Major Depressive DisorderSTRATIDEPNCT05866575
Prediction of the Therapeutic Response in Depression Based on Neuro-computational Modeling Assessment of Motivation
A study testing escitalopram and vortioxetine in people with Major Depressive Disorder, run by Centre Hospitalier St Anne at 5 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- escitalopram and vortioxetine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 5 sitesFrance
- Study dates
- 12 Sep 2023to 12 Nov 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- Valid health care insurance
Who cannot join
- 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
Show all 12Show fewer
- involuntary hospitalisation and legal protection measures
- Healthy volunteers
- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
France5 sites, 5 recruiting
- Not yet recruiting
Groupe hospitalo-universitaire de Grenoble Alpes
La Tronche, Isère, 38700
Mircea Polosan
- Not yet recruiting
Centre hospitalier Universitaire de Lille
Lille, Nord, 59000
Renaud Jardri
- Not yet recruiting
Groupe hospitalo-universitaire Assistance Publique, hôpital Pitié Salpêtrière - Hôpitaux de Paris Sorbonne Université
Paris, 75013
Philippe Fossati
- Recruiting
- Groupe hospitalo-universitaire Paris Psychiatrie et Neurosciences
Paris, 75014
Fabien Vinckier
- Not yet recruiting
Centre hospitalier Universitaire de Saint-Etienne
Saint-Priest-en-Jarez, Pays de la Loire Region, 42270
Eric Fakra
About this study
Official title: Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation
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.
Read the detailed 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.
- Conditions
- Major Depressive Disorder
- Being tested
- escitalopram, vortioxetine
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
escitalopramOther
Patients will receive an antidepressant strategy : escitalopram. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.
vortioxetineOther
Patients will receive an antidepressant strategy : vortioxetine. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the treatment strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.
| Study group | Role | What they receive |
|---|---|---|
| escitalopram strategy | Other | The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. Receives: Other: escitalopram |
| vortioxetine strategy | Other | The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. Receives: Other: vortioxetine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the computational phenotype of depressed patients.
The therapeutic response will be measured with the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is a 10- item scale widely used in depression research to assess the severity of depression. Response will be defined by a score divided by 2 compared to baseline MADRS score, while remission will be defined by a score < 7 (symptom absent) 28 days after the initiation of the antidepressant strategy.
The "computational phenotype" is the outcome of the computationnal analysis of behavior. It is expressed in abstract unit. The change in computationnal phenotype between V1 and V2 will be entered in logistic regression aiming to predict clinical response at 28 days, measured with the MADRS score.
Measured: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)
Secondary outcomes (13)
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the neuro-computational phenotype of depressed patients
Same than outcome 1 but using brain imaging on top of behavior (neurocomputational modeling) to predict clinical response.
Measured: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the initial (baseline state- V1) neuro-computational phenotype of depressed patients
Same than Outcome 2 but using only V1 instead of the change between V1 and V2 to predict clinical response.
Measured: Baseline state (before the start of antidepressant strategy), and V3 (after 28 days of antidepressant)
Prediction of long-term remission (V4) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients
Same than Outcome 2 but to predict clinical remission at V4 instead of clinical response at V3.
Measured: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V4 (6 months after the start of antidepressant)
Prediction functional remission (V5) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients
Same than Outcome 2 but to predict functional remission at V5 instead of clinical response at V3.
Measured: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V5 (1 year after the start of antidepressant)
Prediction of relapse at one year (V5) based on the computationnal phenotype of remitted patients at 6 months (V4).
Same than Outcome 1 but using computational phenotype at V4 to predict predict functional remission at V5.
Measured: V4 (6 months after the start of antidepressant), V5 (1 year after the start of antidepressant)
Description of the motivational deficit of depressed patients at baseline (V1).
Comparison of the computational phenotype of patients with depression and healthy volunteers at V1.
Measured: Baseline state (before the start of antidepressant strategy)
Description of the neural correlates of motivation deficits of depressed patients at baseline (V1).
Comparison of the brain functional statistical maps of patient with depression and healthy volunteers at V1.
Measured: Baseline state (before the start of antidepressant strategy)
Description of the evolution of motivation deficit of depressed patients after one week of antidepressant treatment
Comparison of the computational phenotype of patients with depression at V1 and V2.
Measured: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)
Description of the evolution of the neural correlates of motivation deficits after one week of antidepressant treatment
Comparison of the brain functional statistical maps of patient with depression at V1 and V2.
Measured: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)
Description of the evolution of motivation deficit of depressed patients at 6 months
Comparison of the computational phenotype of patients with depression at V1 and V4.
Measured: Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)
Description of the evolution of the structural neural correlates of depression after 6 months of treatment
Comparison of the structural brain imaging of patients with depression at V1 and V4.
Measured: Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)
Description of the evolution of the functional neural correlates of depression after 6 months of treatment
Comparison of the function brain imaging (ASL) of patients with depression at V1 and V4.
Measured: Baseline state (before the start of antidepressant strategy) V4 (6 months after the start of antidepressant)
Construction of a bio-bank
Serum tubes will be drowned along the study (V1, V2, V3 and V4 for patients - V1 for healthy volunteers) prepared and stored.
Measured: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant), V4 (6 months after the start of antidepressant)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2023
- Study start12 Sep 2023
- Primary completion12 Oct 2026 (estimated)
- Study completion12 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (57)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier St AnneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomization and introduction of the new antidepressant will occur immediately after V1. Patients will receive an antidepressant as monotherapy after randomization between two strategies: escitalopram and vortioxetine. To maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the allocated treatment will not be changed for 4 weeks (until V3). After 4 weeks, the treatment can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.
- Masking
- None (open label)
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier St Anne
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05866575
- Sponsor's protocol ID
- D20-P059
- Acronym
- STRATIDEP
- Status last verified
- Jul 2024
- First submitted
- 15 Nov 2022
- Last updated
- 10 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data obtained from medical visits (clinical informations, biological assessments, cognitive data) and brain MRIs will be kept, coded and archived for a period of two years after the last publication of the research results or until the final research report is signed. These can be used later for collaborative research (academic and/or industrial partners) in the European Union (EU) and/or abroad exclusively for scientific purposes. In case of transfer of the anonymized database resulting from this research abroad (outside the EU), the sponsor undertakes to ensure a level of security equivalent to French or European Union law.
Publications
Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Moller HJ; World Federation of Societies of Biological Psychiatry. Task Force on Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013 Jul;14(5):334-85. doi: 10.3109/15622975.2013.804195. Epub 2013 Jul 3.
PubMed 23879318Lam RW, Kennedy SH, Grigoriadis S, McIntyre RS, Milev R, Ramasubbu R, Parikh SV, Patten SB, Ravindran AV; Canadian Network for Mood and Anxiety Treatments (CANMAT). Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009 Oct;117 Suppl 1:S26-43. doi: 10.1016/j.jad.2009.06.041. Epub 2009 Aug 11.
PubMed 19674794Uher R, Perlis RH, Henigsberg N, Zobel A, Rietschel M, Mors O, Hauser J, Dernovsek MZ, Souery D, Bajs M, Maier W, Aitchison KJ, Farmer A, McGuffin P. Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms. Psychol Med. 2012 May;42(5):967-80. doi: 10.1017/S0033291711001905. Epub 2011 Sep 20.
PubMed 21929846Pessiglione M, Vinckier F, Bouret S, Daunizeau J, Le Bouc R. Why not try harder? Computational approach to motivation deficits in neuro-psychiatric diseases. Brain. 2018 Mar 1;141(3):629-650. doi: 10.1093/brain/awx278.
PubMed 29194534Clery-Melin ML, Schmidt L, Lafargue G, Baup N, Fossati P, Pessiglione M. Why don't you try harder? An investigation of effort production in major depression. PLoS One. 2011;6(8):e23178. doi: 10.1371/journal.pone.0023178. Epub 2011 Aug 10.
PubMed 21853083Mauras T, Masson M, Fossati P, Pessiglione M. Incentive Sensitivity as a Behavioral Marker of Clinical Remission From Major Depressive Episode. J Clin Psychiatry. 2016 Jun;77(6):e697-703. doi: 10.4088/JCP.15m09995.
PubMed 27337420Le Heron C, Plant O, Manohar S, Ang YS, Jackson M, Lennox G, Hu MT, Husain M. Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson's disease. Brain. 2018 May 1;141(5):1455-1469. doi: 10.1093/brain/awy110.
PubMed 29672668Wardle MC, Treadway MT, Mayo LM, Zald DH, de Wit H. Amping up effort: effects of d-amphetamine on human effort-based decision-making. J Neurosci. 2011 Nov 16;31(46):16597-602. doi: 10.1523/JNEUROSCI.4387-11.2011.
PubMed 22090487Treadway MT, Buckholtz JW, Cowan RL, Woodward ND, Li R, Ansari MS, Baldwin RM, Schwartzman AN, Kessler RM, Zald DH. Dopaminergic mechanisms of individual differences in human effort-based decision-making. J Neurosci. 2012 May 2;32(18):6170-6. doi: 10.1523/JNEUROSCI.6459-11.2012.
PubMed 22553023Nutt D, Demyttenaere K, Janka Z, Aarre T, Bourin M, Canonico PL, Carrasco JL, Stahl S. The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. J Psychopharmacol. 2007 Jul;21(5):461-71. doi: 10.1177/0269881106069938. Epub 2006 Oct 18.
PubMed 17050654Culpepper L. Escitalopram: A New SSRI for the Treatment of Depression in Primary Care. Prim Care Companion J Clin Psychiatry. 2002 Dec;4(6):209-214. doi: 10.4088/pcc.v04n0601.
PubMed 15014711Sanchez C, Asin KE, Artigas F. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther. 2015 Jan;145:43-57. doi: 10.1016/j.pharmthera.2014.07.001. Epub 2014 Jul 9.
PubMed 25016186Fervaha G, Foussias G, Agid O, Remington G. Motivational and neurocognitive deficits are central to the prediction of longitudinal functional outcome in schizophrenia. Acta Psychiatr Scand. 2014 Oct;130(4):290-9. doi: 10.1111/acps.12289. Epub 2014 May 22.
PubMed 24850369Fervaha G, Foussias G, Takeuchi H, Agid O, Remington G. Motivational deficits in major depressive disorder: Cross-sectional and longitudinal relationships with functional impairment and subjective well-being. Compr Psychiatry. 2016 Apr;66:31-8. doi: 10.1016/j.comppsych.2015.12.004. Epub 2015 Dec 18.
PubMed 26995233Berwian IM, Wenzel JG, Collins AGE, Seifritz E, Stephan KE, Walter H, Huys QJM. Computational Mechanisms of Effort and Reward Decisions in Patients With Depression and Their Association With Relapse After Antidepressant Discontinuation. JAMA Psychiatry. 2020 May 1;77(5):513-522. doi: 10.1001/jamapsychiatry.2019.4971.
PubMed 32074255
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation
- ClinicalTrials.gov ID
- NCT05866575
- Acronym / sponsor ID
- STRATIDEP / D20-P059
- Conditions
- Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 136 participants (estimated)
- Lead sponsor
- Centre Hospitalier St AnneUniversity, hospital or other
- Study start
- 12 Sep 2023 (actual)
- Primary completion
- 12 Oct 2026 (estimated)
- Study completion
- 12 Nov 2026 (estimated)
- First posted
- 19 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomization and introduction of the new antidepressant will occur immediately after V1. Patients will receive an antidepressant as monotherapy after randomization between two strategies: escitalopram and vortioxetine. To maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the allocated treatment will not be changed for 4 weeks (until V3). After 4 weeks, the treatment can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.
| Arm | Type | Receives |
|---|---|---|
| escitalopram strategy | Other | Other: escitalopramThe strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. |
| vortioxetine strategy | Other | Other: vortioxetineThe strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| escitalopramPatients will receive an antidepressant strategy : escitalopram. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial. | Other | escitalopram strategy |
| vortioxetinePatients will receive an antidepressant strategy : vortioxetine. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the treatment strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial. | Other | vortioxetine strategy |
Primary outcome
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the computational phenotype of depressed patients.
Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)
The therapeutic response will be measured with the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is a 10- item scale widely used in depression research to assess the severity of depression. Response will be defined by a score divided by 2 compared to baseline MADRS score, while remission will be defined by a score < 7 (symptom absent) 28 days after the initiation of the antidepressant strategy. The "computational phenotype" is the outcome of the computationnal analysis of behavior. It is expressed in abstract unit. The change in computationnal phenotype between V1 and V2 will be entered in logistic regression aiming to predict clinical response at 28 days, measured with the MADRS score.
13 secondary outcomes
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the neuro-computational phenotype of depressed patients
Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the initial (baseline state- V1) neuro-computational phenotype of depressed patients
Time frame: Baseline state (before the start of antidepressant strategy), and V3 (after 28 days of antidepressant)
Prediction of long-term remission (V4) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients
Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V4 (6 months after the start of antidepressant)
Prediction functional remission (V5) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients
Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V5 (1 year after the start of antidepressant)
Prediction of relapse at one year (V5) based on the computationnal phenotype of remitted patients at 6 months (V4).
Time frame: V4 (6 months after the start of antidepressant), V5 (1 year after the start of antidepressant)
Description of the motivational deficit of depressed patients at baseline (V1).
Time frame: Baseline state (before the start of antidepressant strategy)
Description of the neural correlates of motivation deficits of depressed patients at baseline (V1).
Time frame: Baseline state (before the start of antidepressant strategy)
Description of the evolution of motivation deficit of depressed patients after one week of antidepressant treatment
Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)
Description of the evolution of the neural correlates of motivation deficits after one week of antidepressant treatment
Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)
Description of the evolution of motivation deficit of depressed patients at 6 months
Time frame: Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)
Description of the evolution of the structural neural correlates of depression after 6 months of treatment
Time frame: Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)
Description of the evolution of the functional neural correlates of depression after 6 months of treatment
Time frame: Baseline state (before the start of antidepressant strategy) V4 (6 months after the start of antidepressant)
Construction of a bio-bank
Time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant), V4 (6 months after the start of antidepressant)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Background: PubMed 23879318Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Moller HJ; World Federation of Societies of Biological Psychiatry. Task Force on Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry. 2013 Jul;14(5):334-85. doi: 10.3109/15622975.2013.804195. Epub 2013 Jul 3.
- Background: PubMed 19674794Lam RW, Kennedy SH, Grigoriadis S, McIntyre RS, Milev R, Ramasubbu R, Parikh SV, Patten SB, Ravindran AV; Canadian Network for Mood and Anxiety Treatments (CANMAT). Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009 Oct;117 Suppl 1:S26-43. doi: 10.1016/j.jad.2009.06.041. Epub 2009 Aug 11.
- Background: PubMed 21929846Uher R, Perlis RH, Henigsberg N, Zobel A, Rietschel M, Mors O, Hauser J, Dernovsek MZ, Souery D, Bajs M, Maier W, Aitchison KJ, Farmer A, McGuffin P. Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms. Psychol Med. 2012 May;42(5):967-80. doi: 10.1017/S0033291711001905. Epub 2011 Sep 20.
- Background: PubMed 29194534Pessiglione M, Vinckier F, Bouret S, Daunizeau J, Le Bouc R. Why not try harder? Computational approach to motivation deficits in neuro-psychiatric diseases. Brain. 2018 Mar 1;141(3):629-650. doi: 10.1093/brain/awx278.
- Background: PubMed 21853083Clery-Melin ML, Schmidt L, Lafargue G, Baup N, Fossati P, Pessiglione M. Why don't you try harder? An investigation of effort production in major depression. PLoS One. 2011;6(8):e23178. doi: 10.1371/journal.pone.0023178. Epub 2011 Aug 10.
- Background: PubMed 27337420Mauras T, Masson M, Fossati P, Pessiglione M. Incentive Sensitivity as a Behavioral Marker of Clinical Remission From Major Depressive Episode. J Clin Psychiatry. 2016 Jun;77(6):e697-703. doi: 10.4088/JCP.15m09995.
- Background: PubMed 29672668Le Heron C, Plant O, Manohar S, Ang YS, Jackson M, Lennox G, Hu MT, Husain M. Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson's disease. Brain. 2018 May 1;141(5):1455-1469. doi: 10.1093/brain/awy110.
- Background: PubMed 22090487Wardle MC, Treadway MT, Mayo LM, Zald DH, de Wit H. Amping up effort: effects of d-amphetamine on human effort-based decision-making. J Neurosci. 2011 Nov 16;31(46):16597-602. doi: 10.1523/JNEUROSCI.4387-11.2011.
- Background: PubMed 22553023Treadway MT, Buckholtz JW, Cowan RL, Woodward ND, Li R, Ansari MS, Baldwin RM, Schwartzman AN, Kessler RM, Zald DH. Dopaminergic mechanisms of individual differences in human effort-based decision-making. J Neurosci. 2012 May 2;32(18):6170-6. doi: 10.1523/JNEUROSCI.6459-11.2012.
- Background: PubMed 17050654Nutt D, Demyttenaere K, Janka Z, Aarre T, Bourin M, Canonico PL, Carrasco JL, Stahl S. The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. J Psychopharmacol. 2007 Jul;21(5):461-71. doi: 10.1177/0269881106069938. Epub 2006 Oct 18.
- Background: PubMed 15014711Culpepper L. Escitalopram: A New SSRI for the Treatment of Depression in Primary Care. Prim Care Companion J Clin Psychiatry. 2002 Dec;4(6):209-214. doi: 10.4088/pcc.v04n0601.
- Background: PubMed 25016186Sanchez C, Asin KE, Artigas F. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther. 2015 Jan;145:43-57. doi: 10.1016/j.pharmthera.2014.07.001. Epub 2014 Jul 9.
- Individual participant dataSharing planned: Yes. The data obtained from medical visits (clinical informations, biological assessments, cognitive data) and brain MRIs will be kept, coded and archived for a period of two years after the last publication of the research results or until the final research report is signed. These can be used later for collaborative research (academic and/or industrial partners) in the European Union (EU) and/or abroad exclusively for scientific purposes. In case of transfer of the anonymized database resulting from this research abroad (outside the EU), the sponsor undertakes to ensure a level of security equivalent to French or European Union law.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing escitalopram and vortioxetine in people with Major Depressive Disorder, run by Centre Hospitalier St Anne at 5 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fabien Vinckier (0033683714083, f.vinckier@ghu-paris.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the computational phenotype of depressed patients. (time frame: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05866575, which also lists 57 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.