Overview
This study aims to better understand the mechanisms of action of antidepressants, but also the neural correlates of motivation deficits. One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. The objective will be to predict the therapeutic response to two first-line antidepressants on the basis of an early neurocomputational assessment of motivation. Antidepressant treatment will be administered as monotherapy after randomization between two drugs: escitalopram and vortioxetine. Patients will undergo six visits and follow-up for one year. The investigators will combine computer modeling and functional MRI to identify motivational deficits and elucidate their brain correlates before initiation, after 7 days and after 6 months of treatment. 36 healthy volunteers will also be included to allow comparison with patients with depression. They will not receive any treatment.
Description
One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. Six visits will be scheduled within a year:
- V0 (inclusion visit): verification of inclusion and exclusion criteria, information, and consent.
- V1 (before randomization - baseline state):
- Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
- Neuro-cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating. Part of the tests will be performed during the functional MRI session.
- Structural (anatomical) and functional MRI, ASL.
- Blood samples.
- Randomization and introduction of the new antidepressant will occur immediately after V1. To maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the assigned treatment will not be changed for 4 weeks (until V3).
- V2 (7 days after the beginning of the new antidepressant - 'early response visit'):
- Similar to V1.
- V3 (28 days after the beginning of the new antidepressant - 'conventional response visit'):
- Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
- Blood samples
- V4 (6 months after the beginning of the new antidepressant - 'remission visit'):
- Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
- Cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating.
- Structural (anatomical) MRI, ASL
- Blood samples
- V5 (one year after the beginning of the new antidepressant - 'functional remission visit'):
- Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
36 healthy volunteers without a history of neurologic or psychiatric disorder, matched for age, gender, and education will be included. They will perform V0-V2 (without MRI and blood sample at V2). Healthy volunteers will not receive any treatment as part of the research.
Eligibility
Patients with major depressive disorder
Inclusion Criteria:
- Meeting DSM-5 criteria for major depressive disorder (single or recurrent episodes)
- With a MADRS score >= 24
- For which a new line of treatment is needed
- No previous line of antidepressant for this episode or wash-out long-enough to avoid carry-over effects
- Valid health care insurance
Exclusion Criteria:
- Treatment-resistant depression (defined as insufficient response despite at least 2 trials of antidepressant prescribed at adequate dose and duration)
- Subjects with a trial of escitalopram and/or vortioxetine for the current episode, or with contra-indication to one of these two drugs
- Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
- Subject with a history of neurological disorder: parkinson's disease, dementia
- Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
- Pregnant or breastfeeding women
- involuntary hospitalisation and legal protection measures
Healthy volunteers
Inclusion Criteria:
- Valid health care insurance
Exclusion Criteria:
- Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
- Subject with a history of neurological disorder: parkinson's disease, dementia
- Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
- Pregnant or breastfeeding women