Course and Prognosis of Schizophrenia.ppt

Course and Prognosis of Schizophrenia

1. COURSE AND PROGNOSIS Schizophrenia-II 20 October 2015 LT COL VS CHAUHAN 1

2. COURSE AND PROGNOSIS Introduction Pre-Neuroleptic Era Post-Neuroleptic Era WHO Sponsored Studies Indian (ICMR Project) Studies Recent Studies and Advancement Developing Vs Developed Countries Outcome in various domains/ Provinces Course & Outcome of Schizophrenia Subtypes Impact of Antipsychotics on Course and Outcome Factors Affecting Course and Prognosis in Schizophrenia 20 October 2015 2

3. INTRODUCTION Course : “Description of the mode and speed of evolution and progression of the disease .” OR “ P athways or trajectory of a disorder” (Ref: New OTP , 2009) Outcome ( end-result or consequence) : “The net result of the clinical and functional description at the end point of observation” (Ref: New OTP , 2009) Prognosis (Greek prognostikos - knowledge beforehand) : A prediction or forecast of the probable course, duration of illness, and outcome. (Campbell’s Psychiatric Dictionary, 8 th Edition) 20 October 2015 3

4. INTRODUCTION What is the need to study course & outcome of a disease? To inform about prognosis. To subtype or sub-classify a disease. To develop etiological hypothesis . To test the diagnostic validity . To construct and revise a prognostic model. To highlight individual, social, cultural, environmental and illness specific contributions to the outcome. 20 October 2015 4

5. INTRODUCTION How course and outcome of a disease is studied: - Prospective cohort studies Randomized control trials Longitudinal follow-up studies Retrospective follow back studies Cross sectional case control designs Admission and discharge rates Observations by treating doctors Each design has its own shortcomings 20 October 2015 5

6. INTRODUCTION Methodological heterogeneity: - Schizophrenia Variation in population. Variation in diagnostic criteria. Variation in the length of illness before starting F/U. Variation in the length of F/U. Variability of attrition rates. Variation in definitions to assess outcome. Variation in long term management of schizophrenia. Still the amount of work done is encouraging. ( Ref: CTP p 1484 – 1485, Tables) 20 October 2015 6

7. PRE-NEUROLEPTIC ERA Emil Kraepelin – Dementia Praecox Equated the course and prognosis with dementia Progressively deteriorating downhill course (‘ Mental weakness’ ). Only 12.5 % of patients did enjoy better outcome ( Permanent cure ) Eugen Bleuler - Schizophrenia Recognized the heterogeneity in the course. Still maintained - that the overall prognosis was grim. Both of them worked on institutionalized patients . Results showed Prognostic pessimism. 20 October 2015 7

8. PRE-NEUROLEPTIC ERA Study by Manfred Bleuler (1942-1965) 100 male and 108 female (Total – 208) patients hospitalized between 1942 and 1943. Diagnosed as schizophrenia by Eugen Bleuler’s criteria. Follow up period of 23 years Studied the onset, course and outcome of the patients and suggested 3 types of courses: - Simple course without remissions —with acute onset or with chronic onset (almost unnoticed over many months or years) Undulating (episodic) course with identifiable separate illness periods of at least 1 week’s duration and times of remission Atypical course 20 October 2015 8

9. PRE-NEUROLEPTIC ERA Study by Manfred Bleuler (1942-1965) contd. Outcomes : constant condition maintained for over 5 years Recovery (full employment, reassumed social roles, and no psychotic symptoms except for some eccentricity or symptom residues) End state S evere (with indifference to surroundings, practical incapability to communicate verbally, and requirement of constant care) M oderately/mild (less impaired but not recovered ) 20 October 2015 9

10. PRE-NEUROLEPTIC ERA Study by Manfred Bleuler (1942-1965) contd. Simple course- 38% Undulating course- 58% Atypical course- 4% Severe end state was identified in 34% of the patients with a simple course and 16% of those with an undulating course. Moderate/Mild end state in 3 6% patients. Recovery in 0% versus 37% of the patients Rule of 1/3 rd : 1/3 rd with chronic & deteriorating course, 1/3 rd recovery & 1/3 rd with intermediate course. 20 October 2015 10

11. PRE-NEUROLEPTIC ERA Study in three countries (Natural History/Never Rx) Scotland (Geddes, J.R and Kendell , R.E. - 1995) India ( Padmawati , R., Rajkumar , S., and Srinivasan , T.N. 1998) China ( Ran,M ., Xiang, M., Huang, M. et all – 2001) Results – Not much different from the outcome in Rx pt. Swedish study 70 patients admitted in 1925 Did not receive any neuroleptics Final outcome Profound deterioration in 43% Intermediate in 24% Good in 33 % ( Ref: New OTP, 2009) 20 October 2015 11

12. PRE-NEUROLEPTIC ERA Meta-analysis of 320 outcome studies (1895-1992) Total of 51,800 subjects. Overall, 40% of patient improved after an average length of follow-up 5.6 years (35.4 % to 49.5%) . A secular trend towards better outcomes with every successive decade had been present since 1895. Significant improvement during the period 1956-1985 compared to 1895-1955, clearly related to introduction of neuroleptics. cont … 20 October 2015 12

13. PRE-NEUROLEPTIC ERA 20 October 2015 13 Meta-analysis of 320 outcome studies (1895-1992) These observations suggest that a transition to a less deteriorating course had occurred even prior to the introduction of neuroleptics. Factors explaining this shift:- Improvement in general care Gradual better understanding Progressive change in attitude Progressive change in hospital regime ( Ref: New OTP, 2009 )

14. POST-NEUROLEPTIC ERTA 20 October 2015 14 Murphy and Raman (1971 ) (Ref: CTP, 9 TH ed ) 12 year follow up study in Mauritius Study population – Ethnic African and Indian Carried out between 1956 and 1968. The following types of courses were identified Course pattern Percentage Continuous total disability 21% Continuous partial disability/several episodes of non-functioning 15% Single episode of non-functioning 5% No clear episode during the course 59%

15. POST-NEUROLEPTIC ERTA 20 October 2015 15 Murphy and Raman (1971) contd. The clinical status of the patients at the end of 12 years ( outcome ) was also assessed. Clinical status/Outcome Percentage Still in hospitalized 16% Probably psychotic, partially or wholly dependent 19% Patient dependent, but no signs of psychosis 64% Patient independent, moderate symptoms Patient independent, no symptoms

16. POST-NEUROLEPTIC ERTA 20 October 2015 16 Murphy and Raman (1971) contd. Compared the outcome with study by Brown et al (1966) The overall outcome for ethnic Africans and Indians of Mauritius was more favorable than the European patients of Brown et al Patient in Mauritius had fewer relapses Spent less time in psychotic episodes in the follow up period Prognostic Optimism Brown et al (1966) Suggested that only 34% patients have favorable outcome rest have poor/intermediate outcomes

17. POST-NEUROLEPTIC ERTA 20 October 2015 17 Kulhara and Wig (1978 ) (Chandigarh cohort) 5 year follow up of treatment seeking population (North India) Used Schneider’s criteria for diagnosis 174 patients included in the study Only 100 (~58%) could be assessed again Course of the illness No disturbance 29% Improving 16% Episodic course 23% Continuous illness 32% Overall outcome Best 45% Worst 32%

18. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 18 Three studies sponsored by WHO International Pilot Study of Schizophrenia (IPSS) Determinants of Outcome of Severe Mental Disorder ( DOSMeD ) Assessment & Reduction of Psychiatric Disability ( RAPyD ) A fourth study coordinated by WHO International Study of Schizophrenia ( ISoS )

19. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 19 International Pilot Study of Schizophrenia (IPSS) Primary aim was to assess feasibility of an international follow up study on Schizophrenia. Initiated by WHO in 1965 and completed in 1972. Done in 3 phases (Baseline, 2 and 5 years follow up). Involved 9 FRCs (Nine countries) including Agra (India ). Use of standardized instruments for diagnosis and follow up ( PSE, f/u Psychiatric history schedule, f/u Social description schedule, f/u Diagnostic assessment schedule). Original cohort – 1202 Patient characteristics Age 15-44 years Mental illness for <5 years

20. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 20 Course of IPSS cohorts at various centers Center % with full remission % with continuous illness 2 years 5 years 2 years 5 years Aarhus 6 6 50 40 Agra 51 42 20 10 Cali 19 11 26 21 Ibadan 58 33 7 10 London 23 5 30 14 Moscow 7 6 18 21 Prague 17 9 30 23 Washington 21 17 47 23 Taipei 27 - 27 -

21. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 21 Major findings of IPSS 2 - year follow up (909 reviewed) Agra, Cali and Ibadan had more asymptomatic patients than Aarhus, London and Washington. Also , the former centers had more patients in the category of best course as compared to the latter. 5 -year follow up (807 reviewed ) Clinical and social outcomes were significantly better for patients in Agra and Ibadan than for those in centers in developed countries. Agra had the highest percentage ( 42% ) with best outcome and least ( 10% ) with worst outcome.

22. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 22 Major findings of IPSS (Cont.) Great variability in the course and outcome of F20. Outcome of the illness not as bleak as was expected. Centers in developing countries had better course and outcome. Culture has an important impact on schizophrenia Social variables have greater predictive importance Acuteness of onset – most significant predictors Better social outcome despite worse clinical outcome in Cali – good family support ?

23. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 23 Determinants of Outcome of Severe Mental Disorders ( DOSMeD ) Primary aim was to estimate the incidence of F20 in different cultures and provide definite evidence about the course and outcome of schizophrenia in different cultures. Carried out at 12 centers in 10 countries India had 2 centers- Agra & Chandigarh ( 02 FRC – CHU & CHR) Assessment at baseline and at 1 & 2 years follow up. 1379 patients were recruited 1014 (74%) could be evaluated during follow up. Patient characteristics 15-54 years First episode, never treated patients

24. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 24 DOSMeD - Findings Acute onset had a good pattern of course in both developing and developed countries . Insidious onset with good premorbid adjustment & younger age predicted a better course in developing countries but not in the case of developed countries. Difference between developing and developed countries in terms of onset and course Mode of onset/Course Developing countries Developed countries Acute/ Mild Course 51.4%/ 56% 29.5%/ 39% Insidious/ Severe Course 28.4%/ 24% 52.1%/ 40%

25. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 25 DOSMeD – Findings (Cont.) Various courses patterns were identified Single episode followed by complete remission Single episode followed by incomplete remission Single episode followed by one or more non-psychotic episodes with complete remission in b/w Single episode followed by one or more non-psychotic episodes with incomplete remission in b/w Two or more psychotic episodes with complete remission in b/w Two or more psychotic episodes with incomplete remission in b/w Continuous psychotic illness Continuous non-psychotic illness Information inadequate

26. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 26 DOSMeD – Findings (Cont .) Differences in course of illness across countries Most patients in developing countries had episodic course They spent less time in psychotic episodes Less impaired social and occupational functioning Tolerance of odd behavior by family members Greater support from joint families and community Lower influence of the medical model Lower expressed emotions Pattern of Course Developing countries Developed countries Single episode, full remission 37% 15.5% Single episode, partial remission 24.6%% 43.5% Multiple episode, full remission 25.7% 21.3% Continuous illness 11.1% 17.4%

27. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 27 International study of Schizophrenia ( ISoS ) Reassessment/ follow up study of all three earlier WHO sponsored studies at 15 and 25 years. ( DOSMeD & RAPyD / 15 – IPSS/ 25 ) Total 18 FRC/Cohort from 14 countries. 14 incidence cohorts – 12 from DOSMeD and RAPyD and 2 invited cohorts, one from Hong Kong and one from Madras – total of 1171 cases 04 prevalence cohorts – 3 from IPSS and 01 invited from Beijing – total of 462 cases Total of 1633 (1171+462) subjects included in the study , traced about 75% cases. All diagnosis were made according to ICD- 10 criteria.

28. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 28 Long term outcome in patient cohort assessed in ISoS . Outcome Variable Percentage of patients Incidence cohorts (N=1171), 15 year f/u Prevalence cohorts (N=462), 25 year f/u Recovered at follow up ( Bleuler’s criteria) 48.1 53.5 Free of active psychotic symptoms in past two years 42.8 40.8 Working most of the time in past two years 56.8 73.9 GAF – S >60 54.0 56.7 (Ref: New OTP, 2009)

29. POST-NEUROLEPTIC ERTA (WHO) 20 October 2015 29 Conclusions – ISoS Global outcomes at 15 & 25 years were favorable for >50% patients. Best predictor - Total time spent experiencing psychotic symptoms in the first 2 years following onset of illness. Early therapeutic interventions ( window of opportunity ) reduces DUP, leading to better outcome. Short term course - strongly predicted long term outcome. Outcome is better in developing countries than developed. Premorbid signs and symptoms suggestive of poor social adjustment, indicates poor long-term outcome. Unexpected findings : Type of onset did not play an independent role in prognosis/outcome.

30. INDIAN STUDY-ICMR PROJECT 20 October 2015 30 ICMR Project Also known as SOFACOS – 1981 to 1988 Three centers – Lucknow in North India, Chennai and Vellore in South India – 2 year f/u study Patients a ttending psychiatric clinic with illness of less than 2 years duration. Original Cohort - 386 ; 96 patients were recruited in Chennai center, 207 in Lucknow & 83 in Vellore Follow up – 321 patients – 174 (L), 83 (C), 64 (V) Ref:- Indian Council of Medical Research, Report on the multicenter study of factors affecting course and outcome of schizophrenia. New Delhi, ICMR, 1988 .

31. INDIAN STUDY-ICMR PROJECT 20 October 2015 31 ICMR Project - Findings About 66 % had a overall good outcome ( 45% very favorable and 26% favorable). About 40 % showed good occupational adjustment, 34% showed good social outcome. Variables associated with overall good outcome Short duration of illness. R egular drug compliance. N o schizoid premorbid traits. A bsence of economic difficulties. I ncrease in socio-economic levels. L ack of dangerous/risk taking behavior New and interesting findings emerged - socio-cultural factors – patients not perceived as dangerous by others, non – avoidance of patients by others, RB , and increase in religious activity – Good outcome.

32. INDIAN STUDY-ICMR PROJECT 20 October 2015 32 The Madras Longitudinal Study - Thara et al 10 (1994) and 20 (2004) year follow up of ICMR Madras cohort. 76 & 61 of original cohort (96) patients could be assessed. In the 20-year period, more than 80% of the original cohort experienced relapses. Findings at 10 year: - Good pattern of course in 67% of cases, the commonest pattern was - Recurrent episode with / without complete remission Nearly 60% of the cohort was able to hold onto a job at the end of 10 years. Significant decline in positive symptoms without a concurrent rise in negative symptoms. Clinical outcome was good in nearly 75% of the patients with almost all symptoms showing a steep decline at the end of 10 years As opposed to most studies, being a male and older age of onset predicted bad prognosis . (More exposed to stressful life events)

33. INDIAN STUDY-ICMR PROJECT 20 October 2015 33 The Madras Longitudinal Study - Thara et al Findings at 20 year: - 5 subjects each ( 5/61) had best and worst outcome. High employment of over 75 % among the men at end of 20 years. Morality rate was much higher (10% in 10 years and 17% in 20 years) as compared to the rates from developed countries. About 50% deaths were from suicide. Clinical and social outcome still was distinctly superior to that observed in the developed countries. Number of relapses occurring between 1 to 10 year did not differ significantly from those occurring between 10 to 20 year

34. DEVELOPING VS. DEVELOPED COUNTRIES 20 October 2015 34 Consistent finding in cross-cultural and Indian studies is that, developing countries have a higher proportion (50-60%) with a good outcome and lower percentage with a worst outcome as compared to developed countries at 2-year and 5-year follow up. ( Murphi & Raman, 1971; IPSS, 1973; DOSMeD , 1978; Eaton & Thara , 1992; Kulhara et al, 2001) Why/ How societies and cultures shape the process of illness? Another consistent finding in the long-term f/u (15 years) is that the pattern of course at 2 years predicted the course and outcome at long –term follow up across cultures/ countries. (Harrison et al., 1996, Thara et al., 2004) Little evidence from low-income countries that clearly demonstrates the beneficial influence of socio-cultural factors. Finding of better outcomes in developing countries needs re-examination. ( Patel et al, 2006)

35. DEVELOPING VS. DEVELOPED COUNTRIES 20 October 2015 35 Methodological limitations of the Cross-cultural studies Significant cross-cultural variation in the incidence of schizophrenia or cultural differences in subtypes of the disorder. Measures of course and outcome may have reflected differences in socioeconomic environments. Much higher attrition rates in the developing countries. Some centers recruited patients at variable periods of time. Chances of misdiagnosis in developing countries eg inclusion of affective disorders of transient psychotic disorders. Lack of evidence on the specific socio-cultural factors which apparently contribute to the better outcomes.

36. KEY POINTS – WHO/ INDIAN STUDIES 20 October 2015 36 Course and outcome of schizophrenia is highly variable and outcome appears to be better in developing countries. Progressive deterioration seems to be less common rather the illness remains stable or improves with time. Up to one third of the patients show complete recovery. About one third may have some residual symptoms. About 3/4 th of the patients are clinically stable after prolonged follow up. Only about 10-15% of patients have continuous psychotic symptoms. Rapid onset of deterioration occurs in 1-4% only.

37. RECENT STUDIES 20 October 2015 37 Harrow et al (2005) Sample derived from the Chicago Follow up Study ( Carone et al, 1991) Subjects included 64 patients with schizophrenia, 81 other patients and 117 non-psychotic control patients P atients followed up for 15 years Major findings Only 10% patients were in recovery at 2 years and 19% at 15 years 41% of the patients with schizophrenia had experienced 1 or more periods of recovery at some point during the 15 years 25–35% of the patients with schizophrenia had chronic course with persistent symptoms

38. RECENT STUDIES 20 October 2015 38 25 studies were meta- analysed regarding the effect of family interventions in schizophrenia treatment. Relapse rate measured either by worsening of symptoms or re-hospitalization within one year. Result of the meta-analysis was that the relapse rate can be reduced by 20 percent if relatives of schizophrenia patients are included in the treatment. The Effect of Family Interventions on Relapse and Re-hospitalization in Schizophrenia: A Meta-Analysis Gabi Pitschel-Walz ,Stefan Leucht , Josef Bäuml , Werner Kissling , Rolf R . Engel ( Volume 2 Issue 1, January 2004, pp. 78-94)

39. RECENT STUDIES 20 October 2015 39 Schizophrenia is a chronic and often debilitating disorder in which stage/duration of illness appears to influence course, outcome, prognosis and treatment response. A sample of 121 patients were randomized in a double fashion to 24 weeks (placebo = 62; NAC = 59). Duration of the illness at baseline was grouped into < 10 years, 10–20  years and > 20  years The effect of illness duration on response to treatment with NAC was explored. Progress in Neuro -Psychopharmacology and Biological Psychiatry, Volume 57, March 2015, p 69-75 Towards stage specific treatments: Effects of duration of illness on therapeutic response to adjunctive treatment with N-acetyl cysteine in schizophrenia Marta Rapado -Castro,  Michael Berk ,   Kamalesh Venugopal , Ashley I. Bush,   Seetal Dodd,  Olivia M. Dean

40. RECENT STUDIES 20 October 2015 40 A significant interaction between duration of the illness and response to treatment with NAC was consistently found for positive symptoms and functional outcome , but not for negative or general symptoms or for side effect related outcomes. More the duration of illness, better the results . Results suggest a potential advantage of adjunctive NAC over placebo on functioning and positive symptoms reduction in those patients with chronic schizophrenia. Progress in Neuro -Psychopharmacology and Biological Psychiatry, Volume 57, March 2015, p 69-75 Towards stage specific treatments: Effects of duration of illness on therapeutic response to adjunctive treatment with N-acetyl cysteine in schizophrenia Marta Rapado -Castro,  Michael Berk ,   Kamalesh Venugopal , Ashley I. Bush,   Seetal Dodd,  Olivia M. Dean

41. OUTCOME IN VARIOUS DOMAINS 20 October 2015 41 Functional Outcome Employment in Schizophrenia is a reflection of symptomatic and social recovery Western studies identified occupational functioning as a major problem especially in male schizophrenics (Sartorius et al, 1987) 40% had no occupational impairment while 18% had severe occupational impairments (ICMR study, 1988) At 13 year follow up only 37% were employed over the previous 2 years while 44% were receiving disability benefits. (Mason et al, 1995)

42. OUTCOME IN VARIOUS DOMAINS 20 October 2015 42 Employment level at baseline was found to be 78% Over 10 year follow up employment status remained between 63-73% N ature of jobs was mainly unskilled labor and industrial work At the end of 10 years 68% had service/trade occupations and 16% had clerical/administrative work. The occupational outcome was significantly associated with the clinical, social and marital outcome but not with pre-morbid occupational status. ( Srinivasan and Thara , 1997)

43. OUTCOME IN VARIOUS DOMAINS 20 October 2015 43 Social outcome Favorable outcome in 34% with no social impairment while only 12% had severe social impairment ( ICMR study, 1988 ) 14% had no social impairment, 36% had mild, 39% had moderate and 11% severe impairment ( Leon et al, 1989) A pproximately one third of subjects had good, one third had intermediate and one third had poor global social adjustment. Social disability was best predicted by longer duration of illness, worse social adjustment levels at inclusion and lower educational level. ( Menezes et al, 1997) Severity of positive symptoms and more than two inpatient episodes in the early course of illness predicted social disabilities. ( Lay et al, 2000)

44. OUTCOME IN VARIOUS DOMAINS 20 October 2015 44 Outcome of marriage Schizophrenia has been associated with a low marital rate, especially in men. M ore men remaining single & more women facing broken marriages. Duration of illness, auditory hallucinations and depression at intake, unemployment and economic slide during the course of illness and a relapsing course of illness were all related to marital outcome. ( Srinivasan and Thara , 1997) W omen with broken marriages reported ‘hostile and very negative attitudes’ of other family members, held no jobs, and received no support from their husbands ( Thara et al, 2003)

45. COURSE OF SCHIZOPHRENIA SUBTYPES 20 October 2015 45 Studies mainly differentiate between paranoid, hebephrenic and undifferentiated subtypes: - Paranoid Acute onset, remittent course with lesser disability. Overall better response to treatment and hence better prognosis. Hebephrenic Insidious onset, poor prognosis Inadequate response to treatment Undifferentiated Intermediate position

46. COURSE OF SCHIZOPHRENIA SUBTYPES 20 October 2015 46 Paranoid patients fared better in functional status assessment, hebephrenic worst. Paranoid more likely to get married prior to onset of illness due to relatively later onset. Illness onset more often acute for paranoid patients. IQ of paranoid patients was highest. Undifferentiated F20 appeared to be an extension of PMP. Hebephrenic and Undifferentiated F20 more likely to be continuously ill. High family loading of psychosis in Hebephrenic patients. ( Kendler , 1984; Fenton & McGlashan , 1991)

47. IMPACT OF ANTIPSYCHOTICS 20 October 2015 47 The impact of antipsychotics can be in terms of: - Symptomatic improvement A ll APs (FGAs and SGAs) have been shown to be efficacious in reducing positive symptoms and global psychopathology Negative symptoms T end to increase over the course of the disease SGAs have been found to be effective Mood symptoms Depressive symptoms are associated with poorer outcome SGAs have been shown to possess antidepressant effects

48. IMPACT OF ANTIPSYCHOTICS 20 October 2015 48 Relapse prevention ~50% patients experience multiple relapses Several studies have reported reduction in relapse rates with continuous APs (Dixon et al, 1995) If taken off APs 45-50% patients relapse within 6 months, 65-70% at 1 year and 80-90% at 2 years Cognitive function Clozapine and R isperidone have been found to improve cognitive functioning in patients. (Green et al, 1997) Morbidity/Mortality High rates of suicides in schizophrenic patients. SGAs esp. Clozapine have been found to reduce the risk due to antidepressant and anti-aggression effects. (Meltzer, 1998)

49. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 49 Variables explored as possible predictors Socio-demographic characteristics Characteristics of PMP and pre-onset functioning Family h/o psychiatric disorders History of past psychiatric episodes and treatment Clinical characteristics of the illness Comorbid illnesses including substance use Treatment related factors Neuro -anatomical findings and neuro -cognitive functioning

50. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 50 Socio-demographic characteristics Late age of onset, female sex, higher educational status are good prognostic factors Single, divorced or widowed bad prognostic factors Higher SES, good occupational functioning (Harrison et al, 1996 ) Clinical characteristics of the illness Acute onset, Paranoid/catatonic type, predominantly positive symptoms inc. paranoid delusions and presence of an obvious precipitating factor are associated with better prognosis. Affective flattening, presence of psychotic assault/violence and religious or sexual delusions in females indicators of poor prognosis ( Thara et al, 96)

51. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 51 Comorbid illnesses Mood disorder symptoms especially depressive symptoms are associated with better prognosis D epressive symptoms at a later stage of illness also predicted a poor psychosocial situation ( Salokangas , 2003) Presence of hypomanic symptoms predicts less time in psychotic phase ( Thara et al, 1994) Presence of substance use especially alcohol and cannabis use has been associated with poor prognosis ( Henquet et al, 2005) Presence of comorbid neurological illness or neurological signs and symptoms favors a bad prognosis Past and Family history Lesser number of episodes predicts a better prognosis Family h/o schizophrenia and mood disorder are poor and good prognositc factors respectively

52. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 52 Treatment related factors Good response to treatment, good compliance to medications and early treatment initiation are considered good prognostic factors Long duration of untreated psychosis (DUP) has been associated with worse prognosis (Clarke et al, 2006 ) Early detection and intervention services should concentrate on shortening the shortest DUPs, since the effect of DUP on recovery is greatest in the early stages of illness. Socio-cultural factors Belonging to a developing country?? Good social support network and more number of social contacts predicts better outcome High familial Expressed emotions is associated with more chances of relapses in follow up ( DOSMeD ; Butzlaff and Hooley, 1998)

53. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 53 Characteristics of PMP and pre-onset functioning Good scholastic achievements and good premorbid social, sexual and work history predicts better outcome H /o birth trauma, delayed development, cognitive difficulties during adolescence, suspicious/impulsive behavior, childhood asociality and withdrawn/autistic behavior associated with poor outcome Other factors Neuro -cognitive deficits esp. verbal memory and processing speed and attention predict poor outcome ( Milev et al, 2005) Neuro -anatomical findings like enlarged ventricles and volumetric changes Service delivery and service utilization. Effect of integrated interventions on outcome.

54. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 54 Short term predictors Predict the relapse of psychotic symptoms after remission Stressful life events Withdrawal of antipsychotic medications Cannabis use Good initial response to neuroleptics Positive response to placebo Previous multiple relapses

55. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 55 Patterns and stages of course indicating good outcome Single episode followed by complete remission Single episode followed by incomplete remission Two or more episodes with complete remission in b/w Two or more episodes with incomplete remission in b/w Continuous unremitting psychotic illness New OTP: - Bleuler , M. 1972, Compi , L. 1980, Huber et al 1980

56. PROGNOSIS IN SCHIZOPHRENIA 20 October 2015 56 Factors that predict a poor outcome Male gender Insidious onset Negative symptoms Younger onset of age Hebephrenic sub-type Enlarged lateral ventricles Previous psychiatric history Long duration of untreated psychosis Single , separated, widowed, or divorced Abnormal premorbid personality Poor psychosexual adjustment Poor treatment compliance Poor work record Substance Abuse Social isolation

57. CONCLUSIONS 20 October 2015 57 Fundamental question still unanswered How much heterogeneity in course and outcome of in schiz is due to: - Methodological difference in studies. Actual etiological subtypes or separate pathophysiological trajectories within the disorder itself. Its interaction with environmental factors/ socio-cultural factors (Black Box) Majority of the available studies have focused primarily on Socio-demographic , Psychopathologic & other behavioral variables as predictors of outcome (e.g. gender differences, acute vs insidious onset, schizophrenia subtypes, family history, premorbid functioning etc )

58. CONCLUSIONS 20 October 2015 58 However, schizophrenia as currently understood from a bio-psychosocial perspective, is largely having Neuro -biological roots ( in addition to the psychosocial factors ). But surprisingly, relatively little attention has been given to the assessment of the predictive potential of pharmacologic and Neuro -biologic variables , which may provide more direct evidence.

59. CONCLUSIONS 20 October 2015 59 Schizophrenia has highly variable course and outcome. Course is episodic or gradually improving in most cases especially after 8-10 years. Outcome is also more favorable than initially thought with high possibility of functional recovery. Several factors including onset, clinical characteristics, DUP, treatment and pre-morbid functioning determine the final outcome. Dynamic process with multiple interacting biological and psychosocial determinants. Prediction of the course and outcome possible with a reasonable certainty.

60. FUTURE DIRECTIONS 20 October 2015 60 Developing a better understanding of the sources of cross-cultural, historical, and individual differences in outcome and applying these findings to the improvement of current clinical and rehabilitative efforts. Focus intensively on the prodromal and early phases of the course of disorder in a concerted effort to prevent disability and chronicity. To study complicated interplay of disease processes, treatment effects, and social and cultural contexts . The impact of integrated psychosocial and pharmacological interventions on long term course to be determined .

61. References 20 October 2015 61 Shorter Oxford text book of Psychiatry; 6 th edition New Oxford Text Book of Psychiatry, Second Edition, 2009. Comprehensive Text Book of Schizophrenia 9 th edition (Kaplan & Sadock’s ) Jeffrey A. Lieberman, T. Scott Stroup, and Diana O. Perkins; Textbook of Schizophrenia 1 st edition. Gordana Rubessa,Lea Gudelj and Natalija Kubinska - Etiology of Schizophrenia and therapeutic options;Psychiatric Danubina 2011;Vol 23 No.3,pp308-15. Kaplan & Sadock’s Synopsis of Psychiatry, 10 th edition. Philip cowen,Paul Harrison, Tom Burns;Shorter Oxford Textbook of Psychiatry, 6 th edition. Madeline H. Meier, et. all. Neuropsychological Decline in Schizophrenia From the Premorbid to the Post-onset Period: Evidence From a Population Representative Longitudinal Study; American Journal of Psychiatry 2014, 171:91-101. Dr Paul Bebbington et al;. Childhood Sexual Abuse, Strong Predictor of Future Psychosis. British Journal of Psychiatry ; Jul 2011 . The Maudsley series; Schizophrenia, The final frontier: A Festschrift for Robin M. Murray .

62. A great deal of work still remains to be done !!! 20 October 2015 62