preventing psychotic disorders by early detection and intervention william r. mcfarlane, m.d.,...
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Preventing Psychotic Disorders by Early Detection and Intervention
William R. McFarlane, M.D., DirectorEarly Detection, Intervention for the Prevention of Psychosis
National Program OfficeRobert Wood Johnson Foundation
Maine Medical Center Research InstitutePortland, Maine
USATufts University
MACMHB Winter ConferenceKalamazoo, MI
February 11, 2015
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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, MDNobel Laureate, Medicine
President and Director, Hutchinson Center
New York Times MagazineDecember 4, 2005, p. 56
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Mental health and substance use disorders account for
60% of the non-fatal burden of disease amongst
young people aged 15-34.
(Public Health Group 2005)
Developed by Patrick McGorry, MD
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CognitiveDeficits
Affective Sx: Depression
Social Isolation
School Failure
Biological Vulnerability: CASIS
Brain Abnormalities
StructuralBiochemical Functional
Disability
Social and Environmental
Triggers
Incr
easin
g Posi
tive
sym
ptom
s
Early Insults
e.g. Disease Genes, Possibly Viral Infections, Environmental Toxins
After Cornblatt, et al., 2005
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Effects of untreated initial psychosis
• Being psychotic is traumatic and can be stigmatizing.
• Psychosis can reduce cognitive and social functioning.
• The individual may lose contact with family and friends, fail
school, or drop out of work/school.
• Without treatment, neurobiological deficits that underlie
symptoms can progress.
• The longer the psychosis lasts, the more difficult it may be for the
therapist to establish a good therapeutic relationship with the
patient.
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Is early intervention indicated prevention of psychotic disorders?
“Yes, we can.”
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Risk of psychosis over 10 years
0
20
40
60
80
100
6 12 24 30 36 48 60 72 84 96 108 114 120
% of at-risk subjects converting to psychosis
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Trials of Indicated Prevention
• Buckingham, UK• OPUS, Denmark• PIER, Maine• EDIPPP, USA• GRN• PACE I, II, Australia• EDIE I, II, III, UK• Addington, Canada• PRIME, North America• Omega-3 FAs, Austria
Family psychoeducation
Cognitive therapy
Biological treatment
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Early intervention is preventionOne year rates for conversion to psychosis
22.9%
7.6%
0
10
20
30
40
PACEPRIM
EOPUS
PIEREDIE O-3
PACE IIGRN
EDIE II
Addington
EDIE III
EDIPPP
Mea
n rate
Controls Experimental
%
23.0%
Fusar-Poli, et al, JAMA Psychiatry, 2013
Risk reduction = 66%
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Meta-analyses of RCTsConversion to psychosis
Study• Fusar-Poli, et al, 2013
• van der Gaag, et al, 2013
• Stafford, et al, 2013
• Integrated treatment (Nordentoft, 2006; Bechdolf, 2012)
Risk ratio (risk reduction)• 0.34 (-66%; n=554)
• 0.46 (-54%)
• 0.54 (-46%; n=1246)
• 0.19 (-81%)
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Early detection makes a difference
Early intervention is associated with:– More rapid and complete recovery
– Preservation of brain functioning
– Preservation of psychosocial skills
– Decreased need for intensive treatments
– Preservation of supports, especially family/friends
– Less stigma and perception of rejection
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Partnering with families in the early phases of psychosis preserves family connections by
increasing understanding, reducing stress and relieving burden.
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Portland Identification and Early Referral(PIER)
Reducing the incidence of major psychotic disorders in a defined
population, by early detection and treatment:
Indicated prevention
Ages 12-35
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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
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Family practitioners
Pediatricians
General Public
Mental health clinicians
Military bases and recruiters
Clergy
Emergency and crisis services
College health
services
PIER Team
Advertising
School teachers, guidance
counselors, nurses, social
workersEmployers
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Family practitioners
Pediatricians
School guidance
counselors, nurses, social
workers
Employers
General Public
Mental health clinicians
Military bases and recruiters
Clergy
Emergency and crisis services
College health
services
PIER Team
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Assessing Risk for Psychosis
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Psychosis occurs on a spectrum
Youth enjoys basketball and plans to attend college on a
full scholarship.
Youth is heading to New York City because he believes he is talented
enough to join the Knicks.
Young woman goes to the mall and feels like people are
looking at her sometimes.
She refuses to go to the mall because she is certain that a
specific person is out to harm her.
Hearing indistinct buzzing or whispering
Hearing a voice clearly outside one’s head saying, “You’re a loser”
or “You’re a failure.”
Grandiosity
Suspiciousness
Auditory hallucinations
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• Feeling “something’s not quite right”
• Having unusual thoughts and confusion
• Experiencing fear for no good reason
• Hearing sounds/voices that are not there
• Declining interest in people, activities and self-care
• Having trouble communicating and understanding
Early warning signs before psychosis starts
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People with emerging psychosis often experience:
• Social withdrawal
• Odd, unusual behaviors
• Decreased motivation
• Inability to enjoy activities
• Mood swings
• Pervasive anxiety
• Disrupted sleep patterns, and
• Changes in appetite and eating
• Preoccupation with physical symptoms
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Signs of prodromal psychosis
• 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
• Social withdrawal – Loss of interest in friends, extracurricular sports/hobbies– Increasing sense of disconnection, alienation– Family alienation, resentment, increasing hostility, paranoia
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Intervening to Prevent Onset
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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• Supported employment and education• Collaboration with schools, colleges and employers• Cognitive assessments used in school or job • Low-dose atypical antipsychotic medication• Mood stabilizers, as indicated by symptoms:
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Components of first episode psychosis services: Evidence level A and rated as essential by
international experts
Components with level of supporting evidence (A-D) Rating (Semi-Interquartile; maximum = 0.5)
Selection of Antipsychotic Medication (Level of evidence: A) .5
Clozapine for Treatment-Resistance (Level of evidence: A). .5
Use of Single Antipsychotics (Level of evidence: A) .5
Psychoeducational Multifamily Group (Level of evidence: A) .5
Supported Employment (Level of evidence: A) .37
Addington, et al., Psych. Servs., 2013
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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– Buffering external stressors
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Relapse Outcomes in Clinical Trials with Schizophrenia
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Stages of a Psychoeducational Multifamily Group
• Families and clients;
• 1 - 2 years
• Problem-solving &
• Networking
JoiningEducational Workshop
Ongoing MFG
Joining
• Families and clients;
• 4 - 6 hours with focus on
Family Guidelines
Educational Workshop
• Family and client separately +
together;
• 3 - 6 weeks;
• Start psychoeducation
Joining
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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.
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Outcomes
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Referral sources
n = 780 %
Family 185 23.7
Educational professionals 158 20.3
Mental health agencies 204 26.2
Tertiary hospitals, ERs 168 21.5
Community physicians, therapists
38 4.9
Self and other 10 1.3
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Treated cases converting to psychosis within 24 months (n = 148)
• Cases not converted 121 81.2%
• Cases converted, 1-30 days 14 9.4%
• Full psychosis conversions 14 9.4%
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First hospitalizations for psychosisMaine Urban controls areas vs. Greater Portland
0
5
10
15
20
Urban Control Areas Portland Area
Historical Control Period 1999-2000 Intervention Period 2001-2007
+8%
-26%
Net difference=34%*
*p<0.0001
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PIER long-term outcome4-12 years after identification of risk
During 2-year treatment, 2001-2009
Received any treatment 139 100%
Severe episode 14 10%
Post-2-year treatment, 2-10 years
Followed-up 72 52%
Severe psychosis or hospitalization 9 13%
In school or working 55 76%
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Early Detection and Intervention for the Prevention of Psychosis
• Effectiveness Trial at six sites:– Portland, Maine / Maine Medical Center– Glen Oaks, New York / Albert Einstein College of Medicine– Ann Arbor, Michigan / University of Michigan– Salem, Oregon / Oregon Health Sciences University– Sacramento, California / University of California at Davis – Albuquerque, New Mexico / University of New Mexico
• Sponsored by RWJF• Large and diverse nationally representative sample• PIER community outreach and identification systems
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Entry and assignment criteria• Ages 12-25• Living in the experimental catchment area• Positive symptom score by SIPS/SOPS criteria:
– Clinical Low Risk (CLR) Control• Sum <7; OR
– Clinical High-Risk (CHR) Treatment• Sum = 7 or more; OR
– Early First Episode Psychosis (EFEP) Treatment• Any 6 for < 1 month
• IQ 70 or higher• No previous psychosis• Not toxic or medical psychosis
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Outcomes
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Early identification across sites
SITE PopulationAge-corrected rate**,
at 25/100,000*
Years of community
outreach
Maine 323,105 63% 8Michigan 344,791 37%Oregon 631,853 29% 2.5California 466,488 26%New York 557,725 17%
1.5New Mexico 662,564 12%
Total 2,986,526 27%
** Proportion (69.2%) of ages 12-35 population represented by ages 12-25 population *Rate for Nottingham, U.K., in Kirkbride, et al., Arch Gen Psychiatry. 2006;63:250-258
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Number of outreach activities and referrals within catchment areas during two years, by town or by zip code• Michigan• One dot = one event Year 2 (3/09-3/10) • Catchment Area Outreach Activities Referrals
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Demographic and Psychosocial CharacteristicsTotal
(n = 337)
Clinical Low Risk
(n = 87)
Treatment High-Risk(n = 250)
Clinical High-Risk (n = 205)
Early 1stEpisode (n = 45)
Age (mean) 16.6 16.2 16.4 17.9Female, n (%) 134 (40%) 26 (30%) 89 (43%) 19 (42%)
Caucasian, % 62% 71% 61% 47%African-American, (%) 9% 6% 8% 22%Asian-American, n (%) 13 (4%) 4 (5%) 9 (4%) 0 (0%)
Hispanic 15% 8 (9%) 33 (17%) 6 (16%)
In School/Working, % 83% 84% 84% 80%
Income (dollars) 40K – 50K 50K – 60K 40K – 50K 30K – 40K
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Clinical Characteristics
Current SCID-IV Axis-I Diagnoses Total
(n = 337)
Clinical Low-Risk (CLR)
(n = 87)
Treatment(High-Risk)
(n = 250)p
Clinical High Risk
(CHR) (n = 205)
Early FirstEpisode (EFEP)(n = 45)
No Diagnosis 14% 22% 14% 0% <.01
Mood Disorder 42% 37% 49% 18% <.01
(1) Bipolar 16 (5%) 2 (2%) 12 (6%) 3 (7%) .38
(2) Major Depression 114 (34%) 27 (31%) 83 (41%) 3 (7%) <.01
Substance Abuse 28 (8%) 8 (9%) 7% 5 (11%) .66
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Rates of Conversion or RelapseOver 24 months
CLR CHR EFEP
n 87 205 45
Severe Psychosis 2.3% 6.3%
Relapse 11%
Negative Events* 22% 25% 40%
*Hospitalizations, incarcerations, suicide attempts, assaults, rape
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Psychotic Symptoms
Baseline 6 Months 12 months 24 months0.00
5.00
10.00
15.00
20.00
25.00Controls
APS
EFEP
CHR vs. CLR = 0.0034EFEP vs. CLR <0.0001
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Negative Symptoms
Baseline 6 Months 12 months 24 months0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00
16.00Controls
APS
EFEP
CHR vs. CLR = 0.099EFEP vs. CLR <0.012
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Global Test: Treatment vs. Control Overall outcomes over 24 months across ten clinical and
functional variables
Clinical High Risk Subsample
Estimate S.E. t p
0.38 0.17 2.26 0.0244
EFEP Subsample t p
1.05 0.28 3.77 0.0002
Both Treatment Subsamples
f p
7.50 0.0007
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In school or working:Baseline and 24 months
88%
79%
84% 83%
75%
77%
79%
81%
83%
85%
87%
89%
CLR CHR +EFEP
Baseline 24 months
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Increases in participation in school, work or work and school from baseline to 24 months*
7.0%
20.6%
0%
5%
10%
15%
20%
25%
CLR (n=57) CHR&EFEP (n=170)
Increasing participation
* Odds Ratio, CHR+EFEP vs. CLR, = 3.44, 95% C.I. 1.16, 11.0, p=0.025
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Hospital Admissions for First Episode Psychosis Intervention areas / control areas: CA, ME, MI, NY, OR
2003 2004 2005 2006 2007 2008 2009 20100.9
1
1.1
1.2
1.3
1.4
1.5
100%
106%
116%
120%
128%
135%
142%
148%
117%
109%
98%100%
R² = 0.977049426297255
Control period
-33%
-20%
Program
starts
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Outcomes in Four California PIER Programs*
N = 125 Baseline 12 Month
Working 15% 49%In school 57% 56%Onset of Psychosis: 21% 3%Hospitalizations: 13% 7%Suicide attempts: 8% 2%
*San Diego, Santa Clara (San Jose), Ventura Counties
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Conclusions
• Community-wide education is feasible.
• Referral of 30% up to 60% of the at-risk population.
• Global outcome in FACT was better than regular treatment.
• The rate of psychosis onset is less than 1/4 of expected.
• Average functioning was in the normal range by 24 months.
• Five cities show a declining incidence.
• Programs in California are showing same results.
• ¾ were in school or working up to 10 years later.
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