Levetiracetam in Early Psychosis
Condition: Psychosis; Schizophrenia; Schizo Affective Disorder; Schizophreniform
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders; Mood Disorders
Intervention: Levetiracetam; Placebo
Intervention description: Levetiracetam is an atypical anticonvulsant that is frequently used in children and adults due to its superior tolerability, ease of use and excellent safety profile.; Prepared in capsules to appear identical to levetiracetam.
Intervention MeSH terms: Levetiracetam
Phase: Phase 2
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 48.0
Sex: All
Minimum age: 16 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Early Psychosis; Levetiracetam

Summary:

      In order to establish target engagement and identify an effective dose the investigators will
      conduct a placebo-controlled single-dose parallel group trial of levetiracetam 185 mg and 500
      mg in 24 medication-naïve early psychosis (EP) patients, measuring hippocampal activity by
      pulsed arterial spin labelling (ASL) pre-dose and 2 hours post-dose. The lower dose is
      calculated to achieve blood levels within the range that were associated with reduced
      hippocampal activity and improved cognition in patients with mild cognitive impairment; the
      higher dose is a typical antiepileptic dose. Successful demonstration of target engagement
      will be defined by an effect size of 0.5 or greater compared to placebo in reduction by
      levetiracetam of hippocampal blood flow measured by ASL. The optimal dose will be defined by
      maximal reduction of hippocampal perfusion in the absence of clinically-significant adverse
      effects. The investigators will also study 8 healthy control subjects to verify that baseline
      hippocampal blood flow is elevated in the sample of EP subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females 16 to 35 years of age, inclusive, at time of informed consent

          2. Must have experienced a first episode of non-affective psychosis within 5 years and
             exhibit current psychosis, as defined by a score of ≥ 2 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

          3. Must have a diagnosis of either schizophrenia, schizoaffective disorder or
             schizophreniform disorder as established by a Structured Clinical Interview for DSMIV
             TR (SCID)

          4. Must not have taken an oral antipsychotic medication within the past 4 weeks prior to
             study enrollment or received a long acting injectable antipsychotic within 3 times the
             dosing interval

          5. If female and of childbearing potential, patients must:

               1. Have a negative urine pregnancy test (all females regardless of childbearing
                  potential will be required to submit a pregnancy test)

               2. Not be nursing or planning a pregnancy for the duration of the study through 30
                  days after the last dosing visit

               3. 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

        Exclusion Criteria:

          1. Current substance abuse or dependence for substances other than nicotine and THC
             (i.e., alcohol, amphetamines, barbiturates)

               1. A positive urine toxic screen (excluding THC, tricyclic antidepressants, or
                  benzodiazepines (if prescribed))

               2. Moderate or severe cannabis use disorder

               3. Use of marijuana within the 72 hours prior to MRI scanning by self report

          2. Diagnosis of major mood disorder or other Axis I disorder other than Schizophrenia,
             Schizoaffective Disorder or Schizophreniform Disorder

          3. 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 and/or PhD or MD level
             clinician completing screening visit

          4. Pregnant, nursing or positive urine pregnancy test

          5. 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

          6. Metal implants, pacemaker, or other metal in the body or medicinal patch

          7. History of claustrophobia

          8. Currently taking any antipsychotic medication (within 4 weeks)