Improving outcome in Schizophrenia

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Improving outcome in Schizophrenia

• Cameron S. Carter MD
• Department of Psychiatry
• University of California at Davis
• cameron.carter_at_ucdmc.ucdavis.edu

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The course of schizophrenia
Episodic, w/o interepisode deficits
Episodic, w/interepisode deficits ( common)
Broad therapeutic window for Prevention/Early
intervention
Chronic, deteriorating
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Strategies for Improving Outcomein Schizophrenia
and other Psychoses

• Understand and treat currently treatment
  refractory symptoms (cognitive deficits and
  negative symptoms)
• Earliest possible intervention

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UCD Clinical and Research Focus

• Early diagnosis, risk prediction and preventive
  interventions clinical care and research into
  early phases of psychotic disorders
• Cognitive neuroscience approach to understanding
  treatment refractory aspects of the illness such
  as cognitive deficits research in people with
  established schizophrenia as well as their
  unaffected relatives

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MIND Institute
Department of Psychiatry Clinical Programs
Psychosis Treatment Research And Education
Program
Center for Neuroscience
Center for Mind and Brain
Imaging Research Center
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Preserving and Enhancing Cognition in
Schizophrenia

• Early intervention itself prevents cognitive
  decline
• Social Cognitive Enhancement Group
• Modafanil Study
• Computer Based Interventions

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Prevention

• Primary Before a disease starts, prevent its
  onset (e.g. by immunization)
• Seconday after a disease has started but before
  it has a clinical effect e.g. treating
  hypertension to prevent cardiovascular disease.
  Pap smear for cervical cancer
• Tertiary identify and alleviate an established
  disease at an early stage to prevent
  complications, improve or maintain functional
  status e.g. aspirin therapy after heart attack
  to prevent recurrence

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EDAPT Clinic Rationale

• Duration of untreated psychosis is associated
  with poor outcome
• Early in illness treatment response is robust
• Loss of function and treatment resistance follow
  repeated relapses
• Early intervention can improve functional outcome
• Tailored treatment pathways and therapies for
  early treatment and rehabilitation

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EDAPT Clinic 2 Target Populations

• Early psychosis first episode patients
• Ultra high risk

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First Episode Cohort

• 12-45 years of age
• Onset within the previous 12 months
• Goal is to engage patient (and family/support
  system) in sustained treatment
• Stabilize, and support recovery of function and
  developmental trajectory

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Key elements of treatment model

• Multidisciplinary treatment team
• Rapid response, extensive medical and psychiatric
  assessment
• Setting, may be better outside of CMH setting
• Medication management
• Individual and group therapy (psychoed,
  motivational, supportive)
• Advocacy (school, vocational, insurance and
  disability etc)
• Multifamily support group

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Some key first episode treatment issues

• Diagnostic uncertainty, symptom based treatment,
  side effects
• Denial of illness, non compliance
• Depression, suicidality
• Family support
• re-entry, socialization, stress, advocacy
• Individualized pathways to recovery, value of
  peer groups

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First Episode Pathway to Recovery
Social Cognitive Enhancement Group
Psychoeducation and Support Group
Initial Assessment Medical and Psychiatric
Individual Rehab and Re-entry Plan
Family Support Group
Individual and Family Based Treatment
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Very Early Intervention Ultra High Risk Cohort

• Can we delay the onset of psychosis and prevent
  functional decline?
• Ultra High Risk strategy possible prodromal
  states, subthreshold psychosis, functional
  decline predict 20-40 conversion rate

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Three Prodromal Risk State Categories

• Attenuated Positive Symptom State
• Onset or worsening in the past year of (a)
  paranoid, grandiose, or referential ideas but
  without full conviction, (b) perceptual
  disturbances but without certainty of an external
  source, or (c) vague, circumstantial or
  tangential communication that is coherent and
  structured under redirection
• Brief Intermittent Psychotic Symptom State
• Onset in the last month of transient
  hallucinations, delusions, and/or thought
  disorder, lasting less than one hour per day
• Genetic Risk and Deterioration State
• A decline of 30 or more on the GAF in the past
  12 months, AND patient either (a) has a
  first-degree relative with schizophrenia or (b)
  meets criteria for schizotypal PD

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Very Early Intervention Ultra High Risk Cohort

• Ultra high risk criteria predict 20-40
  conversion to a psychotic disorder at 1-2 years
• Melbourne and Yale groups have shown that low
  dose antipsychotic treatment markedly reduces
  conversion but
• Treat to prevent ratio is 41
• APA treatment guidelines recommends careful
  monitoring

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Ultra-High Risk Treatment

• Careful diagnostic assessment, SIPS interview,
  plus active diagnoses and comorbidities
• TARGETTED pharmacological therapies
• Psycho ed, supportive therapy, family support and
  therapy, testing and advocacy
• Research for enhanced risk prediction

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Who are we caring for?

• 245 new referrals evaluated, 18 per month
• 44 currently enrolled patients
• 28 male, 16 female
• Average age 20, range 12-33
• 36 with psychosis, 8 ultra high risk

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How did they come to us?

• SCMHTC
• UC Davis Psychiatry
• Adult Access, Child and Family Access
• Sacramento County Primary Care Clinic
• Private Hospitals and RSTs (Heritage Oaks,Sierra
  Vista, Turning Point)
• TAPS, UC Davis CAP
• Self/web

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How are they doing?

• Number of hospitalizations 4
• School 20
• Working 10
• 71 are working or back in school

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Very Early Intervention Ultra High Risk Cohort

• Can we use neurobiological tools (genetic
  material, non-invasive structural and functional
  imaging of the brain) to predict conversion,
  justify very early treatment?
• University of California Prodromal Network (UC
  Davis, UCLA, UCSD and UCSF)

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fMRI measures brain activity associated with
cognition and emotion
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What are Neuronal Oscillations?

• Neurons can fire in a variety of frequency ranges
  e.g. Alpha (8-15Hz), Beta (15-35Hz), Gamma
  (35-80Hz).

• Sometimes populations of neurons will fire at
  different times from each other (asynchronously),
  and sometimes they fire together (synchronously).

Asynchronous firing
Synchronous firing
Encoding and processing occurs when a
population of neurons fires at the same time AND
with the same frequency.
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http//earlypsychosis.ucdavis.edu
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Early Psychosis Treatment Research and Education
Program Department of Psychiatry, University
of California at Davis