Potencial Teraputico de los Acidos Grasos Omega 3 en el Prdromos de la Psicosis

Guillermo Rivera, MD, PhD.

WPA Research Fellow Orygen Youth Health.

Agenda
La intervencin temprana en psicosis cidos grasos Omega 3 Efectos clnicos de Omega 3 en la fase prodrmica de la psicosis. Conclusiones

Edad de inicio de los trastornos mentales

0,7 0,6 0,5 0,4 Relative dominance 0,3 0,2 0,1 0 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 Years Affect Mood disorders Personality disorders Schizophrenia, pos. sxs. Schizophrenia, Neg. sxs.

Disfuncionalidad asociada al nmero de episodios psicoticos

120

100

80
Functioning

60

40

20

3
Number of episodes

Efectos de las mltiples recaidas

140 120 100 80 60 40 20 0 1st 2nd 3rd
Adapted from Lieberman, J., et al., J Clin, Psychiatry, 1996; 57: 5-9

130
Days to remission

76,5 47

Ventanas de prevencin

Institute of Medicine, 2010

High

Validez diagnostica a traves de las fases de la psicosis Neurological disease (Cerebral

Periodo Premorbido
Periodo Prodromico Diagnostico Definido AIDS, SLE, MS. etc.) Dementia praecox, deficit schizophrenia Chronic undifferentiated schizophrenia Paranoid schizophrenia

Validity of clinical differential diagnosis

Schizo-obsessive disorder.

0
Schizo-affective disorder NRG-1 disorder Psychotic bipolar disorder

High

Psychotic depressive disorder Severe agoraphobia

tiempo

Impacto Potencial de la Intervencion Temprana en Psicosis

Mc Gorry, 1998

22% - 54% de sujetos identificados en prodromos desarrollaron Psicosis 12 meses despus Estudio NAPLS: 35% desarrollaron psicosis 30 meses despus.
Cumulativ e surv iv al distribution function modeling time to conv ersion to psychosis in 291 clinical high-risk (prodromal) patients and 134 demographically comparable normal control subj ects (dashed line)

Cannon, T. D. et al. Arch Gen Psychiatry 2008; 65: 28-37.

C o py rig ht r estr ic tio ns may apply .

Prevention And Promotion

Institute of Medicine, 2010

Estudios de prevencion de psicosis: Tasas de conversion 12 meses despus

% converting to psychosis
40 35 30 25 20 15 10 5 0 Controls Experimental 9,9 32 PACE PRIME OPUS PIER EDIE Amminger Mean rate

Indicaciones de Omega 3

Lipidos en el cerebro

El cerebro es el segundo organo con mayor contenido De lipidos, hasta un 50%, porcentaje proximo a los adipocitos

Omega-6
18:2(n-6)

Omega-3
18:3(n-3)

LA
18:3(n-6)

ALA 6-Desaturase
18:4(n-3)

GLA Elongase
20:3(n-6)

20:4(n-3)

DGLA

PGs of series 1 PGs of series 2

20:4(n-6)

5-Desaturase Elongase

20:5(n-3)

ARA
22:4(n-6)

EPA
22:5(n-3)

PGs of series 1

DPA Elongase
24:4(n-6) 24:5(n-3)

6-Desaturase
24:5(n-6) 24:6(n-3)

-Oxidation
22:5(n-6) 22:6(n-3)

DPA

DHA

Senalizacion lipidica y Neuroplasticidad Neuronal, Reparacion Cerebral, y Neuroproteccin

Bazan, 2005

Mecanismos
Neurotransmisores (dopamina, serotonina) Citoquinas (BNDF, IL6, IL10) Glutatione Neuroprotectina D-1

El vinculo metabolico de los acidos grasos

Sensibilidad al dolor y la temperatura Menor incidencia de artritis La fiebre mejora los sntomas de la esquizofrenia Schizophrenia as a Prostaglandin Deficiency Disease David Horrobin, Lancet, 1977.

Evidencia Epidemiologica

Hedelin et al., BMC Psychiatry 2010,

From: Randomized, Placebo-Controlled Study of Ethyl-Eicosapentaenoic Acid as Supplemental Treatment in Schizophrenia

Am J Psychiatry. 2002;159(9):1596-1598. doi:10.1176/appi.ajp.159.9.1596

Figure Legend:
Mean Total Scores on the Positive and Negative Syndrome Scale of Patients Who Received Ethyl-Eicosapentaenoic Acid (E-EPA) or Placebo in a 12-Week Randomized, Parallel-Group, Double-Blind Study of Supplemental Treatment for Schizophrenia a aLast observation carried forward. bSignificant difference between groups (t=2.20, df=38, p<0.05). cSignificant difference between groups (t=2.90, df=38, p<0.05). Date of download: Copyright American Psychiatric Association. dSignificant difference between groups (t=2.20, df=38, p<0.05). 9/15/2012 All rights reserved.

Eicosapentaenoic Acid Interventions in Schizophrenia: Meta-Analysis of Randomized, Placebo-Controlled Studies.

Fusar-Poli, Paolo; Berger, Gregor Journal of Clinical Psychopharmacology. 32(2):179-185, April 2012. DOI: 10.1097/JCP.0b013e318248b7bb

treatment) on psychotic symptoms.20,3438FIGURE 1 . Meta-analysis of double-blind placebo-controlled EPA studies in DSM-IV schizophrenia. Random-effects model of individual and overall (last line of the plot) Hedges' g estimate (95% confidence interval) of the effect of EPA augmentations strategies as compared with placebo (standard antipsychotic
2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 6

Diseo del Estudio

Doble ciego, aleatroizado, contra placebo, estudio en un solo centro Individuos con Ultra Alto Riesgo, entre 1325 a. Tratamientos: 2g Ac 2g Placebo

Por 12 semanas

Seguimiento:

1, 2, 3, 4, 8, 12, 26, y 52 semanas

Gas Chromatography (GC)

Gas Chromatography (GC)

Change n-6/n-3 Ratio

P=0.000000000012

Resultado Primario - Psicosis

Resultados Secundarios

Effects Sizes
Baseline and Follow-up mean difference scores converted to Cohen's D effect sizes 0,8 0,66 0,6
Effect size

0,61 0,53 0,39

0,48

0,4 0,24 0,2 0 -0,2

Woods et al., 2003

PANSS Global PANSS Positive GAF PANSS Negative PANSS Global PANSS Positive GAF PANSS Negative

0,18 0,07

EPA/DHA vs. Placebo Olanzapine vs. Placebo

Relationship: Fatty Acids with Clinical Variables at Baseline

Positive Symptoms NA DHA ARA -.144 .010 .048 Ne gativ e Symptoms -.457** -.223* -.029 Gene ral Symptoms -.395** -.065 -.028 De pre ssi ve Symptoms -.239* .018 -.049 GAF Score .336** .149 .046

**P0.01 *P0.05

Prediction of Psychosis Transition

Figure 1 Baseline erythrocyte fatty acids in ultra-high risk patients who did or did not transition to psychosis by 12-month follow-upa

Non-psychotic

Psychotic

Non-psychotic

Psychotic

Non-psychotic

Psychotic

a Fatty

b Significant

acid values represent percent of the total fatty acids. Error bars are means, 95% CIs. difference between groups (P<0.05).

Amminger et al., resubmitted

The NEURAPRO-E Study: A comparison study of fish oil capsules and psychological therapy versus placebo capsules and psychological therapy in patients at risk of developing a

psychotic disorder

Conclusiones
La intervencin temprana se dirige a promover la recuperacin de la psicosis a travs de la prevencin, la deteccin temprana y los tratamientos ms efectivos para los inicios de la enfermedad El requerimiento de cidos grasos en el cerebro asegura el recambio de las membranas de las clulas y de preservar la integridad de las funciones celulares.

Conclusiones 2
Evidencia creciente apoya fuertemente que los PUFAs -3 puede ofrecer una prevencion viable y una estrategia de tratamiento con minimos riesgos asociados en gente joven en riesgo ultra alto de psicosis, lo que debe continuar siendo explorado.