+ arms at risk mental state (at risk of psychosis) nzeips training forum november 2015 dr lindsay...

+

ARMSAt 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 16.52 yr 20.45 yr 30.110 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


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


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


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


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


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


NNT = 4

High rates of adherence No statistically significant difference between

treatment + placebo groups for adverse events


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


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


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


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.

+ arms at risk mental state (at risk of psychosis) nzeips training forum november 2015 dr lindsay...

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