Neurobiological bases of quetiapine antidepresant effect in the bipolar disorder.

Bipolar disorder is considered an important public health problem in the world. The depressive phase is the most important in terms of frequency, duration, and impairment of the quality of life. Common treatment of bipolar depression usually includes antidepressants, mood stabilizers and antipsychotics in different combinations, despite not having a specific indication for that. Quetiapine is the first drug in Europe that has obtained a specific indication for the treatment of bipolar depression, due to a pharmacologic profile that makes it to act on the three neurotransmitter systems involved in bipolar depression neurobiology. Regarding the dopaminergic pathway, quetiapine leads to an increasing of prefrontal dopamine release by antagonism of5-HT2A receptors, partial agonist of 5-HT1A and antagonism of a2 adrenoceptors. Quetiapine also enhances the serotoninergic transmission by increasing the density of receptors5-HT1A in the prefrontal cortex and by antagonism of 5-HT2A receptors and a2 adrenoceptors. On the other hand, norquetiapine, the main active metabolite of quetiapine, actsas a 5-HT2C antagonist and is a potent inhibitor of norepinephrine transporter (NET). NET inhibition leads to an increase of noerpinephrine in the synapse, and together with the increase of prefrontal dopamine and serotonin, could explain the antidepressive effect demonstrated by quetiapine in several clinical trials. Quetiapine's action on glutamatergicand GABAergic receptors represents an interesting object of research, together with a potential neuroprotective effect that have already been observed in animal models.

Bases neurobiológicas del efecto antidepresivo de la quetiapina en el trastorno bipolar / Neurobiological basis of quetiapine’s antidepressant effect in the bipolar disorder

El trastorno bipolar constituye un importante problema de salud pública en el mundo, siendo la fase depresiva la más importante en términos de frecuencia, duración y afectación de la calidad de vida. El tratamiento habitual de la depresión bipolar suele incluir antidepresivos, eutimizantes y antipsicóticos en diversas combinaciones, sin que ninguno de ellos disponga de la indicación para ello. La quetiapina se ha convertido en el primer fármaco en Europa en conseguir una indicación específica para el tratamiento de la depresión bipolar, gracias a un perfil farmacológico que le permite actuar sobre los tres sistemas de neurotransmisores implicados en la neurobiología de la depresión bipolar. Sobre el sistema dopaminérgicola quetiapina induce un aumento de la liberación de dopamina prefrontal gracias principalmente a su acción antagonista 5-HT2A, agonista parcial 5-HT1A y antagonista a2 adrenérgico. La quetiapina mejora también la neurotransmisión serotoninérgica mediante el aumento de la densidad de receptores 5-HT1A en el córtex prefrontal y el antagonismo 5-HT2A y a2 adrenérgico. Por su parte, el principal metabolito activo de la quetiapina, norquetiapina, actúa como antagonista 5-HT2C y es un potente inhibidor del transportador de noradrenalina (NET). La inhibición del NET se traduce en un aumento de la noradrenalina sináptica que, unido al aumento de dopamina prefrontal y de serotonina explicaría el efecto antidepresivo demostrado por la quetiapina en diferentes ensayos clínicos. La acción de la quetiapina sobre los receptores glutamatérgicos y GABA érgicos constituye un interesante objeto de estudio, al igual que un posible efecto neuroprotector que ya ha empezado a observarse en modelos animales (AU)

Bipolar disorder is considered an important public health problem in the world. The depressive phase is the most important in terms of frequency, duration, and impairment of the quality of life. Common treatment of bipolar depression usually includes antidepressants, mood stabilizers and antipsychotics in different combinations, despite not having a specific indication for that. Quetiapineis the first drug in Europe that has obtained a specific indication for the treatment of bipolar depression, due to a pharmacologic profile that makes it to act on the three neurotransmitter systems involved in bipolar depression neurobiology. Regarding the dopaminergic pathway, quetiapine leads to an increasing of prefrontal dopamine release by antagonism of 5-HT2A receptors, partial agonist of 5-HT1A and antagonism of a2 adrenoceptors. Quetiapine also enhances the serotoninergic transmission by increasing the density of receptors 5-HT1A in the prefrontal cortex and by antagonism of 5-HT2A receptors and a2 adrenoceptors. On the other hand, norquetiapine, the main active metabolite of quetiapine, acts as a5-HT2C antagonist and is a potent inhibitor of norepinephrine transporter (NET). NET inhibition leads to an increase of noerpinephrine in the synapse, and together with the increase of prefrontal dopamine and serotonin, could explain the antidepressive effect demonstrated by quetiapine in several clinical trials. Quetiapine’s action on glutamatergic and GABA ergic receptors represents an interesting object of research, together with a potential neuroprotective effect that have already been observed in animal models (AU)

[Analysis of prescription patterns of antipsychotic agents in psychiatry]. / Análisis de los patrones de prescripción de antipsicóticos en psiquiatría.

INTRODUCTION: We describe the different diseases in which conventional and second generation antipsychotic (APS) prescriptions are made. METHOD: Observational, retrospective, multicenter study based on the review of 300 clinical records of public and private sites, hospital and out-patient clinics, located in Salamanca, Vigo, Bilbao, Barcelona, Valencia, Oviedo and Malaga. RESULTS: The mean age of the population studied was 42 +/- 17 years; 56.6 % were men. Atypical drugs (67 %) were used basically versus classical ones (33 %). Classical APS are basically prescribed in bipolar disorder with/without psychotic symptoms (20.6 %), schizophrenia (18.3%) and delusional disorder (11.5 %). Atypical APS are fundamentally prescribed in schizophrenia (31.5 %), bipolar disorders with/without psychotic symptoms (12.5 %) and other psychotic disorders (8.9 %). When the psychotic disorders are considered by groups (schizophrenia, bipolar disorder with psychotic symptoms, delusional disorder and other psychotic disorders), classical APS are used in 47.4 % and atypical APS in 62.5%. APS were used ((outside the indication)) (off-label) in 32.8%, including resistant depressions, serious obsessive-compulsive disorder and borderline personality disorder, with similar percentages for both conventional and atypical ones. In dementia, atypical APS were used in 5.1 % versus 1.5 % of the conventional ones. The most frequent reasons for prescription of classical APS were control of psychotic symptoms (33.6 %), aggressiveness-agitation (31.3 %), severe insomnia (16 %), impulsivity (6.9 %) and severe anxiety (6.1 %). Atypical APS were preferably used in the control of psychotic symptoms (58.8%) and aggressiveness-agitation (25.5%). CONCLUSIONS: The use of APS basically occurs within their authorized indications (67.2 %). The off-label use (32.8 %) occurs both for the classical as well as atypical APS and occurs in serious diseases in which there are no alternative treatments.

Análisis de los patrones de prescripción de antipsicóticos en psiquiatría / Analysis of prescription patterns of antipsychotic agents in psychiatry

Introducción. Se describen las diferentes patologías en las que se realizan prescripciones de antipsicóticos (APS) convencionales y de segunda generación. Método. Estudio observacional, retrospectivo, multicéntrico, basado en la revisión de 300 historias clínicas de centros públicos y privados, hospitalarios y ambulatorios, localizados en Salamanca, Vigo, Bilbao, Barcelona, Valencia, Oviedo y Málaga. Resultados. La edad media de la población estudiada fue de 42±17 años; el 56,6% eran varones. Se emplearon fundamentalmente atípicos (67 %) frente a clásicos (33 %). Los APS clásicos se prescribieron fundamentalmente en el trastorno bipolar con/sin síntomas psicóticos (20,6%), esquizofrenia (18,3%) y trastorno delirante (11,5%). Los APS atípicos se prescribieron fundamentalmente en esquizofrenia (31,5 %), trastorno bipolar con/sin síntomas psicóticos (12,5 %) y otros trastornos psicóticos (8,9 %). Considerando los trastornos psicóticos agrupadamente (esquizofrenia, trastorno bipolar con síntomas psicóticos, trastorno delirante y otros trastornos psicóticos) se utilizaron APS clásicos en el 47,4% y APS atípicos en el 62,5 %. Se utilizaron APS «fuera de indicación» en el 32,8 %, incluyendo depresiones resistentes, trastorno obsesivo-compulsivo grave y trastorno límite de la personalidad, con porcentajes similares, tanto de los convencionales como de los atípicos. En la demencia se emplearon APS atípicos en un 5,1 frente a 1,5 % de los convencionales. Los motivos de prescripción más frecuentes para los APS clásicos fueron el control de síntomas psicóticos (33,6 %), agresividad-agitación (31,3 %), insomnio severo (16 %), impulsividad (6,9 %) y ansiedad severa (6,1 %). Los APS atípicos se utilizaron preferentemente en el control de síntomas psicóticos (58,8%) y agresividad-agitación (25,5%). Conclusiones. La utilización de APS tiene lugar fundamentalmente dentro de las indicaciones para los que están autorizados (67,2%). El uso «fuera de indicación» (32,8 %) se da de forma similar tanto para los APS clásicos como para los APS atípicos, y se produce en patologías graves en las que no se cuenta con tratamientos alternativos

Introduction. Wed describe the different diseases in which conventional and second generation antipsychotic (APS) prescriptions are made. Method. Observational, retrospective, multicenter study based on the review of 300 clinical records of public and private sites, hospital and out-patient clinics, located in Salamanca, Vigo, Bilbao, Barcelona, Valencia, Oviedo and Malaga. Results. The mean age of the population studied was 42±17 years; 56.6 % were men. Atypical drugs (67 %) were used basically versus classical ones (33 %). Classical APS are basically prescribed in bipolar disorder with/without psychotic symptoms (20.6 %), schizophrenia (18.3%) and delusional disorder (11.5 %). Atypical APS are fundamentally prescribed in schizophrenia (31.5 %), bipolar disorders with/without psychotic symptoms (12.5 %) and other psychotic disorders (8.9 %). When the psychotic disorders are considered by groups (schizophrenia, bipolar disorder with psychotic symptoms, delusional disorder and other psychotic disorders), classical APS are used in 47.4 % and atypical APS in 62.5%. APS were used «outside the indication» (off-label) in 32.8%, including resistant depressions, serious obsessive-compulsive disorder and borderline personality disorder, with similar percentages for both conventional and atypical ones. In dementia, atypical APS were used in 5.1 % versus 1.5 % of the conventional ones. The most frequent reasons for prescription of classical APS were control of psychotic symptoms (33.6 %), aggressiveness-agitation (31.3 %), severe insomnia (16 %), impulsivity (6.9 %) and severe anxiety (6.1 %). Atypical APS were preferably used in the control of psychotic symptoms (58.8%) and aggressiveness-agitation (25.5%). Conclusions. The use of APS basically occurs within their authorized indications (67.2 %). The off-label use (32.8 %) occurs both for the classical as well as atypical APS and occurs in serious diseases in which there are no alternative treatments