Treatment Resistance in Psychiatric Disorders: the Search for Biological Markers Predictive of Response to Treatment

Overview

The disruption of immune system is a key candidate in the pathogenesis of psychiatric disorders, especially those resistant to traditional treatments. Involving complex processes within the brain and peripheral immune system, inflammation may lead to imbalance of neurotransmitter systems and synaptic plasticity and directly contribute to the psychiatric symptoms observed in conditions such as depression, bipolar disorder (BD) and schizophrenia (SCZ). Studies show that treatment-resistant depression (TRD) is associated with elevated levels of inflammatory markers in the blood, which are linked to a lower response to conventional antidepressants. Interventions that modulate this inflammatory response, such as immunomodulatory treatments or therapies targeting pro-inflammatory cytokines, have demonstrated beneficial effects by reducing symptoms and improving patients' quality of life. A thorough understanding of the links between inflammation and treatment resistance therefore paves the way for innovative therapeutic strategies. These approaches could transform current practices by offering more personalized and effective solutions for patients suffering from chronic and resistant psychiatric disorders.

Interventions

• Biological Blood sampling, lumbar puncture, stool sampling, skin microbiopsy and psychometrics scales
  the biomarker research involves different biological sampling : blood, stool, cerebrospinal fluid, skin

Primary outcome measures

• Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3) [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3) [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3) [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3) [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3) [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in disease scale scores at the end of acute phase therapy (V3) [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3). [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3). [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3). [Time frame: Up to 10 weeks]
• Changes from inclusion (V1) in biological parameters at the end of acute phase therapy (V3). [Time frame: Up to 10 weeks]

Secondary outcome measures (12)

• Changes in CRPus from inclusion (V1) to Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes in immunity markers from inclusion (V1) to Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes from inclusion (V1) in standardized clinical disease scale scores at Day 2 (V2) [Time frame: From enrollment to Day 2]
• Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores [Time frame: through study completion, an average of 2 years]
• Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores [Time frame: through study completion, an average of 2 years]
• Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores [Time frame: through study completion, an average of 2 years]
• Changes from inclusion (V1) to end of study (M24) in standardized clinical disease scale scores [Time frame: through study completion, an average of 2 years]

Eligibility criteria

Inclusion criteria

• Patient aged ≥ 18 years old;
• Patient suffering from a psychiatric disorder according to DSM-5 criteria;
• Patient with drug-resistant disease according to the definition of the protocol
• Patient starting a new treatment for his pathology;
• Patient informed and having signed an informed consent;
• Patient covered by the social security system.

Exclusion criteria

• Patient with major neurocognitive disorder diagnosed (dementia syndrome)
• Pregnant, laboring, or breastfeeding female patients
• Patient deprived of liberty by judicial or administrative decision. Patient in psychiatric care under constraints may be included.
• For patients accepting the lumbar punction: patients who are unable to control themselves and are likely to engage in physical or violent behavior.

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

Other

Study locations

France · 1 center

• GHU Paris - Psychiatrie et Neurosciences — Paris

Identifiers

NCT: NCT07741981 · D25-P041 · N°ID-RCB: 2026-A00433-48

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗