R33: Levetiracetam in Early Psychosis

Prior treatment

• Current suicidal ideation. Suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the suicidal ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the Principal Investigator
• Contraindications to MRI: metal implants, pacemaker, or other metal in the body, or claustrophobia. Individuals with tattoos will be excluded from imaging if tattoos cover more than 5% of the body surface, if a tattoo is greater than 20 cm, or if the tattoo is located on the face, neck or genitals. (Individuals with a contraindication to MRI may participate in the trial but will be excluded from the elective MRI component)

Other illness

• Current substance abuse or dependence for substances other than nicotine and THC (i.e. alcohol, amphetamines, barbiturates)
  • A positive urine toxic screen (excluding THC, tricyclic antidepressants, or benzodiazepines (if prescribed))
  • Moderate or severe cannabis use disorder
• Diagnosis of major mood disorder or other Axis I disorder other than Schizophrenia, Schizoaffective Disorder or Schizophreniform Disorder
• Significant medical or neurological illness by history or physical exam including seizure disorder, history of loss of consciousness related to head trauma or developmental disorder including mental retardation
• Significant history of serious violence
  • For both inpatient and outpatient subjects, a history of serious violence as assessed by the Buss-Perry Aggression Questionnaire
  • For outpatient subjects only, a score of 5 (moderately severe) or higher on the BPRS hostility item at screening or baseline

Lab values

• Renal insufficiency (if serum creatinine is greater than laboratory limits for normal, estimated creatinine clearance must be greater than 80)

Other

• Pregnant, nursing or positive urine pregnancy test

• Males and females 16 to 40 years of age, inclusive, at time of informed consent
• Must have experienced a first episode of nonaffective psychosis within 5 years and exhibit current psychosis, as defined by a score of ≥ 4 on one of the following psychosis items on the BPRS: conceptual disorganization, suspiciousness, hallucinations, unusual thought content, or grandiosity, for at least 4 days per week for at least 4 weeks
• Must have a diagnosis of either schizophrenia, schizoaffective disorder or schizophreniform disorder as established by a Structured Clinical Interview for DSM-V (SCID)
• Must have taken antipsychotic medication for a minimum of 8 weeks and at a stable dose for at least 4 weeks prior to randomization
• If assigned female at birth and of childbearing potential, patients must:
  • Have a negative urine pregnancy test (all participants assigned female at birth regardless of childbearing potential will be required to submit a pregnancy test) and
  • Not be nursing or planning a pregnancy for the duration of the study through 30 days after the last dosing visit and
  • Be abstinent or willing to use a reliable method of birth control from the screening visit and continue with the same method until termination from the study