1. Treatment of Schizophrenia THE DEBATE OF THE YEAR! EFFICACY vs. TOLERABILITY: WHICH TRUMPS? POINT- COUNTERPOINT

2. OCCUPATIONAL SETTING 1.RESEARCH 2.CLINICAL 3.OTHER

3. DURATION OF CAREER 1.LESS THAN 10 YEARS 2.10-20 YEARS 3.MORE THAN 20 YEARS

4. USE OF ANTIPSYCHOTICS IN YOUR SETTING 1.VERY COMMON 2.OCCASIONAL 3.RARE

5. DO YOU BELIEVE THAT.. 1EFFICACY TRUMPS 2SAFETY TRUMPS 3BOTH ARE EQUALLY IMPORTANT

6. WHAT IN YOUR OPINION IS THE MAJOR EFFICACY ISSUE? 1.Positive Symptoms 2.Negative Symptoms 3.Cogntive Symptoms 4.Mood symptoms

7. What, in your opinion, is the most serious tolerability issue? 1.Sedation 2.Dizziness 3.Dry mouth 4.Sexual dysfunction

8. What, in your opinion, is the most serious safety issue? 1.Movement disorders 2.Weight gain/obesity 3.Diabetes 4.QTc prolongation

9. WE HAVE A CURE, BUT….. If a new drug can CURE schizophrenia but causes 5% incidence of mortality would you use the drug 1.Yes 2.No 3.I’ll ask my mother

10. In an off label use of antipsychotics, which is the worst in your opinion? 1.Above approved dose 2.Combination of 2 Antipsychotics 3.Use in an unapproved indication

11. Do pharmaceutical companies minimize the side effects of their drug? 1.Always 2.Often 3.Sometimes 4.Never

12. Options for Antipsychotic Therapies Prior to Antipsychotics Conventional or Typical Antipsychotics (First Generation) Atypical Antipsychotics (Second Generation) 19521980s2000s Chlorpromazine Haloperidol Fluphenazine Thioridazine Loxapine Perphenazine Trifluoperazine Thiothixene Molindone Clozapine Aripiprazole Paliperidone Iloperidone Asenapine Lurasidone 1960s1990s Risperidone Olanzapine Quetiapine Ziprasidone

13. Antipsychotic Practice Major changes in antipsychotic practice over the past decade. New, atypical antipsychotics now comprise vast majority of antipsychotic prescriptions –considered more effective than typical antipsychotics –thought to have fewer side-effects –much more costly than typicals

14. Questions about Utility of Atypical Agents Relative utility of the atypicals has recently been questioned: – Are they really more effective? – Are their side-effects (eg., obesity, diabetes) not a significant concern? – Are they all essentially similar? Before the Typical-Atypical Controversy: –WHAT MATTERS –EFFICACY versus TOLERABILITY

15. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? POINT- COUNTERPOINT DEBATE WHERE DO YOU STAND?Efficacy Side effects

16. POINT-COUNTERPOINT LET THE DEBATE BEGIN……

17. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? FGA’S ARE EQUIVALENT IN EFFICACY TO SGA’S EFFICACY IS SIMILAR ACROSS ALL SGA’S EFFICACY MATTERS MORE THAN SIDE EFFECTS IN FIRST EPISODE SCHIZOPHRENIA EPS/TD WEIGHT GAIN/HYPERLIPIDEMIA/HYPERGLYCEMIA HYPERPROLACTINEMIA/SEXUAL DYSFUNCTION ANTICHOLINERGIC/DRY MOUTH/CONSTIPATION SOMNOLENCE/SEDATION

18. HOW DO WE KNOW? EVIDENCE-BASED MEDICINE Preponderance of data about antipsychotic effectiveness in schizophrenia – Large-scale clinical trials – Meta-analyses

19. Series of Effectiveness Studies Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) - USA Cost Utility of the Latest Antipsychotics in Severe Schizophrenia (CUtLASS) - UK Treatment of Early-Onset Schizophrenia (TEOSS) - USA European Union First Episode Schizophrenia Trial (EUFEST) - Europe

20. CATIE-Schizophrenia Trial: All- Cause Discontinuation Time to discontinuation for any cause (mo) Lieberman JA et al. N Engl J Med. 2005;353:1209-1223. Olanzapine (n=330) Perphenazine (n=257) Risperidone (n=333) Quetiapine (n=329) Ziprasidone (n=183) 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 1.0 0369121518 Proportion of patients without event

21. Second-Generation Antipsychotics Compared to Haloperidol Clozapine: More effective than Hal., Low-potency FGA Amisulpride: More effective than Hal., Low-potency FGA Risperidone: More effective than Hal., Low-potency FGA Olanzapine: More effective than Hal., Low-potency FGA Zotepine: NOT more effective Sertindole: NOT more effective Aripiprazole: NOT more effective Quetiapine: NOT more effective Ziprasidone: NOT more effective Favor s SGA Favors FGA Leucht et al.,. Lancet. 2009(January);373:31-41

22. Findings of Meta-analysis Controlling for major biases NO DIFFERENCE IN EFFICACY BETWEEN NON-CLOZAPINE ATYPICALS –Dosing bias (non-equivalent doses) –Differences in comparator haloperidol dose –Differences in study population (more refractory for later agents) Tandon and Nasrallah, Archives of General Psychiatry 2006; 63: 935-937

23. Does Evidence-Based Medicine Matter? AUDIENCE DISCUSSION

24. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? FGA’S ARE EQUIVALENT IN EFFICACY TO SGA’S

25. FGA’S ARE EQUIVALENT IN EFFICACY TO SGA’S: AUDIENCE DISCUSSION

26. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? EFFICACY IS SIMILAR ACROSS ALL SGA’S

27. AUDIENCE DISCUSSION

28. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? EFFICACY MATTERS MORE THAN SIDE EFFECTS IN FIRST EPISODE

29. EFFICACY MATTERS MORE THAN SIDE EFFECTS IN FIRST EPISODE AUDIENCE DISCUSSION

30. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? EPS/TD

31. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? WEIGHT GAIN HYPERLIPIDEMIA HYPERGLYCEMIA

32. EPS/TD VS METABOLICS

33. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? HYPERPROLACTINEMIA/ SEXUAL DYSFUNCTION

34. AUDIENCE DISCUSSION

35. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? ANTICHOLINERGIC/DRY MOUTH/CONSTIPATION

36. AUDIENCE DISCUSSION

37. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? SOMNOLENCE/SEDATION

38. AUDIENCE DISCUSSION

39. EFFICACY vs. TOLERABILITY: WHICH TRUMPS? A POINT- COUNTERPOINT DEBATE WHERE DO YOU STAND NOW ? Efficacy Side effects

40. DO YOU BELIEVE THAT ? 1EFFICACY TRUMPS 2SAFETY TRUMPS 3BOTH ARE EQUALLY IMPORTANT

41. GENERAL DISCUSSION AND FINAL QUESTIONS