1. Treating Schizophrenia in Low And Middle Income (LAMI) Countries: Challenges and opportunities Treating Schizophrenia in Low And Middle Income (LAMI) Countries: Challenges and opportunities Prof. Saeed Farooq, Department of Psychiatry, Post Graduate Medical Institute Lady Reading Hospital, Peshawar, PAKISTAN.

2.  The prevalence of psychotic disorders in LAMI.  System of care for Chronic disorders  Staging in Schizophrenia

3.  Duration of Untreated Psychosis (DUP) in LAMI, its relationship with the income status and outcome of Schizophrenia  Early Intervention for Schizophrenia

4.  Supervised Treatment in Outpatients for Schizophrenia (STOPS): The concept and Randomised Controlled Trial  Research and Clinical Guidelines Development

5. Objectives  Critically examine the concept of ‘natural’ course of Schizophrenia  To introduce the concept of Clinical staging in Schizophrenia

6. Objectives  Discuss the Duration of Untreated Psychosis (DUP), its correlates and consequences in context of Low and Middle Income Countries  To identify the opportunities for research and clinical practice development.

7. The challenge at Health systems level  Continuity of care and maintaining long term medication.

8. Challenge at individual level  Compliance/adherence with treatment

9. Present level of untreated, partially treated cases  Unknown but must be close to 90%

10. Chronic conditions – Present system of care

12. Adherence with Treatment in Schizophrenia  About 59% of patients may fail to adhere to their treatment.  CATIE Trial :1493 patients with follow up for 18 months  74 percent of patients discontinued the medication before 18 months of the study period.

13. Adherence with Treatment in Schizophrenia  With the exception of Olanzapine ( discontinued by 64 percent ) atypical antipsychotic did not fare better than the typical antipsychotic ( 82 percent for quetiapine, 74 percent in risperidone, and 79 percent of those assigned to ziprasidone could not continue the drug for trial period versus 75 percent of those assigned to Perphenazine)

14. Non adherence to drugs in schizophrenia  Lack of insight  Cultural belief  Affects mostly poor people who can not afford treatment  Chronic condition & needs continuity of care  Schizophrenia has stigma associated with it and relatives and patients are reluctant to have treatment or seek help for this disorder..

15.  What is the most important determinant of outcome in Schizophrenia

16. Duration of Untreated Psychosis

17. Poor outcome for untreated schizophrenia Poor outcome for untreated schizophrenia Co-morbid substance abuse Suicide Suicide Increased treatment resistance Increased treatment resistance Impairment in cognitive and neuropsychological functions Offending behavior Offending behavior Vocational failure Overall poor outcome. Each relapse in schizophrenia results in additional costs and miseries for the patient

19. Clinical staging for Schizophrenia?? (McGorry et al; World Psychiatry 2008;7:148-156)  Stage 1: Ultra-high risk: Pre psychosis stage.  Stage 2: Early detection and treatment of first episode psychosis.

20. Clinical staging for Schizophrenia?? (McGorry et al; World Psychiatry 2008;7:148-156)  Stage 3: The critical period of the first 5 years after diagnosis:

21. Clinical staging for Schizophrenia?? (McGorry et al; World Psychiatry 2008;7:148-156)  period of maximum risk for disengagement, relapse and suicide, as well as coinciding with the major developmental challenges of forming a stable identity, peer network, vocational training and intimate relationships.  Treatment goals in this phase are the management of effective medication and the use of effective psychosocial interventions to minimize the development of disability and maximize functioning.

22. Gap of 1-10 days in medication  The medication status is also the strongest predictor of relapse; discontinuation of medication increases the relapse risk five folds 9. Even a gap as small as 1-10 days in medication over one year period has been found to be significantly associated with increased risk of hospitalization with an odds ratio of 1.98

23. The prevalence  The large populations in developing countries have much high prevalence of chronic mental disorders.  One state in India has amore people suffering from Schizophrenia than those living in whole of Americas 2.

24. 45% < 45.  The age structure of LAMI countries  In Pakistan, 45% of population is below 45 years of ag  The prevalence of those with first episode psychosis will be much higher than those in the industrialized countries.

25. Where is the evidence for LAMI?  The “natural course” of Schizophrenia in developing countries

26. “Natural’’ course of schizophrenia  “Our original expectancy was that the natural course of schizophrenia would be favourable in a rural area of China. In every instance, however, the results also supported the conclusion that the natural course of schizophrenia, especially clinical outcome, was poor - even in a Chinese rural area”.

27. Present level of “ Natural” course  “One disappointment is that the proportion of patients receiving no treatment at all has increased (30.6% in this study), rather than decreased (20.3% in 1982)”, M. S., Xiang, M. Z., Huang, M. S., et al (2001) Natural course of schizophrenia: two-year follow-up study in a rural Chinese community. British Journal of Psychiatry, 178, 154 -158.

28. “ Natural” course  Unknown but must be close to 90% of untreated and partially treated.

30. The relationship between the duration of untreated psychosis and outcome in low-and-middle income countries: A systematic review and meta analysis Saeed Farooq Matthew Large,Olav Nielssen, Waquas Waheed. Schizophrenia Research.(109);2009. 15-23 Significant negative correlation between DUP and improvement in symptoms after treatment (r=−0.290, 95% CI=−0.483 to −0.069, z=−2.559, p<0.011). The value remained unchanged using both random effect model and fixed effect model.

31. The relationship between the duration of untreated psychosis and outcome in low- and-middle income countries: A systematic review and meta analysis  Prolonged DUP was also associated with increased levels of disability.  Longer DUP associated with a higher mortality ? mortality ?

32. Cohen et al. Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World? Schizophrenia Bulletin,2008. 34, 229–244. Cohen et al. Questioning an Axiom: Better Prognosis for Schizophrenia in the Developing World? Schizophrenia Bulletin,2008. 34, 229–244.

33. Relationship between Gross Domestic Product and Duration of Untreated Psychosis in low and middle-income countries Matthew Large, Saeed Farooq, Olav Nielssen and Tim Slade The British Journal of Psychiatry (2008) 193, 272–278. doi: 10.1192/bjp.bp.107.041863  The average mean DUP in studies from LAMI countries was 125.0 weeks compared with 63.4 weeks in studies from high income countries (P=0.012). Within the studies from LAMI countries, mean DUP fell by 6 weeks for every $1000 of GDP purchasing power parity.

34. Relationship between gross domestic product and duration of untreated psychosis in low and middle-income countries  There appears to be an inverse relationship between income and DUP in LAMI countries. The cost of treatment is an impediment to care and subsidised antipsychotic medication would improve the access to treatment and the outcome of psychotic illness in LAMI countries.

35. The Challenge for Mental Health Professionals  Change the Culture of Care in Chronic mental illness,  Strive for the “Unnatural “ course of illness

36. Conclusion  Natural Course of Schizophrenia in LAMI is not benign  DUP is related with poor outcome and income  Clinical staging in schizophrenia may be possible  We must aim to change the ‘natural’ course.

37. Thank you – break now!!

38. DOTS IS COST EFFECTIVE  The World Bank considers DOTS to be one of the most cost effective health interventions. DOTS is more cost effective than self-administered treatment.

39. What DOTS can offer for chronic conditions like schizophrenia  Regular Follow up  Regular free supply of drugs  Continuity of care  Education for the relatives  Reduced Stigma?

40. RATIONALE  Patients suffering from Schizophrenia need supervision and it is possible.

41. RATIONALE: We owe it to the family  Our family has largely ‘subsidized’ the treatment of schizophrenia for the society and the state at large by providing the social, psychological, residential and occupational support which constitute the major proportion of the cost of treatment

42. OR PERHAPS!! STOPS (Supervised Treatment in Out Patients for Schizophrenia, Short course ) ? STOPS (Supervised Treatment in Out Patients for Schizophrenia, Short course ) ?  Short course: At least two years

43. How STOPS work?  Referral  Evaluation  Schizophrenic from district Peshawar  consent for a relative to supervise his/her treatment  Key Care Supervisor (KCS) who agrees to supervise the treatment of the patient

44. Essential components of DOTS  A regular uninterrupted provision of FREE DRUGS TO THE ACTIVE CASES  Standardized treatment regimen of six to eight months of  DRUG THERAPY UNDER SUPERVISION

46. How STOPS works?...... cont Provision of drugs free of cost for one month Provision of drugs free of cost for one month Involving family in overall management plan Involving family in overall management plan  Family education regarding  Nature of disorder and its likely outcome.  Supervision of treatment (monitoring the drug compliance by observing and recording the correct medication)  Early relapse signs and its management by the family

47. How DOTSS work?.......cont  The patients collect supply of the drugs every month and relatives have to satisfy the staff that patient is taking drugs regularly.  If patient is unable to come and misses an appointment, we will contact him her at home and persuade to continue the treatment.  If patient has a relapse despite being on treatment, he will either be admitted in psychiatry unit or will be seen more frequently

48. Review After One Month  Assess psychopathology  Rate for improvement/ worsening G.A.F.  Check for compliance ( check tablets/relatives report Stable Continue the drug according to the phase of treatment Not stable Continue the drug according to the phase of treatment  Relapse  No improvement  Worsening of symptoms  Doubtful compliance Review by the consultant psychiatrist Stable &discharge Admit Continue out-patient assessment weekly till patient is stable

49. 1.Patient presents with psychotic features Assessment by consultant psychiatrist 2.Diagnosis of schizophrenia or schizo effective disorder according to ICD-10 criteria (Appendix –A) Meets the criteria for inclusion in programme. (Appendix – B), included in STOPS. Meets the criteria for inclusion in programme. (Appendix – B), included in STOPS. Assessment for severity of disease, compliance and G.A.F (see Appendix-C) Consent obtained for supervision (Appendix-D)  Key Care Giver identified  KCG trained in drug monitoring and supervision ( Appendix – E) Provide one month of supply of drugs. Provide one month of supply of drugs.

50. The Pilot Project  Started in Sept 2004  Patients enrolled=92  Male 70  Female 22  No follow up after 1 st assessment 13  Mean age 34.84 SD=10.58

51.  GAF at baseline= 60.4% patients have GFA less than 50 Mean GAFat baseline=41.46 sd=28.84 Mean GAFat baseline=41.46 sd=28.84  GAF at six months follow up= 75.7% have GAF more than 50  Mean GAF after six months=61.43 sd=23.76

54. A SOLUTION?  An intervention based on principles of DOTS?

55. WHAT IS DOTS?  Tuberculosis can spread the disease to 10-15 persons on average  Partially treated cases  Multiple Drug Resistant Tuberculosis (MDRTB)  Failure to receive treatment TB epidemic TB epidemic

56. DOTS IS COST EFFECTIVE  The World Bank considers DOTS to be one of the most cost effective health interventions. DOTS is more cost effective than self-administered treatment.

57. RATIONALE: We owe it to the family  The family in developing countries has largely ‘subsidized’ the treatment of schizophrenia for the society and the state at large by providing the social, psychological, residential and occupational support which constitute the major proportion of the cost of treatment

58. Short course : At least two years  The Critical period in care of schizophrenia  Compliance intervention work optimally for upto 18 months.  No developing country can afford to provide indefinite free treatment  Measureable

59. How STOPS works.......cont  The patients collect supply of the drugs every month and relatives have to satisfy the staff that patient is taking drugs regularly.  If patient is unable to come and misses an appointment, we will contact him her at home and persuade to continue the treatment.  If patient has a relapse despite being on treatment, he will either be admitted in psychiatry unit or will be seen more frequently

60. Follow up visits  Assess psychopathology  Rate for improvement/ worsening G.A.F.  Check for compliance ( check tablets/relatives report)

61.  The primary outcome was to compare the effectiveness of STOPS in improving the adherence with a regimen of standard doses of antipsychotic medication in patients suffering from Schizophrenia and Schizoaffective Disorders compared to Treatment As Usual (TAU)

62.  50% of the patients with Schizophrenia adhere to medication over a period of one year 5, 7  We expected the rate of medication adherence to be 75% in the intervention group.

63.  The power calculation showed that with 55 patients in each arm of the trial, and assuming a drop out rate of nearly 20%, there was a 90% chance of detecting a 25% difference in treatment adherence at the 0.01% level of significance, should a such difference exist.

64.  The randomization was done using computer generated numbers.  The random allocation of the patients for each group was enclosed in series of opaque envelopes which were sealed and numbered sequentially.

65.  These allocations were placed away from the site of assessment. After assessment and satisfying the inclusion criteria, the independent staff in the administration office was asked to open the sealed envelope and reveal the treatment arm for each patient.

67.  Fifty five patients recruited in each arm.  95 (86.36%) patients completed the study; 49 in STOPS and 46 TAU group.  The mean age of patients in STOPS group was 29 (SD= 8.1) which did not differ significantly from the TAU group (mean 30, SD= 8.5, P<.699).  The baseline sociodemographic and clinical variables were not significantly different in two groups  Both groups had long duration of illness (67.36 months SD=59 in STOPS Vs 83.8 months in TAU; SD=91 P<.485).

68. Adherence with medication  The rates of adherence with medication improved significantly in the intervention arm. At one year follow up, 37 (67.3%) patients in STOPS group had complete adherence with medication compared to 25 (45.5%) in the TAU group (P<.02).

69. PANSS Scores  Analysis of Covariance (ANCOVA):  PANSS Total Scores, (time effect, Wilks’ lambda=0.90, F(3,105)=3.54, P=0.017, and between the subject effect, F=9.0, df=1, P=0.003).  PANSS Positive Symptoms (time effect, Wilks’ lambda=0.91, F(3,102)=3.31, P=0.011, and between the subject effect, F=5.9, df=1, P=0.003). 

70. PANSS  General PANSS scores, (time effect was significant, Wilks’ lambda=0.92, F(3,101)=2.57, P=0.058, and for between the subject effect, F=7.7, df=1, P=0.007)  PANSS Negative symptoms, Wilks’ lambda=0.94, F (3,102) =1.2, P=0.303, nor between the subject effect, F=2.11, df=1, P=0.149

72. GAF Scores  Using ANCOVA, GAF scores were found to have significantly improved over time in treatment group as compared with the treatment as usual group ( Wilks’ lambda=0.90, F (3,106) =3.66, P=0.036, and for between the subject effect, F=7.3, df=1, P=0.008).

74. Conclusion  The two challenges:  Compliance/adherence with treatment Supervised Treatment  Continuity of care and maintaining long term medication Public Health Intervention on the model of DOTS with free drug provision under STOPS like programme for at least two years in First Episode Psychosis.