1. Recovery from schizophrenia – a meta-analysis Erika Jääskeläinen (née Lauronen) and Jouko Miettunen University of Oulu, Finland

2. The structure of this presentation Background – Recovery and outcome in schizophrenia Recovery in schizophrenia – preliminary results from a meta-analysis

3. Background - Exploring recovery and the course of illness Why is it important to study prognosis and recovery in schizophrenia (and other serious mental disorders)?  brings new information about the aetiology and prognosis of the disorder; information for the patient, the significant others and nursing staff  it may be a proxy measure of the quality of life as well brings information about the quality and effectiveness of treatment  developing better treatments and treatment models

4. Background - Definitions 1.Treatment response decrease in symptoms, remission as the goal 2.Remission absence of symptoms, lasting for certain length of time (e.g. 6 months) 3.Recovery: when remission has lasted longer  but how long? quality of life, functioning (working ability), social relationships, need for treatment, use of health care services returning to premorbid level of functioning  realistic? and what is the premorbid level of functioning? There is no structured or generally accepted definition or criteria for recovery. But: During last years increasing interest on the topic, and Andreasen N et al. Am J Psychiatry 2005 have proposed structured criteria for remission in schizophrenia.

5. Background - Earlier literature In a meta-analysis of Hegarty et al (Am J Psychiatry) 1994: –appr. 40 % of schizophrenia cases good outcome, though the good outcome has slightly declined during last decades In some classic studies amount of recovered individuals is proposed to be 6-58% (Bland et al. 1976, Ciompi 1980, Bleuler 1987, McGlashan 1984) In population based studies the rate of recovery have varied from 3% to 16% (Goater et al. 1999, Harrison et al. 2001, Ran et al. 2001, Svedberg et al. 2001) In our own study in the Northern Finland 1966 Birth Cohort recovery percentage was 3.4% (Lauronen et al. J Clin Psychiatry 2005) But: the rate of recovery very much depents on the methods of the study! There is no systematic review or consensus about the rate of recovery in schizophrenia.

6. Aims What is the best estimate percentage of recovered individuals with schizophrenia? Our aim was to collate studies related to this topic and to synthesize these data with meta- analytic techniques. We aimed also to estimate effect of study methods on recovery percentages

7. Methods – literature search PsycINFO, Pubmed, Ovid, Web of Science, Elsevier Science Direct, EBSCOhost, CINAHL - Nursing & Allied Health Manual literature search As a title search we used keywords “schizo* or psychotic or psychos*s” and “recovery or remission or outcome* or course or prognosis or longitudinal or follow-up”. The second search in abstracts included keywords “schizophrenia” and “recovery or remission”. All abstracts and articles were critically analyzed by two authors (E Jääskeläinen and J Miettunen).

8. Methods - Criteria for inclusion to analyses sample included individuals with schizophrenia, schizophreniform, or schizoaffective disorder follow-up and data about some outcome measure at least for 2 years outcome criteria including both clinical and social dimensions subjects not selected a priori for good or poor outcome number of cases at least 15 English language article not drug or other trial

9. Methods - Statistical methods Recovery rates are presented by using forest plots The rates are pooled using random effects Meta regression was used to estimate effect of study years, length of follow-up, location, diagnostic system and sex The analyses were done with STATA 9 programme.

10. Results - Results from literature search The search from databases identified ~5950 unique articles. After further screening, we have identified 746 articles for inclusion. So far in total appr. 85% of these articles have been evaluated. From these 50 studies have met all our criteria and were included to deeper examination and statistical analyses. From these 13 samples were from the World Health Organization (WHO) incidence and prevalence cohorts (unpublished data from Dr Kim Hopper)

11. Results – Recovery percentage 0 - 52% of the subjects ‘recovered’ (mean 17.4%, median 16.7). In the 20 older studies (started -1965) on average 20.8% of the subjects recovered, while in the 20 more recent studies (started 1965-), 16.8% of the subjects recovered (meta-regression, z test 1.07, p=0.29). Recovery percentages were 9.8% in studies using DSM diagnostic system (9 studies), 18.7% in ICD (18 studies), and 19.5% in other studies (23, mainly older studies).

12. Results – Recovery percentage In the 28 studies with at least 10 year follow-up the recovery percentage was in average 18.9% and in studies with shorter follow-up it was 15.6%. Recovery percentages were larger (p=0.03) in the 10 samples from Asia, Africa and South America (24.4%) than in studies from Europe and North America (15.7%, 40 samples).

13. Results – Recovery percentage So far 12 studies have reported recovery percentages by sex In 9 studies men have higher percentage and in 3 women When pooled recovery percentages do not differ – men 19.1% and women 18.4%

14. recovery percentage 0510152025303540455055 Combined Agra (WHO) Chandigarh (rural, WHO) Opjorsmoen 1988 Chennai (WHO) Moscow (WHO) Ogawa et al. 1987 Cali (WHO) Dixon and Innes 1966 Holmboe and Astrup 1957 Fallik and Liron 1976 Ciompi 1980 Errera 1957 Henisz 1966 Huber et al. 1980 Rajotte and Denber 1963 Vazquez-Barquero et al. 1999 Christensen 1974 Silverman 1941 Nottingham (WHO) Guttmann et al. 1939 Achte 1967a Achte 1967b Angst and Preisig 1995 Stenberg 1948 Langfeldt 1937 Robinson et al. 2004 Bland and Orn 1978 Helgason 1990 Walsh et al. 1991 Modestin et al. 2003 Prague (WHO) Beijing (WHO) Sofia (WHO) Mannheim (WHO) Obembe et al. 1995 Nyman and Jonsson 1983 Gottlieb 1940 DeLisi et al. 1998 Auslander and Jeste 2004 Rupp and Fletcher 1940 McGlashan 1984 Selten et al. 2007 Nagasaki (WHO) Dublin (WHO) Eitinger et al. 1958 Myers and Witmer 1937 Lauronen et al. 2005 Harrow et al. 1997 Hong Kong (WHO) Pillmann and Marneros 2005 17.4% (95% CI 15.0-19.9%) 51.9% 37.0% 36.6% 36.4% 32.4% 31.8% 31.1% 29.0% 27.7% 26.6% 25.9% 24.7% 24.0% 23.0% 21.0% 20.7% 20.4% 19.7% 18.8% 18.6% 18.4% 17.1% 17.0% 16.4% 16.3% 15.9% 14.0% 12.9% 12.5% 12.1% 10.0% 9.1% 9.0% 8.0% 7.7% 6.4% 6.0% 5.8% 5.0% 4.8% 4.4% 3.4% 2.8% 0.0%

15. Discussion First systematic review and meta-analysis on the topic Large differences between studies The proportion of patients meeting recovery criteria appears lower in Western studies and studies using DSM diagnostics system

16. Discussion Despite several studies on outcomes, this systematic review has identified a relative paucity of primary data about recovery (taking into account both clinical and functional dimensions) in schizophrenia. Various conceptual and methodological pitfalls cause challenges when studying this topic. Thus, more accurate reporting of multidimensional recovery is needed!

17. Discussion In the future we should focus on: –larger samples, general population samples –longer follow-ups –multi-dimensional assessment of outcomes –general definition for recovery and good outcome! –efforts in tracking the loss-to follow-up cases

18. Discussion In the future we aim to analyze results of all published recovery studies, with special reference to diagnosis (schizophrenia vs. schizoaffective vs. schizophreniform), different follow-up times and criteria for recovery. We hope other researchers to contact us if they know schizophrenia studies reporting recovery as defined here. (jouko.miettunen@oulu.fi and erika.jaaskelainen@oulu.fi)

19. Research group Department of Psychiatry, University of Oulu, Finland: Erika Jääskeläinen, MD, PhD Johanna Heikkinen, MA Matti Isohanni, MD, PhD Academy of Finland, Finland: Jouko Miettunen, PhD Juha Veijola, MD, PhD Queensland Centre for Mental Health Research, Australia: John McGrath, MD, PhD Sukanta Saha, MSc This study has been supported by the Academy of Finland (grant #120 479 )