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Problema de Salud AUGE N°75

Tratamiento de personas de 15 años y más con Trastorno Bipolar

Juicio del Panel y Evidencia

En personas con trastorno bipolar cursando episodio maníaco, el Ministerio de Salud SUGIERE utilizar antipsicóticos atípicos como monoterapia por sobre estabilizador del ánimo como monoterapia.
Comentarios del panel:
► La elección del tratamiento de la fase aguda debe considerar la eficacia y las reacciones adversas durante la futura fase mantención. La terapia específica debe ser individualizada, dependiendo de la severidad de la enfermedad, perfil de reacciones adversas y valores y preferencias de cada paciente.
► Pacientes más graves como psicóticos, hospitalizados, agitados, con riesgo suicida, entre otros, en los cuales la velocidad de respuesta es crítica, se beneficiarían en mayor medida del uso de antipsicóticos atípicos. En algunos de estos pacientes podría indicarse la combinación de antipsicóticos atípicos y estabilizadores del ánimo.
► Considerar el uso de litio en manías leves a moderadas en atención a su eficacia en el tratamiento de mantención.

El Panel de Expertos analizó y debatió cada uno de las preguntas de la “Tabla de la evidencia a la decisión”, considerando tanto la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes. Una vez consensuada la postura del panel respecto a las preguntas, emitieron un juicio seleccionando la opción de respuesta que mejor representaba la opinión del conjunto (destacada con color). Finalmente cuando el panel emitió su juicio sobre todas las preguntas, se emitió la recomendación.

A continuación se presenta la “Tabla de la evidencia a la decisión” con el resumen de los juicios, la evidencia de investigación evaluada, consideraciones adicionales y comentarios planteados por el panel.

 1.- ¿El problema es una prioridad?
No Probablemente no Probablemente sí Varía No lo sé

El problema ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad.

 2.- ¿Qué tan significativos son los efectos deseables anticipados?
Trivial Pequeño Moderado Grande Varía No lo sé

Pequeños: El equipo elaborador de la Guía estimó que los efectos deseables de «utilizar antipsicóticos atípicos como monoterapia» en comparación a «utilizar estabilizador del ánimo como monoterapia» son pequeños, considerando la evidencia, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud.
El equipo plantea que, desde su experiencia, en fase aguda el uso de antipsicóticos atípicos como grupo son efectivos, sin embargo, su elección debería considerar la efectividad y tolerancia en la fase de mantención. En pacientes más graves (psicóticos, hospitalizados, agitados) en los cuales la velocidad de respuesta es crítica, se prefiere el uso de antipsicóticos atípicos. Considerar el uso de litio en manías leves a moderadas, dado su eficacia en el tratamiento de mantención.

Evidencia de investigación

Tabla de Resumen de Resultados (Summary of Findings)

Antipsicóticos atípicos comparado con otro estabilizador del ánimo para bipolar con episodio maniaco.

 

Pacientes

Personas con trastorno bipolar, cursando episodio maníaco. 

 

Intervención

Antipsicóticos atípicos como monoterapia.

 

Comparación

Otro estabilizador del ánimo como monoterapia.

 

Desenlaces

Efecto relativo

(IC 95%)

Estudios/

pacientes

Efecto

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

Efectividad

1 metanálisis en red (network metanálisis) [13]

La efectividad de los antipsicóticos atípicos fue DME: 0,44 (IC 95%: 0,36 a 0,51) y otros estabilizadores del ánimo de 0,39 (IC 95%: 0,28 a 0,49), ambos resultados comparados contra placebo. Esta diferencia se reporta como no estadísticamente significativa.

⊕⊕◯◯1,2

Baja

El uso de antipsicóticos atípicos podría tener efectividad levemente superior que otros estabilizadores del ánimo, pero la certeza de la evidencia es baja.

Efectos adversos

El efecto comparativo entre la intervención y comparación de interés sobre el desenlace efectos adversos no fue reportado

IC 95%: Intervalo de confianza del 95%.
DME: Diferencia de medias estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* La diferencia de medias estandarizada se utiliza cuando el desenlace ha sido medido en diferentes escalas y es difícil de interpretar clínicamente. Una regla general es que valores menores a 0,2 son de poca relevancia clínica, valores de 0,5 de relevancia moderada y 0,8 relevancia clínica importante.
1 Se disminuyó un nivel de certeza de evidencia por indirecto, ya que los resultados provienen de un metanálisis en red (network metanálisis).
2 Se disminuyó un nivel de certeza de evidencia por imprecisión, ya que cada extremo del intervalo de confianza conlleva una decisión diferente.
Fecha de elaboración de la tabla: Noviembre, 2018.

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Búsqueda y Síntesis de Evidencia

 3.- ¿Qué tan significativos son los efectos indeseables anticipados?
Grande Moderado Pequeño Trivial Varía No lo sé

Varía: El equipo elaborador de la Guía consideró que existen componentes que pueden afectar de distinta manera los efectos indeseables de «utilizar antipsicóticos atípicos como monoterapia» en comparación a «utilizar estabilizador del ánimo como monoterapia».
El equipo plantea que, según su experiencia, en fase aguda la diferencia de las reacciones adversas son mínimas respecto entre los fármacos. Sin embargo, al mediano/largo plazo, los antipsicóticos atípicos podrían tener más reacciones adversas metabólicas y cognitivas que los estabilizadores del ánimo. En pacientes usuarios de olamzapina, se debe considerar la posibilidad de reacción adversos hematológicos.

Evidencia de investigación

Tabla de Resumen de Resultados (Summary of Findings)

Antipsicóticos atípicos comparado con otro estabilizador del ánimo para bipolar con episodio maniaco.

 

Pacientes

Personas con trastorno bipolar, cursando episodio maníaco. 

 

Intervención

Antipsicóticos atípicos como monoterapia.

 

Comparación

Otro estabilizador del ánimo como monoterapia.

 

Desenlaces

Efecto relativo

(IC 95%)

Estudios/

pacientes

Efecto

Certeza de la evidencia

(GRADE)

Mensajes clave en términos sencillos

Efectividad

1 metanálisis en red (network metanálisis) [13]

La efectividad de los antipsicóticos atípicos fue DME: 0,44 (IC 95%: 0,36 a 0,51) y otros estabilizadores del ánimo de 0,39 (IC 95%: 0,28 a 0,49), ambos resultados comparados contra placebo. Esta diferencia se reporta como no estadísticamente significativa.

⊕⊕◯◯1,2

Baja

El uso de antipsicóticos atípicos podría tener efectividad levemente superior que otros estabilizadores del ánimo, pero la certeza de la evidencia es baja.

Efectos adversos

El efecto comparativo entre la intervención y comparación de interés sobre el desenlace efectos adversos no fue reportado

IC 95%: Intervalo de confianza del 95%.
DME: Diferencia de medias estandarizada.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* La diferencia de medias estandarizada se utiliza cuando el desenlace ha sido medido en diferentes escalas y es difícil de interpretar clínicamente. Una regla general es que valores menores a 0,2 son de poca relevancia clínica, valores de 0,5 de relevancia moderada y 0,8 relevancia clínica importante.
1 Se disminuyó un nivel de certeza de evidencia por indirecto, ya que los resultados provienen de un metanálisis en red (network metanálisis).
2 Se disminuyó un nivel de certeza de evidencia por imprecisión, ya que cada extremo del intervalo de confianza conlleva una decisión diferente.
Fecha de elaboración de la tabla: Noviembre, 2018.

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Búsqueda y Síntesis de Evidencia

 4.- ¿Cuál es la certeza general de la evidencia sobre efectos?
Muy baja Baja Moderada Alta Ningún estudio incluido

Baja: Existe cierta incertidumbre respecto del efecto de «utilizar antipsicóticos atípicos como monoterapia» en comparación a «utilizar estabilizador del ánimo como monoterapia».

Evidencia de investigación

Desenlaces

Importancia

Certainty of the evidence

 (GRADE)

Efectividad

CRÍTICO

⨁⨁◯◯

BAJAa,b

Efectos adversos – no reportado

CRÍTICO

a. Se disminuyó un nivel de certeza de evidencia por indirecto, ya que los resultados provienen de un metanálisis en red (network metanálisis).
b. Se disminuyó un nivel de certeza de evidencia por imprecisión, ya que cada extremo del intervalo de confianza conlleva una decisión diferente.

 5.- ¿Hay incertidumbre importante o variabilidad sobre qué tanto valora la gente los desenlaces principales?
Incertidumbre o variabilidad importantes Posiblemente hay incertidumbre o variabilidad importantes Probablemente no hay incertidumbre ni variabilidad importantes No hay variabilidad o incertidumbre importante

Posiblemente hay incertidumbre o variabilidad importantes: En función de la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud, el equipo elaborador de la Guía consideró que posiblemente existe incertidumbre o variabilidad importante respecto a lo que escogería una persona informada de los efectos deseables e indeseables de «utilizar antipsicóticos atípicos como monoterapia» y «utilizar estabilizador del ánimo como monoterapia».
Según su experiencia clínica del equipo, la adherencia en Chile es más baja que la reportada por el estudio citado. Dada la semejanza de la efectividad entre los grupos de fármacos, serán las reacciones adversas las tendrán más peso al momento de elegir un tratamiento, sobre todo considerando el uso a largo plazo.

Evidencia de investigación

Se identificó un estudio finlandés (1) que evaluó la adherencia y causas de interrupción del tratamiento en una cohorte prospectiva donde participaron pacientes psiquiátricos y ambulatorios con trastorno bipolar.
Durante un período de 18 meses, una cuarta parte de los pacientes que usan estabilizadores del ánimo (23,5%) o antipsicóticos atípicos (25,7%) descontinuaron al menos una fase de tratamiento de forma autónoma. Las interrupciones autónomas de estos tratamientos tuvieron lugar principalmente en la depresión (41,5%) o la eutimia (35,4%), rara vez durante los otros estados.
Las principales razones que los pacientes atribuyeron a la falta de adherencia fueron los efectos secundarios, la falta de motivación y la actitud negativa. A pesar de las marcadas diferencias farmacológicas entre los estabilizadores del estado de ánimo, los antipsicóticos y los antidepresivos, no surgieron grandes diferencias en cuanto a las razones para su suspensión.

Referencias

1. Arvilommi P, Suominen K, Mantere O, Leppämäki S, Valtonen H, Isometsä E. Predictors of adherence to psychopharmacological and psychosocial treatment in bipolar I or II disorders – an 18-month prospective study. J Affect Disord [Internet]. 2014 Feb [cited 2018 Nov 26];155:110–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24262639

Búsqueda y Síntesis de Evidencia

 6.- El balance entre efectos deseables e indeseables favorece la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía No lo sé

Probablemente favorece la intervención: Considerando que la intervención es «utilizar antipsicóticos atípicos como monoterapia» y la comparación es «utilizar estabilizador del ánimo como monoterapia», el equipo elaborador de la Guía opinó que el balance entre efectos deseables e indeseables probablemente favorece «utilizar antipsicóticos atípicos como monoterapia».

 7.- ¿Qué tan grandes son los recursos necesarios (costos)?
Costos extensos Costos moderados Costos y ahorros despreciables Ahorros moderados Ahorros extensos Varía No lo sé

Costos y ahorros despreciables: El equipo elaborador de la Guía consideró que los costos y ahorros de «utilizar antipsicóticos atípicos como monoterapia» son despreciables si se compara con «utilizar estabilizador del ánimo como monoterapia», en función de los antecedentes, experiencia clínica, conocimiento de gestión o experiencia de los pacientes.

Evidencia de investigación

Tabla: Precios Referenciales
El porcentaje de cobertura del seguro de salud sobre el precio de las prestaciones sanitarias, dependerá del tipo de seguro de cada paciente.

Fármacos

Estabilizadores del ánimo antipsicóticos atípicos

Otros estabilizadores del ánimo

Risperidona 3 mg – cm1

$32,3

Quetiapina 100 mg – cm1

$62,3

Olanzapina 10 mg – cm1

$84,1

Clozapina 100 mg – cm 1

$180,0

Aripiprazol 15 mg – cm1

$229,1

Carbamazepina 200 mg – cm 1

$26,2

Lamotrigina 100 mg – cm1

$77,4

Ácido valproico 500 mg – cm1

$86,9

Litio carbonato 300 mg – cm1

$99,6

Haloperidol 5 mg – cm

$129,3

Rango de precio por comprimido

$32,3 a $229,1 

$15,6 a $152,4 

Rango de precio mensual por un comprimido mensual

$969 a $6.872

$785 a $3.789

Referencias

1. Precio de compra por Establecimientos de Salud Públicos a través de plataforma Mercado Público, al 2018. Precio incluye IVA.

Búsqueda y Síntesis de Evidencia

 8.- ¿La costo-efectividad de la intervención beneficia la intervención o la comparación?
Favorece la comparación Probablemente favorece la comparación No favorece la intervención ni la comparación Probablemente favorece la intervención Favorece la intervención Varía Ningún estudio incluido

Ningún estudio incluido: No se encontraron estudios que respondieran la preguntan de interés.

Evidencia de investigación

No se realizó la búsqueda de estudios que abordaran la costo-efectividad de las intervenciones evaluadas ya que no son consideradas de alto costo (Anual $2.418.399 y Mensual $201.533), según lo establecido por el Ministerio de Salud en el “Decreto 80: Determinar umbral nacional de costo anual al que se refiere el artículo 6° de la Ley 20.850”.

 9.- ¿Cuál sería el impacto en equidad en salud?
Reducido Probablemente reducido Probablemente ningún impacto Probablemente aumentado Aumentado Varía No lo sé

Probablemente ningún impacto: El equipo elaborador de la Guía consideró que probablemente no tendría ningún impacto en la equidad en salud si se recomendase «utilizar antipsicóticos atípicos como monoterapia», dado que los fármacos están cubiertos por el Régimen de Garantías Explícitas de Salud.

 10.- ¿La intervención es aceptable para las partes interesadas?
No Probablemente no Probablemente sí Varía No lo sé

Probablemente sí: El equipo elaborador de la Guía consideró que «utilizar antipsicóticos atípicos como monoterapia» probablemente SÍ es aceptable para las partes interesadas. Para los pacientes podría ser variable dicha aceptabilidad, dependiendo de sus preferencias.

 11.- ¿Es factible implementar la intervención?
No Probablemente no Probablemente sí Varía No lo sé

Sí: El equipo elaborador de la Guía consideró que «utilizar antipsicóticos atípicos como monoterapia» SÍ es factible implementar, contemplando que está cubierto por el Régimen de Garantías Explícitas de Salud.