Search

Background: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). Objective: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. Methods: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. Results: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label "death" was the top cause in the world (46 %) and in the UK (33 %). "Pneumonia" was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1-10 % of the UK clozapine fatal outcome number. Conclusions: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases.

Background: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). Objective: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. Methods: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. Results: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label “death” was the top cause in the world (46 %) and in the UK (33 %). “Pneumonia” was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1–10 % of the UK clozapine fatal outcome number. Conclusions: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases.

La psicosis es un síndrome heterogéneo que se puede expresar en multitud de patologías, que comparten síntomas y características entre sí. Todas ellas se presentan al inicio como un primer episodio psicótico (PEP), un evento de suma importancia cuyo manejo y caracterización repercutirán en el pronóstico. El PEP puede desembocar en cualquiera de las patologías del espectro psicótico, como por ejemplo la esquizofrenia, una patología con una enorme repercusión vital y social, que puede llegar a ser incapacitante. Para llevar a cabo un abordaje individualizado del PEP sería de inestimable ayuda contar con un biomarcador que pudiese predecir fenotipos concretos en su evolución. Para esto es necesario entender que las patologías psicóticas son multifactoriales y enormemente poligénicas y pleiotrópicas, con interacción entre factores genéticos comunes y factores ambientales compartidos. Estos factores genéticos son en su mayoría SNP (variantes de un único nucleótido), que se suman para conferir el mencionado riesgo genético. Se llama estima de riesgo poligénico o PRS (por sus siglas en inglés), al cálculo derivado de la suma de SNP de riesgo que tiene una persona, ponderadas por su efecto calculado en un estudio genómico independiente, conocido como GWAS (Genome Wide Association Study). Aunque se han realizado estudios sobre la PRS y diferentes trastornos mentales que pueden presentarse como un PEP, esta es la primera revisión sistemática que estudia la utilidad de la PRS como biomarcador predictor de fenotipos en pacientes con PEP, a través de la revisión de siete estudios que tratan la relación entre la PRS y distintos fenotipos relacionados con el diagnóstico, perfil sintomático, evolución y respuesta al tratamiento de pacientes con PEP. Los datos encontrados son prometedores de cara a continuar el estudio de las PRS como herramientas de pronóstico, como una forma de acercar la genética a la práctica clínica diaria, A psicose é unha síndrome heteroxénea que pode expresarse en multitude de patoloxías, que comparten síntomas e características comúns. Todas elas se presentan ao inicio como un primeiro episodio psicótico (PEP), un evento de suma importancia cuxo manexo e caracterización repercutirán na prognose. O PEP pode desembocar en calquera das patoloxías do espectro psicótico, como por exemplo a esquizofrenia, unha patoloxía cunha enorme repercusión vital e social, que pode chegar a ser incapacitante. Para levar a cabo unha abordaxe individualizada do PEP, sería de inestimable axuda contar cun biomarcador que puidese predecir fenotipos concretos na súa evolución. Para isto é necesario entender que as patoloxías psicóticas son multifactoriais e enormemente polixénicas e pleiotrópicas, con interacción entre factores xenéticos comúns e factores ambientais compartidos. Estes factores xenéticos son na súa maioría SNP (variantes dun único nucleótido), que se suman para outorgar o mencionado risco xenético. Chámase estima de risco polixénico ou PRS(polas súas siglas en inglés), ao cálculo derivado da suma de SNP de risco que posúe unha persoa, ponderadas polo seu efecto calculado nun estudo xenómico independente, coñecido como GWAS (Genome Wide Association Study). Aínda que se teñen realizado estudos sobre a PRS e diferentes trastornos mentais que poden presentarse coma un PEP, esta é a primeira revisión sistemática que estuda a utilidade da PRS como biomarcador predictor de fenotipos en doentes con PEP, mediante a revisión de sete estudos que tratan a relación entre a PRS e distintos fenotipos relacionados ca diagnose, perfil sintomático, evolución e resposta ao tratamento en doentes con PEP. Os feitos atopados son prometedores cara a continuar o estudo das PRS como ferramentas de prognose, como un xeito de achegar a xenética á práctica clínica cotiá, Psychosis is a heterogeneoussyndrome that can be expressed in multiple pathologies, which usually share symptoms and characteristics with each other. All of them tend to appear initially as a first episode psychosis (FEP), an extremely important event whose management and assessment will have an impact on the prognosis. FEP can lead to any of the pathologies included on the psychotic spectrum, such as schizophrenia, a disease with extremely important vital and social repercussions, which can be disabling. To carry out an individualized approach to FEP, it would be helpful to have a biomarker that could predict specific phenotypes in its evolution. For this, it is important to understand that psychotic pathologies are multifactorial and highly polygenic and pleiotropic, due to the interaction between common genetic factors and shared environmental factors. These genetic factors are mostly SNPs (Single-Nucleotide Polymorphisms), which come together to confer this genetic risk. Polygenic risk score (PRS) is the calculation derived from the sum of risk SNPs that a person has, weighted by their effect calculated in an independent genome-wide association study (GWAS). Although a few studies have been carried out about PRS and different mental disorders that can first appear as a FEP, this is the first systematic review that studies the usefulness of PRS as a phenotype predictive biomarker in FEP patients. Seven studies that address the relationship between PRS and different phenotypes related to diagnosis, symptoms, evolution and treatment response in FEP patients were included in this systematic review. Available data support further studies of PRS as prognostic tools, as a way of bringing genetics closer to daily clinical practice

Introdución. O cannabis é a terceira substancia máis consumida a nivel mundial, así como a máis consumida dentro do grupo das drogas ilegais. O inicio da pandemia da COVID-19 supuxo importantes cambios nas relacións sociais, a saúde mental e a calidade de vida das persoas, o que puido traer consigo importantes modificacións nos patróns de uso de substancias poboacionais, en especial no poboamento adolescente, un colectivo vulnerábel en período de desenvolvemento social e emocional. O obxectivo deste traballo céntrase na elaboración dunha revisión sistemática sobre a variación dos patróns de consumo de cannabis en adolescentes durante a pandemia, así como os factores asociados a un maior ou menor uso. Material e métodos. Para levar a cabo a revisión, efectuouse unha busca sistematizada na base de datos MEDLINE-PubMed de traballos publicados dende o inicio da pandemia, relacionados coa variación dos patróns de uso de cannabis en adolescentes e os potenciais factores ligados a un consumo de risco. Resultados. En total, 7 estudos foron incluídos nesta revisión, dos cales 3 reportaron unha diminución do consumo tras o comezo da pandemia, mentres que outro reflectiu unha maior tendencia á estabilización, cunha propensión superior ao consumo grupal que individual. En dous deles, os homes reportaron un maior descenso significativo do consumo, mentres que noutro se presentou un maior descenso global de uso xunto cun aumento da frecuencia de consumo nas mulleres. A diminución do consumo de risco resultou unicamente significativa nas mulleres. Así mesmo, durante a evolución da pandemia ao longo dos meses percibiuse unha tendencia ao incremento paulatino do uso. A presenza de síntomas depresivos e conflitos de moderación afectiva nas mulleres, así como unha maior idade en ambos xéneros, ligáronse a un maior consumo, en contraposición con outros factores como unha mellor saúde mental, o benestar social e psicolóxico previo, puntuacións máis elevadas nos parámetros de intelixenci, Introducción. El cannabis es la tercera sustancia más consumida a nivel mundial, así como la más consumida dentro del grupo de las drogas ilegales. El inicio de la pandemia de la COVID-19 ha supuesto importantes cambios en las relaciones sociales, la salud mental y la calidad de vida de las personas, lo que ha podido traer consigo importantes modificaciones en los patrones de uso de sustancias poblacionales, en especial en la población adolescente, un colectivo vulnerable en período de desarrollo social y emocional. El objetivo de este trabajo se centra en la elaboración de una revisión sistemática sobre la variación de los patrones de consumo de cannabis en adolescentes durante la pandemia, así como los factores asociados a un mayor o menor uso. Material y métodos. Para llevar a cabo la revisión, se efectuó una búsqueda sistematizada en la base de datos MEDLINE-PubMed de trabajos publicados desde el inicio de la pandemia, relacionados con la variación de los patrones de uso de cannabis en adolescentes y los potenciales factores ligados a un consumo de riesgo. Resultados. En total, 7 estudios fueron incluidos en esta revisión, de los cuales 3 reportaron una disminución del consumo tras el comienzo de la pandemia, mientras que otro reflejó una mayor tendencia a la estabilización, con una propensión superior al consumo grupal que individual. En dos de ellos, los hombres reportaron un mayor descenso significativo del consumo, mientras que en otro se presentó un mayor descenso global de uso junto a un aumento de la frecuencia de consumo en las mujeres. La disminución del consumo de riesgo resultó únicamente significativa en las mujeres. Así mismo, durante la evolución de la pandemia a lo largo de los meses se percibió una tendencia al incremento paulatino del uso. La presencia de síntomas depresivos y conflictos de moderación afectiva en las mujeres, así como una mayor edad en ambos géneros, se asociaron a un mayor consumo, en contraposición con otros factores como una, Introduction. Cannabis is the third most consumed substance worldwide, as well as the most consumed within the group of illegal drugs. The onset of the COVID-19 pandemic has brought about important changes in people's social relationships, mental health, and life quality, which may have been able to bring about important changes in population substance use patterns, especially in the adolescent population, a vulnerable group experiencing a social and emotional development period. The aim of this work focuses on the elaboration of a systematic review on the variation in cannabis use patterns in adolescents during the pandemic, as well as the factors associated with greater or lesser use. Material and methods. To bring in this survey, a systematic search was carried out in the MEDLINE-PubMed database for papers published since the beginning of the pandemic, related to the variation in cannabis use patterns in adolescents and potential factors linked to a risky consumption. Results. Altogether, 7 studies were included in this review. 3 of them reported a decrease in consumption since the pandemic started, while another one reported a greater tendency towards stabilization, with a greater propensity for group than individual consumption. In two cases, men reported a greater significant decrease in consumption, while another one reported a greater overall decrease in use beside an increase in consumption frequency in women. Risky consumption decrease was only significant in women. Likewise, along the pandemic evolution over the months, a gradual increase in use was perceived. Depressive symptoms and affective moderation conflicts in women, as well as elder age in both genders, associated greater consumption, as opposed to other factors such as better mental health, previous social and psychological well-being, higher scores in the emotional intelligence parameters or greater family support, which were linked to a lower consumption. Conclusion. Outcomes obtained in this r

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid bipolar disorder (BD) and substance use disorders (SUDs) while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Very few of the randomized trials performed so far have provided consistent evidence for the management of both mood symptoms and substance use in patients with a BD. No clinical trials are available for bipolar patients using cannabis. Some treatments have shown benefit for mood symptoms without benefits for alcohol or illicit substance use. Our results suggest that 1) we can (weakly) recommend the use of adjuvant valproate or naltrexone to improve symptoms of alcohol use disorder; 2) Lamotrigine add-on therapy seems to reduce cocaine-related symptoms and is therefore recommended (moderate strength); and 3) Varenicline is (weakly) recommended to improve nicotine abstinence. Integrated group therapy is the most-well validated and efficacious approach on substance use outcomes if substance use is targeted in an initial treatment phase, Esta revisión resume las intervenciones farmacológicos y psicosociales que se han realizado en trastorno bipolar (TB) y un diagnóstico comórbido de trastorno por uso de sustancias (TUS) y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias versus los síntomas de estado de ánimo en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Muy pocos de los ensayos aleatorizados realizados hasta la fecha han proporcionado evidencia consistente para el manejo tanto de los síntomas de estado de ánimo como del uso de sustancias en pacientes con TB. No hay disponibilidad de ensayos clínicos para pacientes con TB que utilizan el cannabis. Algunos tratamientos han mostrado beneficios para los síntomas de estado de ánimo sin beneficios para el uso de alcohol o sustancias ilícitas. Nuestros resultados sugieren que 1) podemos (débilmente) recomendar el uso de ácido valproico o naltrexona adyuvante para aliviar los síntomas del trastorno por consumo de alcohol; 2) el tratamiento complementario con lamotrigina parece reducir los síntomas relacionados con la cocaína y, por tanto, es recomendable (fuerza moderada); y 3) la vareniclina es recomendable (débilmente) para mejorar la abstinencia de la nicotina. La terapia grupal integrada es el enfoque con más validación y eficacia sobre los resultados en el uso de sustancias cuando este uso es abordado durante la fase inicial de tratamiento

Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence, La concurrencia de depresión y un trastorno por uso de sustancias (TUS) en pacientes que presentan patología dual ha sido reconocida desde hace mucho tiempo como una consideración importante en la práctica clínica. Esta revisión sintetiza la evidencia de intervenciones farmacológicas y psicosociales para trastornos comórbidos de depresión y uso de sustancias y además proporciona recomendaciones clínicas respecto de las mejores intervenciones para tratar a estos pacientes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Nuestros resultados sugieren que: 1) en pacientes con depresión y consumo de alcohol, se recomienda la administración de antidepresivos inhibidores de la recaptación de serotonina (ISRS) no selectivos en lugar de los ISRS para mejorar los síntomas depresivos (recomendación fuerte). No se recomiendan antidepresivos ISRS (recomendación fuerte) ni antidepresivos no ISRS (recomendación débil) para reducir el consumo de alcohol; 2) en pacientes con depresión y consumo de cannabis, no se recomienda el uso de venlafaxina (recomendación débil); 3) en pacientes con depresión y consumo de cocaína, no se recomienda el uso de antidepresivos ISRS para mejorar los síntomas depresivos (recomendación débil) o para reducir el consumo de cocaína (recomendación fuerte). El uso de antidepresivos no ISRS solo se recomienda para mejorar los síntomas depresivos (recomendación fuerte); 4) no se recomienda la administración de bupropión para reducir el consumo de nicotina (recomendación fuerte), y 5) en cuanto al tratamiento psicológico, en pacientes con depresión y trastorno de alcohol concurrente, tanto la farmacoterapia como la terapia cognitivoconductual tienen efectos positivos en la internalización de los síntomas y en la reducción del consumo de alcohol (recomendación débil). Nuestra revisión sugiere la necesidad de realizar más investig

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people fr

La terapia electroconvulsiva nació en el año 1938 de la mano de Lucio Bini y Ugo Cerletti. Desde aquel momento ha ido evolucionando y perfeccionándose para conseguir mejores resultados con los menores efectos secundarios, sin embargo , el cine y los medios de comunicación siguen difundiendo una imagen anticuada de este tratamiento. Se trata de un procedimiento médico en el que mediante el empleo de descargas eléctricas se pretende lograr inducir una convulsión en el paciente. Todo el proceso se lleva a cabo con el empleo de anestesia y relajación muscular para aumentar su seguridad. El mecanismo mediante el cual ejerce su efecto terapéutico no está demostrado con certeza. Se está investigando la capacidad que posee en la regulación de algunos neurotransmisores, así como de favorecer cambios morfológicos en estructuras cerebrales como el hipocampo. Los últimos estudios revelan que también puede jugar un papel en la neuroplasticidad. Los efectos secundarios que antiguamente eran graves y frecuentes como las roturas óseas y musculares, hoy en día son anecdóticos y se han sustituido por las náuseas y el dolor de cabeza. Las pérdidas de memoria siguen siendo la principal preocupación de los pacientes, pero mediante el desarrollo de nuevas técnicas como las descargas ultrabreves unilaterales derechas, se pueden reducir en pacientes predispuestos. La terapia electroconvulsiva ha demostrado su efectividad en múltiples patologías como la depresión mayor, la catatonía, incluso obteniendo mejores resultados que los tratamientos farmacológicos. A pesar de ello, sigue estando infrautilizada en la práctica médica. Los pacientes y sus familiares, una vez han finalizado su tratamiento con la terapia electroconvulsiva, se sienten satisfechos con los resultados y la atención recibida e incluso refieren que repetirían el tratamiento si fuera necesario, A terapia electroconvulsiva naceu no ano 1938 da man de Lucio Bini e Ugo Cerletti. Dende aquel momento desenvolveuse e perfeccionouse para acadar mellores resultados cos menores efectos secundarios posibles. Sen embargo, o cine e os medios de comunicación seguen difundindo unha imaxe anticuada deste tratamento. Trátase dun procedemento médico no que mediante o emprego de descargas eléctricas, preténdese inducir unha convulsión no paciente. Todo o proceso lévase a cabo mediante o emprego de anestesia e relaxación muscular para aumentar a súa seguridade. O mecanismo mediante o cal exerce o seu efecto terapéutico non está demostrado con certeza. Estase a investigar a capacidade que ten na regulación dalgúns neurotransmisores, así como de favorecer os cambios morfolóxicos en estructuras cerebrais coma o hipocampo. Os derradeiros estudos revelan que tamén pode xogar un papel na neuroplasticidade. Os efectos secundarios que antigamente eran graves e frecuentes como as roturas óseas e musculares, hoxe en día son anecdóticos e sustituíronse polas náuseas e a dor de cabeza. As pérdidas de memoria seguen sendo a principal preocupación dos pacientes, pero mediante o desenvolvemento de novas técnicas coma as descargas ultrabreves unilaterais dereitas, pódense disminuir nos pacientes predispostos. A terapia electroconvulsiva demostrou a sua efectividade en múltiples patoloxías como a depresión maior, a catatonía e incluso obtendo mellores resultados ca os tratamentos farmacolóxicos. A pesar disto, segue estando infrautilizada na práctica médica. Os pacientes e os seus familiares, unha vez finalizou o seu tratamento coa terapia electroconvulsiva, séntense satisfeitos cos resultados e a atención recibida, e incluso contan que repetirían o tratamento se fora preciso, The electroconvulsive therapy was born in the year 1938 by the hand of Lucio Bini and Ugo Cerletti. Since that moment, it has been developed and improved in order to achieve better results with the fewer side effects. However, the cinema and the media continue to share an outdated image of the electroconvulsive therapy. It is a medical procedure in which, through the use of electric shocks, it is intended to induce a seizure in the patient. The whole process is carried out with the use of anesthesia and muscle relaxation to improve safety. The mechanism by which it makes its therapeutic effect has not been proven with certainty. The ability to regulate some neurotransmitters is being investigated, as well as to promote morphological changes in brain structures such as the hippocampus. The latest studies reveal that it may also play a role in the neuroplasticity. The side effects that were once serious and frequent such as bone and muscle breaks, today are anecdotal and have been replaced by nausea and headache. Memory losses remain the main concern of patients, but through the development of new techniques such as right unilateral ultra-brief pulse, they can be reduced in predisposed patients. Electroconvulsive therapy has proven its effectiveness in multiple pathologies such as major depression, catatonia, even obtaining better results than pharmacological treatments. Despite this, it is still underused in medical practice. Patients and their families, once they have finished their treatment with electroconvulsive therapy, feel satisfied with the results and the care received and even report that they would repeat the treatment if necessary

Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of life

Introducción: Se han considerado una gran cantidad de factores de riesgo para el trastorno por estrés postraumático. En el ámbito de la personalidad previa al trauma, los rasgos neuróticos se han asociado por su propia definición con el desarrollo de TEPT. Las dificultades inherentes al estudio de los trastornos de estrés han impedido determinar con exactitud el verdadero mecanismo por el que se observa dicha asociación. Objetivos: estudiar la naturaleza de la relación entre el neuroticismo y el trastorno por estrés postraumático a través de una revisión sistemática. Métodos: se llevó a cabo una revisión sistemática y posterior evaluación de la evidencia disponible en la base de datos Medline. Tras una primera revisión, se seleccionaron 44 artículos, incluyendo finalmente 9 artículos relevantes para el estudio prospectivo de la relación entre neuroticismo y TEPT. Resultados: en la evaluación inicial de la relación entre el nivel de neuroticismo pre-trauma y la incidencia de TEPT, todos los estudios hallaron diferencias estadísticamente significativas. Al introducir variables relevantes, los resultados de los análisis multivariante restaron gran parte de su intensidad o incluso negaron la existencia de dicha asociación entre neuroticismo y TEPT. Se observó que gran parte de la asociación encontrada en un principio se explicaba según la variable ‘Historia previa de trauma’. Conclusiones: Existe una mayor incidencia de TEPT en los individuos con personalidad de base neurótica, fenómeno explicado en gran parte por la historia acumulada de traumas previos. El papel del neuroticismo es por tanto favorecer el aumento de la psicopatología de base del sujeto, haciéndolo más propenso a desarrollar TEPT ante el subsecuente trauma., Introduction: a large amount of risk factors for PTSD has been considered. In the field of personality prior to the trauma, neurotic traits have been linked for their own definition to the development of PTSD. The inherent difficulties of the study of stress disorders have hindered the exact determination of the mechanism through which this association occurs. Objectives: to study the nature of the relationship between neuroticism and post-traumatic stress disorder through a systematic review. Methodology: a systematic review and subsequent evaluation of the available evidence were conducted in the Medline database. After a first review, 44 articles were selected, eventually including 9 relevant articles for the prospective study of the association between neuroticism and PTSD. Results: at the initial evaluation of the relationship between the level of pre-trauma neuroticism and the incidence of PTSD, all the studies found statistically significant differences. When relevant variables were introduced, the results of multivariate analysis diminished a great amount of the intensity of the association between neuroticism and PTSD or even denied its existence. The most part of the association previously observed was explained through the variable ‘Previous history of trauma’. Conclusions: there is a stronger incidence of PTSD in individuals with basal neurotic traits, a phenomenon explained for the most part by the accumulated history of previous trauma. The part that neuroticism plays is to boost the basal psychopathology of the subject, making him prone to develop PTSD from a subsequent trauma.

Introducción: La polidipsia primaria es una observación clínica frecuente en personas con enfermedad mental, especialmente con esquizofrenia. Se trata de un trastorno complejo e infraestimado, de difícil de reconocimiento y manejo. Objetivos: Estudiar la relación entre polidipsia primaria y enfermedad mental con una revisión sobre los diferentes aspectos históricos, epidemiológicos, etiopatogénicos, clínicos, diagnósticos y terapéuticos de la polidipsia. Analizar la prevalencia de polidipsia en personas con enfermedad mental, y más concretamente en personas con esquizofrenia. Analizar los factores relacionados con la polidipsia en personas con enfermedad mental, y más concretamente en personas con esquizofrenia. Métodos: Se realizaron búsquedas en Pubmed utilizando los términos “polydipsia and mental illness” y “psychogenic polydipsia” en poblaciones de entre 19 y 65 años y escritos en inglés, francés o español. Se identificaron 256 y 107 artículos respectivamente. Tras eliminar duplicados, y revisión de originales y referencias bibliográficas se escogieron 90 publicaciones. Resultados: Se define polidipsia primaria como la ingesta excesiva de fluidos sin explicación fisiológica o farmacológica. Su fisiopatología implica múltiples mecanismos, tanto genéticos como anatómicos, endocrinos, psicológicos y farmacológicos. Para su diagnóstico, se combinan los informes del personal sanitario y determinaciones biológicas (SPGU, UCR, NDWG). Se han descrito rangos de prevalencia en enfermos crónicos de entre un 3,1 y un 39,6 %; de ellos, entre un 14-86 % (1-10,5 % del total de pacientes psiquiátricos crónicos institucionalizados) desarrollarían una segunda fase con hiponatremia y episodios de intoxicación hídrica. Entre los factores asociados al trastorno destacan la cronicidad, la enfermedad mental (sobre todo esquizofrenia), el tabaquismo intenso y el alcohol. Para el tratamiento de la polidipsia se combinan medidas conductuales con tratamiento farmacológico. Conclusiones, Introdución: A polidipsia primaria é unha observación clínica frecuente en persoas con enfermidade mental, especialmente con esquizofrenia. Trátase dun trastorno complexo e infraestimado, de difícil recoñecemento e manexo. Obxectivos: Estudar a relación entre polidipsia primaria e enfermidade mental cunha revisión sobre os aspectos históricos, epidemiolóxicos, etiopatoxénicos, clínicos, diagnósticos e terapéuticos da polidipsia. Analizar a prevalencia de polidipsia en persoas con enfermidade mental, e máis concretamente en persoas con esquizofrenia. Analizar os factores relacionados coa polidipsia en persoas con enfermidade mental, e máis concretamente en persoas con esquizofrenia. Métodos: Realizáronse procuras en Pubmed, utilizando os termos “polydipsia and mental illness” e “psychogenic polydipsia” en poboacións de entre 19 e 65 anos e escritos en inglés, francés ou español. Identificáronse 256 e 107 artigos, respectivamente. Tras eliminar duplicados, e revisión de orixinais e referencias bibliográficas elixíronse 90 publicacións. Resultados: Defínese polidipsia primaria como a inxestión excesiva de fluídos sen explicación fisiolóxica ou farmacolóxica. A súa fisiopatoloxía implica múltiples mecanismos, tanto xenéticos como anatómicos, endocrinos, psicolóxicos e farmacolóxicos. Para o seu diagnóstico, combínanse os informes do persoal sanitario e determinacións biolóxicas (SPGU, UCR, NDWG). As prevalencias publicadas na bibliografía presentan marxes moi amplas (3-39,6% para a polidipsia simple); entre o 14-86% destes enfermos chegarán a desenvolver hiponatremia con episodios de intoxicación hídrica. Entre os factores asociados ao trastorno destacan a cronicidade, a enfermidade mental (sobre todo esquizofrenia), o tabaquismo intenso e o alcol. Para o tratamento da polidipsia combínanse medidas conductuais con tratamento farmacolóxico. Conclusións: A polidipsia pode chegar a ser un grave problema médico, resultando fundamental un diagnóstico e un tratamento temperá., Introduction: Primary polydipsia is a common clinical observation in people with mental illness, frequently seen in patients with schizophrenia. It is a complex and underestimated disorder, difficult to be identified and managed. Objectives: To study the relationship between primary polydipsia and mental illness reviewing the historical, epidemiological, etiopathogenic, clinical, diagnostic, and therapeutic aspects of polydipsia. To analyse the prevalence of polydipsia in people with mental illness, and more specifically in people with schizophrenia. To analyse the factors related to polydipsia in people with mental illness, and more specifically in people with schizophrenia. Methods: A search was conducted in Pubmed using the terms "polydipsia and mental illness" and "psychogenic polydipsia" in human, adult (19-65 years) and articles written in English, French or Spanish. 256 and 107 records, respectively, were identified. After eliminating duplicates, and reviewing originals and bibliographic references, 90 publications were selected. Results: Primary polydipsia is defined as an excessive fluid intake without physiological or pharmacological explanation. Its physiopathology involves multiple mechanisms, such as genetic, anatomical, endocrine, psychological and pharmacological. For its diagnosis, staff report and biological determinations (SPGU, UCR, NDWG) are combined. Prevalence data published in the literature show very wide margins (3-39.6% for simple polydipsia); among 14-86% of these patients will develop hyponatremia with water intoxication episodes. Factors associated include chronicity, mental illness (usually schizophrenia), heavy smoking and alcohol. Treatment for psychogenic polydipsia may involve behavioural and pharmacological approaches. Conclusions: Ultimately, polydipsia can become a serious medical problem, so early diagnosis and an appropriate therapy are essential.

Background Due to the progressive aging of the population, programs to promote active aging have been recommended. However, older adults have difficulty accessing them. Interventions administered through online video games may increase their accessibility, and complementing these with a smartphone app will likely increase adherence and allow for ongoing professional monitoring. The objective of this study is to evaluate the efficacy of a cognitive-behavioral intervention for active aging administered through an online interactive multimedia video game that includes a smartphone app companion. The secondary objectives are to analyze the moderators and mediators of the change in the outcome variables and to evaluate the adherence to the intervention. Methods/design A randomized controlled clinical trial will be conducted. Adults 45 years and older will be randomly assigned to a cognitive-behavioral intervention administered through an online multimedia video game that includes a smartphone app companion or to a control group that will receive online information on active aging (274 participants per group). The intervention will be administered in eight weekly 45-min modules. An investigator-blinded evaluation will be conducted using online self-administered tests at baseline, post-intervention, and 6- and 12-month follow-ups. The primary outcome will be mental health status as evaluated using the 36-item Short-Form Health Survey (SF-36) at post-intervention. Secondary outcomes will be emotional well-being, depressive symptoms, reinforcement, negative thoughts, self-reported memory, cognitive task performance, sleep hygiene behaviors, physical activity, eating habits, body mass index, social support, dropout, treatment adherence, and satisfaction with the intervention. Discussion If the results are favorable, this study would involve the development of the first evidence-based active aging promotion intervention based on a video game that includes a smartphone app comp

Introduction: White noise speech illusions index liability for psychotic disorder in case–control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control -> sibling -> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls -> siblings -> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02–1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79–1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85–1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09–1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84–1.05; ORlow cognitive ability 1.43, 95% CI 1.23–1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82–1.04; ORhigh adversity 1.31, 95% CI 1.1

Background: Due to the appeal and recent technological advances of video games, the games have gained interest as an intervention tool for active aging. The aim of this systematic literature review and meta-analysis was to determine the efficacy of video games for active aging and to examine the influence of potential moderator variables. Methods: A systematic search was done using the following databases: Medline, PsycINFO, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. In addition, previous reviews and meta-analyses were used to identify randomized controlled trials (RCT) of video game-based interventions for active aging published through February 28, 2018. An evaluation of the methodological quality of the articles and a meta-analysis and moderator analysis was conducted. Results: A total of 22 articles depicting 21 RCT with 1125 participants were included. The results indicated that video game-based interventions produced positive effects on objectively measured physical health, negative affect and social health, with small effect sizes (d = 0.41, d = 0.26 and d = 0.40, respectively). The magnitude of this effect was moderated by the presence of subclinical conditions of participants, the type of game (exergames), the presence of physical activity, the type of prevention (indicated), non-blinded assignation, and older age of participants. The methodological quality of the studies was acceptable, the weakest area being external validity. Conclusion: These finding indicate that video game-based interventions may assist adults in leading active aging processes and preventing secondary aging. Although more research is needed, video game-based interventions are a promising and accessible tool for active aging promotion

Background: The purpose of this study was to gain an understanding of the profiles of the new treatment demands posed by opioid addicts between 2005 and 2010 at the addictive disorders assistance units in Galicia, Spain. Methods: A cluster analysis was performed using data from 1,655 treatment entrants. Clusters were constructed using sociodemographic and medicolegal variables. A cluster analysis was also conducted according to age. Once clusters were defined, their association with the following variables was analyzed: age at first use of opioids, years of use, frequency of opioid use in the previous month, psychiatric treatment, cocaine use, existence of a drug-dependent partner, and source of referral. Results: Four clusters were obtained in the main analysis. Cluster 1 (34.01%) consisted of young males, cluster 2 (16.19%) consisted of not-so-young males, cluster 3 (32.62%) consisted mainly of older males and a small group of females, and cluster 4 (17.18%) was made up entirely of women. With regard to age-related clusters, two clusters were obtained in those under the age of 30 years: cluster 1 (73%) without medicolegal complications and cluster 2 (27%) with medicolegal complications. For those over the age of 30 years, two clusters were obtained: cluster 1 (53.92%) with hardly any medicolegal complications and cluster 2 (46.08%) with medicolegal complications. Conclusion: Cluster analysis suggests that there have been no substantial changes in variables indicating greater severity in this new group of patients. Women are likely to seek help earlier, which reduces their duration of opioid use. The younger the patient, the shorter the duration of opioid use and the greater the likelihood of cessation of intravenous use. Public health systems should use a two-pronged treatment strategy of short but intense cessation therapies for women and younger treatment entrants and longer maintenance and replacement therapies for older treatment entrants with more psychosocia