Novel Candidate Genes for Treatment Response to Antipsychotics in Schizophrenia (GEXANT)

Fundación Marques de Valdecilla

Status: Unknown

Conditions: Schizophrenia

Study type: Observational

Funder types: Other; NETWORK

Identifiers

NCT02205437

GEXANT

Details and patient eligibility

About

Schizophrenia is a severe and chronic mental disorder. The lifetime risk of schizophrenia is around 1%. Its course is chronic and frequently disabling. The keystone of schizophrenia treatment is antipsychotic medications. The use of antipsychotics represents a huge public health and economic burden to society. Most of antipsychotics drugs are "metoo" drugs, directly or indirectly replicating dopamine D2 receptor blockade. Pharmaceutical companies have aimed to produce drugs with a general indication for all patients with schizophrenia with a "one-size-fits-all" strategy with no targeting or stratification. Second generation antipsychotics partly improve positive symptoms and are quite often associated to weight gain, metabolic changes and increased risk of cardiovascular diseases. Antipsychotics only achieve a certain degree of clinical improvement in a percentage of patients (45%) and 30% of the patients are treatment resistant. In light of the current deadlock, there is an urgent need to expand the horizon of pharmacological research by elucidating new mechanisms related to antipsychotic actions. An alternative strategy is the comparison of gene expression profiles in drug-naive accurately ill patients before and after antipsychotic treatment has been initiated. Our research group has a great experience in the field and has been working on this hypothesis in the latest years. We propose a continuation project to thoroughly explore the clinical implications (clinical response to antipsychotic drugs or emergence of metabolic side effects) of the variants in gene expression we have recently described in schizophrenia patients. This project takes advantage of an exceptional (regarding to the detailed knowledge of clinical outcome and side effect profile) longitudinal cohort of drug-naive patients with schizophrenia who had been followed up for three years at the University Hospital Marqués de Valdecilla.

Enrollment: 200 estimated patients

Sex: All

Ages: 15 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Patients followed up for 3 years in the First Episode Psychosis Clinical Program (PAFIP).
• 15-60 years.
• Living in the catchment area.
• Experiencing their first episode of psychosis.
• No prior treatment with antipsychotic medication or, if previously treated, a total life time of adequate antipsychotic treatment of less than 6 weeks.
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for brief psychotic disorder, schizophreniform disorder, schizophrenia, or schizoaffective disorder.

Exclusion criteria

• Meeting DSM-IV criteria for drug dependence.
• Meeting DSM-IV criteria for mental retardation.
• Having a history of neurological disease or head injury.

Trial design

200 participants in 6 patient groups

Controls

Description:

Healthy subjects without psychotic disorder.

Drug-naive patients

Description:

Drug-naive (never medicated) schizophrenia patients.

Patients responder to treatment

Description:

Patients with a good clinical response to treatment (define by a marked improvement of positive symptoms) at 3 months and at 1 year.

Patients non-responder to treatment

Description:

Patients with a poor clinical response to treatment at 3 months and at 1 year.

Patients with metabolic side effects

Description:

Patients with metabolic side effects associated to treatment.

Patients with non-metabolic side effects

Description:

Patients with no metabolic side effects associated to treatment.