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Preventing Psychotic Disorders by Early Detection and Intervention. William R. McFarlane, M.D., Director Early Detection, Intervention and Prevention of Psychosis Program (EDIPPP) National Program Office Robert Wood Johnson Foundation Center for Psychiatric Research

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preventing psychotic disorders by early detection and intervention

Preventing Psychotic Disorders by Early Detection and Intervention

William R. McFarlane, M.D., Director

Early Detection, Intervention and Prevention of Psychosis Program (EDIPPP)

National Program Office

Robert Wood Johnson Foundation

Center for Psychiatric Research

Maine Medical Center Research Institute

and

Spring Harbor Hospital

Portland, Maine

University of Vermont

Tufts University

Columbia University, College of Physicians and Surgeons

collaborators
William L. Cook, PhD

Donna Downing, MS, OTR/L

Anita Ruff, MPH

Brenda Joly, PhD

Kimberly Pukstas

Diane Parham, O.T.R./L

Karen Milner, MD

Cameron Carter, MD

Barbara Cornblatt, PhD

Steven Adelsheim, MD

Bentson McFarland, MD, PhD

Collaborators
early detection and prevention in another illness

Early detection and prevention in another illness

“If you catch cancer at Stage 1 or 2, almost everybody lives. If you catch it at Stage 3 or 4, almost everybody dies.

We know from cervical cancer that by screening you can reduce cancer up to 70 percent. We’re just not spending enough of our resources working to find markers for early detection.”

---Lee Hartwell, MD

Nobel Laureate, Medicine

President and Director,

Hutchinson Center

New York Times Magazine

December 4, 2005, p. 56

slide4

Shortened productive lives

Source: Mental Health Report of the Surgeon General

10 million

$10 million

Lifetime costs for each new case of schizophrenia

slide6

25

Years of life lost by people with schizophrenia due to all causes, including heart disease, cancer and suicide

empirical evidence for a relationship between a long dup and a poor prognosis
Empirical evidence for a relationship between a long DUP and a poor prognosis
  • Johnstone et al. 1986: Many psychotic patients did not get appropriate treatment early, even when they sought help.
  • Crow et al. 1986: DUP more important for the course than maintenance medication.
  • Rabiner et al 1986: Long DUP was related to a poor one year outcome.
  • Wyatt 1991,Opjordsmoen 1991: Earlier treatment predicted better course.
effects of untreated initial psychosis
Effects of untreated initial psychosis
  • Being psychotic is a personal disaster and the longer it lasts, the more it can become traumatic and stigmatizing.
  • Being psychotic reduces cognitive and social function. They may lose contact with family and friends, fail school, or drop out of work.
  • The longer the psychosis lasts, the more difficult it may be for the therapist to establish a good therapeutic relationship with the patient.
  • Neurobiological deficit processes linked to symptom formation may possibly proceed unlimited as long as the patient is untreated.
validity of diagnosis across phases of illness
Validity of diagnosis across phases of illness

Neurological disease (Cerebral AIDS, SLE, MS. etc.)

High

Premorbid period

Prodromal period

Defined Diagnosis

Dementia praecox, deficit schizophrenia

Chronic undifferentiated schizophrenia

Paranoid schizophrenia

Schizo-obsessive disorder.

0

Validity of clinical differential diagnosis

Schizo-affective disorder

“NRG-1 disorder”

Psychotic bipolar disorder

Psychotic depressive disorder

High

Severe agoraphobia

time

slide11

Early Insults

Social and Environmental Triggers

e.g. Disease Genes, Possibly Viral Infections, Environmental Toxins

Psychosis

Increasing Positive symptoms

Biological Vulnerability: CASIS

Disability

Cognitive

Deficits

Affective Sx: Depression

Social

Isolation

School Failure

Brain

Abnormalities

Structural

Biochemical Functional

After Cornblatt, et al., 2005

non genetic biologic and psychosocial risk factors
Non-genetic biologic and psychosocial risk factors
  • Prenatal infections (influenza, rubella, toxoplasma, herpes s.)
  • Winter birth
  • Prenatal toxic exposure (lead)
  • Obstetrical complications
  • Head trauma (perinatal to adolescence)
  • Autoimmune (Rh incompatibility, thyroid, type 1 diabetes, celiac disease)
  • Nutrition (starvation, omega-3 deficiency)
  • Heavy metal exposure, maternal/fetal
  • Heavy cannabis, other drug exposure
  • Urban residence
  • Exposure to trauma, with PTSD
  • Negative emotional experience
expressed emotion
Expressed emotion
  • Critical comments
  • Hostility
  • Over-involvement
  • Warmth
effects of genetic risk and family functioning on eventual schizophrenia spectrum disorders
Effects of genetic risk and family functioning on eventual schizophrenia-spectrum disorders

* p < 0.001

**p = 0.582

G X E interaction: p=0.018

Tienari, Wynne, et al, BJM, 2004

mutual causal effects patient symptoms and family interaction
Mutual causal effects: Patient symptoms and family interaction

+

Family interaction

Patient symptoms

+

slide19

Withdrawal

"Oddness"

Functional deterioration

Social & performance deficits

Social deficits

Critical comments CD, EOI

Anxiety

Panic

Misattribution

High EE

Psychosis

Illusions

Dread

Insomnia

Anorexia

Perceptual distortions

Pervasive anxiety

Biosocial causal interactions in late schizophrenic prodrome

Late prodrome

Acuteonset

Early prodrome

Structural

Family/Social

Physiological

social networks in schizophrenia
Social networks in schizophrenia
  • Family network size
    • diminishes with length of illness
    • decreases in the period immediately following a first episode
    • is smaller at the time of first admission
  • Networks
    • buffer stress and adverse events
    • determine treatment compliance
    • predict relapse rate
    • correlate with coping skills and burden.
is early intervention indicated prevention of psychotic disorders

Is early intervention indicated prevention of psychotic disorders?

Probably

“Yes, we can?”

trials of indicated prevention
Trials of Indicated Prevention
  • Buckingham, UK
  • EDIE, UK
  • German Research Network
  • OPUS, Denmark
  • TIPS, Norway, Denmark
  • PACE, Australia
  • PRIME, North America
  • Omega-3 FAs, Austria
  • PIER, Maine
  • EDIPPP, USA
slide24

Portland Identification and Early Referral(PIER)

Reducing the incidence of major psychotic disorders in a defined population, by early detection and treatment:

Indicated prevention

slide26

BIOLOGICAL RISK FACTORS

Greater Portland Area

Population 33O,OOO

slide28

Professional and Public Education

  • Reducing stigma
  • Information about modern concepts of psychotic disorders
  • Increasing understanding of early stages of mental illness and prodromal symptoms
  • How to get consultation, specialized assessments and treatment quickly
  • Ongoing inter-professional collaboration
youth education
Youth Education
  • Public service announcements by mainstream television and health information programs
  • Interviews and spot announcements by youth television cable network
  • 2-3 sessions on early warning signs as part of the obligatory 10th grade health curriculum
  • Widespread distribution of bookmarks and posters throughout catchment area schools, colleges, bookstores
  • Art and literature contest
  • Major publicity events during Mental Illness Awareness Week
  • Youth oriented website:

www.preventmentalillness.org

slide31

Welcome

Mental illness

Getting help

About PIER

Resources

News

Contact

slide32

Family practitioners

College health services

Mental health clinicians

Pediatricians

Military bases and recruiters

School teachers, guidance counselors, nurses, social workers

PIER Team

Clergy

Emergency and crisis services

Employers

Advertising

General Public

slide33

Family practitioners

College health services

Mental health clinicians

Pediatricians

Military bases and recruiters

School guidance counselors, nurses, social workers

PIER Team

Clergy

Employers

Emergency and crisis services

General Public

slide35

Signs of prodromal psychosisSchedule of Prodromal Syndrome (SOPS), McGlashan, et al

  • A clustering of the following:
  • Changes in behavior, thoughts and emotions, with preservation of insight, such as:
    • Heightened perceptual sensitivity
      • To light, noise, touch, interpersonal distance
    • Magical thinking
      • Derealization, depersonalization, grandiose ideas, child-like logic
    • Unusual perceptual experiences
      • “Presence”, imaginary friends, fleeting apparitions, odd sounds
    • Unusual fears
      • Avoidance of bodily harm, fear of assault (cf. social phobia)
    • Disorganized or digressive speech
      • Receptive and expressive aphasia
    • Uncharacteristic, peculiar behavior
      • Satanic preoccupations, unpredictability, bizarre appearance
    • Reduced emotional or social responsiveness
      • “Depression”, alogia, anergia, mild dementia
slide36

Signs of prodromal psychosis

  • Changes in behavior, thoughts and emotions, with preservation of insight, such as:
    • Unusual perceptual experiences
      • “Presence”, shadows, visual trails, ghosts
      • Imaginary friends
      • Fleeting apparitions
      • Odd sounds
      • Somatic illusions or hallucinations
      • Heightened or dulled perceptions
      • Vivid sensory experiences
      • Sensations and thoughts located outside the body
      • Frequent distortions or illusions
      • Brief but frank hallucinations, minimal effect on behavior or thinking
slide37

Signs of prodromal psychosis

  • Changes in behavior, thoughts and emotions, with preservation of insight, such as:
    • Unusual fears
      • Marked guardedness, distrustful
      • Fear of assault (not social phobia)
      • Avoidance of bodily harm
      • Somatic delusions
      • Severe nihilism
      • Persistent persecutory self-referential thoughts
      • Paranoia
      • Extreme guilt, fear of harming others
      • Bizarre obsessional preoccupations
      • Fears of mind-reading
      • Frank delusions, without full conviction
slide38

Signs of prodromal psychosis

  • Changes in behavior, thoughts and emotions, with preservation of insight, such as:
    • Disorganized or digressive speech and thoughts
      • Receptive aphasia: “Can’t understand others.”
      • Expressive aphasia: “Can’t be understood.”
      • Odd, circumstantial, tangential, paralogical speech
      • Overly simple speech
      • Loss of gist of conversation, poor abstracting
      • Rigid, concrete, almost autistic thinking
      • Loosening of associations
      • Marked vagueness, lack of clarity of subjects and objects
      • Racing speech
      • Stereotyped ideas, speech
      • Over-elaborate speech
      • Poor problem-solving
signs of prodromal psychosis
Signs of prodromal psychosis
  • 2. Significant deterioration in functioning
    • Unexplained decrease in work or school performance
    • Decreased concentration and motivation
    • Decrease in personal hygiene
    • Decrease in the ability to cope with life events and stressors
  • 3. Social withdrawal
    • Loss of interest in friends, extracurricular sports/hobbies
    • Increasing sense of disconnection, alienation
    • Family alienation, resentment, increasing hostility, paranoia
slide40

Family-aided Assertive Community Treatment (FACT): Clinical and functional intervention

  • Rapid, crisis-oriented initiation of treatment
  • Psychoeducational multifamily groups
  • Case management using key Assertive Community Treatment methods
    • Integrated, multidisciplinary team; outreach PRN; rapid response; continuous case review
  • Supported employment and education
    • Collaboration with schools, colleges and employers
slide41

Family-aided Assertive Community Treatment (FACT): Clinical and functional intervention

  • Cognitive assessments used in school or job
  • Low-dose atypical antipsychotic medication
    • aripiprazole 10-20 mg, quetiapine 300-600 mg, olanzapine 2.5-7.5 mg, risperidone 0.25-3 mg
  • Mood stabilizers, as indicated by symptoms:
    • Mood stabilizing drugs: lamotrigine 50-150 mg, valproate 500-1500mg, lithium by blood level
  • SSRIs, with caution, especially with aripiprazole and/or a family history of manic episodes
key clinical strategies in family intervention specific to prodromal psychosis
Key clinical strategies in family intervention specific to prodromal psychosis
  • Strengthening relationships and creating an optimal, protective home environment:
    • Reducing intensity, anxiety and over-involvement
    • Preventing onset of negativity and criticism
    • Adjusting expectations and performance demands
    • Minimizing internal family stressors
      • Marital stress
      • Sibling hostility
      • Conceptual and attributional confusion and disagreement
key clinical strategies in family intervention specific to prodromal psychosis1
Key clinical strategies in family intervention specific to prodromal psychosis
  • Strengthening relationships and creating an optimal, protective home environment:
    • Buffering external stressors
      • Academic and employment stress
      • Social rejection at school or work
      • Cultural taboos
      • Entertainment stress
      • Romantic and sexual complications
key clinical strategies in family intervention specific to prodromal psychosis2
Key clinical strategies in family intervention specific to prodromal psychosis
  • Individualized, responsive education for single families
  • Little discussion of atrophic aspects of brain functioning emphasis on transient, stress-induced hyperactivity in some brain areas and some biochemical systems
  • Accelerated recovery, reentry and rehabilitation
  • Emphasis on careful forward progress.
    • "Slow down personal and career advancement, until stability and motivation returns."
pier outcomes after one year of treatment

PIER: Outcomes after one year of treatment

Data for 148 at-risk cases from the first 6 years intake:

May 7, 2001- September 6, 2007

figure 1 disposition of all contacts with pier 5 7 2001 9 1 2007

Figure 1. Disposition of all contacts with PIER, 5/7/2001-9/1/2007

All contacts

N=1333

Request for information

N=180

Case Referrals

N=1103

Request for presentation

N=50

In catchment area

N=921

Age 12-35

N=780

No further

contact required

N=51 (6.5%)

Screened for formal assessment

N=404 (51.8%)

Referred

Elsewhere

N=240 (30.8%)

Contact

withdrawn

N=85 (10.9%)

Referred

Elsewhere

N= 74 (18.3%)

Presumed

Psychotic

N=47 (11.6%)

Contact withdrawn or did not complete SIPS

N=9 (2.2%)

Completed

SIPS

N=271 (67.1%)

Psychotic by POPS criteria

N=32 (11.8%)

Met SOPS criteria

N=148 (54.6%)

Did not meet SOPS criteria

N=94(34.7%)

Treated > 3 months

N=118 (79.7%)

Declined treatment

N=10 (6.8%)

Dropped out in

< 3 months

N=22 (14.9%)

slide52

Treated cases converting to psychosis within 12 months (n = 93)

  • Cases not converted 72 77.4%
  • Cases converted, 1-6 days 5 5.4%
  • Cases converted, 7-30 days 7 7.5%
  • SOPS psychosis conversions 5 5.4%
  • Schizophrenic disorder 4 4.3%
  • Total SOPS conversions 9 9.7%
sops scores at baseline and 12 months
SOPS scores at baseline and 12 months

p<.001

p<.001

p<.001

p<.001

n=94

components of expressed emotion prodromal vs chronic phase
Components of expressed emotion: Prodromal vs. chronic phase

All differences, prodromal vs. chronic: p<0.01

difference in initial admissions portland vs 3 maine urban areas ages 12 25
Difference in Initial Admissions Portland vs. 3 Maine Urban Areas, Ages 12-25

Incidence difference, mean:

Portland vs 3 urban areas: 65/100,000

% of Portland baseline: 60%

difference in initial admissions rates for psychosis portland minus 3 maine urban areas ages 12 25
Difference in Initial Admissions Rates for PsychosisPortland minus 3 Maine urban areas, Ages 12-25

PIER begins

slide60

Differences In Initial Admission Rates/100,000 For All Psychoses, Ages 12-35, 1994-2000 Vs. 2001-2007: Portland Vs. Control Catchment Areas In Maine

first admissions to maine hospitals for a psychotic or major mood disorder 1990 2007 ages 12 25
First admissions to Maine hospitals for a psychotic or major mood disorder, 1990-2007Ages 12-25

Source: MHDO data, analyzed by Maine Health Information Center and Maine Medical Center Research Institute

hospitalization costs avoided portland vs 3 other maine cities
Hospitalization costs avoided*Portland vs. 3 other Maine cities

*Savings from avoided initial hospitalizations in Portland. Cost estimates based on incidence rate differences (i.e., resulting fewer cases) between greater Portland and the other 3 Maine urban areas. Amounts are based on time period—2002, 2007 or the average for 2001-2007—days in hospital for first admission and daily rate in dollars. Population based on US Census estimates for the respective years.

differences between treated prodromal and post psychotic states
Differences between treated prodromal and post-psychotic states

Prodromal young persons have manifested:

  • Maintenance of insight (prevention of loss)
  • Continued ego-dystonic response to psychotic symptoms
  • High acceptance of, and adherence to, treatment
  • Low rates of substance abuse
  • More open to discontinuing heavy drug and alcohol abuse
  • Less resistance to family inclusion by patient
  • Higher motivation to continue schooling and/or work
  • More trusting and grateful therapeutic relationships
  • Higher sensitivity to treatments
  • Higher likelihood of improving course of functioning
conclusions
Conclusions
  • Public education is influencing attitudes, knowledge and behavior.
  • Accurate referrals are coming from outside the mental health system.
  • Treatment is blocking the final common pathway to psychosis.
  • Medication at low doses is adequate but appears essential for prevention of imminent, and perhaps later, psychosis.
  • Very low conversion rates and functional improvement accompany comprehensive treatment (~15%; ~5% for schizophrenic disorders).
  • A substantial proportion of the incident population can be identified and prevented from developing psychosis.
slide66

PIER Sponsors

PIER has been made possible with the generous support of:

Robert Wood Johnson Foundation

National Institute of Mental Health

Center for Mental Health Services (SAMHSA)

State of Maine

Maine Health Access Foundation

Bingham Fund

Betterment Fund

Brain Foundation

American Psychiatric Foundation

UnumProvident Foundation

Wrendy Haines Fund