Food for thought: Psychological approaches to cognitive decline in schizophrenia

1. Food for thought: Psychological approaches to cognitive decline in schizophrenia Til Wykes Institute of Psychiatry King’s College London June 2011

2. What happened in the last century? • UK reduced the number of inpatient beds • 140,000 in 1950s to 40,000 in 1994 • Long stay hospitals closed • To reduce institutionalism • Increased care opportunities in the community • To increase assimilation • Rehabilitation options • To improve work outcomes and daily living skills

3. Where did that leave people with a diagnosis of schizophrenia? • Still a high cost of acute care beds in UK • £652m : 5.4% all UK NHS costs • No improvements in social outcomes (Mason et al, 1996) • Poor employment record • High re-admission rates, particularly following a first episode

4. In the USA for Serious mental illness • $193.2 billion in lost earnings • $100.1 billion in Health care • $24.3 in disability benefits • Grand total --- $317.6 billion Kessler et al, AJP 2008

5. Aims • Do people with a diagnosis of schizophrenia experience cognitive problems? • Are these cognitive problems important for recovery? • How might we treat them?

6. Between episodes “My concentration is very poor. I jump from one thing to another. If I am talking to someone they only need to cross their legs or scratch their head and I am distracted and forget what I was saying.” McGhie and Chapman, 1961

7. During an episode “Where did all this start and could it possibly have started the possibility operates some of the time having the same decision as you and possibility that I must now reflect or wash out any doubts that’s bothering me ……” From Wykes and Leff, 1982

8. “I was looking at A or B for some subjects now I’m looking at C or D if I’m lucky.” “Memory loss is the new thing that’s bothering me.” “I have low concentration” “I’m coming to terms with the fact that I have got a learning difficulty.” Michael, Aged 16 years Inside my head - Channel 4, June 2002 First episode

9. Do cognitive problems predate the onset of disorder? • Jones et al (1998, 2000) • UK Birth cohort • Cognitive abnormalities in children pre-schizophrenia • Lewis et al (1998, 1999) • Conscripts in Denmark • Lower IQ in conscripts pre-schizophrenia • Cannon M. et al (2001) • New Zealand birth cohort • Cognitive difficulties at all stages pre-schizophrenia

10. Learning from service users “I want to be able to do things that other people do, like have a boyfriend and a job …” Vocational Functioning “I want to have friends” Social functioning “I want to be able to cook and eat when I want” Life skills “I want to live in my own place not a hostel” Dependence on services

11. Work From Bell et al (2001) Cognitive variables (in yellow) Memory, Attention, Flexibility, Learning What did symptoms add? Nothing

12. Social functioning • What effect do positive symptoms add? • NOTHING

13. Life Skills Velligan et al 1999 Positive symptoms Life skills Cognition Negative symptoms

14. Life Skills Velligan et al 1999 Positive symptoms Life skills Cognition 42% Negative symptoms

15. Dependence on careThe Netherne Series Wykes, Katz, Hemsley, Dunn & Sturt, 1990 -1994 Thinking flexibility Positive symptoms Dependence on psychiatric services 60% Negative symptoms Length of illness Previous skills

16. Average weekly costs for service users in SL&M NHS Trust Wykes, Reeder, Williams, Corner, Rice and Everitt, 2003

17. Thinking, symptoms and outcomes Occupational Functioning Cognition Social Functioning Positive and/or negative symptoms Life Skills Dependence on psychiatric care

18. Thinking, symptoms and outcomes Occupational Functioning Cognition Social Functioning Positive and/or negative symptoms Life Skills Dependence on psychiatric care Perlick et al, 2008

19. Community activities Bowie et al 2006

20. What do we know about cognition in schizophrenia? • Definition of schizophrenia • Cognition is important (Kraepelin and Bleuler) • DSMV considering cognition as a diagnostic adjunct • Cognitive disturbances present • before onset • during episodes • between episodes of acute symptoms

21. Summary: Cognitive difficulties experienced by people with schizophrenia • Speed • Memory • Attention • Reasoning • Tact/Social cognition • Synthesis © Keshavan

22. About cognitive difficulties in schizophrenia • Start early – before onset • Persist even when symptoms are absent • Interfere with functioning outcomes • Not related to medication (although it can make them worse)

23. Pharmacological Treatments for Cognition 1 0.9 (L) ) 0.8 d 0.7 0.6 (M) 0.5 Effect Size (Cohen's 0.4 0.3 (S) 0.2 0.1 0 Antipsychotics (Keefe d-Cycloserine Glycine Galantamine PracticeEffect (Buchanan et (Buchanan et (Buchanan et (Goldberg et et al., 2007) al., 2007) al., 2007) al., 2008) al., 2007) © Keshavan

24. The basis of clinical decisionsIsaacs and Fitzgerald BMJ 1999 • Eminence • seniority of the protagonist with a touching faith in clinical experience • Vehemence • Volume substitutes for evidence • Eloquence • Good dress sense and verbal skill • Confidence • Only applicable to surgeons • Evidence • Randomised controlled trials, meta-analyses

25. What does this mean for treatments? • Methodologically rigorous evaluation to assess success • Evidence of how to match therapy to patients • Treatments are feasible and acceptable • Avoiding: • Presumptions such as statistical significance is the same as clinical significance • Preventing treatment failure

26. What do we know about the treatment of cognition?

27. ‘Scientific evidence has shown that regular brain training, as offered by the CD, can help defer the onset of age-related brain decline’ “prevent brain ageing, .. improve memory". 26th Feb 2009 Nintendo brain-trainer 'no better than pencil and paper' Brain training? Think again, says study Experts say they are no better than a crossword 'Brain training' claims dismissed

28. Few reports in the peer reviewed literature Experimental data was not collected on the specific training product When there was a study No independent data Studies often had no control group Improvements in performance on the task only (practice) When there was a comparison group No differences between the product and comparison groups Comparison group was better Why? 26th Feb 2009

29. Brain training tested • 11,000+ participants (normal people?) randomly assigned to: • 2 Expt groups • Playing specially designed games for reasoning and problem solving • Wide range of games similar to commercial software • Control group • Surfed the web to answer obscure questions but no games • at least 10 mins per day 3 times per week for 6 weeks • Looked at generalisation to other tasks • RESULTS • No evidence that brain training worked • Despite improvements on trained tasks there was no improvement in the generalisation tasks – more than the control Owen et al, Nature May 2010

30. Rate of accumulation of information on therapies

31. Can we change cognition? • Cognitive rehabilitation for schizophrenia: Is it possible? Is it necessary? • Bellack, 1992 • Cognitive Remediation in schizophrenia: Proceed … with caution! • Hogarty and Flesher, 1992

32. Why was there therapeutic pessimism? • Cognitive difficulties are • part of the diagnosis genesis (Kraepelin and Bleuler) • apparent before onset (Cannon et al, 2001) • Cross-sectional studies and longitudinal studies show few changes over time except in some elderly patients • But stability does not mean immutability

33. What is Cognitive Remediation Therapy (CRT) .. • Is a therapy • Designed to improve cognitive processes • Such as: attention, memory, executive, social cognition and metacognition • Involves training Cognitive Remediation Experts Workshop (CREW) Florence April 2010

34. What has been developed? • Cognitive rehabilitation programmes: • Neurocognitive Enhancement Therapy (NET) • Computer Assisted Cognitive Remediation (CACR) • Brain Fitness • NEAR • REHACOM • COGREHAB • Cognitive enhancement Therapy (CET) • IPT • Cognitive Remediation Therapy - CIRCuiTS

35. Training usually involves …. Errorless learning Trying not to allow errors Keeps reinforcement high and learning accurate Verbal monitoring Overtly then covertly Scaffolding So that tasks are always a manageable challenge

36. What do people think they are changing? • The brain • Neuroplasticity (a bit vague but somehow to increased the potency of some connections) • Cognition • Specifically to increase the use of sustained attention, cognitive flexibility • Metacognition • Increase the use of metacognitive knowledge or regulation (knowing what you know and how to use this information)

37. Does it work?Meta-analysis of CRT studies • Studies had a random allocation procedure • CRT vs any control • Contact with all major contributors • 40 treatments in 39 trials in 109 reports Til Wykes, Vyv Huddy, Caroline Cellard, Susan McGurk, Pal Czobar (2011)

38. Global cognition effect sizes1982 participants

39. * Significant effects

40. Is our job done?

41. Issue date: March 2009 Schizophrenia Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care This is an update of NICE clinical guideline 1 NICE clinical guideline 82 Developed by the National Collaborating Centre for Mental Health www.nice.org.uk

42. CTAM – total score 100 • Sample • Allocation • Assessment • Control • Analysis • Treatment Description Thornley & Adams, 1998 Moher et al, 1998, 1995 Marshall et al, 2000 Schultz et al, Chalmers et al 1981 Jadad et al, 1996 Juni et al, 1999, 2001 Kazdin and Bass, 1989 Sterne et al, 2002 Added Therapy description manual treatment fidelity Wykes et al, 2008; Tarrier and Wykes 2004

43. CTAM Scores for 40 CRT studies Individual Studies

44. Clinical Trials rating (CTAM*)40 studies • CRT mean score 57 (35-87) • CBTp mean score 61 (27-100) • Not different from each other *Tarrier and Wykes, 2004; Wykes et al, 2008

45. Effect of methodology on CBTp outcome Wykes et al 2008

46. Effect of methodology on CBTp outcome * Better method * Only target (positive) symptoms show significant effect Wykes et al 2008

47. Effect of method on CRT outcome Wykes et al 2011

48. Effect of method on CRT outcome * * Better method Wykes et al 2011

49. Do CRT effects last? Wykes et al 2011

50. Do CRT effects last? Durable change Wykes et al 2011