A Prospective, Exploratory Analysis of Immune and Inflammatory Response Associated With Clozapine

The specific aim of this protocol is to compare Clozapine treatment vs Non-Clozapine antipsychotic treatment in a population of treatment-refractory individuals with schizophrenia. Specifically, it is to test if Clozapine leads to a decrease in levels of inflammatory markers, namely interleukin-6 but with an exploratory view of other markers. Clozapine has superior efficacy and is the only medication approved for treatment-refractory schizophrenia in addition to decreasing the risk of suicidal behavior as well. It is unclear why Clozapine has increased efficacy from a mechanistic viewpoint. We will look at the role of inflammatory markers and prospectively track them over the course of 4 months in 4 week intervals along with rating scales for psychosis and suicidality, the other entities which Clozapine has been shown to improve.

Inclusion Criteria:All participants:Between 18 and 40 years of agePhysically healthy (no clinically significant medical condition as confirmed by medical history and physical examination)Able to give informed consentTreatment-Refractory SchizophreniaClozapine treatment group (n = 30)Newly initiating treatment with Clozapine for the first time and have not yet been given more than 4 days (96 hours) of the Clozapine before initial lab work obtained Non-Clozapine treatment, active comparator group (n = 30)Continued treatment with non-Clozapine antipsychotic but would be eligible for Clozapine with the provider/patient electing to not pursue such for clinical reasonsExclusion Criteria:Clinically significant medical condition; cardiovascular, pulmonary, endocrine, or renal condition requiring in depth medical treatmentActive or recent (within 4 weeks) bacterial or viral infectionChronic viral infection (hepatitis, HIV)History of autoimmune, or chronic inflammatory conditionCurrent treatment with lithiumTreatment with Clozapine in the past 6 monthsCurrent treatment with immunomodulatory or anti-inflammatory therapyVaccination within the past 3 monthsCurrent alcohol or substance use disorder of moderate or severe severityIntellectual disability (i.e. intelligence quotient <70)Unwilling or unable to sign informed consent documentPregnancyAny patient deemed ineligible by PI discretion