 weeks after baseline (W12)
Montgomery Asberg Depression Rating Scale (MADRS) score differences	Differences in MADRS scores	Baseline (D0) and 6 weeks after baseline (W6)
Montgomery Asberg Depression Rating Scale (MADRS) score differences	Differences in MADRS scores	6 weeks after baseline (W6) and 12 weeks after baseline (W12)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol Use DIsorders Test (AUDIT)	A questionnaire rating consumption of alcoholic drinks	Baseline (D0)
Fagerström test	A questionnaire rating cigarette consumption	Baseline (D0)
Montgomery-Asberg Depression Rating Scale (MADRS) self	An auto-rating scale measuring depressive symptoms	Baseline (D0)
Montgomery-Asberg Depression Rating Scale (MADRS) self	An auto-rating scale measuring depressive symptoms	6 weeks after baseline (W6)
Montgomery-Asberg Depression Rating Scale (MADRS) self	An auto-rating scale measuring depressive symptoms	12 weeks after baseline (W12)
Hamilton Anxiety Rating Scale (HAM-A)	A questionnaire rating level of anxiety	Baseline (D0)
Hamilton Anxiety Rating Scale (HAM-A)	A questionnaire rating level of anxiety	6 weeks after baseline (W6)
Hamilton Anxiety Rating Scale (HAM-A)	A questionnaire rating level of anxiety	12 weeks after baseline (W12)
Geriatric Depression Scale (GDS)	A questionnaire measuring depressive symptoms for patients over 65	Baseline (D0)
Geriatric Depression Scale (GDS)	A questionnaire measuring depressive symptoms for patients over 65	6 weeks after baseline (W6)
Geriatric Depression Scale (GDS)	A questionnaire measuring depressive symptoms for patients over 65	12 weeks after baseline (W12)
Medication Adherence Report Scale (MARS)	A questionnaire assessing patients' adherence to antidepressants	Baseline (D0)
Medication Adherence Report Scale (MARS)	A questionnaire assessing patients' adherence to antidepressants	6 weeks after baseline (W6)
Medication Adherence Report Scale (MARS)	A questionnaire assessing patients' adherence to antidepressants	12 weeks after baseline (W12)
Pittsburgh Sleep Quality Index (PSQI)	A questionnaire assessing the subjective quality of sleep during the past month	Baseline (D0)
Pittsburgh Sleep Quality Index (PSQI)	A questionnaire assessing the subjective quality of sleep during the past month	6 weeks after baseline (W6)
Pittsburgh Sleep Quality Index (PSQI)	A questionnaire assessing the subjective quality of sleep during the past month	12 weeks after baseline (W12)
Epworth sleepiness scale (ESS)	A questionnaire assessing the daytime sleepiness	Baseline (D0)
Epworth sleepiness scale (ESS)	A questionnaire assessing the daytime sleepiness	6 weeks after baseline (W6)
Epworth sleepiness scale (ESS)	A questionnaire assessing the daytime sleepiness	12 weeks after baseline (W12)
Insomnia Severity Index (ISI)	A questionnaire assessing the severity of insomnia	Baseline (D0)
Insomnia Severity Index (ISI)	A questionnaire assessing the severity of insomnia	6 weeks after baseline (W6)
Insomnia Severity Index (ISI)	A questionnaire assessing the severity of insomnia	12 weeks after baseline (W12)

Collaborators and Investigators

• Sponsor: Centre Psychothérapique de Nancy
• Investigators: Principal Investigator: Schwitzer Thomas, Pr, Centre Psychothérapique de Nancy

Publications and helpful links

General Publications

• de Deus M, Petit C, Moulard M, Cosker E, Mellouki Bendimred N, Albuisson E, Maruani J, Geoffroy PA, Schwitzer T. Exploring the ElectroRetinoGraphy as a biomarker for predicting and monitoring therapeutic response to antidepressants in major depressive disorder: study protocol for the MESANTIDEP trial. Front Psychiatry. 2025 Apr 25;16:1501166. doi: 10.3389/fpsyt.2025.1501166. eCollection 2025.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Antidepressant; Selective Serotonin Reuptake Inhibitor; Electroretinography; Retinal function; Precision psychiatry; Alpha-2 adrenergic receptor antagonists
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis; Diagnostic Techniques, Ophthalmological; Electroretinography
• Other Study ID Numbers: 2024-A00551-46; RIPH 2024-01 (Other Identifier: Centre Psychothérapique de Nancy)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No