Browsing by Author "Mena, Cristian"
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Item Early treatment resistance in a Latin-American cohort of patients with schizophrenia(2018) Mena, Cristian; González-Valderrama, Alfonso; Iruretagoyena, Bárbara; Undurraga, JuanBackground: Failure to respond to antipsychotic medication in schizophrenia is a common clinical scenario with significant morbidity. Recent studies have highlighted that many patients present treatment-resistance from disease onset. We here present an analysis of clozapine prescription patterns, used as a real-world proxy marker for treatment-resistance, in a cohort of 1195 patients with schizophrenia from a Latin-American cohort, to explore the timing of emergence of treatment resistance and possible subgroup differences. Methods: Survival analysis from national databases of clozapine monitoring system, national disease notification registers, and discharges from an early intervention ward. Results: Echoing previous studies, we found that around 1 in 5 patients diagnosed with schizophrenia were eventually prescribed clozapine, with an over-representation of males and those with a younger onset of psychosis. The annual probability of being prescribed clozapine was highest within the first year (probability of 0.11, 95% confidence interval of 0.093-0.13), compared to 0.018 (0.012-0.024) between years 1 and 5, and 0.006 (0-0.019) after 5years. Age at psychosis onset, gender, dose of clozapine used, and compliance with hematological monitoring at 12months, was not related to the onset of treatment resistance. A similar pattern was observed in a subgroup of 230 patients discharged from an early intervention ward with a diagnosis of non-affective first episode of psychosis. Conclusions: Our results highlight that treatment resistance is frequently present from the onset of psychosis. Future studies will shed light on the possible different clinical and neurobiological characteristics of this subtype of psychosis.Item Gender, age and geographical representation over the past 50 years of schizophrenia research(2022) Alliende, Luz María; Czepielewski, Leticia; Aceituno, David; Castañeda, Carmen Paz; Diaz, Camila; Iruretagoyena, Bárbara; Mena, Carlos; Mena, Cristian; Ramírez, Juan Pablo; Tepper, Ángeles; Vásquez, Javiera; Fonseca, Lais; Machado, Viviane; Hernández, Camilo; Vargas, Cristian; Gómez, Gladys; Kobayashi, Luis; Moncada, Tomás; Evans, Sara; Bressan, Rodrigo; Gama, Clarissa; López, Carlos; De la Fuente, Camilo; González, Alfonso; Undurraga, Juan; Gadelha, Ary; Crossley, Nicolás; ANDES NetworkPrevious studies have suggested that subjects participating in schizophrenia research are not representative of the demographics of the global population of people with schizophrenia, particularly in terms of gender and geographical location. We here explored if this has evolved throughout the decades, examining changes in geographical location, gender and age of participants in studies of schizophrenia published in the last 50 years. We examined this using a meta-analytical approach on an existing database including over 3,000 studies collated for another project. We found that the proportion of studies and participants from low-and-middle income countries has significantly increased over time, with considerable input from studies from China. However, it is still low when compared to the global population they represent. Women have been historically under-represented in studies, and still are in high-income countries. However, a significantly higher proportion of female participants have been included in studies over time. The age of participants included has not changed significantly over time. Overall, there have been improvements in the geographical and gender representation of people with schizophrenia. However, there is still a long way to go so research can be representative of the global population of people with schizophrenia, particularly in geographical terms.Item High prevalence of metabolic alterations in Latin American patients at initial stages of psychosis(John Wiley & Sons, Inc., 2020) Iruretagoyena, Bárbara; Castañeda, Carmen; Undurraga, Juan; Nachar, Rubén; Mena, Cristian; Gallardo, Carlos; Crossley, Nicolas; Gonzalez-Valderrama, AlfonsoAim Studies conducted in the United States have highlighted a higher prevalence of metabolic alterations (MA) in Latino population and Latino psychotic patients. Metabolic risk in psychosis is known to be present from initial stages of the disease. To better characterize this population, we explored the prevalence of MA and metabolic syndrome (MS) in early psychosis patients in a Latin American country. Methods Transversal, observational study comparing the prevalence of MA and MS in patients with early psychosis from an outpatient program in Chile (n = 148) with a community representative sample from the 2009‐2010 National Health Survey (n = 568). ANOVA and regression analysis were performed obtaining odds ratio for MA and MS. Results The prevalence of MS was 44.7% in patients compared to 11.4% in the community sample (odds ratio [OR] 5.28, confidence interval [CI] 95% 3.07‐9.08; P‐value <0.001). There was no effect of gender. Subgroup analyses showed no significant association of MS with clozapine/olanzapine use, treatment duration or tobacco use. There was an association between treatment duration and hypertriglyceridemia (P = 0.024; OR 1.02, CI 95% 1.00‐1.04) and obesity (P = 0.007; OR 5.93, CI 95% 1.82‐20.22). Clozapine/olanzapine use was associated with hyperglycaemia (P = 0.007; OR 6.04, CI 95% 1.63‐22.38) and high low density lipoprotein (P = 0.033 ANOVA; OR 5.28, CI 95% 1.14‐24.37). Conclusion Latino psychotic patients have a high risk of MA and MS at initial stages of the disease which is not entirely explained by the higher risk in the whole Latino population, is irrespective of gender, and does not seem to be entirely a response to atypical antipsychotic use.Item Predictors of clozapine discontinuation at 2 years in treatment-resistant schizophrenia(2021) Iruretagoyena, Bárbara; Castañeda, Carmen Paz; Mena, Cristian; Diaz, Camila; Nachar, Ruben; Ramirez, Juan Pablo; González, Alfonso; Undurraga, JuanIntroduction: Little is known about predictors of clinical response to clozapine treatment in treatment-resistant psychosis. Most published cohorts are small, providing inconsistent results. We aimed to identify baseline clinical predictors of future clinical response in patients who initiate clozapine treatment, mainly focusing on the effect of age, duration of illness, baseline clinical symptoms and homelessness. Methodology: Retrospective cohort of patients with treatment-resistant schizophrenia, aged between 15 and 60 years, that initiated clozapine between 2014 and 2017. Sociodemographic characteristics, years from illness diagnosis, and clinical presentation before the initiation of clozapine were collected and analyzed. All-cause discontinuation at two years follow-up was used as the primary measure of clozapine response. Results: 261 patients were included with a median age at illness diagnosis of 23 years old (IQR 19-29) and a median age at clozapine initiation of 25 (IQR: 21-33). 72.33% (183/253) continued clozapine after two years follow-up. Being homeless was associated to higher clozapine non-adherence, with an OR of 2.78 (95%CI 1.051-7.38) (p = 0.039, controlled by gender). Older age at clozapine initiation and longer delay from first schizophrenia diagnosis to clozapine initiation were also associated with higher clozapine non-adherence, with each year increasing the odds of discontinuation by 1.043 (95%CI 1.02-1.07; p = 0.001) and OR 1.092 (95%CI 1.01-1.18;p = 0.032) respectively. Conclusion: Starting clozapine in younger patients or shortly after schizophrenia diagnosis were associated with better adherence.Publication The enduring gap in educational attainment in schizophrenia according to the past 50 years of published research: a systematic review and meta-analysis(2022) Crossley, Nicolás; Alliende, Luz; Czepielewski, Leticia; Aceituno, David; Castañeda, Carmen; Diaz, Camila; Iruretagoyena, Bárbara; Mena, Carlos; Mena, Cristian; Ramírez, Juan; Tepper, Angeles; Vásquez, Javiera; Fonseca, Lais; Machado, Viviane; Hernández, Camilo; Vargas, Cristian; Gómez, Gladys; Kobayashi, Luis; Moncada, Tomás; Arango, Celso; Barch, Deanna; Carter, Cameron; Correll, Christoph; Freimer, Nelson; McGuire, Philip; Evans, Sara; Undurraga, Eduardo; Bressan, Rodrigo; Gama, Clarissa; López, Carlos; De la Fuente, Camilo; González, Alfonso; Undurraga, Juan; Gadelha, AryBackground: Educational attainment is associated with wellbeing and health, but patients with schizophrenia achieve lower levels of education than people without. Several effective interventions can ameliorate this situation. However, the magnitude of the education gap in schizophrenia and its change over time are unclear. We aimed to reconstruct the trajectories of educational attainment in patients with schizophrenia and, if reported, their healthy comparator controls. Methods: We did a systematic review and meta-analysis including all studies reporting on patients with schizophrenia (of mean age ≥18 years) and describing the number of years of education of the participants, with or without healthy controls. There were no other design constraints on studies. We excluded studies that included only patients with other schizophrenia spectrum disorders and studies that did not specify the number of years of education of the participants. 22 reviewers participated in retrieving data from a search in PubMed and PsycINFO (Jan 1, 1970, to Nov 24, 2020). We estimated the birth date of participants from their mean age and publication date, and meta-analysed these data using random-effects models, focusing on educational attainment, the education gap, and changes over time. The primary outcome was years of education. The protocol was registered on PROSPERO (CRD42020220546). Findings: From 32 593 initial references, we included 3321 studies reporting on 318 632 patients alongside 138 675 healthy controls (170 941 women and 275 821 men from studies describing sex or gender; data on ethnicity were not collected). Patients' educational attainment increased over time, mirroring that of controls. However, patients with schizophrenia in high-income countries had 19 months less education than controls (-1·59 years, 95% CI -1·66 to -1·53; p<0·0001), which is equivalent to a Cohen's d of -0·56 (95% CI -0·58 to -0·54) and implies an odds ratio of 2·58 for not completing 12 years of education (ie, not completing secondary education) for patients compared with controls. This gap remained stable throughout the decades; the rate of change in number of total years of education in time was not significant (annual change: 0·0047 years, 95% CI -0·0005 to 0·0099; p=0·078). For patients in low-income and middle-income countries, the education gap was significantly smaller than in high-income countries (smaller by 0·72 years, 0·85 to 0·59; p<0·0001), yet there was evidence that this gap was widening over the years, approaching that of high-income countries (annual change: -0·024 years, -0·037 to -0·011; p=0·0002). Interpretation: Patients with schizophrenia have faced persistent inequality in educational attainment in the last century, despite advances in psychosocial and pharmacological treatment. Reducing this gap should become a priority to improve their functional outcomes. Funding: Ciencia y Tecnología para el Desarrollo (CYTED) to the Latin American Network for the Study of Early Psychosis (ANDES).