Cognitive remediation in Recent Onset Schizophrenia: Results of an effectiveness trial

Transcription

1 The Brain Dynamics Centre Westmead Hospital & University of Sydney Cognitive remediation in Recent Onset Schizophrenia: Results of an effectiveness trial Dr Anthony Harris University of Sydney & PEIRS, Sydney West Area Mental Health Service Funding This research was funded by the following bodies Eli Lilly Answers that Matter Perpetual Trustees Research Trust Fund of the Schizophrenia Fellowship of New South Wales

2 What are we treating when we treat schizophrenia? Positive Symptoms Negative Symptoms An old paradigm A more complex picture Positive Negative Excitement Cognitive Anxiety / Depression

3 Outcome determined overwhelmingly by two domains Positive Negative Excitement Cognitive Anxiety / Depression Dementia praecox there is an inevitable and progressive mental deterioration, the most striking feature of which are the patient s inexplicable lack of judgment and incoherence of thinking. And later: the premorbid level of mental ability is never fully recovered (Kraepelin, 1896)

4 Commonly described cognitive deficits in psychotic disorders Schizophrenia Bipolar Disorder Attention, concentration, & vigilance Memory Verbal memory Executive function Language skills Planning and executive function Major Depression Verbal memory Slowed mental speed Concentration deficits Severity of Cognitive Impairments in FEP Mean Z score Schizophrenia Affective Other Controls Current IQ Attn/vig Work Mem Verb Acq Verb Recall Vis Recall Visuospatial Cog Flex Verb Fluency Speed Fitzgerald et al, 2004 ANZJP 38,

5 WSFEP Project neuropsychological results Baseline 1-Year Follow-up Schiz T1 (n = 29) Affective T1 (n =11) Substance Induced T1 (n = 7) Schiz T2 (n = 29) Affective T2 (n = 11) Substance Induced T2 (n = 7) Current IQ Attn/Vig Work Mem Verb Acq Verb Recall Vis Recall Visuospatial Cog Flex Verb Fluency Speed Current IQ Attn/Vig Work Mem Verb Acq Verb Recall Vis Recall Visuospatial Cog Flex Verb Fluency Speed Relationship of cognitive function to psychosocial functioning Return to work influenced by negative symptoms & cognitive deficits Cognitive deficits appear to relate more directly to level of real life functioning than positive symptoms For FES, premorbid functioning, DUP, comorbid substance abuse also important

6 Can we treat cognitive deficits? Role of medication Older typical antipsychotics appear to do little to assist and may harm cognition Second Generation Antipsychotics (SGA) have all been shown to help cognitive problems Effect size of SGA on cognition = 0.20 (Twamley et al, 2003) Computer assisted Cognitive Remediation Use of set batteries of computer tasks from commercially available software Structured, standardised, based on learning principles Self paced High status, hopefully enjoyable Can be run in small groups Use feedback embedded in software Effect size = 0.43 (Twamley et al, 2003) (effect size of SGA on cognition = 0.20)

7 Commercial game and educational software

8 Who were our subjects? Diagnosis: Schizophrenia, schizophreniform or schizoaffective disorder Age: years No current substance abuse Evidence of a decrement in cognitive functioning Drawn from a range of early psychosis, community rehabilitation services and inpatient rehabilitation units Who were our therapists All clinicians project supported by area health Range of backgrounds including :- Nursing Occupational therapist Psychology masters and undergraduate degrees 1 week training Fortnightly supervision for first 6 months and then regular contact Log checked for treatment fidelity

9 What did our subjects do? Cognitive problems were assessed Familiarised with the computer (1-3 sessions) Attend treatment twice a week for weeks with centre s normal treating clinician 20 sessions defined as an adequate dose Worked at various computer games Therapist selects games on the basis of cognitive profile, guides, helps suggest ways of getting around problems, helps motivate Hypotheses That cognitive remediation would improve cognition over 20 session That improvements on scores would persist over a 15 week follow-up That subjects with a recent-onset disease (<2 yrs illness) would have a greater improvement compared with those with chronic illness Functional improvement would accompany cognitive improvement

10 Dropout n=14 n=36 Screen & Randomised n=69 n=33 Dropout n=12 Assess Assess Waitlist Control 15 weeks (n=25) Immediate Treatment 15 weeks (n=22) Assess Assess Treat 15 weeks (n=18) Dropout n=7 Dropout n=0 Follow-up 15 weeks (n=38) Assess Dropout n=2 Assess Cognitive Assessment Domain Attention Working Memory Delayed Verbal Recall Delay Visual Recall Cognitive Flexibility Executive Function Processing Speed Test Connors CPT omission WAIS digit span backwards RAVLT Delayed recall Delayed recall (Rey CF or Taylor CF) Tower Test DKEFS Sorting Test DKEFS Trail Making Test A

11 Subject characteristics Immediate Treat M:F = 21:15 Waitlist M:F = 20:13 mean SE mean SE Age CPZ equi PANSS PANSS PANSS gen Calgary DRS SOFAS Rosenberg SES Hypothesis 1: That cognitive remediation would improve cognition over 20 session

12 Results : Immediate Treatment vs Waitlist Domain Attention Working Memory Delayed Verbal Recall Delay Visual Recall Cognitive Flex. Executive Fx Processing Speed Treat Vs Wait trend trend trend t(45)= , p=.066 t(45)= ; p=.065 t(45)= , p=.035 t(45) = ; p=.012 t(44)= ; p=.077 t(45)= ; p=.001 t(45)=-2.353, p=0.023 p < 0.05 Results: Treat vs Waitlist Clinical Domains PANSS + PANSS - PANSS gen Calgary DRS CPZ equi SOFAS Self Esteem Treat vs Waitlist t(42)= 1.098; p=.278 t(41)=.218; p=.829 t(42)=.536; p=.595 t(44)= 1.018; p=.314 t(41)=.480; p=.633 t(42)= ; p=.004 t(41)= -.838; p=.407

13 Hypothesis 2: That improvement in cognition would persist over a 15 week follow-up Results: Follow-up Domain Attention Working Memory Delayed Verbal Recall Delay Visual Recall Cognitive Flex. Executive Fx Processing Speed Followup vs End of Treatment n.s t(32)=.432; p=.669 t(37)= -.845; p=.404 t(37)=.927; p=.360 t(36)= -.912; p=.368 t(36)= ; p=.008 t(37)= -.832; p=.411 t(37)= -.764; p=.450

14 Results: Follow-up Clinical Domains PANSS + PANSS - PANSS gen Calgary DRS CPZ equi SOFAS Self Esteem Followup vs End of Treatment t(34)=.704; p=.486 t(33)=.261; p=.796 t(33)= 1.111; p=.275 t(34)= -.509; p=.614 t(26)= ; p=.186 t(33)= -.022; p=.983 t(25)= -.866; p=.395 Occupational Outcome Occupational Outcome 35 After Treat Follow-up per cent in-pt Comm. SB Unemp. S.W. P/T F/T Wilcoxon Z= ; p = 0.003

15 Hypothesis 3: That recent onset schizophrenia would have greater improvement than chronic schizophrenia Demographics Age Illness (yrs) CPZ equi Recent Onset Sz Mean SE Chronic Sz Mean SE Calgary DRS PANSS PANSS PANSS gen SOFAS Rosenberg SES

16 Results: Recent Onset vs Chronic Schizophrenia Domain RO vs CSz Treat vs Base Interaction Attention p < p = Working Memory p = p = Delayed Verbal Recall p = Delay Visual Recall p = p < p = Cognitive Flex. p = p < Executive Fx p = p < Processing Speed p = p = Change in function SOFAS score Baseline Post-treat 10 0 Recent Onset Chronic Sz Trend p = 0.07

17 Conclusions Cognitive remediation improves performance of people with schizophrenia over a wide range of cognitive domains These effects persist at least over a three month period They are accompanied by indications of some functional improvement Slight advantage for recent onset schizophrenia in treatment effect Continuing research Is there a threshold of improvement before effects can generalise to social functioning? Are there specific cognitive domains that need to be targeted? Is improvement restricted to certain social domains? What is the dose of treatment required? Do you need booster sessions to keep the effect? How long does the effect last?

18 Contributors to the Research Cognitive Remediation Team Daniella Siciliano Antoinette Redoblado- Hodge Pam Rogers David Cairns Clinicians at the treatment centres All our patients Centres Cumberland Hospital Macquarie Hospital PEIRS Granville Rehabilitation EPIP / Hornsby Brookvale Early Psychosis Team Chatswood MHT Wahroonga MHT Windsor MHT