TOP Conference 18-19th November 2015 Long term outcomes in First Episode Psychosis – results from the OPUS cohort Stephen F. Austin Psychiatric Center North Zealand Copenhagen University, Denmark
Overview of presentation • Description of OPUS trial • 3 studies on long term outcomes in OPUS cohort 1. Rates and predictors of recovery 2. Development of symptoms over time- trajectories 3. Consequences of persistent negative symptoms • Study limitations • Clinical implications and future research
OPUS Trial (1998-2000) • OPUS trial (1998-2000) RCT -578 people with First Episode Psychosis (ICD10 F20-28)- effect of assertive intensive treatment vs standard treatment (Petersen 2005, Bertelsen 2008) • OPUS Cohort- systematic follow-up (1 yr, 2yrs, 5yrs & 10yrs) Domain Measure Diagnosis Schedules for Clinical Assessment in Neuropsychiatry Symptoms Schedule for Assessment of positive and negative symptoms (SAPS/SANS) Functioning GAF: Global Assessment of Functioning (GAF) Personal and Social Function Scale (PSP) Course of illness Life Chart Schedule Psychiatric admissions Danish Psychiatric Central Research Register Accommodation Supported accommodation register
Study 1: Recovery
Long term recovery in FEP • Traditional view of schizophrenia as deteriorating, chronic condition- but many methodological problems (sampling, high dropout, no consensus in defining & measuring outcomes). • Evidence base- need for FEP cohorts to be followed up systematically over several years (EPPIC, AESOP, TIPS) • Recognized criteria for symptom remission (Andreasson 2005) functioning (vocation, social living skills) – Recovery AIM: Examine rates and baseline predictors of recovery at 10 year follow-up
Symptom remission & recovery • Symptom remission rates range from 26-52% (Robinson 2004, Henry 2009, Bertelsen 2009, Hegelstad 2013, Morgan 2014) • Functional remission rates range from 10-33% (Harrow 2005, Robinson 2004, Lambert 2006, Bobes 2007, Henry 2009, Wolff 2009) • Recovery rates range from 10-25% (Harrow 2005, Lambert 2006, Bobes 2007, Wunderink 2009, Bertelsen 2009) • Predictors of recovery- DUP, premorbid functioning, negative/positive symptoms, onset of illness, diagnosis, cognition, depression and work/education status
Definitions remission & recovery • Symptom remission- minimal to mild symptoms across three dimensions (negative disorganisation and psychoticism) for a minimum of 6 months (Andreasson 2005) • Recovery- symptom remission, no psychiatric admissions or supported accommodation over 2 years, GAF 60+, working or engaged study (Based on Liberman 2002)
Flow of participants at 10 yr follow-up Included in OPUS (1998-2000) (n=578) Removed from analysis (n=82) Schizotypal Diagnosis Lost to follow up (n=192) Deceased (n=33) Emigrated (n=18) Declined (n=137) Unable to locate (n=2) Too ill to consent (n=1) Participated in 10 year follow-up (n=304) -61% (Age-36 years, 55%- men, 25% -substance abuse) • No significant differences between participators and non-participators (baseline symptoms, diagnosis, DUP, pre-morbid functioning or sex or age). • Participators slightly higher baseline functioning GAF 41 versus 37, p<0.01)
Rates of remission & recovery 1 4 1 6 1 7 Recovery 2 5 2 2 2 9 Symptom Remission Positive and/or Negative 4 8 Symptoms 4 2 5 4 Institutionalised 1 3 1 3 7 2 years 5 years 1 0 years • Rates of symptom remission & recovery similar to other FEP studies* • Across 10 years rates of recovery similar within OPUS cohort but they are not the same people (2yrs to 5yrs 35%, 5yrs to 10yrs 45%)
Functioning of participants (n=304) Characteristic of functioning Participants meeting criteria Functioning (GAF-F -60 +) 33% (n=99) Currently working or studying 25% (n=76) Not living in supported accommodation (last 2 yrs) 82% (n=250) Adequate functioning in socially useful activities (PSP-A) 38% n=115 (work, education, household chores, parenting) Adequate social functioning (PSP-B) 69% (n=211) Adequate self-care (PSP-C) 78% (n=236) No aggressive/disruptive behaviour (PSP-D) 95% (n=289) Receiving disability pension 64% (n=195) Many people functioning well despite not meeting full recovery criteria
Baseline predictors for recovery Baseline Univariate Multivariate Characteristics Odds Ratio (C.I. 95%) p value Odds Ratio (C.I. 95%) p value Sex 0.73 (0.38-1.40) 0.35 - - Age included in trial 0.93 (0.88-0.99) 0.03 0.92 (0.86-0.99) 0.039 Schizoaffective Diag. 5.02 (1.49-16.32) 0.009 3.71 (0.78-17.81) 0.101 Psychotic - - 1.08 (0.84-1.38) 0.57 Disorganized 0.99 (0.99-1.00) 0.38 - - Negative Symptoms 0.56 (0.41-0.76) 0.001 0.51 (0.34-0.75) 0.001 GAF Functioning - - 1.02 (1.00-1.05) 0.051 High school finished 2.68 (1.38-5.21) 0.003 2.13 (0.94-4.87) 0.072 Social contact 9.57 (1.28-71.25) 0.028 4.85 (0.58-40.24) 0.144 DUP - - 0.99 (0.98-1.00) 0.377 PAS social 0.77 (0.06-8.56) 0.788 0.08 (0.01-0.55) 0.01 PAS academic 0.84 (0.01-0.58) 0.012 0.31 (0.03-3.76) 0.363 GAF-Global Assessment of Functioning DUP-Duration of untreated psychosis PAS- Pre-morbid adjustment scale
Age included & Negative symptoms Age included OR 0.92 (C.I 95% 0.86-0.99) For each year diagnosis/treatment is later, risk of recovery decreases by approx. 8% (3yrs+ 22%) Negative symptoms OR 0.51 (C.I. 95% 0.34-0.75) For each increase of 1 pt on negative symptom scale (0-5) risk of recovery decreases by approx. 49% (+2pts 74% ) Negative symptoms at 1 year independently contributed to recovery after controlling for baseline symptoms (OR 0.49 C:I 95% 0.25-0-98 )
Study 2: Trajectories
Symptom Trajectories I • Traditionally long term studies in FEP are based on cross sectional data (recovered vs not recovered). • These studies do not capture how the illness manifests over time- symptom trajectories. • Analysis of data using dichotomous outcomes may be inefficient (Royston 2006) • Newer statistical techniques (Latent Class Analysis (LCA) identify patterns of outcome in large data sets .
Symptom Trajectories II • Studies- identified 4-5 positive symptom trajectories (reduction and stabilization) but used proxy for symptoms- hospitalization (Levine 2011, Rabinowitz 2007). • Studies using clinical data (4-trajectories) but based on three month follow-up (Schennach et al 2012) • No studies have examined long term trajectories for negative symptoms (Case 2010) AIM: Identify positive and negative symptom trajectories and baseline predictors
Positive symptom trajectories 5 4 Positive Symptoms (SAPS) No response 13% 3 Relapse 15% 2 1 Episodic 13% Delayed 12% Response 47% 0 0 1 2 3 4 5 6 7 8 9 10 Years Positive symptoms- pattern of reduction and stabilization over time (70%)
Negative symptom trajectories 5 4 Negative Symptoms (SANS) 3 No response 27% 2 Relapse 26% 1 Delayed 19% Response 28% 0 0 1 2 3 4 5 6 7 8 9 10 Years Negative symptoms- relatively little change over time (80%)
Predictors for positive symptom trajectories Baseline characteristics Relapse Delayed Episodic No response Odds ratio (OR) Odds ratio (OR) Odds ratio (OR) Odds ratio (OR) (95% C.I.) (95% C.I.) (95% C.I.) (95% C.I.) Duration of untreated 1.47** 1.27** 1.32** 1.34** psychosis (1.21-1.80) (1.07-1.52) (1.04-1.68) (1.12-1.61) Functioning (GAF-F) 0.99 1.23 0.62 0.68* (0.53-1.82) (0.92-1.65) (0.35-1.11) (0.47) Substance abuse 5.9** 2.33 1.64 3.47** (1.1.81-19.2) (0.89-6.12) (0.45-6.00) (1.39-8.65) Schizophrenia diagnosis 2.24 7.09 1.9 2.20 (F20) (0.69-7.27) (1.34-37.5) (0.60-6.04) (0.67-7.21) Response trajectory reference group C.I.- 95% confidence interval * p<0.05, ** p<0.01, *** p<0.001 OR reflects a one year increase in DUP, OR reflects 10 point increase in functioning on GAF- F
Predictors for negative symptom trajectories Baseline characteristics Relapse Delayed No response Odds ratio (OR) Odds ratio (OR) Odds ratio (OR) (95% C.I.) (95% C.I.) (95% C.I.) Disorganized symptoms (SAPS) 2.01* 1.44 2.38** (1.09-3.71) (0.76-2.40) (1.38-4.22) Functioning (GAF-F) 0.79 0.86 0.52** (0.55-1.12) (0.52-1.43) (0.35-0.78) Sex (male) 1.94 1.31 3.43*** (0.83-4.52) (0.47-2.74) (1.45-8.13) Schizophrenia diagnosis (F20) 5.70** 3.32 8.86*** (1.65-19.72) (0.86-12.84) (2.75-28.53) Inadequate social contact 3.13* 3.44** 5.55*** (1.25-7.69) (1.29-9.09) (2.22-12.50) Pre-morbid social function (PAS) 1.34** 0.99 1.33** (1.08-1.67) (0.77-1.28) (1.13-1.69) Response trajectory reference group C.I.- 95% confidence interval * p<0.05, ** p<0.01, *** p<0.001 OR reflects 1 point increase in disorganized symptoms, OR reflects 10 point increase in functioning , Inadequate social contact less than one contact a week with family or friend, OR reflects 0.1 point decrease in PAS scale (range 0.0-1.0)
Study 3: Persistent Negative Symptoms
Negative symptoms • Primary negative symptoms as core pathology versus secondary negative symptoms as consequence of illness (Carpenter 1988) • Current psychometric approaches- affective flattening, alogia, anhedonia, asociality, avolition. (New measures: CAINS- Blanchard et al. , BNSS- Kirkpatrick et al.) • Expressive deficits and avolition most common groupings in factor analysis (Messinger 2011, Carpenter 1988) • Numerous studies have identified negative symptoms implicated with poor outcomes (Ho 1998, Milev 2005, Blanchard 2005, Austin, Nordentoft et al. 2013)
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