Clozapine for the Prevention of Violence in Schizophrenia: a Randomized Clinical Trial

Inclusion Criteria:

• Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of schizophrenia orschizoaffective disorder by the Structured Clinical Interview for DSM-5 (SCID-5)

• commission of a minor or serious act of violence as measured by the MCVI in the lastsix months

• willing and able to provide informed consent

• medically stable in judgment of physician providing study treatment

• appropriate for treatment with either clozapine or TAU, i.e., that there is clinicalequipoise between the two treatment options. Individuals who are currentlymedication free or on any antipsychotic, with the exception of clozapine orlong-acting injectable medication with a dosing interval of more than 30 days willbe eligible

Exclusion Criteria:

• An unstable of serious medical or neurological condition including amyeloproliferative disorder or condition that surprises the bone marrow

• A history of intolerance/allergy to clozapine (e.g., agranulocytosis, small bowelobstruction, or myocarditis)

• A history of intellectual impairment

• pregnant or lactating women; women who are able to become pregnant but who are notwilling to sue effective methods of birth control

• Individuals who score a 3, 4, or 5 within the previous month on the suicidalideation section of the Columbia Suicide Severity Rating Scale (CSSRS), have anysuicidal behavior (not including Not Suicidal Self Injury) within the previous 3months, or are, in the opinion of the investigator, at too high of a risk forsuicide to be safety treated in a randomized trial in which they may not be treatedwith clozapine

• Documented intolerance to or lack of any therapeutic benefit with clozapine after afull trial