How the immune system affects response to antipsychotic medicines

Immune Mechanisms of Antipsychotic Treatment Response

Observational King's College London · NCT06687694

This study will test whether immune and inflammation markers in blood and cerebrospinal fluid can help predict or track treatment response in adults with psychosis who are starting or changing antipsychotic medication.

Quick facts

Study typeObservational
Enrollment500 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorKing's College London Academic / other
Drugs / interventionsrituximab, methotrexate, cyclophosphamide
Locations1 site (London, United Kingdom)
Trial IDNCT06687694 on ClinicalTrials.gov

What this trial studies

This is an observational biomarker study enrolling adults with psychosis who are due to start or change regular antipsychotic medication, alongside age- and sex-matched healthy controls. Investigators collect blood and cerebrospinal fluid at two main timepoints: baseline (week 0, at medication start/change) and follow-up around 4 ± 2 weeks. Clinical measures of symptoms and treatment response will be compared with immune, inflammatory, and autoantibody profiles to identify signals linked to diagnosis, prognosis, treatment selection, and response tracking. No investigational drug is administered; the study examines biological mechanisms associated with routine antipsychotic treatment.

Who should consider this trial

Good fit: Adults aged 18–65 with active psychosis thought to fall under ICD F20–F39 who are about to start or change a regular antipsychotic medication, plus age- and sex-matched healthy controls without psychosis or autoimmune disease.

Not a fit: People not starting or changing antipsychotic treatment, those who pose an unacceptable safety risk (for example severe behavioural disturbance), those outside the 18–65 age range, or those unable to safely undergo blood or CSF sampling may not benefit or be eligible.

Why it matters

Potential benefit: If successful, the findings could help clinicians choose and monitor antipsychotic treatments more quickly and precisely using blood or CSF biomarkers.

How similar studies have performed: Previous research has reported immune and inflammatory changes in psychosis and some small studies have linked such markers to treatment response, but robust, clinically validated predictive biomarkers are not yet established.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria

Participants with psychosis symptoms:

* Age 18-65
* Currently experiencing psychosis symptoms warranting treatment by secondary care mental health services, as confirmed by a psychiatrist involved in their treatment.
* Psychosis symptoms likely to be attributable to a disorder represented by ICD codes F20-F39, in the opinion of the treating clinical team.
* Due to start or change to a new regular antipsychotic medication. (Participants who are initiating antipsychotic treatment for the first time, transitioning to a different antipsychotic medication, or resuming a formerly prescribed antipsychotic medication that was discontinued for a minimum of two weeks may be recruited.)

Control Participants

* Age 18-65
* No active autoimmune disorder.
* No history of psychosis symptoms.

Exclusion Criteria

Participants with psychosis symptoms:

* Unacceptable risk of harm to participant or study staff due to risk of behavioural disturbance.
* Currently taking or having taken in the last four weeks any medication known to grossly affect the production or function of immune cells (e.g. corticosteroids, methotrexate, cyclophosphamide, mycophenolate mofetil, rituximab or other monoclonal antibody therapies).
* Inability to have blood tests.

Control participants:

* Unacceptable risk of harm to participant or study staff due to risk of behavioural disturbance.
* Currently taking or having taken in the last four weeks any medication known to grossly affect the production or function of immune cells (e.g. corticosteroids, methotrexate, cyclophosphamide, mycophenolate mofetil, rituximab or other monoclonal antibody therapies).
* Inability to have blood tests.

Optional lumbar puncture only:

* Significant lower spinal deformity (such as spina bifida), injury (such as stenosis) or previous lower spinal surgery.
* Antiplatelet or anticoagulant therapy within the 14 days prior to Lumbar Puncture procedure.
* Known or suspected clotting disorder.
* Clinically significant abnormality in full blood count.
* Known or suspected raised intracranial pressure, assessed by study clinician.
* Known or suspected allergy to local anaesthetic agent or an ingredient of the anaesthetic solution.
* History of chronic or recurrent headaches, in the opinion of the investigator.

Where this trial is running

London, United Kingdom

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions PsychosisAntipsychoticNeuroimmunologyInflammationAutoantibodySchizophreniaSchizotypal disorderPersistent delusional disorders
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.