+
ARMS
At Risk Mental State
(at risk of psychosis)
NZEIPS Training Forum
November 2015
Dr Lindsay Twiss
+
ARMS

Daniel, Anthony, William

Staging model of psychosis

Assessment of ARMS

Natural hx of ARMS

Goals of intervention

Evidence for intervention

Risks with intervention

Daniel, Anthony, William
+
Daniel

19 yr old, Maori man, isolated, not working/studying

GP referral low mood

Daniel: “everything is crap”

Grief with romantic relationship ending + family hx mood
disorders

Multiple depressive sx, including thoughts of suicide
+
Daniel

Feeling of a presence when in bed at night, feels sinister,
most nights for a couple of months, hard to get to sleep

Associated with this, some nights sees shadowy figures in
darkness

For a couple of weeks, a month ago, could some nights, hear
something moving in the corner of his room, would get up
and check his ph
+
Anthony

22 yr old, Pakeha, unitech student

CAS f/u following urgent assessment in police station after
indicating intention to suicide to friends

Recent low mood, improving with GP initiated escitalopram,
no longer considering suicide

Reluctant/vague historian
+
Anthony

“voices”, “inner chatter”, “they sound like me”, derogatory,
improved as mood improved, ?several times/week, less than
an hour each time

Feelings of being judged + watched, ?a couple of
times/week, for an hour or more

5x in past year, referential messages from TV + books

Coincidences + déjà vu more prominent than usual
+
William

20yr old, Pakeha man, unemployed musician

GP referral: “fluctuating mood + ?psychosis”

William: “feeling down”, “paranoid + anxious”

Low mood “on + off” several years, not currently meeting
criteria for MDE

Family hx mood disorders including attempted suicide

Frequent/heavy alcohol + cannabis from early teens,
moderated though still binge drinking couple x/week,
cannabis 1-2x/week
+
William

For past 2 months:

Feels like people are watching him/out to get him, but not
sure who or why. Occurs ~ once/week, knows its not true but
stops him from going out, lasts half a day

Sees things/people out of corner of his eye, ~ once/week,
fleeting

“sometimes” the world feels different/changed/unfamiliar

Feels like people know what he is thinking, ~ once/week
+
William

Feels like TV/radio are talking to him, ~ once/week

Feels like he is here to do something special, but not yet sure
what that is

Subjective sense of occasional difficulty organizing his
speech/communicating with others, but no evidence TFD on
examination
+
ARMS

A sustained and clinically significant deviation from the
premorbid level of experience and behaviour.

Individuals who appear to be at risk for psychoses but in
whom psychoses is not inevitable


McGorry and Singh 1995
Transition rate into psychoses of 15 – 35%

Yung et al 2007, McGorry 2008
+
ARMS by other names

ARMSp

UHR

PLE

CHR

Psychosis Risk Syndrome

Early Initial Prodrome state

Basic Sx

Prodrome (but not prodrome)
+
ARMS vs Prodrome

At risk of developing illness vs certainty of developing illness

ARMS is a prospective concept whereas prodrome is
retrospective

Interventions at an early stage can prevent full blown
psychoses
+
Goals of Intervention for ARMS

Reduce risk of transition to pscyhosis

Delay transition to pscyhosis

Reduction in symptoms, distress + disability

Treatment of co-morbidity

Maintenance of vocational, educational and social function/or
early rehabilitation if indicated so as to maintain
‘developmental trajectory’

Early development of a therapeutic relationship
+
Goals of Intervention for ARMS

Reduction of DUP in case of transition to psychosis

Facilitating engagement while social function and networks
are intact

Increased acceptance of treatments in case of transition to
psychoses

Effective early treatment avoids the need for hospitalization
+ limits damage to relationships

Assist in research (eg PACE)

Prevent/minimize neurobiological change during transition
+
CAARMS

Comprehensive Assessment At Risk Mental State

ARMS Identified from mid 90s

“Melbourne Criteria”

Operationalized to CAARMS, CARRMS II

Abbreviated vs full
+
CAARMS

Threshold for ARMS at initial assessment

Mapping changes with time

Rule out/confirm threshold for psychosis
+
CAARMS

Trait + State Risk Factors/Genetic Risk

Attenuated Psychotic Sx (APS)


Sub threshold intensity

Sub threshold frequency
Brief Limited Intermittent Psychotic Sx (BLIPS)
+
Trait + State Risk Factors

Schizoptypal PD in individual or a first degree relative with a
psychotic disorder

Recent drop in functioning/or longer term low functioning
+
Attenuated Psychotic Sx

Presence of 1+ ideas reference, odd beliefs, magical
thinking, perceptual disturbances, paranoid ideation, odd
thinking + speech, odd behaviour + appearance

Frequency of sx: several times/week

Within past year

At least 1 week, less than 5 years

Recent drop in functioning/or longer term low functioning
+
BLIPS

Transient psychotic sx

1+ ideas of reference, magical thinking, perceptual
disturbance, paranoid ideation, odd thinking or speech

Duration of sx: less than 1 week

Frequency of sx: several x/week

Sx resolve spontaneously

Within last year

Recent drop in functioning/or longer term low functioning
+
Psychosis

Frank psychotic sx (delusions, hallucinations, thought
disorder)

For > 1 week

Frequency of sx: at least 3x/week if more than 1 hr/occasion,
or daily < 1 hr
+
CAARMS

Pre 2006 age range 15-30, since 2006 15-25

Help seeking

Recent functional decline or chronic low functioning

Identify if substance using (doesn’t preclude inclusion)

Identify level of distress in relation to sx
+
SOFA

Social and Occupational Functioning Assessment Scale

Continuum from 1 -100

Eg:

1-10: persistent inability to maintain minimal personal hygiene.
Unable to function without harming self or others without
considerable support

41-50: moderate difficulty in social, occupational or school
functioning (eg: no friends, unable to keep a job)

81-90: good functioning in all area, occupationally + socially
effective
+
SOFA

For each of the 3 domains, ….. PLUS

30% drop in SOFA score from premorbid level, sustained for
a month, within past 12 months, or

SOFA score of 50 of less for past 12 months or longer
+
CAARMS domains

Unusual thought content

Non bizarre ideas

Perceptual abnormalities

Disorganized Speech
+
+
+
+
+
CAARMS ratings

Daniel:




Perceptual abnormalities: Moderately Severe (4), frequency/duration of 3-4.
SOFA ~ 30 (major impairment, very socially isolated, not leaving the house,
impaired ADLs)
= sub threshold intensity APS
Anthony:







harder to score given limited history:
Unusual thought content: severe (5), frequency/duration of 1
Non bizarre ideas: moderately severe (3), frequency/duration of 3
Perceptual abnormalities: moderately severe (4), frequency/duration of 3
SOFA ~ 60 (difficulty in social relationships + uni functioning)
= sub threshold intensity APS
? BLIPS
+
CAARMS ratings

William

Unusual thought content: moderately severe (4),
frequency/duration of 2

Non bizarre ideas: severe (5), frequency/duration of 3

Perceptual abnormalities: moderate (3), frequency/duration of 2

Disorganized speech, mild (2), frequency/duration of 2

SOFA ~ 50 (not working or studying, withdrawn from friends)

= Sub threshold intensity APS
+
Other Assessment Tools/Scales

Structured Interview for Prodromal Symptoms and Scale of
Prodromal Symptoms (SIPS/SOPS).


Miller et al 1999, McGlashan et al 2001
Bonn Scale for the Assessment of Basic Symptoms (BSABS)

Kloster Kotter et al 2001
+
Progression of ARMS

15-40% transition to full psychosis over 12 months

Compared with ~ 5% pre-diabetes transition to DM

Decreasing transition rates?

Greatest risk in first years

But risk still elevated at 10yrs
+
“PACE 400”
Nelson et al (2013)

416 subjects followed 10+ yrs
Transition Rate (%)
1 yr
16.5
2 yr
20.4
5 yr
30.1
10 yr
34.9
+
Risk of progression to psychosis

Nelson, Yueng, Yung 2010

817 subjects

Outcome: transition to psychosis over 6 months

Only 9% transitioned (receiving intervention)

Genetic risk < APS < BLIPS

Increased risk with >1 criteria

Other risk factors: low baseline GAF, duration of sx at
presentation
+
Other risk factors for progression

“PACE 400”, Nelson et al,2013

baseline thought disorder

baseline negative sx
+
Other risk factors for progression

North American Prodromal Longitudinal Study

> 300 treatment seeking individuals with ‘psychosis risk
syndrome’, 2.5 yr f/u

Addington et al 2007, Cannon et al 2008

Genetic risk

Deterioration in function

Greater social impairment

Higher levels unusual thoughts

Higher levels of suspicion/paranoia

Hx substance use
+
Role of Substance Use

PACE study found cannabis didn’t significantly increase risk
transition to psychosis

But, majority have found significantly increased risk of
development of psychosis in those at risk, if using cannabis
or other illicit substances

Miller et al 2001, Henquet et al 2005, Verdoux et al 2003
+ At Clinical High Risk for Psychosis:
Outcomes for Non Converters. Addington et
al 2011

North American Prodromal Longitudinal Study

71% (2.5 yr f/u) did NOT transition to psychosis

BUT still 1+ APS present for 43% at 1yr, 41% 2yrs

AND social + role functioning significantly poorer (compared
with non psychiatric controls)

Significant axis 1 comorbidity at baseline (anxiety disorders
in 53%, depression in 35%), improved at 1 + 2yrs f/u (but
confounded by treatment for non-psychotic disorders)

Small proportion only of emergent axis 2 disorders.
+ PACE 400:
Non Psychotic Syndrome
Lin et al, Am J Psych
+
Non Psychotic Outcome

From Pat McGorry APA presentation 2014, PACE data

1/3 transitioned to psychosis

2/3 did not

But only 7% no dx at f/u (mostly mood, also anxiety,
substance use).

~ 1/3 APS at f/u
+
Efficacy of Interventions

PACE clinic trial, McGorry et al 2002

CBT + risperidone vs usual case management. Significantly
lower transition to psychosis in active vs control group (9.7%
vs 35%)after 6months treatment phase but advantages lost
with longer follow up.

Ie: psychosis was delayed

Not known if CBT or medication effective
+
Efficacy of Interventions

US study McGlashen 2006

12 months low dose olanzapine vs placebo

Trend toward lower transition to psychosis, but didn’t reach
clinical significance

Side effects, mostly weightgain
+
Efficacy of Interventions

British study, Morrison et al, 2004

CBT vs monitoring of mental state

Significantly lower rate of transition to psychosis (6% vs
26%)

But differences not maintained at 3 years
+
Efficacy of Interventions

German study, Bechdolf et al 2007

‘early initial prodrome state’

Presence of self identified deficits in thoughts + perception
(basic sx)

Cognitive therapy superior to supportive counseling in
reducing progression to sub threshold + full threshold
psychotic sx over 24 months
+
Long Chain Omega3 Fatty Acids for Indicated
Prevention of Psychotic Disorders. Amminger et
al. Arch Gen Psychiatry. 2010; 67(2): 146-134
 Possible
mechanisms of action: Membrane fluidity,

Membrane fluidity

Receptor responsiveness in cell membranes

Interactions with dopaminergic + serotonergic systems

Increasing glutathione (protecting neurons from excitotoxicity +
oxidative stress
+ Long Chain Omega3 Fatty Acids for
Indicated Prevention of Psychotic Disorders

13-25yrs old, majority presenting as out pts, Medical
University of Vienna, also other youth + adult MHS

1+ of attenuated psychotic sx, transient psychosis, genetic
risk (fm hx or schizotypal PD) + fn decline >30% (GAF)

81 subjects
+ Long Chain Omega3 Fatty Acids for
Indicated Prevention of Psychotic Disorders

Randomized, double blind, placebo controlled, 12 week
treatment trial of omega 3 PUFAs

12 month follow up

Active treatment = 700mg EPA + 400mg DHA

Primary outcome measure: transition to psychosis

Secondary measures: PANSS, MADRAS, GAF
+ Long Chain Omega3 Fatty Acids for Indicated
Prevention of Psychotic Disorders


Conversion to psychosis at 12 months:

4.9% (2/41) in omega 3 group

27.5% (11/40) in placebo group
Secondary outcomes:

Omega 3 group significantly lower PANNS (positive, negative,
general) from 12 weeks to 12 months compared to control group

No effect on MADRAS

Omega 3 group significantly higher GAF from 12 weeks to 12
months compared to control group
+ Long Chain Omega3 Fatty Acids for
Indicated Prevention of Psychotic Disorders

NNT = 4

High rates of adherence

No statistically significant difference between treatment +
placebo groups for adverse events
+ Long Chain Omega3 Fatty Acids for
Indicated Prevention of Psychotic Disorders

Omega 3 PUFAs appear to prevent (or at least delay) onset of
psychotic episode

Safe (SEs: fishy eructation, nausea, loose stools)

Tolerable, publically acceptable, low cost, benefit general
health

Benefit sustained following cessation of intervention

Neurapro: large multisite study aiming to replicate findings
+ Pharmacy Field Trip

Nature’s Own Fish Oil ‘double strength’ 2000mg

2 tablets = 720mg EPA + 480 DHA

$20-40 for 200 tablets = 100 days

~ $10 month
+
Efficacy of Intervention: Meta
analysis

Van der Gaag (2013)

10 trials

NNT = 8

“Early detection and intervention in people at ultra high risk
of developing psychosis can be successful to prevent or
delay a first psychosis”

Antipsychotic medication is NOT first line, probable over
treatment
+
NNT

Antibiotics for acute otitis media (absence signs + sx at 7-14
days): 7

‘Flu Vacination (no ‘flu): 23

Statins as primary prevention (‘all bad things’): 35

Statins as secondary prevention (‘all bad things’): 11
+
NNT


Cochrane review of antidepressants:

TCAs NNT: 9

SSRIs NNT: 7
Cochrane review of antipsychotics

Risperidone vs haloperidol: NNT 4-8

Clozapine vs typicals: NNT 6-20
+
Efficacy of Interventions

In addition to effects on transition to psychosis, treatment of
ARMS ameliorates non psychotic sx + distress
+
What do we offer?

Initial assessment

CAARMS

Assessment of co-morbidities

Psycho education, including risk of transition to psychosis

Treatment for comorbidities, eg: medication, talking therapy,

MI or CADS referral

Recommendation of fish oils

Family support/pscyho-education/family work

Ongoing assessment/monitoring, esp re: transition to psychosis

Assistance with vocational/interpersonal/family/social issues

Case management

Crisis support
+
Risks?

Resources

False positives

Stigma (self stigma/external stigma)

Non pathologizing language

NOT: prodromal, pre-psychotic, preschizophrenic

Minimize stigma

Antipsychotic medication is over treatment
+
Daniel, Anthony, William updated

Daniel: mood and APS have remitted with antidepressant
medication and fishoils, ongoing social + occupational
impairment, engaging with OT + psychologist
+
Daniel, Anthony, William updated

Anthony: transitioned to psychosis within next few months,
good response to low dose risperidone, now ‘prn’, ongoing
psychological work, largely choosing psychological
strategies to manage sx, minimal distress or impairment
+
Daniel, Anthony, William updated

William: ongoing low mood + APS, mood reached threshold
for MDE, treated with antidepressant medication, family more
concerned + more involved, recommendation of fishoils
eventually followed, CADS involvement, now working as an
apprentice, more socially engaged, getting on better with his
family, APS have resolved.