Effectiveness of AstraZeneca vaccine against SARS-CoV-2 (ChAdox1-S) in reducing in-hospital mortality in individuals with COVID-19 and schizophrenia: A retrospective cohort study.

ChAdOx1-S is a viral vector vaccine developed by AstraZeneca. We aimed to assess the effectiveness of 1 and 2 doses of the ChAdOx1-S vaccine in reducing COVID-19-related in-hospital mortality in individuals with schizophrenia. This is a retrospective cohort study using a nationwide hospital database in Brazil. Individuals diagnosed with COVID-19 and schizophrenia were included in the study. The exposures were 0, 1, and 2 doses of ChAdOx1-S. The outcome of mortality was measured in hazard ratios (HR), calculated using multivariable Cox regression models. The study included 1,929 positive cases of COVID-19 in schizophrenia patients. After adjusting for age, socioeconomic factors, and comorbidities, we observed a significant 55% decrease in the hazard of mortality in the 2-dose vaccination group (HR 0.45, 95% CI: 0.310-0.652) compared to the unvaccinated. Surprisingly, our results did not show any significant reduction in the hazard of mortality in the 1 dose vaccination group (HR 1.278, 95% CI: 0.910-1.795). The effectiveness of two doses of ChAdOx1-S in individuals with schizophrenia aligns with findings from studies on the general population. That one dose was insignificant. Overall, these findings are important for informing public health decisions - prioritizing individuals with schizophrenia for vaccinations and managing acceptance of vaccines.

Dopamine D2 receptor antagonism of antipsychotics and the risk of death due to choking.

The risk of fatal choking for people with schizophrenia and associations with antipsychotic medication are largely unknown. Therefore, we calculated the choking-related standardized mortality ratio for schizophrenia relative to the general population (SMRchoking). We also computed adjusted hazard ratios (aHR) of choking-related mortality for antipsychotics in a nationwide cohort of patients with schizophrenia (N = 59,916). SMRchoking was 20.5 (95 % confidence interval (CI)=17.1-23.9). The aHR was 1.74 (95 %CI=1.19-2.55) for strong dopamine 2-antagonists. For other antipsychotics, CIs included 1. Importantly, aHRs were particularly high for high dose categories of strong dopamine D2 receptor (D2R) antagonists. In conclusion, a schizophrenia diagnosis is associated with a 20-fold risk of death due to choking. This risk is elevated during use of strong D2R antagonist antipsychotics, particularly when prescribed in high dosages.

Regional differences in mortality risk and in attenuating or aggravating factors in schizophrenia: A systematic review and meta-analysis.

People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09-8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92-2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08-18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07-4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.

Schizophrenia is associated with severe consequences / Asociación de la esquizofrenia con consecuencias graves

Schizophrenia is an illness that affects millions of individuals. It is typically accompanied by positive, negative and cognitive symptoms. These symptoms are typically associated with the onset and progression of schizophrenia. However, aside from these known symptoms, there are consequences of having schizophrenia. In particular, metabolic syndrome, early death and suicide, diseases, lowered pain perception, sexual dysfunction, aggressive behavior/victimization, stigma, and cognitive deficit are all consequences of having schizophrenia. In this paper, we review the various consequences of having schizophrenia. These consequences should be monitored for, much like the typical symptoms, but are usually omitted from treatment. (AU)

La esquizofrenia es una enfermedad que afecta a millones de individuos, y que normalmente se acompaña de síntomas positivos, negativos y cognitivos. Dichos síntomas están normalmente asociados al inicio y progresión de la esquizofrenia. Sin embargo, aparte de estos síntomas conocidos, existen consecuencias de padecer esquizofrenia. En particular, el síndrome metabólico, la muerte prematura y el suicidio, las enfermedades, la disminución de la percepción del dolor, la disfunción sexual, el comportamiento agresivo/victimización, el estigma, y el déficit cognitivo son consecuencias de padecer esquizofrenia. En este documento, revisamos las diversas consecuencias del padecimiento de esquizofrenia. Deberán supervisarse dichas consecuencias, al igual que los síntomas típicos, aunque normalmente se omiten del tratamiento de la enfermedad. (AU)

Schizophrenia pinpointed as a key factor in heat deaths.

The mental illness tripled the risk of death during a searing 2021 heat wave, researchers find.

COVID-19 hospitalisation, mortality, vaccination, and postvaccination trends among people with schizophrenia in Israel: a longitudinal cohort study.

BACKGROUND: Individuals with schizophrenia have an increased risk of severe COVID-19 outcomes, nonetheless, no previous study has provided a year-long account of this risk, or assessed postvaccination trends in this population. This study assessed temporal trends in COVID-19 hospitalisation and mortality among people with schizophrenia during the first year of the pandemic, the predictors for COVID-19 vaccination, postvaccination infection, admission to hospital, and mortality. METHODS: In this longitudinal cohort study, people with schizophrenia (n=25 539) and controls (n=25 539) were assessed for COVID-19 outcomes before and after vaccination, up to April 30, 2021. Cox proportional hazard regression models and Kaplan-Meier analyses were done to assess longitudinal trends. The study used the databases of Clalit Health Services, the largest health-care organisation in Israel. FINDINGS: The sample included 51 078 participants, of which 31 141 (61·0%) male and 19 937 (39·0%) female participants, with a mean age of 51·94 years (SD 15·62). Most of the sample was from the general Jewish population (75·9%), followed by the Arab (19·1%) and Jewish Ultraorthodox population (5·1%). Overall of 51 078 individuals, 356 (0·7%) people had been hospitalised, 133 (0·3%) had died, and a total of 27 400 (53·6%) had been vaccinated. People with schizophrenia showed a higher risk for COVID-19 hospitalisation (HR 4·81, 95% CI 3·57-6·48, p<0·0001) and mortality (HR 2·52, 95% CI 1·64-3·85, p<0·0001), and showed a sharper decline in survival as time progressed. The control group showed a sharper incline in probability to vaccinate (log-rank=309·88, p<0·0001). Medical comorbidity of diabetes, hypertension, obesity, or ischaemic heart disease played a significant role in predicting vaccination rates in the schizophrenia group (all p<0·0001), but not in the control group. Hospitalisation and mortality disparities remained higher among people with schizophrenia who had not been vaccinated in comparison to controls (incidence rate difference of 6·2 and 3·2, respectively) but substantially declined in fully vaccinated groups (incidence rate difference of 1·1 and -0·9, respectively). INTERPRETATION: People with schizophrenia have higher hospitalisation and mortality risk, yet have lower rates of vaccination than in the general population. Disparities in COVID-19 severe outcomes can be substantially reduced by national vaccination plans aimed at actively reaching out to people with schizophrenia. FUNDING: No funding.

Covid-19, hypercoagulability and risk of mortality in schizophrenia.

Covid-19 disease has been linked to a high risk of hyper- coagulability that can severely condition the evolution of this respiratory syndrome in the acute phase; and also due to the possible sequelae of a chronic thrombosis, as is the case of chronic pulmonary thromboembolism; or due to complications associated with anticoagulant treatment such as bleeding.

Comparison of Long-Acting Injectable Antipsychotics With Oral Antipsychotics and Suicide and All-Cause Mortality in Patients With Newly Diagnosed Schizophrenia.

Importance: Schizophrenia is generally considered to be among the most severe psychiatric disorders because of the excessive mortality associated with it. Research to find means to reduce this excessive mortality is warranted. Objective: To investigate associations of long-acting injectable antipsychotics (LAIs) with all-cause, natural-cause, and suicide mortality risks as well as the impacts of early use of LAIs in patients with newly diagnosed schizophrenia. Design, Setting, and Participants: This cohort study used data from the Taiwan National Health Insurance Research Database to construct a population-based cohort of patients with schizophrenia who received oral antipsychotics (OAPs) from January 1, 2002, to December 31, 2017. Within this cohort, the LAI group was defined as patients who switched to LAIs and were prescribed LAIs at least 4 times within 1 year. The LAI group was propensity matched 1:1 to patients who continued receiving OAPs of the same compounds. All patients were followed up until switching the antipsychotic administration route, death, or the end of the study (December 31, 2018), whichever occurred first. Data analysis was performed from January 2002 to December 2018. Main Outcomes and Measures: All-cause mortality, natural-cause mortality, suicide mortality, and suicide attempts. Results: In total, 2614 patients who switched to LAIs (median [interquartile range] {IQR} age, 30 [23-39] years) and 2614 who received OAPs (median [IQR] age, 30 [23-39] years) were included (1333 male patients [51.0%] in each group). During the 16-year follow-up period (median [IQR] follow-up of 14 [10-17] years), patients who switched to LAIs had lower risks of all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.54-0.81), natural-cause mortality (aHR, 0.63; 95% CI, 0.52-0.76), and suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55-0.93) compared with patients who received the corresponding OAPs. A 47% lower suicide mortality risk (aHR, 0.53; 95% CI, 0.30-0.92) was observed in patients who switched to LAIs within the first 2 years of OAP initiation. Conclusions and Relevance: These findings suggest that LAI use in patients with newly diagnosed schizophrenia is associated with decreased all-cause mortality and suicide risk. Furthermore, early treatment with LAIs within the first 2 years of OAP initiation was associated with a decrease in suicide mortality risk. Thus, LAI use in the early stage of treatment should be actively considered for patients with newly diagnosed schizophrenia.

Schizophrenia hospitalization in the US 2005-2014: Examination of trends in demographics, length of stay, and cost.

ABSTRACT: Primarily we aimed to examine the crude and standardized schizophrenia hospitalization trend from 2005 to 2014. We hypothesized that there will be a statistically significant linear trend in hospitalization rates for schizophrenia from 2005 to 2014. Secondarily we also examined trends in hospitalization by race/ethnicity, age, gender, as well as trends in hospitalization Length of Stay (LOS) and inflation adjusted cost.In this observational study, we used Nationwide Inpatient Sample data and International Classification of Diseases, Eleventh Revisions codes for Schizophrenia, which revealed 6,122,284 cases for this study. Outcomes included crude and standardized hospitalization rates, race/ethnicity, age, cost, and LOS. The analysis included descriptive statistics, indirect standardization, Rao-Scott Chi-Square test, t-test, and adjusted linear regression trend.Hospitalizations were most prevalent for individuals ages 45-64 (38.8%), African Americans were overrepresented (25.8% of hospitalizations), and the gender distribution was nearly equivalent. Mean LOS was 9.08 days (95% confidence interval 8.71-9.45). Medicare was the primary payer for most hospitalizations (55.4%), with most of the costs ranging from $10,000-$49,999 (57.1%). The crude hospitalization rates ranged from 790-1142/100,000 admissions, while the US 2010 census standardized rates were 380-552/100,000 from 2005-2014. Linear regression trend analysis showed no significant difference in trend for race/ethnicity, age, nor gender (P > .001). The hospitalizations' overall rates increased while LOS significantly decreased, while hospitalization costs and Charlson's co-morbidity index increased (P < .001).From 2005-2014, the overall US hospitalization rates significantly increased. Over this period, observed disparities in hospitalizations for middle-aged and African Americans were unchanged, and LOS has gone down while costs have gone up. Further studies addressing the important disparities in race/ethnicity and age and reducing costs of acute hospitalization are needed.

Functional Outcomes of Patients with Schizophrenia After Hip Fracture Surgery: A 1-Year Follow-up from an Institutional Hip Fracture Registry.

BACKGROUND: Schizophrenia impairs a patient's self-care abilities, which are crucial after a hip fracture. Studies on the outcomes of patients with schizophrenia after a hip fracture are dated. This study aims to investigate the complication rates, 1-year mortality, and functional outcomes of surgically managed hip fractures in elderly patients with schizophrenia. METHODS: This is a retrospective, single-institution cohort study based on a prospectively maintained registry of patients with hip fracture. In this study, 3,056 patients who were ≥60 years of age were treated under a geriatric-orthopaedic hip fracture pathway from January 2014 to December 2018. Baseline demographic characteristics and the Modified Barthel Index (MBI) scores were obtained at admission and at 6 months and 1 year after the fracture. Complications from the fracture and the surgical procedure were recorded during a minimum follow-up period of 2 years. A matching process (based on age, sex, and the MBI at admission) of up to 6 patients without schizophrenia per 1 patient with schizophrenia was utilized to increase power. Differences in perioperative, 6-month, and 1-year outcomes were compared for significance among surgically managed patients with schizophrenia and patients without schizophrenia. RESULTS: Thirty-eight patients with schizophrenia were compared with 170 geriatric patients without schizophrenia who underwent a surgical procedure for a hip fracture. Patients with schizophrenia were more likely to be institutionalized postoperatively (26.3% compared with 4.7%; p < 0.001). Patients with schizophrenia had poorer MBI scores at 12 months (76 compared with 90 points; p = 0.006). The 1-year mortality rate was comparable (p = 0.29) between patients with schizophrenia (5.7%) and those without schizophrenia (2.4%). Similar trends in MBI were observed in the conservatively managed group of patients. CONCLUSIONS: There was no increase in postoperative complications after a surgical procedure for a hip fracture in elderly patients with schizophrenia. The 1-year mortality after a surgical procedure for hip fracture is similar in both patients with schizophrenia and those without schizophrenia. Patients with schizophrenia and hip fracture who were surgically managed had poorer 1-year functional outcomes compared with patients without schizophrenia matched for age, sex, and MBI at admission. This information will be useful in shared decision-making discussions with patients and families. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Genetic architecture of schizophrenia: a review of major advancements.

Schizophrenia is a severe psychiatric disorder with high heritability. Consortia efforts and technological advancements have led to a substantial increase in knowledge of the genetic architecture of schizophrenia over the past decade. In this article, we provide an overview of the current understanding of the genetics of schizophrenia, outline remaining challenges, and summarise future directions of research. World-wide collaborations have resulted in genome-wide association studies (GWAS) in over 56 000 schizophrenia cases and 78 000 controls, which identified 176 distinct genetic loci. The latest GWAS from the Psychiatric Genetics Consortium, available as a pre-print, indicates that 270 distinct common genetic loci have now been associated with schizophrenia. Polygenic risk scores can currently explain around 7.7% of the variance in schizophrenia case-control status. Rare variant studies have implicated eight rare copy-number variants, and an increased burden of loss-of-function variants in SETD1A, as increasing the risk of schizophrenia. The latest exome sequencing study, available as a pre-print, implicates a burden of rare coding variants in a further nine genes. Gene-set analyses have demonstrated significant enrichment of both common and rare genetic variants associated with schizophrenia in synaptic pathways. To address current challenges, future genetic studies of schizophrenia need increased sample sizes from more diverse populations. Continued expansion of international collaboration will likely identify new genetic regions, improve fine-mapping to identify causal variants, and increase our understanding of the biology and mechanisms of schizophrenia.

Excess mortality in patients with schizophrenia spectrum disorders in Malaga (Spain): A cohort study.

AIMS: There is evidence that patients with schizophrenia spectrum disorders present higher mortality in comparison with the general population. The aim of this study was to analyse the causes of mortality and sociodemographic factors associated with mortality, standardised mortality ratios (SMRs), life expectancy and potential years of life lost (YLL) in patients with schizophrenia spectrum disorders in Spain. METHODS: The study included a cohort of patients from the Malaga Schizophrenia Case Register (1418 patients; 907 males; average age 42.31 years) who were followed up for a minimum of 10 years (median = 13.43). The factors associated with mortality were analysed with a survival analysis using Cox's proportional hazards regression model. RESULTS: The main causes of mortality in the cohort were circulatory disease (21.45%), cancer (17.09%) and suicide (13.09%). The SMR of the cohort was more than threefold that of the population of Malaga (3.19). The life expectancy at birth was 67.11 years old, which is more than 13 years shorter than that of the population of Malaga. The YLL was 20.74. The variables associated with a higher risk of mortality were age [adjusted hazard ratio (AHR) = 1.069, p < 0.001], male gender (AHR = 1.751, p < 0.001) and type of area of residence (p = 0.028; deprived urban zone v. non-deprived urban area, AHR = 1.460, p = 0.028). In addition, receiving welfare benefit status in comparison with employed status (AHR = 1.940, p = 0.008) was associated with increased mortality. CONCLUSIONS: There is excess mortality in patients with schizophrenia spectrum disorders and also an association with age, gender, socioeconomic inequalities and receiving welfare benefits. Efforts directed towards improved living conditions could have a positive effect on reducing mortality.

Cancer and schizophrenia.

PURPOSE OF REVIEW: On the basis of articles published in 2018, 2019 and 2020, the first aim of this review is to present estimates of incidence rates and excess mortality of overall cancer and organ-specific cancers for patients with schizophrenia compared with the general population.The second aim is to explore if underdiagnosis and undertreatment can explain - at least partly - the increased mortality of cancer in patients with schizophrenia compared with the general population. RECENT FINDINGS: Patients diagnosed with schizophrenia have an approximately 50% increased risk of death by cancer compared to age and sex-matched people in the general population. Studies have confirmed an increased mortality from breast, lung and colon cancer in patients with schizophrenia.Analyses of incidence of cancer revealed contradicting results, with some studies showing no increase in incidence and others a modestly increased incidence in overall cancer. Studies of incidence of specific types of cancers showed modestly increased risk of pancreas, oesophagus, breast cancer and contradicting results regarding lung cancer.In studies identified that compared to the general population, patients with schizophrenia were at an increased risk of not being diagnosed or treated for cancer before death of cancer. In addition, patients with schizophrenia had lower chances of getting optimal treatment for colon cancer after diagnosis. SUMMARY: This review indicates that patients with schizophrenia are at increased risk of dying of cancer and of several specific types of cancer. This increased mortality can be reduced if the price of tobacco is increased, if smoking cessation programmes are offered systematically, screening programs better implemented in this highly vulnerable group, and if procedures to facilitate access to early diagnosis and effective treatment are implemented.

The impact of psychiatric and medical comorbidity on the risk of mortality: a population-based analysis.

BACKGROUND: As life expectancy increases, more people have chronic psychiatric and medical health disorders. Comorbidity may increase the risk of premature mortality, an important challenge for health service delivery. METHODS: Population-based cohort study in Ontario, Canada of all 11 246 910 residents aged ⩾16 and <105 on 1 April 2012 and alive on 31 March 2014. Secondary analyses included subjects having common medical disorders in 10 separate cohorts. Exposures were psychiatric morbidity categories identified using aggregated diagnosis groups (ADGs) from Johns Hopkins Adjusted Clinical Groups software® (v10.0); ADG 25: Persistent/Recurrent unstable conditions; e.g. acute schizophrenic episode, major depressive disorder (recurrent episode), ADG 24: Persistent/Recurrent stable conditions; e.g. depressive disorder, paranoid personality disorder, ADG 23: Time-limited/minor conditions; e.g. adjustment reaction with brief depressive reaction. The outcome was all-cause mortality (April 2014-March 2016). RESULTS: Over 2 years' follow-up, there were 188 014 deaths (1.7%). ADG 25 conferred an almost threefold excess mortality after adjustment compared to having no psychiatric morbidity [adjusted hazard ratio 2.94 (95% CI 2.91-2.98, p < 0.0001)]. Adjusted hazard ratios for ADG 24 and ADG 23 were 1.12 (95% CI 1.11-1.14, p < 0.0001) and 1.31 (95% CI 1.26-1.36, p < 0.0001). In all 10 medical disorder cohorts, ADG 25 carried significantly greater mortality risk compared to no psychiatric comorbidity. CONCLUSIONS: Psychiatric disorders, particularly those graded persistent/recurrent and unstable, were associated with excess mortality in the whole population, and in the medical disorder cohorts examined. Future research should examine whether service design accounting for psychiatric disorder comorbidity improves outcomes across the spectrum of medical disorders.

Increased in-hospital mortality from COVID-19 in patients with schizophrenia.

BACKGROUND: There is limited information describing the presenting characteristics and outcomes of patients with schizophrenia (SCZ) requiring hospitalization for coronavirus disease 2019 (COVID-19). AIMS: We aimed to compare the clinical characteristics and outcomes of COVID-19 SCZ patients with those of non-SCZ patients. METHOD: This was a case-control study of COVID-19 patients admitted to 4 AP-HM/AMU acute care hospitals in Marseille, southern France. COVID-19 infection was confirmed by a positive result on polymerase chain reaction testing of a nasopharyngeal sample and/or on chest computed scan among patients requiring hospital admission. The primary outcome was in-hospital mortality. The secondary outcome was intensive care unit (ICU) admission. RESULTS: A total of 1092 patients were included. The overall in-hospital mortality rate was 9.0%. The SCZ patients had an increased mortality compared to the non-SCZ patients (26.7% vs. 8.7%, P=0.039), which was confirmed by the multivariable analysis after adjustment for age, sex, smoking status, obesity and comorbidity (adjusted odds ratio 4.36 [95% CI: 1.09-17.44]; P=0.038). In contrast, the SCZ patients were not more frequently admitted to the ICU than the non-SCZ patients. Importantly, the SCZ patients were mostly institutionalized (63.6%, 100% of those who died), and they were more likely to have cancers and respiratory comorbidities. CONCLUSIONS: This study suggests that SCZ is not overrepresented among COVID-19 hospitalized patients, but SCZ is associated with excess COVID-19 mortality, confirming the existence of health disparities described in other somatic diseases.

Viewpoint: do antipsychotics protect against early death? A critical view.

In the past 15 years, researchers utilizing prescription databases to assess medication usage have concluded that antipsychotics reduce mortality in patients diagnosed with schizophrenia and other psychotic disorders. These findings stand in contrast to studies in non-psychiatric patients that have found that antipsychotics, because of their adverse effects on physical health, increase the risk of early death. A critical review of the evidence reveals that the worry remains. There is reason to conclude that antipsychotics contribute to the 'mortality gap' between the seriously mentally ill and the general population and that the database studies are plagued with methodological and reporting issues. Most importantly, the database studies tell of mortality rates within a drug-centered paradigm of care, which confounds any comparison of mortality risks when patients are on or off antipsychotics.

Metabolic predictors for mortality among patients treated with long-term clozapine - A longitudinal study.

Clozapine is the only antipsychotic compound indicated for refractory-schizophrenia. However, it is associated with emergent metabolic dysregulation and cardiovascular risk which may lead to mortality. In this study we aimed to explore predictors for mortality in a large cohort of schizophrenia patients treated with long-term clozapine, using the electronic medical records of the largest health care provider in Israel. Among 27,929 patients diagnosed with schizophrenia, 1817 were prescribed clozapine during the years 2012-2014. We compared patients who survived (n=1705) and patients who died (n=112) during the 3-year follow-up period. Socio-demographic background, cardiovascular morbidity, medication prescriptions and health-care utilization were compared between groups. Cox proportional hazard models were used to assess the association of variables with survival. Chronic hypertension was found to be the only metabolic factor associated with significant hazard ratio (HR) for mortality (HR: 1.55 95% CI: 1.03-2.34). Moreover, those who died had more prevalent ischemic heart disease (14% vs 3%, p<0.005) as well as more frequent hospitalizations (0.01±0.02 vs 0.11±0.18 average per month, p<0.005), for longer periods (2.22±9.87 vs 20.38±33.76 days per month, p<0.005). Among those who died, less patients received prescriptions of statins for hyperlipidemia (13.7% vs. 52.9% in survivors, p<0.005) and hypoglycemics for diabetes mellitus (16.3% vs. 67.1% in survivors, p<0.005). Inadequate treatment of metabolic syndrome, under chronic clozapine treatment, was found to be an independent predictor for mortality. Adequate rigorous regimen for diagnosis and treatment of metabolic risk factors, especially hyperlipidemia and diabetes mellitus, might lower complications rate and prolong life expectancy among this population.