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El CATIE EN LA PRACTICA El SOHO HOY

. Parte 1: Destacar algunos conceptos de SOHO y CATIE y compararlos con nuestras observaciones en la clnica diariaParte 2: Presentar una nueva conceptualizacin de los antipsicticos atpicos, ms acorde con los nuevos descubrimientos de mecanismos y modos de accin y su aplicabilida

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El CATIE EN LA PRACTICA El SOHO HOY

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    1. El CATIE EN LA PRACTICA El SOHO HOY Qu sabemos? Qu aprendimos?

    2. Parte 1: Destacar algunos conceptos de SOHO y CATIE y compararlos con nuestras observaciones en la clnica diaria Parte 2: Presentar una nueva conceptualizacin de los antipsicticos atpicos, ms acorde con los nuevos descubrimientos de mecanismos y modos de accin y su aplicabilidad clnica

    3. Parte 1 Destacar algunos conceptos CATIE y SOHO y compararlos con nuestra clnica diaria

    4. Efectividad Key Points: The concept of treatment effectiveness considers the impact of the medication on controlling the various symptoms of the illness, as well as the safety and tolerability of the medication.1 Despite the established need for a patient to continue on their prescribed treatment, many patients with schizophrenia fail to adhere to their medication. Interruption of antipsychotic treatment in patients with schizophrenia, through treatment discontinuation or inconsistent adherence, is associated with increases in rates of relapse, hospitalization, and treatment costs.2-5 Background: Poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude. Adherence to long-term therapy for chronic illnesses in developing countries averages 50%.6 References: 1. Swartz MS, Perkins DO, Stroup TS, et al. Assessing clinical and functional outcomes in the clinical antipsychotic trials of intervention effectiveness (CATIE) schizophrenia trial. Schizophr Bull 2003;29(1):33-43. 2. Herz MI, et al. Intermittent vs. maintenance medication in schizophrenia: two-year results. Arch Gen Psychiatry 1991;48:333-339. 3. Svarstad BL, Shireman TI, Sweeney JK. Using drug claims data to assess the relationship of medication adherence with hospitalization and costs. Psychiatr Serv 2001;52:805-811. 4. Ascher-Svanum H, Zhu B, Faries D, et al. A comparison of olanzapine and risperidone on the risk of psychiatric hospitalization in the naturalistic treatment of patients with schizophrenia. Ann Gen Hosp Psychiatry 2004;3(1):11. 5. Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry 2004;161(4):692-699. 6. Haynes RB. Interventions for helping patients to follow prescriptions for medications. Cochrane Database of Systematic Reviews 2001;1. 7. Lehman AF, Lieberman JA, Dixon LB, et al. APA practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry 2004;161(suppl 2):1-56.Key Points: The concept of treatment effectiveness considers the impact of the medication on controlling the various symptoms of the illness, as well as the safety and tolerability of the medication.1 Despite the established need for a patient to continue on their prescribed treatment, many patients with schizophrenia fail to adhere to their medication. Interruption of antipsychotic treatment in patients with schizophrenia, through treatment discontinuation or inconsistent adherence, is associated with increases in rates of relapse, hospitalization, and treatment costs.2-5 Background: Poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude. Adherence to long-term therapy for chronic illnesses in developing countries averages 50%.6 References: 1. Swartz MS, Perkins DO, Stroup TS, et al. Assessing clinical and functional outcomes in the clinical antipsychotic trials of intervention effectiveness (CATIE) schizophrenia trial. Schizophr Bull 2003;29(1):33-43. 2. Herz MI, et al. Intermittent vs. maintenance medication in schizophrenia: two-year results. Arch Gen Psychiatry 1991;48:333-339. 3. Svarstad BL, Shireman TI, Sweeney JK. Using drug claims data to assess the relationship of medication adherence with hospitalization and costs. Psychiatr Serv 2001;52:805-811. 4. Ascher-Svanum H, Zhu B, Faries D, et al. A comparison of olanzapine and risperidone on the risk of psychiatric hospitalization in the naturalistic treatment of patients with schizophrenia. Ann Gen Hosp Psychiatry 2004;3(1):11. 5. Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry 2004;161(4):692-699. 6. Haynes RB. Interventions for helping patients to follow prescriptions for medications. Cochrane Database of Systematic Reviews 2001;1. 7. Lehman AF, Lieberman JA, Dixon LB, et al. APA practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry 2004;161(suppl 2):1-56.

    5. ESTUDIOS OBSERVACIONALES Eficacia Discontinuacin por falta de respuesta

    6. SOHO: ESTUDIO OBSEVACIONAL DE ESQUIZOFRENIA A 2 AOS.

    7. SOHO EVALUACIN A 2 AOS. Section 7 Page 282 (started on mono analysis) By definition, patients that had an overall CGI-S of 1 or 2 at baseline were excluded from the analysis of responders. Following 24 months of treatment, there was a greater proportion of responders in the olanzapine group compared with the quetiapine, risperidone or haloperidol treatment groups Comparison adjusted for baseline differences The likelihood of response to treatment in the olanzapine group was significantly greater compared with quetiapine, risperidone or haloperidol (p<0.001; odds ratio comparisons) The likelihood of response to treatment in the risperidone group was not significantly greater compared with quetiapine (p=0.071; odds ratio comparison). There was no significant difference for odds ratio comparisons between the haloperidol and quetiapine groups, however; for the comparison of risperidone with haloperidol the p-value =0.094 not significant at the p<0.001 level set for ICR study. Section 7 Page 282 (started on mono analysis) By definition, patients that had an overall CGI-S of 1 or 2 at baseline were excluded from the analysis of responders. Following 24 months of treatment, there was a greater proportion of responders in the olanzapine group compared with the quetiapine, risperidone or haloperidol treatment groups Comparison adjusted for baseline differences The likelihood of response to treatment in the olanzapine group was significantly greater compared with quetiapine, risperidone or haloperidol (p<0.001; odds ratio comparisons) The likelihood of response to treatment in the risperidone group was not significantly greater compared with quetiapine (p=0.071; odds ratio comparison). There was no significant difference for odds ratio comparisons between the haloperidol and quetiapine groups, however; for the comparison of risperidone with haloperidol the p-value =0.094 not significant at the p<0.001 level set for ICR study.

    8. SOHO TIEMPO PARA CAMBIO DESDE EL TRATAMIENTO INICIAL

    10. CATIE Diseo Estudio

    11. CATIE I TIEMPO DE DICONTINUACIN POR CUALQUIER CAUSA. The Kaplan Meier median is the time by which half of the patients have discontinued The hazard ratio for olanzapine vs. quetiapine is 0.63: at any given time, patients on olanzapine are 63% less likely to discontinue treatment compared to patients on quetiapine. The Hazard ratio is from Cox proportional hazards regression, and is the ratio of the probability of discontinuing the phase at any timepoint for one treatment group vs. another.The Kaplan Meier median is the time by which half of the patients have discontinued The hazard ratio for olanzapine vs. quetiapine is 0.63: at any given time, patients on olanzapine are 63% less likely to discontinue treatment compared to patients on quetiapine. The Hazard ratio is from Cox proportional hazards regression, and is the ratio of the probability of discontinuing the phase at any timepoint for one treatment group vs. another.

    12. CATIE I TIEMPO DE DISCONTINUACIN POR FALTA DE EFICACIA. The Kaplan Meier 25th %ile is the time by which 25% of the patients have discontinued. The median can not be estimated due to low event rates. The hazard ratio for olanzapine vs. quetiapine is 0.41: at any given time, patients on olanzapine are 41% less likely to discontinue treatment for lack of efficacy compared to patients on quetiapine. The Hazard ratio is from Cox proportional hazards regression, and is the ratio of the probability of discontinuing the phase at any timepoint for one treatment group vs. another.The Kaplan Meier 25th %ile is the time by which 25% of the patients have discontinued. The median can not be estimated due to low event rates. The hazard ratio for olanzapine vs. quetiapine is 0.41: at any given time, patients on olanzapine are 41% less likely to discontinue treatment for lack of efficacy compared to patients on quetiapine. The Hazard ratio is from Cox proportional hazards regression, and is the ratio of the probability of discontinuing the phase at any timepoint for one treatment group vs. another.

    13. CATIE FASE 2

    14. CATIE II TIEMPO DE DISCONTINUACIN POR CUALQUIER CAUSA

    15. CATIE II (I) TIEMPO DISCONTINUACIN POR FALTA DE EFICACIA

    16. CATIE II (II) TIEMPO DISCONTINUACIN POR CUALQUIER CAUSA

    17. CLINICA DIARIA Tenemos en nuestros pacientes un 74% de discontinuacin?

    18. CATIE vs CLINICA DIARIA No se incluyeron pacientes de primer episodio No se combinaron drogas Dosis son suficientes? Tpicos evaluadas son vlidos?

    19. CATIE vs CLINICA DIARIA No se incluyeron pacientes de primer episodio No se combinaron drogas Dosis son suficientes? Tpicos evaluadas son vlidos?

    20. PRIMER EPISODIO - Si es menor de seis meses: psicosis reactiva breve o trastorno esquizofreniforme DSM IV - Sintomatologa florida Schooler 86, Lieberman 95 - Generalmente hay prodromos de duracin variable Lieberman 95 - El grado de respuesta teraputica es mayor y ms rpida. Loebel 92 - Requieren menos dosis antipsicticos Meltzer 92 - Son ms sensibles a reacciones de extrapiramidalismo. Lieberman 95 Keks 96

    21. RESPUESTA AL TRATAMIENTO DEL PRIMER EPISODIO Remisin completa: 73% Remisin parcial: 16% Sin remisin: 11%

    22. CATIE vs CLINICA DIARIA No se incluyeron pacientes de primer episodio No se combinaron drogas antipsicticas Dosis son suficientes? Tpicos evaluadas son vlidos?

    23. CATIE I: MEDICACIONES CONCOMITANTES.

    24. CLINICA DIARIA Qu porcentaje de nuestros pacientes esquizofrnicos estn solo con monoterapia de antipsicticos atpicos ?

    25. CLINICA DIARIA Asociacin de antipsicticos Atpico ms tpico en bajas dosis Atpico ms atpico Asociacin antipsictico ms antirrecurrencial Asociacin antipsictico ms antidepresivos Asociacin antipsictico ms BDZ

    26. CATIE vs CLINICA DIARIA No se incluyeron pacientes de primer episodio No se combinaron drogas Dosis son suficientes? Tpicos evaluadas son vlidos?

    27. SOHO DOSIS SEGN GRUPO Section 7 Page 398 (started on mono) Olanzapine: Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp.409-410 (no depot available) Quetiapine : Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp. 411-412, Stats (no depot available) Risperidone : Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp. 413-415 (oral and depot) Haloperidol : Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp. 404-405 (oral and depot) Daily dose of each treatment is shown. Mean is the average dose, mode is the most commonly prescribed dose (or most common value). In situations where there was more than one mode, no mode is reported. Results include oral and depot. The median dose of olanzapine and haloperidol remained at 10.0 mg/day throughout the 24 months. The median dose of quetiapine increased from 200.0 mg/day at baseline to 300.0 mg/day at 3 months, and 400 at 24 months. The median dose of risperidone also increased during treatment from 3.0 mg/day at baseline to 4.0 mg/day at 3, 6, 12 and 24 months. Note: The dose summary at each time point is based on patients remaining on the same drug, therefore the patient numbers reduce over time.Section 7 Page 398 (started on mono) Olanzapine: Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp.409-410 (no depot available) Quetiapine : Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp. 411-412, Stats (no depot available) Risperidone : Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp. 413-415 (oral and depot) Haloperidol : Table 7.9.2 Dose (mg/day) of antipsychotics prescribed at each visit pp. 404-405 (oral and depot) Daily dose of each treatment is shown. Mean is the average dose, mode is the most commonly prescribed dose (or most common value). In situations where there was more than one mode, no mode is reported. Results include oral and depot. The median dose of olanzapine and haloperidol remained at 10.0 mg/day throughout the 24 months. The median dose of quetiapine increased from 200.0 mg/day at baseline to 300.0 mg/day at 3 months, and 400 at 24 months. The median dose of risperidone also increased during treatment from 3.0 mg/day at baseline to 4.0 mg/day at 3, 6, 12 and 24 months. Note: The dose summary at each time point is based on patients remaining on the same drug, therefore the patient numbers reduce over time.

    28. CATIE II (I) DOSIS EN FASE Intent-to-treat (ITT) patients received at least one dose of study medication. Dose and efficacy assessments are reported for the ITT patients. Safety assessments are reported for all randomized patients.Intent-to-treat (ITT) patients received at least one dose of study medication. Dose and efficacy assessments are reported for the ITT patients. Safety assessments are reported for all randomized patients.

    29. CATIE II (II) RANDOMIZACION Y TRATAMIENTO Intent-to-treat (ITT) patients received at least one dose of study medication. Dose and efficacy assessments are reported for the ITT patients. Safety assessments are reported for all randomized patients.Intent-to-treat (ITT) patients received at least one dose of study medication. Dose and efficacy assessments are reported for the ITT patients. Safety assessments are reported for all randomized patients.

    30. CATIE II (III) RANDOMIZACIN Y TRATAMIENTO. Intent-to-treat (ITT) patients received at least one dose of study medication. Dose and efficacy assessments are reported for the ITT patients. Safety assessments are reported for all randomized patients.Intent-to-treat (ITT) patients received at least one dose of study medication. Dose and efficacy assessments are reported for the ITT patients. Safety assessments are reported for all randomized patients.

    31. CLINICA DIARIA Qu dosis son suficientes y habituales en la clnica?

    32. CATIE vs CLINICA DIARIA No se incluyeron pacientes de primer episodio No se combinaron drogas Dosis son suficientes? Tpicos evaluadas son vlidos?

    33. CLINICA DIARIA Perfenazina es igual a haloperidol? Dosis de haloperidol elejida por profesional en SOHO Dosis de perfenazina elejida por diseo de protocolo en CATIE

    34. Key Points: The concept of treatment effectiveness considers the impact of the medication on controlling the various symptoms of the illness, as well as the safety and tolerability of the medication.1 Despite the established need for a patient to continue on their prescribed treatment, many patients with schizophrenia fail to adhere to their medication. Interruption of antipsychotic treatment in patients with schizophrenia, through treatment discontinuation or inconsistent adherence, is associated with increases in rates of relapse, hospitalization, and treatment costs.2-5 Background: Poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude. Adherence to long-term therapy for chronic illnesses in developing countries averages 50%.6 References: 1. Swartz MS, Perkins DO, Stroup TS, et al. Assessing clinical and functional outcomes in the clinical antipsychotic trials of intervention effectiveness (CATIE) schizophrenia trial. Schizophr Bull 2003;29(1):33-43. 2. Herz MI, et al. Intermittent vs. maintenance medication in schizophrenia: two-year results. Arch Gen Psychiatry 1991;48:333-339. 3. Svarstad BL, Shireman TI, Sweeney JK. Using drug claims data to assess the relationship of medication adherence with hospitalization and costs. Psychiatr Serv 2001;52:805-811. 4. Ascher-Svanum H, Zhu B, Faries D, et al. A comparison of olanzapine and risperidone on the risk of psychiatric hospitalization in the naturalistic treatment of patients with schizophrenia. Ann Gen Hosp Psychiatry 2004;3(1):11. 5. Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry 2004;161(4):692-699. 6. Haynes RB. Interventions for helping patients to follow prescriptions for medications. Cochrane Database of Systematic Reviews 2001;1. 7. Lehman AF, Lieberman JA, Dixon LB, et al. APA practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry 2004;161(suppl 2):1-56.Key Points: The concept of treatment effectiveness considers the impact of the medication on controlling the various symptoms of the illness, as well as the safety and tolerability of the medication.1 Despite the established need for a patient to continue on their prescribed treatment, many patients with schizophrenia fail to adhere to their medication. Interruption of antipsychotic treatment in patients with schizophrenia, through treatment discontinuation or inconsistent adherence, is associated with increases in rates of relapse, hospitalization, and treatment costs.2-5 Background: Poor adherence to treatment of chronic diseases is a worldwide problem of striking magnitude. Adherence to long-term therapy for chronic illnesses in developing countries averages 50%.6 References: 1. Swartz MS, Perkins DO, Stroup TS, et al. Assessing clinical and functional outcomes in the clinical antipsychotic trials of intervention effectiveness (CATIE) schizophrenia trial. Schizophr Bull 2003;29(1):33-43. 2. Herz MI, et al. Intermittent vs. maintenance medication in schizophrenia: two-year results. Arch Gen Psychiatry 1991;48:333-339. 3. Svarstad BL, Shireman TI, Sweeney JK. Using drug claims data to assess the relationship of medication adherence with hospitalization and costs. Psychiatr Serv 2001;52:805-811. 4. Ascher-Svanum H, Zhu B, Faries D, et al. A comparison of olanzapine and risperidone on the risk of psychiatric hospitalization in the naturalistic treatment of patients with schizophrenia. Ann Gen Hosp Psychiatry 2004;3(1):11. 5. Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry 2004;161(4):692-699. 6. Haynes RB. Interventions for helping patients to follow prescriptions for medications. Cochrane Database of Systematic Reviews 2001;1. 7. Lehman AF, Lieberman JA, Dixon LB, et al. APA practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry 2004;161(suppl 2):1-56.

    35. ESTUDIOS OBSERVACIONALES Discontinuacin por intolerancia Efectos colaterales

    36. ESTUDIOS OBSERVACIONALES y CONTROLADOS Discontinuacin por intolerancia Efectos colaterales

    37. CATIE I TIEMPO DE DISCONTINUACIN POR INTOLERANCIA Kaplan Meier medians and 25th %ile can not be estimated due to low event rates The hazard ratio for risperidone vs. olanzapine is 0.62: at any given time, patients on risperidone are 62% less likely to discontinue treatment for intolerability compared to patients on olanzapine. This difference is not significant since the overall p-value was not less than 0.05. The Hazard ratio is from Cox proportional hazards regression, and is the ratio of the probability of discontinuing the phase at any timepoint for one treatment group vs. another.Kaplan Meier medians and 25th %ile can not be estimated due to low event rates The hazard ratio for risperidone vs. olanzapine is 0.62: at any given time, patients on risperidone are 62% less likely to discontinue treatment for intolerability compared to patients on olanzapine. This difference is not significant since the overall p-value was not less than 0.05. The Hazard ratio is from Cox proportional hazards regression, and is the ratio of the probability of discontinuing the phase at any timepoint for one treatment group vs. another.

    38. RAZONES DE DISCONTINUACIN POR INTOLERANCIA:. FYI: the percentages of patients discontinued for intolerability differ slightly between this slide and the previous one because this slide is based on all randomized patients, and the previous slide is limited to ITT patients who took at least one dose of study medication.FYI: the percentages of patients discontinued for intolerability differ slightly between this slide and the previous one because this slide is based on all randomized patients, and the previous slide is limited to ITT patients who took at least one dose of study medication.

    39. Discontinuacin por intolerancia Efectos colaterales

    40. CATIE EFECTOS ADVERSOS

    41. CATIE ESCALA DE MOVIMIENTOS ANORMALES

    42. CATIE: SIMPSON-ANGUS (SEP)

    43. CATIE BARNES AKATHISIA RATING SCALE

    44. CRITERIOS de EXCLUSIN Es esto un bias? En CATIE se excluyeron para perfenazina pacientes con antecedentes de SEP No se excluyeron para olanzapina o cloza antecedentes de desorden metablico No se excluyeron para risperidona antecedentes de SEP No se excluyeron para ziprasidona antecedentes de cardiopata.

    45. SOHO DISKINESIA TARDIA EN PAC. QUE MANTUVIERON TERAPIA INICIAL Section 8 Page 529 of 1166 Cumulative treatment emergent events from T1 to T6 This graph is a measure of TD that was not present at baseline and emerged during treatment within each treatment group. Treatment emergent TD was greatest in the haloperidol group. Olanzapine was significantly different to haloperidol and risperidone. Small patient numbers in the quetiapine group make it hard to draw statistical conclusions. Section 8 Page 529 of 1166 Cumulative treatment emergent events from T1 to T6 This graph is a measure of TD that was not present at baseline and emerged during treatment within each treatment group. Treatment emergent TD was greatest in the haloperidol group. Olanzapine was significantly different to haloperidol and risperidone. Small patient numbers in the quetiapine group make it hard to draw statistical conclusions.

    46. CLINICA DIARIA MOVIMIENTOS ANORMALES POR AP:

    47. PARKINSONISMO Parkinsonismo Motor EPS Distona Diskinesia tarda Parkinsonismo Cognitivo Pensamiento enlentecido y pobre Sentimiento de vaco Dificultades de concentracin

    48. PARKINSONISMO Parkinsonismo Social Falta de iniciativa Disminucin de las energas Pobreza de contactos sociales Parkinsonismo Emocional Indiferencia emocional Anhedonia Falta de placer en las actividades

    49. PROLACTINA (NG/ML) EN ENSAYOS CONTROLADOS CON OLANZAPINA

    50. LA PROLACTINA ES MS QUE UNA HORMONA DE MATERNAJE Funcin sexual y maternal Funcin en coping (afrontamiento) al stress Funcin metablica (hormona anablica) Funcin sobre SNC (crecimiento neuronal, sinaptognesis y poda dendrtica) Funcin sobre inmunomodulacin

    51. CLINICA DIARIA AUMENTO PROLACTINA POR AP:

    52. CLINICA DIARIA OTROS EFECTOS ADVERSOS ENDCRINOS POR AP. Disminucin de LH y FSH Osteoporosis Intolerancia a la glucosa Sndrome metablico

    53. SOHO: GANANCIA MAYOR A 7 % DEL PESO CORPORAL PREVIO. Section 7 Pages 1188-1192 (started on mono) Clinically significant weight gain is thought to be a gain >7% of the starting body weight. the proportion of patients in the olanzapine group gaining >7% of their starting body weight was higher when compared with the other groups.Section 7 Pages 1188-1192 (started on mono) Clinically significant weight gain is thought to be a gain >7% of the starting body weight. the proportion of patients in the olanzapine group gaining >7% of their starting body weight was higher when compared with the other groups.

    54. CATIE I: PROPORCIN DE SUJETOS QUE GANARON MS DEL 7 % DEL PESO CORPORAL.

    55. CATIE I: CAMBIOS DESDE BASAL HASTA 2 ENTREVISTAS POSTERIORES patients were instructed to fast, nonfasting results were not excluded Exposure-adjusted means are the estimated mean values that we would see at the average treatment duration across all groups (8.3 months). They are least squares means from an ANCOVA model adjusting for treatment duration.patients were instructed to fast, nonfasting results were not excluded Exposure-adjusted means are the estimated mean values that we would see at the average treatment duration across all groups (8.3 months). They are least squares means from an ANCOVA model adjusting for treatment duration.

    56. CAMBIO EN PESO CON ANTIPSICOTICOS.

    57. CAMBIO DE PESO EN LA ERA PREANTIPSICOTICA The taking of food fluctuates from complete refusal to the greatest voracity. The body weight usually falls at first, often to a considerable degree, even to extreme emaciation, in spite of the most abundant nourishment. Later, on the contrary, we see the weight not infrequently rise quickly in the most extraordinary way, so that patients in short time acquire an uncommonly well-nourished turgid appearance

    58. POR QU LOS PACIENTES GANAN PESO CON ANTIPSICTICOS?

    59. INTERVENCIONES CONDUCTUALES PARA LA PRDIDA DE PESO [Keywords] 530, Maguire, Justice, CME, Optima Q, Optima, 6/18/2001, neuroscience, schizophrenia, psychosis, Zyprexa, Olanzapine, critical, breakthroughs, psychiatric, treatment, redefining, standard, care, Lilly, Echo Swinford, Angela Sisson, choices, results , weight, change ### [Narration] Behavioral interventions in patients on atypical antipsychotics have been studied as to effectiveness. In a study by Wirshing et al (1), a stepwise approach was taken such that patients were subject to increasingly intensive interventions (self-weighing, food diary, nutrition consult, education, group support, exercise classes) depending on their ability to control their weight. ### [Narration] The maximum weight gained during therapy and final weight gain after interventions is depicted in this graph for different drugs. Only clozapine showed a sustained increase in weight unresponsive to intervention.### [Narration] It is important to note that these patients were not enrolled in one large, comparative trial but were rather enrolled in multiple controlled trials at Dr. Wirshing's site. Thus, they should be taken as pilot data but nonetheless suggest that behavioral interventions may be successful in moderating olanzapine-associated weight gain.### [Narration] Average Duration of Treatment:### [Narration] Clozapine, 27.2 wks### [Narration] Olanzapine, 73.1 wks### [Narration] Risperidone 25.8 wks### [Narration] Haloperidol, 24.7 wks### [Narration] Sertindole, 42.5 wks### [Narration] 1 "Novel Antipsychotics: Comparison of Weight Gain Liabilities" by Wirshing DA et al. J Clin Psych 1999; 60(6):358-3### [Keywords] 530, Maguire, Justice, CME, Optima Q, Optima, 6/18/2001, neuroscience, schizophrenia, psychosis, Zyprexa, Olanzapine, critical, breakthroughs, psychiatric, treatment, redefining, standard, care, Lilly, Echo Swinford, Angela Sisson, choices, results , weight, change ### [Narration] Behavioral interventions in patients on atypical antipsychotics have been studied as to effectiveness. In a study by Wirshing et al (1), a stepwise approach was taken such that patients were subject to increasingly intensive interventions (self-weighing, food diary, nutrition consult, education, group support, exercise classes) depending on their ability to control their weight. ### [Narration] The maximum weight gained during therapy and final weight gain after interventions is depicted in this graph for different drugs. Only clozapine showed a sustained increase in weight unresponsive to intervention.### [Narration] It is important to note that these patients were not enrolled in one large, comparative trial but were rather enrolled in multiple controlled trials at Dr. Wirshing's site. Thus, they should be taken as pilot data but nonetheless suggest that behavioral interventions may be successful in moderating olanzapine-associated weight gain.### [Narration] Average Duration of Treatment:### [Narration] Clozapine, 27.2 wks### [Narration] Olanzapine, 73.1 wks### [Narration] Risperidone 25.8 wks### [Narration] Haloperidol, 24.7 wks### [Narration] Sertindole, 42.5 wks### [Narration] 1 "Novel Antipsychotics: Comparison of Weight Gain Liabilities" by Wirshing DA et al. J Clin Psych 1999; 60(6):358-3###

    60. ESTRATEGIAS PARA PREVENIR AUMENTO DE PESO Estrgenos Metformina (Glucophage ) Sibutramina (Ipomex Aderan ) Fluoxetina (Prozac ) Amantadina (Symmetrel) Quetiapina (Seroquel) Topiramato (Topamax) Orlistat Antagonistas H2 ; Nizatadine (Axid) , Ranitidina (Taural) Cimetidina (Tagamet)

    61. CLINICA DIARIA AUMENTO DE PESO POR AP:

    62. CATIE I ELECTOCARDIOGRAMA Y CATARATAS

    63. CLINICA DIARIA RIESGO DE EVENTOS CARDIOLGICOS POR AP:

    64. EFECTOS ADVERSOS NEUROCOGNITIVOS Sedacin Confusin Deterioro de memoria Enlentecimiento psicomotor Delirium Descenso del umbral convulsivo

    65. CLINICA DIARIA RIESGO DE EVENTOS NEUROCOGNITIVO POR AP:

    66. CLINICA DIARIA RIESGO DE SIADH POR AP:

    67. RIESGO DE AUMENTO DE DESORDEN INMUNITARIO POR ANTIPSICTICOS

    68. Parte 2 Presentar una nueva conceptualizacin de los antipsicticos atpicos ms acorde con los nuevos conocimientos cientficos y desafios clnicos .

    69. Tamayo,J; Lpez-Mato,A; Tllez,J; Calil,HM; Fernndez,A Revista Latinoamericana de Psiquiatra, v.3, n.1, p. 5-36, 2003.

    70. AA Y FUNCIN RECEPTORIAL This slide is a simplistic way to discuss the differences between the antipsychotics from a mechanistic point of view. It is important to point out the broad receptor binding affinity of olanzapine and how this relates to improvement in a wide range of psychiatric symptoms.This slide is a simplistic way to discuss the differences between the antipsychotics from a mechanistic point of view. It is important to point out the broad receptor binding affinity of olanzapine and how this relates to improvement in a wide range of psychiatric symptoms.

    72. FARMACODINMIA DE AA

    73. ATIPICIDAD: PROPUESTAS EXISTENTES

    74. ATIPICIDAD: PROPUESTAS

    82. PORQU ES AMPLIO ESPECTRO? Mecanismo de accin ms all de la interaccin DA con perfil de afinidad por otros receptores: D1 (clozapina y olanzapina), 5-HT1A (clozapina y ziprasidona), 5-HT2C (sertindol, clozapina, olanzapina y ziprasidona), 5HT6 (clozapina, olanzapina y sertindol), 5HT7 (clozapina y risperidona), ?2 (risperidona), H1 (clozapina, olanzapina, risperidona y quetiapina) M4 (clozapina y olanzapina).

    84. SPECTRUM II Accin teraputica sobre algn otro trastorno psiquitrico como trastorno bipolar, trastornos depresivos, tratornos de personalidad, drogodependencia, trastorno obsesivo-compulsivo, enfermedad de Parkinson, demencias

    85. SPECTRUM III Efectividad en resocializacin (calidad de vida, funcionamiento global) Eficacia a largo plazo Eficacia en pacientes refractarios Seguridad con mnimos efectos extrapiramidales, hormonales y otros

    89. AA EFICACIA EN: ESQUIZOFRENIA TRASTORNO BIPOLAR TRASTORNO UNIPOLAR REFRACTARIO TRASTORNOS DE PERSONALIDAD TRASTORNO DE CONDUCTA DEMENCIAS TRASTORNOS DE ALIMENTACIN TRASTORNOS DE ANSIEDAD (TAG,PTSD) ??????????

    90. POR QU SEGUIR LLAMANDOLOS ANTIPSICTICOS? POR QU SEGUIR LLAMANDOLOS ATPICOS?

    91. QU ANTIPSICTICO ELEGIRA UN PSIQUITRA PARA L Y SUS FAMILIARES?

    92. LA MISMA MOLCULA NO ASEGURA EL MISMO MEDICAMENTO!!! Se analizaron distintas olanzapinas, algunas de ellas provienen de farmacias que las prepararon como recetas magistrales no parece muy magistral lo que les salio-. Y otras fueron tomadas del mercado por el breve periodo en que fueron comercializadas, como el caso de la olanzapina de Luar en Cordoba y la de Dosa. El ketolactam, la amida y el ketotiolactam son productos de degradacion de la olanzapina y el N-oxido es una impureza de sintesis. En rojo se destacan los valores mas fuera de especificaciones. Hay casos pateticos como el de la olanzapina que fabricaba la Farmacia Vasallo, no solamente tenia el 8% la la olanzapina que deberia tener, sino que ademas tenia 10 veces mas impurezas que el maximo admisible.Se analizaron distintas olanzapinas, algunas de ellas provienen de farmacias que las prepararon como recetas magistrales no parece muy magistral lo que les salio-. Y otras fueron tomadas del mercado por el breve periodo en que fueron comercializadas, como el caso de la olanzapina de Luar en Cordoba y la de Dosa. El ketolactam, la amida y el ketotiolactam son productos de degradacion de la olanzapina y el N-oxido es una impureza de sintesis. En rojo se destacan los valores mas fuera de especificaciones. Hay casos pateticos como el de la olanzapina que fabricaba la Farmacia Vasallo, no solamente tenia el 8% la la olanzapina que deberia tener, sino que ademas tenia 10 veces mas impurezas que el maximo admisible.

    93. DEGRADACIN DE UNA OLANZAPINA GENRICA EN UN ENSAYO DE ESTABILIDAD ACELERADA La velocidad de degradacion de la olanzapina de Biocrom actualmente en el mercado demuestra que solo 45 dias a 33C y 76% de humedad son suficientes para alcanzar el limite superior de impurezas admisible. La curva de degradacion muestra un perfil exponencial con un R casi perfecto.La velocidad de degradacion de la olanzapina de Biocrom actualmente en el mercado demuestra que solo 45 dias a 33C y 76% de humedad son suficientes para alcanzar el limite superior de impurezas admisible. La curva de degradacion muestra un perfil exponencial con un R casi perfecto.

    94. DIFERENTES FORMAS CRISTALINAS DE OLANZAPINA SE DISUELVEN DIFERENTEMENTE La olanzapina tiene varias formas de cristalizacion. Algunas son estables como la forma polimorfica 2 que presenta Zyprexa (y Midax) y otras forma son metaestables como la forma polimorfica 1 y 3. En Chile se vende Olivin que es una olanzapina que es una mezcla de polimorfos 1 y 3. Como claramente se ve la velocidad de disolucion, y por lo tanto los perfiles de absorcion son marcadamente diferentes de los de Zyprexa.La olanzapina tiene varias formas de cristalizacion. Algunas son estables como la forma polimorfica 2 que presenta Zyprexa (y Midax) y otras forma son metaestables como la forma polimorfica 1 y 3. En Chile se vende Olivin que es una olanzapina que es una mezcla de polimorfos 1 y 3. Como claramente se ve la velocidad de disolucion, y por lo tanto los perfiles de absorcion son marcadamente diferentes de los de Zyprexa.

    95. SI CREE QUE ELIGE LO MEJOR ELIJA LO SEGURO

    96. LA CLINICA ES SOBERANA.. Y MUCHO MS DIVERTIDA MUCHAS GRACIAS POR ATENDER...

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