Uso de Antidepresivos y Suicidio en el Trastorno Bipolar

[spa] Introducción. El trastorno bipolar (TB) tiene un gran impacto en las personas que lo padecen y una mortalidad por suicidio hasta 20 veces mayor que el resto de la población. La depresión bipolar es uno de los principales factores de riesgo de suicidio, sin embargo existe escasa evidencia en relación a su tratamiento. Uno de los temas más controversiales es el uso de antidepresivos, que a pesar de ser el tratamiento más utilizado, su eficacia y seguridad han sido puestos en duda. Hipótesis. Los pacientes expuestos a AD vs los no expuestos tienen características clínicas y un curso de enfermedad diferente, presentando un mayor número de complicaciones, entre ellas, una mayor incidencia de suicidabilidad. Objetivos. Caracterizar los factores demográficos y clínicos asociados al uso de antidepresivos en pacientes con depresión bipolar, así como los factores asociados a ideación o actos suicidas. Valorar la asociación entre uso de antidepresivos y conductas suicidas e identificar los factores predictores de riesgo suicida en el trastorno bipolar. Método. Estudio naturalístico de cohorte. Se reclutaron pacientes adultos en seguimiento en la Unidad de Trastorno Bipolar de nuestro hospital. Se recogieron variables clínicas basados en entrevistas semiestructuradas y escalas. Asimismo, se realizó un seguimiento bisemanal de un episodio depresivo index durante 12 semanas y se recogieron variables clínicas, de respuesta al tratamiento y de suicidabilidad. Para el tercer estudio, se reclutaron pacientes con trastorno bipolar en seguimiento sistemático, provenientes de 5 centros en distintos países. Análisis de resultados. Se realizaron análisis bivariados para buscar asociaciones entre factores demográficos y clínicos y uso de antidepresivos. Con los resultados de este análisis preliminar, se realizó un modelo de regresión logística múltiple con uso de AD como variable dependiente. Se utilizó el mismo procedimiento para valorar factores asociados a suicidabilidad y establecer un modelo predictivo de suicidabilidad en depresión bipolar. Resultados/Conclusiones. La prevalencia de uso de antidepresivos para el tratamiento de la depresión bipolar aguda es muy alta (cercana al 80%), incluso en un centro especializado como el nuestro, y está asociado a una historia de depresión más severa. Los virajes fueron 7 veces más altos en el grupo expuesto a antidepresivos, incluso con tratamiento coadyuvante con estabilizadores del ánimo. Los factores de riesgo asociados a la ideación y los actos suicidas en el trastorno bipolar tienen que ver con una mayor severidad de la enfermedad y con la presencia de síntomas mixtos y polaridad predominante depresiva, así como el sexo femenino y la mayor latencia en el diagnóstico. Asimismo, observamos que el riesgo de ideación y conductas suicidas en el trastorno bipolar tipo II es tan alto como en el tipo I, lo que sugiere que éste subtipo no es una variante más leve de la enfermedad, sino clínicamente diferente. La clasificación por polaridad predominante es un buen diferenciador del curso clínico y pronóstico de los pacientes con trastorno bipolar. Destaca la asociación entre polaridad predominante depresiva y el debut de enfermedad con episodios depresivos o mixtos, la presencia de mas episodios mixtos durante la evolución y el aumento del riesgo de actos suicidas. Asimismo, sumar los episodios mixtos a la polaridad predominante depresiva, aumenta significativamente su asociación con los actos suicidas y la capacidad predictiva de morbilidad a largo plazo de los primeros episodios. Por último, esta clasificación permite planificar las intervenciones terapéuticas según las características clínicas de los pacientes, además de abrir la posibilidad de buscar marcadores biológicos a partir de subgrupos con comportamiento clínico diferente. Limitaciones. Los estudios observacionales no permiten establecer relaciones causales. El hecho de haberse realizado en un centro académico especializado podría limitar la generalización de los resultados.[eng] Introduction. Suicide accounts for 15-20% of bipolar patients overall mortality. Depression is one of the most important risk factors and its treatment is a matter of controversy, especially regarding antidepressant use. Objective. To characterize clinical and demographic factors associated to suicidality and antidepressant use. In addition, to evaluate the association between antidepressant use and suicidal behaviour. Methods. Naturalistic cohort study. We recruited 290 systematically followed-up bipolar patients from our program at Hospital Clínic (Barcelona, Spain). We assessed them through semistructured clinical interviews and scales during a depressive index episode and followed them for 12 weeks. For the third study, we recruited 928 bipolar I patients from five academic centers in different countries and tested the replicability and usefulness of the predominant polarity concept and its association with suicide. Results/Conclusions. Despite the scarce evidence available, the proportion of patients receiving antidepressants for the treatment of bipolar depression is strikingly high and its use is associated with more severe depressive morbidity. Regarding acute complications associated with treatment, the risk of treatment associated manic switch in the antidepressant group was seven times higher. In addition, risk for suicidal thoughts/behaviour and rapid cycling was two times higher in the antidepressant group, although the difference was not statistically significant. These results suggest that antidepressant use may be related with a higher proportion of adverse outcomes in bipolar depression. Risk factors associated with suicidal thoughts and acts in bipolar disorder, are associated with a more severe illness and depressive morbidity, such as the presence of mixed symptoms, depressive predominant polarity and longer delay between illness onset and the diagnosis of bipolar disorder. Suicidal thoughts and acts in bipolar disorder type II are as prevalent as in type I. This strongly suggests that bipolar type II is not a milder form of disorder, but clinically different. Finally, predominant polarity is a relevant and useful way of classifying bipolar disorder patients, with different clinical course and prognosis. Depressive predominant polarity is associated with a depressive or mixed episode at onset, the presence of more mixed episodes during the clinical course of the disorder and a two-fold increase in suicidal risk, when compared to manic/hypomanic predominant polarity. Including mixed-states with predominant depressions markedly increased association with suicidal risk (two-fold), which confirms mixed symptoms as an important risk factor. Limitations. Causal relationships cannot be established properly through observational studies. Nevertheless, such naturalistic experiences may serve as useful representations of current clinical practices and results. Sampling at a prominent university referral center may not generalize to other sites

Is bipolar disorder an endocrine condition? Glucose abnormalities in bipolar disorder

The World Health Organisation placed bipolar disorder at the top ten causes of disability worldwide, due not only to its functional impairment but also to its increased medical morbidity and mortality. An increased suicide rate, poor healthcare access, poor health habits, and medication side‐effects contribute to the increased morbidity and mortality. However, the leading contributors to the excess of mortality are cardiovascular pathologies 1, a finding already highlighted by Derby in 1933 in a cohort of manic‐depressive patients admitted to a general hospital. Cardiovascular risk factors, such as obesity, hypertension, type 2 diabetes mellitus (T2DM) 2, and lipid disturbances, are highly increased in bipolar disorder. In between those, glycemic abnormalities are the most repeated finding, taking into account that since the onset of the 20th century, several authors had raised the attention toward an unexpected relationship between manic‐depressive illness and glucose metabolism 3. In addition, the prevalence of T2DM in bipolar disorders ranges from 8% to 17% a threefold increase compared with the general population and bipolar patients with comorbid T2DM may have a more severe course of the psychiatric illness (greater number of depressive and manic episodes, more hospitalizations, and suicidality) and refractoriness to treatment. In addition, studies regarding metabolic disturbances in relatives of bipolar disorder and non‐affective psychosis have described an increased risk of developing glucose abnormalities, adding more scientific background to the unexpected relationship. However, pharmacological treatment, including both antipsychotic agents, antidepressants and mood stabilizers, may have confounded this relationship

A 12-month prospective study on the time to hospitalization and clinical management of a cohort of bipolar type I and schizoaffective bipolar patients

Background: Schizoaffective disorder, bipolar type (SAD) and bipolar disorder I (BD) present a large clinical overlap. In a 1-year follow-up, we aimed to evaluate days to hospitalization (DTH) and predictors of relapse in a SAD-BD cohort of patients. Methods: A 1-year, prospective, naturalistic cohort study considering DTH as primary outcome and incidence of direct and indirect measures of psychopathological compensation as secondary outcomes. Kaplan-Meyer survival analysis with Log-rank Mantel-Cox test compared BD/SAD subgroups as to DTH. After bivariate analyses, Cox regression was performed to assess covariates possibly associated with DTH in diagnostic subgroups. Results: Of 836 screened patients, 437 were finally included (SAD = 105; BD = 332). Relapse rates in the SAD sample was n = 26 (24.8%) vs. n = 41 (12.3%) in the BD sample (p = 0.002). Mean ± SD DTH were 312.16 ± 10.6 (SAD) vs. 337.62 ± 4.4 (BD) days (p = 0.002). Patients with relapses showed more frequent suicide acts, violent behaviors, and changes in pharmacological treatments (all p 0.0005). Conclusions: SAD patients relapse earlier with higher hospitalization rates and violent behavior during psychotic episodes whereas bipolar patients have more suicide attempts. Psychiatric/psychological follow-up visits may delay hospitalizations by closely monitoring symptoms of self- and hetero-aggression

Self-monitoring and psychoeducation in bipolar patients with a smart-phone application (SIMPLe) project: design, development and studies protocols

Background: New technologies have recently been used for monitoring signs and symptoms of mental health illnesses and particularly have been tested to improve the outcomes in bipolar disorders. Web-based psychoeducational programs for bipolar disorders have also been implemented, yet to our knowledge, none of them have integrated both approaches in one single intervention. The aim of this project is to develop and validate a smartphone application to monitor symptoms and signs and empower the self-management of bipolar disorder, offering customized embedded psychoeducation contents, in order to identify early symptoms and prevent relapses and hospitalizations. Methods/design: The project will be carried out in three complementary phases, which will include a feasibility study (first phase), a qualitative study (second phase) and a randomized controlled trial (third phase) comparing the smartphone application (SIMPLe) on top of treatment as usual with treatment as usual alone. During the first phase, feasibility and satisfaction will be assessed with the application usage log data and with an electronic survey. Focus groups will be conducted and technical improvements will be incorporated at the second phase. Finally, at the third phase, survival analysis with multivariate data analysis will be performed and relationships between socio-demographic, clinical variables and assessments scores with relapses in each group will be explored. Discussion: This project could result in a highly available, user-friendly and not costly monitoring and psychoeducational intervention that could improve the outcome of people suffering from bipolar disorders in a practical and secure way. Trial registration: Clinical Trials.gov: NCT02258711 (October 2014). Keywords: Bipolar disorder, Psychoeducation, Monitoring, Smartphones, Self-managemen

Emotional intelligence: A comparison between patients after first episode mania and those suffering from chronic bipolar disorder type i

Deficits in emotional intelligence (EI) were detected in patients with Bipolar Disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients. Methods: The Emotional Intelligence Quotient (EIQ) was calculated with the MayerSalovey-Caruso Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model. Results: 184 subjects were included (FEM n=48, euthymic chronic BD type I n=75, HC n=61). BD patients performed significantly worse than HC on the EIQ (Mean Difference MD=10.09, Standard Error SE=3.14, p=0.004) and on the Understanding emotions branch (MD=7.46, SE=2.53, p=0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex (β=-0.293, p=0.034) and verbal memory performance (β=0.374, p=0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains. Conclusions: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness

Country-level gender inequality is associated with structural differences in the brains of women and men

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality

Self-monitoring and psychoeducation in bipolar patients with a smart-phone application (SIMPLe) project: design, development and studies protocols

Background: New technologies have recently been used for monitoring signs and symptoms of mental health illnesses and particularly have been tested to improve the outcomes in bipolar disorders. Web-based psychoeducational programs for bipolar disorders have also been implemented, yet to our knowledge, none of them have integrated both approaches in one single intervention. The aim of this project is to develop and validate a smartphone application to monitor symptoms and signs and empower the self-management of bipolar disorder, offering customized embedded psychoeducation contents, in order to identify early symptoms and prevent relapses and hospitalizations. Methods/design: The project will be carried out in three complementary phases, which will include a feasibility study (first phase), a qualitative study (second phase) and a randomized controlled trial (third phase) comparing the smartphone application (SIMPLe) on top of treatment as usual with treatment as usual alone. During the first phase, feasibility and satisfaction will be assessed with the application usage log data and with an electronic survey. Focus groups will be conducted and technical improvements will be incorporated at the second phase. Finally, at the third phase, survival analysis with multivariate data analysis will be performed and relationships between socio-demographic, clinical variables and assessments scores with relapses in each group will be explored. Discussion: This project could result in a highly available, user-friendly and not costly monitoring and psychoeducational intervention that could improve the outcome of people suffering from bipolar disorders in a practical and secure way. Trial registration: Clinical Trials.gov: NCT02258711 (October 2014). Keywords: Bipolar disorder, Psychoeducation, Monitoring, Smartphones, Self-managemen

Is bipolar disorder an endocrine condition? Glucose abnormalities in bipolar disorder

The World Health Organisation placed bipolar disorder at the top ten causes of disability worldwide, due not only to its functional impairment but also to its increased medical morbidity and mortality. An increased suicide rate, poor healthcare access, poor health habits, and medication side‐effects contribute to the increased morbidity and mortality. However, the leading contributors to the excess of mortality are cardiovascular pathologies 1, a finding already highlighted by Derby in 1933 in a cohort of manic‐depressive patients admitted to a general hospital. Cardiovascular risk factors, such as obesity, hypertension, type 2 diabetes mellitus (T2DM) 2, and lipid disturbances, are highly increased in bipolar disorder. In between those, glycemic abnormalities are the most repeated finding, taking into account that since the onset of the 20th century, several authors had raised the attention toward an unexpected relationship between manic‐depressive illness and glucose metabolism 3. In addition, the prevalence of T2DM in bipolar disorders ranges from 8% to 17% a threefold increase compared with the general population and bipolar patients with comorbid T2DM may have a more severe course of the psychiatric illness (greater number of depressive and manic episodes, more hospitalizations, and suicidality) and refractoriness to treatment. In addition, studies regarding metabolic disturbances in relatives of bipolar disorder and non‐affective psychosis have described an increased risk of developing glucose abnormalities, adding more scientific background to the unexpected relationship. However, pharmacological treatment, including both antipsychotic agents, antidepressants and mood stabilizers, may have confounded this relationship

Shaped before birth: Obstetric complications identify a more severe clinical phenotype among patients presenting a first affective or non-affective episode of psychosis

Obstetric complications (OCs) may contribute to the heterogeneity that characterizes psychiatric illness, particularly the phenotypic presentation of first episode psychoses (FEP). Our aim was to examine the relationship between OCs and socio-demographic, clinical, functioning and neuropsychological characteristics in affective and non-affective FEP. We performed a cross-sectional,study where we recruited participants with FEP between 2011 and 2021, and retrospectively assessed OCs using the Lewis-Murray scale. OCs were used as a dichotomous variable and further stratified into three subtypes: complications of pregnancy, abnormal fetal growth and development, and difficulties in delivery. We performed a logistic stepwise forward regression analysis to examine variables associated with the presence of OCs. Of the 104 participants (67 affective FEP and 37 non-affective FEP), 31.7% (n = 33) had experienced OCs. Subjects with OCs showed a more gradual emergence of prodromal symptoms as well as higher negative and total Positive and Negative Syndrome Scale (PANSS) scores. In the multivariate analysis, the presence of OCs was independently associated with a younger age at first episode of any type (OR = 0.904, p = 0.003) and slower emergence of prodromal symptoms (OR = 0.274, p = 0.011). When considering specific types of OCs, those related with fetal growth were associated with worse neuropsychological performance, while OCs at delivery were related to earlier onset of illness and more severe symptoms. In conclusion, OCs signaled a specific FEP phenotype characterized by earlier and more protracted onset of illness as well as more burdensome symptoms, independently of FEP type (i.e., affective vs non-affective). These results indicate a potential target of early intervention in FEP