EARLY INTERVENTION FOR EMERGING MENTAL AND DISORDERS IN YOUNG PEOPLE

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EARLY INTERVENTION FOR EMERGING MENTAL AND
DISORDERS IN YOUNG PEOPLE

• STRENGTHENING THE SYSTEM WHERE ITS
  WEAKEST

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T. Insel (Arch Gen Psychiatry 2009, 66128-133)

• Currently, mental disorders are diagnosed by
  symptoms that emerge at a late stage, presumably
  years after brain systems veer from more typical
  development. Diagnosing schizophrenia or bipolar
  disorder with the emergence of psychosis may be
  analogous to diagnosing coronary artery disease
  by myocardial infarction. One of the most
  hopeful approaches to reducing the morbidity and
  mortality of serious mental illness borrows a
  page from the cardiology playbook. By developing
  biomarkers for early diagnosis, we may be able to
  preempt many of the most disabling aspects of our
  most severe mental illnesses.

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Two Complementary Paradigms

• EPIDEMIOLOGICAL/ONSET OF DISORDER
• EARLY INTERVENTIONPOPULATION HEALTH

• DEVELOPMENTAL/TRANSITION
• TRANSITION AGE YOUTH

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• Mental illness and substance use disorders
  account for 60 of the non-fatal burden of
  disease amongst young people aged 15-34 (Public
  Health Group 2005)
• 75 of mental health problems occur before the
  age of 25 (Kessler et al 2005)
• 14 of young people aged 12-17, and 27 of young
  people aged 18-24 experience a mental health
  problem in any 12 month period (Sawyer et al
  2000, Andrews et al 1999, ABS 2008)

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AUSTRALIAN NATIONAL SURVEY OF MENTAL HEALTH AND
WELL BEING (SWMHWB) 2008
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NEED IN YOUTH MENTAL HEALTH A RISING TIDE
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The rising tide of psychosocial disorder in young
people 12 -26 yrs (Rutter Smith 1995)

• Phenomenon of recent decades
• Paradox physical health never better vs
  psychological health never worse
• Challenges the orthodoxy (Eckersley 2008)
• Multiple disorders and MH problems
• Suicide, drugs, offending, core psychiatric
  disorders, usually blends
• Youth trends (Collishaw et al, 20042007) and
  AIHW data (2007) but Costello et al 2006.
• High awareness and concern in government, media
  and community

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DEVELOPMENTAL PERSPECTIVE

• Youth Transitions
• Emerging Adults

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• The transition to adulthood is poorly
  understood in spite of the fact that it is
  probably the age period when most adult disorders
  have their peak rates of incidence
• - Mrazek Haggerty, 1994

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DEFINITIONS YOUNG PEOPLE

• WHO 10-24
• United Nations 15-24
• Australian Institute for Health and Welfare 12-24
• Children 0-14
• ABS 12-25
• Local Government 12-25
• Headspace (Australia) 12-25
• Headstrong (Ireland) 12-25
• Mission Australia 11-24
• Prof Philip Graham 14 emerging adults
• US NIMH transition age youth ?14 25/30
• 20 of population in Australia

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Youth as a distinct developmental phase

• Adolescence begins earlier and finishes later
  than ever
• Brain development dynamic from puberty until mid
  20s
• However the phase is culturally specific so in
  LAMIC eg in Hmong and Bangladeshi cultures (WHO
  2005)
• Key developmental tasks
• Transition more complex and desynchronous
• Cohesive yet heterogeneous youth culture
• Generational and cohort effects (Wyn, Arnett)
• Graduates of statutory care data/aging out
  TAY (Davis)
• Service system is weakest where it needs to be
  strongest

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The Developmental Ecology of TransitionThe Need
for Scaffolding (Masten et al 2006) During EA
Transition

• Family, peer networks, education,
  apprenticeships, military service, mentors etc
• Aging out from care - (prosthetic) scaffolding
  withdrawn abruptly without alternatives
• Newly emergent and persistent mental disorders
  can damage or inhibit the scaffolding
• Options
• Strengthen mainstream scaffolding
• Add additional supports and mentors
• Create new scaffolding
• Early intervention and quality care for emerging
  mental and substance use disorders

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Average brain surface contraction rates in
converters and non-converters (Sun et al 2009)
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CLINICAL STAGING A HEURISTIC STRATEGY

• Towards a Clinicopathological Model

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J-O Johannessen
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CLINICAL STAGING

• Diagnosis in psychiatry increasingly struggles to
  fulfil its key purposes, namely to guide
  treatment and to predict outcome
• It works esp. poorly for young people in the
  early stages of disorder and in primary care
  settings
• In general medicine staging is a useful strategy
  to help select safe and effective treatments and
  predict outcome for individual patients
• It is a therefore a more refined method of
  diagnosis
• Staging could restore the utility of diagnosis,
  promote early intervention and also make more
  sense of the confusing array of biological
  research findings in psychiatry, by organising
  data into a coherent clinico-pathological
  framework.
• (McGorry et
  al 2006 McGorry 2007)

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CLINICAL STAGING

• Key principles
• Treatment needs differ by phase/stage
• Treatment more benign and effective in earlier
  phases (depends on pattern of disorder)

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THE GRAND DSM V RAILROAD
Psychosis Risk Syndrome
Tenacious Depression Syndrome
Bipolar Risk Syndrome
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Level 5 Schizophrenia
Level 4 FEP Frank psychotic symptoms
Level 3 PLEs associated with distresshelp-seekin
g, decreased functioning, comorbidity
Level 2 Other psychiatric syndromes with
incidental PLEs
Level 1 PLEs, no distress, help-seeking,
decreased functioning, or comorbidity
No psychiatric symptoms
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Pyramid of Power
Mt Psychosis
Mt Mania
Mt Tenacious D
ARMS (At Risk Mountain State)
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Progression through the prodromal period
depression
mania
Psychosis
schizophrenia
Stage 1a
Stage 2
Stage 1b
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• We want to know what to ask to split clearly
  between the people who are having trouble in
  living and the people who are in grave risk of
  serious psychosis
• Harry Stack Sullivan (1938)

To achieve this maybe we really need to firstly
distinguish between those who are NOT having
trouble in living and those who are?
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The Close-In Strategy Bell (1992)

• Traditional HR studies eg GHR characterised by
  low incidence and long lead time. Close-in
  strategy designed to overcome this
• Most serious mental and substance use disorders
  dont happen overnight
• Prodromal or subthreshold symptomatic stages are
  typical and are associated with significant
  distress and functional impairment
• Using clinical features as risk factors for
  more severe disorder was proposed by Eaton for
  depression, endorsed by Mrazek and Haggerty and
  has worked well in psychosis/schizophrenia
• Need to identify the more proximal features which
  connote maximum risk eg positive psychotic
  symptoms (like predicts like)
• Clinical features have higher RR than traditional
  risk factors eg urban birth, family history
• Close in strategy combines RFs eg FHx plus
  subthreshold symptoms

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Clinical experience and recent research has shown
2 things

• There are many people with something resembling
  the clinical phenotype of psychosis who
  apparently do not have a need for care (van Os et
  al 2001) Some subthreshold, some full threshold,
  some just false positives
• Most people who develop a sustained psychotic
  disorder experience a significant period of
  subthreshold symptoms, distress and serious
  functional decline long before they become
  frankly psychotic and ultimately access treatment
  (Sullivan 1927 Meares 1959, Häfner et al 1989)
• So while we may wish to protect one group from
  care/intervention or at least not seek them out,
  we must try to find ways to offer it to another
• We therefore need to decide who needs care, how
  early and where it should be offered, and what
  should be the range and sequence of interventions

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Potential Obstacles to Prepsychotic Intervention

• FALSE POSITIVES
• Can we define subthreshold caseness? I.e. with
  high PPV
• Iatrogenic harm esp drug therapies, stigma
• Enhanced by fear of schizophrenia and the
  reality of standard care
• Poor context for this approach in most settings -
  Needs to be developed in generic/primary
  care/youth environments
• Can decrease false positives to 10 - 20 but
  also decrease sensitivity _ the prevention
  paradox
• INACCESSIBLE POSITIVES (unaware, reluctant or
  unrecognised) 90!
• Can we find them anyway? Do they want or need
  help - are they really cases? (van Os et al
  2001)
• Increasing access may reduce the true positive
  rate
• An ounce of prevention is better than a pound
  of cure but is 15 ounces of prevention worth the
  effort? (Eaton Harrison 1996)

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Symptom-Disability Gap in Early Psychosis
Disability
Symptoms

• Providing access during usually prolonged phase
• when major psychosocial disability develops
  (Agerbo et al 2003)

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TREATMENT TARGETS IN PLURIPOTENTIAL STAGES

• 1 Current Syndromes and Needs (eg Depression,
  Substance Abuse, Interpersonal Problems)
• 2 Future Syndromes (Dimensional Worsening of
  Current or Development of New Syndromes)
• Are different treatments required for these two
  sets of targets?
• According to the Staging Model risks must be
  lower if treatment occurs earlier and treatment
  for ultimately more serious/exit syndrome more
  effective in longer term

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Features of the subthreshold stage(s)
Clinical Phenotype Depression/anxiety/hypomania Ch
anges in salience, belief and
perception Disturbed experience of
self Neurocognitive impairments Substance abuse
Biological Putative abnormalities in neuronal
integrity and glial function Disturbed
neurotransmission Subtle structural brain changes
Social Withdrawal, isolation Impaired
relationships with family and peers Decline in
scholastic or work performance
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Participants - Inclusion Criteria

• Aged between 14-30 years
• ARMS due to
• Group 1 Vulnerability Group
• Group 2 Attenuated Psychotic Symptoms Group
• Group 3 BLIPS Group
• Operationalised using CAARMS (Yung et al, 1996
  2005)
• English-speaking

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Transition from UHR to frank psychosis by centre
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UHR in a broad clinical sample (n292) of young
people 15 -24 years (Yung et al 2006) presenting
to OYH

• Transition rate has reduced from 34 to 10 over
  initial 6 months - WHY?
• Dilution effect due to sampling?
• More benign cases detected?
• Are more being referred without a need for
  care? (No since GAF is 54)
• Yet the numbers of referred cases to OYH has
  increased from 1000 to 2000 pa in recent years
  (number accepted same or less however)
• So could be less enriched sample ie true
  positive base rate less
• Increased effectiveness of treatment?
• Earlier detection of UHR cases?
• Duration of follow up (maybe UHR being
  detected earlier) Have we shifted the focus to an
  earlier stage (our DUP median is 45 days)

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Possibilities not mutually exclusive
Lead time bias
Lengthtime bias
Different, more dilute sample
Early intervention more effective
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Mean Duration of Symptoms (Days) Prior to
Receiving Care in Successive PACE UHR Cohorts
1995 - 2000
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Survival Curves Initial PACE RCT (1996-1999)
1.0
SPI, full adherence, n 14
0.8
SPI, n 31
0.6
Proportionnot Psychotic
SPI, no or partialadherence, n 17
0.4
NBI, n 28
0.2
0
200
400
600
800
1000
No. of Days From Entry
NBI needs-based intervention SPI specific
intervention. SPI vs NBI P 0.087 SPI, full
adherence vs NBI P 0.032. P-values are from
log-rank test.
McGorry et al 2002 Arch Gen Psychiatry
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Survival curves of transition to
psychosisrandomized (n115) and monitoring
(n78) groupsRIS AUS 9 (n193)
3 trial groups p .60 4 groups p .59
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OMEGA-3 FATTY ACIDS REDUCE THE RISK OF EARLY
TRANSITION TO PSYCHOSIS IN ULTRA-HIGH RISK
INDIVIDUALSA double-blind randomized,
placebo-controlled treatment studyAmminger GP
(1,3), Schäfer MR (1), Papageorgiou K (1), Becker
J (1), Mossaheb N (2), Harrigan SM (3), McGorry
PD (3), Berger GE (3)
Transition rate at 3-months Follow-up
50
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(N) psychotic by 3 months
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21.1 (8)
20
10
2.6 (1)
0
Placebo
EFA
n38
n38
Chi-square Fishers exact test 6.2, df1,
p0.028 OR9.9
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Clinical staging model

• Less differentiated early phases of psychiatric
  disorders may benefit from broad spectrum,
  simpler treatments
• As clearer target syndromes emerge they can
  attract more specific interventions
• However preemptive treatment another issue
• All UHR referrals have clinical need - high
  levels of non-psychotic disorders or emerging
  non-psychotic disorders

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Guidelines for now (also see BJPsych Suppl 2005)

• Treat help seekers in stepped care model with
  simple interventions first
• Support, psychoed, family support, minimise
  substance use, stress management, problem solving
  etc
• If no early remission, add CBT for multiple
  targets incl positive symptoms (NS will improve
  too) Could consider omega 3 here
• Treat current threshold syndromes esp.
  depression. If latter is severe offer SSRIs with
  care (NB adolescent issue re SSRIs)
• If condition persists or worsens with continuing
  or prominent PS, or transition, and/or
  deteriorating role and interpersonal functioning,
  increased risk of harm to self or others - trial
  of SGA such as quetiapine, risperidone or
  aripiprazole
• Note this is a conservative not preemptive stance
  - the latter reserved for RCTs

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TIPS McGlashan/Johannessen/Vaglum (Larsen et
al, Melle et al 2004 - 8)

• ED reduces suicidal behaviour and other
  collateral damage at entry but lowering threshold
  to care
• Even long DUP cases are in better shape
• Effects of NS persist - that is lower NS at 12,
  24 months and 5 years

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EARLY INTERVENTION Phase- and needs-specific
content a focus for EBM in FEP

• Atypicals vs Typicals (Emsley et al 1999,
  Lieberman et al 2003, Schooler et al 2003)
• CATIE and CUtLASS - focused on established
  schizophrenia
• EUFEST (Kahn et al 2008)
• Dose-finding (Merlo et al 2002, McGorry et al
  2003, Berger et al in press)
• Adjunctive Therapies (EPA Berger et al 2003,
  Estrogen Kulkarni et al 2001, NAC Berk et al
  2008)
• Duration of initial medication (Gitlin et al
  2002, Robinson et al 1999)
• Psychological Interventions for recovery, TR,
  cognitive deficits (Jackson et al 1998, 2001,
  Lewis et al 2002, Birchwood, Edwards etc)
• Vocational Recovery (Killackey et al 2008)
• Relapse Prevention (Gleeson et al 2008)
• Suicide prevention (Power et 2003)
• Comorbidity esp SUD (Edwards et al 2002)

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LEO Trial ResultsSocial Functioning at 18
months GAF (N98)
GAF Score
plt0.01
(Craig, Garety et al, 2003)
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OPUS trial psychotic symptoms at one- and
two-year follow-up
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COMMENT No difference in 5 year as compared to 2
year clinical outcomes However still
underpowered to detect moderate rather than
large effects Social benefits maintained eg
independent living and hospital readmission rates
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Long-term economic evaluation
1 year after initial stabilization
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Long-term outcomes psychopathology, functioning
and quality of life

• The EPPIC group
• showed a lower level of positive psychotic
  symptoms (p0.007) and overall better functioning
  (p0.039)
• showed higher levels of past and current paid
  employment
• 31.3 of the EPPIC group were currently employed,
  compared to 15.2 of the control group
• 56.3 of the EPPIC group had been employed during
  the last 2 years of the follow-up period,
  compared to 33.3 of the control group
• were less reliant on government support
• The EPPIC group received disability support for
  49.5 of the previous 2 years, compared to 62.3
  for the control group

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Long term outcomes course of illness

• The EPPIC group
• were significantly more likely to achieve
  symptomatic remission on both the BPRS criteria
  (OR4.5 95 CI (1.4, 13.7)) and the BPRS-SANS
  criteria (OR3.3 95 CI (1.02, 10.3))
• achieved social and vocational recovery more
  frequently than the control group
• 33.4 of the EPPIC group recovered, compared to
  21.2 of the control group
• showed a more favourable course of illness over
  the last 2 years of the follow-up period (?29.0
  df2 p0.011)
• 62.5 were not actively psychotic, compared to
  33.3 of the control group
• 18.8 were continuously symptomatic compared to
  54.5 of the control group

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Long term cost results
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Is early intervention in psychosis cost-effective?

• Specialized programmes delivering timely and
  assured care during the early illness period give
  better clinical and functional outcomes at a
  third of the cost of standard public mental
  health services
• Investment in early intervention programmes
  provides excellent value for money and should be
  considered as an additional stream of care within
  the specialist mental health services

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STRENGTHENING THE SYSTEM WHERE ITS WEAKEST..

• Early Intervention and Developmentally
  Appropriate Mental Health Care for Young People
  Aged 12 - 25

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Current system of care young people

• Only a minority of people (40) with mental
  disorders access treatment (MHCA 2003)
• An even smaller proportion (lt20) of young people
  (esp 15 -25) access treatment (Sawyer et al 2000
  OYH 2004) with less than 2 accessing specialist
  care (Zubrick et al 1995)
• Access to GPs across lifespan is also worst for
  young people (Issakidis and Andrews 2006,
  Rickwood et al 2003)
• Specialist MH system fractured at worst point (16
  - 18 years), CAMHS and adult systems different
  cultures, values, resources
• Paediatric/adult model services mental health
  very poorly

So the system is weakest where it needs to be
strongest!
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TREATMENT
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Current services - too little, too late
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Unmet need in the northwestern area of Melbourne

• 1,000,000 in catchment area
• 50,000 cases - mild- severe - (15 -24 years) in
  any one year
• 5000 approx with SMI
• 2,000 referrals to intake per annum now stable -
  only 7-800 can be accepted to OYH with current
  resources
• 2/3 of those NOT accepted have significant mental
  disorders, with poor functioning, and 22 have a
  recent history of suicide attempt
• Those not accepted do very poorly at 2 year
  follow up (Cosgrave et al 2007)

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An air of desolation more calculated to fix than
to remove
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WHERE THERE IS NO EARLY INTERVENTION..

• Services just seemed to passively wait until he
  was really ill - the service oozed pessimism,
  lack of investment and lack of imagination
• Family member, Rethink 2006

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GENERIC SERVICES

• No change in outcome for Schizophrenia over 100
  years
• Apalling FE scenario described by Garety et al
  2001
• Long DUPs
• Must escalate risk or prove chronicity to gain
  access and secure tenure
• Stigma
• Overmedication
• Poor engagement
• Traumatic experiences for young treatment naïve
  patients and families
• Increased suicide rates

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The growing movement for reform in youth mental
health
The Youth Mental Health public forum 29/06/04
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THE CHALLENGE

• Awareness
• Recognition Engagement
• Access
• Quality Care

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Access and Engagement
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Current health/welfare service system for young
people
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The ideal health service system for young people
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Headspace The National Youth Mental Health
Foundation

• A collaboration involving
• ORYGEN Youth Health Research Centre
• University of Melbourne
• Brain and Mind Research Institute
• Australian General Practice Network
• Australian Psychological Society

• The 2005-2006 Australian government budget
  included a commitment of 69M over four years to
  better assist young people with mental health
  problems
• Included in this allocation was 54M in funding
  for the establishment of a National Youth Mental
  Health Foundation
• Refunded from 1st July 2009 36m over 3 years

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Mental Health Literacy and First Aid

• Team Leader Prof Tony Jorm
• Self-help for depressive symptoms finding
  messages suitable for population-wide promotion
• Guidelines for parents on dealing with under-age
  drinking
• Development of guidelines for mental health first
  aid
• Mental health first aid guidelines for Aboriginal
  and Torres Strait Islander people

• Team Leader Betty Kitchener
• Youth mental health first aid
• Mental health first aid training by e-learning

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coordinated by headspace national
headspace support
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HEADSPACE CENTRAL COAST NSW
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HEADSPACE NEWCASTLE
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National Health and Hospitals Reform Commission
2009
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BECAUSE MENTAL HEALTH MATTERS 2009
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Victoria - unmet need
Public mental health service utilisation and
relative need for children and young people
Because mental health matters, May 2008.
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New Structure for Expanded Child and Youth Mental
Health Services for Victoria, Australia 2009
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progress with headspace

• 30 headspace one-stop centres operating across
  all States and Territories
• 10000 young people accessed these up to May 2009
• 2000 visitors to the website daily
• Headspace National Youth Reference Group (hYNRG)
  established and flourishing
• Federal Government in process of establishing
  headspace as a standalone company to operate the
  program during the next phase
• Engine room of clinical and translational
  research via OYHRC and BMRI

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Resources
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SUMMARY

• Pattern of onset and the concentration on young
  people 12 -25 years
• No system of care which provides access and
  engagement for young people
• Need for EI to spread across diagnostic silos
• Progress in some societies but limited in many
  others
• Innovators, early adopters, early and late
  majority and laggards
• Need to learn the lessons of wider early
  diagnostic efforts in medicine
• EI has a great deal to offer psychiatry as a
  field
• Need a youth focus

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ACKNOWLEDGMENTS

• All clinicians, researchers, patients and
  families at University of Melbourne, EPPIC, PACE,
  ORYGEN, MNC and BMRI especially
• Henry Jackson - Gregor Berger
• Alison Yung - Paul
  Amminger
• Lisa Phillips - Stephen
  Wood
• Jane Edwards - Chris Pantelis
• Kerryn Pennell - Warrick Brewer
• John Moran - Philippe
  Conus
• Ian Hickie - Tony Jorm
• Andrew Chanen - Rosemary Purcell
• Michael Berk - Helen Herrman
• Bruce Singh - Barnaby
  Nelson
• Eoin Killackey
• IEPA leadership group and many international
  colleagues
• All sponsors and funders esp Colonial Foundation,
  NHMRC, Stanley Foundation, NARSAD, Janssen,
  Lilly, Astra Zeneca, BMS, Pfizer.

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