Study of Electrophysiological Markers of Antidepressants in Major Depressive Disorder

Overview

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.

Interventions

• 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 respective

Primary outcome measures

• ERG amplitudes at baseline [Time frame: Baseline (D0)]
• ERG implicit times at baseline [Time frame: Baseline (D0)]
• Montgomery Asberg Depression Rating Scale score differences between D0 and W12 [Time frame: Baseline (D0) and 12 weeks after baseline (W12)]

Secondary outcome measures (9)

• ERG amplitudes [Time frame: Baseline (D0)]
• ERG amplitudes [Time frame: 6 weeks after baseline (W6)]
• ERG amplitudes [Time frame: 12 weeks after baseline (W12)]
• ERG implicit time [Time frame: Baseline (D0)]
• ERG implicit time [Time frame: 6 weeks after baseline (W6)]
• ERG implicit time [Time frame: 12 weeks after baseline (W12)]
• Montgomery Asberg Depression Rating Scale (MADRS) score differences [Time frame: Baseline (D0) and 12 weeks after baseline (W12)]
• Montgomery Asberg Depression Rating Scale (MADRS) score differences [Time frame: Baseline (D0) and 6 weeks after baseline (W6)]
• Montgomery Asberg Depression Rating Scale (MADRS) score differences [Time frame: 6 weeks after baseline (W6) and 12 weeks after baseline (W12)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Centre Psychothérapique de Nancy — Laxou

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. PMID 40352365

Identifiers

NCT: NCT06532604 · 2024-A00551-46 · RIPH 2024-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗