Clinical TrialTreatment-Resistant Depression (TRD)KetamineRecruiting

Belief Updating in Treatment Resistant Depression

Prospective observational study (n=120) assessing belief-updating in TRD patients before and 24 hours after a single antidepressant dose; a 60-patient subset will undergo fMRI (ketamine or monoaminergic treatments in routine care).

Target Enrollment
120 participants
Study Type
Phase NA observational
Design
Randomized

Detailed Description

This prospective case-control observational study examines neural mechanisms of belief updating about the future in patients with treatment-resistant depression (TRD) before and 24 hours after a single antidepressant dose given in routine clinical care.

Participants complete a 40-trial belief-updating task and rating scales; 60 of 120 participants will have fMRI scans pre- or 24 h post-treatment to assess BOLD responses to positive versus negative disconfirming information.

Primary outcome is the interaction of testing time (before vs after a single dose) and information valence (positive vs negative) on BOLD response; secondary aims include behavioural bias changes and correlation with global clinical improvement (MADRS).

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

Before treatment

experimental

Behavioural testing and fMRI prior to first antidepressant dose

Interventions

  • Compound
    via Other• single session

    Functional MRI with 40-trial belief updating task; behavioural ratings (valence, familiarity, vividness, relevance, controllability, arousal).

After treatment

experimental

Behavioural testing and fMRI 24 hours after a single antidepressant dose (ketamine or monoaminergic)

Interventions

  • Ketamine
    via IV• single dose• 1 doses total

    Single subanaesthetic ketamine infusion administered in routine clinical care; fMRI performed 24 h after infusion.

  • Compound
    via Other• single session

    Single monoaminergic antidepressant dose administered in routine care with behavioural testing only (behavioural-only subgroup of 60 patients).

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Demographic criteria:
  • Age: 18 to 70 years
  • Male and female
  • Diagnostic criteria, severity and clinical course:
  • Major depressive disorder (MDD) according to DSM-5
  • MADRS ≥ 20
  • Treatment resistant depression (TRD) defined by failure to respond to at least two trials of different antidepressant treatments
  • Affiliation to a social security regime
  • Treatments/strategies/procedures:
  • At the start of new antidepressant treatment involving glutamate receptor modulators or monoaminergic antidepressants.

Exclusion Criteria

  • Exclusion criteria:
  • Associated pathologies carrying specific risks:
  • Mental disorder other than MDD: ADHD, personality disorder, schizophrenia, autism spectrum disorder, eating disorder, PTSD, social phobia, OCD, substance use disorder
  • Inability to understand task instructions or perform the behavioural task
  • Mini Mental Score (MMS) ≤ 25
  • Antidepressant treatment involving dopaminergic agonists, triple reuptake inhibitors, or MAOIs
  • Medical history: epilepsy, brain tumour, nervous system disease, visual and/or auditory deficit
  • Contraindications for MRI exam (research-added):
  • Metallic implant, pacemaker, artificial heart valve, vascular malformation, aneurysm clips, metallic fragments exposure, peripheral or neuronal stimulator, insulin pump, intravenous catheter, metallic contraceptive device, claustrophobia, unwillingness to be informed in case of significant MRI abnormality
  • Vulnerable populations:
  • Pregnancy
  • Patient on state medical aid (AME)
  • Patient under guardianship, curatorship, or legal protection

Study Details

Locations

GH Pitié Salpêtrière — Paris, France

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